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Case Based Oral Mucosal Lesions PDF
Case Based Oral Mucosal Lesions PDF
Mucosal Diseases
Qianming Chen
Xin Zeng
Editors
123
Case Based Oral Mucosal Diseases
Qianming Chen • Xin Zeng
Editors
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Preface
The catch-all term, oral mucosal diseases, refers to various diseases of the
oral mucosa and related soft tissues. Aside from certain individual cases that
can be attributed to local factors, a majority of oral mucosal diseases occur
due to a combination of both local and systemic factors. In recent years, the
model of biological-psychological-social medicine has become especially
significant in studying the pathogenicity and management of oral mucosal
diseases.
Since an increase has been recorded in the incidence rate and the number
of complicated cases of oral mucosal diseases, the Department of Oral
Mucosal Diseases has been tasked with the regular development of novel
diagnostic and treatment methods. As a result, we have left no exceptions in
exploring clinical cases. In addition to a large number of common cases, an
increasing number of rare, anomalous cases of oral mucosal diseases have
been recorded. Often, it is difficult to provide immediate and definitive diag-
noses for the latter type of cases. In order to provide definitive diagnoses, as
well as out of curiosity, we took the initiative to review pictures, books, and
other literature, as well as communicate with experts in relevant disciplines.
Based on the information from such data and communications, we further
examined patients to provide an accurate diagnosis and treatment. We feel
gratified and accomplished because our expertise has allowed us to help
patients who seek medical attention from us. Such experiences have left us
even more intrigued by the complexity of oral mucosal diseases, further ignit-
ing our strong interest in this discipline.
“A picture is worth a thousand words.” This is an inspirational quote that
comes to our mind every time we review the collected images of clinical
cases. Looking back at medical records and recalling the situation of each
patient, the educational process of diagnosis and treatment, as well as our
experiences after reaching a definitive diagnosis on the disease, we realize
that each picture has a story. Therefore, we have also gained a deeper insight
into two criteria that need to be fulfilled to be a good physician: (1) medical
skills and (2) empathy toward patients. This brings to memory the epitaph of
an American physician, Dr. Edward Livingston Trudeau: “To Cure Sometimes,
To Relieve Often, To Comfort Always.” Truly, this is particularly the case
with medical practitioners working on rarely studied oral mucosal diseases.
We are passionate about this profession. We enjoy the ideas and discover-
ies in the diagnosis and treatment of each patient. Besides, we also enjoy the
v
vi Preface
recognition of our careers, as well as the sentiment behind the story of each
patient.
Due to the abovementioned reasons, we desired to write a reference book
on the clinically common and rare cases of oral mucosal diseases. One of our
students, Jin Xin, also repeatedly suggested, while arranging the image
resources of clinical cases, that we should not leave them as they are. After
careful consideration, we began to write a book about oral mucosal diseases
based on those pictures of clinical cases with the involvement and support of
Dr. Jin Xin, Assoc. Prof. Jiang Lu, Assoc. Prof. Zhou Yu, and Assoc. Prof.
Dan Hong-Xia from the Department of Oral Mucosal Diseases; Professor Wu
Lan-Yan and Assoc. Prof. Geng Ning from the Department of Oral Pathology;
as well as Assoc. Prof. Li Wei from the Department of Dermatology, West
China College of Stomatology, Sichuan University. We look forward to seek
an appropriate way to reveal, share, and discuss with our colleagues and stu-
dents the clinical manifestations of oral mucosal diseases and the process of
diagnosis and treatment for such cases. Besides, we also aim to provide a
desk reference book for freshmen in this discipline.
On the occasion of completing this book, we would like to thank our men-
tor, Prof. Li Bing-Qi, for his care, support, and enlightenment. We would also
like to express our gratitude to Dr. Jin Xin for his participation and great
effort throughout the entire writing process, as well as Li Xiao-Ying (Deputy
Chief Nurse) and Wu Yuan (Nurse) from the Department of Oral Mucosal
Diseases, West China College of Stomatology, Sichuan University, for the
photography of all the clinical pictures used in the book. Last but not least, we
would also like to express our appreciation to all colleagues at the Department
of Oral Mucosal Diseases, West China College of Stomatology, Sichuan
University.
vii
Oral Infectious Diseases
1
Xin Jin, Xin Zeng, and Qianming Chen
X. Jin
College of Stomatology, Chongqing Medical
University, Chongqing Key Laboratory of Oral
Diseases and Biomedical Sciences,
Chongqing, China
X. Zeng b
State Key Laboratory of Oral Diseases, National
Clinical Research Center for Oral Diseases,
Department of Oral Medicine, West China Hospital
of Stomatology, Sichuan University,
Chengdu, Sichuan, China
Q. Chen (*)
Changjiang Scholars Program, Ministry of Education,
Beijing, China
State Key Laboratory of Oral Diseases, National
Clinical Research Center for Oral Diseases,
Department of Oral Medicine, West China Hospital
of Stomatology, Sichuan University, Chengdu, Fig. 1.1 (a) Red and swollen gums with erosions in clus-
Sichuan, China ters on the gingiva. (b) Red and swollen gums with ero-
e-mail: qmchen@scu.edu.cn sions in clusters on the gingiva and tongue
© Springer Nature Singapore Pte Ltd. and People’s Medical Publishing House 2018 1
Q. Chen, X. Zeng (eds.), Case Based Oral Mucosal Diseases,
https://doi.org/10.1007/978-981-13-0286-2_1
2 X. Jin et al.
Fig. 1.3 Clusters of vesicles involving the left vermilion Fig. 1.4 Spotlike erosions in clusters on the right part of
border of the lower lip and adjacent skin palate
4 X. Jin et al.
cough can arise. One to 3 days later, mucocu- min C. If the course of disease is more than 5 days,
taneous vesicle ruptured. It typically affects the antiviral drugs are not recommended. The usage
lips, tongue, gingiva, buccal mucosa, and palate. of acyclovir is as follows: for children younger
The oral lesions manifest as blisters with 1–2 mm than 2 years old, 100 mg orally, five times per
in diameter, which rupture rapidly and coalesce day, for 5 days, is the course of treatment, and for
to shallow, painful, and usually irregular ulcers. children older than 2 years old, 200 mg orally,
They are often covered by a yellowish-gray five times per day, for 5 days, is the course of
pseudomembrane, with surrounding hyperemia. treatment [10]. Because it is a self-limiting ill-
The ulcers gradually heal in 10–14 days, with- ness with short disease course, acyclovir is not
out scarring. The swelling gingiva is one of the recommended if the symptom is mild. For adults,
gingival features, which may be misdiagnosed as 200 mg orally, five times daily, for 5–7 days, is
gingivitis caused by dental plaque and calculus. the course of treatment. Adult patients can also
Perioral lesions are found in approximately 2/3 of take valaciclovir hydrochloride tablets orally,
affected children. Most children have a fever of 300 mg, on an empty stomach before meal, twice
>38.0 °C for approximately 4 days, with enlarged a day, for 7 days. Kouyanning granules should
cervical lymph nodes, increased saliva secretion, be taken as follows: 3–6 g, three times a day,
dehydration, coated tongue, bad breath, and skin for 3–5 days, with a gradual dosage reduction
rash. The severity of illness is associated with the according to weight and age in children.
host immunoreactions [1]. Virus spread widely or Topical treatments include gargarism (com-
secondary bacteremia is rare [7]. pound chlorhexidine solution, three times a day,
Recurrent herpes simplex typically affects the 1:1 diluted for children use), topical-use drug
lips, vermilion commissures, and perioral skin, (recombinant human epidermal growth fac-
termed as recurrent herpes labialis (RHL) [9]. tor hydrogel, once daily, compound ulcer paste
RHL is preceded by premonitory symptoms such or glucocorticoids such as 0.1% triamcinolone
as burning, tingling, soreness, or swelling at the acetonide dental paste, 0.1% dexamethasone
site where the lesions will occur [2]. In about 6 h, ointment, prednisolone acetate injection, triam-
the lesions are usually red macules that rapidly cinolone acetonide injection, 1:5 diluted or dexa-
become vesicular, following scabs and ulcers. methasone paste, three times a day), and spray
Healing happens in 10 days from initial symp- (stomatitis spray, three times a day). Acyclovir
tom onset, without scarring [1, 2]. The intraoral eye drops can be topically used on herpes labialis
recurrent herpes simplex often occurs on the pal- three times a day. Glucocorticoids should be used
ate and gingival mucosa, which is characterized with caution for children under 6 years because
by erosions in clusters. they can cause growth retardation and bone loss,
The diagnosis of herpes simplex is based on the even the topical application is not suitable for
clinical history and features [7]. Laboratory tests long-term and extensive use. Moreover, gluco-
such as tissue culture techniques and detection corticoids for herpes labialis should not be used
of viral DNA are not the conventional diagnostic on the perioral skin to avoid hyperpigmentation
methods. All the cases of this unit are diagnosed on the orofacial skin.
by the typical history and clinical features. Aerosol therapy could have additional use for
Treatments of acute herpetic gingivostomatitis serious cases, including dexamethasone sodium
include systemic therapy and topical treatment. phosphate injection, gentamycin sulfate injec-
Topical treatment is mainly applied in recurrent tion, vitamin C injection, and vitamin B12 injec-
herpes simplex. tion, once or twice a day. For children younger
Oral drugs include antiviral drugs (acyclovir than 6 years old, gentamycin sulfate injection is
and valaciclovir), Kouyanning granules, and vita- not recommended for aerosol therapy.
6 X. Jin et al.
a b
c d
Fig. 1.5 (a) Vesicles in clusters involving the left vermil- erosions on the left lateral and ventral tongue, covered by
ion border of the lower lip and adjacent skin. (b) Multiple a yellowish pseudomembrane, and the rash does not cross
blisters distributed on the left buccal mucosa. (c) Multiple the midline. (d) Vesicles on the left preauricular region
Age: 46 years appeared on the left lower lip and perioral and
Sex: male preauricular region (Fig. 1.5).
Chief Complaint: Laboratories and Imaging Studies: None.
46-year-old man with oral ulcers for 1 week Diagnosis:
History of Present Illness: Herpes Zoster
A 46-year-old man presented to our clinic with Diagnosis Basis:
painful ulcers on the oral mucosa for 1 week after
a cold, and painful blisters on the preauricular 1. Oral and cutaneous lesions are unilateral and
region appear 3 days ago. do not cross the midline.
Past Medical History: None. 2. Multiple blisters and erosions are observed.
Allergy: None.
Management:
Physical Examination:
Multiple blisters and erosions were distributed on 1. Aerosol therapy
the left dorsum, lateral and ventral tongue, left Rp.: Dexamethasone sodium phosphate
buccal mucosa, and the left mandibular lingual injection 1 ml × 1
gingiva, and part of them coalesced covered by a Gentamycin sulfate injection 2 ml × 1
yellowish pseudomembrane. Many vesicles Vitamin B12 injection 1 ml × 1
1 Oral Infectious Diseases 7
a b
Fig. 1.6 (a) Clear vesicles in clustered at the right perioral skin and lips, and do not cross the midline. (b) Blisters and
erosions on the right palate, and do not cross the midline
Age: 23 years ular rashes were unilateral and do not cross the
Sex: male midline. There were erosions in clusters on the
Chief Complaint: right buccal mucosa covered by a yellowish-
23-year-old man with oral and facial blisters for white pseudomembrane (Fig. 1.6).
2–3 days Laboratories and Imaging Studies: None.
History of Present Illness: Diagnosis:
A 23-year-old man presented to our clinic with Herpes Zoster
oral and facial blisters for 2–3 days, with unbear- Diagnosis Basis:
able pain. He caught a cold 1 week ago.
Past Medical History: None. 1. Oral and cutaneous lesions are unilateral and
Allergy: None. do not cross the midline.
Physical Examination: 2. Multiple blisters and erosions are observed.
The clear vesicles were clustered at the right
nose, perioral skin, and lip; bead-like blisters on Management:
the right palate can also be noticed. All the vesic- The same as Case 5
8 X. Jin et al.
a b
c d
Fig. 1.7 (a) Widespread fluid-filled vesicles of different (c) Miliary blisters and erythematous macules spread all
sizes on the lips. (b) Multiple erosions coalesced on the over the palms. (d) Erythematous macules and vesicles on
ventral tongue, covered by a yellowish pseudomembrane. the face
Management:
1. Medication
b Rp.: Kouyanning granules 3 g × 10
Sig.: 3 g p.o. t.i.d.
Vitamin C 0.1 g × 100
Sig.: 0.1 g p.o. t.i.d.
Compound chlorhexidine solution
300 ml × 1
Sig.: rinse t.i.d.
Recombinant human epidermal growth
factor hydrogel 20 g × 1
Sig.: topical use q.d.
2. Hospitalization in the dermatological depart-
Fig. 1.8 (a) Several erosions covered by white pseudo-
membranes on the tip of the tongue, with crusting on the ment is recommended. Exclusion from child-
left perioral skin. (b) Erythema and vesicles on the skin of care in order to avoid infection until the
chest and abdomen blisters disappeared.
10 X. Jin et al.
[Review] Herpes Zoster and Varicella Varicella lesions in adult are more serious than in
Herpes zoster is the manifestation of herpes children; the specialist should be alert to compli-
varicella-zoster virus (VZV) infections. It occurs cations such as pneumonia, neurologic disease,
when the varicella-zoster virus, which causes and bacterial infection. Hospitalization for fur-
both varicella and herpes zoster, is reactivated ther treatment is required if serious complica-
and spreads through the afferent nerve to the tions are noticed.
skin, with intense pain [11]. Herpes zoster can Herpes zoster is characterized by a band-like
develop in anyone who has had varicella, and rash in the skin that corresponds to the affected
the frequency increases with increasing age [12]. nerve. The rash is unilateral and does not cross
Some patients, who have not suffered varicella the midline. Chest herpes zoster is most com-
in childhood, may manifest when varicella when monly involved, followed by trigeminal herpes
infected with VZV as adults. zoster. Localized sensations are ranging from
Primary VZV infection (varicella) causes mild itching or tingling to severe pain that pre-
VZV-specific antibody to be produced and cedes the development of the skin lesions by
VZV-specific T cell-mediated immune response, 1–5 days. As the cutaneous disease progresses,
which can be detected within 1–2 weeks after vesicles usually coalesce into larger fluid-filled
appearance of lesions. The response is essential lesions, following postulation and scabbing.
for recovery from varicella, due to both CD4 and Unilateral blisters are common oral lesions,
CD8 effectors and memory T cells included. The which break down and coalesce to form extensive
memory T cell response during varicella will pro- ulcers covered by a thick pseudomembrane. The
tect against infection during reexposure to VZV lesions usually heal within 2–4 weeks, with com-
[13]. Varicella also results in lifelong latency plications of fatigue, headache, and photophobia;
of VZV in neurons of cranial nerve and dorsal fever is unusual [11].
root ganglia [14]. VZV-specific T cell-mediated The Ramsay Hunt syndrome is a rare disease
immune response is also essential to maintain caused by an infection of the geniculate ganglion
VZV latency in sensory ganglia at a subclini- by the varicella-zoster virus. The main clinical
cal state. When these responses are impaired, features of the syndrome are as follows: Bell’s
as occurs with aging or immunosuppression, palsy, unilateral or bilateral, vesicular eruptions
the latent VZV will be reactivated. It will cause on the ears, and ear pain [16].
a ganglionitis with associated dermatomal neu- The diagnosis of herpes zoster is usually based
ropathic pain and following painful dermatomal on the clinical history and features. All the cases
vesicular rash, leading to herpes zoster [13]. of this unit are diagnosed by the typical history
Incubation period of varicella is generally and clinical features.
ranging from 14 to 16 days. The initial cutane- Systemic treatment in the dermatological
ous manifestations often involve the scalp, face, department is recommended due to band-like rash
and trunk. They are pruritic erythema, with sys- presenting as the typical cutaneous lesions. The
temic symptoms of fever, fatigue, and anorexia. treatment agents include antiviral drugs, immuno-
Then the maculopapular phase progresses to a modulatory drugs, painkillers, and neurotrophic
vesicular phase, during which small fluid-filled drugs. Acyclovir (200 mg orally, five times a day,
vesicles occur with the range of number from for 5–10 days, or 400 mg orally, three times a day,
100 to 300 lesions. Approximately 24–48 h after for 5 days), valaciclovir (300 mg orally, twice a
the appearance of each lesion, crusting phase day for 7 days), and famciclovir (250 mg orally,
begins. Hypopigmentation is common and scar- three times a day for 7 days) are all effective anti-
ring is rare during healing. The cutaneous rash viral drugs for treating herpes zoster. For patients
is centripetally distributed, starting with the face, with renal impairment, dose reduction is required.
following the trunk and limbs. Ulcerative and Immunomodulatory drugs include pidotimod
painful lesions appear on mucous membranes, (0.4 g orally, twice a day), transfer factor capsules
such as the oropharynx and conjunctivae [15]. (6 mg orally, three times a day), and thymopeti-
1 Oral Infectious Diseases 11
dum enteric-coated tablets (20 mg orally, one to develop mild infections after exposure to natu-
three times a day). Neurotrophic drugs include ral virus, but the rashes are fewer with no fever
vitamin B1 (10 mg orally, three times a day), in most cases [19]. However, it is unclear if the
vitamin B12 injections (0.025–0.2 mg, intramus- vaccine can affect the morbidity and severity of
cular injection, q.o.d.), and mecobalamin (0.5 mg herpes zoster.
orally, three times a day).
Topical treatment of oral lesions for varicella
and herpes zoster includes gargle, coated drugs, 1.3 Hand-Foot-Mouth Disease
and spray. Gargle includes compound chlorhexi-
dine solution, three times a day (1:1 diluted for Case 9 Hand-Foot-Mouth Disease
children). Coated medicine includes recombi-
nant human epidermal growth factor hydrogel
or recombinant bovine basic fibroblast growth a
factor gel, once daily, or compound ulcer paste
and glucocorticoids such as prednisolone acetate
injection, triamcinolone acetonide injection (1:5
diluted), triamcinolone acetonide dental paste,
and 0.1% dexamethasone ointment or dexameth-
asone paste, topical use three times a day. Spray
such as stomatitis spray can be used three times a
day. Painkiller such as compound chamomile and
lidocaine hydrochloride gel or compound benzo-
caine gel can be applied as well, topical use three
b
times a day. For children younger than 6 years
old, glucocorticoid is not recommended.
Zostavax is a concentrated formula-
tion of Varivax that the US Food and Drug
Administration (FDA) has approved to prevent
herpes zoster and its complications in immuno-
competent adults aged ≥60 years. The vaccine
was designed to boost cell-mediated immune
responses, which should keep latent varicella-
zoster virus from reactivating and thus prevent
herpes zoster [17]. A randomized, double-blind, c
placebo-controlled trial of 38,546 adults 60 years
of age or older discovered that the zoster vaccine
markedly reduced morbidity from herpes zoster
and postherpetic neuralgia among older adults,
with a median of 3.12 years of follow-up [18].
Varicella vaccine is an effective means for pre-
vention, and it plays a vital role in controlling the
outbreaks for varicella. Therefore, the vaccine is Fig. 1.9 (a) Scattered ulcers or erosions on the right buc-
cal mucosa. (b) Blisters on the palms and fingers. (c)
recommended to prevent varicella in all children Blisters on the toes and soles
and adults who are seronegative for antibodies
to varicella-zoster virus [11]. The great majority Age: 7 years
of vaccine recipients were under prolonged pro- Sex: female
tection, which were supervised for 7 years from Chief Complaints:
clinical trial. Some subjects with vaccine injected Oral ulcers and red spots on the hands for 1 day
12 X. Jin et al.
[Review] Herpangina
Fig. 1.10 Ulcers and erosions on posterior soft palate
Herpangina is an oral lesion mainly caused by the
infection of Coxsackie virus A (CV-A). The virus
Age: 2 years 8 months types vary with the outbreak year and the area,
Sex: male and the main types are CV-A2, CV-A4, CV-A5,
Chief Complaints: CV-A6, CV-A8, CV-A9, CV-A10, CV-A16,
Oral pain for 1 day CV-A22, etc. [29–31]. The illness is highly
History of Present Illness: infectious and spreads fast, which usually affects
The teacher noticed that oral ulcers were located children. The incidence of herpangina is greatest
on their child’s throat, with pain for 1 day. He had in summer and autumn. It is characterized by an
a history of cold 5 days ago. acute onset of fever and sore throat with mild pre-
Past Medical History: None. cursory and general symptoms [32]. The clinical
Allergy: None. features are blisters with 1–2 mm in diameter on
14 X. Jin et al.
the posterior oral mucosa, which often become diluted for children) can be used as rinse solution,
erosions or ulcers. The site of lesions is limited to three times a day. Liniment such as recombinant
the posterior oral cavity, such as the soft palate, human epidermal growth factor hydrogel, once a
uvula, and tonsil. The disease usually lasts about day; or compound ulcer paste, 0.1% triamcinolone
7 days. Diagnosis is mainly based on the history acetonide dental paste, and 0.01% dexamethasone
of the disease and the typical lesions on the pos- compound three times a day; or prednisolone ace-
terior oral cavity. tate injection and triamcinolone acetonide injec-
Systemic treatment of the disease can use tion (1:5 diluted), three times a day, can be applied.
Kouyanning granules orally, 1.5–3.0 g continuous Stomatitis spray can be selected as the spray, three
for 3–5 days, and vitamin C tablets, 0.05–0.1 g times a day. Glucocorticoids should be used with
orally three times a day; vitamin B tablets can also caution for children under 6 years because they
be taken orally, 0.5–1 tablet a day. Topical medica- can cause growth retardation and bone loss, even
tions include rinse (cleansing) solutions, spreads, the topical application is not suitable for long-term
and sprays. Compound chlorhexidine solution (1:1 and extensive use.
a b
Fig. 1.11 (a) Widespread confluent white velvety removed by gentle rubbing of the lesion. (c) Widespread
plaques on the upper labium mucosa, which can be confluent white velvety plaques on the palate, which can
removed by gentle rubbing of the lesion. (b) White vel- be removed by gentle rubbing of the lesion
vety plaques on the right buccal mucosa, which can be
1 Oral Infectious Diseases 15
a b
Fig. 1.12 (a) Disperse and irregular reddened lesions on the dorsum of the tongue. (b) Disperse hyperemia on the left
buccal mucosa
a b
Fig. 1.13 (a) Fissures running in the corner of the mouth. (b) Atrophic dorsum of the tongue. (c) Widespread reddened
lesions on the palate, with edema and papillary hyperplasia on the alveolar ridges and the palate
on the palate, with edema and papillary hyperplasia 3. Fungi were detected by smear method.
on the alveolar ridges. The dorsum of the tongue was
atrophic, and fissures running in the corner of the Management:
mouth occurred. Fungi were detected from samples
1. Medication
taken from the corner of the mouth, dorsum of the
Rp.: Pidotimod 0.4 g × 18 tablets
tongue, and the palate by smear method (Fig. 1.13).
Sig.: 1 tablet b.i.d. p.o.
Diagnosis:
Compound vitamin B 100 tablets
Chronic Erythematous Candidosis; Candidal
Sig.: 2 tablets t.i.d. p.o.
Angular Cheilitis
2% sodium bicarbonate solution 250 ml × 4
Diagnosis Basis:
Sig.: rinse t.i.d.
Nystatin liniment 15 g × 2
1. The patient was an old lady with complete
Sig.: topical use t.i.d.
denture.
2.
Attention to clean dentures followed
2. Widespread reddened lesions with edema and
by soaked with 2% sodium bicarbonate
papillary hyperplasia were observed on the
solution
maxillary denture-supporting area.
a b
Fig. 1.14 (a) A 14 mm × 11 mm plaque on the posterior and middle dorsum of the tongue. (b) The plaque with white
granular surface that protrudes from the mucosal surface. (c) The white lesion recessed mostly 1 week later
Past Medical History: None. dosis has markedly increased, mainly owing
Allergy: None. to the escalation of human immunodeficiency
Physical Examination: virus (HIV) infection, organ and bone marrow
There was a 14 mm × 11 mm plaque on the pos- transplantation, and increasing use of immuno-
terior and middle dorsum of the tongue, with suppressive therapies as well as broad-spectrum
white granular surface. No local hyperemia or antibiotics [33].
erosion was observed. It cannot be removed by A change from the harmless commensal exis-
gentle rubbing of the lesion. Smear method failed tence of Candida to a pathogenic state appears
to detect fungi from the lesion (Fig. 1.14a, b). following alteration of the oral environment to
Clinical Impression: one that favors the growth of Candida. The causes
Chronic Hyperplastic Candidosis? of such alterations are the so-called predisposing
Management: factors including host factors for Candida infec-
tion. With regard to the opportunistic pathogenic
1. Medication
nature of Candida, candidiasis is often described
Rp.: Pidotimod 0.4 g × 18 tablets
as being “diseases of the diseased” [34]. Candida
Sig.: 1 tablet b.i.d. p.o.
albicans is the most common in everyone, and
Compound vitamin B 100 tablets
mycological studies have revealed that C. albi-
Sig.: 2 tablets t.i.d. p.o.
cans represents more than 80% of the specimen
2% sodium bicarbonate solution 250 ml × 4
from all types of human candidosis [35]. It is
Sig.: rinse t.i.d.
noteworthy that the incidence of non-C. albicans
Nystatin liniment 15 g × 2
species is increased in human candidosis. The
Sig.: topical use t.i.d.
reasons may partly relate to improved diagnos-
Fluconazole 50 mg × 6 tablets
tic methods. However, it could also reflect that
Sig.: 50 mg b.i.d. suck
more and more antifungal drug resistance was
2. Subsequent visit 1 week later was suggested.
observed in some non- Candida albicans spe-
Excision or biopsy would be considered if no
cies compared with C. albicans [36]. The most
remission occurred
predilection mucosa is superficial and moist,
which is common in the vagina and oral cav-
Subsequent Treatment:
ity. Systemic infections are rare but are severe
One week later, the white lesion recessed mostly
if they do develop, with mortality rates of up to
(Fig. 1.14c); 2 weeks later, the lesions disap-
60% [37]. In the past 10 years, candidemia that
peared completely.
has increased fivefold has been reported, with
Diagnosis:
susceptible individuals suffering from leukemia
Chronic Hyperplastic Candidosis
or blood stem cell transplantation. In addition to
Diagnosis Basis:
candidosis, it has been considered that Candida
1. The dorsum of the tongue is a predilection site species may be pathogenic factors in some oral
of chronic hyperplastic candidosis. disorders, including oral cancer, burning mouth
2. The plaque presented as white granular
syndrome, taste disorders, and endodontic dis-
appearance. ease, although the pathogenesis remains unclear
3. Although definite diagnosis requires biopsy, [38–41].
complete recovery was achieved by antifungal C. albicans is heat-labile and is stable in acidic
therapy in this case. conditions. The pathogenic significance of being
able to generate hyphae could associate with the
greater enhanced adherence to host surfaces and
[Review] Oral Candidosis invade epithelial layers resulting in tissue dam-
Oral candidosis is a fungal infection of Candida age. Putative virulence factors have been identi-
species on the mucous membranes of the mouth. fied, including adherence to host by cell surface
In recent decades, the incidence of oral candi- hydrophobicity and expression of cell surface
1 Oral Infectious Diseases 19
denture wearers have clinical signs of this condi- Case 14 was diagnosed by the clinical features
tion [46]. and good response to antifungal therapy.
Chronic hyperplastic candidosis mainly mani- Management of oral candidosis requires iden-
fests as a thickened white plaque, most com- tification and correction of the specific underly-
monly on the dorsum of the tongue. It has the ing predisposing factors in an individual patient,
potential of squamous cell carcinoma develop- such as cessation of antibiotics and glucocorti-
ment at lesion locations, although the function of coid abuse, cleaning the denture, and appropriate
Candida in carcinogenesis remains unclear [47]. oral hygiene practices.
Several studies have shown that antifungal treat- Local treatment has good effect on oral can-
ment may alter the clinical features of this lesion didosis. Commonly used is 2–4% sodium bicar-
from a nonhomogeneous to a homogeneous leu- bonate solution and nystatin liniment. Nystatin
koplakia, while others have demonstrated that liniment is a tetraene antibiotic, and l mg is
part of the lesions completely disappears after equivalent to 2000 U. Aqueous suspensions of
antifungal therapy alone, thus confirming its fun- 0.05–0.1 million U/ml can be used for topical
gal etiology [34]. use, once every 2–3 h, and it can be swallowed
Candidal angular cheilitis manifests as ery- after coated. For infants and young children
thematous lesions at one or both of the angles with oral thrush, the lesions will regress after
of the mouth. The spectrum of microorgan- the application of the above drugs but are easy to
isms discovered from this disorder includes relapse. Not only boiling the contact items (such
Staphylococcus aureus, streptococcal species, as bottles, spoon, cup, bowl, and toys) followed
etc., other than Candida. As a result, the exact by soaking with 1–2% sodium bicarbonate solu-
role of Candida in angular cheilitis remains tion disinfectant but also adhering to the medi-
uncertain [34]. cation after the lesion regression for 10–14 days
Candidal cheilitis lacks the specific clinical should be noted. In addition, if the child is still
features, which could manifest as erosions, crust- in the breastfeeding stage, the mother’s nipple
ing, or small granular lesions on the lips. should also be cleaned with 1–2% sodium bicar-
The diagnosis of oral candidosis is usually bonate solution and coated with nystatin liniment
based on the clinical history and features; labora- or water suspension.
tory examinations are also needed [43]. The com- For patients with stubborn condition, com-
mon tests include smear method, isolated culture, bination of oral drugs that include antifungal
and histopathological examination. Generally, agents, immunoenhancers, and vitamins can be
pseudomembranous and erythematous candido- effective. Oral antifungal drugs such as flucon-
sis can be diagnosed without a biopsy. azole tablets are suggested to be taken on the first
A characteristic feature of chronic hyper- day by 200 mg, followed by 50 mg, two times
plastic candidosis is hyperparakeratosis on the daily for 7–14 days, or itraconazole capsules,
superficial mucosa with inflammatory cell infil- 100–200 mg orally, one time per day. However, it
tration and microabscesses formed. Epithelial is critical to notice that the abovementioned oral
cell edema, mild to moderate epithelium dyspla- antifungal drugs should not be used in infants
sia, and a dense infiltration of lymphocytic cells and patients with serious systemic diseases.
into the mesenchyme of lamina propria were also Immunoenhancers include pidotimod, 0.4–0.8 g
found. The penetration of the oral mucosa by C. each time, two times per day for 7–14 days; or
albicans hyphae, which are detected in biopsy thymopetidum enteric-coated tablets, 20 mg
sections following Periodic Acid-Schiff (PAS) or orally, two to three times daily, for 15–30 days;
equivalent staining methods. Case 11 was diag- or transfer factor capsule, 6 mg each time, two to
nosed by the typical pseudomembranous lesions; three times daily, for 15–30 days. Vitamin drugs
Cases 12 and 13 were diagnosed by the typical include compound vitamin B, mecobalamin,
history, clinical features, and smear method; and folic acid, vitamin C, and so on.
1 Oral Infectious Diseases 21
Staphylococci, and Diplococcus pneumonia. The immune mechanisms, leading to systemic infec-
balance between the host and oral microflora tions, which should be noticed in clinical prac-
breaking down relates to lots of predisposing tices [50].
factors, including cold and fever, acute infec- A patient accompanied by the systemic infec-
tious disease, radiotherapy and chemotherapy tion should be evaluated firstly. Targeted antibiot-
for malignancies, and long-term use of immu- ics should be chosen based on results of bacterial
nosuppressants, which could reduce the immune culture and drug sensitivity test, including peni-
function, resulting in abnormal proliferation and cillins, cephalosporins, and macrolides. The fol-
virulence increase of bacteria responsible for lowing drugs can be applied if without systemic
coccigenic stomatitis. Advanced age, suffering infection: pidotimod, 0.4 g orally, twice a day
from other oral mucosal disorders, dentures, and for 1–2 weeks; compound vitamin B, two tablets
orthodontic materials may also be predisposing orally, three times a day; 1% povidone iodine
factors [48, 49]. solution or compound chlorhexidine solution
Primary coccigenic stomatitis is uncom- for oral rinse, three times a day; and topical use
mon, often occurred in weak patients with low of compound ulcer paste. Lozenges can also be
resistance. Secondary coccigenic stomatitis is used, such as the cydiodine tablets, 1.5 mg suck,
commonly seen in clinical practice occurring four to six times a day; lysozyme hydrochloride
following other oral mucosal lesions, such as tablets, 20 mg suck, four to six times a day; and
herpes simplex, allergies stomatitis, or erosive dequalinium chloride buccal tablet, 0.5 mg suck,
oral lichen planus. The anti-infectious treatment four to six times a day. During the medication
together with the treatment of primary lesions process, 2–4% sodium bicarbonate solution for
should be considered. Patient in Case 15 of this oral rinse and topical use of nystatin liniment
unit had medication history before oral erosion; should be administrated to avoid fungal infection.
therefore, drug allergic stomatitis initially, fol-
lowed by secondary coccigenic stomatitis, was
considered. 1.7 Oral Tuberculosis
Coccigenic stomatitis can occur in any part
of the oral mucosa, mainly for hyperemia and
local erosions or ulcers. The ulcers and erosions
are covered by a gray or yellowish-brown pseu-
domembrane, which is dense, smooth, and thick
that are not easily removed by gentle rubbing of
the lesion, leaving an erosive surface. So it is also
called membranous stomatitis. The surround-
ing mucosal hyperemia and swelling could be
observed, with obvious inflammatory reaction.
The patients show significant pain and increased
saliva, with bad breath, and lymphadenopathy
may be accompanied by systemic symptoms
Fig. 1.16 A 20 mm × 10 mm ulcer with undermined
such as fever. Coccigenic stomatitis may be the edges, clear boundary, and a granulating floor on the right
mixed infection that is caused by several kinds of mandibular buccal gingival sulcus
Coccus coexistence. If necessary, smear or bacte-
rial culture can be made to determine the main Case 16 Tuberculosis Ulcer
pathogens. Age: 46 years
Increased permeability of the mucosal bar- Sex: male
rier because of mucositis may result in microbial Chief Complaints:
dissemination into the bloodstream. Bacteremia 46-year-old man with ulcers on the right man-
poses a lethal threat to individuals with impaired dibular gingiva for 6 months
1 Oral Infectious Diseases 23
Mycobacterium tuberculosis infects all parts skin. The term “lupus” may be derived from
of the mouth. Oral tuberculous lesions include the rapacity and virulence of the disease. Tissue
tuberculous chancre, tuberculosis ulcers, and necrosis and defect resembling wolf bites can be
lupus vulgaris, among which the most common observed if combined with secondary infection.
symptoms are tuberculosis ulcers. The differential diagnoses of oral tubercu-
Tuberculous chancre (primary tuberculosis lous ulcers include recurrent aphthous ulcers,
syndrome) is rare and more widely in children traumatic ulcers, squamous cell carcinoma, lym-
and adolescents [55]. The dorsal surface of the phoma, metastatic tumors, and so on [56].
tongue is affected most commonly, followed by The diagnosis of oral tuberculosis is mainly
the buccal mucosa and lips. For those with nega- confirmed by the histopathological examination.
tive tuberculin skin test, oral mucosa may be the The lesion is consisted of small tubercles, the
first area invaded by Mycobacterium tuberculosis. center of which is unstructured caseous mate-
Following an incubation period of 2–3 weeks, a rial, surrounded by multiple epithelioid cells and
nodule occurs at the entry part and develops into Langhans-type giant cells, with dense inflamma-
an intractable painless ulcer with surrounding tory cellular infiltration. Proliferation of fibroblasts
induration, which is called tuberculous chancre. among tubercles can be observed. For confirma-
Enlarged cervical lymph nodes are common in tion and differential diagnosis, the bacilli could
primary infection. be identified by acid-fast stains and culture. In
Tuberculosis ulcer is the most common sec- addition, sputum culture, history of tuberculosis,
ondary tubercular lesion in the mouth. It tends tuberculin skin test, and chest X-ray would be ben-
to occur in the middle-aged and elderly, with the eficial in the diagnosis of oral tuberculosis [57].
tongue and hard palate as the predilection sites. Patients with oral tuberculosis should be
In addition, gums, floor of the mouth, lips, and advised to the department of infectious diseases
buccal mucosa can also be involved. The typi- for further inspection and antituberculosis ther-
cal oral lesions consist of a stellate ulcer with apy. Most oral lesions can be healed after receiv-
undermined edges and clear boundary. After ing generalized anti-TB treatment. Intralesional
removing purulent exudates of the superficial injection can be adopted for oral tuberculosis
ulceration, a granulating floor can be noticed. ulcers simultaneously: streptomycin 0.5 g, once
There are yellowish- brown miliary nodules at daily, or isoniazid 0.1 g, once daily or every other
the margin of the ulcers, which ruptured to form day, for ten times as a treatment course. Topical
dark red mulberry-like granulomas, following the therapeutic options are mainly symptomatic
increased ulcers accordingly. Irregular appearance treatment, including compound chlorhexidine
of tuberculosis ulcers is caused by variable loca- solution, oral rinse, three to four times daily. The
tions of these nodules. The pain degree varies, but patients still need to finish the course of anti-TB
the lingual ulcers are obviously painful [54]. If the treatment in the department of infectious dis-
patients have poor resistibility, lesions can appear eases, although oral lesions are healed.
at the junction of the oral mucosa and skin. It is
characteristic of superficial granulomatous ulcer
initially, followed by widespread tissue damages References
and deformation tendency, which is called tuber-
culosis cutis ulcerosa with poor prognosis. 1. Arduino PG, Porter SR. Herpes simplex virus type 1
infection: overview on relevant clinico-pathological
Lupus vulgaris are rare cutaneous tuberculosis features. J Oral Pathol Med. 2008;37(2):107–21.
skin lesions and appear mostly in adolescent or 2. Siegel MA. Diagnosis and management of recur-
children with good immune function. It begins rent herpes simplex infections. J Am Dent Assoc.
as painless reddish-brown nodules which is soft 2002;133(9):1245–9.
3. Gilmour TK, Meyer PA, Rytina E, et al. Antiepiligrin
with clear boundaries. On diascopy, it shows (laminin 5) cicatricial pemphigoid complicated and
characteristic “apple-jelly” color in the central exacerbated by herpes simplex virus type 2 infection.
area of the nodules, surrounded by pale normal Australas J Dermatol. 2001;42(4):271–4.
1 Oral Infectious Diseases 25
4. Itin PH, Lautenschlager S. Viral lesions of the 22. McMinn P, Stratov I, Nagarajan L, et al. Neurological
mouth in HIV-infected patients. Dermatology. manifestations of enterovirus 71 infection in chil-
1997;194(1):1–7. dren during an outbreak of hand, foot, and mouth
5. Cataldo F, Violante M, Maltese I, et al. Herpetic gingi- disease in Western Australia. Clin Infect Dis.
vostomatitis in children: the clinico-epidemiological 2001;32(2):236–42.
aspects and findings with acyclovir treatment. A 23. Chan KP, Goh KT, Chong CY, et al. Epidemic hand,
report of the cases of 162 patients. Pediatr Med Chir. foot and mouth disease caused by human enterovirus
1993;15(2):193–5. 71, Singapore. Emerg Infect Dis. 2003;9(1):78–85.
6. Wutzler P, Doerr HW, Farber I, et al. Seroprevalence 24. Lin TY, Twu SJ, Ho MS, et al. Enterovirus 71 out-
of herpes simplex virus type 1 and type 2 in selected breaks, Taiwan: occurrence and recognition. Emerg
German populations-relevance for the incidence of Infect Dis. 2003;9(3):291–3.
genital herpes. J Med Virol. 2000;61(2):201–7. 25. Chan LG, Parashar UD, Lye MS, et al. Deaths of chil-
7. Amir J. Clinical aspects and antiviral therapy in pri- dren during an outbreak of hand, foot, and mouth dis-
mary herpetic gingivostomatitis. Paediatr Drugs. ease in Sarawak, Malaysia: clinical and pathological
2001;3(8):593–7. characteristics of the disease. For the Outbreak Study
8. Kiderman A, Furst AL, Miller T, et al. How suc- Group. Clin Infect Dis. 2000;31(3):678–83.
cessfully do general practitioners diagnose her- 26. Puenpa J, Theamboonlers A, Korkong S, et al.
petic gingivo-stomatitis clinically. Br J Gen Pract. Molecular characterization and complete genome
2002;52(479):481–2. analysis of human enterovirus 71 and coxsackievi-
9. Arduino PG, Porter SR. Oral and perioral herpes rus A16 from children with hand, foot and mouth
simplex virus type 1 (HSV-1) infection: review of its disease in Thailand during 2008–2011. Arch Virol.
management. Oral Dis. 2006;12(3):254–70. 2011;156(11):2007.
10. World Health Organization. WHO model formulary 27. Frydenberg A, Starr M. Hand, foot and mouth disease.
for children. Geneva: WHO Press; 2010. Aust Fam Physician. 2003;32(8):594–5.
11.
Wilson JF. Herpes zoster. Ann Intern Med. 28. Bryant PA, Tingay D, Dargaville PA, et al. Neonatal
2011;154(5):ITC31-15; quiz ITC316. coxsackie B virus infection—a treatable disease. Eur
12. Schmader KE, Dworkin RH. Natural history and treat- J Pediatr. 2004;163(4–5):223–8.
ment of herpes zoster. J Pain. 2008;9(Suppl 1):S3–9. 29. Huang YC, Chu YH, Yen TY, et al. Clinical fea-
13. Weinberg A, Levin MJ. VZV T cell-mediated immu- tures and phylogenetic analysis of Coxsackievirus
nity. Curr Top Microbiol Immunol. 2010;342:341–57. A9 in northern Taiwan in 2011. BMC Infect Dis.
14. Levy O, Orange JS, Hibberd P, et al. Disseminated 2013;13:33.
varicella infection due to the vaccine strain of 30. Chen YJ, Chang SC, Tsao KC, et al. Comparative
varicella-zoster virus, in a patient with a novel genomic analysis of coxsackievirus A6 strains
deficiency in natural killer T cells. J Infect Dis. of different clinical disease entities. PLoS One.
2003;188(7):948–53. 2012;7(12):e52432.
15. Arvin AM. Varicella-zoster virus. Clin Microbiol Rev. 31. Park K, Lee B, Baek K, et al. Enteroviruses isolated
1996;9(3):361–81. from herpangina and hand-foot-and-mouth disease in
16. Pereira FP, Guskuma MH, Luvizuto ER, et al.
Korean children. Virol J. 2012;9:205.
Unilateral facial paralysis caused by Ramsay hunt 32. Yamashita T, Ito M, Taniguchi A, et al. Prevalence of
syndrome. J Craniofac Surg. 2011;22(5):1961–3. coxsackievirus A5, A6, and A10 in patients with her-
17. Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention pangina in Aichi Prefecture, 2005. Jpn J Infect Dis.
of herpes zoster: recommendations of the advi- 2005;58(6):390–1.
sory committee on immunization practices (ACIP). 33.
Reichart PA, Samaranayake LP, Philipsen
MMWR Recomm Rep. 2008;57(RR-5):1–30; quiz HP. Pathology and clinical correlates in oral can-
CE2-4. didiasis and its variants: a review. Oral Dis.
18. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine 2000;6(2):85–91.
to prevent herpes zoster and postherpetic neuralgia in 34. Williams DW, Kuriyama T, Silva S, Malic S, Lewis
older adults. N Engl J Med. 2005;352(22):2271–84. MA. Candida biofilms and oral candidosis: treat-
19. Kuter BJ, Weibel RE, Guess HA, et al. Oka/Merck ment and prevention. Periodontol 2000. 2011;55(1):
varicella vaccine in healthy children: final report of 250–65.
a 2-year efficacy study and 7-year follow-up studies. 35. Pfaller MA, Diekema DJ. Epidemiology of invasive
Vaccine. 1991;9(9):643–7. candidiasis: a persistent public health problem. Clin
20. Muppa R, Bhupatiraju P, Duddu M, et al. Hand, foot Microbiol Rev. 2007;20(1):133–63.
and mouth disease. J Indian Soc Pedod Prev Dent. 36. González GM, Elizondo M, Ayala J. Trends in spe-
2011;29(2):165–7. cies distribution and susceptibility of bloodstream
21. Chang ZR, Zhang J, Sun JL, et al. Epidemiological isolates of Candida collected in Monterrey, Mexico,
features of hand, foot and mouth disease in China, to seven antifungal agents: results of a 3-year (2004
2008–2009. Zhonghua Liu Xing Bing Xue Za Zhi. to 2007) surveillance study. J Clin Microbiol.
2011;32(7):676–80. 2008;46(9):2902–5.
26 X. Jin et al.
Keywords
Hypersensitivity ∙ Erythema multiforme ∙
Angioneurotic edema ∙ Erosion ∙ Bulla
Y. Zhou
State Key Laboratory of Oral Diseases, National
Clinical Research Center for Oral Diseases,
Department of Oral Medicine, West China Hospital
of Stomatology, Sichuan University,
Chengdu, Sichuan, China
X. Jin
College of Stomatology, Chongqing Medical
University, Chongqing Key Laboratory of Oral
Diseases and Biomedical Sciences,
Chongqing, China
Q. Chen (*)
Changjiang Scholars Program, Ministry of Education,
Beijing, China
State Key Laboratory of Oral Diseases,
National Clinical Research Center for Oral Diseases,
Department of Oral Medicine,
West China Hospital of Stomatology,
Sichuan University, Chengdu, Sichuan, China
e-mail: qmchen@scu.edu.cn
© Springer Nature Singapore Pte Ltd. and People’s Medical Publishing House 2018 27
Q. Chen, X. Zeng (eds.), Case Based Oral Mucosal Diseases,
https://doi.org/10.1007/978-981-13-0286-2_2
28 Y. Zhou et al.
Management:
c 1. Medication
Rp.: Prednisone acetate 5 mg × 35
Sig.: 25 mg p.o. q.m.
Loratadine 10 mg × 6
Sig.: 10 mg p.o. q.d.
Vitamin C 0.1 g × 100
Sig.: 0.2 g p.o. t.i.d.
Compound chlorhexidine solution 300 ml × 1
Sig.: rinse t.i.d.
Dexamethasome paste 15 g × 2
Fig. 2.1 (a) Multiple sizes of blisters on hard palate sur-
Sig.: topical use t.i.d.
rounding with hyperemia. (b) Diffuse hyperemia, edema, 2. Aerosol therapy
and blister seen on the inside of the upper lip. (c) Rp.: Dexamethasone sodium phosphate injec-
Hyperemia swelling on the left side of tongue abdomen tion 1 ml × 1
with blood blister and small dot erosion
Gentamycin sulfate injection 2 ml × 1
Vitamin B12 injection 1 ml × 1
Age: 46 years
Vitamin C injection 2.5 ml × 1
Sex: Male
Sig.: Aerosol therapy b.i.d.
Chief Complaints:
3. Drink more water and avoid using the sensiti-
46-year-old man with hyperemia and blister in
zation sticker.
oral cavity for one day
2 Oral Hypersensitive Reactive Diseases 29
a b
c d
Fig. 2.2 (a) Extensively erosion seen on the left buccal brane. (c) Extensively irregular erosion seen on the inside
mucosa, covering with yellow membrane. (b) Extensively of the upper lip, surrounding with hyperemia. (d) Multiple
erosion seen on the lower lip, covering with yellow mem- sizes of blisters on left toe, parts of which busted
pollen, spices, medicinal liquor, and so on. But if drugs and treating process; it is often cured within
it is similar to the onset and damage of allergic 10 days, but pigmentation is observed [2, 3]. The
medicamentosa stomatitis, then it also can be lips and perioral skin are its predilection site.
diagnosed as allergic medicamentosa stomatitis Allergic medicamentosa stomatitis is typical
(or allergic stomatitis). The patient of case 18 in delayed-type hypersensitivity (DTH) induced by
this unit denied taking drugs or special food, CD8+ T lymphocytes. Once CD8+ T lymphocytes
which can cause such symptoms, but according within the skin have been activated, it will not
to its characteristics of acute damage process and only kill the keratinocytes surrounding but also
the onset of clinical disease, it also can be diag- release cytokines such as IFN-γ and cytotoxic
nosed as allergic stomatitis. granules, recruit CD4+ T lymphocytes and neu-
Lots of drugs can cause allergic medicamen- trophil, and cause the damage location [4]. It has
tosa stomatitis, among which antipyretic analge- been reported that lymphocyte transformation
sics, sleeping sedatives, sulfa drugs, and antibiotic test (LTT) can be successfully used to identify
medicine are common to see. Some so-called drug allergens [5].
“safe” drugs such as vitamins and herbs may also Lyell syndrome, also called toxic epidermal
have allergenic. Corticosteroid drugs could also necrolysis, is a severe allergic medicamentosa
be allergen. Most of allergic medicamentosa sto- stomatitis. Bulla is widely distributed to the
matitis is type I allergy. The performance of aller- whole body and orifices such as the eyes, the
gic medicamentosa stomatitis is acute. Lesions nose, the vagina, the urethra, the anus, and the
can be seen in any part of oral cavity. Sometimes internal organs.
at the beginning of the disease, a larger blister The first thing to treat allergic medicamentosa
can be found on the mucous membrane. It often stomatitis is to find suspicious allergen and avoid
appears as large and irregular edema, congestion, it immediately. Common drugs include cortin
and erosion in the lip buccal, tongue, and palate (prednisone acetate 15–30 mg, q.m.), antihista-
with a large number of effusions. It is covered mine (Loratadine 10 mg p.o. q.d.), and vitamin C
with yellowish-white coating membrane in oral (100–200 mg t.i.d. p.o.). The course of treatment
cavity, with thick yellow-black scab shells on is about 1 week. Local drugs include 0.05% com-
lips. Sometimes patients feel discomfort and pound chlorhexidine solution or 0.01% dexa-
pain. Thus it is difficult to feed. methasone solution (rinse t.i.d.) hydropathical
Allergic medicamentosa stomatitis may be compress on lips or mouthwash, 0.1% triamcino-
accompanied with the skin and other parts of lone acetonide oral ointment, 0.1% dexametha-
mucosal lesions. It is common to see the lesions sone ointment, prednisone acetate injection, or
at the hand and foot, characterized by erythema, triamcinolone acetonide injection (1:5 dilution,
papule, bulla, and so on, among which circular topical use t.i.d.). Analgesic agents include com-
erythema is the most common. It is often accom- pound chamomile, lidocaine hydrochloride gel,
panied with itching but is painful. and compound benzocaine gel. Otherwise, coop-
If the pathogenic damage caused by allergic erating with excessive atomization treatment is
medicamentosa stomatitis happens in the same another choice, including prednisone acetate
position and form repeatedly, it is called fixed injection, vitamin C injection, and vitamin B12
drug eruption (FDE). Avoid using sensitized injection.
32 Y. Zhou et al.
c Management:
1. Medication
Rp.: Prednisone acetate 5 mg × 35
Sig.: 25 mg p.o. q.m.
Loratadine 10 mg × 6
Sig.: 10 mg p.o. q.d.
Vitamin C 0.1 g × 100
Sig.: 0.2 g p.o. t.i.d.
Compound chlorhexidine solution 300 ml × 1
Sig.: rinse t.i.d.
Fig. 2.4 (a) Erosions and crusts appeared on the lips and Dexamethasone paste 15 g × 2
corner of the mouth, multiple irregular erosions appeared Sig.: topical use t.i.d.
on the front of the dorsum. (b) Multiple target lesions of
erythema on palms. (c) Target lesions appeared on upper 2. Aerosol therapy
limbs Rp.: Dexamethasone sodium phosphate injec-
tion 1 ml × 1
Gentamycin sulfate injection 2 ml × 1
Age: 68 years Vitamin B12 injection 1 ml × 1
Sex: Female Vitamin C injection 2.5 ml × 1
Chief Complaints: Sig.: aerosol therapy q.d.-b.i.d. for 3 days
Oral erosive lesions for 7 days 3. Drink more water.
2 Oral Hypersensitive Reactive Diseases 33
surface. The oral lesions initially manifest with includes fever, pharyngitis, headache, and arthral-
edema, erythema, and erythematous macules, gias/myalgias, and rarely pneumonia, nephritis,
followed by the development of multiple vesicles or myocarditis. There is a risk of scarring of
and bullae that quickly rupture and result in pseu- mucosal lesions, which may lead to synechiae
domembrane formation. The lips tend to become formation of the conjunctiva or laryngeal and/or
swollen and show diagnostically distinctive vaginal strictures [13, 15].
bloody encrustations. Prodromal symptoms are Toxic epidermal necrolysis occurs in patients
usually absent in most instances of the EM minor, after receiving suspected stimulation: develop
but some patients may experience mild systemic fever, sore throat, and other precursor symptoms,
symptoms such as fever or chills [13]. followed by the development of blistering in 1–16
Erythema multiforme major spans a wide range days. Extensive blisters cover the body, with epi-
of clinical presentations that include mucocutane- dermal detachment of >30% of the body surface
ous involvement. Some authors have suggested which is similar to second-degree burns. More
that EMM differs from EMm by the involvement mucosa lesions are involved including oral mucosa,
of at least two different mucosal sites. The oral oropharynx, esophagus, conjunctiva, genitals, and
mucosa is the most commonly involved mucosal so on. The overall mortality rate of TEN is approxi-
surface, but any mucosal site can be affected in the mately 30–40% with poor prognosis [17].
course of EMM, including the epithelium of the A retrospective study of patients with recur-
trachea, bronchi, or gastrointestinal tract. The rent erythema multiforme showed that most
involvement of conjunctival and nasal mucosa is patients did not have a clear onset for recurrent
quite common too. In EMM oral lesions are larger EM. HSV infection rate is not high and not statis-
than that of EMm, and in more than 50% of cases, tically significant. Moreover, the effect for con-
patients have ulceration of all oral mucosal sur- tinuous antiviral and immunosuppressive therapy
faces, which are manifested by superficial irregu- is not clear [18].
lar erosions with red margins and are usually The diagnosis of erythema multiforme is mainly
covered by a yellow fibrinous pseudomembrane. based on the onset and recurrence, oral mucosal
The oral lesions often occur on the tongue, buccal lesions, and characteristic multiform skin lesions.
mucosa, and lips, with difficulties in mouth open- There is no specific diagnostic method, and the sig-
ing. After healing, the lesions don’t leave scars. nificance of pathological diagnosis mainly serves
The cutaneous involvement of EMM is usually to different EM from bullous disease.
less than 10% of the body surface but is generally First step for treating erythema multiforme
more severe and lasts 1–6 weeks [6, 13]. should be stopping suspicious drugs or allergens.
Stevens-Johnson syndrome is characterized Use of medication should be with caution. Avoid
by sudden onset of erosions of the mucous mem- using drugs unless urgently needed ones to pre-
branes (predominantly the oral mucosa, lips, and vent exposure to new allergens and aggravate
conjunctivae) together with widespread blister- allergic reactions. Treatment of mild erythema
ing of the skin. Stevens-Johnson affects up to multiforme is the same with drug-allergic stoma-
10% of the body surface and has mucosal involve- titis. Systemic medication includes glucocorti-
ment of two or more sites. SJS lesions extend to coid, such as prednisone 15–30 mg/d, q.m. for
involve the nasal cavity, pharynx, larynx, and 5–7 days; antihistamines such as oral administra-
esophagus. The oral lesions sometimes precede tion of loratadine 10 mg, 1 time/day, for 6 days;
skin involvement by several days. The skin and oral administration of vitamin C tablets,
lesions of SJS are primarily atypical flat target 0.2 g for 3 times/day. Topical use medications
lesions and macules rather than classic target include compound chlorhexidine solution or
lesions, are more widespread (rather than involv- 0.01% dexamethasone solution for hydropathic
ing only the acral areas), and can lead to signifi- compress and rinse, three times/day; 0.1% triam-
cant percutaneous loss of fluid and electrolytes. cinolone acetonide dental paste, 0.1% dexameth-
Nikolsky’s sign is positive. One third of affected asone ointment, prednisolone acetate injection,
individuals have a prodromal symptom that and intralesional triamcinolone acetonide (TA)
2 Oral Hypersensitive Reactive Diseases 35
Management:
1. Medication
Rp.: Prednisone acetate 5 mg × 35
Sig.: 25 mg p.o. q.m.
Vitamin C 0.1 g × 100
b Sig.: 0.2 g p.o. t.i.d.
Compound chlorhexidine solution 300 ml × 1
Sig.: rinse t.i.d.
Dexamethasone paste15 g × 2
Sig.: topical use t.i.d.
2. Aerosol therapy
Rp.: Dexamethasone sodium phosphate injec-
tion 1 ml × 1
Gentamycin sulfate injection 2 ml × 1
Vitamin B12 injection 1 ml × 1
Vitamin C injection 2.5 ml × 1
Sig.: aerosol therapy q.d.-b.i.d. for 3 days
Fig. 2.6 (a) Widespread congestion and irregular ero-
sions on the lower lip, with white pseudomembrane and
3. Transferring the patient to the internal medi-
plenty of inflammatory exudate. (b) Widespread erosions cine department in a general hospital immedi-
on the dorsum of the tongue, with white pseudomembrane ately to exclude the possibility of toxication.
and plenty of inflammatory exudate
36 Y. Zhou et al.
Management:
1. Medication
Rp.: Zhongtong’an capsules 0.28 g × 48
Sig.: 0.56 g p.o. t.i.d.
Dexamethasone sodium phosphate injec-
tion 1 ml × 5
b
Sig.: 50-fold dilution rinse t.i.d.
Compound chlorhexidine solution 300 ml × 1
Sig.: rinse t.i.d.
Dexamethasone paste 15 g × 2
Sig.: topical use t.i.d.
2. Aerosol therapy
Rp.: Dexamethasone sodium phosphate injec-
tion 1 ml × 1
Gentamycin sulfate injection 2 ml × 1
Vitamin B12 injection 1 ml × 1
Fig. 2.7 (a) Congestion and erosions covered with white Vitamin C injection 2.5 ml × 1
pseudomembrane on the buccal gingival margin. (b) Sig.: aerosol therapy q.d.-b.i.d. for 3 days
White lesions with fine wrinkles appeared on the left buc-
cal mucosa
Case 23 Allergic Contact Cheilitis
Age: 35 years
Sex: Female
Chief Complaints:
Gingival erosion for 3 days
History of Present Illness:
Three days ago, her tongue appeared to have
“mung bean”-sized ulcers with pain, which is
rinsed with white spirit to treat it, contributing to
white lesion in the whole oral cavity and too
much pain when eating.
Past Medical History: None
Allergy: None Fig. 2.8 Swelling and congestion with fine erosions and
Physical Examination: thin crusts on the lips
The buccal gingival margin in the oral cavity
developed congestion and erosion covered with Age: 42 years
white pseudomembrane that can be wiped. White Sex: Female
lesions with fine wrinkles were observed on the Chief Complaints:
left buccal mucosa (Fig. 2.7). Lips swelling for 1 week after tattooing on them
2 Oral Hypersensitive Reactive Diseases 37
treatment of hereditary angioedema. Rev Alerg Mex. pulmonary thromboembolism. Int Immunopharmacol.
2011;58(2):112–9. 2011;11(9):1384–5.
24. Warnock JK, Knesevich JW. Adverse cutaneous
26. Mishra B, Sahoo S, Sarkar S, et al. Clozapine-
reactions to antidepressants. Am J Psychiatry. 1988; induced angioneurotic edema. Gen Hosp Psychiatry.
145(4):425–30. 2007;29(1):78–80.
25. Ekmekci P, Bengisun ZK, Kazbek BK, et al.
27. Akkaya C, Sarandol A, Aydogan K, et al. Urticaria and
Oropharyngeal angioneurotic edema due to recombi- angio-oedema due to ziprasidone. J Psychopharmacol.
nant tissue plasminogen activator following massive 2007;21(5):550–2.
Ulcerative Lesions of the Oral
Mucosa 3
Yu Zhou, Xiaoying Li, Xin Jin, and Qianming Chen
Y. Zhou
State Key Laboratory of Oral Diseases, National
Clinical Research Center for Oral Diseases,
Department of Oral Medicine, West China Hospital
of Stomatology, Sichuan University,
Chengdu, Sichuan, China
X. Li Fig. 3.1 A rounded ulcer appeared on the inner side
State Key Laboratory of Oral Diseases, National mucosa of the upper lip, with the characteristics of “red,
Clinical Research Center for Oral Diseases, yellow, concave, tenderness”
Department of Oral Medicine, West China Hospital
of Stomatology, Sichuan University,
Chengdu, Sichuan, China Age: 46 years
X. Jin Sex: Male
College of Stomatology, Chongqing Medical Chief Complaints:
University, Chongqing Key Laboratory of Oral Recurrent oral ulcer for 6 years, aggravation
Diseases and Biomedical Sciences,
Chongqing, China 6 months, recurrence 3 days
History of Present Illness:
Q. Chen (*)
Changjiang Scholars Program, Ministry of Education, The patient was recurring oral ulcers for 6 years.
Beijing, China The oral ulcer always recurs once a month with
State Key Laboratory of Oral Diseases, National one ulcer at a time, lasting 5–6 days. For the last
Clinical Research Center for Oral Diseases, 6 months, the oral ulcer recurred in every
Department of Oral Medicine, West China Hospital 2 weeks, 1–2 ulcers every time, and lasted for
of Stomatology, Sichuan University,
1 week. Three days ago, there was an ulcer
Chengdu, Sichuan, China
e-mail: qmchen@scu.edu.cn recurring in the inner side mucosa of the upper
© Springer Nature Singapore Pte Ltd. and People’s Medical Publishing House 2018 43
Q. Chen, X. Zeng (eds.), Case Based Oral Mucosal Diseases,
https://doi.org/10.1007/978-981-13-0286-2_3
44 Y. Zhou et al.
a b
c d
Fig. 3.2 (a) Dozens of small rounded ulcers appeared on Dozens of small rounded ulcers appeared on the soft pal-
the inner side mucosa of the lower lip, presenting like ate. (d) Dozens of small rounded ulcers appeared on the
stars in the sky. (b) Dozens of small rounded ulcers left buccal mucosa
appeared on the right buccal mucosa and right tongue. (c)
3 Ulcerative Lesions of the Oral Mucosa 45
1 . History of recurrence
2. Dozens of small ulcers presenting like stars in Fig. 3.3 Two large and deep ulcers on the left soft palate,
the sky with the characteristics of “red, yellow, concave,
tenderness”
Management:
Age: 42 years
1. Medication Sex: Male
Rp.: Prednisone acetate 5 mg × 25 tablets Chief Complaints:
Sig.: 25 mg p.o. q.m. Recurrent oral ulcer for 6 years, aggravation for
Zhongtong’an capsules 0.28 g × 48 tablets 1 year
Sig.: 0.56 g p.o. q.d. History of Present Illness:
Compound vitamin B 100 tablets The patient was recurring oral ulcers for 6 years.
Sig.: two tablets p.o. t.i.d. The oral ulcer always recurred one at a time
Dexamethasone sodium phosphate injec- occasionally, lasting 2–3 days. For the last
tion 1 ml × 5 1 year, the oral ulcer recurred frequently, 2–3
Sig.: 1:50 dilution rinse t.i.d. times in every month, 2–3 ulcers every time, and
Compound chlorhexidine solution lasted for 10–20 days, with the intermission of
300 ml × 1 2–3 days. Twenty days ago, the oral ulcer
Sig.: rinse t.i.d. recurred and had yet to heal. He didn’t have any
Dexamethasone paste 15 g × 1 medical history of ocular disease and genital
Sig.: topical use t.i.d. ulcers.
2. Aerosol therapy Past Medical History: None
Rp.: Dexamethasone sodium phosphate injec- Allergy: None
tion 1 ml × 1 Physical Examination:
46 Y. Zhou et al.
ficiency virus (HIV) infection, neutropenia, and RAU are conventionally classified, based on
vitamin B12, folic acid, and zinc deficiencies. their size, duration, and presence or absence of
These patients need to actively improve the sys- scarring after healing into minor, major, and her-
temic factors. However, neither iron nor vitamin petiform ulcers [8]. Minor aphthae comprise
supplementation has been shown to enhance the about 75–85% of RAU and present as one to five
resolution of ulcers [5, 6]. painful ulcers each less than 1.0 cm in diameter
Microbial infection is the incidence of RAU or that last for 10–14 days and heal spontaneously
secondary infection and is still controversial. without scarring. Regional lymphadenopathy
There are studies to indicate that RAU may be a may rarely be present depending on the severity
T-cell-mediated response to antigens of and number of lesions. The process is self-lim-
Streptococcus sanguis, which cross-react with ited but recurs with high variability. In some
the mitochondrial heat shock protein and induce patients, ulcer activity is almost continuous with
oral mucosal damage [4]. The evidence that vari- new ulcers developing as old ones heal.
ous bacteria and viruses can cause ulcers is not Major aphthae (periadenitis mucosa necrotica
very reliable. recurrens) comprise about 10–15% of cases.
Anxiety and stress have been associated with Ulcers are greater than 1.0 cm in diameter,
the onset and recurrence of RAU. There are deeper, and more painful and may take up to
reports that by avoiding allergic food (e.g., choc- weeks or longer to heal. Dysphagia and fever are
olate, wheat flour, tomato, strawberry, and pea- common. Scarring is common (Fig. 3.5). Ulcers
nut), the clinical symptoms of RAU can be occur on the posterior oral cavity where they
improved. Because nicotine may promote kera- may interfere with eating. Ulcers may be sec-
tinized mucosa, thus smoking can induce ondarily infected with bacteria or fungi. When it
RAU. Hormonal changes related to the menstrual appears in teenagers, it is known as juvenile peri-
cycle may also be related to RAU, but the clinical glandular aphtha, characterized by great and
evidence is scarce. What’s more, RAU develop- deep ulcer. The inflammation of mucosa sur-
ment is related to several chemical compounds rounding the ulcer is not obvious. And the ulcer
and medications. These include nonsteroidal always recurs on the tip of buccal pad and lateral
anti-inflammatory agents, nicorandil, beta-block- and tip of the tongue in the boys. Patients often
ers, angiotensin-converting enzyme inhibitors, bite the cheek or tongue due to the symptom of
antiarrhythmic drugs, and sodium lauryl sulfate itchiness.
(a detergent in some oral healthcare products) [5, Herpetiform ulcers are seen in 5–10% of cases
6]. and present as crops (as many as 100) of 1–3 mm
RAU present, as well as demarcated, oval or ulcers that heal within 10–14 days without scar-
round recurrent oral ulcers with a white or yellow ring. They may appear anywhere throughout the
pseudomembrane and a surrounding erythema-
tous halo. They may rarely appear initially as red
macules or papules but quickly form the classic
ulcer. Especially for longer-lasting ulcers, a gray
membrane may replace the central yellow pseu-
domembrane. The ulcers are painful and interfere
with eating and speaking. A prodromal burning
or tingling sensation may occur. Aphthous ulcers
have a predilection for lining mucosa and spe-
cialized mucosa, like the labial mucosa, buccal
mucosa, floor of the mouth, soft palate, ventral
and lateral tongue, and oropharynx [7]. Generally
ulcers do not occur on the masticatory mucosa Fig. 3.5 The white mucosa on the right soft palate is
like the hard palate and gingiva. MaRAU scar after healing
3 Ulcerative Lesions of the Oral Mucosa 49
oral cavity except masticatory mucosa. Women and edge, infiltration and hard in quality of sur-
are more frequently affected. rounding tissue, and cauliflower-like of the bot-
The diagnosis of RAU is based on the charac- tom, without recurrence and self-healing. These
teristics of recurrence, periodicity, and self-heal- characteristics are different from the characteris-
ing and the features of “painful round hollow tics of RAU.
ulcers with white or yellow pseudomembrane It is noteworthy that RAU is also available for
and a surrounding erythematous halo.” RAU is the extraintestinal manifestations of inflamma-
not cancerous ulcer and also has no malignant tory bowel disease (Figs. 3.7 and 3.8). The
potential. However, for the deep, large, long inflammatory bowel disease refers to ulcerative
course and different with the past of the ulcer, colitis and Crohn’s disease. The investigation
we should be vigilant. Conduct a biopsy to rule should be carried out in inflammatory bowel dis-
out cancerous ulcer or other diseases when ease, if the RAU patients have persistent or recur-
necessary. Cancerous ulcer (Fig. 3.6) occurs in rent diarrhea, purulent stools accompanied by
elderly patients, characterized by uneven depth abdominal pain and tenesmus.
Fig. 3.6 Ulcer with unclear border and cauliflower-like Fig. 3.7 Deep ulcer with 1cm in diameter on the left pos-
surface on the right root of the tongue terior maxillary palatal gingiva, surrounding with small
ulcers
Because of the multiple and complex factors injections (like triamcinolone acetonide injec-
of RAU, it still has no definitive treatment [5]. tion, compound betamethasone injection).
The goals of therapy are to decrease frequency of For patients with minor RAU, who had only a
recurrence, prolong the interval, decrease pain, few days or no significant intermittent periods,
and promote healing. and with a major RAU or a herpetiform ulcer,
Commonly used systemic agents for the treat- they can take prednisone (sig.: 15–30 mg p.o.
ment of RAU include glucocorticoid (like predni- q.m), 1–2 weeks as a course, or thalidomide
sone), immunosuppressant (like thalidomide), (Sig.: 50 mg p.o. q.n.), 10–14 days as a course,
Chinese patent medicine with immunosuppres- together with vitamins, trace elements, and topi-
sive effect (like tripterygium glycoside tablet, cal agents. For the patients with deep and pro-
tripterygium hypoglaucum tablet), and immuno- longed unhealed ulcers, cancer was excluded,
modulator (like thymosin, transfer factor, licor- eliminating malignant lesion; we suggest patients
zine granules). Commonly used topical agents take multiple-point injection of small dose at the
include gargle (chlorhexidine solution, dexa- base of the ulcer with triamcinolone acetonide
methasone solution), paste (like amlexanox injection plus equal water for injection or 2%
paste, dexamethasone paste, triamcinolone ace- lidocaine.
tonide dental paste, dexamethasone ointment), For patients with poor constitution, reduced
spray (like recombinant human epidermal growth immune function, and minor RAU, they can
factor spray, recombinant bovine basic fibroblast choose thymopeptide enteric-coated tablets (Sig.:
growth factor spray), lozenge (like penicillin V 20 mg p.o. q.d. or b.i.d), 1–2 months as a course;
potassium lozenge), patch (amlexanox patch, or transfer factor capsules (Sig.: 6 mg p.o. b.i.d. or
dexamethasone patch), gelatin (like compound t.i.d), 1–2 months as a course; or use Bacillus
chamomile and lidocaine hydrochloride gel, Calmette-Guerin polysaccharide nucleic acid
compound benzocaine gel, recombinant bovine (Sig.: 1 ml i.m. q.o.d.), 18 times as a course. The
basic fibroblast growth factor gel, recombinant above drugs can be used in combination with the
human epidermal growth factor hydrogel), and use of vitamins, trace elements, and topical agents.
a b
Fig. 3.9 (a) Dozens of rounded ulcer appeared on the after needling. (d) Round and small ulcers appeared on
inner side mucosa of lower lip and tongue tip, with the the genitalia, with the characteristic of “red, yellow, con-
characteristics of “red, yellow, concave, tenderness”. (b) cave, tenderness”. (e) Round and small ulcers appeared on
Acneiform lesions appeared on the perioral skin. (c) The the perianal region, with the characteristic of “red, yellow,
acupuncture point in the hand emerged red and swollen concave, tenderness”
3 Ulcerative Lesions of the Oral Mucosa 51
c d
Fig. 3.9 (continued)
1. Recurrent oral ulcers and history of genital tory disease [12]. Our current understanding is
ulcers that an exogenous trigger(s) modulating the
2. Acnes on the facial skin and redness and
immune system in a genetically susceptible host
swelling around the skin acupuncture points lead to disease expression in BD [13]. The exog-
enous trigger(s) include viruses, bacteria, and
Management: heat shock proteins [14]. BD’s regional differ-
ences are obvious and often occur in Asia and the
1. Medication Middle East; many of the local patients with
Rp.: Thalidomide 25 mg × 40 tablets recurrent aphthous ulcers well develop to BD and
Sig.: 75 mg p.o. q.n. often involve multi-systems with severe symp-
Zhongtong’an capsules 0.28 g × 48 toms. However, in Western Europe and North
tablets America, many patients have RAU, but very few
Sig.: 0.56 g p.o. q.d. of patients have BD; the symptoms are mild, and
Compound vitamin B 100 tablets the prognosis is well [6].
Sig.: two tablets p.o. t.i.d. BD’s clinical manifestations include common
Dexamethasone paste 15 g × 1 signs and rare signs of two categories. Common
Sig.: topical use t.i.d. signs include oral, genital, skin, eye, and other
symptoms. Rare symptoms include joint, cardio-
Subsequent Management: vascular, nervous, digestive, urinary, and other
After disease is controlled, Bacillus Calmette- systemic diseases.
Guerin polysaccharide nucleic acid (BCG-PSN), Oral ulcerations are seen in almost all patients
intramuscular injection, 1 ml each time, every of BD, mostly minor, or herpetiform RAU also
other day can be used. If the disease is poorly can be major.
controlled, increase dose of thalidomide as The incidence of genital ulcers accounts for
appropriate to 100 mg each time; or replacement about 75% of patients with BD. It is also often
with tripterygium hypoglaucum tablet, 2 g each recurrent but with fewer occurrences and fewer
time, three times a day; or replacement with numbers. The ulcers are often seen in the labia,
tripterygium glycoside tablet could be penis, glans, and scrotum and can also be found
considered. in the perianal, etc. [15].
The incidence of skin lesions in patients with
[Review] Behcet’s Disease BD is second only to oral ulcers, including:
Behcet’s disease is a systemic disease caused by
an unknown etiology, with vasculitis as the path- 1. Erythema nodosums are frequently seen at the
ological basis, with the features of chronic pro- lower limbs in the form of several 1–2-cm-
gressive, recurrent, system damage and so on [9]. diameter erythema lesions and are of moder-
The etiology of Behcet’s disease and the per- ate hardness and painful when touched. The
formance of oral ulcers are similar to recurrent erythema lesions usually spend 1 month to
aphthous ulcers, but most scholars still believe self-heal, and the new erythema lesions would
that the two are different independent diseases. emerge.
The specific etiology of Behcet’s disease is also 2. Folliculitis-like lesions are mainly seen at the
not clear; some scholars believe that it is a sys- head, the face, the upper chest, and the upper
temic vasculitis with an unknown etiology affect- back and present as papulopustular lesions
ing the small and large vessels of the venous and with wide flush around.
arterial systems [10]. Behcet’s disease has a 3. Skin prick reaction is a nonspecific hyperre-
genetic basis; the most consistent genetic associ- activity of the peripheral vessel to trauma
ation has been with HLA-B51, which explains and is a BD’s characteristic performance
only about 20% of the disease heritability [11]. It having a diagnostic value and accounting for
is also in vogue to group BD with autoinflamma- about 65%.
3 Ulcerative Lesions of the Oral Mucosa 53
Management:
1. Medication
Rp.: Compound chlorhexidine solution
300 ml × 1
Sig.: rinse t.i.d.
b 2% sodium bicarbonate solution
250 ml × 1
Sig.: rinse t.i.d.
Dexamethasone paste 15 g × 2
Sig.: topical use t.i.d.
Recombinant human epidermal growth
factor hydrogel 20 g × 1
Sig.: topical use q.d.
2. Aerosol therapy
Rp.: Dexamethasone sodium phosphate injec-
Fig. 3.11 (a) Widespread irregular hyperemia and ero- tion 1 ml × 1
sions appeared on the palate, covered with yellow-white Gentamicin sulfate injection 2 ml × 1
pseudomembrane. (b) Irregular hyperemia and erosions Vitamin B12 injection 1 ml × 1
appeared on the lower lip, covered with yellow-white
Vitamin C injection 2.5 ml × 1
pseudomembrane
Sig.: aerosol therapy b.i.d.
treatment is based on the location and type of The treatment of radiation stomatitis is
malignant disease and whether or not radiother- mainly through local therapy to promote erosion
apy will be used on its own or in combination healing and anti-infection and relieve pain and
with other treatment options. The severity of oral dry mouth. Local therapies include aerosol ther-
complications is related to the daily and total apy, g argarism rinse, and topical use or hydro-
cumulative dose of radiation, the volume of irra- pathic compress. Medications include: 0.05%
diated tissue, and use of concurrent radiation- compound chlorhexi-dine solution or 0.01%
sensitizing drugs [18–20]. dexamethasone solution, soak or mouthwash,
Radiation stomatitis has a clear etiology and is three times a day; 0.1% triamcinolone acetonide
associated with radiation. Its specific mechanisms dental paste or 0.1% dexamethasone ointment,
still have different views. High-energy radiation coat, three times a day; recombinant human epi-
can induce the damage and necrosis of basal kera- dermal growth factor hydrogel (or spray),
tinocytes, resulting in the gradual decrease of the recombinant bovine basic fibroblast growth fac-
number of epithelial cells. As radiotherapy contin- tor gel, or recombinant human acidic fibroblast
ues, a temporary steady state between death and growth factor spray, once or twice a day; analge-
regeneration of mucosal cells could occur because sic can chose compound chamomile and lido-
surviving cells are produced at an increased rate. caine hydrochloride gel and compound
However, cell regeneration often cannot keep up benzocaine gel, or chose 2% lidocaine to rinse
with the rate of cell death, resulting in some or after diluting with water. In addition, ultrasonic
complete denudation of the mucosa, presenting a aerosol therapy is also suggested, medications
variety of clinical manifestations [21]. In addition include dexamethasone sodium phosphate injec-
to the abovementioned direct tissue injury, the oral tion, gentamicin sulfate injection, vitamin C
microbial flora is also contributed to radiotherapy- injection, and vitamin B12 injection, twice a
induced mucositis. Some scholars believe that day. If the aerosol therapy lasts for more than 3
endotoxins produced by gram-negative bacilli are days, it needs to combine with 2–4% sodium
potent mediators of the inflammatory process. bicarbonate solution to rinse and nystatin lini-
Resident bacteria on ulcerated surfaces can ment to topical use, to prevent secondary fungal
amplify inflammatory response and enhance local infection.
injury. Mucosal barrier injury associated with
mucositis promotes adherence and invasion by
oral organisms [17, 22]. 3.4 Traumatic Mucosal
According to the course of the disease, radia- Hematoma and Traumatic
tion stomatitis can be divided into acute and Ulceration
chronic. Acute lesions occur early in the course
of radiotherapy, lasting up to 2–3 weeks after Case 31 Traumatic Mucosal Hematoma
radiotherapy. Chronic or advanced symptoms can
occur at any time after radiotherapy, ranging
from weeks to years. Clinical symptoms of radia-
tion-induced mucositis include oral intense pain,
odynophagia, dysphagia, anorexia, and difficulty
speaking. Signs of radiation-induced mucositis
might include oral mucosa hyperemia, erosion
and ulceration formation, pseudomembrane cov-
ered, easy bleeding, and obvious tenderness.
These complications often seriously affect the
quality of life and the radiotherapy effect of
patients and sometimes can be forced to change
the treatment or termination of radiotherapy Fig. 3.12 Mucosal hematoma on the left lateral part of
because it is difficult to tolerate [23, 24]. the tongue
56 Y. Zhou et al.
a b
Fig. 3.14 (a) Residual roots of C5, C6, and C7 with sharp edges. An ulcer on nearby ventrum of the tongue with white
margins. (b) Sharp edges of residual roots were removed, and after a week, the patient returned with the ulcer healed
2. Medication Management:
Rp.: Compound chlorhexidine solution
300 ml × 1 1. Medication
Sig.: rinse t.i.d. Rp.: Compound ulcer paste 15 g × 1
Dexamethasone paste 15 g × 1 Sig.: topical use t.i.d.
Sig.: topical use t.i.d. Recombinant human epidermal growth
3. The patient is advised to return to clinic after factor hydrogel 20 g × 1
a week, and excision biopsy is needed if Sig.: topical use q.d.
necessary. 2. His parents were advised to use a softer paci-
fier and adjust their posture when feeding.
Case 34 Traumatic Ulcer (Bednar Ulcer)
Case 35 Traumatic Ulcer (Rida-Fede Ulcer)
dibular bilateral central incisors was sharp, and boy scratched the dorsum of his tongue repeat-
the lingual frenum was short (Fig. 3.16). edly because of the itchy tongue. After that his
Diagnosis: tongue began to ache. Medication from other
Traumatic ulcer (Riga-Fede ulcer) hospital which was unknown was ineffective.
Diagnosis Basis: Past Medical History: None
Allergy: None
1. The ulcer happened to a child on his lingual Physical Examination:
frenum. A 3 mm × 5 mm ulcer was seen on the left dor-
2. The lingual frenum was short, and the incisal sum of the tongue. It was sunken and coated with
ridge of the opposite newly erupted incisors yellow pseudomembrane. The ulcer is tough
was sharp. when touched, and its nearby mucosa was whit-
ened (Fig. 3.17).
Management: Diagnosis:
Traumatic ulcer (factitial ulcer)
1 . Grind C1 and D1 to remove the sharp edges. Diagnosis Basis:
2. Medication
Rp.: Compound chlorhexidine solution 1 . The ulcer occurred in an active little boy.
300 ml × 1 2. The history of self-injury where matched up
Sig.: topical rinse t.i.d. with the location of the ulcer.
Dexamethasone paste 15 g × 1
Sig.: topical use t.i.d. Management:
Recombinant human epidermal growth
factor hydrogel 20 g × 1 1. Medication
Sig.: topical use q.d. Rp.: Dexamethasone paste 15 g × 1
Sig.: topical use t.i.d.
Case 36 Traumatic Ulcer (Factitial Ulcer) Recombinant human epidermal growth
factor hydrogel 20 g × 1
Sig.: topical use q.d.
2. The patient was advised not to scratch his
tongue.
Hematomas caused by bites often happen on 1. Decubital Ulcer: Decubital ulcer usually
the buccal mucosa near the corner of the mouth happens to the elderly. It is caused by chronic
and occlusion line. They also tend to happen on stimulation by residual root or crown and the
the lateral part of the tongue. The edges of cor- bad prosthesis. It can also be caused by
responding teeth are usually sharp. After the chronic stimulation by massive calculus on
hematoma ruptures, an erosion or ulcer forms, the lingual side of mandibular anterior teeth.
and it will soon heal. The ulcer usually reaches submucosal layer.
Traumatic mucosal hematoma should be dis- The margin of the ulcer is slightly swollen,
tinguished from mucosal hematoma caused by and the color is pale. It is often accompanied
idiopathic thrombocytopenic purpura. Hematoma by pain [25].
caused by ITP is usually multiple. Patients with 2. Bednar Ulcer: Bednar ulcer which is caused
hematomas caused by ITP do not have obvious by sucking thumbs or hard pacifiers often hap-
history of eating too fast. Blood routine often pens to infants. It usually occurs on the hard
shows extremely low level of blood platelet, and palate or mucosa near pterygoid hamulus. If it
coagulation function test is often abnormal [2]. happens bilaterally, the lesion often is sym-
Besides ITP, traumatic mucosal hematoma metrically distributed. The ulcer is superficial.
should be distinguished from mucosal hematoma The infant usually cries a lot and refuses to
caused by blood system diseases like eat.
hemophilia. 3. Riga-Fede Ulcer: Riga-Fede ulcer refers to
Under the premise of ruling out blood system ulcers which happen to children on the lingual
diseases, for large unruptured hematomas, we frenum. It is caused by longtime friction
could use sterilized syringes to suck out blood between short lingual frenum and sharp newly
or cut the wall of hematoma to let out blood. For erupted central incisors. Congestion, swell-
small ones, no treatment is required. For those ing, and ulceration can be seen on the lingual
ruptured hematomas, we could use sterilized frenum. The longtime unhealed ulcer tends to
surgical scissors to trim the residual wall of the transform into granulomatous ulcer, which
hematoma and then proceed to topical treatment often toughens when touched [26] (Fig. 3.18).
of ulcer. 0.05% chlorhexidine solution or 0.01% 4. Factitial Ulcer: Factitial ulcer refers to the
dexamethasone solution can be used to rinse the ulcer which is caused by bad habits including
ulcer three times a day. Recombinant human biting lips or buccal mucosa and using sharp
epidermal growth factor hydrogel or spray can objects like pencils or chopsticks to stab buc-
also be applied to the ulcer once a day. 0.1% cal mucosa. It appears mostly in active chil-
triamcinolone acetonide oral paste or 0.1% dren or children suffering from attention
dexamethasone ointment is suggested three
times a day. To relieve pain, compound chamo-
mile and lidocaine hydrochloride gel are recom-
mended. Besides, if the wound surface is quite
large after the hematoma ruptures, aerosol ther-
apy is advised which includes dexamethasone
sodium phosphate injection, gentamicin sulfate
injection, vitamin C injection, and vitamin B12
injection (one each).
Traumatic ulceration is a series of mucosal
lesions which are caused by physical, m
echanical,
or chemical stimulus. According to different trau-
matic stimulus, traumatic ulceration is divided
into these types: Fig. 3.18 Riga-Fede ulcer on the child’s ventral tongue
3 Ulcerative Lesions of the Oral Mucosa 61
deficit hyperactivity disorder. The ulcer is 0.01% dexamethasone solution can be used to
usually deep. The longtime unhealed ones rinse the ulcer three times a day. Compound
have slightly tough base or granulation tissue. ulcer paste could be applied, three times per
The pain is often not obvious, and sometimes, day. Recombinant human epidermal growth
it is accompanied by itchiness. factor hydrogel or spray can also be applied
5. Chemically Burnt Ulcer: It is usually caused to the ulcer once a day. (If the ulcer tends to
by chemical stimulus including taking strong cancerate, it must be used with caution.) 0.1%
acid or alkali by mistake, iodophenol over- triamcinolone acetonide oral paste and 0.1%
flowing into the mouth during dental treat- dexamethasone ointment or prednisolone
ment, taking aspirin or alcohol, and applying acetate injection and triamcinolone acetonide
propolis due to toothache. On the surface of injection (in 1:5 dilution level) are suggested
the ulcer, there are usually pieces of fragile three times a day. Steroid preparations must be
membrane. The ulcer is often superficial, and used with caution when treating children below
the pain is obvious. the age of 6. But if the condition of the patient
6 . Thermally Burnt Ulcer: It is usually caused is rather severe, steroid preparations can be
by drinking hot water or drinks. It mostly topically used as appropriate. To relieve pain,
manifests as large scale of erosion or superfi- compound chamomile and lidocaine hydro-
cial ulceration with sharp pain. chloride gel or compound benzocaine gel is
recommended. After a series of therapies men-
Ulcers caused by chemical or thermal burns of tioned above, if the ulcer is deep and large and
wide range can also be diagnosed as primary con- longtime unhealed, especially those that hap-
tact stomatitis. pened to the elderly, biopsy should be taken
Traumatic ulceration is easily diagnosed into consideration to rule out the possibility of
according to definite cause and history of disease. cancerization.
Usually the location and the shape of ulcer cor-
respond to the stimulating factor. And there is no
recurrent history. After removing the stimulus, 3.5 Necrotizing Sialometaplasia
the ulcer will soon improve or heal.
The priority of the treatment of traumatic Case 37 Necrotizing Sialometaplasia
ulceration is removing the stimulus, which
includes extracting the residual root or crown,
grinding or using composite resin to cover the
sharp cusp or marginal ridge, modifying the bad
prosthesis, as well as correcting bad habits like
biting lips or buccal mucosa. For Bednar ulcer,
the feeding pattern of the infant should be
changed. Softer pacifiers, little spoon instead of
bottle-feeding, and pacifiers with larger holes
will all help improve the ulcer. For Riga-Fede
ulcer, besides changing feeding pattern into
spoon-feeding, ankylotomy is another option to
correct short lingual frenulum. When the lesion is Fig. 3.19 Oral ulcer on the left side of the hard palate
quite severe and the conventional treatment is with well-defined borders and raised margins
ineffective, extraction of the incisors or excision
of the ulcer could be used. Age: 70 years
After removing the stimulating factor, there Sex: Male
are several drugs as alternatives for topical Chief Complaint:
treatment. 0.05% chlorhexidine solution or A burning sensation on the palate for 10 days
62 Y. Zhou et al.
sialometaplasia resolves spontaneously, and the treatment such as the expanded resection of NSM
lesion heals by secondary intention within lesions at the same time. Rely mainly on intraop-
3–12 weeks [33]. However, a number of cases erative frozen section examination at this
manifested as a fluctuant mass on the palate. A moment, and pay attention to regular follow-up
biopsy was performed, and the diagnosis of NSM observation.
was rendered; no further treatment was performed,
and the lesion healed completely [34, 35].
Histopathological examination is necessary
for the diagnosis of necrotizing sialometaplasia,
References
because the clinical features of this condition 1. Akintoye SO, Greenberg MS. Recurrent aphthous
can mimic other malignant diseases, particularly stomatitis. Dent Clin North Am. 2015;49(1):31–47,
squamous cell carcinoma. Histopathological fea- vii-vii.
tures of NSM include pseudoepitheliomatous 2. Sawair FA. Recurrent aphthous stomatitis: do we
know what patients are using to treat the ulcers. J
hyperplasia of the overlying epithelium; the squa- Altern Complement Med. 2010;16(6):651–5.
mous metaplasia of minor salivary gland ducts 3. Lewkowicz N, Lewkowicz P, Banasik M, et al.
and acini may contain apoptotic cells and areas of Predominance of type 1 cytokines and decreased
inflammation as well as mucin spillage. The pres- number of CD4+CD25+ high T regulatory cells in
peripheral blood of patients with recurrent aphthous
ervation of the normal lobular architecture of the ulcerations. Immunol Lett. 2005;99(1):57–62.
salivary glands is a key feature [27]. While there 4. Femiano F, Lanza A, Buonaiuto C, et al. Guidelines
is no definitive immunophenotype, a properly ori- for diagnosis and management of aphthous stomatitis.
ented HE section remains the gold standard for Pediatr Infect Dis J. 2007;26(8):728–32.
5. Messadi DV, Younai F. Aphthous ulcers. Dermatol
diagnosis. But a study shows Ki-67, p53 down- Ther. 2010;23(3):281–90.
expression [36], and calponin overexpression 6. Baccaglini L, Lalla R, Bruce A, et al. Urban leg-
[37] in NSM compared with squamous cell carci- ends series: recurrent aphthous stomatitis. Oral Dis.
noma. It has been suggested that using the pattern 2011;17(8):755–70.
7. Chattopadhyay A, Chatterjee S. Risk indica-
of cytokeratin expression, p53, calponin may aid tors for recurrent aphthous ulcers among adults
in the differentiation of NS from its mimics. The in the US. Community Dent Oral Epidemiol.
patient of case 37 underwent fever and sweating 2007;35(2):152–9.
at night, so in symptomatic treatment to observe 8. Rogers RS 3rd. Recurrent aphthous stomatitis: clini-
cal characteristics and associated systemic disorders.
the curative effect of 1 week suggest that patients Semin Cutan Med Surg. 1997;16(4):278–83.
with chest X-ray, to eliminate TB. 9. Yazici Y, Yurdakul S, Yazici H. Behcet’s syndrome.
NSM is self-limiting and usually requires only Curr Rheumatol Rep. 2010;12(6):429–35.
supportive treatment, including pain control and 10. Yurdakul S, Hamuryudan V, Fresko I, et al. Behcet’s
syndrome. In: Hochberg MC, Silman AJ, Smolen YS,
local antiseptics. Necrotizing sialometaplasia et al., editors. Rheumatology. 4th ed. Philadelphia,
does not usually recur. Overtreatment such as PA: Mosby Elsevier; 2008. p. 1561–5.
surgical excision is avoided. Although there is 11. Verity DH, Marr JE, Ohno S, et al. Behcet’s disease, the
usually no need for surgery in treatment of NSM, Silk Road and HLA-B51: historical and geographical
perspectives. Tissue Antigens. 1999;54(3):213–20.
rare cases may reach significantly large sizes. In 12. Gul A. Behcet’s disease as an autoinflamma-
these cases, surgical debridement should be con- tory disorder. Curr Drug Targets Inflamm Allergy.
sidered as a viable treatment option, providing 2005;4(1):81–3.
better conditions for healing as well as decreas- 13. Dalvi SR, Yildirim R, Yazici Y. Behcet’s syndrome.
Drugs. 2012;72(17):2223–41.
ing the risk of sepsis [33]. But when NSM and 14. Gul A. Behcet’s disease: an update on the pathogene-
malignant neoplasm (e.g., adenoid cystic carci- sis. Clin Exp Rheumatol. 2001;19(5 Suppl 24):S6–12.
noma) coexist, the situation is more complicated 15. Mat MC, Goksugur N, Engin B, et al. The frequency
[38]. To confirm the range of biopsy and accept- of scarring after genital ulcers in Behcet’s syndrome: a
prospective study. Int J Dermatol. 2006;45(5):554–6.
ing parts become extremely critical. The doctors 16. Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, et al.
should choose standard biopsy site and prevent Uveitis in Behcet disease: an analysis of 880 patients.
misdiagnosis of malignant lesions and excessive Am J Ophthalmol. 2004;138(3):373–80.
64 Y. Zhou et al.
17. Feller L, Essop R, Wood NH, et al. Chemotherapy- 29. Imai T, Michizawa M. Necrotizing sialometaplasia in
and radiotherapy-induced oral mucositis: patho- a patient with an eating disorder: palatal ulcer accom-
biology, epidemiology and management. SADJ. panied by dental erosion due to binge-purging. J Oral
2010;65(8):372–4. Maxillofac Surg. 2013;71(5):879–85.
18. Herrestedt J. Prevention and management of muco- 30. Solomon LW, Merzianu M, Sullivan M, et al.
sitis in patients with cancer. Int J Antimicrob Agents. Necrotizing sialometaplasia associated with bulimia:
2000;16(2):161–3. case report and literature review. Oral Surg Oral Med
19. Raber-Durlacher JE, Elad S, Barasch A. Oral mucosi- Oral Pathol Oral Radiol Endod. 2007;103(2):e39–42.
tis. Oral Oncol. 2010;46(6):452–6. 31. Penner CR, Thompson LD. Necrotizing sialometapla-
20. Scardina GA, Pisano T, Messina P. Oral muco-
sia. Ear Nose Throat J. 2003;82(7):493–4.
sitis. Review of literature. N Y State Dent J. 32. Randhawa T, Varghese I, Shameena P, et al.
2010;76(1):34–8. Necrotizing sialometaplasia of tongue. J Oral
21. Sciubba JJ, Glodenberg D. Oral complications of
Maxillofac Pathol. 2009;13(1):35–7.
radiotherapy. Lancer Oncol. 2006;7(2):175–83. 33. Kaplan I, Alterman M, Kleinman S, et al. The clini-
22. Scully C, Epstein J, Sonis S. Oral mucositis. Head cal, histologic, and treatment spectrum in necrotizing
Neck. 2003;25(12):1057–70. sialometaplasia. Oral Surg Oral Med Oral Pathol Oral
23. Napenas JJ, Shetty KV, Streckfus CF. Oral mucosi- Radiol. 2012;114(5):577–85.
tis: review of pathogenesis, diagnosis, prevention, and 34. Oliveira AMG, Kitakawa D, Carvalho YR, et al.
management. Gen Dent. 2007;55(4):335–44; quiz Necrotizing sialometaplasia as a cause of a non-ulcer-
345-346, 376. ated nodule in the hard palate: a case report. J Med
24. Wong PC, Dodd MJ, Miaskowski C, et al. Mucositis Case Rep. 2011;5:406.
pain induced by radiation therapy: prevalence, sever- 35. Brannon RB, Fowler CB, Hartman KS. Necrotizing
ity, and use of self-care behaviors. J Pain Symptom sialometaplasia. A clinicopathologic study of sixty-
Manage. 2006;32(1):27–37. nine cases and review of the literature. Oral Surg Oral
25.
Santangelo A, Testai M, Ossino MC, et al. Med Oral Pathol. 1991;72(3):317–25.
Management and treatment of decubital ulcers of an 36.
Dadfarnia T, Mohammed BS, Eltorky
elderly population in the assisted sanitary residence MA. Significance of Ki-67 and p 53 immunoexpres-
of Futura-Viagrande (Catania, Sicily, Italy). Arch sion in the differential diagnosis of oral necrotizing
Gerontol Geriatr. 2009;48(3):332–4. sialometaplasia and squamous cell carcinoma. Ann
26. van der Meij EH, de Vries TW, Eggink HF, et al. Diagn Pathol. 2012;16(3):171–6.
Traumatic lingual ulceration in a newborn: Riga-Fede 37. Rizkalla H, Toner M. Necrotizing sialometaplasia ver-
disease. Ital J Pediatr. 2012;38:20. sus invasive carcinoma of the head and neck: the use of
27. Carlson DL. Necrotizing sialometaplasia: a practi- myoepithelial markers and keratin subtypes as an adjunct
cal approach to the diagnosis. Arch Pathol Lab Med. to diagnosis. Histopathology. 2007;51(2):184–9.
2009;133(5):692–8. 38. Lee DJ, Ahn HK, Koh ES, et al. Necrotizing sialo-
28. Fava M, Cherubini K, Yurgel L, et al. Necrotizing sialo- metaplasia accompanied by adenoid cystic carci-
metaplasia of the palate in a cocaine-using patient. A noma on the soft palate. Clin Exp Otorhinolaryngol.
case report. Minerva Stomatol. 2008;57(4):199–202. 2009;2(1):48–51.
Bullous Oral Mucosal Diseases
4
Xin Jin, Xin Zeng, and Wei Li
Keywords
Pemphigus ∙ Pemphigus Vulgaris ∙ Benign
Mucous Membrane Pemphigoid ∙
Paraneoplastic Pemphigus ∙ Linear IgA
Disease
X. Jin
College of Stomatology, Chongqing Medical
University, Chongqing Key Laboratory of Oral
Diseases and Biomedical Sciences,
Chongqing, China
X. Zeng (*)
State Key Laboratory of Oral Diseases, National
Clinical Research Center for Oral Diseases,
Department of Oral Medicine, West China Hospital
of Stomatology, Sichuan University,
Chengdu, Sichuan, China
W. Li
Department of Dermatology, West China Hospital,
Sichuan University,
Chengdu, Sichuan, China
© Springer Nature Singapore Pte Ltd. and People’s Medical Publishing House 2018 65
Q. Chen, X. Zeng (eds.), Case Based Oral Mucosal Diseases,
https://doi.org/10.1007/978-981-13-0286-2_4
66 X. Jin et al.
4.1 Pemphigus
a b
c d
e f
Fig. 4.1 (a) Extensive, irregular, and well-defined ero- covered by yellowish pseudomembrane. (c) Blisters, ero-
sions on the soft palate bilaterally, with a red, clean sur- sions, and crusts on the nasal skin and mucosa. (d) Blisters
face. (b) Erosions distributed on the right posterior on the neck. (e) Blisters and erosions on the right axilla.
mandibular buccal gingiva and the nearby buccal mucosa (f) Erosions and crusts on the scalp
tured and leave irregularly shaped erosions with a Compound chlorhexidine solution
yellowish slough that were refractory. 300 ml × 1
Past Medical History: None Sig.: rinse t.i.d.
Allergy: None Dexamethasone paste 15 g × 1
Physical Examination: Sig.: topical use t.i.d.
There were extensive, irregular, and well-defined 2. Aerosol therapy
erosions on the soft palate bilaterally, which had Rp.: Dexamethasone sodium phosphate injec-
a red, clean surface. No evident inflammatory tion 1 ml × 1
reaction had been found around the erosions. Gentamycin sulfate injection 2 ml × 1
Multifocal small erosions distributed on the right Vitamin B12 injection 1 ml × 1
posterior mandibular buccal gingiva and the Vitamin C injection 2.5 ml × 1
nearby buccal mucosa bilaterally, covered by yel- Sig.: aerosol therapy b.i.d.
lowish pseudomembrane which can be removed. 3. The patient was transferred to dermatology
Nikolsky’s sign was positive. There were blisters, department for hospitalization.
erosions, and crusts on the noses, right axilla,
back, neck, and scalp (Fig. 4.1). Case 39 Pemphigus Vulgaris (Involving the
Laboratories and Imaging Studies:
a
1. There was no obvious abnormality in full
blood count, blood glucose, and liver and kid-
ney functions.
2. Incisional biopsy of perilesional mucosa which
appears normal: Hematoxylin and eosin (HE)
staining revealed intraepithelial blister forma-
tion which was in accordance with pemphigus
vulgaris. Direct immunofluorescence (DIF)
microscopy showed the reticular intercellular
deposition of IgG and C3.
3. There was no abnormality in chest X-ray and b
ultrasonography of abdomen.
Diagnosis:
Pemphigus vulgaris
Diagnosis Basis:
1. Chronic onset.
2. Blisters involving skin and mucosa.
3. Characteristics of erosion: (1) clear boundary,
(2) irregular shape, (3) clean surface, and (4)
no evident inflammatory reaction around the
Fig. 4.2 (a) Irregular and well-defined erosions involv-
erosions. ing the left buccal mucosa, with a red, clean surface. (b)
4. Positive Nikolsky’s sign. Irregular erosions covered by pseudomembrane involving
5. The diagnosis was confirmed by HE staining the labial mucosa and gingiva
and DIF.
Oral Mucosa Only)
Management: Sex: Male
Age: 41 years
1. Medication Chief Complaint:
Rp.: 2% Sodium bicarbonate solution 250 ml × 1 Recurrent oral ulcers for 2 years and ulcers
Sig.: rinse t.i.d. relapsed 1 month ago
68 X. Jin et al.
History of Present Illness: Sig.: 40 mg p.o. q.m. and 20 mg p.o. p.m.
He presented to our department with recurrent Calcium carbonate D3 tablets 600 mg × 30
oral ulcers for 2 years. And he had an episode, Sig.: 1tablet p.o. q.d.
every 3–4 months, with one or two ulcers that Sucralfate tablets 1 g × 100
healed within 10 days. One month ago the condi- Sig.: 1 g p.o. t.i.d.
tion became worse with multiple ulcers in his Potassium chloride sustained-release
mouth which did not heal so far. tablets 0.5 g × 24
Past Medical History: None Sig.: 0.5 g p.o. b.i.d.
Allergy: None 2% sodium bicarbonate solution 250 ml × 1
Physical Examination: Sig.: rinse t.i.d.
Multiple well-defined erosions covered by a few Compound chlorhexidine solution
pseudomembranes involved the labial mucosa, left 300 ml × 1
buccal mucosa, ventrum of the tongue, and gin- Sig.: rinse t.i.d.
giva, without evident inflammatory reaction Dexamethasone paste 15 g × 1
around the erosions (Fig. 4.2). Nikolsky’s sign was Sig.: topical use t.i.d.
positive. No skin and scalp lesion has been found. 2. Aerosol therapy
Laboratories and Imaging Studies: Rp.: Dexamethasone sodium phosphate injec-
tion 1 ml × 1
1. There was no obvious abnormality in full
Gentamycin sulfate injection 2 ml × 1
blood count, blood glucose, and liver and kid- Vitamin B12 injection 1 ml × 1
ney functions. Vitamin C injection 2.5 ml × 1
2. Incisional biopsy of perilesional mucosa
Sig.: aerosol therapy b.i.d.
which appears normal: Hematoxylin and 3. Subsequent visit 1 week later was suggested.
eosin (HE) staining revealed intraepithelial
blister formation which was in accordance Follow-Up Treatment:
with pemphigus vulgaris. Direct immunofluo- If no new blister is seen 2–4 weeks later after the
rescence (DIF) microscopy showed the reticu- treatment, the dose of prednisone should be
lar intercellular deposition of IgG and C3. reduced by 10% within 2–4 weeks. If erosions
3. There was no abnormality in chest X-ray and are limited, intralesional injection of mixture of
ultrasonography of abdomen. triamcinolone injection and water for injection or
2% lidocaine in the same amount is considered.
Diagnosis: During the treatment, patients should recheck
Pemphigus vulgaris blood routine, blood glucose, liver and kidney
Diagnosis Basis: function, and electrolytes one time/1–2 months.
If the blister formation and erosions cannot be
1. Chronic onset. controlled, the dose of prednisone should be
2. Characteristics of erosion: (1) clear boundary, increased, and the patient should be transferred to
(2) irregular shape, (3) clean surface, and (4) the department of dermatology.
no evident inflammatory reaction around the
erosions. [Review] Pemphigus
3. Positive Nikolsky’s sign. Pemphigus is a group of potentially life-threat-
4. The diagnosis was confirmed by HE staining ening, chronic, and autoimmune disease that is
and DIF. caused by autoantibodies directed against inter-
cellular adhesion substances. The main clinical
Management: characteristic is blistering cutaneous and muco-
sal lesions. Since oral blisters rupture soon after
1. Medication forming, erosive or ulcerated lesions are pro-
Rp.: Prednisone acetate 5 mg × 72 duced. Oral lesions are most commonly detected
4 Bullous Oral Mucosal Diseases 69
There is extension of the blister and/or epithelial mucosa. The papillomatous and verrucous vege-
desquamation in the applied pressure area which tations are commonly formed on the base of blis-
is considered positive. Licking of the mucosa ters. The skin lesions of pemphigus vegetans may
can make normal mucosa of normal appearance resemble exfoliative dermatitis and its prognosis
slough off. All of them are phenomenon of acan- as well. Pemphigus erythematosus resembles
tholysis which are indicative for primary diagno- cutaneous lupus erythematosus clinically with
sis. The final diagnosis is based on examination butterfly lesions on the face.
of HE staining and direct immunofluorescence. Glucocorticoids are the first choice for ini-
Oral lesions have more difficulties in healing tial treatment. The initial dose of prednisone is
than cutaneous lesions. The chronic erosions are identified by the extent and rate of progression of
usually covered by pseudomembrane. Increased lesions. If lesions are limited to oral mucosa and
saliva and difficulties in eating and swallowing are not extensive, the single dose of oral pred-
are the chief complaints. It is worth noting that nisone was 40 mg/day at 7:00–8:00 a.m. If oral
sometimes the clinical manifestation of pemphi- lesions are extensive, the dose of prednisone was
gus vulgaris is atypical and easy to be misdiag- 60–80 mg/day which should be taken twice a day
nosed as recurrent aphthous ulcers. At this point, (at 7:00–8:00 a.m. and 2:00–3:00 p.m.). If the
it is important to examine whether the ulcers are condition is controlled, which means that there
concave or not, which may be indicative of the are no new blisters and existing erosions or ulcers
need for biopsy. are almost healed, the dose of prednisone should
Expect for oral cavity, lesions may affect be tapered by 10% reduction of the original dose
the sites of conjunctiva, nose, pharynx, lar- every 2–4 weeks. And the maintenance dose is
ynx, esophagus, and genital. Flaccid bullae are 5 mg/day. Patients should not reduce or stop tak-
commonly seen in the skin. The flaccid blisters ing glucocorticoids on by themselves.
rupture easily and produce red erosions. Slow The long term and high dose of glucocorti-
healing is ordinary state but with no scars [4, 5]. coids may induce many adverse effects such as
Nikolsky’s sign is elicited by tangential pressure peptic ulcer, diabetes, hypertension, osteopo-
with a finger over the normal skin or mucosa. rosis, Cushing’s syndrome, a variety of infec-
There is extension of the blister and/or removal tions, and toxicity of central nervous system.
of epidermis in the applied pressure area which Therefore, regular monitoring of blood pres-
is considered positive. Although the sign is char- sure, blood glucose, liver and kidney function,
acteristically seen in pemphigus, it can be seen in fecal occult blood test, electrolyte, etc. are rec-
other diseases, such as pemphigoid in the acute ommended. Adjuvant drugs should be applied
phase and erythema multiform with bullae. properly in order to prevent and mitigate adverse
Acantholysis, discontinuous epithelial, and effects. For example, calcium carbonate D3 tab-
the blisters or cleft formation within the epithe- lets (one tablet each time, one to two times per
lium are the main histological finding. Typical day) are used to prevent osteoporosis. To protect
prickle cells, also known as Tzanck cell, can be gastric mucosa, sucralfate tablets (1 g each time,
found by scraping the base of a blister. Both indi- four times per day) are used. Potassium chloride
rect immunofluorescence assays on serum and sustained-release tablets (0.5–1 g each time, one
direct immunofluorescence assays on biopsy tis- to three times per day) are applied for supplement
sue show the reticular intercellular deposition of of potassium according to serum potassium level.
IgG, C3 [6]. Rinsing with 2–4% sodium bicarbonate solution
Oral cavity is less involved in other types of or topical application with nystatin liniment can
pemphigus. The oral manifestations of other prevent Candida albicans infection.
types of pemphigus were similar to that of pem- If the treatment with glucocorticoids is inef-
phigus vulgaris. fective or the patients have contraindications for
Pemphigus vegetans usually affects inter- glucocorticoids, immunosuppressants can be
triginous sites such as anogenital and nasolabial used as monotherapy or in combination with glu-
4 Bullous Oral Mucosal Diseases 71
cocorticoids, such as azathioprine (1–2 mg/kg/ ate solution and nystatin liniment. Refractory
day, to be taken once daily or several times daily) erosions may be treated with intralesional corti-
or tripterygium glycosides tablet (1–1.5 mg/kg/ costeroid injection (triamcinolone acetonide or
day, three times daily). compound betamethasone injection mixed with
Topical treatments include antiseptic such as water for injection or 2% lidocaine, multipoint
compound chlorhexidine solution; topical glu- low-dose injection).
cocorticoids including dexamethasone gargle, For patients with skin lesions and systemic
dexamethasone paste, triamcinolone acetonide diseases such as diabetes and hypertension, hos-
dental paste, and dexamethasone ointment; and pitalization in the department of dermatology
antifungal agent such as 2–4% sodium bicarbon- should be suggested.
a b
Fig. 4.5 (a) Blister and hyperemia on the left maxillary buccal gingiva. (b) Blister and erosion on the left maxillary
palatal gingiva. (c) Erosions on the right mandibular buccal gingiva
after the rupture of blisters, and it could be self- 3 . Nikolsky’s sign was negative.
healing. She denied any discomfort of eyes. 4. The diagnosis was confirmed by HE staining
Past Medical History: Hepatitis B, cholecysti- and DIF.
tis, myocardial ischemia, rheumatoid arthritis
Allergy History: Penicillin Management:
Physical Examination:
Multiple small erosions were detected on the marginal 1. Medication
gingiva and a blister with the diameter of 4–5 mm on Rp.: Tripterygium hypoglaucum tablet
the buccal and palatal side of the maxillary gums, 1 g × 100
respectively (Fig. 4.5). Nikolsky’s sign was negative. Sig.: 2 g p.o. t.i.d.
Laboratories and Imaging Studies: Vitamin B6 10 mg × 100 tablets
Sig.: 5 mg p.o. t.i.d.
1. There was no obvious abnormality in full
Compound chlorhexidine solution
blood count, blood glucose, and liver and kid- 300 ml × 1
ney functions. Sig.: rinse t.i.d.
2. Hematoxylin and eosin (HE) staining of the Dexamethasone paste 15g × 1
gingiva biopsy revealed that stratified squa- Sig.: topical use t.i.d.
mous epithelium was stripped completely. 2. The lesions were dealed with double-diluted
Direct immunofluorescence (DIF) showed lin- triamcinolone acetonide (TA) injection (Sig.:
ear deposition of immunoglobulin G and com- multipoint low-dose intralesional injection st.).
plement C3 along the basement membrane. 3. Subsequent visit after 2 weeks.
a b
Fig. 4.6 (a) Widespread gingival erythema with scat- Erythema with small erosions on the right buccal man-
tered mung bean size of erosions. (b) Erythema with dibular gingiva. (d) Chronic blister and erosion on the
small erosions on the left buccal mandibular gingiva. (c) posterior soft palate
4 Bullous Oral Mucosal Diseases 73
c d
Fig. 4.6 (continued)
[Review] Pemphigoid
Pemphigoid mainly includes benign mucous
membrane pemphigoid (MMP) and bullous pem-
phigoid (BP).
MMP mainly occurs in the elderly. The clini-
cal manifestations are recurrent blisters, skin can
also be involved. Due to scar formation left after
healing, it is also called cicatricial pemphigoid.
The pathogenesis of MMP is not clear, with
complex immune genetic background. The HLA
DQB1*0301 may be involved, which plays a
role in recognizing the autoantigen (BP180, lam- Fig. 4.7 Intact blisters on the posterior palate, with blis-
inin332, β4-integrin) of basement membrane zone ters rupture partly
(BMZ). The autoantibody induces complement-
mediated release of cytokines and enzyme by
acting on the antigen of BMZ or hemidesmo-
some or induces cytolysis to separate basal cell
from the basement membrane [7]. The diagnosis
depends on the biopsy and direct immunofluores-
cence (DIF). The histological pathology reveals
the blister or fissure between the epithelium and
connective tissue. DIF showed linear deposition
of immunoglobulin (Ig) G and complement C3,
sometimes accompany with IgA or IgM, along the
basement membrane. MMP mainly mediated by
IgG, which is different from linear IgA disease [8].
Seventy-five percent of cases of MMP involve Fig. 4.8 Well-defined erosion on the right buccal mucosa
the oral mucosa. Gingival lesion is initial and
common, and the typical manifestation of it is should observe closely to the eyes of the patient
desquamative gingivitis. Widespread erythema with MMP. Other common mucosal features
with 2–6 mm vesicles locate on the gingiva, with include erosions of nose and pharynx, epistaxis,
clear or bloody vesicular fluid. If the lesions dysphagia, anogenital scar, and adhesion. The
occur on the palate or other sites, they often man- skin lesions appear on 20–30% of cases of MMP,
ifest as blisters or erosions after blisters rupture which manifest as widespread blisters with thick
(Figs. 4.7 and 4.8). The fresh erosions are similar walls. Blisters are restricted to the scalp and upper
to pemphigus vulgaris (PV), covered by the pseu- limb occasionally, leaving scars after healing [6].
domembrane subsequently. Because of the white Bullous pemphigoid (BP) is another type
stripes around the erosions, it is often misdiag- of pemphigoid, which is characterized by ten-
nosed as oral lichen planus (OLP). The pain is sion blisters on the trunk and limbs, without scar
less severe than PV. Restriction of mouth opening occurs after the healing. Involvement of oral cavity
and microstomia may be induced by the scar at is uncommon, with chronic oral ulcers affecting
corners of the mouth, due to scar formation left 10–30% of the patients. The precipitating factors
after healing in MMP. include medicine such as sulfasalazine, penicil-
Forty percent of cases of MMP involve the lin, diazepam, furosemide, angiotensin-convert-
eyes. The initial manifestation is conjunctivi- ing enzyme inhibitors (ACEI), sulfonamides,
tis, which can develop into entropion, trichiasis, isoniazid, and ultraviolet (UV), but they are still
synechia, and atrophy of the cornea due to scar uncertain. The incidence of BP is also increased
formation. Unfortunately, 20% of patients may as the age increases [6]. It is hard to differentiate
lose their sight [9]. Therefore, the clinicians between BP and MMP from the histopathology
4 Bullous Oral Mucosal Diseases 75
Suspected
Autoimmune bullous disorders
diagnosis
Intraepithelial(or
Histology Intraepithelial Subepidermal
additionally Subepidermal
DIF: direct immunofluorescence; IIF: indirect immunofluorescence; DEJ: dermo-epidermal junction; IB: immunoblot; IP: immunoprecipitation
and DIF, but they are slightly different in the clini- be given simultaneously. If the aforementioned
cal manifestations and laboratory tests: (1) the oral therapy is not effective, minocycline hydrochlo-
lesions are common in MMP, while the cutaneous ride tablets (100 mg p.o. b.i.d.) or combination of
lesions occur only in BP mostly; (2) scars forma- tetracycline (250 mg p.o. t.i.d.) and nicotinamide
tion after healing are always in MMP, while not in (200 mg p.o. t.i.d. or 500 mg p.o b.i.d.) is another
BP; (3) the autoantigen of MMP are BP180, lam- available therapy. Moreover, the dosage should be
inin332, and β4-integrin, while the BP of which tapered after 3 months according to the literature.
are BP180 and BP230; (4) the result of salt split- The topical agents include disinfectants and
skin immunofluorescence is different. Therefore, antiseptics (e.g., compound chlorhexidine solu-
the differential diagnosis depends on the clinical tion), glucocorticoid preparation (e.g., dexametha-
manifestations and laboratory tests (Fig. 4.9). sone solution, dexamethasone paste, triamcinolone
The systemic therapy of MMP is as follows. acetonide dental paste), and antifungal preparation
If the oral condition is severe, it is necessary to (e.g., 2–4% sodium bicarbonate solution, nystatin
take systemic glucocorticoid into consideration liniment). For the refractory circumscribed ero-
(≤30 mg/day, orally for 7–14 days and then grad- sions, they could be dealed with double-diluted
ually taper). If the oral condition is mild, clini- triamcinolone acetonide (TA) injection or com-
cian can choose tripterygium glycoside tablet pound betamethasone injection (Sig.: multipoint
(1–1.5 mg kg−1 day−1 t.i.d., orally for 1 month) low-dose intralesional injection st.).
or tripterygium hypoglaucum tablet (two tablets During the course of treatment, closely obser-
p.o. t.i.d., orally for 1 month). If the condition vation of the ocular and cutaneous lesions is
is controlled, the tablets can be tapered or given required. If the lesions appear, the patients should
intermittently. In order to relieve the gastrointes- be advised to visit the ophthalmological and der-
tinal discomfort, vitamin B6 (5 mg p.o. t.i.d.) can matological department.
76 X. Jin et al.
a b
c d
e f
Fig. 4.10 (a) Extensive and irregular-shaped erosions on shaped erosions on the lower labial mucosa, covered with
the lips, covered with pseudomembrane. (b) Extensive pseudomembrane. (e) Extensive and irregular-shaped ero-
and irregular-shaped erosions on the labial mucosa and sions on the right palate, covered with pseudomembrane.
tongue, covered with pseudomembrane. (c) Extensive and (f) Conjunctival congestion. (g) Blisters and erosions on
irregular-shaped erosions on the left buccal mucosa, cov- the genital mucosa. (h) Multiple milia on the chest skin
ered with pseudomembrane. (d) Extensive and irregular-
4 Bullous Oral Mucosal Diseases 77
g h
Fig. 10 (continued)
Mucosal lesions of PNP can occur in any plete resolution of PNP. However, poor prognosis
part of the oral mucosa such as buccal mucosa, is indicated due to the progressive course of the
labial mucosa, gingiva and tongue, and nasal malignancy. The topical treatment is similar to
mucosa, pharynx, tonsil, vulva mucosa can also that of pemphigus.
be involved. The features of oral lesions include
extensive erosions with obvious exudation and
severe pain, positive probing test, and positive 4.4 Linear IgA Disease
Nikolsky’s sign. In addition, blisters and erosions
can occur in the mucosa of digestive tract and Case 43 Linear IgA Disease
respiratory tract, which may lead to the death of
respiratory failure. The damage to the eyes may
range from mild conjunctivitis to symblepharon a
accompanied with corneal scarring.
The involvement of skin is extensive, with
pain and itching. Multiple manifestations may
appear, including scattering or exfoliative ery-
thema, blisters, papules, scales, ulcers, and ero-
sions. Skin lesions occur as erythema initially,
such as spotlike, wheal-like, and target-like, fol-
lowed by blisters and erosions.
Patients with PNP are always suffered from
dysphagia, fatigue, muscle pain, which ulti-
mately results in poor general condition. b
The histological findings have shown simi-
larities with other known bullous dermatoses,
including intraepidermal or subepidermal blis-
tering with no or few mononuclear cells. Direct
immunofluorescence (DIF) is considered as one
of the main diagnostic criteria for PNP/PAMS,
which reveals the deposition of IgG and comple-
ment C3 in an intercellular and/or linear pattern.
By indirect immunofluorescence (IIF), PNP
antibodies stain the simple, columnar, and tran- Fig. 4.11 (a) Regional erythema and erosions on the
sitional epithelial tissue substrates (typically rat anterior maxillary gingiva. (b) Localized erythema and
bladder) in addition to the stratified squamous erosions on the left mandibular gingiva
epithelium. IIF has higher sensitivity and speci-
ficity than DIF [10, 12]. Age: 41 years
PNP should be suspected if the following Sex: Female
points occur: a youth suffered from extensive Chief Complaints:
and refractory lesions in the oral mucosa, inter- Gingival erythema and pain for 2 years
cellular and basement membrane deposition of History of Present Illness:
IgG and complement C3 showed in the DIF, and A 41-year-old female presented to our clinic with
the poor response to the conventional therapy for gingival erythema and pain, as well as difficulty
pemphigus. in eating for 2 years. She denied any lesions of
The treatments for PNP is mainly target the skin.
neoplasms. In patients with a benign tumor, sur- Past Medical History: None
gical resection would lead to remission or com- Allergy History: None
80 X. Jin et al.
18. Ikeya S, Urano S, Tokura Y. Linear IgA bullous der- dermatosis of childhood (linear IgA dermatosis).
matosis following human papillomavirus vaccination. Indian J Dermatol. 2011;56(56):573–5.
Eur J Dermatol. 2012;22(6):787–8. 21. Dan H, Lu R, Li W, et al. Linear IgA disease lim-
19.
Kasperkiewicz M, Zillikens D, Schmidt ited to the oral mucosa. J Am Acad Dermatol.
E. Pemphigoid diseases: pathogenesis, diagnosis, and 2011;65(3):677–9.
treatment. Autoimmunity. 2012;45(1):55–70. 22. Ng SY, Venning VV. Management of linear IgA dis-
20. Fahad AS, Ammar AR. Unusual clinicopathological ease. Dermatol Clin. 2011;29(4):629.
and immunological presentation of chronic bullous
Oral Mucosal Patches Striae
Diseases 5
Hongxia Dan, Xin Jin, and Qianming Chen
H. Dan
State Key Laboratory of Oral Diseases, National
Clinical Research Center for Oral Diseases, Fig. 5.1 A well-defined homogenous white plaque on the
Department of Oral Medicine, West China Hospital buccal gingiva of the right maxillary premolar and molar
of Stomatology, Sichuan University, teeth
Chengdu, Sichuan, China
X. Jin Age: 47 years
College of Stomatology, Chongqing Medical
Sex: female
University, Chongqing Key Laboratory of Oral
Diseases and Biomedical Sciences, Chief Complaints:
Chongqing, China A 47-year-old woman complained of color
Q. Chen (*) change of the maxillary gingiva for 1 month.
Changjiang Scholars Program, Ministry of Education, History of Present Illness:
Beijing, China A 47-year-old woman came to our clinic, com-
State Key Laboratory of Oral Diseases, National plaining of a 1-month history of color change of
Clinical Research Center for Oral Diseases, the maxillary gingiva. There was no pain or any
Department of Oral Medicine, West China Hospital
obvious discomfort. The patient denied the his-
of Stomatology, Sichuan University, Chengdu,
Sichuan, China tory of smoking and drinking.
e-mail: qmchen@scu.edu.cn Past Medical History: None.
© Springer Nature Singapore Pte Ltd. and People’s Medical Publishing House 2018 83
Q. Chen, X. Zeng (eds.), Case Based Oral Mucosal Diseases,
https://doi.org/10.1007/978-981-13-0286-2_5
84 H. Dan et al.
a b
Fig. 5.2 (a) A rough, verrucous, highly keratinized whit- the lower lip, gingiva, and vestibular groove of mandibu-
ish lesion was seen on the buccal mucosa close to the left lar incisors. (c) Whitish plaques, slightly raised and rough,
commissure of mouth. (b) White plaques, slightly raised were widely distributed on the left buccal mucosa
and partially verrucous, were observed on the mucosa of
5 Oral Mucosal Patches Striae Diseases 85
Fig. 5.4 Well-defined wrinkled leukoplakia on the left Fig. 5.6 Ulcerated leukoplakia on the left buccal mucosa.
buccal mucosa. Histological findings were in accord with Histological findings were in accord with leukoplakia
leukoplakia without epithelial dysplasia with moderate to severe epithelial dysplasia
5 Oral Mucosal Patches Striae Diseases 87
Fig. 5.5 Speckled OLK on the left side of the tongue. Fig. 5.7 Verrucous leukoplakia on the left upper lip.
Histological findings were in accord with leukoplakia Histological findings were in accord with leukoplakia
with mild epithelial dysplasia with moderate epithelial dysplasia
Proliferative verrucous leukoplakia (PVL), a be associated with tobacco chewing and smok-
special type of OLK, usually has multiple lesions ing [5]. There were other studies indicating that
which are characterized by chronic prolifera- non-smoking female patients had a higher risk of
tion and intractability. The reported malignant malignant transformation compared with other
transformation rate of PVL is up to 100%. PVL patients. Elder people had a higher risk of malig-
is most common in middle-aged women. The nant transformation than people in a younger age
typical lesion is a well-defined verrucous white group [6]. Leukoplakia on the ventral surface of
plaque, which usually starts on the gingiva and the tongue and the floor of the mouth is associ-
then spreads to other regions of the mouth [3]. It ated with a risk of malignant transformation up to
is very difficult to be differentiated from verru- 43%, probably due to higher permeability of these
cous carcinoma. The pathological process of PVL areas that leads to increased exposure to carcino-
may start as simple keratosis and then develop to gens in saliva and the oral cavity. Compared with
leukoplakia or even invasive squamous cell car- homogeneous OLK, nonhomogeneous OLK has
cinoma. The histological morphology of PVL higher risk of malignant transformation. Cancer
usually overlaps with other types of OLK, but development can happen in 80% of patients with
the abnormal keratinization is more severe. PVL PVL [3].In addition, lesions larger than 200
usually has no or only mild epithelial dysplasia at square mm or lesions dispersedly distributed are
early stages of the disease. If the lesion is verru- also considered to be at high risk.
cous leukoplakia with severe dysplasia, it is more Epithelial dysplasia reflects the abnormal
appropriate to be diagnosed as carcinoma in situ differentiation of the epithelium. It is present in
rather than PVL [4]. 1–30% of OLK cases. It was reported that up to
The reported malignant transformation rate of 36% of OLK with dysplasia would develop to
OLK varies from 0.13% to 17.5% in a follow- squamous cell carcinoma [7]. The grade of epi-
up time that ranges from 1 to 30 years [2]. This thelial dysplasia is important in the treatment
variation could be a result of different research and prognosis prediction of OLK. However, the
methods, such as the choice of the control group, judgment of the severity of epithelial dysplasia
length of the follow-up period, and different can be very subjective. Lesions with moderate to
smoking habits. There are many factors that severe dysplasia do not necessarily develop into
may be related to the risk of malignant trans- squamous cell carcinoma, some of them may be
formation. Some researchers in India suggested resected at the time of biopsy and some of them
that the malignant transformation rate of OLK may get better as time goes by. On the other hand,
was higher in men than in women, which may malignant transformation can also occur in OLK
88 H. Dan et al.
without dysplasia [8]. Therefore, it is difficult to sidered to be at high risk of malignant transfor-
predict the risk of malignant transformation of an mation [13].
individual patient. Genes associated with dysplasia include p53,
The development of OLK is related to local cyclooxygenase 2, prostaglandin E synthase, and
irritation factors and some infections. Tobacco so on. p53 is a tumor suppressor gene. Wild-type
chewing, smoking, and betel nut chewing are p53 can induce apoptosis, but the mutant type
common local irritation factors, all of which are inhibits apoptosis [14].
associated with the development of leukoplakia. Protein markers associated with malignant
There is much debate about whether Candida transformation of OLK include integrins, the
infection is the etiological factor of OLK or just CD44 family, cell cycle regulators, matrix metal-
a type of secondary infection. Different types of loproteinase 11, vascular endothelial growth fac-
Candida species have been isolated from non- tor, etc. [3]. However, all of these markers are still
homogeneous OLK with epithelial dysplasia. being studied. Until now, no recognized markers
Eradication of Candida does not lead to vanishing can be widely applied clinically.
of the lesion but may facilitate the transformation Diagnosis of OLK is established after rul-
of high-risk nonhomogeneous OLK to low-risk ing out other well-defined entities that may
homogenous OLK [9]. HPV is probably associ- appear as whitish plaques on the oral mucosa,
ated with the occurrence and malignant transfor- such as linea alba, leukoedema, white sponge
mation of OLK. PVL is closely related with HPV nevus, morsicatio buccarum, contact stomati-
infection. Infection of HPV-16 is an independent tis, verrucous carcinoma, oral hairy leukopla-
risk factor of malignant transformation of OLK kia, oral lichen planus, oral lesions of discoid
[10]. EBV has been related with various cancers. erythematosus, and secondary syphilis. A
Some studies suggested that it might play a part biopsy should be conducted if no remission
in oral carcinogenesis. However, no solid evi- is achieved in 2–4 weeks after removing the
dence has been found regarding the relationship local irritation factors. Biopsy not only rules
between OLK and EBV [11]. out other well-defined diseases histologically
Elucidation of the mechanisms of cancer but also gives us information about the exis-
development can help us with the prediction of tence and grade of epithelial dysplasia. This
the malignant transformation of OLK, with or is the basis of the diagnosis and treatment
without epithelial dysplasia. The development of of OLK. The site of biopsy is usually deter-
OLK is associated with various molecular abnor- mined based on the findings of the physical
malities, such as aneuploidy, aberrant telomerase examination, but the results of supplementary
activity, and loss of heterozygosity (LOH). techniques, such as toluidine blue staining and
LOH in the chromosome of tumor suppres- auto-immunofluorescence, may help the doc-
sor gene has some predictive value for malignant tor with the judgment.
transformation risk of OLK. LOH at 3p, 4q, 8p, Various factors should be considered when the
9p, 11q, 13q, and 17p loci have been reported to treatment plan of OLK is formulated. Common
be associated with increased risk of malignant factors include type of lesion, site, size, severity
transformation. LOH does not appear in OLK of dysplasia, and reaction to drugs. The initial
with low risk of malignant transformation [12]. treatment is to eliminate local irritation factors
The DNA ploidy provides information on the such as smoking, residual roots, or sharp edges
degree of genetic instability and aberrations. In of teeth. If the lesion is homogeneous, small,
OLK with dysplasia, diploid cells are considered and located in non-hazardous sites, with no or
to be at low risk, tetraploid cells are considered to mild epithelial dysplasia, it can be treated using
be at mediate risk, while aneuploid cells is con- topical agents only. Retinoids, such as tretinoin
5 Oral Mucosal Patches Striae Diseases 89
paste and 0.1–0.3% retinoic acid ointment, can dropping pill (ten pills, t.i.d.). The above treat-
be applied to the white plaques once or twice per ment can be used for 1 month or longer if needed.
day. Application of the agent to erosive or ery- Regular follow-up visits should be scheduled
thematous lesions should be avoided. Vitamin A every 1–2 months.
and D drops or vitamin E can also be applied, If the lesion is located in high-risk sites, or
three to four times per day. nonhomogeneous, or with severe dysplasia, sur-
If the lesion is large, with multiple sites involved gical resection should be considered. However,
or moderate epithelial dysplasia, systemic medi- tissue surrounding the white plaques, even with a
cation regimen could be adopted, such as thymo- normal appearance, could be altered molecularly.
sin enteric-coated tablets (20 mg, q.d. or b.i.d.), Thus, complete resection of the lesion does not
antioxidants beta-carotene (6 mg, q.d. or b.i.d.), necessarily mean that it could not recur. Regular
vitamin E (0.1 g, q.d.), and compound danshen follow-up visits should be scheduled.
a b
Fig. 5.8 (a) Homogeneous white patches widely distrib- linea alba of the right buccal mucosa. (c) Soybean-sized
uted on the hard palate. Openings of the palatine glands white patch, rough and ill-demarcated, was observed on
were very clear on the whitish background. (b) White the mucosa of the right lower lip, almost the location
patches, flat and ill-demarcated, distributed along the where cigarettes were hold
90 H. Dan et al.
edema of spinous cells and thickening of epithe- mouth to the molar teeth (Fig. 5.11). It is commonly
lium. Patients with leukoedema seldom have any seen in adults and is probably caused by irritation
discomfort. No malignant transformation of this from the teeth. Similar white line could also appear
condition has been reported. There’s no need for along the border of the tongue due to long-term
treatment [16]. stimulation from the lingual edge of mandibular
Linea alba refers to an asymptomatic linear ele- teeth. The pathological feature is hyperkeratosis.
vation on the buccal mucosa, level with the occlu- No treatment is needed, and spontaneous remission
sal plane. It usually extends from the angle of the can be achieved in some cases [16].
Fig. 5.9 White patches, flat, dispersed, and ill-demarcated, Fig. 5.10 Right buccal mucosa with a diffuse, grayish
were found on the right buccal mucosa white, milky, and wrinkled surface
Fig. 5.11 Linear
elevation at the level of
occlusal line on the
inner surface of the left
buccal mucosa
92 H. Dan et al.
a b
c d
e f
Fig. 5.12 (a) White spongy patches widely distributed on on the right buccal mucosa. (f) The mother of the patient
the right buccal mucosa. (b) White spongy patches widely also had white spongy lesions on the left buccal mucosa.
distributed on the left buccal mucosa. (c) White spongy (g) The mother of the patient also had white spongy lesions
patches widely distributed on the dorsum of the tongue. (d) on the lower lip and mucosa lining on the vestibular groove
White spongy patches widely distributed on the upper lip. of the mandibular incisors
(e) The mother of the patient also had white spongy lesions
5 Oral Mucosal Patches Striae Diseases 93
a b
Fig. 5.13 (a) White spongy patches widely distributed on the right buccal mucosa. (b) White spongy patches widely
distributed on the left buccal mucosa. (c) White spongy patches widely distributed along the border of the tongue
94 H. Dan et al.
a b
Fig. 5.14 (a) Pearl white streaks on the lower lip. (b) Pearl white streaks on the right buccal mucosa. (c) Pearl white
patches on the dorsum of the tongue
Follow-Up Treatment:
Fig. 5.15 Pearl white lacy streaks and patches with inter- In the follow-up visit, the erosions got localized,
spersed erythematous and erosive lesions on the buccal
mucosa intra-lesional injection of triamcinolone ace-
tonide was given, and the oral medication was
Age: 58 years switched to tripterygium hypoglaucum tablets
Sex: Female (two tablets t.i.d. p.o.).
Chief Complaints:
A 58-year-old woman with erosion and pain on [Review] Oral Lichen Planus
the buccal mucosa for 2 months Oral lichen planus (OLP) is a chronic inflamma-
History of Present Illness: tory disorder of the oral mucosa. It affects about
A 58-year-old woman complained of erosion 0.5–3% of the population, especially women aged
and pain on the buccal mucosa for 2 months. from 30 to 60 years. Compared with the normal
The pain got worse when she was eating hot or oral mucosa, OLP has a higher risk of cancer
spicy food. development and is thus classified by the World
Past Medical History: None. Health Organization as one of the oral potentially
Allergy: None. malignant disorders [22].
Physical Examination: Although the etiology of OLP is still unclear,
Pearl white lacy streaks and patches with inter- the association of immune dysregulation with the
spersed erythematous and erosive lesions were pathogenesis of this disease is widely accepted.
seen on the buccal mucosa. No abnormality was The primary event of this process is the interac-
found on the fingernails and skin (Fig. 5.15). tion between endogenous and exogenous fac-
Diagnosis: tors (antigens, drugs, viruses, psychological
Oral lichen planus (erosive type). stress [23], and so on) with keratinocytes (KCs),
Diagnosis Basis: which then leads to degranulation of mast cells,
activation of macrophages, and release of pro-
1. Pearl white lacy streaks and patches with ery- inflammatory cytokines such as tumor necro-
thematous and erosive lesions. sis factor-α (TNF-α). TNF-α not only affects
2. No obvious inducing factors. T-lymphocyte homing but also induces the
expression of adhesion molecules by endothelial
Management: cells and KCs. The expression of adhesion mol-
ecules promotes the infiltration of lymphocytes,
1. Medication which further promote degranulation of mast
Rp.: Prednisone acetate tablets 5 mg × 35 cells and produce interferon-γ (IFN-γ), leading
tablets to extension of the lesion. IFN-γ not only upregu-
Sig.: 25 mg q.m. p.o. lates expression of major histocompatibility com-
Compound chlorhexidine solution 300 ml × 1 plex (MHC) class I but also induces expression of
5 Oral Mucosal Patches Striae Diseases 97
MHC class II by KCs. Modified surface antigens is still controversial [32].Some researchers sug-
of KCs can be recognized by Langerhans cells gested that patients with or without HCV had
(LC) and presented to T lymphocytes. KCs then different hereditary basis, which might be related
become the target of cytotoxic T cells. Damaged with the allele of HLA-DR6 gene [32].
keratinocytes release cytokines which could fur- There are six types of OLP lesions: papular,
ther stimulate the differentiation and chemotaxis reticular, plaque-like, atrophic, erosive/ulcer-
of Langerhans cells, as well as the growth of T ative, and bullous. Reticular OLP usually presents
lymphocytes. as asymptomatic pearl white lacy streaks distrib-
Although the relationship between genetic uted in a reticular or circular pattern (Fig. 5.16).
factors and OLP is still controversial, studies This type of lesion is most commonly seen on
have shown that gene polymorphisms of several the buccal mucosa but can also be observed on
cytokines, such as TNF-α and interleukin (IL)- the lips, gingiva, and tongue. Papular OLP is
10, may be associated with individual’s suscepti- clinically characterized by small white dots on
bility to OLP [24–27]. the mucosa (Fig. 5.17), which usually intermin-
Studies on the association between OLP and gles with other forms of OLP. Plaque-like OLP
infective factors mainly focus on hepatitis C often locates on the buccal mucosa and dorsal
virus (HCV) infection. Researches carried out surface of the tongue. This type of lesion is usu-
in different regions provide us with different ally smooth, flat, or slightly elevated, similar to
results, some of them are contradictory [28–31]. homogeneous oral leukoplakia (Figs. 5.18 and
The association of OLP and HCV infection HCV 5.19). Atrophic OLP is most frequently observed
Fig. 5.16 Reticular form: pearl white lacy streaks on left Fig. 5.18 Plaque-like form: single pearl white patch on
buccal mucosa dorsum of the tongue
Fig. 5.17 Papular form: lots of white dots densely dis- Fig. 5.19 Plaque-like form: multiple pearl white patches
tributed on the left buccal mucosa on dorsum of the tongue, flat or slightly elevated
98 H. Dan et al.
on dorsum of the tongue, presenting as atrophy a waxy luster and white streaks (Wickham’s
of lingual papilla surrounded by white streaks striae) (Figs. 5.22 and 5.23). Skin lesions can be
(Fig. 5.20). Patients with atrophic OLP may have itchy. If the scalp is involved, hair follicles can
burning sensation and pain while eating. Erosive/ be destroyed, leading to alopecia. Affected nails/
ulcerative OLP are characterized by erosive/ toenails are usually thin, wrinkled, and reluster,
ulcerative lesions surrounded by white streaks with tiny scales, longitudinal grooves, pits, and
[33].The bullous lesions in OLP are usually quite ridges (Fig. 5.22). Skin of the scrotum is occa-
small, with a diameter of about 2 mm; sometimes sionally involved [33].
larger bulla can also be seen (Fig. 5.21). The OLP is considered as an oral potentially malig-
forms mentioned above can be divided into two nant disorder (Fig. 5.24); however, due to the
major types: erosive type and non-erosive type. heterogenicity of different studies, the reported
Some OLP patients have skin lesions, with frequency of malignant transformation varies a
predilection for the flexor aspects of the extremi- lot. A recent study carried out by a Chinese group
ties. Cutaneous lesions are mostly symmetrical, showed that the malignant transformation rate
presenting as flat violaceous papules. The papules of OLP was less than 1% [34]. Since malignant
can get confluent and form patches or plaques transformation was frequently found at locations
that are slightly elevated, well-demarcated, with distant to OLP lesions, some researchers thought
a b
Fig. 5.25 (a) White striae and ulcerative lesion on the mucosa next to the amalgam restoration. (b) White striae on the
mucosa next to the amalgam restoration
a b
Fig. 5.26 (a) White striae with interspersed erythema on the right buccal mucosa. (b) White striae on the left buccal
mucosa, with erythematous and erosive lesions on the mucosa lining the vestibular groove of the left mandibular molars
a b
Fig. 5.30 (a) Blanching of right buccal mucosa. (b) Blanching of left buccal mucosa. (c) Blanching of the palatal mucosa
One hypothesis is that HSPs are unveiled by UV is still debatable whether these deposits directly
radiation; this process is followed by interac- participate in the pathogenesis of DLE or are just
tion of HSPs with accumulated T cells, leading secondary to the development of DLE lesions. It
to liquefactive degeneration of basal epithelial is noticeable that increased immunoglobulin pro-
cells [67]. duction has been reported in DLE, most of which
Genetic background also played an important are induced by activation of B cells, indicating
part in the pathogenesis of DLE. Several haplo- that humoral and cellular immune responses are
types, such as human histocompatibility (HLA) both involved in DLE [67] .
-B7, B8, and Cw7, have been related with indi- The skin lesion of DLE usually emerged in
vidual’s susceptibility to DLE. HLA-DQA-0102 the form of an erythematous papule and then fol-
and HLA-DRB-1601 alleles have also been con- lowed by hyperkeratosis with follicular plugging.
sidered as potential genetic marker for DLE [68, Pigmentary changes may happen. The center of
69]. Recently, genome-wide association studies the lesion is usually atrophic and hypopigmented,
(GWAS) have shed a new light on the genetic while the periphery is often hyperpigmented.
background of systemic lupus erythematosus The face, scalp, ears, and chest are frequently
(SLE). Nevertheless, it is still uncertain whether affected. The lesions are persistent and may pro-
those genes recognized by GWAS have exactly duce scarring [71] (Fig. 5.33).
the same role in the development of DLE. Approximately 20% of the patients with DLE
Several observations suggest that DLE may be have oral lesions, with or without skin involve-
affected by hormones. For instance, the incidence ment [67, 72]. The vermilion, buccal mucosa,
of DLE is higher in women and the severity of and tongue are commonly affected. Although
DLE in women’s menstrual cycle, pregnancy, the lesions most often locate on the lower lip,
and menopause [70]. both the upper and lower lip can be involved at
Even though defined autoantibodies of SLE the same time (Figs. 5.34, 5.35, and 5.36). The
are not often detected in DLE, tissue binding typical lesion is a well-demarcated plaque with
of immunoglobulins and complements are usu- central erythema surrounded with short white
ally found at the dermo-epidermal junction. streaks in a radial pattern. The cutaneous side of
Therefore, DLE is considered as a chronic auto- the lesion could be pigmented, with or without
immune mucocutaneous disorder. However, it white striae. The borderline of mucosa and skin
can be blurry, and the lesion has a tendency to
invade into the skin.
The diagnosis of DLE may be made accord-
ing to the clinical appearance and be further con-
firmed by histopathological findings.
Fig. 5.33 DLE lesions involving the lower lip and the
skin of the right cheek. Erosive lesion with radiating white
striae and blood crust was observed on the lower lip, while
atrophic lesion with central hypopigmentation and periph-
eral hyperpigmentation was observed on the skin of the
right cheek Fig. 5.34 DLE lesions involving the upper and lower lips
110 H. Dan et al.
Fig. 5.35 DLE lesion on the left buccal mucosa Fig. 5.36 DLE lesion on the ventrum of the tongue
Typical histopathological changes include of patients at high risk. The patient may also
vacuolar degeneration of basal cells, lympho- be referred to rheumatologists or nephrologists
cyte infiltration surrounding the blood vessels, when necessary. It has been reported that treat-
and appendages in the dermis. Epidermal atro- ment with hydroxychloroquine or chloroquine
phy, hyperkeratosis with follicular plugging, at an early stage could delay the occurrence of
and vascular dilation with colloid bodies may be SLE in DLE patients and may prevent or alleviate
observed [67]. damage to peripheral organs [76] .
Direct immunofluorescence (DIF) can be used The recommended first-line systemic therapy
for the differential diagnosis of DLE and other for DLE is hydroxychloroquine (0.1 g b.i.d. for
diseases. Linear or granular deposits of immuno- 2 weeks or longer). Vitamin B6 (5 mg b.i.d.) is sup-
globulins and complement components along the posed to be taken at the same time to ameliorate
dermo-epidermal junction may be detected. gastrointestinal reaction. Besides, thalidomide
DLE is classified as one of the oral poten- (50–100 mg q.d.) or tripterygium hypoglaucum
tially malignant disorders by World Health tablets (2 g t.i.d. for 2 weeks or longer) can also
Organization. Although the incidence of DLE is be used. Systemic prednisone acetate (15–25 mg
higher in women and people of African descents, daily, in a single morning dose, for 5–7 days)
the malignant transformation is more likely to is often given in short courses to patients with
happen in European males. It has been reported widespread lesions or acute exacerbation, before
that in a follow-up period of 26–41 years, 3.3% switching the treatment plan to the reagents men-
of the patients developed squamous cell carci- tioned above. Total glucosides of paeony capsules
noma [73]. In another retrospective study, 6 out (0.6 g b.i.d./t.i.d. for 3 weeks or longer) can be
of 87 patients with diagnosis of oral DLE devel- used by patients with mild symptoms. Topical
oped oral cancer [74]. agents that had been reported effective for DLE
Around 5% of DLE cases may develop to SLE, include mouth rinse and liniments. Mouth rinses,
especially patients with HLA-B8 [75]. Identified including compound chlorhexidine solution, com-
clinical risk factors include widespread DLE pound borax solution (diluted fivefold with water
lesions, telangiectasias, arthritis, arthralgias, and before use), and 1% povidone iodine solution, can
Raynaud’s phenomenon. Laboratory risk factors be used for hydropathic compress, three times a
include anemia, leucopenia, thrombocytopenia, day. Liniments are mainly topical corticosteroids,
high erythrocyte sedimentation rates (ESRs), such as dexamethasone paste, prednisolone ace-
high levels of anticardiolipin antibodies, high tate suspension, triamcinolone acetonide, triam-
titres of antinuclear antibodies (ANAs), and cinolone acetonide oral paste, and dexamethasone
positive DIF findings in skin with normal appear- ointment. Additionally, triamcinolone acetonide
ance. More aggressive treatments and frequent injection or compound betamethasone injection
follow-up may be necessary for the management combined with sterile water or 2% lidocaine
5 Oral Mucosal Patches Striae Diseases 111
(at a ratio of 1:1) can be used for intra-lesional must be minimized by avoiding the peak hours for
injection. Aerosol therapy with dexamethasone sun exposure and by wearing protective clothing
sodium phosphate injection, gentamycin sulfate and high efficiency sunscreens. Diet containing
injection, vitamin C injection, and Vitamin B12 large amount of spicy food and seafood should be
injection, once or twice a day for 3–5 days, is an avoided. A regular follow-up is necessary to pre-
optional topical therapy. Moreover, sun exposure vent potentially malignant transformation.
a b
Fig. 5.37 (a) Yellowish-white spots were observed on the vermillion. (b) Yellowish-white spots on the right buccal
mucosa. (c) Yellowish-white spots on the left buccal mucosa
5.10 M
orsicatio Buccarum et
Labiorum
a b
Fig. 5.38 (a) The inner surface of the lower lip was cov- the underneath mucosa was intact and didn’t have any sig-
ered by squama that was partially attached to the epithe- nificant color change or ulceration. (c) The right buccal
lium. In the area where the squama was peeled off, the mucosa was covered by squama that was partially attached
underneath mucosa was intact and didn’t have any signifi- to the epithelium. In the area where the squama was peeled
cant color change or ulceration. (b) The left buccal mucosa off, the underneath mucosa was intact and didn’t have any
was covered by squama that was partially attached to the significant color change or ulceration
epithelium. In the area where the squama was peeled off,
5 Oral Mucosal Patches Striae Diseases 113
References 19. Zhang JM, Yang ZW, Chen RY, Gao P, Zhang YR,
Zhang LF. Two new mutations in the keratin 4 gene
causing oral white sponge nevus in Chinese family.
1. Banoczy J, Gintner Z, Dombi C. Tobacco use and oral
Oral Dis. 2009;15(1):100–5.
leukoplakia. J Dent Educ. 2001;65(4):322–7.
20. Shibuya Y, Zhang J, Yokoo S, Umeda M, Komori
2. Amagasa T, Yamashiro M, Uzawa N. Oral premalig-
T. Constitutional mutation of keratin 13 gene in
nant lesions: from a clinical perspective. Int J Clin
familial white sponge nevus. Oral Surg Oral Med Oral
Oncol. 2011;16(1):5–14.
Pathol Oral Radiol Endod. 2003;96(5):561–5.
3. Martorell-Calatayud A, Botella-Estrada R, Bagan-
21. Cutlan JE, Saunders N, Olsen SH, Fullen DR. White
Sebastian JV, Sanmartin-Jimenez O, Guillen-Barona
sponge nevus presenting as genital lesions in a 28-year-
C. Oral leukoplakia: clinical, histopathologic, and
old female. J Cutan Pathol. 2010;37(3):386–9.
molecular features and therapeutic approach. Actas
22. Farhi D, Dupin N. Pathophysiology, etiologic fac-
Dermosifiliogr. 2009;100(8):669–84.
tors, and clinical management of oral lichen pla-
4. Ge L, Zhou HM, Zeng X, Wu LY, Lin M. A case report
nus, part I: facts and controversies. Clin Dermatol.
on canceration of proliferative verrucous leukoplakia.
2010;28(1):100–8.
Hua Xi Kou Qiang Yi Xue Za Zhi. 2007;25(3):310–2.
23. Li ZW, Zhou Y, Zhao M. Progresses in studies on
5. Gupta PC, Mehta FS, Daftary DK, et al. Incidence
association between psychological factors and oral
rates of oral cancer and natural history of oral pre-
lichen plans. Zhonghua Kou Qiang Yi Xue Za Zhi.
cancerous lesions in a 10-year follow-up study of
2009;44(4):250–2.
Indian villagers. Community Dent Oral Epidemiol.
24. Krasowska D, Chodorowska G, Koziol-Monrewka M,
1980;8(6):283–333.
et al. The -308 promoter polymorphism in the tumour
6. Banoczy J. Follow-up studies in oral leukoplakia. J
necrosis factor gene in patients with lichen planus.
Maxillofac Surg. 1977;5(1):69–75.
Acta Derm Venereol. 2005;85(5):400–3.
7. Larsson A, Warfvinge G. Malignant transformation of
25. Bai J, Jiang L, Lin M, et al. Association of polymor-
oral lichen planus. Oral Oncol. 2003;39(6):630–1.
phisms in the tumor necrosis factor-alpha and inter-
8. Cowan CG, Gregg TA, Napier SS, McKenna SM,
leukin-10 genes with oral lichen planus: a study in
Kee F. Potentially malignant oral lesions in northern
Chinese cohort with Han ethnicity. J Interf Cytokine
Ireland: a 20-year population-based perspective of
Res. 2009;29(7):381–8.
malignant transformation. Oral Dis. 2001;7(1):18–24.
26. Xavier GM, de Sa AR, Guimaraes AL, et al.
9. Reibel J. Prognosis of oral pre-malignant lesions: sig-
Investigation of functional gene polymorphisms inter-
nificance of clinical, histopathological, and molecular
leukin-1 beta, interleukin-6, inerleukin-10 and tumor
biological characteristics. Crit Rev Oral Biol Med.
necrosis factor in individuals with oral lichen planus.
2003;14(1):47–62.
J Oral Pathol Med. 2007;36(8):467–81.
10. D’Souza G, Kreimer AR, Viscidi R, et al. Case-control
27. Kimkong I, Hirankarn N, Nakkuntod J, et al.
study of human papillomavirus and oropharyngeal
Tumor necrosis factor-alpha gene polymorphisms
cancer. N Engl J Med. 2007;356(19):1944–56.
and susceptibility to oral lichen planus. Oral Dis.
11. Bagan JV, Jimenez Y, Murillo J, et al. Epstein-Barr
2011;17(2):206–9.
virus in oral proliferative verrucous leukoplakia and
28. Stojanovice L, Lunder T, Poljak M, et al. Lack of evi-
squamous cell carcinoma: a preliminary study. Med
dence for hepatitis C virus infection in association with
Oral Patol Oral Cir Bucal. 2008;13(2):E110–3.
lichen planus. Int J Dermatol. 2008;47(12):1250–6.
12. Zhang L, Rosin MP. Loss of heterozygosity: a poten-
29. Zhou Y, Jiang L, Liu J, et al. The prevalence of hepa-
tial tool in management of oral premalignant lesions.
titis C virus infection in oral lichen planus in an eth-
J Oral Pathol Med. 2001;30(9):513–20.
nic Chinese cohort of 232 patients. Int J Oral Sci.
13. Sudbo J, Lippman SM, Lee JJ, et al. The influence of
2010;2(2):90–7.
resection and aneuploidy on mortality in oral leuko-
30. Gimenez-Garcia R, Perez-Castrillon JL. Lichen
plakia. N Engl J Med. 2004;350(14):1405–13.
planus and hepatitis C virus infection. J Eur Acad
1 4. Poeta ML, Manola J, Goldwasser MA, et al.
Dermatol Venereol. 2003;17(3):291–5.
TP53 mutations and survival in squamous-cell
31. Beaird LM, Kahloon N, Franco J, et al. Incidence of
carcinoma of the head and neck. N Engl J Med.
hepatitis C in lichen planus. J Am Acad Dermatol.
2007;357(25):2552–61.
2001;44(2):311–2.
15. Bouquot JE, Gorlin RJ. Leukoplakia, lichen planus,
32. Lodi G, Scully C, Carrozzo M, Griffiths M, Sugerman
and other oral keratoses in 23,616 white Americans
PB, Thongprasom K. Current controversies in oral
over the age of 35 years. Oral Surg Oral Med Oral
lichen planus: report of an international consensus
Pathol. 1986;61(4):373–81.
meeting. Part 1. Viral infections and etiopathogenesis.
16.
Bhattacharyya I, Chehal HK. White lesions.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod.
Otolaryngol Clin N Am. 2011;44(1):109–31, vi.
2005;100(1):40–51.
17. Martin JL. Leukoedema: an epidemiological study
33. Sousa FA, Rosa LE. Oral lichen planus: clini-
in white and African Americans. J Tenn Dent Assoc.
cal and histopathological considerations. Braz J
1997;77(1):18–21.
Otorhinolaryngol. 2008;74(2):284–92.
18. Damm DD. Bilateral white cheeks. White sponge
34. Shen ZY, Liu W, Feng JQ, Zhou HW, Zhou
nevus. Gen Dent. 2010;58(6):539–40.
ZT. Squamous cell carcinoma development in pre-
5 Oral Mucosal Patches Striae Diseases 115
viously diagnosed oral lichen planus: de novo or 52. Ranganathan K, Devi MU, Joshua E, Kirankumar
transformation. Oral Surg Oral Med Oral Pathol Oral K, Saraswathi TR. Oral submucous fibrosis: a case-
Radiol Endod. 2011;112(5):592–6. control study in Chennai, South India. J Oral Pathol
35. Krutchkoff DJ, Cutler L, Laskowski S. Oral lichen Med. 2004;33(5):274–7.
planus: the evidence regarding potential malignant 53. Harvey W, Scutt A, Meghji S, Canniff JP. Stimulation
transformation. J Oral Pathol. 1978;7(1):1–7. of human buccal mucosa fibroblasts in vitro by betel-
36. Ismail SB, Kumar SK, Zain RB. Oral lichen planus nut alkaloids. Arch Oral Biol. 1986;31(1):45–9.
and lichenoid reactions: etiopathogenesis, diagnosis, 54. Meghji S, Scutt A, Harvey W, Canniff JP. An in-
management and malignant transformation. J Oral vitro comparison of human fibroblasts from normal
Sci. 2007;49(2):89–106. and oral submucous fibrosis tissue. Arch Oral Biol.
37. Schlosser BJ. Lichen planus and lichenoid reactions of 1987;32(3):213–5.
the oral mucosa. Dermatol Ther. 2010;23(3):251–67. 55. Utsunomiya H, Tilakaratne WM, Oshiro K, et al.
38. Crincoli V, Di BMB, Scivetti M, Lucchese A, Tecco Extracellular matrix remodeling in oral submucous
S, Festa F. Oral lichen planus: update on etiopatho- fibrosis: its stage-specific modes revealed by immu-
genesis, diagnosis and treatment. Immunopharmacol nohistochemistry and in situ hybridization. J Oral
Immunotoxicol. 2011;33(1):11–20. Pathol Med. 2005;34(8):498–507.
39. Mohty M, Kuentz M, Michallet M, et al. Chronic 56. Kuo MY, Chen HM, Hahn LJ, Hsieh CC, Chiang
graft-versus-host disease after allogeneic blood stem CP. Collagen biosynthesis in human oral sub-
cell transplantation: long-term results of a random- mucous fibrosis fibroblast cultures. J Dent Res.
ized study. Blood. 2002;100(9):3128–34. 1995;74(11):1783–8.
40. Imanguli MM, Alevizos I, Brown R, Pavletic SZ, 57. Shieh DH, Chiang LC, Lee CH, Yang YH, Shieh
Atkinson JC. Oral graft-versus-host disease. Oral Dis. TY. Effects of arecoline, safrole, and nicotine on
2008;14(5):396–412. collagen phagocytosis by human buccal mucosal
41. Flowers ME, Parker PM, Johnston LJ, et al.
fibroblasts as a possible mechanism for oral sub-
Comparison of chronic graft-versus-host dis- mucous fibrosis in Taiwan. J Oral Pathol Med.
ease after transplantation of peripheral blood stem 2004;33(9):581–7.
cells versus bone marrow in allogeneic recipients: 58. Shieh DH, Chiang LC, Shieh TY. Augmented mRNA
long-term follow-up of a randomized trial. Blood. expression of tissue inhibitor of metalloproteinase-
2002;100(2):415–9. 1 in buccal mucosal fibroblasts by arecoline and saf-
42.
Kramer IR, Lucas RB, Pindborg JJ, Sobin role as a possible pathogenesis for oral submucous
LH. Definition of leukoplakia and related lesions: an fibrosis. Oral Oncol. 2003;39(7):728–35.
aid to studies on oral precancer. Oral Surg Oral Med 59. Chang YC, Yang SF, Tai KW, Chou MY, Hsieh
Oral Pathol. 1978;46(4):518–39. YS. Increased tissue inhibitor of metalloproteinase-1
43. Villa A, Villa C, Abati S. Oral cancer and oral erythro- expression and inhibition of gelatinase A activity in
plakia: an update and implication for clinicians. Aust buccal mucosal fibroblasts by arecoline as possible
Dent J. 2011;56(3):253–6. mechanisms for oral submucous fibrosis. Oral Oncol.
44. Hashibe M, Mathew B, Kuruvilla B, et al. Chewing 2002;38(2):195–200.
tobacco, alcohol, and the risk of erythroplakia. Cancer
60. Haque MF, Harris M, Meghji S, Barrett
Epidemiol Biomark Prev. 2000;9(7):639–45. AW. Immunolocalization of cytokines and growth factors
45. Reichart PA, Philipsen HP. Oral erythroplakia—a
in oral submucous fibrosis. Cytokine. 1998;10(9):713–9.
review. Oral Oncol. 2005;41(6):551–61. 61. Chiang CP, Hsieh RP, Chen TH, et al. High inci-
46. Hosni ES, Salum FG, Cherubini K, Yurgel LS,
dence of autoantibodies in Taiwanese patients
Figueiredo MA. Oral erythroplakia and speckled leu- with oral submucous fibrosis. J Oral Pathol Med.
koplakia: retrospective analysis of 13 cases. Braz J 2002;31(7):402–9.
Otorhinolaryngol. 2009;75(2):295–9. 62. Tilakaratne WM, Klinikowski MF, Saku T, Peters
47. Shear M. Erythroplakia of the mouth. Int Dent J. TJ, Warnakulasuriya S. Oral submucous fibrosis:
1972;22(4):460–73. review on aetiology and pathogenesis. Oral Oncol.
48. Duvvi SK, Thomas L, Vijayanand S, Reddy KT. Two- 2006;42(6):561–8.
week rule for suspected head and neck cancer. A study 63. Ma RH, Tsai CC, Shieh TY. Increased lysyl oxidase
of compliance and effectiveness. J Eval Clin Pract. activity in fibroblasts cultured from oral submucous
2006;12(6):591–4. fibrosis associated with areca nut chewing in Taiwan.
49. van der Waal I. Potentially malignant disorders of the J Oral Pathol Med. 1995;24(9):407–12.
oral and oropharyngeal mucosa; terminology, clas- 64. Rajendran R, Kumari KR, Kumar AS. Liver ultra-
sification and present concepts of management. Oral sound and faecal copper estimation in oral submucous
Oncol. 2009;45(4–5):317–23. fibrosis. Indian J Dent Res. 2003;14(1):13–21.
50. Mignogna MD, Fedele S. Oral cancer screening: 5 min- 65. Angadi PV, Rao SS. Areca nut in pathogenesis of oral
utes to save a life. Lancet. 2005;365(9475):1905–6. submucous fibrosis: revisited. Oral Maxillofac Surg.
51. Auluck A, Rosin MP, Zhang L, Sumanth KN. Oral 2011;15(1):1–9.
submucous fibrosis, a clinically benign but potentially 66. Tebbe B. Clinical course and prognosis of cutane-
malignant disease: report of 3 cases and review of the ous lupus erythematosus. Clin Dermatol. 2004;22(2):
literature. J Can Dent Assoc. 2008;74(8):735–40. 121–4.
116 H. Dan et al.
67. Donnelly AM, Halbert AR, Rohr JB. Discoid lupus 76. Chong BF, Song J, Olsen NJ. Determining risk fac-
erythematosus. Australas J Dermatol. 1995;36(1):3–10; tors for developing systemic lupus erythematosus in
quiz 11–2. discoid lupus erythematosus patients. Br J Dermatol.
68. Knop J, Bonsmann G, Kind P, et al. Antigens of the 2012;166(1):29–35.
major histocompatibility complex in patients with 77. Mansur AT, Aydingoz IE. Unilateral buccal Fordyce
chronic discoid lupus erythematosus. Br J Dermatol. spots with ipsilateral facial paralysis: a sign of
1990;122(6):723–8. neuro-sebaceous connection? Acta Derm Venereol.
69. Volc-Platzer B, Anegg B, Milota S, Pickl W, Fischer 2012;92(2):177–8.
G. Accumulation of gamma delta T cells in chronic 78. Yuan H, et al. Corticotrophin-releasing hormone
cutaneous lupus erythematosus. J Invest Dermatol. (CRH) facilitates axon outgrowth. Spinal Cord.
1993;100(1):84S–91S. 2010;48(12):850–6.
70. Yell JA, Burge SM. The effect of hormonal changes 79. Toyoda M, Nakamura M, Morohashi M. Neuropeptides
on cutaneous disease in lupus erythematosus. Br J and sebaceous glands. Eur J Dermatol. 2002;12(5):
Dermatol. 1993;129(1):18–22. 422–7.
71. Hordinsky M. Cicatricial alopecia: discoid lupus ery- 80. Deplewski D, Rosenfield RL. Growth hormone and
thematosus. Dermatol Ther. 2008;21(4):245–8. insulin-like growth factors have different effects
72. Burge SM, Frith PA, Juniper RP, Wojnarowska
on sebaceous cell growth and differentiation.
F. Mucosal involvement in systemic and chronic cutane- Endocrinology. 1999;140(9):4089–94.
ous lupus erythematosus. Br J Dermatol. 1989;121(6): 81. Ocampo-Candiani J, et al. Treatment of Fordyce spots
727–41. with CO2 laser. Dermatol Surg. 2003;29(8):869–71.
73. Dhingra M, Bhalla M, Thami GP, Mittal P. Metastasizing 82. Glass LF, Maize JC. Morsicatio buccarum et labiorum
squamous cell carcinoma arising from chronic discoid (excessive cheek and lip biting). Am J Dermatopathol.
lupus erythematosus plaque of recent onset. Indian J 1991;13(3):271–4.
Dermatol Venereol Leprol. 2011;77(5):626. 83. Wang JY, Liu WZ, Li XY, Li ZW, Zeng X. Morsicatio
74. Liu W, Shen ZY, Wang LJ, et al. Malignant potential of buccarum et labiorum: two cases report. Hua Xi Kou
oral and labial chronic discoid lupus erythematosus: a Qiang Yi Xue Za Zhi. 2009;27(6):681–2. 685
clinicopathological study of 87 cases. Histopathology. 84. Damm DD, Fantasia JE. Bilateral white lesions of
2011;59(2):292–8. buccal mucosa. Morsicatio buccarum. Gen Dent.
75. Harper JG, Pilcher MF, Szlam S, Lind DS. Squamous 2006;54(6):442. 444
cell carcinoma in an African American with discoid 85. Sewerin I. A clinical and epidemiologic study mor-
lupus erythematosus: a case report and review of the sicatio buccarum-labiorum. Scand J Dent Res.
literature. South Med J. 2010;103(3):256–9. 1971;79(2):73–80.
Labiolingual Diseases
6
Lu Jiang, Xin Jin, and Qianming Chen
L. Jiang
State Key Laboratory of Oral Diseases, National
Clinical Research Center for Oral Diseases,
Fig. 6.1 Many scattered vertical fissures distributed on
Department of Oral Medicine, West China Hospital
mucosa of upper and lower lips, with exudate and yellow
of Stomatology, Sichuan University,
crust
Chengdu, Sichuan, China
X. Jin Age: 17 years
College of Stomatology, Chongqing Medical
Sex: Male
University, Chongqing Key Laboratory of Oral
Diseases and Biomedical Sciences, Chief Complaints:
Chongqing, China A 17-year-old boy complained of cracked lips
Q. Chen (*) associated with pain for 2 months
Changjiang Scholars Program, Ministry of Education, History of Present Illness:
Beijing, China A 17-year-old boy presented to our clinic com-
State Key Laboratory of Oral Diseases, National plaining of dry and scaly lips, which were fol-
Clinical Research Center for Oral Diseases, lowed by painful, cracked, and bleeding lesions
Department of Oral Medicine, West China Hospital
for the past 2 months. He habitually licked his lips.
of Stomatology, Sichuan University, Chengdu,
Sichuan, China Past Medical History: None
e-mail: qmchen@scu.edu.cn Allergy: None
© Springer Nature Singapore Pte Ltd. and People’s Medical Publishing House 2018 117
Q. Chen, X. Zeng (eds.), Case Based Oral Mucosal Diseases,
https://doi.org/10.1007/978-981-13-0286-2_6
118 L. Jiang et al.
Case 62 Cheilitis Glandularis between the lips for over 30 years. She had no
other symptoms, such as dryness, pain, or
a itching.
Past Medical History: None
Allergy: None.
Physical Examination:
Mild dryness and small scales were present on
the upper and lower lips. Oral cavity examination
revealed multiple nodules on the vermilion bor-
der of the upper lip and the inner aspect of the
lower labial mucous membrane (Fig. 6.3a).
Enlarged ostia that secreted clear tenacious
mucus were visible (Fig. 6.3b).
b Diagnosis:
Cheilitis glandularis
Diagnosis Basis:
Management:
1. Medication
Rp.: Loratadine 10 mg × 12 tablets
b Sig.: 10 mg q.d. p.o.
Multivitamin formula with minerals 60
tablets
Sig.: 1 tablet q.d. p.o.
2% sodium bicarbonate solution 250 ml × 1
Sig.: rinse t.i.d.
Dexamethasone paste 15 g × 1
Sig.: topical use t.i.d.
Nystatin liniment 15 g × 1
Sig.: topical use t.i.d.
2.
Triamcinolone acetonide (TA) injection
Fig. 6.4 (a) Edema and induration of the upper lip. (b)
40 mg × 1
Deep grooves in dorsum of the tongue
Sig.: multipoint low-dose injection st.
tions of eczema and erosion. Actinic cheilitis or hydroxychloroquine 0.1 g twice a day, for a
is caused by an allergy to ultraviolet radiation. period of 2 weeks.
After exposure to sunlight, melanin deposition Local therapies for eczematous cheili-
occurs in normal individuals, which makes tis mainly include hydropathic compresses
their skin darker, causing the symptoms to with chlorhexidine solution or topical ste-
regress spontaneously. However, individuals roids, such as dexamethasone paste, pred-
with sun allergy, on being exposed to an over- nisolone acetate injection, or triamcinolone
dose of sunlight, can have changes in mela- acetonide injection (dilution, 1:5) thrice a
nin deposition, intracellular or extracellular day. Recombinant human epidermal growth
edema, collagen denaturation, and increased factor hydrogels or solutions are also used.
cellular proliferation; these changes may initi- For cases with copious exudates, severe ero-
ate pathogenesis. Cheilitis of benign lymphad- sions, and thick crusts, aerosol therapy with
enosis is related to the remnants of the primary dexamethasone sodium phosphate, genta-
lymphoid hyperplasia, which resulted follow- micin sulfate, vitamin C, and vitamin B12
ing exposure to radiation during embryonic injections once or twice daily for 3 days is
development. recommended. Besides, local and multipoint
The histopathological changes of actinic low-dose injections of triamcinolone aceton-
cheilitis include epithelial hyperkeratosis (or ide may be administered to the labial lesions
parakeratosis), intracellular or extracellular once a week or every 2 weeks.
edema, bullous changes, infiltration of inflam- 2. Exfoliative cheilitis: The etiology of exfolia-
matory cells around the blood vessels and in the tive cheilitis is complicated; it may be related
submucosa, and basophilic changes in the col- to dry climate; windy environment; cold
lagen subepithelially [2]. Histopathologically, weather; irritation due to tobacco, alcohol,
cheilitis of benign lymphadenosis is charac- hot food, and repeated lip licking; and fungal
terized by the presence of lymphoid follicle- infection. The clinical features of exfoliative
like structures in the subepithelial connective cheilitis primarily include dryness and the
tissue. Sometimes, there may be a focal col- presence of several scales on the vermilion
lection of numerous lymphoid cells with less border. Vertical fractures, such as shallow
lymphoid follicles. cracks or deep fissures extending to the peri-
The main clinical features of eczematous oral skin, associated with bleeding, can be
cheilitis are erosions of the red lip, especially found in lesions of the red lip. Gray scales
the lower red lip. Light yellow exudates and may be seen along the completely vermilion
edema may be present on the vermilion bor- border. Patients with exfoliative cheilitis sec-
der. If deep erosion or secondary infection ondary to fungal infection complain of itch-
occurs, an obvious swelling of the vermilion ing and gray scales on the vermilion border
border with bleeding, ulceration, and crust- and surrounding skin. Histopathologically,
ing may be present. In addition, the cardinal the disease shows nonspecific inflammatory
symptom of benign lymphoproliferative chei- changes.
litis is paroxysmal severe itching. Systemic therapies for exfoliative cheilitis
Systemic therapies for eczematous cheili- include administration of micronutrient and
tis include administration of micronutrients vitamin supplements. Patients are adminis-
and vitamin supplements. Patients are usu- tered one tablet of multivitamin formula with
ally administered one tablet of multivitamin minerals each day, for a period of 30 days.
formula with minerals each day, for a period Local therapies mainly include hydropathic
of 30 days. In case of more serious manifesta- compresses with chlorhexidine solution
tions, the patients are administered prednisone or topical steroids such as dexamethasone
acetate 15–25 mg once a day in the morning, paste, prednisolone acetate injection, or tri-
122 L. Jiang et al.
Management:
1. Medication
Rp.: Pidotimod 0.4 g × 18 tablets
Fig. 6.9 Redness at the bilateral labial angles, obvious Sig.: 0.4 g q.d. p.o.
chapping on right side Folic acid 5 mg × 100 tablets
Sig.: 10 mg t.i.d. p.o.
Age: 82 years Compound vitamin B 100 tablets
Sex: Female Sig.: 2 tablets t.i.d. p.o.
Chief Complaints: 2% sodium bicarbonate solution 250 ml × 1
Red lesions and rhagades in both commissures of Sig.: rinse t.i.d.
the mouth for 6 months in an 82-year-old woman Nystatin liniment 15 g × 1
History of Present Illness: Sig.: topical use t.i.d.
An 82-year-old woman visited our clinic with
redness and rhagades in both commissures of the [Review] Angular Cheilitis
mouth lasting for 6 months, together with pain Angular cheilitis is the inflammation of bilateral
and hemorrhagic tendency when she opened her commissures of the upper and lower lips. The
mouth to the limit. morbidity is 0.7–3.8% for adults and 0.2–15.1%
Past Medical History: Cataract for children.
Allergy: None Angular cheilitis, clinically characterized by
Physical Examination: erythema, moist maceration, ulceration, crusting
Erythematous lesions were observed in bilateral at the corners of the mouth, and scales covering
angles of the mouth, and rhagades on the right adjacent areas, is usually accompanied by various
side were more obvious. Additionally, the filiform amounts of pain, burning, and itching sensation.
papilla on the dorsum of the tongue appeared to To date, few studies have been conducted to
be slightly atrophic and erythematous, while the explore the etiology and mechanisms of angular
palate mucosa presented with congestion and red- cheilitis. However, it is generally believed to be
ness (Fig. 6.9). The patient was toothless in both one disease caused by multiple local and sys-
dentitions. No obvious abnormalities were temic factors, acting alone or in combination [8].
observed during routine blood examination. Angular cheilitis associated with local factors
Clinical Impression: is primarily categorized as irritant, allergic, or
Angular cheilitis infectious.
Further Examination: Irritant angular cheilitis accounts for approxi-
No apparent results were obtained during routine mately 22% of all cases. Compared with other
blood examination and blood glucose testing. sites, the corners of the mouth and lips are
Positive results for fungal infection were obtained exposed to stagnant saliva for a longer period
in the smear test of the mouth and both angular and are therefore more likely to be infused and
areas. digested by the stagnant salivin, exacerbating
126 L. Jiang et al.
irritation and inflammation. Angular cheilitis 11.3–31.8% of patients with angular cheilitis.
is more easily induced by prolonged contact Additionally, the deficiency of nicotinic acid,
with these irritants and anatomical changes, for folic acid, and zinc is related to angular cheilitis.
instance, deeper wrinkles in the skin adjacent Therefore, angular cheilitis is frequently accom-
to the corners of the mouth [9]. The reduction panied by atrophic glossitis.
of vertical distance enables the formation of Angular cheilitis is associated with various
grooves in the skin in the corners of the mouth, systemic diseases, including Down’s syndrome,
which is a significant factor contributing to angu- xerostomia, inflammatory bowel disease, Sjogren
lar cheilitis in older people, as seen in 11% of syndrome, diabetes, and some systemic infec-
elderly patients with angular cheilitis and 18% of tious diseases, namely, acquired immune defi-
denture-wearing patients with angular cheilitis. ciency syndrome, syphilis, and so on.
In addition, common irritant factors in the clinic Angular cheilitis might also be caused by the
include anodontia, tooth displacement, wearing adverse effects of some medicines. The conven-
orthodontic devices, destruction of elastic tissue tional medicine mainly contains isotretinoin,
by prolonged ultraviolet radiation and smoking, indinavir against HIV, and narcotics like cocaine
hygrostomia, and mechanical stimulation of pen- and heroin [17].
cils, dental floss, and oral mirror handles. All of Local and systemic factors usually work
the above factors can cause or exaggerate angular together. There might be diverse causative factors
cheilitis [8, 10, 11]. for the same patient; for instance, angular cheili-
Cheilitis can be induced when allergens tis in weak elderly people is collectively caused
come into contact with oral mucosa and the lips. by the reduction of vertical distance in the mouth,
Allergens can permeate the mucosa more easily malnutrition, dryness of the mouth, and coloniza-
in the presence of irritant angular cheilitis, and in tion by candida or bacteria.
turn, patients may suffer from allergic cheilitis. Hence, it is necessary to inquire about the
Several factors, namely, lipsticks, toothpastes, patients’ history of angular cheilitis comprehen-
cosmetics, mouthwash, amalgam, and dental res- sively, including initial site, duration, suspected
toration materials, can trigger angular cheilitis allergens, exaggerated or attenuated factors, as
[12–14]. well as whether the patient takes drugs or has
Infectious angular cheilitis is primarily caused malnutrition, anemia, or gastrointestinal dis-
by Candida albicans, followed by Staphylococcus eases. Close attention should be paid to the
aureus [10, 15]. Recurrent herpes labialis, asso- presence of vertical distance reduction in the
ciated with virus infection, also classified as lower face, oral hygiene, and whether the patient
infectious angular cheilitis, is usually seen in the wears denture or not, combined with the cultur-
vermilion border and can resemble the symptoms ing results for bacteria and fungi. Topical treat-
of angular cheilitis when it occurs in the corners ment is primarily dependent on the removal of
of the mouth. Pivotal clues for diagnosing her- local irritant factors, including adjusting and
pes simplex in the corners of the mouth based cleaning dentures and maintaining oral hygiene.
on medical history are recurrence at the same Additionally, antibiotic ointments, such as chlor-
site, a history of blistering, and duration of about tetracycline eye ointment, or nystatin liniment
5–7 days [16]. and compound ketoconazole creams against
Angular cheilitis is also correlated with vari- fungi, compound ulcer pastes for rhagades, and
able systemic factors. recombinant human epidermal growth factor
Angular cheilitis can sometimes predict hydrogel or solution may be applied to target the
nutritional deficiencies. About 25% of patients possible causes. In addition, specifically systemic
are lacking in iron and vitamin B, mainly vita- treatment should be employed to handle the pos-
min B2, B6, and B12. Anemia can be found in sible systemic etiology.
6 Labiolingual Diseases 127
Age: 24 years
Sex: Male
Chief Complaints:
Striae on the dorsum of the tongue for 1 year in a
24-year-old male
History of Present Illness:
A 24-year-old male presented to our clinic with
striae on the dorsum of his tongue lasting for
1 year. The location of the striae on the dorsum
changed over time, accompanied by irritant pain
when eating. The patient was highly susceptible
to the cold virus. Fig. 6.11 Many scattered regions of filiform papillary
atrophy on the dorsum of the tongue, proliferation of
Past Medical History: None peripheral filiform papillae, presenting as geographic
Allergy: None tongue
Physical Examination:
Atrophy of the filiform papillae was observed in Age: 3.5 years
the central area of the lesion on bilateral sides of Sex: Female
the tongue, surrounded by hyperplasic filiform Chief Complaints:
papillae in the peripheral zone. The whole area Striae on the dorsum of the tongue for 3.5 years
resembled a geographic map (Fig. 6.10). in a 3.5-year-old girl
Diagnosis: History of Present Illness:
Geographic glossitis A 3.5-year-old girl visited our clinic with striae on
Diagnosis Basis: the dorsum of her tongue that had persisted since
she was born. The location and shape of the striae
1. The dorsum of the patient’s tongue was cov- on the dorsum changed over time, and no impact
ered by geographic striae. on her eating was noted. The little girl was in
2. The lesion was migratory. good condition and not selective about food.
128 L. Jiang et al.
have any pain or discomfort. She was prone to Past Medical History: None
developing colds and had preferences for certain Allergy: None
foods. Physical Examination:
Past Medical History: None The foliate papillae over the root of the tongue on
Allergy: None the left were red and swollen (Fig. 6.20). There
Physical Examination: was no other oral mucosal involvement.
The fungiform papillae on the dorsum of the Diagnosis:
tongue were swollen, and the filiform papillae Foliate papillitis
were atrophic. The tongue was reddish and with- Diagnosis Basis:
out its coating, thus exhibiting the appearance of
a strawberry tongue (Fig. 6.19). 1 . The patient had subjective symptoms.
Diagnosis: 2. Slight redness of foliate papillae on left tongue
Fungiform papillitis root.
Diagnosis Basis:
The dorsum of the tongue was swollen, and the Management:
filiform papillae were atrophic.
Management: 1. Medication
Rp.: Compound chlorhexidine solution 300 ml × 1
1. Medication Sig.: rinse t.i.d.
Rp.: Compound chlorhexidine solution 300 ml × 1 Compound ulcer paste 15 g × 1
Sig.: rinse t.i.d. Sig.: topical use t.i.d.
2. Psychological counseling.
Case 73 Foliate Papillitis
[Review] Lingual Papillitis
Lingual papillae include filiform, fungiform,
circumvallate, and foliate papillae. Pathologies
involving the filiform papillae mainly present as
atrophic lesions, and others present as nonspe-
cific inflammation, such as congestion, swelling,
and pain.
The cause of lingual papillitis is not clearly
known. Filiform papillitis is related to systemic
factors, such as certain anemias, blood disor-
ders, fungal infections, antibiotic abuse, and
vitamin deficiencies. Fungiform papillitis may
Fig. 6.20 Slight redness of foliate papillae on left tongue be a presentation of the mucocutaneous lymph
root node syndrome (Kawasaki disease [33]) or it
may present in association with some anemias.
Age: 59 years Stimulation by local factors, such as sharp teeth,
Sex: Female dental calculi, ill-fitting prostheses, and spicy
Chief Complaints: and hot food, also plays an important role in the
A 59-year-old woman with discomfort of the pathogenesis of fungiform and foliate papillitis.
tongue root for the past 10 days Foliate papillitis is also related to pharyngeal
History of Present Illness: inflammation.
A 59-year-old woman presented with discomfort Filiform papillitis mainly presents as atro-
and mild pain at the root of the tongue for the past phic glossitis with thinning of the epithelium.
10 days. Several reddish vesicles were noted at Additionally, the dorsum of the tongue often has
the root of the tongue on the left. shallow grooves and fissures.
134 L. Jiang et al.
Fungiform papillitis presents with swollen and Past Medical History: None
congested fungiform papillae. Affected patients Allergy: None
complain of burning sensation over the tongue and Physical Examination:
pain. The papillae are swollen, giving the appear- The filiform papillae on his tongue were enlarged
ance of a strawberry or raspberry tongue [34]. and elongated. The tongue was coated and had a
Circumvallate papillitis is very rare. brown to black coloration (Fig. 6.21).
Foliate papillae are located on either side at the Diagnosis:
base of the tongue and adjacent to the pharynx. Coated tongue
They usually appear as 5–8 vertically parallel Diagnosis Basis:
mucosal folds at the margins of the tongue with The filiform papillae on the tongue were enlarged
abundant lymphoid tissue. Foliate papillitis and elongated.
may present with swollen foliate papillae and Management:
increased concavity of the mucosal folds. These
patients often experience pain or discomfort. 1. Medication
Moreover, the discomfort and pain may develop Rp.: Pidotimod 0.4 g × 18 tablets
into a fear of cancer, which usually makes the Sig.: 0.4 g q.d. p.o.
symptoms worse [1]. Vitamin B 100 tablets
Regarding treatment, if patients with lingual Sig.: 2 tablets t.i.d. p.o.
papillitis have evident causes such as anemia and 2% sodium bicarbonate solution 250 ml × 1
vitamin deficiencies, they should be treated sys- Sig.: rinse t.i.d.
temically by correcting the anemia and supple- Nystatin liniment 15 g × 1
menting the appropriate vitamins, respectively. Sig.: topical use t.i.d.
Local therapy includes antibacterial gargling 2. He was instructed to brush the dorsum of his
using compound chlorhexidine solution or rins- tongue with a soft bristle toothbrush.
ing using compound borax solution (fivefold
dilution). Adjuvant therapy includes removal of [Review] Coated Tongue
the local irritants (e.g., grinding sharp teeth and Coated tongue is a chronic condition in which
periodontal scaling). the tiny bumps on the surface of the tongue
(called filiform papillae) enlarge and elongate
to form hair-like projections. The hyperplastic
6.8 Coated Tongue papillae subsequently become pigmented, taking
on a black, brown, white, yellow, or green col-
Case 74 Coated Tongue oration; thus, the tongue is called black, brown,
Age: 61 years
Sex: Male
Chief Complaints:
A 61-year-old man presented with a coated
tongue for the past 4 months
History of Present Illness:
A 61-year-old man presented to our clinic with a
coated and black tongue for the past 4 months.
He was administered antibiotics for pneumonia
and halitosis in the past; he did not complain of
pain. He also reported a foreign body sensation.
A recent blood glucose evaluation showed nor-
mal results. He had a history of chronic Fig. 6.21 Proliferation of filiform papillae on dorsum of
bronchitis. the tongue, tongue coating with dark brown color
6 Labiolingual Diseases 135
white (Fig. 6.22), yellow, or green hairy tongue, Case 75 Lingual Tonsil Hypertrophy
respectively. Age: 57 years
Normally, the friction between the food and Sex: Female
the mucosa of the tongue and palate causes shed- Chief Complaints:
ding of the keratinocyte layer of the filiform “Vesicles” over the base of the tongue on the left
papillae; subsequently, it is replaced with new for over 2 months
basal epithelial cells. Decreased activity of the History of Present Illness:
tongue due to some disease or pain may lead to A 57-year-old woman presented to our clinic
impaired desquamation of the filiform papillae. with “vesicles” over the base of her tongue on the
Subsequently, the tongue becomes coated with left for over 2 months; she also had oral paresthe-
bacteria and fungi, leading to the hairy clinical sia and slight pain while having a cold.
appearance. Long-term smoking of tobacco can Past Medical History: None
stimulate epithelial hyperplasia. Long-term abuse Allergy: None
of antibiotics can lead to oral fungal infections; Physical Examination:
infections with Rhizopus nigricans and Mucor The lingual tonsil at the base of the tongue on the left
mucedo are the most common fungal infections. was enlarged with limited vertical thickness; it was
Rare examples of black coated tongue include reddish, smooth, and soft on palpation (Fig. 6.23).
conditions with decreased immunity, such as
head and neck radiotherapy and diabetes [19, 35].
Coated tongue may be seen in adults above
30 years of age, manifesting as hyperplastic and
hairy filiform papillae. Elongated filiform papil-
lae may cause nausea. These patients also have
obvious halitosis without any other discomfort.
A coated tongue may be seen in adults above
30 years of age, manifesting as hyperplastic and
hairy filiform papillae. Elongated filiform papil-
lae may cause nausea. These patients also have
obvious halitosis without any other discomfort.
A coated tongue should be differentiated from
a black coating. Filiform papillae do not become Fig. 6.23 Edema of lingual tonsil visible at the left
elongated in a black coating, which is caused by tongue root and margin, with nodular shape, slight red-
colored foods or drugs [36]. ness, and glossy surface
136 L. Jiang et al.
Lingual tonsil
Base of
tongue
Circumvilate papilla
Foliate papilla
Dorsal surface Anterior 2/3
Lateral border (mobile)
tongue
Median sulcus
Fig. 6.25 Normal
structure of the tongue Tip
138 L. Jiang et al.
researches mainly focus on the capsaicin recep- 7. Banks T, Gada S. A comprehensive review of current
tors, which are related to neuronal adjustment treatments for granulomatous cheilitis. Br J Dermatol.
2012;166(5):934–7.
and inflammation [45, 51]. 8. Park KK, Brodell RT, Helms SE. Angular cheilitis,
Other systemic factors include metabolic and part 1: local etiologies. Cutis. 2011;87(6):289–95.
endocrine diseases, such as diabetes mellitus, 9. Ophaswongse S, Maibach HI. Allergic contact cheili-
hypothyroidism, and deficiencies of iron, zinc, tis. Contact Dermatitis. 1995;33(6):365–70.
10. Konstantinidis AB, Hatziotis JH. Angular cheilosis: an
and vitamin B. analysis of 156 cases. J Oral Med. 1984;39(4):199–206.
In addition, local factors are also implicated, 11. Garcia-Pola VMJ, Martinez DAI, Garcia MJM,
including dentures, smoking, morsicatio buc- et al. Risk factors for oral soft tissue lesions in an
carum, lip biting, and tartar [42]. adult Spanish population. Community Dent Oral
Epidemiol. 2002;30(4):277–85.
There is no unified standard for the diagno- 12. Strauss RM, Orton DI. Allergic contact cheilitis in the
sis of BMS. Generally, a diagnosis cannot be United Kingdom: a retrospective study. Am J Contact
made solely on the basis of complaints of burn- Dermat. 2003;14(2):75–7.
ing pain and discomfort over the oral mucosa in 13. Lim SW, Goh CL. Epidemiology of eczematous
cheilitis at a tertiary dermatological referral centre in
the absence of significantly positive signs and Singapore. Contact Dermatitis. 2000;43(6):322–32.
organic pathological changes. 14. Zoli V, Silvani S, Vincenzi C, et al. Allergic contact
The therapy for BMS includes psychological cheilitis. Contact Dermatitis. 2006;54(5):296–7.
counseling, followed by administration of oral 15.
Smith AJ, Robertson D, Tang MK, et al.
Staphylococcus aureus in the oral cavity: a three-year
medications, such as oryzano (20 mg, three times retrospective analysis of clinical laboratory data. Br
per day), appropriate use of patented Chinese Dent J. 2003;195(12):701–3; discussion 694.
medicine lusun capsules (0.3–0.6 g, 2–3 times 16. Fatahzadeh M, Schwartz RA. Human herpes simplex
per day), and compound danshen dripping pills virus infections: epidemiology, pathogenesis, symp-
tomatology, diagnosis, and management. J Am Acad
(ten pills, three times per day) for 0.5–1 month. Dermatol. 2007;57(5):737–63; quiz 764–766.
Intralesional use of compound chlorhexidine solu- 17. Park KK, Brodell RT, Helms SE. Angular cheilitis,
tion, 2–4% sodium bicarbonate solution, nystatin part 2: nutritional, systemic, and drug-related causes
liniment, or compound ulcer paste is also advo- and treatment. Cutis. 2011;88(1):27–32.
18. Koay CL, Lim JA, Siar CH. The prevalence of tongue
cated. Vitamin B12 and B1 injections mixed with lesions in Malaysian dental outpatients from the
2% lidocaine may be used for intralesional injec- Klang Valley area. Oral Dis. 2011;17(2):210–6.
tion into the lingual nerve. 19. Reamy BV, Derby R, Bunt CW. Common tongue
conditions in primary care. Am Fam Physician.
2010;81(5):627–34.
20. Yun SJ, Lee JB, Kim SJ, et al. Recurrent geographical
References tongue and fissured tongue in association with pregnancy.
J Eur Acad Dermatol Venereol. 2007;21(2):287–9.
1. Chen Q. Oral medicine. 4th ed. Beijing: People’s 21. Miloglu O, Goregen M, Akgul HM, et al. The
Medical Publishing House; 2013. prevalence and risk factors associated with benign
2. Vieira RA, Minicucci EM, Marques ME, et al. Actinic migratory glossitis lesions in 7619 Turkish dental out-
cheilitis and squamous cell carcinoma of the lip: clini- patients. Oral Surg Oral Med Oral Pathol Oral Radiol
cal, histopathological and immunogenetic aspects. An Endod. 2009;107(2):e29–33.
Bras Dermatol. 2012;87(1):105–14. 22. Zadik Y, Drucker S, Pallmon S. Migratory stomatitis
3. Nico MM, Melo JN, Lourenco SV. Cheilitis glandu- (ectopic geographic tongue) on the floor of the mouth.
laris: immunohistochemical expression of protein water J Am Acad Dermatol. 2011;65(2):459–60.
channels (aquaporins) in minor labial salivary glands. J 23.
Kalifatidis A, AlbanidouFarmaki E, Daniilidis
Eur Acad Dermatol Venereol. 2014;28(3):382–7. M, et al. HLA alleles and fissured tongue. Int J
4. Nico MM, Melo JN, Lourenco SV. Cheilitis glandu- Immunogenet. 2010;37(6):509–11.
laris: a clinicopathological study in 22 patients. J Am 24. Daneshpazhooh M, Moslehi H, Akhyani M, et al.
Acard Dermatol. 2010;62(2):233–8. Tongue lesions in psoriasis: a controlled study. BMC
5. Der Waal RI, Schulten EA, van de Scheur MR, Dermatol. 2004;4(1):16.
et al. Cheilitis granulomatosa. J Eur Acad Dermatol 25. Chi AC, Neville BW, Krayer JW, et al. Oral mani-
Venereol. 2001;15(6):519–23. festations of systemic disease. Am Fam Physician.
6. Goncalves DU, de Castro MM, Galvao CP, et al. Cheilitis 2010;82(11):1381–8.
granulomatosa associated with. Melkersson-Rosenthal 26. Lehman JS, Bruce AJ, Rogers RS. Atrophic glos-
syndrome. Braz J Otorhinolaryngol. 2007;73(1):132–3. sitis from vitamin B12 deficiency: a case misdi-
140 L. Jiang et al.
agnosed as burning mouth disorder. J Periodontol. 40. Souza FT, Santos TP, Bernards VF, et al. The impact
2006;77(12):2090–2. of burning mouth syndrome on health-related quality
27. Terai H, Shimahara M. Atrophic tongue associated of life. Health Qual Life Outcomes. 2011;9:57.
with Candida. J Oral Pathol Med. 2005;34(7):397–400. 41. Klasser GD, Epstein JB, Villines D, et al. Burning
28. Bohmer T, Mowe M. The association between atro- mouth syndrome: a challenge for dental practitioners
phic glossitis and protein-calorie malnutrition in old and patients. Gen Dent. 2011;59(3):210–20.
age. Age Ageing. 2000;29(1):47–50. 42. Mock D, Chugh D. Burning mouth syndrome. Int J
29. Espinoza I, Rojas R, Aranda W, et al. Prevalence of Oral Sci. 2010;2(1):1–4.
oral mucosal lesions in elderly people in Santiago, 43. Sardella A, Gualerzi A, Lodi G, et al. Morphological
Chile. J Oral Pathol Med. 2003;32(10):571–5. evaluation of tongue mucosa in burning mouth syn-
30. Darwazeh AM, Almelaih AA. Tongue lesions in a drome. Arch Oral Biol. 2012;57(1):94–101.
Jordanian population. Prevalence, symptoms, sub- 44. Kenchadze R, Iverieli M, Okribelashvili N, et al. The
ject’s knowledge and treatment provided. Med Oral psychological aspects of burning mouth syndrome.
Patol Oral Cir Bucal. 2011;16(6):e745–9. Georgian Med News. 2011;194:24–8.
31. Goregen M, Miloglu O, Buyukkurt MC, et al. Median 45.
Minguez-Sanz MP, Salort-Llorca C, Silvestre-
rhomboid glossitis: a clinical and microbiological Donat FJ. Etiology of burning mouth syndrome: a
study. Eur J Dent. 2011;5(4):367–37. review and update. Med Oral Patol Oral Cir Bucal.
32. Noonan V, Kabani S. Median rhomboid glossitis. J 2011;16(2):e144–8.
Mass Dent Soc. 2011;59(4):41. 46. Silvestre-Rangil J, Silvestre FJ, Tamarit-Santafe C,
33. Grouteau E, Debuisson C, Brochard K, et al. Severe et al. Burning mouth syndrome: correlation of treat-
global inflammatory involvement of ocular segments and ment to clinical variables of the disease. Med Oral
optic disc swelling in a 12-year-old girl with Kawasaki Patol Oral Cir Bucal. 2011;16(7):e890–4.
disease. Eur J Ophthalmol. 2011;21(1):112–4. 47. Bogetto F, Maina G, Ferro G, et al. Psychiatric comor-
34. Brannon RB, Flaitz CM. Transient lingual papillitis: bidity in patients with burning mouth syndrome.
a papulokeratotic variant. Oral Surg Oral Med Oral Psychosom Med. 1998;60(3):378–85.
Pathol Oral Radiol Endod. 2003;96(2):187–91. 48. Wardrop RW, Hailes J, Burger H, et al. Oral discom-
35. Nisa L, Giger R. Black hairy tongue. Am J Med. fort at menopause. Oral Surg Oral Med Oral Pathol.
2011;124(9):816–7. 1989;67(5):535–40.
36. Jover-Diaz F, Cuadrado-Pastor JM, Talents-Bolos A, 49.
Jaaskelainen SK, Forssell H, Tenovuo
et al. Black tongue associated with linezolid. Am J O. Abnormalities of the blink reflex in burning mouth
Ther. 2010;17(4):e115–7. syndrome. Pain. 1997;73(3):455–60.
37. Obata R, Obata Y, Adachi YU, et al. Successful intu- 50. Svensson P, Kaaber S. General health factors and
bation in a patient with extreme lingual tonsil hyper- denture function in patients with burning mouth syn-
trophy using an intubating laryngeal mask. Acta drome and matched control subjects. J Oral Rehabil.
Anaesthesiol Scand. 2008;52(7):1030. 1995;22(12):887–95.
38. Asbjornsen H, Kuwelker M, Softeland E. A case of 51. Guarneri F, Guarneri C, Marini H. Contribution of
unexpected difficult airway due to lingual tonsil hyper- neuroinflammation in burning mouth syndrome:
trophy. Acta Anaesthesiol Scand. 2008;52(2):310–2. indications from benzodiazepine use. Dermatol Ther.
39. Patel AB, Davidian E, Reebye U. Complicated airway 2008;21(Suppl 2):S21–4.
due to unexpected lingual tonsil hypertrophy. Anesth
Prog. 2012;59(2):82–4.
Syphilis
7
Hongxia Dan and Xin Zeng
Fig. 7.1 Round ulcer with a raised edge was observed on 1. Full blood count didn’t show any significant
the upper lip, covered by a little blood scab
abnormality.
2. Serologic tests for syphilis: rapid plasma
H. Dan · X. Zeng (*) reagin (RPR) card test (+) and anti-treponema
State Key Laboratory of Oral Diseases, National pallidum enzyme-linked immunosorbent
Clinical Research Center for Oral Diseases,
assay (anti-TP ELISA) test (+).
Department of Oral Medicine, West China Hospital
of Stomatology, Sichuan University, 3. Human immunodeficiency virus (HIV) anti-
Chengdu, Sichuan, China body (−).
© Springer Nature Singapore Pte Ltd. and People’s Medical Publishing House 2018 141
Q. Chen, X. Zeng (eds.), Case Based Oral Mucosal Diseases,
https://doi.org/10.1007/978-981-13-0286-2_7
142 H. Dan and X. Zeng
Diagnosis:
a
Chancre (primary syphilis)
Diagnosis Basis:
1. Single, round, indurated ulcer on the lip with
a short course of disease.
2. Serologic tests for syphilis were positive.
3.
Lesions disappeared after anti-syphilis
therapy.
Management:
b
1. Medication
Rp.: Benzathine penicillin G 2.4 × 106 U × 3
Sig.: IM (on the buttocks) q.w.
Compound chlorhexidine solution 300 ml × 1
Sig.: rinse t.i.d.
2. In the subsequent visit after the treatment, the
lesions disappeared, and result of RPR was
negative.
c
Case 78 Chancre (Primary Syphilis)
Age: 42 years
Sex: Female
Chief Complaints:
A 42-year-old woman with painful bumps on the
lips for 2 months
History of Present Illness:
A 42-year-old woman presented to our clinic
with painful bumps on the lips for 2 month. She
was diagnosed with herpes labialis at a local hos- Fig. 7.2 (a) Two round bumps covered by thick blood
pital. Acyclovir was prescribed for 1 week but crust were observed in the middle of the upper lip and the
right side of the lower lip, respectively. (b) After hydro-
didn’t show any significant effect. pathic compress, the blood crust was removed and a con-
Past Medical History: None gestive lesion with a smooth surface was revealed. (c)
Allergy: None Sizes of the lesions reduced after topical treatment with
Physical Examination: anti-inflammatory agents for 1 week
Two round, indurated bumps covered by thick
blood crust were observed in the middle of the 2. At the first visit, tolulized red unheated serum
upper lip and the right side of the lower lip test (TRUST) and anti-TP ELISA test were
(Fig. 7.2a), respectively. Linear erosion could be both negative. Human immunodeficiency virus
seen around the edge of the lesions. After hydro- (HIV) antibody was negative. After topical
pathic compress, the blood crust was removed, and treatment with prednisolone for 1 week, the
a congestive lesion with a smooth surface was sizes of the lesions reduced (Fig. 7.2c). When
revealed (Fig. 7.2b). we reviewed the history of present illness, the
Clinical Impression: patient didn’t deny history of unprotected sex.
Labial bumps (chancre?) TRUST and anti-TP ELISA tests were carried
out again, and the results were both positive.
Laboratory Investigations:
1. Full blood count didn’t show any significant Diagnosis:
abnormality. Chancre (primary syphilis)
7 Syphilis 143
Diagnosis:
Syphilitic mucosa patches (secondary syphilis)
Diagnosis Basis:
Management:
1. Medication
Rp.: Benzathine penicillin G 2.4 × 106 U × 3
Sig.: IM (on the buttocks) q.w.
Compound chlorhexidine mouth rinse
300 ml × 1
Sig.: rinse t.i.d.
Fig. 7.3 (a) White oval patches with a shiny surface were
2. In the subsequent visit after the treatment, the
observed on the mucosa of the left angle of the mouth. (b)
White oval patches with a shiny surface were observed on lesions disappeared, and result of TRUST was
the mucosa of the right palatoglossal pillar negative.
144 H. Dan and X. Zeng
Laboratory Investigations:
Diagnosis:
Syphilitic mucositis (secondary syphilis)
Diagnosis Basis:
Clinical Impression:
c
1.
Pharyngeal mucous patches (secondary
syphilis)
2. Multiple nodules (probably oral manifesta-
tions of secondary syphilis)
Laboratory Investigations:
Fig. 7.8 Syphilitic mucous patches on the soft palate Fig. 7.10 Syphilitic mucous patches on the ventral sur-
(secondary syphilis) face of the tongue (secondary syphilis)
Fig. 7.9 Syphilitic mucous patches on the lateral surface Fig. 7.11 Snail-track lesions on the inner surface of the
of the tongue (secondary syphilis) lower lip (secondary syphilis)
Fig. 7.13 Macular syphilitic eruptions (secondary Fig. 7.14 Leukoplakia-like lesions (secondary syphilis)
syphilis)
lump which usually infiltrates the surrounding
syphilitic eruptions are rare. They usually affect tissue. Ulceration and necrosis may occur in the
the buccal mucosa or the angles of the mouth and center of the gumma, leading to scar formation
appear as red papules that are firm, raised, and after healing.
round in shape, with or without ulcer in the cen- Gummas on the hard palate, tongue, and lips
ter. Nodular syphilitic lesions are rare. They are are the common oral manifestations of tertiary
usually observed on the face, palms, and soles. syphilis. The gummas may initially appear as
When lesions appear on the vermillion, they may single or multiple painless lumps which may
masquerade as squamous cell carcinoma or develop into ulcerations or even destruction of
keratoacanthoma. bone underneath. When the palate is involved,
Moreover, oral lesions associated with sec- perforation of the palate may occur, leading to
ondary syphilis could be diverse and nonspecific, communication between the oral and nasal cav-
often clinically and histologically mimicking ity. X-ray shows radiolucency with unclear bor-
other oral diseases, such as multiple oral nodules der that resembles malignant lesions.
[8], leukoplakia [5] (Fig. 7.14), and pemphigus A less common oral manifestation of tertiary
vulgaris [9]. syphilis is syphilitic leukoplakia. It usually
The results of non-treponemic and treponemic affects the dorsal surface of the tongue and car-
tests are usually positive in patients with second- ries a high risk of malignant transformation [5].
ary syphilis. The lesions of secondary syphilis Neurosyphilis can cause unilateral or bilateral
will resolve in 3–12 weeks spontaneously. If the trigeminal neuropathy and facial nerve paralysis.
disease is untreated, recurrence of secondary Cardiovascular syphilis is rare and mainly mani-
syphilis will occur in 25% of the patients [2, 5, 7, fest as inflammation of the aorta.
10–12]. The characteristic pathological change of
After secondary stage of syphilis, there is a syphilis is endovasculitis, which can be seen in
period of latent syphilis, during which patients all stages. Chancre is characterized by inflamma-
have no symptoms. The first 12 months of latent tory infiltration of lymphocytes and macro-
syphilis is called early latency; the carrier has phages, with large amount of T. pallidum. Gumma
strong infectivity. After that, it is called late latent is a granulomatous lesion, with necrosis in the
syphilis, and the infectivity is decreased. Latent center, accompanied by endovasculitis and peri-
syphilis can be diagnosed by serologic tests. vasculitis. T. pallidum is rarely detected.
Tertiary syphilis occurred in 1/3 patients with- Congenital syphilis has its particular mani-
out treatment. It is progressive and may affect festations. T. pallidum get through the placenta
multiple organs, leading to a series of complica- after the 16th week of pregnancy; due to the
tions. The characteristic skin lesion of tertiary schedule of fetal organ development, it mainly
syphilis is the “gumma,” a painless brownish-red affects facial structures. Congenital syphilis
150 H. Dan and X. Zeng
can be divided into two stages: early and late. HIV may have a significant effect on the clini-
Infants with early congenital syphilis can be cal process of syphilis. Due to the immunodefi-
asymptomatic or with manifestations such as ciency induced by HIV, coinfection is more
skin rashes, rhinitis, hepatosplenomegaly, and aggressive than single one. Some studies indi-
meningitis. If left untreated, late congenital cated that HIV might not significantly affect
syphilis may occur, at least 24 months after manifestation of syphilis, except for an increas-
birth. Common signs of late congenital syphilis ing incidence of genital ulcers in the secondary
include Hutchinson’s teeth, interstitial keratitis, stage. Some researchers found that HIV infection
and deafness. The incisal edges of the incisors, might extend the duration of primary and second-
more often the maxillary ones, are usually ary syphilis, accelerate progression of neuro-
notched and narrower than the cervical area of syphilis, and increase the incidence of
the teeth. The first molar can be bud-shaped, nodular-ulcerative lesions [15, 16].
and even smaller than the second molar hypo- Once the diagnosis of syphilis is confirmed,
plasia of the dental enamel is often observed. patients can be referred to the department of der-
Other manifestations, such as hard palate defect matology and STD. The treatment of syphilis
and saddle nose, can also be observed in some depends on the stage of the disease.
cases [13]. Early syphilis: benzathine penicillin G,
Serologic tests are necessary for diagnosis of 2.4 × 106 U, IM (on the buttocks), q.w., three
syphilis. Nontreponemal tests, including rapid times in total. Procaine penicillin G, 8 × 105 U,
plasma reagin (RPR), venereal disease research IM, q.d., consecutively for 10–15 days,
laboratory (VDRL), unheated serum reagin 8~12 × 106 U in total. For patients allergic to peni-
(USR), and toluidine red unheated serum test cillin, ceftriaxone sodium can be used. 1.0 g cef-
(TRUST), are used to detect nonspecific antibod- triaxone sodium IV, consecutively for 10–14 days,
ies which react to cardiolipin-cholesterol-lecithin or tetracycline hydrochloride 500 mg p.o., q.i.d.,
antigens. These tests are used for screening of consecutively for 15 days, or doxycycline 100 mg
syphilis and follow-up of patients after treatment. p.o., b.i.d., consecutively for 15 days.
Treponemal tests, including fluorescent trepone- Late syphilis: benzathine penicillin G,
mal antibody absorption (FTA-ABS), T. pallidum 2.4 × 106 U, IM (on the buttocks), q.w., three
hemagglutination test (TPHA), T. pallidum par- times in total. Procaine penicillin G, 8 × 105 U,
ticle agglutination (TPPA), and enzyme-linked IM, q.d., consecutively for 20 days. For patients
immunosorbent assay (TP-ELISA), are used to allergic to penicillin, ceftriaxone sodium can be
confirm the infection if the results of the non- used. 1.0 g ceftriaxone sodium IV, consecutively
treponemal tests are positive [14]. Treponemal for 30 days, or doxycycline 100 mg p.o., bid,
tests detect treponema-specific IgG antibodies in consecutively for 30 days.
the serum, which usually persist for a long time After regular treatment, patients should make
or even lifetime after the infection has been suc- return visits and repeat nontreponemal antibody
cessfully treated. They can’t be used for evalua- serologic tests to rule out possible relapse.
tion of treatments. Follow-up of 2–3 years is recommended.
Coinfection of T. pallidum and HIV is usually Examination, including clinical examination and
caused by sexual transmission. Syphilitic ulcers serologic tests (nontreponemal antibody serologic
of the genital area increase the risk of HIV infec- test), should be scheduled every 3 months during
tion. HIV can also be transmitted by oro-genital the first year and every 6 months after that.
contact. Oral syphilis with ulceration may facili- Patients with active or latent syphilis can resist
tate transmission of HIV through oral sex. It was repeated infection of T. pallidum. Though the dis-
also reported that non-ulcerative syphilis could ease can be cured, patients with a history of syphi-
promote HIV infection. lis are still susceptible to T. pallidum [17].
7 Syphilis 151
L. Jiang
State Key Laboratory of Oral Diseases, National
Clinical Research Center for Oral Diseases,
Department of Oral Medicine, West China Hospital b
of Stomatology, Sichuan University,
Chengdu, Sichuan, China
X. Jin
College of Stomatology, Chongqing Medical
University, Chongqing Key Laboratory of Oral
Diseases and Biomedical Sciences,
Chongqing, China
Q. Chen (*)
Changjiang Scholars Program, Ministry of Education,
Beijing, China
State Key Laboratory of Oral Diseases, National
Clinical Research Center for Oral Diseases, Fig. 8.1 (a) Widespread, thick, white pseudomembrane
Department of Oral Medicine, West China Hospital visible on the dorsum of tongue. (b) Widespread, thick,
of Stomatology, Sichuan University, Chengdu, white pseudomembrane visible on the palate
Sichuan, China
e-mail: qmchen@scu.edu.cn
© Springer Nature Singapore Pte Ltd. and People’s Medical Publishing House 2018 153
Q. Chen, X. Zeng (eds.), Case Based Oral Mucosal Diseases,
https://doi.org/10.1007/978-981-13-0286-2_8
154 L. Jiang et al.
Fig. 8.5 AIDS-related hairy leukoplakia (dorsum of the Fig. 8.7 AIDS-related Kaposi sarcoma (skin)
tongue)
Fig. 8.6 AIDS-related hairy leukoplakia lateral tongue Fig. 8.8 AIDS-related Kaposi sarcoma (tongue mucosa)
most common oral manifestation of HIV-positive As OHL is asymptomatic and has no malignant
children. Accelerated eruption of permanent potential, it rarely needs to be treated. Although
teeth and over-retention of primary teeth have acyclovir and valacyclovir have been used to treat
also been observed in some HIV-infected chil- OHL, unfortunately, acyclovir resistance may pre-
dren, owing to HIV-associated xerostomia [21]. vent the clinical resolution of OHL [22].
HIV infection should be considered in young At present, there is no effective vaccine or anti-
adults with these mentioned oral lesions, espe- viral agent to treat AIDS-related KS. Consequently,
cially accompanied by recent (3–6 months) the aim of the treatment is the elimination or at
weight loss (>10%), chronic diarrhea/cough for least reduction of cosmetically unacceptable
more than 1 month, or intermittent/persistent lesions, relief of pain, or unsightly edema and
fever for more than 1 month. lymphadenopathy. Local therapy may be effective
The gold standard for the clinical diagnosis of for limited disease, while systemic therapy is
HIV is HIV antibody testing. The most widely required for disseminated KS. Treatment
used serological methods with high sensitivity approaches for oral KS include local radiation,
and specificity are enzyme-linked immunosor- laser therapy, surgical excision, and cytotoxic
bent assay (ELISA) and Western blotting (WB). therapy with vinca alkaloids (vinblastine, vincris-
ELISA with the appropriate sensitivity and speci- tine, and vinorelbine) and bleomycin. However,
ficity can be used as the primary screening test; only five agents are approved by the Food and
furthermore, twice positive reactions should be Drug Administration (FDA) for the treatment of
regarded as indicative of HIV infection. WB tests KS alitretinoin gel for topical therapy, liposomal
the structural proteins of the virus, including pro- daunorubicin, liposomal doxorubicin, paclitaxel,
tein capsid p24, glycoprotein (gp) 41, and and interferon-alpha for systemic therapy [1, 23].
gp120/160; it has a high specificity and is used as Up till now, systemic therapy with intensive,
a confirmatory test. high-dose chemotherapy and autologous stem
A patient with HIV antibody-positive with cell transplantation are utilized to treat oral NHL;
any of the following may be diagnosed as a however, these therapies do not cure NHL.
patient with AIDS:
8. Coogan MM, Greenspan J, Challacombe SJ. Oral 16. Feller L, Masipa J, Wood N, Raubenheimer E, Lemmer
lesions in infection with human immunodeficiency J. The prognostic significance of facial lymphoedema
virus. Bull World Health Organ. 2005;83(9):700–6. in HIV-seropositive subjects with Kaposi sarcoma.
9. Hodgson TA, Naidoo S, Chidzonga M, Ramos-Gomez AIDS Res Ther. 2008;5:2.
F, Shiboski C. (A1) Identification of oral health care 17. Coutlee F, Trottier AM, Ghattas G, et al. Risk factors
needs in children and adults, management of oral dis- for oral human papillomavirus in adults infected and
eases. Adv Dent Res. 2006;19(1):106–17. not infected with human immunodeficiency virus. Sex
10. Ranganathan K, Hemalatha R. Oral lesions in HIV Transm Dis. 1997;24(1):23–31.
infection in developing countries: an overview. Adv 18. Kreimer AR, Alberg AJ, Daniel R, et al. Oral human
Dent Res. 2006;19(1):63–8. papillomavirus infection in adults is associated with
11. Arendorf T, Holmes H. Oral manifestations associated sexual behavior and HIV serostatus. J Infect Dis.
with human immunodeficiency virus (HIV) infection 2004;189(4):686–98.
in developing countries – are there differences from 19. Arora A, Chiao E, Tyring SK. AIDS malignancies.
developed countries. Oral Dis. 2000;6(3):133–5. Cancer Treat Res. 2007;133:21–67.
12. Greenspan JS, Greenspan D. The epidemiology of the 20. Navarro CM, Shibli JA, Ferrari RB, d’Avila S, Sposto
oral lesions of HIV infection in the developed world. MR. Gingival primary extranodal non-Hodgkin’s lym-
Oral Dis. 2002;8(Suppl 2):34–9. phoma as the first manifestation of acquired immu-
13. Patton LL. Sensitivity, specificity, and positive pre- nodeficiency syndrome. J Periodontol. 2008;79(3):
dictive value of oral opportunistic infections in adults 562–6.
with HIV/AIDS as markers of immune suppression 21. Yengopal V, Bhayat A, Coogan M. Pediatric oral
and viral burden. Oral Surg Oral Med Oral Pathol HIV research in the developing world. Adv Dent Res.
Oral Radiol Endod. 2000;90(2):182–8. 2011;23(1):61–6.
14. Martro E, Esteve A, Schulz TF, et al. Risk factors for 22. Walling DM, Flaitz CM, Nichols CM, Hudnall SD,
human Herpesvirus 8 infection and AIDS-associated Adler-Storthz K. Persistent productive Epstein-Barr
Kaposi’s sarcoma among men who have sex with virus replication in normal epithelial cells in vivo. J
men in a European multicentre study. Int J Cancer. Infect Dis. 2001;184(12):1499–507.
2007;120(5):1129–35. 23. Dezube BJ. Management of AIDS-related Kaposi’s
15. Leao JC, Hinrichsen SL, de Freitas BL, Porter
sarcoma: advances in target discovery and treatment.
SR. Human herpes virus 8 and Kaposi’s sarcoma. Rev Expert Rev Anticancer Ther. 2002;2(2):193–200.
Assoc Med Bras. 1999;45(1):55–62.
Human Papillomavirus Infections
of Oral Mucosa 9
Xin Jin and Xin Zeng
X. Jin
College of Stomatology, Chongqing Medical
University, Chongqing Key Laboratory of Oral
Diseases and Biomedical Sciences,
Chongqing, China
X. Zeng (*)
Fig. 9.1 (a) Multiple soft, protruding nodules on the
State Key Laboratory of Oral Diseases, National
upper labial mucosa. (b) Multiple soft, protruding nodules
Clinical Research Center for Oral Diseases,
on the upper and lower labial mucosa (Reproduced from
Department of Oral Medicine, West China Hospital
Liu et al. 2012)
of Stomatology, Sichuan University,
Chengdu, Sichuan, China
© Springer Nature Singapore Pte Ltd. and People’s Medical Publishing House 2018 161
Q. Chen, X. Zeng (eds.), Case Based Oral Mucosal Diseases,
https://doi.org/10.1007/978-981-13-0286-2_9
162 X. Jin and X. Zeng
performed, and all results were negative. Past Medical History: None
HPV 32 was positive in DNA samples Allergy: None
extracted from the paraffin-embedded block Physical Examination:
of the specimen. Two growths were detected on the labial mucosa
with diameters of 3 mm and 9 mm, respectively.
Diagnosis: The color of the right one was normal-appearing.
Focal epithelial hyperplasia The left one was whitish with rough surface, and
Diagnosis Basis: tiny cauliflower-like protuberances were
detected, which was not painful (Fig. 9.3).
1. Multiple soft circumscribed sessile nodular
Laboratories Studies:
elevations of oral mucosa.
2. The histopathologic examination of biopsy
1. HPV 6 and 11 were positive in DNA samples
indicated virus infection. extracted from the paraffin-embedded
3. Amplification of HPV DNA from biopsies
specimen.
showed HPV 32 (+). 2. Hematoxylin and eosin staining of lesions
revealed epithelial parakeratosis, thickened stra-
Management: tum spinosum, and elongated epithelial pegs
Regular follow-up visit and observation was like papillomatosis. Upper epithelial cell showed
suggested. swelling, edema, and vacuolar degeneration
along with inflammatory cell infiltration.
Case 86 Oral Condyloma Acuminatum
Diagnosis:
Oral condyloma acuminatum
Diagnosis Basis:
Management:
Excisional biopsy and subsequent visit was
suggested.
Fig. 9.3 Two growths with the surface covered by cauli-
Case 87 Papilloma
flower-like protuberances on the labial mucosa
Age: 42 years
Sex: Male
Chief Complaints:
42-year-old man with masses on the lower lip for
2 months
History of Present Illness:
A 42-year-old man presented to our clinic with
masses on the lower lip for 2 month. The masses
were painless and easily got bitten. The sizes of
the lesions were stable. He had feculent sexual
intercourse history recently. Fig. 9.4 Whitish and soft masses with burrlike surface on
the right retromolar region
164 X. Jin and X. Zeng
Age: 45 years proteins (L1, L2) which form the shell of the
Sex: Female virus. The L1 is the most conserved OFR and can
Chief Complaints: be used to identify new HPV types. If the L1
45-year-old woman with “foreign matter in ORFs DNA sequence differ more than 10% from
mouth” for 20 days the known HPV types, it can be defined as a new
History of Present Illness: HPV genotype. HPV has been described as more
A 45-year-old woman presented to our clinic than 120 types according to its different gene
with foreign matter at the right back side of sequences. According to the target site of the
mouth for 20 days, without any discomfort. infection, HPV has been classified as cutaneous
Past Medical History: None or mucosal types. High-risk and low-risk sub-
Allergy: None types could also be defined according to the
Physical Examination: malignant degree. To date, there are 30 HPV gen-
Whitish and soft hyperplastic lesion was seen on otypes: 15 high-risk types, 3 types that probably
the right retromolar region. The lesion was 3 mm are high risk, and 12 low-risk types have been
in diameter, with burrlike protuberances on its identified [1–3]. HPV 6 and HPV 11 are the most
surface (Fig. 9.4). common low-risk types, and the most common
Laboratories Studies: high-risk types are HPV 16 and HPV 18 [4].
Hematoxylin and eosin staining of the excised Life cycle of HPV is closely related to the dif-
lesion biopsy revealed oral mucosa squamous ferentiation program of the host keratinocytes.
papillary hyperplasia. HPV entry into the epithelial basal layer requires
Diagnosis: epithelial wounding, and the HPV receptors
Oral squamous cell papilloma include alpha 6 integrin, extracellular laminin 5,
Diagnosis Basis: and heparan sulfate proteoglycans [5–7]. After
entry, HPV establishes itself in nucleus as an epi-
1. Single hyperplastic lesion with burrlike
some. At this stage, the viral proteins E1, E2, E6,
surface. and E7 are lower expressed, and no virus is pro-
2. Oral lesions biopsy confirmed oral squamous ductive. After cell division, the infected cells
cell papilloma. migrate toward the suprabasal layer and begin to
differentiate, which activate the transcriptional
Management: cascade of viral genome. Viral proteins, mainly
The lesion was completely excised for biopsy E6 and E7, can delay or terminate differentiation
and observation was suggested. through inducing cell proliferation and lead to
high-level amplification of the viral genome
[Review] Human Papillomavirus Infections of through interfering with and preventing the
Oral Mucosa expression of cell cycle regulators. Viral proteins
Human papillomavirus (HPV) is one of the most E1, E2, E4, and E5 are essential for replication,
common virus groups, and the infection rate of which are increased in upper layers of the
HPV tends to increase year by year. HPV affects epithelium. Capsid proteins, such as L1 and L2,
the human skin and mucosa, leading to epithelial are also produced. In terminally differentiated
hyperplasia, which could cause verrucous dam- cells, the viral DNA is packaged in viral capsids
age, even involved in tumor formation. and shed from the epithelium surface [5, 8].
HPV are small double-stranded DNA viruses, HPV affects most of the cutaneous and muco-
containing about 7900 nucleotide base pairs. sal area, such as the anogenital tract, urethra,
Human can be infected only by HPV, not papillo- skin, larynx, tracheobronchial mucosa, nasal cav-
mavirus from animals. The HPV genome includes ity, and oral mucosa. Oral HPV infection may be
eight open reading frames (ORFs), which are cod- associated with a variety of oral diseases, but the
ing sites of six early proteins (E1, E2, E4, E5, E6, specific mode of transmission is still unclear.
E7) involved in viral gene regulation and two late HPV can lead to latent subclinical infection,
9 Human Papillomavirus Infections of Oral Mucosa 165
which probably from cervical infected mother which could proliferate and coalesce to soft
when they delivered. However, horizontal trans- growths. They are rare seen in oral cavity, with
mission is common, such as sexual contact (oro- cauliflower-like surface. Patients often had a his-
genital contact), nonsexual transmitted (wet tory of feculent sexual intercourse.
towel sharing, etc.), and autoinoculation. A sys- Histopathologic examination shows koilocytes.
tematic review showed that 4.5% of 4070 indi- Intranuclear viral inclusions have been demon-
viduals were positive for any type of HPV, and strated by electron microscope. HPV 6 and 11
HPV16 accounted for 28% of HPV detected in have often been isolated from these lesions.
the oral cavity [9]. Another meta-analysis of the Surgical resection or laser treatment could be
relationship between HPV and oral cancer performed. Close observation during follow-up is
revealed that 12% of control group were HPV needed as it is easy to relapse. It is hard to be dif-
positive [10], which indicated that HPV may be ferentiated from oral squamous cell papilloma if
detected on normal oral mucosa. the lesion is single, so the medical history should
Oral HPV infection can lead to different clini- be considered.
cal manifestations. Low-risk HPV types often Verruca vulgaris occasionally observed on the
cause benign oral lesions, such as common wart, oral mucosa. They manifests as firm, whitish,
condyloma acuminatum, focal epithelial hyper- sessile well-defined lesions. Pathological exami-
plasia, and oral papilloma. The most common nation show significant hyperkeratosis of the
low-risk types are HPV 6 and HPV 11 and also upper epithelia and thickening of stratum spino-
the HPV 13 and HPV 32 mentioned in this unit. sum. The mucosal HPV types (HPV 6, 11, 16)
The cutaneous HPV types, such as HPV 2 and and cutaneous HPV types (HPV 1, 2, 4, 7) have
HPV 4, have also been detected in oral verrucous been reported in oral verruca. Surgical resection
lesions [2]. is often applied.
Focal epithelial hyperplasia (FEH) is a benign Oncogenic HPV have a well-established asso-
disorder caused by HPV, which is characterized ciation with uterine cervical carcinoma. Their
by multiple soft well-demarcated sessile nodules relationship to oral premalignant conditions and
on the oral mucosa. Histologically, koilocytes, OSCC, however, is less well defined. Our under-
virions, and HPV antigens can be detected in standing of the role of HPV in oncogenic devel-
FEH lesions, which suggest the etiology of the opment of OSCC remains limited, and its
disease related to virus. HPV 1, 6, 13, and 32 prevalence varies widely in different studies.
have been reported in many studies. People with Researches about relationship between HPV and
human leukocyte antigen beta chain 1 × 0404 oral premalignant diseases mainly concentrated
allele are at an increased risk of developing it. No on oral leukoplakia. The likelihood of detecting
treatment is necessary in view of the benign HPV in benign leukoplakia (22.2%) was signifi-
nature of the disease. cantly more than of detecting normal oral mucosa
Oral squamous cell papilloma is a benign (10.0%) [11]. HPV 6 and HPV 11 were found in
lesion which is commonly seen in patients of 55.8% of HPV-positive leukoplakia compared
30–40 years. HPV etiology is considered as HPV with HPV 16 and HPV 18 (28.8%) [12]. These
virus particles are detected in the lesions. HPV 6 findings provided evidence for the HPV etiology
and HPV 11 are the most common types. The of oral leukoplakia.
lesions are prone to be single and palate is the Some studies suggested that during oral carci-
predilection site. It usually presents with circum- nogenesis, massive episomes can lead to viral
scribed pedunculated papillary growths, which integration into the host genome. The viral E2
appear as whitish and hairlike lesions. Surgical gene is interrupted, leading to the loss control of
removal of the elevations is the preferred E6 and E7 mRNA expression. By inhibition of the
treatment. protein p53 and pRb, they could stimulate the host
Oral condyloma acuminatum is often charac- gene mutation, and change the DNA repair mech-
terized by lots of small white or pink nodules, anisms, leading to get involved in the regulation
166 X. Jin and X. Zeng
of cell cycle. Continuous and abnormal expres- plicated to be used in large-scale clinical appli-
sion of E6 and E7 genes of high-risk HPV type cation. At present, hybrid capture II (HC-II)
can lead to genomic instability of the host cells, assay with sensitivity and specificity has been
accumulation of mutational events, and finally granted US FDA approval in detection of HPV
malignant transformation. Malignant transfor- DNA [2]. But at this stage in China, PCR is still
mation of epithelial cells requires several step- the most commonly performed to detect HPV
wise processes with other cofactors and DNAs of lesions.
carcinogens such as smoking, radiation, etc.
Therefore, HPV-associated malignancy is a rare
event when compared with the frequency of References
infection in persons [13].
HPV 16 and 18 are associated with oral can- 1. Rautava J, Syrjänen S. Human papillomavirus
infections in the oral mucosa. J Am Dent Assoc.
cer. Recently, a meta-analysis about oral cavity 2011;142(8):905–14.
and oropharyngeal dysplasia (OOPD) showed 2. Kumaraswamy KL, Vidhya M. Human papillomavi-
that the overall prevalence of HPV 16/18 in rus and oral infections: an update. J Cancer Res Ther.
OOPD lesions was 24.5%, while the prevalence 2011;7(2):120–7.
3. Lacour DE, Trimble C. Human papillomavirus in
for HPV 16 alone was 24.4%. HPV 16/18 were 3 infants: transmission, prevalence, and persistence. J
times more common in dysplastic lesions and Pediatr Adolesc Gynecol. 2012;25(2):93–7.
invasive cancers. There was no significant differ- 4. Syrjänen S. Human papillomavirus infection and its
ence in HPV-16/18 infection ratio between dys- association with HIV. Adv Dent Res. 2011;23(1):84–9.
5. Joyce JG, Tung JS, Przysiecki CT, et al. The L1 major
plastic lesions and cancers [14]. Some capsid protein of human papillomavirus type 11
researchers found pooled prevalence of HPV recombinant virus-like particles interacts with hepa-
DNA in OSCC was 38.1%, and PCR-based stud- rin and cell-surface glycosaminoglycans on human
ies reported a higher prevalence rate than ISH- keratinocytes. J Biol Chem. 1999;274(9):5810–22.
6. Giroglou T, Florin L, Schäfer F, Streeck RE, Sapp
based rates [15]. Study examined 66 OSCCs for M. Human papillomavirus infection requires cell sur-
HPV-16 infection to assess the prognostic sig- face heparan sulfate. J Virol. 2001;75(3):1565–70.
nificance. Cox regression analysis of 5-year sur- 7. Yoon CS, Kim KD, Park SN, et al. Alpha (6) inte-
vival indicated that patients with HPV 16 inside grin is the main receptor of human papillomavi-
rus type 16 VLP. Biochem Biophys Res Commun.
the tumor showed better prognosis compared 2001;283(3):668–73.
with their counterpart, perhaps because HPV- 8. Doorbar J, Griffin H. Intrabody strategies for the
positive exophytic tumors are easily found and treatment of human papillomavirus associated dis-
could be completely excised leading to better ease. Expert Opin Biol Ther. 2007;7(5):677–89.
9. Kreimer AR, Bhatia RK, Messeguer AL, González P,
prognosis [16]. Low-risk HPV types can also be Herrero R, Giuliano AR. Oral human papillomavirus
detected in OSCC, not only the benign lesions in healthy individuals: a systematic review of the lit-
[17]. Oral verrucous carcinoma (OVC) is a rare erature. Sex Transm Dis. 2010;37(6):386–91.
variant of SCC, with an exogenous cauliflower- 10. Syrjänen S, Lodi G, von BI, et al. Human papil-
lomaviruses in oral carcinoma and oral potentially
like warty appearance. Recently, the association malignant disorders: a systematic review. Oral Dis.
between HPV 6/11/16/18 and OVC has been 2011;17(Suppl 1):58–72.
confirmed [18]. 11. Miller CS, Johnstone BM. Human papillomavirus as a
HPV cannot be cultured in vitro, and detec- risk factor for oral squamous cell carcinoma: a meta-
analysis, 1982-1997. Oral Surg Oral Med Oral Pathol
tion of HPV infections mainly depends on the Oral Radiol Endod. 2001;91(6):622–35.
molecular biology techniques, including dot 12. Miller CS, White DK. Human papillomavirus expres-
blotting, in situ hybridization (ISH), Southern sion in oral mucosa, premalignant conditions, and
blotting, polymerase chain reaction (PCR), squamous cell carcinoma: a retrospective review of
the literature. Oral Surg Oral Med Oral Pathol Oral
hybrid capture, etc. ISH and PCR methods are of Radiol Endod. 1996;82(1):57–68.
high sensitivity. PCR has limited specificity and 13. Sinal SH, Woods CR. Human papillomavirus
higher false-positive rate, while ISH is too com- infections of the genital and respiratory tracts
9 Human Papillomavirus Infections of Oral Mucosa 167
in young children. Semin Pediatr Infect Dis. 16. Sugiyama M, Bhawal UK, Kawamura M, et al.
2005;14(4):306–16. Human papillomavirus-16 in oral squamous cell car-
14. Jayaprakash V, Reid M, Hatton E, et al. Human papil- cinoma: clinical correlates and 5-year survival. Br J
lomavirus types 16 and 18 in epithelial dysplasia of Oral Maxillofac Surg. 2007;45(2):116–22.
oral cavity and oropharynx: a meta-analysis, 1985- 17. Mendelsohn AH, Lai CK, Shintaku IP, et al.
2010. Oral Oncol. 2011;47(11):1048–54. Histopathologic findings of HPV and p16 positive
15. Termine N, Panzarella V, Falaschini S, et al. HPV HNSCC. Laryngoscope. 2010;120(9):1788–94.
in oral squamous cell carcinoma vs head and neck 18. Walvekar RR, Chaukar DA, Deshpande MS, et al.
squamous cell carcinoma biopsies: a mata-analysis Verrucous carcinoma of the oral cavity: a clinical
(1988-2007). Ann Oncol. 2008;19(10):1681–90. and pathological study of 101 cases. Oral Oncol.
2009;45(1):47–51.
Oral Mucosal Lesions of Systemic
Diseases 10
Xin Jin, Xin Zeng, and Lanyan Wu
Keywords
Thrombocytopenic Purpura ∙ Leukemia ∙
Acute Monocytic Leukemia ∙ Myeloid
Sarcoma ∙ Lymphoma ∙ NK-/T-Cell
Lymphoma ∙ Langerhans Cell Histiocytosis ∙
Amyloidosis ∙ Florid Papillomatosis ∙
Acanthosis Nigricans Maligna ∙ Focal Dermal
Hypoplasia
X. Jin
College of Stomatology, Chongqing Medical
University, Chongqing Key Laboratory of Oral
Diseases and Biomedical Sciences,
Chongqing, China
X. Zeng (*)
State Key Laboratory of Oral Diseases, National
Clinical Research Center for Oral Diseases,
Department of Oral Medicine, West China Hospital
of Stomatology, Sichuan University,
Chengdu, Sichuan, China
L. Wu
Department of Oral Pathology, West China Hospital
of Stomatology, Sichuan University,
Chengdu, Sichuan, China
© Springer Nature Singapore Pte Ltd. and People’s Medical Publishing House 2018 169
Q. Chen, X. Zeng (eds.), Case Based Oral Mucosal Diseases,
https://doi.org/10.1007/978-981-13-0286-2_10
170 X. Jin et al.
a b
Fig. 10.1 (a) Multiple blood blisters of different sizes on pinhead-size petechiae and small blood blisters on the
the left buccal mucosa. (b) Multiple blood blisters of dif- chest skin
ferent sizes on the dorsum of the tongue. (c) Dozens of
2. Clotting check: prothrombin time (PT) and Epstein-Barr virus, cytomegalovirus, and hepati-
activated partial thromboplastin time (APTT) tis A), hypersplenism, and disseminated intravas-
are normal. cular coagulation may also be related to
thrombocytopenia [2].
Diagnosis: Oral manifestations include spontaneous gin-
Thrombocytopenic purpura gival bleeding which can be aggravated by mild
Management: stimulus like teeth-brushing and sucking. Oral
She was transferred to the hematology depart- lesions manifest as multiple petechiae, ecchy-
ment for further treatment promptly. moses, and hematomas of different sizes, espe-
cially on the buccal mucosa and tongue. The
[Review] Thrombocytopenic Purpura hematomas rupture easily, leaving round or oval
Thrombocytic purpura is a hemorrhagic disease erosions with clear borders.
caused by platelet disorder, leading to oral, cuta- Skin lesions are mainly presented by pur-
neous, and visceral hemorrhage. It could be pura, ecchymoses, blood blisters, or hemato-
divided into two categories: thrombocytopenic mas, accompanied with nasal bleeding and
purpura and purpura caused by platelet dysfunc- menorrhagia. Rare visceral hemorrhage such as
tion. Thrombocytopenic purpura includes immune hemoptysis, hematemesis, and hematuria can be
thrombocytopenic purpura, thrombotic thrombo- noticed in severe cases, with potentially fatal
cytopenic purpura, drug-related thrombocytope- consequences.
nia, thrombocytopenic purpura secondary to some Diagnosis could be made according to the
primary diseases, etc. The reasons of platelet dys- clinical manifestations and blood routine exami-
function include thrombopathy, Glanzmann’s nation. The patients should be transferred to the
thrombasthenia, uremia, abnormal globulinemia, hematology department for further checks and
drugs, etc. Symptoms of drug-induced thrombo- treatment promptly.
cytopenia range from no bleeding to intracranial Patients with secondary thrombocytopenia
hemorrhage causing death. The physician should should stop taking suspected drugs or get active
be especially alert to this kind of adverse drug treatment of primary disease. Systemic treat-
reaction. The most common drugs which can lead ment for thrombocytopenic purpura should be
to thrombocytopenia include anti-infective drugs conducted by hematologist; and glucocorticoid
(ampicillin, aspirin, cephalosporins, azithromy- is the priority. Keep the mouth clean, and oral
cin, levofloxacin, moxifloxacin, compound sulfa- rinse with 1–3% hydrogen peroxide could be
methoxazole, rifampicin, chloramphenicol, prescribed.
sulfanilamide, etc.), antipyretic analgesics (aspi- Pressure hemostasis (periodontal dressing,
rin, acetaminophen, diclofenac, etc.), antimeta- gelatin sponge, or gauze) and hemostatics
bolic agents, cytotoxic drugs, and heparin [1]. (adrenaline, thrombin, Yunnan Baiyao, injection
Primary diseases which can cause thrombocyto- of vitamin K1 or K3) can be applied to stop gin-
penia consist of chronic lymphocytic leukemia, gival bleeding, while suture hemostasis can be
acute leukemia, lymphoma, systemic lupus ery- used in severe cases. Local application of anti-
thematosus, rheumatoid arthritis, hyperthyroid- inflammatory and antiseptic drugs can be helpful
ism, liver diseases, and so on. In addition, for erosions or secondary infection of oral
bacterial, fungal, or viral infection (rubella, mucosa.
172 X. Jin et al.
10.2 Leukemia
a b
Fig. 10.2 (a) Widespread necrotic ulcers on the right extending to the hard palate, with smooth and thick yel-
maxillary gingiva, extending to the hard palate, with lowish-white pseudomembrane. (c) Widespread necrotic
smooth and thick yellowish-white pseudomembrane. (b) ulcers on the left mandibular gingiva, with smooth and
Widespread necrotic ulcers on the left maxillary gingiva, thick yellowish-white pseudomembrane
a b
c d
e f
Fig. 10.3 (a) Diffuse enlargement of the right maxillary ment of the right maxillary and mandibular gingiva with
gingiva, with fine granular appearance changes. (b) fine granular appearance. (e) Two weeks later, more
Diffuse enlargement of the left maxillary gingiva, with severe enlargement of the left maxillary gingiva with fine
fine granular appearance and irregular superficial ulcers. granular appearance. (f) Two weeks later, more severe
(c) Hemispheric enlargement of the posterior maxillary swelling of the left submandibular region
palatal mucosa. (d) Two weeks later, widespread enlarge-
174 X. Jin et al.
early symptoms, and bleeding may occur at each Myeloid sarcoma mentioned in Case 90 is a
part of the body. Leukemic cells may also infil- solid malignant tumor consisting of immature
trate the spleen and lymph nodes, causing myeloid cells and occurring at an extramedullary
lymphadenopathy, hepatosplenomegaly, and site, mostly infiltrated by acute leukemia blasts. It
other lesions. Chronic leukemia is usually slow could be identified as the precursor of acute
progression; patients mainly suffer from low- myeloid leukemia; however, a few patients will
grade fever, profuse sweating, weight loss, ane- not progress to acute leukemia [11].
mia, bleeding, and splenomegaly [4, 5]. In some cases, due to the myeloperoxidase,
Gingival infiltration of leukemic cells is one green color is observed in the fresh tumor tissue,
of the most common clinical signs and symp- which is defined as chloroma. Myeloid sarcoma
toms, especially in the acute phase; thereby typically appears as localized mass or the com-
many timely diagnoses are made by dentists. pression symptoms, which can often be misdi-
Some diagnoses are further confirmed because agnosed mainly as lymphoma [12]. Intraoral
of unremitting bleeding after teeth extraction, MS is extremely rare, and gingival and palatal
subgingival scaling, and root planing. Gingival enlargement with superficial ulcerations has
overgrowth, hyperplasia, and edema are typical been reported [13, 14]. The diagnosis and
oral features. As a result of direct infiltration by immunophenotyping of MS rely mainly on
malignant leukocytes, the height of the hyper- immunohistochemical staining. MPO-positive
plastic gingiva could be close to the occlusal staining is very informative for diagnosis of
surface, with irregular shape and flabby texture. MS. The following markers are also the useful:
Spontaneous bleeding is always seen in the oral CD43, CD56, CD15 (a marker for the granulo-
mucosa and gums; blood clots, petechiae, cytic series), and CD 68 (the accepted marker
ecchymosis, and hematoma are also noted. The for cells from the monocytic series despite its
patients sometimes present with mucosal pallor absence of specificity) [12].
and irregular superficial ulcers which are not Treatments of leukemia or MS need combina-
easy to heal. Gingival inflammation, necrosis, tion chemotherapy and other comprehensive
pyorrhea, and loosening of the teeth could be treatment measures. Keep oral cavity clean, and
identified [6–10]. use compound chlorhexidine acetate solution to
Diagnosis of leukemia relies on clinical fea- prevent secondary infection [15].
tures, characteristic of hemogram, and bone mar-
row. Dentists and physicians should be vigilant
about the diffuse hyperplasia, erosion, and ulcers 10.3 Lymphoma
of oral mucosa, especially gingiva. Furthermore,
biopsy should be avoided without clear systemic Case 91 NK/T-Cell Lymphoma (Palatal
condition. Ulcer)
a b
Fig. 10.4 (a) Ulcer and necrosis on the hard palate with an area of 4 × 5 cm (Reproduced from [16]). (b) Atrophic
tongue with smooth surface
176 X. Jin et al.
a b
c d
Fig. 10.5 (a) Serious erosion and congestion on the mucosa covered by yellowish-white pseudomembrane.
labial aspect of anterior maxillary gingiva covered by (c) Half a month later, widespread ulcer and necrosis of
yellowish-white pseudomembrane, with partial necrosis. maxillary palatal gingiva, extending to the palate covered
(b) Half a month later, diffuse ulcer and necrosis of ante- by yellowish-white pseudomembrane. (d) Half a month
rior maxillary gingiva, extending to the upper labial later, obvious swelling of the left face
3. Hematoxylin and eosin staining of the gingi- Organization (WHO) classification includes two
val biopsy revealed gingival inflammatory main categories as types of lymphoma: Hodgkin’s
ulcer. Swelling of the left face was obvious. lymphomas and non-Hodgkin’s lymphomas. The
Oral examination showed widespread ulcers latter category is comprised of precursor lym-
on the labial and lingual aspect of maxillary phoid neoplasms, mature B-cell lymphomas, and
anterior gingiva, the corresponding labial ves- mature T-cell and NK-cell lymphomas [17].
tibule, and mucous membrane inside the upper The data from the Chinese Anti-Cancer
lip and the palate, which were covered by a Association estimated 84,000 new patients of
yellowish-white pseudomembrane, with lymphoma and more than 47,000 deaths each
increased necrosis (Fig. 10.5b–d). year, which indicate that the mortality of lym-
4. Maxillofacial contrast-enhanced CT revealed phoma in China is rising by 5%. Lymphoma inci-
increased density of the soft tissue in bilateral dence is gradually approaching the crowd of
nasal cavity, nasolabial fold, left wing of the young people and middle-aged. Because of the
nose, and the upper lip, and inflammation was active period of lymphatic system, high sensitiv-
considered. ity makes the young adults at high risk of lym-
5. The second biopsy was suggested, and results phoma (Chinese Center for Disease Control and
of HE staining and immunohistochemical Prevention, 2013). The constituent ratio of lym-
studies supported the diagnosis of nasal-type phoma is ranked second in oral and maxillofacial
extranodal NK-/T-cell lymphoma. malignancies after oral squamous cell carcinoma,
with increasing morbidity.
Diagnosis: The etiology remains unknown. It’s generally
Nasal-type extranodal NK-/T-cell lymphoma accepted that it is closely associated with Epstein-
Diagnosis Basis: Barr virus (EBV) and HIV infection, far greater
risk of lymphoma in HIV patients than general
1. Oral lesion manifested as gingival and palatal populations. Moreover, abnormal immunity,
ulcer, which was unresponsive to regular anti- autoimmune diseases, repeated infection, and
inflammation treatment. xenogenic organ transplantation can cause reac-
2. Results of HE staining and immunohisto-
tive lymphoid hyperplasia stimulated by host
chemical studies of the second biopsy con- antigens. Loss or dysfunction of T-cell lympho-
firmed the diagnosis. cytes results in lack of self-adjusting feedback
control and unlimited proliferation of lymphoid
Management: tissues, which lead to lymphoma finally. In addi-
tion, environmental pollution solvent dyes, heavy
1. She was transferred to the hematology depart- traffc fumes, great work and psychological pres-
ment for further therapy. sure, psychentonia, irregular life and fatigue,
2. Topical use of compound chlorhexidine solu- could reduce immune function, inducing lym-
tion, oral rinse, 3 times daily. phoma [18, 19].
Oral involvement of extranodal natural killer/
T-cell lymphoma (ENKTL) is more common.
[Review] Lymphoma ENKTL belongs to a group of mature NK-/T-cell
Lymphoma is a group of malignancies that lymphoma, which often present at extranodal
develop from lymph nodes or extranodal lym- sites with a broad morphological spectrum. It is
phoid tissues. In 2008, the World Health designated as an “NK-/T-cell” lymphoma
10 Oral Mucosal Lesions of Systemic Diseases 179
because, although most of the cases are believed The disease may be easily misdiagnosed.
to be of “true” natural killer (NK)-cell origin, First, it is hard to make the accurate impressions
“some” of the cases are known to demonstrate a at the early stage, because low incidence of the
T-cell phenotype. The actual proportion of cells disease, unawareness of the doctor, and atypical
is not well established. NK-/T-cell lymphomas symptoms and signs, especially primary, present
that originate from the nasal cavity/nasopharynx at extranodal sites. Second, the necrotic lesion is
may manifest similar signs and symptoms, clini- the main clinical signs, so it is relatively difficult
cal features, and immunophenotype; therefore, to choose the biopsy site. Repeated biopsy is con-
the diagnosis of ENKTL covers these kinds of sidered, if necessary. In addition, it is difficult to
malignancies [20]. distinguish from chronic inflammation due to
ENKTL often present intranasally characteris- neoplastic cell infiltration with diffused inflam-
tic of septal perforation and destruction. But matory cells.
some extranodal sites can be affected, such as the Cases 91 and 92 showed atypical clinical
hard palate, orbital cavity, gastrointestinal tract, symptoms and signs at first visit. Anti-
lung, and skin, and even the spine is involved. inflammatory therapeutic response could not
Most (80–90%) patients present with stuffy or be qualified for a diagnosis of common ulcer-
runny noses, hemorrhinia, sore throat, and dys- ative diseases. Therefore, repeated biopsy,
phagia. The major sign presents as ulcerative combined with nasal endoscopy, was sug-
neoplasms, with dry and puric crust covered on gested. The definite diagnosis was made by
the ulcer. Some patients also have local bone multidisciplinary consultation. As a conse-
destruction, presented by perforation of nasal quence, oral medicine specialists should pay
septum or hard palate, and bridge collapse, even attention to the repeated biopsy in the diagnos-
involving the midline facial tissues [16, 21]. Oral tic process, as well as close collaboration with
cases are often manifested as palatal necrotic pathology department, otorhinolaryngological
ulcers; bone destruction on the palate could be department, and oral surgery. We also highlight
found. the honest and patient communications with
The typical pathological findings are diffusely the sufferers, in order to gain the understand-
infiltrating lymphoma cells, large- or medium- ing and support of complex diagnostic process
sized. The nuclear contours are irregular. Tumor from them.
cells infiltrated in the area of necrosis mixed with The patients would be transferred to the hema-
abundant lymphocytes, plasma cells, eosinophils, tology or oncology department for further treat-
and histiocytes, which may be easily misdiag- ment by chemoradiotherapy. Median survival
nosed as chronic inflammation. was 4.2 years, and 5-year overall survival was
The immunohistochemistry demonstrated a 46% (median follow-up, 3.8 years). Extranasal
characteristic phenotype expressing CD2, CD56, type of ENKTL correlated with poorer prognosis
and CD3 epsilon and cytotoxic granule-associ- [22]. The two patients described above were
ated protein, such as TIA-1, granzyme B, and transferred to the hematology department imme-
perforin. In situ hybridization with a specific diately after diagnosis; unfortunately, they both
RNA probe demonstrated strong EBER-1(EBV- died 6 months later.
encoded small nuclear RNA) expression in neo-
plastic cells. Strong positive Ki-67 and negative
CD3 can be observed. According to the typical 10.4 Langerhans Cell
morphological features, with immunophenotypic Histiocytosis
and in situ hybridization profiling, we could
make an early and actual diagnosis [16, 19]. Case 93 Langerhans Cell Histiocytosis
180 X. Jin et al.
a b
Fig. 10.6 (a) Widespread swelling and masses on the palate and maxillary palatal gingiva. (b) Ulcers and masses
gradually normalized after chemotherapy (Reproduced from Jin et al. 2014)
[Review] Langerhans Cell Histiocytosis in local lesions. X-ray shows localized bone
Langerhans cell histiocytosis (LCH) is character- destruction, presenting as a round or oval shape
ized by anomalous proliferation of bone marrow- with clear border. No bone sequestration could be
derived Langerhans cells, as well as lots of seen and has a good prognosis.
leucocytes, eosinophils, neutrophils, lympho- Chronic diffuse LCH (Hand-Schüller-
cytes, plasma cells, and giant multinucleated Christian disease) usually appears in children or
cells, leading to tissue damage. It is a group of young adults, with slow onset. Hospital admis-
neoplastic disorders with widespread violation of sions are mainly due to skull soft tissue mass or
multiple systems and organs. The bone, skin, teeth loose and loss. The bone is damaged by
internal organs, and mucocutaneous system may numerous proliferated Langerhans cells and
be involved. LCH is a rare disease, which is esti- granulation tissues. It often affects the skull, dura
mated at approximately 2–5 cases per million mater, and adjacent bone tissue; the skull base,
inhabitants per year. It is more common in chil- sella turcica, and orbital cavity are also involved.
dren [23–25]. Moreover, hyperplasia of the tissue may press on
The etiology of LCH remains unclear. It may neurohypophysis and hypothalamus, which can
be caused by immune dysfunction, manifesting lead to diabetes insipidus; and pressure on eye-
as a hypersensitive response to an unknown stim- balls could result in exophthalmos. The common
ulation of the histiocyte-macrophage system [26, clinical manifestation was triad of exophthalmos,
27]. Failure of suppressor lymphocytes, altered osteolysis of the cranium, and diabetes insipidus.
autoantibodies, abnormal lymphocytic reactions Other manifestations may also occur, such as
to multiple mitogens, and structural modification petechiae, purpura, seborrheic dermatitis, and
in the thymus have been observed in all the lung dysfunction [25, 30].
advanced forms of LCH individuals [28]. The Acute disseminated LCH (Letterer-Siwe dis-
origin of inflammation or bacteriology is also ease) generally affects children under 3 years old
suspected [26, 27]. It is also associated with virus and progresses rapidly. It manifests in multiple
infection, such as human herpesvirus 6, Epstein- organs and systems, such as the liver, lung, lymph
Barr virus, and herpes simplex virus. Moreover, nodes, skin, bone marrow, and bone, presenting
accumulation of Langerhans cell infiltrate could clinically with eczema, hepatosplenomegaly, oti-
produce different systemic alterations depending tis media, anemia, hemorrhages, lymphadenopa-
on the location [29]. thies, and osteolytic lesions. Therefore, it has a
LCH was classified into four clinical forms poor prognosis, and death usually occurred
depending on the first-onset age and their distri- within few months.
bution sites, including chronic focal LCH Congenital reticulohistiocytosis (Hashimoto-
(eosinophilic granuloma), chronic diffuse LCH Pritzker syndrome) is characterized by the clinical
(Hand-Schüller-Christian disease), acute dissem- features of dark nodules on the trunk, face, and
inated LCH (Letterer-Siwe disease), and congen- scalp. The mucosa and skin are always involved,
ital reticulohistiocytosis (Hashimoto-Pritzker without implication of other organs [31].
syndrome) [23–25]. For the case of this unit, we could not confirm
Chronic focal LCH (eosinophilic granuloma) the subtype based on the present results. Because
is the most common form. It appears as a unifocal it should also be determined in consultation with
or multifocal lesion in a single or occasionally an oncologist to make a typing diagnosis, other
various bones. Long bones and skulls are mainly than examinations mentioned, which can be help-
affected, as well as the mandible. The soft tissue ful for predicting prognosis.
could be involved, without systemic manifesta- Oral lesions may be the initial manifestation
tions [25]. Swelling and pain could be found of LCH, and sometimes the only location
182 X. Jin et al.
involved [29]. There are 77% of the LCH well as abundant eosinophils, lymphocytes, and
patients who suffered from oral lesions, which mononuclear phagocytes. Immunohistochemical
often occur in the bone, mucosa, and periodon- results show S-100 and/or CD1a protein positiv-
tal tissue [28]. ity of lesional cells.
The cranium, maxilla, and mandible are the LCH in most patients is self-limited, with
most affected bones, usually infiltrating together. alternate period of relapse and remission. The
Mandibular lesions are the most frequent in all prognosis is unpredictable. Firstly, the outcome
three forms of LCH. Studies have found that pos- is poor if internal organs are involved (liver, lung,
terior zone and ramus of mandible were the most bone marrow). Secondly, the mortality rises to
sites for bone lesions [24]. Solitary intra-bony 50% in case of the age less than 2 years at the first
lesions always appeared in the initial phases, admission. Thirdly, the disease spreading to vari-
localized outside the alveolar process. Multiple ous bones or soft tissues may worsen the progno-
alveolar lesions, “scooped-out” alveolar lesions, sis [23, 25].
alveolar lesions with bone sclerosis, and alveolar Diverse therapeutic options are available,
lesions with bone neoformation were noted. including antibiotic treatment, chemotherapy,
Oral mucosal involvement tends to manifest radiotherapy, surgery, adrenocorticotropic hor-
as round and painful ulceration, with surrounding mone (ACTH), and glucocorticoids (both sys-
hyperemia. They are always limited to the buccal temic and intralesional) performed either
mucosa and hard palate. Red and white lesions individually or in combination. Correct mucosal
on anterior mandibular vestibule were also shown and periodontal treatment involves tartar removal
in other studies [32]. and subgingival scaling and planing, as well as
Skin lesions such as the typical eczematoid rigorous hygiene and maintenance to conserve
rash are mainly presented, which could be con- both teeth and periodontal tissue. Systemic che-
fused with sebaceous dermatitis. Subcutaneous motherapy could participate in accelerating oral
nodules are detected occasionally; therefore care- ulcer healing. In mucosal forms, complete reso-
ful checkups should be considered [33]. In addi- lution of a palatal lesion after the perilesional
tion, enlarged lymph nodes are found. infiltration of triamcinolone acetonide (eight ses-
Periodontal lesions are usually caused by sions over a 6-month period, for a total dose of
underlying alveolar bone destruction, accompa- 200 mg) has been reported. Another patient was
nying gingival ulceration, gingivitis, periodontal treated successfully with radiotherapy to the oral
pocket formation, and teeth mobility. lesions [31].
The diagnosis is made by pathological obser-
vation combined with clinical and radiographic
examinations. Histologic appearance reveals 10.5 Amyloidosis
large atypical histiocytic cells with round shape.
The kidney-shaped nuclei and a moderate num- Case 94 Amyloidosis (Macroglossia,
ber of eosinophilic cytoplasm can be detected, as Yellowish-White Nodular Lesions)
10 Oral Mucosal Lesions of Systemic Diseases 183
a b
c d
Fig. 10.7 (a) Increased tongue volume which cannot be Sporadic yellowish-white granular materials deposited in
extended outside the mouth. (b) Obvious teeth marks on the lower labial mucosa. (e) Yellowish-white granular
the right lateral tongue. (c) Yellowish-white granular materials deposited in the left buccal mucosa
materials deposited in the frenulum of tongue. (d)
184 X. Jin et al.
a b
c d
e f
Fig. 10.8 (a) Purple bulla-like lesions on the upper lip. left buccal mucosa. (e) Purple and red-purple bulla-like
(b) Purple bulla-like masses on the lower lip. (c) Purple lesions on the dorsum of the tongue. (f) Purple and red-
and red-purple bulla-like lesions on the right buccal purple bulla-like lesions on the ventral tongue. (g) Swelling
mucosa. (d) Purple and red-purple bulla-like lesions on the of the submandibular area (Reproduced from [34])
186 X. Jin et al.
ing fibril deposition. Accordingly, the disease is They remained minimal dysfunction and symp-
designated as amyloid protein plus a suffix, in tom-free after being treated surgically [41].
which A represents amyloid and the suffix spec- The head and neck region is affected in
ifies the protein. The most common types are 12–90% of amyloidosis patients, typically with
immunoglobulin/light-chain related (AL) and the larynx and tongue affected [42]. The most
familial transthyretin-associated (ATTR). common manifestations are hoarseness, nasal
Secondary amyloidosis is caused by amyloid congestion, odynophagia, articulation prob-
derived from serum amyloid A, an acute-phase lems, mandibular deformities, deglutition diffi-
protein produced in response to chronic inflam- culties, airway obstruction, speech disorders,
mation (AA). and hypogeusia. Amyloidosis involvement of
AL amyloidosis is characterized by deposition the tongue is usually secondary to systemic dis-
of monoclonal immunoglobulin light chains. The eases, consisting of tuberculosis, rheumatoid
presence of monoclonal paraprotein contains arthritis, and multiple myeloma. Macroglossia
amyloid light chains in urine and serum, is also occurs in 26–83% of patients with multiple
known as Bence-Jones protein (BJP). It often myeloma, often with enlarged tongue beyond
appears in urine of patients with myeloma, which the alveolar ridge, speech impairment, and dys-
may have the diagnostic significance [37]. Serum phagia. Yellowish-white granular materials
or urine BJP will be detected in up to 88% of indi- deposited along the lateral border can also be
viduals with primary systemic amyloidosis and observed, as shown in Case 94 [37]. Oral amy-
100% of patients with multiple myeloma [37]. loidosis could also present as widespread purple
The initial symptoms of AL amyloidosis are most bulla-like masses of the oral mucosa, as shown
frequently fatigue and weight loss, and the organs in Case 95 [34].
most commonly involved are the kidney and the The diagnosis of amyloidosis is made based
heart. Renal amyloidosis may manifest as protein- on pathology. When stained with Congo red, the
uria and mild renal dysfunction, with profound deposits of protein fibrils show apple-green bire-
edema and hypoalbuminemia. Cardiac lesions fringence on polarized light microscopy. Once
often present as congestive heart failure and thick- the diagnosis has been made, an extensive workup
ened ventricle, and the ejection fraction is reduced. for systemic disorders should be undertaken.
AA amyloidosis occurs secondary to chronic In AL amyloidosis, monoclonal paraprotein
inflammatory conditions such as tuberculosis or composed of amyloid light chains could be
rheumatoid arthritis [38]. Renal deposition is detected by immunofixation electrophoresis of
the most common lesion that is often asymp- serum or urine. Immunohistochemical staining of
tomatic. Hepatomegaly and splenomegaly can a bone marrow biopsy to search for κ- or λ-light
be involved. In this condition, fibrils may be chains should be performed to exclude plasma
easy to deposit in the joints [39]. In addition, cell dyscrasia. Monoclonal immunoglobulin or
autonomy and sensory neuropathy, gastrointes- immunoglobulin fragment may be produced by
tinal hemorrhage, and spontaneous periorbital abnormal proliferation of a monoclonal group of
purpura are the uncommon features of AL and plasma cells. The related disorders include mul-
AA amyloidosis. tiple myeloma, solitary plasmacytoma, extra-
ATTR amyloidosis rarely affects the kidney medullary plasmacytoma, paraproteinemia, and
and tongue, but peripheral sensory/motor and heavy-chain disease.
autonomic neuropathies are more common, as A variant transthyretin could be inspected by
well as diarrhea and weight loss [37, 40]. isoelectric focusing of the serum, which will sep-
Localized amyloidosis, which occurs without arate variant from wild-type transthyretin. AA
any evidence of systemic involvement, is much amyloidosis is suspected under chronic inflam-
more rare than the others. In a review of 236 cases matory condition in whom AL and ATTR amy-
of amyloidosis, only 22 cases (9%) were local- loidosis have been excluded. Definite diagnosis
ized. None of these individuals progressed to sys- is then made by immunohistochemical staining
temic amyloidosis in a follow-up of 10 years. for the AA protein (Fig. 10.9).
188 X. Jin et al.
Fig. 10.9 Diagnostic
flow chart for History and examination
amyloidosis
Positive Negative
Isoelectric focusing /
AL amyloidosis RFLP of DNA
Positive Negative
Amyloidosis of the tongue is more related to of patients with MM, the erythrocyte sedimenta-
multiple myeloma (MM) currently. MM accounts tion rate increased in 84% (>20 mm/h), and lytic
for approximately 10% of hematologic malig- lesions in about 67% [45]. Enlarged submandibu-
nancies and tends to occur in middle-aged and lar glands present in about 40% of individuals
elderly. The common clinical features are osteo- with MM-associated amyloidosis [46, 47].
lytic bone lesions, anemia, hypercalcemia, renal The median survival time for patients without
failure, and infections. MM was 15 months, compared to 5 months for
The diagnostic criteria are 10% or more clonal those with MM [41]. Suspected patients with
plasma cells on bone marrow inspection or a MM-associated amyloidosis should be performed
biopsy that confirmed plasmacytoma and end- with biopsy and Congo red staining as soon as pos-
organ damage (hypercalcemia, renal insuffi- sible. It is important to carry out comprehensive
ciency, anemia, or bone lesions) that is related to inspections for an early and accurate diagnosis,
the underlying plasma cell disorder. In addition, such as blood routine, erythrocyte sedimentation
the presence of 60% or more clonal plasma cells rate, urine routine, chest CT, abdominal ultraso-
in the marrow could also be considered as nography, ultrasonic cardiogram, serum or urine M
myeloma regardless of the presence or absence of protein, and bone marrow biopsy.
end-organ damage [43]. The serum or urine M There is no specific therapy for amyloidosis.
protein is an abnormal immunoglobulin fragment The commonly used drugs include colchicine,
or immunoglobulin light chain that is produced in melphalan, and prednisone. Once patients with
excess by an abnormal monoclonal proliferation secondary amyloidosis have some primary disor-
of plasma cells, typically in multiple myeloma. ders, the underlying systemic diseases should be
Therefore, an increase in single κ- or λ-light timely treated. In case of the localized form,
chain should be highly suspected of MM. In intralesional triamcinolone acetonide multipoint
addition, autoimmune disease, infection, tumor, low-dose injection could be used. Surgical and
hepatitis, and cirrhosis are generally present laser treatment could be employed [48].
increasing both κ- and λ-light chains. Among the AL amyloidosis is a subtype with poor progno-
patients with multiple myeloma, 15% may sis if left untreated, with a median survival time of
develop some form of amyloidosis [44]. A review 1–2 years. The survival time of AA amyloidosis is
study has found that anemia was present in 73% affected by associated systemic diseases.
10 Oral Mucosal Lesions of Systemic Diseases 189
a b
c d
e f
Fig. 10.10 (a) Widespread exuberant papillomatosis of palate. (g) Multiple “wartlike” papillomatous on the
the upper lip. (b) Widespread exuberant papillomatosis of insteps. (h) Hyperkeratotic soles with prominence of the
the right buccal mucosa. (c) Widespread exuberant papil- papillomatous growths and hyperpigmentation. (i)
lomatosis of the left buccal mucosa. (d) Widespread exu- Multiple “wartlike” papillomatous on the back of the
berant papillomatosis of dorsum of the tongue. (e) hand. (j) Brownish hyperpigmentation of the axilla. (k)
Widespread exuberant papillomatosis of dorsum of the Brownish hyperpigmentation of the mammary areola
tongue. (f) Widespread exuberant papillomatosis of the
190 X. Jin et al.
g h
i j
Fig. 10.10 (continued)
against the tumor. Although the etiology and tumor markers, and biopsy performed immedi-
pathogenesis of PNS still remain unclear, the auto- ately should be the most effective.
immune abnormality is believed to the leading Topical fade creams or cosmetic surgery can
cause. Antigens expressed by tumor cells trigger lighten skin cosmetically in less severe cases.
various antibodies to start an antitumor immune Malignant AN may regress following tumor-spe-
response. Normal tissues expressing similar pro- cific therapy and usually worsens with cancer
tein can then be attacked by these autoantibodies progression.
[56]. It is important to make early diagnosis if
widespread verrucous lesions or multiple papillo-
matous lesions occur, in order to detect underlying 10.7 Focal Dermal Hypoplasia
malignancy as soon as possible. If malignant AN
is suspected, computed tomography, serological Case 97 Focal Dermal Hypoplasia
a b
c d
e f
Fig. 10.11 (a) Raspberrylike papilloma over the corner face hypoplasia, skin hypopigmentation, red proliferation
of the mouth. (b) Raspberrylike papilloma on the upper on the right abdomen (area was 5 × 8 cm2), linear dermal
lip. (c) Widespread raspberrylike papilloma on the tongue. atrophy along Blaschko’s lines of the right legs, hypoplas-
(d) Raspberrylike papilloma on the ventral tongue and tic nails with longitudinal splitting, and partial absence of
enamel hypoplasia of incisors. (e) Enamel hypoplasia of the fingernails and toenails (Reproduced from [57])
molars and papilloma on the gingiva. (f) Skin lesions: mid-
10 Oral Mucosal Lesions of Systemic Diseases 193
sis of oral manifestations. Med Oral Patol Oral Cir adenocarcinoma: a case report and literature review. J
Bucal. 2009;14(5):E222–8. Am Acad Dermatol. 2000;42(2 Pt 2):357–62.
33. Zhang K, Zeng H, Chen WQ. Clinical features and 51. Tyler MT, Ficarra G, Silverman S Jr, Odom RB,
diagnosis of langerhans cell hyperplasia. Ai Zheng. Regezi JA. Malignant acanthosis nigricans with florid
2006;25(1):88–91. papillary oral lesions. Oral Surg Oral Med Oral Pathol
34. Li Y, Liu N, Xu Y, et al. Widespread purple bulla-like Oral Radiol Endod. 1996;81(4):445–9.
masses of the oral mucosa. Oral Surg Oral Med Oral 52. Brinca A, Cardoso JC, Brites MM, Tellechea O,
Pathol Oral Radiol. 2012;114(5):552–7. Figueiredo A. Florid cutaneous papillomatosis and
35. Khan MF, Falk RH. Amyloidosis. Postgrad Med J. acanthosis nigricans maligna revealing gastric adeno-
2001;77(913):686–93. carcinoma. An Bras Dermatol. 2011;86(3):573–7.
36. Steciuk A, Dompmartin A, Troussard X, et al.
53. Weger W, Ginter-Hanselmayer G, Hammer HF, Hodl
Cutaneous amyloidosis and possible associa- S. Florid cutaneous papillomatosis with acanthosis
tion with systemic amyloidosis. Int J Dermatol. nigricans in a patient with carcinomas of the lung and
2002;41(3):127–32; discussion 133–4. prostate. J Am Acad Dermatol. 2007;57(5):907–8.
37. Fahrner KS, Black CC, Gosselin BJ. Localized amy- 54. Csete B, Moezzi M, Lengyel Z, Hodosi B, Zombai
loidosis of the tongue: a review. Am J Otolaryngol. E, Battyani Z. Florid cutaneous papillomato-
2004;25(3):186–9. sis leading to social exclusion. Br J Dermatol.
38. Angiero F, Seramondi R, Magistro S, et al. Amyloid 2005;153(3):667–9.
deposition in the tongue: clinical and histopathologi- 55. Janniger EJ, Schwartz RA. Florid cutaneous papillo-
cal profile. Anticancer Res. 2010;30(7):3009–14. matosis. J Surg Oncol. 2010;102(6):709–12.
39. Danesh F, Ho LT. Dialysis-related amyloidosis:
56. Koyama S, Ikeda K, Sato M, et al. Transforming
history and clinical manifestations. Semin Dial. growth factor-alpha (TGF alpha)-producing gastric
2001;14(2):80–5. carcinoma with acanthosis nigricans: an endocrine
40. Falk RH, Comenzo RL, Skinner M. The systemic effect of TGF alpha in the pathogenesis of cutaneous
amyloidoses. N Engl J Med. 1997;337(13):898–909. paraneoplastic syndrome and epithelial hyperplasia of
41. Kyle RA, Bayrd ED. Amyloidosis: review of 236 the esophagus. J Gastroenterol. 1997;32(1):71–7.
cases. Medicine (Baltimore). 1975;54(4):271–99. 57. Wang L, Jin X, Zhao X, et al. Focal dermal hypopla-
42. Kerner MM, Wang MB, Angier G, Calcaterra TC, sia: updates. Oral Dis. 2014;20(1):17–24.
Ward PH. Amyloidosis of the head and neck. A 58. Goltz RW, Peterson WC, Gorlin RJ, Ravits HG. Focal
clinicopathologic study of the UCLA experience, dermal hypoplasia. Arch Dermatol. 1962;86:708–17.
1955–1991. Arch Otolaryngol Head Neck Surg. 59. Lasocki AL, Stark Z, Orchard D. A case of mosaic
1995;121(7):778–82. Goltz syndrome (focal dermal hypoplasia) in a male
43. Rajkumar SV. Multiple myeloma: 2013 update on patient. Australas J Dermatol. 2011;52(1):48–51.
diagnosis, risk-stratification, and management. Am J 60. Grzeschik KH, Bornholdt D, Oeffner F, et al.
Hematol. 2013;88(3):225–35. Deficiency of PORCN, a regulator of Wnt signaling,
44. Oliveira EV, Pozetti AC, Pozetti EM, Antonio JR, is associated with focal dermal hypoplasia. Nat Genet.
Michalany NS. Primary systemic amyloidosis asso- 2007;39(7):833–5.
ciated with multiple myeloma. An Bras Dermatol. 61. Lombardi MP, Bulk S, Celli J, et al. Mutation update
2012;87(1):119–22. for the PORCN gene. Hum Mutat. 2011;32(7):723–8.
45. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 62. Quain RD, Militello G, Junkins-Hopkins J, Yan AC,
patients with newly diagnosed multiple myeloma. Crawford GH. Erythematous atrophic macules and
Mayo Clin Proc. 2003;78(1):21–33. papules following the lines of Blaschko. Focal der-
46. Prokaeva T, Spencer B, Kaut M, et al. Soft tissue, mal hypoplasia (FDH), or Goltz syndrome. Arch
joint, and bone manifestations of AL amyloidosis: Dermatol. 2007;143(1):109–14.
clinical presentation, molecular features, and survival. 63. Baxter AM, Shaw MJ, Warren K. Dental and oral
Arthritis Rheum. 2007;56(11):3858–68. lesions in two patients with focal dermal hypoplasia
47. Chang SS, Lu CL, Tsay SH, Chang FY, Lee
(Goltz syndrome). Br Dent J. 2000;189(10):550–3.
SD. Amyloidosis-induced gastrointestinal bleeding in 64. Balmer R, Cameron AC, Ades L, Aldred MJ. Enamel
a patient with multiple myeloma. J Clin Gastroenterol. defects and lyonization in focal dermal hypoplasia.
2001;32(2):161–3. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.
48. Thibault I, Vallieres I. Macroglossia due to systemic 2004;98(6):686–91.
amyloidosis: is there a role for radiotherapy. Case Rep 65. Seoane J, Gibson RL, Almagro M, Pintos E. Oral
Oncol. 2011;4(2):392–9. manifestations associated with focal dermal hypopla-
49. Bottoni U, Dianzani C, Pranteda G, et al. Florid cuta- sia. Dermatology. 2009;219(4):368–70.
neous and mucosal papillomatosis with acanthosis 66. Marcus DM, Shore JW, Albert DM. Anophthalmia
nigricans revealing a primary lung cancer. J Eur Acad in the focal dermal hypoplasia syndrome. Arch
Dermatol Venereol. 2000;14(3):205–8. Ophthalmol. 1990;108(1):96–100.
50. Yeh JS, Munn SE, Plunkett TA, Harper PG, Hopster 67. Prenner JL, Ciaccia S, Capone A Jr, Trese MT. Retinal
DJ, du Vivier AW. Coexistence of acanthosis nigricans detachment in focal dermal hypoplasia. Eur J
and the sign of Leser-Trelat in a patient with gastric Ophthalmol. 2004;14(2):166–8.
10 Oral Mucosal Lesions of Systemic Diseases 197
6 8. Bhatia AM, Clericuzio CL, Musemeche 75. Kimonis VE, Goldstein AM, Pastakia B, et al.
CA. Congenital ventral hernia in association Clinical manifestations in 105 persons with nevoid
with focal dermal hypoplasia. Pediatr Dermatol. basal cell carcinoma syndrome. Am J Med Genet.
1995;12(4):336–9. 1997;69(3):299–308.
69. Han XY, Wu SS, Conway DH, et al. Truncus arterio- 76. Bleeker-Wagemakers LM, Hamel BC, Hennekam RC,
sus and other lethal internal anomalies in Goltz syn- Beemer FA, Oorthuys HW. Oculocerebrocutaneous
drome. Am J Med Genet. 2000;90(1):45–8. syndrome. J Med Genet. 1990;27(1):69–70.
70. Suskan E, Kurkcuoglu N, Uluoglu O. Focal dermal 77. Prabhu NT, John R, Munshi AK. Rieger’s syndrome:
hypoplasia (Goltz syndrome) with horseshoe kidney a case report. Quintessence Int. 1997;28(11):749–52.
abnormality. Pediatr Dermatol. 1990;7(4):283–6. 78. Happle R, Daniels O, Koopman RJ. MIDAS syn-
71. Lopez-Porras RF, Arroyo C, Soto-Vega E. Focal der- drome (microphthalmia, dermal aplasia, and sclero-
mal hypoplasia with uterus bicornis and renal ecto- cornea): an X-linked phenotype distinct from Goltz
pia: case report and review of the literature. Case Rep syndrome. Am J Med Genet. 1993;47(5):710–3.
Dermatol. 2011;3(2):158–63. 79. Alster TS, Wilson F. Focal dermal hypoplasia (Goltz’s
72. Kanemura H, Hatakeyama K, Sugita K, Aihara
syndrome). Treatment of cutaneous lesions with the
M. Epilepsy in a patient with focal dermal hypoplasia. 585-nm flashlamp-pumped pulsed dye laser. Arch
Pediatr Neurol. 2011;44(2):135–8. Dermatol. 1995;131(2):143–4.
73. Smigiel R, Jakubiak A, Lombardi MP, et al.
80. Liu J, Hsu PT, Vanderwielen BA, Teng JM. Treatment
Co-occurrence of severe Goltz-Gorlin syndrome and of recalcitrant excessive granulation tissue with pho-
pentalogy of Cantrell—case report and review of the todynamic therapy in an eight-year-old patient with
literature. Am J Med Genet A. 2011;155A(5):1102–5. focal dermal hypoplasia syndrome. Pediatr Dermatol.
74. Reddy J, Laufer MR. Congenital anomalies of the 2012;29(3):324–6.
female reproductive tract in a patient with Goltz syn-
drome. J Pediatr Adolesc Gynecol. 2009;22(4):e71–2.
Oral Mucosal Pigmentation
11
Yu Zhou, Xin Jin, and Qianming Chen
Keywords
Melanoplakia ∙ Vitiligo
Y. Zhou
State Key Laboratory of Oral Diseases, National
Clinical Research Center for Oral Diseases,
Department of Oral Medicine, West China Hospital
of Stomatology, Sichuan University,
Chengdu, Sichuan, China
X. Jin
College of Stomatology, Chongqing Medical
University, Chongqing Key Laboratory of Oral
Diseases and Biomedical Sciences,
Chongqing, China
Q. Chen (*)
Changjiang Scholars Program, Ministry of Education,
Beijing, China
State Key Laboratory of Oral Diseases, National
Clinical Research Center for Oral Diseases,
Department of Oral Medicine, West China Hospital
of Stomatology, Sichuan University,
Chengdu, Sichuan, China
e-mail: qmchen@scu.edu.cn
© Springer Nature Singapore Pte Ltd. and People’s Medical Publishing House 2018 199
Q. Chen, X. Zeng (eds.), Case Based Oral Mucosal Diseases,
https://doi.org/10.1007/978-981-13-0286-2_11
200 Y. Zhou et al.
a b
c d
Fig. 11.1 (a) Scattered brownish black patches on the brownish black patches on the lower lip and gingiva,
lower lip, which were flat, soft, and not erosive. (b) which were flat, soft, and not erosive. (d) Scattered
Scattered brownish black patches on the dorsum of brownish black patches on the hard palate, which were
tongue, which were flat, soft, and not erosive. (c) Scattered flat, soft, and not erosive
Management:
Advise observing. If the patient is in a stable con-
dition, he should have regular reexamination
every 6 months. If the melanin patch enlarges,
bulges or festers, he should have reexamination
timely.
syndrome is sporadic cases and occurs in middle- adenomas after the surgery of removal of bilat-
aged adults. Pigmented spots gradually aggravate eral adrenal for treating Cushing’s syndrome.
with age increasing and are not associated with These oral mucosa pigmentation related with
colon polyps, the abdominal symptoms above, systematic disease generally do not need treat-
and the genetic mutations of STK11/LKB1 [6, 7]. ment, and the disappearance of oral dark spots
Addison disease, also called primary hypoad- may follow the treatment of the systematic dis-
renalism, is caused by the damages of the bilat- ease [1, 11].
eral adrenal glands induced by tuberculosis, Hemochromatosis is a disease induced by iron
autoimmune reaction, malignant tumor metasta- metabolism disorder (disorder of iron metabo-
sis, lymphoma, leukemia, systemic fungal infec- lism) which is caused by the excessive accumula-
tions, etc. The gland damage causes insufficient tions of iron in the body. High-iron diet, much
secretion of adrenocortical hormone, which stim- blood transfusion, or systemic disease can cause
ulates adenohypophysis to produce more adreno- excessive accumulations of iron. This disease can
corticotropic hormone (ACTH), leading to the also be found in the hemolytic disease like globin
melanocyte-stimulating hormone increase, generation barrier anemia. Middle-aged men are
finally manifesting as diffuse dark spots on the easily affected and women are rarely affected.
skin and oral mucosa. Pigmentation is one of the Clinical manifestations are the skin of the face,
early symptoms and is also the most characteris- upper limbs, opisthenar, and armpit, perineal skin
tic manifestation of the disease. Pigmentation is representing bronze-colored or gray black. There
most obvious in the exposed parts and location can be bluish-gray or bluish-black pigmented
where it is easily influenced by friction and can spots on the oral mucosa, usually observed in the
also be observed in mucous membrane. In addi- junction between hard and soft palate. There are
tion, symptoms like fatigue, weakness, weight also clinical manifestations of abnormal liver
loss, the drop in blood pressure, appetite loss, function and diabetes. The disease can be diag-
mental disorders, etc., can also occur. This dis- nosed by abnormal liver function, blood glucose,
ease is more common among adults and is rarely pigmentation of the skin or mucosa, increased
found among the elderly and young children [8, serum iron content, etc. [11, 12].
9]. The diagnosis of the disease needs to detect Oral melanoacanthoma is rare and presented
the basic level of cortisol in the blood and urine as brown and brownish-black patch or plaque
and the ACTH level in the blood and do ACTH with clear boundary, which is similar to skin
excitation test. melanoacanthoma. The etiology is not clear. The
Polyostotic fibrous dysplasia, also known as buccal mucosa, lip, upper palate, tooth, and gin-
McCune-Albright syndrome, is a rare congenital gival mucosa are the most common locations.
disease found in children and adolescents. It The average age is 28, and it has predilection for
shows a little higher rate among women com- females. It may be associated with stimulated
pared to men. The course progresses slowly, and factors and is a benign disease without malignant
it has a tendency of self-limiting. The character- potential [1].
istics are the pigmentation on the oral mucosa or Melanocytic nevus is divided into junctional
skin, multiple fibrous osteitis, and precocious nevus, intradermal nevus, and compound nevus
puberty. Oral mucosa pigmentation is presented and is rarely observed on the oral mucosa. It clin-
as brown spot, and the lip is the most common ically is presented as small, slightly protuberant,
location [10]. The definite diagnosis needs clini- brown, bluish-gray, or black papules with clear
cal three major characteristics with bone X-ray border. It is difficult to distinguish pigmented
film. nevus from melanoma in early stage especially
Other endocrine diseases associated with oral the lesion on the palate clinically.
mucosa pigmentation include hyperfunction of Malignant melanoma is one of the high malig-
thyroid, Nelson syndrome. The latter is progres- nant degree tumors of oral and maxillofacial
sive skin pigmentation of melanin and pituitary region. The skin and mucosa can be involved, and
11 Oral Mucosal Pigmentation 203
it can be observed more on the mucosa than the biopsy can be taken during the surgery. After
skin. Malignant melanomas of oral and maxillo- making a definite diagnosis, it should complete
facial region often originate from pigmented the radical resection at the same time [14–16].
nevus, mainly malignant transformation from Some heavy metal poisoning, such as chronic
junctional nevus; also melanoplakia can be lead poisoning, bismuth poisoning, and mercury
involved [13]. Ultraviolet ray, heredity, endo- poisoning, will form lead lines, bismuth lines, or
crine, chronic stimulation, and injury have a cer- mercury lines on gingival margin presenting
tain relationship with the incidence of malignant black-blue and bluish-gray pigmentation band or
melanoma. It is more commonly found in people gray-black and bluish-gray pigmented spots on
at the age of around 40. There is no significant the lips, tongue, and buccal membrane with
difference in rates between genders. It represents inflammation of oral mucosa when the disease is
the lesion of pigmented nevus or melanoplakia in severe. The diagnosis needs to measure heavy
the early stage. When it undergoes malignant metal content in the blood and urine [11].
transformation, it becomes bigger quickly, its Excessive smoking can make oral mucosa
pigment becomes deep, it has radiated extension, representing brown to black; irregular melanin
it ruptures (errhysis), satellite nodules occur sur- spots which can be found in 25–31% of smokers
rounding it, and lymph nodes increase sharply. and the lips, buccal mucosa, and labial attached
The palate, gingiva, and buccal mucosa are com- gingiva of the lower anterior teeth are mainly
monly involved in malignant melanoma involved. Some reports have said it can fade after
(Fig. 11.4). It often presents as slightly elevated, 3 years of quitting smoking [1, 3].
bluish-brown lesions, with surface rupture and A variety of drugs such as diazepam, contra-
rapid growth. When alveolar process and the jaw ceptive drugs, antimalarial drugs, imidazole tet-
bone are affected, it can cause teeth to loosen. racycline, and cell inhibitors can cause oral
Malignant melanoma often has early and exten- membrane pigmentation. After stopping taking
sive lymph node metastasis. First of all it metas- drugs, pigmented spots will sustain for some
tasizes to submandibular lymph nodes and upper time. In addition, some gargle such as chlorine or
deep cervical lymph node groups. The rate of the traditional Chinese medicine also can make
blood metastasis is high, it can amount to 40%, the temporary pigmentation of oral mucosa.
and it mainly metastasizes to the lung, liver, bone, Long-term inflammation of oral mucosa such
brain, and other organs. The diagnosis is mainly as oral lichen planus and pemphigus can cause
based on its clinical manifestations. Because pigmentation on mucosa. The etiology is not
biopsy can promote tumor proliferation and clear, and the darker-skinned people are more
metastasis, it is generally not suitable for biopsy. commonly affected. Dark brown-colored area is
But because of the difficulties of diagnosis, frozen adjacent to reticular, ulcerative, bullous lesion on
the oral mucosa. In general, pigmentation turns
for the better after inflammation is relieved [1].
Some other abnormal color diseases of the
oral mucosa related to vascular lesions are com-
mon found in [3].
Kaposi’s sarcoma mainly occurs in patients
with HIV infection. Early lesions on infected
patients may present as a flat or slightly raised
brown, purple lesion. Advanced lesions appear as
deep red or purple patches, nodules, and it may
have ulceration, bleeding, and necrosis (Fig. 8.12).
Hemangioma is a benign lesion caused by
vascular endothelial cell proliferation. Vascular
Fig. 11.4 Malignant melanoma on the palate malformation refers to the structural abnormali-
204 Y. Zhou et al.
ties of blood vessels without endothelial cell pro- color will not fade when pressing it, and throm-
liferation. Two kinds of lesions are involved in bus are commonly found in lower lip and buccal
dysplasia and are often found in infants and mucosa.
young children. Hemangioma can be relieved Hemorrhagic diseases such as hematoma, pete-
with age increasing, and vascular malformation chia, and ecchymosis are generated by blood spill-
has no obvious change. The tongue is the most ing into the soft tissue. The lesion is raised or flat,
commonly affected on the oral mucosa. Two and the color will not fade when pressing it. It may
kinds of vascular lesions have similar clinical occur after trauma or thrombocytopenic purpura;
manifestations, and the lesions are flat or slightly the color depends on the time after the blood
raised. The color depends on the type of the blood spilled out of the vessel; because of the hemoglo-
vessels and depth of the lesion in the organiza- bin degradation, it will appear red, purple, blue,
tion, ranging from dark red to purple. In general, dark blue, etc. The color will gradually be normal
the color fades when doing diascopic examina- in 2 weeks. If traumatic stimulated factors are
tion (Fig. 11.5). unchecked, the platelet disease and blood coagula-
Varix is abnormal swollen veins, and it is tion disorders should be considered (Fig. 10.1).
commonly found in the patients at the age of The diagnosis of oral melanoplakia can be
more than 60. The ventral of the tongue mucosa made after excluding the diseases above. At pres-
is the most common location in the oral. It is pre- ent, it is regarded as benign lesions, and conven-
sented much bluish-violet, irregular, soft protu- tional biopsy is not advocated. There is no
berance, and the color fades when doing diascopic effective therapy yet, so the observation and reg-
examination (Fig. 11.6). If the vessel contains ular subsequent visit are suggested. If color or
thrombus, it presented solid purple nodules, the size of melanoplakia changes, especially if pro-
trusion, ulceration, or bleeding of the surface
appears, the patients should return immediately
to rule out melanoma.
Fig. 11.7 The color of upper and lower lip is not uni-
form, with more color shallow white area. Upper and
lower lip and lip red skin appeared with depigmentation
Fig. 11.6 Varicose veins on the ventral surface of tongue area, which is around with brown pigmentation
11 Oral Mucosal Pigmentation 205
4. Higham P, Alawi F, Stoopler ET. Medical management 14. Mihajlovic M, Vlajkovic S, Jovanovic P, et al. Primary
update: Peutz Jeghers syndrome. Oral Surg Oral Med mucosal melanomas: a comprehensive review. Int J
Oral Pathol Oral Radiol Endod. 2010;109(1):5–11. Clin Exp Pathol. 2012;5(8):739–53.
5. Daley TD, Armstrong JE. Oral manifestations 15. Knight DA, Ngiow SF, Li M, et al. Host immunity
of gastrointestinal diseases. Can J Gastroenterol. contributes to the anti-melanoma activity of BRAF
2007;21(4):241–4. inhibitors. J Clin Invest. 2013;123(3):1371–81.
6. Ma DL, Vano-Galvan S. Hyperpigmentation 16. Bhullar RP, Bhullar A, Vanaki SS, et al. Primary mela-
in Laugier-Hunziker syndrome. CMAJ. noma of oral mucosa: a case report and review of lit-
2011;183(12):1402. erature. Dent Res J (Isfahan). 2012;9(3):353–6.
7. Wang WM, Wang X, Duan N, et al. Laugier-Hunziker 17. Alikhan A, Felsten LM, Daly M, et al. Vitiligo: a com-
syndrome: a report of three cases and literature review. prehensive overview. Part I. Introduction, epidemiol-
Int J Oral Sci. 2013;4(4):226–30. ogy, quality of life, diagnosis, differential diagnosis,
8. Chi AC, Neville BW, Krayer JW, et al. Oral mani- associations, histopathology, etiology, and work-up. J
festations of systemic disease. Am Fam Physician. Am Acad Dermatol. 2011;65(3):473–91.
2010;82(11):1381–8. 18. El Madani HA, Tancrede-Bohin E, Bensussan A,
9. Shah SS, Oh CH, Coffin SE, et al. Addisonian pig- et al. In vivo multiphoton imaging of human skin:
mentation of the oral mucosa. Cutis. 2005;76(2):97–9. assessment of topical corticosteroid-induced epi-
10. Collins MT, Singer FR, Eugster E. McCune-Albright dermis atrophy and depigmentation. J Biomed Opt.
syndrome and the extraskeletal manifestations of 2012;17(2):026009.
fibrous dysplasia. Orphanet J Rare Dis. 2012;7(Suppl 19. Kanwar AJ, Parsad D, De D. Mucosal involvement in
1):S4. vitiligo: a comprehensive review of 241 cases. J Eur
11. Meleti M, Vescovi P, Mooi WJ, et al. Pigmented
Acad Dermatol Venereol. 2011;25(11):1361–3.
lesions of the oral mucosa and perioral tissues: a flow- 20. Mchepange UO, Gao XH, Liu YY, et al. Vitiligo in
chart for the diagnosis and some recommendations North-Eastern China: an association between muco-
for the management. Oral Surg Oral Med Oral Pathol sal and acrofacial lesions. Acta Derm Venereol.
Oral Radiol Endod. 2008;105(5):606–16. 2010;90(2):136–40.
12. Pietrangelo A. Hereditary hemochromatosis: patho- 21. De D, Kanwar AJ, Saikia UN, et al. Colocalization of
genesis, diagnosis, and treatment. Gastroenterology. mucosal vitiligo and oral pemphigus vulgaris. Indian
2010;139(2):393–408, 408.e1–2. J Dermatol Venereol Leprol. 2012;78(1):111–3.
13. Chan RC, Chan JY, Wei WI. Mucosal melanoma of the 22. Korobko IV. Review of current clinical studies of
head and neck: 32-year experience in a tertiary refer- vitiligo treatments. Dermatol Ther. 2012;25(Suppl
ral hospital. Laryngoscope. 2012;122(12):2749–53. 1):S17–27.
Other Oral Mucosal Diseases
12
Xin Jin and Xin Zeng
Age: 67 years
X. Jin Sex: Female
College of Stomatology, Chongqing Medical Chief Complaints:
University, Chongqing Key Laboratory of Oral A 67-year-old woman with bilateral buccal irrita-
Diseases and Biomedical Sciences, tive pain for 6 months
Chongqing, China
History of Present Illness:
X. Zeng (*) A 67-year-old woman presented to our clinic
State Key Laboratory of Oral Diseases, National
Clinical Research Center for Oral Diseases, claiming that she has felt pain at the bilateral buc-
Department of Oral Medicine, West China Hospital cal mucosa when taking in spicy or hot food for
of Stomatology, Sichuan University, 6 months.
Chengdu, Sichuan, China
© Springer Nature Singapore Pte Ltd. and People’s Medical Publishing House 2018 207
Q. Chen, X. Zeng (eds.), Case Based Oral Mucosal Diseases,
https://doi.org/10.1007/978-981-13-0286-2_12
208 X. Jin and X. Zeng
Past Medical History: None case reports and research articles about this dis-
Allergy: None ease, mostly from China.
Physical Examination: The etiology of BLOM is not known. Some
Plaque-like mixed with papular lesions and stria- researchers considered BLOM as a proliferation
tions were on the left buccal mucosa from labial disease of the regional humoral immune reaction
mucosa near commissure extending to the retro- mediated by B-lymphocytes. In the epithelium
molar region. Furthermore, soft, plaque-like, and layer, the pathological changes of BLOM are
slightly erosive lesions were detected on the left characterized by parakeratosis, acanthosis, thick-
mandibular molar vestibule (Fig. 12.1). ening of basement membrane, and liquefaction
Clinical Impression: degeneration of basal cells, possibly accompa-
Oral lichen planus? nied with epithelium dysplasia. While, in lamina
Laboratories Studies: propria, inflammation cells widely infiltrate, lym-
Tissue biopsy of papular-like lesion on left buc- phoid follicles are formed, along with capillary
cal is performed. Histological examination proliferation and swelling of endothelial cells [2].
revealed lymphoid tissue proliferation in the lam- BLOM usually occurs in lips, the so-called
ina propria, the formation of lymphoid follicles, pruritic cheilitis, follicular cheilitis, or cheilitis of
and the acanthosis of partial epithelium, support- benign lymphadenosis. The major clinical fea-
ing the diagnosis of benign lymphadenosis of the tures are labial lesions with regional intense itch-
oral mucosa. ing, possibly with erosion, crust, and leak of
Diagnosis: yellow mucus, which is clinically indistinguish-
Benign lymphadenosis of the oral mucosa able from chronic cheilitis. Clinical manifesta-
tions of BLOM in other oral parts are lack of
Diagnosis Basis: typical features, which is usually diagnosed as
oral lichen planus, especially the buccal lesions.
1. The clinical manifestations are similar to oral It could be confirmed by tissue biopsy (Fig. 12.2).
lichen planus. Studies showed that treatment method of local
2. The diagnosis was confirmed by tissue biopsy. resection or 32P topical application is effective,
with a good prognosis [2]. Clinically, the symp-
Management: tomatic approach is sufficient. Management is
similar to that of erosive OLP if the lesion is
1. Medication. widespread. Close observation and regular fol-
Rp.: Dexamethasone paste 15 g × 1 low-up visit are required.
Sig.: Topical use t.i.d.
2. Regular follow-up visit and close observation
were suggested.
Age: 49 years
Sex: Female
Chief Complaints:
Fig. 12.4 Natal teeth of 3 months of age: erupted teeth A 49-year-old woman with left maxillary gingi-
exhibiting variable shape, loose, with enamel hypoplasia val pain when taking food for 6 months
12 Other Oral Mucosal Diseases 211
suggested as an essential role in the pathogenesis treated with chemotherapy and corticosteroid ther-
of VX [11]. Others suggested that VX is also apy in stable condition. Forty-five days ago, the
associated with HPV and EB virus infections blood culture demonstrated Candida parapsilosis,
[12]. A recent study revealed that local stimuli or suggesting the complication of fungal septicemia
trauma accompanied with galectin-7 overexpres- during his hospitalization. Serologic tests for
sion is considered to induce cholesterol synthe- syphilis and HIV were negative. Chest X-ray and
sis, epidermal apoptosis, and subsequent lipid abdominal ultrasound examination results were
incontinence via HMG-CoA synthase normal. Microbiological culture of the secretion
1(HMGCS1). The excessive lipid scavenged by from the palatal lesion revealed negative result.
macrophages and the formation of lipophage are Past Medical History: ALL
the characteristic feature of VX [13]. Allergy: None
VX is a benign disease with good prognosis Physical Examination:
and low relapse rate. The treatment for oral VX is A 30 mm × 20 mm palatal ulcer in the posterior
often surgical resection. part of the hard palate was observed, with well-
defined borders. In the lesion area, part of the
bone tissue is exposed and blackened, with a
12.4 Palate Perforation 9 mm in diameter perforation filled with food
debris located at the mid-right. The surrounding
Case 103 Palate Perforation (Invasive Fungal tissues were soft (Fig. 12.8).
Infection Related?) Clinical Impression:
Palate perforation (invasive fungal infection
related?)
Diagnosis Basis:
Case 104 Palate Ulcer and Perforation with type 2 diabetes mellitus and right orbital
Related to Mucormycosis cellulitis based on the high blood glucose level
(33.9 mmol/L) in the local hospital. After cefix-
a ime, levofloxacin and hypoglycemic agents were
prescribed; orbital swelling and blurred vision
were improved slightly. Fourteen days ago, she
was hospitalized in the Department of Infectious
Diseases. Her blood glucose level was under
control. Blood routine examination showed the
decreased RBC count (3.32 × 1012/L) and HGB
level (101 g/L), with normal liver and kidney
function. Serological tests for HBV, HCV, syphi-
lis, and HIV are all clear. CT scan and MRI indi-
cated the right nasal sinusitis, involving the right
b maxillofacial and temporal soft tissue, the right
mastoid region, and frontal lobe brain tissues,
mainly due to the diffusion of nasal sinusitis.
Nasal secretion smear demonstrated G+ bacillus
and coccus, and saliva smear revealed yeast-like
fungi. The level of fungal G test (beta-glucan
antigenemia assay) is 95.99 pg/mL. Thus, she
was diagnosed with right orbital and facial cel-
lulitis (suspected deep fungal infection) and was
under antibiotic therapy.
Past Medical History: Hypertension and
Fig. 12.9 (a) Deep ulcer on the posterior hard palate, diabetes
with congestive margin and yellowish pseudomembrane,
the central part of the ulcer with bone loss formed a perfo-
Allergy: None
ration. (b) Swelling on the right side of the cheek and Physical Examination:
right orbital region, with difficulty in opening the eyes Oral examination showed a 1.8 cm × 4 cm deep
ulcer in the posterior region of the right hard pal-
Age: 57 years ate, with congestive margin and yellowish pseu-
Sex: Female domembrane. The central part of the ulcer with
Chief Complaints: bone loss formed a perforation. Extraoral exami-
A 57-year-old woman with an ulcer on the right nation revealed swelling on the right side of the
side of the palate for 20 days cheek and right orbital region, with difficulty in
History of Present Illness: opening the eyes (Fig. 12.9).
A 57-year-old woman was referred to our clinic Clinical Impression:
from the Department of Infectious Diseases, Palate ulcer and perforation (invasive fungal
with the main complaint of a 2 cm ulcer on the infection related?)
right palate, expanding in size gradually for the
past 20 days. History revealed that her maxillary Laboratories and Imaging Studies:
posterior teeth (seven teeth altogether) were
extracted in a dental clinic 38 days ago. One 1. Tissue biopsy of the palatal ulcer margin was
week after the tooth extraction, she had flu-like performed. Histopathology exam showed
symptoms, with eyelid pain and blurred vision of chronic inflammation, with pseudoepithelio-
her right eye, followed by slight fever and right matous hyperplasia in the epithelial layer.
orbital swelling. Then she had been diagnosed Plasmocytes, monocytes, and lymphocytes are
214 X. Jin and X. Zeng
infiltrated surrounding the submucosal vessels 2. Continue the antifungal therapy in the
and salivary glands. Localized lymphadenia, Department of Infectious Diseases. The
bone trabecula, and blood clot were also debridement for the necrotic tissue and palato-
observed. plasty could be considered if the infection is
2. Tissue biopsy of the nasal lesion was performed. under control.
Histopathology exam revealed severe chronic
inflammation in the nasal and sinus mucosa, [Review] Palate Perforation
localized erosion, and interstitial edema accom- Palate perforations are rear oral lesions without
panied with inflammatory polyps. Extensive unified definition. Palate perforation denotes a
inflammatory exudation and necrosis, sporadic collection of lesions manifesting as hard or soft
bone chips with multifocal abscess, and local- palate tissue necrosis, even localized tissue
ized fungi (Mucorales?) were observed. defect. The etiology is complicated; the main
3. The nasal secretion culture demonstrated causes are discussed as follows:
Mucorales.
nosuppression, bone marrow transplantation, the susceptible area. The lesions are often
acquired immunodeficiency syndrome, and dia- segmental with “skip” areas of normal regions;
betes. The definition of deep fungal infection or therefore, CD is also known as regional enteritis
invasive fungal infection is still controversial. or segmental ileitis. Oral lesions could be
Some researchers considered that all fungal observed in the buccal, labial, gingival, and
infection could be invasive. However, the term laryngeal mucosa, manifestations of which are
deep fungal infection should be used only to “knife-cut” linear ulcers with a rolled edge,
characterize systemic, generalized, deep-seated, hyperplastic folds, and nodular or granular
visceral and severe, life-threatening fungal hyperplasia. Other oral features include diffuse
infections, in contrast to superficial, local, benign, lip swelling, erythematous and granular gingivi-
self-limiting fungal diseases [23]. Several case tis, and minor or major recurrent aphthous sto-
reports demonstrated that palate perforation was matitis. In a case report of a patient suffering
caused by mucormycosis or aspergillosis in chil- from CD for 4 years, with the intraintestinal
dren who had acute lymphoblastic leukemia condition worsened, she has developed saddle
(ALL) under chemotherapy [24–26], such as the nose deformity, alar collapse, and palatal perfo-
case 103 in this unit. In case 104, the palate per- ration as extraintestinal manifestations of the
foration of the patient with diabetes was also disease [28].
proved to be related to opportunistic deep fungal Extranodal natural killer/T-cell lymphoma
infection based on several tests and effective anti- (ENKL), nasal type, is a rare disease related to EB
fungal treatment. virus infection. A case report of ENKL presents a
palatal perforation in a 21-year-old man, who was
diagnosed through immunophenotyping after
12.4.2 Systemic Disorders excluding bacterial osteomyelitis, invasive fungal
infection, and Wegener’s granulomatosis [29].
Wegener’s granulomatosis (WG) is a systemic Other disorders such as maxillary sinus carci-
disease characterized by necrotizing granulo- noma and mucoepidermoid carcinoma may
mas and extensive small vessel vasculitis. WG induce palate perforation as well [30, 31].
is widely thought to be an autoimmune disease.
Patients present with symptoms based on the
affected organs, including the respiratory tract, 12.4.3 Development Defect
kidney, and skin. Necrotizing granulomatous
ulcers in the soft palate or pharynx are com- Cleft palate is the birth defects which could cause
mon oral lesions, which are less common palate perforation. Its embryologic basis is a fail-
located in the gingiva and other parts. Deep ure of the mesenchymal masses of the lateral
pain-free oral ulcers expand rapidly with spe- palatine processes to meet and fuse with each
cific bad breath. Ulceration and osteonecrosis other, with the nasal septum, and/or with the pos-
on the palate would result in the exposure of terior margin of the median palatine process or
the underlying bone and finally palatal perfora- primary palate. Congenital palate perforation is
tion. Cutaneous manifestations include palpa- common birth defects in children [32].
ble purpura, erythema, necrotic nodules,
papules, and ulcers [27].
Crohn’s disease (CD) is a chronic recurrent 12.4.4 Drug Abuse
granulomatous inflammatory disease which
occurs in the digestive tract. CD can affect any Cocaine abuse increased worldwide, with
part of the gastrointestinal (GI) tract, but the ter- reported cases of palate perforations increased.
minal ileum (TI), with rich lymphoid tissue, is The drug can result in direct irritation and isch-
216 X. Jin and X. Zeng
12.4.5 Trauma b
and eating. She also claimed dry eyes and joint Sig.: Rinse t.i.d.
pain. Drug treatment was actually ineffective. Nystatin liniment 15 g × 1
Past Medical History: Stomach illness Sig.: Topical use t.i.d.
Allergy: None 2. The patient was referred to a rheumatologist
Physical Examination: for further treatment.
Oral examination showed that the mucosa is dry, and
no saliva drainage was observed when pressing the [Review] Xerostomia
major salivary gland. Dry appearance and atrophic Xerostomia is a symptom with multiple causes,
area were noted on the dorsum of the tongue, accom- not an independent disease. The diagnosis could
panied by irregularly fissured lines (Fig. 12.10). be made once a subjective complaint of patients
Clinical Impression: is dry mouth [38, 39]. Ten percent of the general
Xerostomia, Sjögren’s syndrome? population experiences long-lasting oral dryness.
Laboratories and Imaging Studies: Complaints of dry mouth are more prevalent in
older people, which more than 25% are affected
1. Blood routine, liver and kidney function, and [40]. In the majority of the cases, it results from
blood sugar level are normal. Rheumatoid fac- salivary gland hypofunction. However, clinicians
tor (RF) was found to be greatly increased encounter numbers of patients with symptoms of
(1100 IU/mL), and antinuclear antibodies xerostomia in the clinic of oral medicine.
(ANAs) (++++), anti-SSA (++), and anti-SSB The causes of xerostomia are complicated.
(++) were strongly positive. Medication is the most common cause of dry
2. Dynamic salivary scintigraphy of the salivary mouth; approximately 64% of xerostomia is
gland function showed severe impaired func- related to medication use. Hundreds of medicines
tion of the salivary gland. could induce xerostomia [41]. Medications with
3. The diagnosis of xerophthalmia was made by anticholinergic activity (e.g., atropine and sco-
Department of Ophthalmology. polamine) are antagonists of some acetylcholine
receptors and thus inhibit salivary secretion and
Diagnosis: induce dry mouth. Antihypertensive agents
Xerostomia, Sjögren’s syndrome (reserpine, methyldopa) could suppress sympa-
Diagnosis Basis: thetic nervous system, resulting in the interfer-
ence of saliva secretion. Antidepressants,
1. Patients with symptoms suggestive of SS: long- especially tricyclic antidepressants (TCAs),
lasting dry mouth, dry eye, and joint pain. could induce xerostomia due to the similar func-
2. Clinical diagnosis of xerostomia and tion as that of atropine. Other medications include
xerophthalmia. parasympatholytic agents, antithyroid medicine,
3. Serological examination showed strongly
sedative, diuretic agents, and alpha- and beta-
positive of anti-SSA (++) and anti-SSB (++). receptor-blocking drugs. Some Chinese herbal
4. Dynamic salivary scintigraphy showed severe medicines, even some plants such as gingko,
damage of salivary gland function. Urtica dioica, dandelion, chilis, and garlic, could
induce oral dryness [42, 43].
Management: Many salivary gland diseases and hypoplasia
could lead to dysfunction which triggers xerosto-
1. Medication. mia. In the case of acute purulent parotitis, swell-
Rp.: Lusun capsules 0.3 g × 81 tablets ing epithelium and narrowed or even blocked
Sig.: 0.6g p.o. t.i.d. duct decrease the salivary secretion. When the
Anethol trithione 25 mg × 48 tablets acute condition turns into chronic disease, glan-
Sig.: 25 mg p.o. t.i.d. dular tissue is damaged and replaced by fibrotic
Sodium bicarbonate solution (4%) connective tissue and adipose tissue, markedly
250 mL × 1 decreasing the salivary flow. Besides, salivary
218 X. Jin and X. Zeng
gland tumors, sialolith, cystic fibrosis, under- Salivary gland lesions are reported to occur in
sized salivary glands, and glandular hypoplasia 4–8% of HIV-positive patients. The damages
all can be the causes of xerostomia [44, 45]. commonly manifest as repeating salivary gland
Radiation therapy (RT) of the head and neck enlargements and xerostomia. Salivary gland
regions is another common cause of xerostomia. dysfunction is common in patients with chronic
Ionizing radiation can injure the major and minor hepatitis C, with prevalence ranging from 10% to
salivary glands; this can lead to atrophy, even 33%, in which saliva flow rate is obviously
death of the secretory components. When the decreased and xerostomia is induced.
radiation dose is in excess of 52 Gy, RT will lead Furthermore, hyperthyroidism, sinusitis, graft-
to rapid and remarkable damage [46, 47]. versus-host disease, ganglia lesion, and disorders
Previous studies considered that these damages in the central nervous system could result in
are permanent and irreversible. However, recent xerostomia [50–52].
researches revealed that secretory function could Psychological conditions such as anxiety or
not recover with the dose higher than 30 Gy, fear, especially depression, also may give rise to
while the function could gradually return when subjective symptoms of dry mouth. Bergdahl et al.
the dose is lower than 25 Gy, which needs to be examined the depressive symptoms in 94 subjects
further confirmed [48]. with a sensation of a dry mouth. The results
Numerous systemic disorders will lead to sali- showed that individuals with a subjective dry
vary gland dysfunction. Patients with diabetes mouth condition were significantly more depres-
mellitus are vulnerable to xerostomia due to the sive, indicating that subjective dry mouth may be
increased plasma osmotic pressure and polyuria of psychological origin. The underlying mecha-
which lead to excessive water loss. nisms are as follows: (1) degradation of catechol-
Sjögren’s syndrome (SS) is a chronic autoim- amine in the adrenal medulla reduces blood
mune disease characterized by progressive flowing to the salivary glands, affecting the saliva
destruction of exocrine glands leading to mucosa flow rate; (2) psychological stress diminishes taste
and conjunctiva dryness, accompanied with vari- perception and reduces the activity of glandular
ous autoimmune disorders. Dry mouth and dry motor nerves, incapacitating the saliva draining
eye caused by dysfunction of salivary and lacri- from glandular acini; and (3) blockade of acetyl-
mal glands are the major clinical manifestations, choline M receptors induces xerostomia [53].
and dryness of other mucosal areas such as the Oral dryness may also be caused by mouth
nasopharynx, skin, and vulva could also be breathing due to nasal disorders. Mouth breath-
affected due to the damage in other exocrine ing accelerates the evaporation of saliva, leading
glands and organs. Signs of systemic autoim- to xerostomia. Because of the dry mouth, patients
mune disease include purpuma, arthralgias, myo- always wake up during the night [54].
sitis, interstitial pulmonary fibrosis, and It is controversial that age is a risk factor of
polyneuritis [49]. The etiology of SS is unclear. xerostomia. Although it was previously thought
Serologic test showed positive autoantibodies, that salivary function declined with age, it is
suggesting SS is an autoimmune disease. SS is recently accepted that salivary gland secretion is
classified as primary or secondary. Primary similar between elderly and younger patients. It
Sjögren’s syndrome occurs only in the presence is likely that numerous systemic diseases and
of exocrine gland destruction, whereas secondary medications contribute significantly to dry mouth
SS occurs accompanied with autoimmune dis- in older people [55].
eases such as rheumatoid arthritis. Xerostomia is Clinical manifestations are various.
the early symptom of SS, with various degrees Hyposalivation, saliva pool disappeared and no
depending on the destruction level of salivary saliva drainage observed when pressing the major
glands. Oral examination indicates little or no salivary gland, does exist in some patients com-
saliva drainage from bilateral parotid gland ducts. plaining of dry mouth. However, other patients
12 Other Oral Mucosal Diseases 219
whose clinical signs are not obvious may need vary secretion. Usual dose is 25 mg orally
psychological counseling. three times daily.
Management of underlying disorders such as 3. Mucolytic agents such as bromhexine HCl
salivary gland diseases and systemic or psycho- (30 mg orally three times daily) and ambroxol
logical conditions is the first step in treatment of hydrochloride (8–16 mg orally three times
the dry mouth. The side effects of medications daily) could reduce viscosity of saliva in
may be alleviated by alternative drugs or altering patients with xerostomia.
the doses or dosage forms. Prophylaxis for 4. Chinese herbal medicines such as Zhibai
radiation-induced xerostomia includes: Dihuang pills, nourishing yin and clearing
heat, and lusun capsules, inducing saliva and
1. Radioprotective agents, such as amifostine,
slaking thirst, are both effective in treating dry
could reduce the damage caused by RT and mouth.
thus decrease the incidence of xerostomia in
patients undergoing head and neck radiother- Approaches such as oral rinses with sodium
apy. Amifostine use has been approved by bicarbonate solution and topical use of nystatin
FDA, but the decreased sensitivity of tumor liniment are suggested to prevent and treat fungal
cells makes its application controversial. infection.
2. Precise radiation is critically important for
Daily symptomatic approaches such as sip-
protecting salivary gland tissue, especially ping water throughout the day are necessary for
parotid glands from radiotherapy. patients with xerostomia. There are a number of
3. Submandibular gland transposition, prevent- oral rinses, mouthwashes, gels, spray, and artifi-
ing exposure of the gland, has been reported cial saliva available for dry mouth patients to
being effective for preventing post-RT relieve discomfort and substitute partially the
xerostomia. function of saliva. The use of room humidifiers,
particularly at night, may lessen discomfort
A night guard device that covered the dental markedly. Chewing sugar-free gums or lozenge
arch and the hard palate is reported by Yamamoto can be effective in stimulating salivary flow, thus
K et al. to be used for the management of sleep- improving symptoms.
related xerostomia [56]. In patients with a subjective sensation of dry
Symptomatic treatments should be adopted. mouth without local or systemic disorders, the
The commonly used drugs include: combination of psychological counseling and
management similar to that of burning mouth
1. Pilocarpine and cevimeline belong to cholino- syndrome is recommended.
mimetic drugs; they are effective for salivary
stimulation. But the side effects, such as
excessive sweating, flushing, and urinary and References
gastrointestinal disturbances, should be the
concern. The use of pilocarpine and cevime- 1. Li S, Yu S. Study of the benign lymphadenosis of oral
line is contraindicated in patients with uncon- mucosa. J Mod Oral Med. 2007;4:340–2.
2. Cheng B, Chen X. Clinicopathological features
trolled asthma, angle-closure glaucoma, and immunohistochemical analysis of the benign
cardiovascular diseases, Parkinson’s disease, lymphadenosis of oral mucosa. J Compr Stomatol.
or chronic obstructive pulmonary disease. 1998;14(2):99–101.
Common dose of pilocarpine is 5–10 mg 3. Tonouchi K, Ohta K, Tomizawa M, et al. A clinical
observation of epithelial pearls in newborn babies.
orally 3–4 times daily, while cevimeline is 1 Appearances and continuous changes. Shoni
30 mg orally three times daily. Shikagaku Zasshi. 1990;28(3):786–97.
2. Anethole trithione is a cholagogue that has 4. Thesleff I, Tummers M. Tooth organogenesis and
been shown in clinical trials to increase sali- regeneration. BTI-StemBook. 2008.
220 X. Jin and X. Zeng
5. Arnold WH, Rezwani T, Baric I. Location and distri- 22. Garg R, Schalch P, Pepper JP, et al. Osteomyelitis of
bution of epithelial pearls and tooth buds in human the hard palate secondary to actinomycosis: a case
fetuses with cleft lip and palate. Cleft Palate Craniofac report. Ear Nose Throat J. 2011;90(3):E11–2.
J. 1998;35(4):359–65. 23. Hof H. IFI = invasive fungal infections. What is that?
6. Mhaske S, Yuwanati MB, Mhaske A, et al. Natal and A misnomer, because a non-invasive fungal infection
neonatal teeth: an overview of the literature. ISRN does not exist. Int J Infect Dis. 2010;14(6):e458–9.
Pediatr. 2013;2013:956269. 24. Barrak HA. Hard palate perforation due to mucor-
7. Shahrabi FS, Treister NS, Khan Z, et al. Oral verruci- mycosis: report of four cases. J Laryngol Otol.
form xanthoma associated with chronic graft-versus- 2007;121(11):1099–102.
host disease: a report of five cases and a review of the 25. Karabulut AB, Kabakas F, Berkoz O, et al. Hard
literature. Head Neck Pathol. 2011;5(2):193–8. palate perforation due to invasive aspergillosis in
8. Bhalerao S, Bhat P, Chhabra R, et al. Verruciform xan- a patient with acute lymphoblastic leukemia. Int J
thoma of the buccal mucosa: a case report with review Pediatr Otorhinolaryngol. 2005;69(10):1395–8.
of the literature. Contemp Clin Dent. 2012;3(Suppl 26. Castro LG, Muller AP, Mimura MA, et al. Hard palate
2):S257–9. perforation: an unusual finding in paracoccidioidomy-
9. Oliveira PT, Jaeger RG, Cabral LA, et al. Verruciform cosis. Int J Dermatol. 2001;40(4):281–3.
xanthoma of the oral mucosa. Report of four 27. Kasifoglu T, Cansu D, Korkmaz C. Clinical images:
cases and a review of the literature. Oral Oncol. perforation of the nasal septum and palate due
2001;37(3):326–31. to Wegener’s granulomatosis. Arthritis Rheum.
10. Cheng YS, Wright J, Lucente J, et al. Oral and max- 2008;58(8):2564.
illofacial pathology case of the month. Verruciform 28. Oghan F, Pekkan G, Ozveren O. Saddle nose defor-
xanthoma. Tex Dent J. 2010;127(1):126–7. 130–131. mity, palatal perforation and truncus arteriosus in a
11. Lu S, Rohwedder A, Murphy M, et al. Verruciform patient with Crohn’s disease. J Craniomaxillofac
xanthoma: localized lymphedema (elephantiasis) Surg. 2012;40(1):17–9.
is an essential pathogenic factor. J Cutan Pathol. 29. Bhatt VR, Koirala B, Terjanian T. Extranodal natu-
2012;39(3):391–4. ral killer/T cell lymphoma, nasal type presenting as
12. Maldonado-Cid P, Noguera-Morel L, Beato-Merino a palatal perforation and naso-oral fistula. BMJ Case
MJ, et al. Verruciform xanthoma associated with reac- Rep. 2011;2011:bcr1120103511.
tivation of Epstein-Barr virus. Actas Dermosifiliogr. 30. Nishimura G, Sano D, Tanigaki Y, et al. Maxillary sinus
2013;104(5):445–6. carcinoma: the only symptom was neck lymph node
13. Fujimoto N, Asano C, Ono K, et al. Verruciform xan- swelling. Auris Nasus Larynx. 2006;33(1):57–61.
thoma results from epidermal apoptosis with galec- 31. Kolude B, Lawoyin JO, Akang EE. Mucoepidermoid
tin-7 overexpression. J Eur Acad Dermatol Venereol. carcinoma of the oral cavity. J Natl Med Assoc.
2013;27(7):922–3. 2001;93(5):178–84.
14. Bains MK, Hosseini-Ardehali M. Palatal perfora-
32. Dixon MJ, Marazita ML, Beaty TH, et al. Cleft lip
tions: past and present. Two case reports and a litera- and palate: understanding genetic and environmental
ture review. Br Dent J. 2005;199(5):267–9. influences. Nat Rev Genet. 2011;12(3):167–78.
15. Boldsen JL. Leprosy in medieval Denmark – osteo- 33.
Padilla-Rosas M, Jimenez-Santos CI, Garcia-
logical and epidemiological analyses. Anthropol Anz. Gonzalez CL. Palatine perforation induced by cocaine.
2009;67(4):407–25. Med Oral Patol Oral Cir Bucal. 2006;11(3):E239–42.
16. Thomas M, Emmanuel M. A case of advanced lep- 34. Silvestre FJ, Perez-Herbera A, Puente-Sandoval A,
romatous leprosy with rhino-oro-laryngological et al. Hard palate perforation in cocaine abusers: a sys-
involvement in the post-elimination era. Indian J Lepr. tematic review. Clin Oral Investig. 2010;14(6):621–8.
2009;81(2):81–2. 35. Bartlett E, Mahabir RC, Verheyden CN. Traumatic
17. Dhawan AK, Verma P, Sharma S. Oral lesions in lep- palatal perforation after orotracheal intubation: a
rosy revisited: a case report. Am J Dermatopathol. case report and a review of the literature. Cleft Palate
2012;34(6):666–7. Craniofac J. 2013;50(5):614–7.
18. Baruah B, Goyal A, Shunyu NB, et al. Tuberculosis 36. Vincent RD Jr, Wimberly MP, Brockwell RC, et al.
of nose and palate with vanishing uvula. Indian J Med Soft palate perforation during orotracheal intubation
Microbiol. 2011;29(1):63–5. facilitated by the GlideScope videolaryngoscope. J
19. Gaafar HA, Gaafar AH, Nour YA. Rhinoscleroma: an Clin Anesth. 2007;19(8):619–21.
updated experience through the last 10 years. Acta 37. Samanta DR, Senapati SN, Sharma PK, et al. Hard
Otolaryngol. 2011;131(4):440–6. palate perforation in acute lymphoblastic leukemia
20. Nimare K, Shukla RK. A rare case of rhinoscle-
due to mucormycosis-a case report. Indian J Hematol
roma. Indian J Otolaryngol Head Neck Surg. Blood Transfus. 2009;25(1):36–3.
1999;52(1):74–5. 38. Hay KD, Morton RP. Optimal nocturnal humidifica-
21. De D, Dogra S, Kanwar AJ, et al. Actinomycosis pre- tion for xerostomia. Head Neck. 2006;28(9):792–6.
senting as a destructive ulcerated plaque on the palate 39. Fox PC. Salivary enhancement therapies. Caries Res.
and gingiva. J Am Acad Dermatol. 2011;65(6):1235–6. 2004;38(3):241–6.
12 Other Oral Mucosal Diseases 221
40. Orellana MF, Lagravere MO, Boychuk DG, et al. 49. Kassan SS, Moutsopoulos HM. Clinical manifesta-
Prevalence of xerostomia in population-based sam- tions and early diagnosis of Sjogren syndrome. Arch
ples: a systematic review. J Public Health Dent. Intern Med. 2004;164(12):1275–84.
2006;66(2):152–8. 50. von Bültzingslöwen I, Sollecito TP, Fox PC, et al.
41. Ciancio SG. Medications’ impact on oral health. J Am Salivary dysfunction associated with systemic dis-
Dent Assoc. 2004;135(10):1440–8; quiz 1468–1469. eases: systematic review and clinical management
42. Abebe W. An overview of herbal supplement utiliza- recommendations. Oral Surg Oral Med Oral Pathol
tion with particular emphasis on possible interactions Oral Radiol Endod. 2007;103(Suppl: S57):e1–15.
with dental drugs and oral manifestations. J Dent 51. De Vita S, Damato R, De Marchi G, et al. True primary
Hyg. 2003;77(1):37–46. Sjogren’s syndrome in a subset of patients with hepatitis
43. Sreebny LM, Schwartz SS. A reference guide to
C infection: a model linking chronic infection to chronic
drugs and dry mouth – 2nd edition. Gerodontology. sialadenitis. Isr Med Assoc J. 2002;4(12):1101–5.
1997;14(1):33–47. 52. Ooi SE, Tsai CY, Chou CT. Interstitial lung disease
44. Ono K, Tanaka T, Inoue H, et al. Small salivary gland and xerostomia as initial manifestations in a patient
size in patients with xerostomia of unknown etiology. with human immunodeficiency virus infection. J
Arch Oral Biol. 2009;54(4):369–73. Microbiol Immunol Infect. 2005;38(2):145–8.
45. Fox PC, et al. Dent Assist. 2008;77(5):18, 20, 44–48; 53. Bergdahl M, Bergdahl J, Johansson I. Depressive
quiz 50–51. symptoms in individuals with idiopathic subjective
46. Sciubba JJ, Goldenberg D. Oral complications of
dry mouth. J Oral Pathol Med. 1997;26(10):448–50.
radiotherapy. Lancet Oncol. 2006;7(2):175–83. 54. Napenas JJ, Brennan MT, Fox PC. Diagnosis and
47. Dirix P, Nuyts S, Van den Bogaert W. Radiation-
treatment of xerostomia (dry mouth). Odontology.
induced xerostomia in patients with head 2009;97(2):76–83.
and neck cancer: a literature review. Cancer. 55. Ship JA, Pillemer SR, Baum BJ. Xerostomia and the
2006;107(11):2525–34. geriatric patient. J Am Geriatr Soc. 2002;50(3):535–43.
48. Li Y, Taylor JM, Ten HRK, et al. The impact of dose 56. Yamamoto K, Nagashima H, Yamachika S, et al. The
on parotid salivary recovery in head and neck cancer application of a night guard for sleep-related xero-
patients treated with radiation therapy. Int J Radiat stomia. Oral Surg Oral Med Oral Pathol Oral Radiol
Oncol Biol Phys. 2007;67(3):660–9. Endod. 2008;106(3):e11–4.
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