October University for Modern Sciences and Arts

BY
Prof. Dr. Fatheya Zahran

The Best of British Higher Education in the Best Environment

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CONTENTS
Pages

Oral ulcers 3
• Herpes Simplex Virus Infection 4
• Varicella –Zoster infection 11
• Hand-foot-and-mouth Disease 15
• Herpangina 16
• Tuberculosis 16
• Syphilis 17
• Traumatic Ulcers 19
• Recurrent Aphthous Stomatitis 20
• Behcet's Disease 25
• Reiter's disease 27
• Erythema multiforme 27
• Pemphigus vulgaris 32
• Mucous membrane pemphigoid 35
• Desquamative gingivitis 35
• Oral Reactions to Drugs 37

White and red lesions 40
- Hereditary white lesions 41
• Leukodema 41
• White spongy nevus 41
• Herditary benign intraepithelial dyskeratosis 42
• Darrier’s disease 43
- Reactive and inflammatory white lesion 45
• Frictional keratosis 45
• Cheek chewing 46
• Chemical injuries 47
• Actinic keratosis 48
• Smokeless tobacco-induced keratosis 49
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• Nicotine stomatitis 51
- Infectious white lesions and white and red lesions 52
• Oral hairy leukoplakia 52
• Oral candidosis 53
- Idiopathic leukoplakia 63
- Erythroplakia 67
- Lichen planus 68
- Lichenoid Reactions 74
- Lupus erythematosus 75
- Miscellaneous 79
• Oral submucous fibrosis 79
• Skin Graft 81

Orofacial pigmented lesions 82
- Melanotic 83
- Non melanotic 97

Terminology in oral Medicine 112

Differential Diagnosis of white mucosal
mucosal lesions 124

Differential Diagnosis of red mucosal lesions 125

Differential Diagnosis of oral ulcers 126

Differential Diagnosis of recurring oral ulcers 127

Differential Diagnosis of autoimmune oral ulcers 128

Differential Diagnosis of acute oral ulcers 129

References 130
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ORAL ULCERS
Important Causes of Oral Mucosal Ulcers:
Vesiculo-
Vesiculo-Bullous Diseases:
Infective
• Primary and recurrent Herpes simplex lesions.
• Herpes zoster and chickenpox
• Hand-foot-and-mouth disease
• Herpangina
Non-infective
• Pemphigus vulgaris
• Mucous membrane pemphigoid
• Erythema multiforme
• Contact allergy

Ulceration Without Preceding Vesiculation:

Infective
• Cytomegalovirus-associated ulceration
• Some acute specific fevers
• Tuberculosis
• Syphilis
Non-infective
• Traumatic ulcers
• Aphthous stomatitis
• Behcet’s disease
• Reiter’s syndrome
• Lichen planus
• Acute necrotizing ulcerative gingivitis/stomatitis
• Some mucosal drug reactions
• Carcinoma
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Infective Stomatitis:
I) Herpes Virus Infections:
Infections:
Several herpes viruses cause human disease:
1- Herpes simplex virus (HSV) 1 and 2
2- Varicella-Zoster virus
3- Cytomegalovirus (causes oral ulcers in immunocompromised
patients)
4- Epstein-Barr virus
5- Human herpes virus 6 (HHV6)

Herpes Simplex Virus Infection:

Usually:

 Herpes simplex type 1: causes oral and pharyngeal infection,

meningoencephalitis and dermatitis above the waist.

 Herpes simplex type 2: causes genital infection and dermatitis

below the waist.

However, both strains can cause oral and genital lesion, which can
even occur concurrently.

Primary Herpetic Stomatitis:

Stomatitis
Primary infection is caused by Herpes simplex virus usually type 1,
which in the non-immune. can cause an acute vesiculating stomatitis.
However, most primary infections are subclinical. Thereafter recurrent
(reactivation) infections usually take the form of herpes labialis (cold sores
or fever blisters) orrecurrent intra oral herpes It is more common in the
 -5-

immunocompromised, when it can be persistent or recurrent. Transmission

of herpes is by close contact.

Clinical Features:
Children 2-10 years old are most commonly affected, however, non-
immune adults can also manifest the primary attack. Infection is unexpected
below 6 months of age due to presence of maternal antibodies gained by the
enfant during intrauterine life.
The sequence of events is as follows:
1- Prodrome: consisting of generalized symptoms; fever, headache,
malaise, lymphadenitis, nausea and vomiting. These precede the
appearance of oral vesicles by 1-2 days. Fever and malaise may
be so severe, particularly in adults.
2- The early lesions: are vesicles which can affect any part of the
oral mucosa, but the hard palate and dorsum of the tongue are
favoured sites. The vesicles are domeshaped and usually 2-3 mm
in diameter. Rupture of vesicles leaves circular, sharply defined,
shallow ulcers with yellowish or grayish floors and red margins.
The ulcers are painful and may interfere with eating.
3- The gingival margins: are frequently swollen and red,
particularly in children, and the regional lymph nodes are
enlarged and tender.
4- Oral lesions usually resolve within a week to ten days (Self-
limiting).

Sometimes labial and facial lesions appear without intraoral

involvement.
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Primary
Herpetic
Gingivo-
stomatitis

Pathology:
Vesicles are sharply defined and form in the upper epithelium
(intraepithelial vesicles). Virus-damaged epithelial cells with swollen nuclei
and marginated chromatin (ballooning degeneration) are seen in the floor of
the vesicle and in direct smears from early lesions. Incomplete division of
cells leads to formation of multinucleated cells. Also, intranuclear inclusion
bodies (lipschutz bodies) are seen in infected cells. Later, the full thickness
of the epithelium is destroyed to produce a sharply defined ulcer.
Diagnosis:
1- History:
a) History of prodromal symptoms 1-2 days before oral
lesions
b) Negative history of recurrent herpes labialis
c) Positive history of contact with a patient with primary or
recurrent lesions.
2- The clinical picture (as described before)
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3- Lab investigations:
a) A smear showing virus-damaged cells
b) A rising titre of antibodies reaching a peak after 2-3 weeks
provides absolute but retrospective confirmation of the
diagnosis.

Treatment:
A- Supportive measures sometimes are all that is needed (the
lesions in normal healthy individuals are self-limiting)
• Bed rest
• Antipyretic (Aspirin, acetaminophen) for fever
• Fluids for hydration and electrolyte balance
• Nutritive non-irritating diet.
B- Acyclovir is a potent antiherpetic drug and is life-saving for
potentially lethal herpetic encephalitis or disseminated infection.
It inhibits DNA replication in HSV-infected cells but has no
effect on normal cells.
Dose: adult: 200 mg 5 times/day (5 days)
Children: 100 mg 5 times /day (5 days)
To summarize:
Typical features of herpetic stomatitis:
• Usually caused by H. simplex virus type I
• Transmitted by close contact
• Preceded by prodrome including lymphadenopathy and fever
of variable severity
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• Vesicles followed by ulcers , affect any part of the oral

mucosa
• Gingivitis usually associated
• Self-limiting except in immunocompromised patients
• Smears from vesicles show ballooning degeneration of viral
damaged cells, intranuclear inclusion bodies and
multinucleated giant cells.
• Rising titre of antibodies to HSV confirms the diagnosis

Recurrent Herpes Simplex Lesions:

Lesions:
Due to reactivation of latent virus residing in cells after a previous
primary attack (not a re-infection)

A) Recurrent Herpes Labialis:

After the primary infection, the latent virus can be reactived in 20-
30% of patients to cause cold sores (fever blisters). Triggering factors
include the common cold and other febrile infections, exposure to strong
sunshine, menstruation or, occasionally emotional upsets or local irritation
such as dental treatment.
Clinically, changes follow a consistent course with prodromal
paraesthesia or burning sensations then erythema at the site of the attack.
Vesicles form after an hour or two usually in clusters along the
mucocutaneous junction of the lips but can extend onto the adjacent skin.
The vesicles enlarge, coalesce and weep exudates. After two or three
days they rupture and crust over but new vesicles frequently appear for a
day or two only to scab over and finally heal, usually without scarring. The
whole cycle may take up to 10 days. Secondary bacterial infection may
change the lesions into pustules.
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Recurrent Herpes Labialis Recurrent Intra oral Herpes

B) Recurrent Intra oral Herpes:

Clusters of small vesicles that break into ulcers, 1-2 mm in diameter,
appear mainly on keratinized oral mucosa (gingival, hard palate, …).

Treatment:
In view of the rapidity of the viral damage to the tissues, treatment
must start as soon as the premonitory sensations are felt. Acyclovir cream
may be effective if applied at this time.

Chronic Herpes Simplex

Simplex Lesions:
It is a variant of recurrent herpes simplex lesion occurring in
immunocompromised patients (AIDS, immunosuppressive therapy,
leukaemia, lymphoma, …..)
Lesions appear on skin or mucosal surfaces as an ordinary recurrent
herpetic lesion but: remain for weeks or months and develop into large
ulcers (up to several centimeters in diameter).
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Treatment:
Systemically administered acyclovir, doubling the dose; i.e. 400 mg
5 times/day, till healing takes place.

Herpetic Cross-
Cross-infections:
Both primary and secondary herpetic infections are contagious.
Herpetic whitlow, which is an infection of fingers after manipulation of
herpetic lesions, is a hazard to dental surgeons and their assistants. Herpetic
whitlows, in turn, can infect patients and have led to outbreaks of infection
in hospitals and among patients in dental practices. Now that gloves are
universally worn when giving dental treatment, such cross-infections should
no longer happen. In immunodeficient patients such infections can be
dangerous but acyclovir has dramatically improved the prognosis in such
cases and may be given on suspicion.
Mothers applying antiherpetic drugs to children’s lesions should
wear gloves.

Herpetic whitlow
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Varicella –Zoster infection:

(1) Herpes Zoster of the Trigeminal Area:

Zoster (shingles) is characterized by pain, a vesicular rash and

stomatitis in the related dermatome. The varicella zoster virus (VZV) causes
chickenpox in the non-immune (mainly children), while reactivation of the
latent virus causes zoster, mainly in the elderly.
Unlike herpes labialis, repeated recurrences of zoster are very rare.
Occasionally there is an underlying immunodeficiency. Herpes zoster is a
hazard in organ transplant patients and can be an early complication of
some tumours, particularly Hodgkin’s disease, or increasingly, of AIDS.
Herpes zoster may involve one of the divisions of trigeminal nerve.
When the ophthalmic division is involved, blindness due to corneal scarring
may occur. When 2nd (maxillary) and 3rd (mandibular) divisions are
involved, oral lesions are seen

Clinical Features:

A) Chicken Pox:
A childhood disease characterized by:
• Mild systemic symptoms.
• Generalized pruritic eruption of maculopapular lesions
that rapidly develop into vesicles on erythematous base.
• Oral vesicles that rapidly rupture giving ulcers.
But: Oral lesions are not an important problem regarding
symptoms, diagnosis or management.
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B) Herpes Zoster:

Prodrome: 2-4 days of sharp shooting pain, paresthesia, burning and

tenderness a long the course of affected nerve.
Then, vesicles, often confluent, form on one side of the face and in
the mouth up to the midline. The regional lymph nodes are enlarged and
tender. The acute phase usually lasts about a week. Pain continues until the
lesions crust over and start to heal, but secondary infection may cause
suppuration and scarring of the skin. Malaise and fever are usually
associated.
Patients are sometimes unable to distinguish the pain of trigeminal
zoster from severe toothache, this has sometimes led to unnecessary dental
extraction. Also, sometimes pain occurs without rash or oral lesions,
(herpes sine eruption) which leads to problems in diagnosis.

Pathology:
The varicella zoster virus produces similar epithelial lesions to those
of herpes simplex, in addition to inflammation of the related posterior root
ganglion.
Herpes zoster of the trigeminal area: key features:
• Recurrence of VZV infection occurs typically in the elderly
• Pain precedes the rash
• Facial rash accompanies the stomatitis
• Lesions are localized to one side (absolutely unilateral),
within the distribution of any of the divisions of the
trigeminal nerve
• Malaise can be severe
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• Can be life-threatening in immunocompromised patients.

• Sometimes followed by post-herpetic neuralgia, particularly
in the elderly.

Herpes Zoster of mandibular nerve

Herpes Zoster of maxillary nerve

Treatment:
According to the severity of the attack oral acyclovir (800 mg five
times daily, usually for 7 days) should be given at the earliest possible
moment, together with analgesics. The addition of prednisolone
(corticosteroids) may accelerate relief of pain and healing and prevent post-
herpetic neuralgia in elderly patients. In immunodeficient patients,
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intravenous acyclovir is required and may also be justified for the elderly in
whom this infection is debilitating.

Complications:
Post-herpetic neuralgia which mainly affects the elderly and is
difficult to relieve.

(2) Ramsay Hunt Syndrome:

Herpes zoster of the geniculate ganglion i.e. affecting the facial
nerve which contain both motor and sensory fibers (rare), characterized by:
1. Prodrome of facial pain which may radiate to the jaws and be
misdiagnosed as tooth ache.
2. Bell’s palsy.
3. Unilateral vesicles of external ear (herpetic oticus)
4. Unilateral vesicles of oral mucosa which soon trun into ulcers,
on erythematous base. The areas affected are the anterior 2/3
of the tongue and soft palate on the same side (distribution of
chorda tympani).

Complications:
Permanent facial paralysis.

Management:
Corticosteroids or ACTH are given in addition to antiviral drugs
(acyclovir) to avoid permanent fibrosis of the facial nerve.
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Hand-
Hand-foot-
foot-and-
and-mouth Disease:
Disease:
This common mild viral infection which often causes minor
epidemics among school children is characterized by ulceration of the
mouth and a vesicular rash on the extremities.
Hand-foot-and-mouth disease is usually caused by strains of
Coxsackie A virus. It is highly infectious, frequently spreads through a
classroom in schools and may also infect a teacher or parent. The incubation
period is probably between 3-10 days.

Clinical Features:
The small scattered oral ulcers usually cause little pain. Intact
vesicles are rarely seen and gingivitis is not a feature. Regional lymph
nodes are not usually enlarged and systemic upset is mild or absent.
The rash consists of vesicles, sometimes deep-seated, or occasionally
bullae, mainly seen around the base of fingers or toes, but any part of the
limbs may be affected. In some outbreaks either the mouth or the
extremities alone may be affected.
Hand-foot-and-mouth disease: key features.
• Caused mainly be Coxsackie A viruses
• Highly infectious
• School children predominantly affected
• Occasionally spreads to teacher or parent.
• Typically mild vesiculating stomatitis and/or vesiculating
rash on extremities.
• Rarely severe enough for dental opinion to be sought.
• Confirmation of diagnosis (if required) is by serology.
• No specific treatment available or needed.
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Herpangina:
• Another Coxsackie virus A infection (usually A4).
• Children 3-10 years are mostly affected (but other ages are
possible).
• Frequently occurs in epidemics.
Clinical Features:
• Incubation period: 2-10 days
• Prodrome: fever, chills, anorexia, sore throat, dysphagia
• Lesions (soft palate, tonsils, pharynx): macules → papules
and vesicles → small (1-2 mm) ulcers.
• Ulcers heal without treatment in about 7 days.

Herpangina Primary HSV infection

1) Occurs in epidemics 1) Doesn’t
2) Milder infection 2) Symptoms more severe
3)Affects mainly the posterior aspect of mouth 3) Affects mainly the anterior part
4) No gingivitis 4) Acute generalized gingivitis
5) Smaller ulcers 5) larger ulcers

Tuberculosis:
The typical lesion is an ulcer on the mid-dorsum or tip of the tongue;
the lip or other parts of the mouth are infrequently affected. The ulcer is
typically angular or stellate with over-hanging edges and a pale floor, but
can be ragged and irregular. It is painless in its early stages and regional
lymph nodes are usually unaffected.

Pathology:
Typical tuberculous granulomas are seen in the floor of the ulcers.
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Management:
Diagnosis is confirmed by biopsy, chest radiography and a specimen
of sputum. Mycobacterial infection is confirmed by culture or PCR.
Oral lesions clear up rapidly if vigorous multi-drug chemotherapy is
given for the pulmonary infection. No local treatment is needed.

Syphilis:
Primary Syphilis:
An oral chancre appears 3-4 weeks after infection and may form on
the lip, tip of the tongue or rarely, other oral sites. It consists initially of a
firm nodule about a centimeter across. The surface breaks down after a few
days, leaving a rounded ulcer with raised indurated edges. This may
resemble a carcinoma, particularly if on the lip. A chancre is typically
painless but regional lymph nodes are enlarged, rubbery and discrete.
Serological reactions are negative at first. Diagnosis therefore
depends on clinical finding. Treponema pallidum can be demonstrated by
dark-ground illumination of a smear from the chancre, but they must be
distinguished from other oral spirochaetes.
Clinical recognition of oral chancres is difficult but important. They
are highly infective, and treatment is most effective at this stage.
After eight or nine weeks the chancre heals, often without scarring.

Secondary Syphilis:
The secondary stage develops 1-4 months after infection. It typically
causes mild fever with malaise, headache, sore throat and generalized
lymphadenopathy, soon followed by a rash and stomatitis.
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The rash is variable, but typically consists of asymptomatic pinkish

(coppery) macules, symmetrically distributed and starting on the trunk. It
may last for a few hours or weeks and its presence or history is a useful aid
to diagnosis. Oral lesions, which rarely appear without the rash, mainly
affect the tonsils, lateral borders of the tongue and lips. They are usually flat
ulcers covered by grayish membrane and may be irregularly linear (snail
track ulcers) or coalesce to form well-defined rounded areas (mucous
patches).
Discharge from the ulcers contains many spirochaetes and saliva is
highly infective. Serological reactions are positive and diagnostic at this
stage, but biopsy is unlikely to be informative.

Tertiary Syphilis:
Late stage syphilis develops in many patients about three or more
years after infection. The onset is insidious and during the latent period, the
patient may appear well. A characteristic lesion is the gumma.
Clinically, a gumma, which may affect the palate, tongue or tonsils
can vary from one to several inches in diameter. It begins as a swelling,
sometimes with a yellowish centre which undergoes necrosis, leaving a
painless deep ulcer. The ulcer is rounded, with soft, punched-out edges. The
floor is depressed and pale (wash-leather) in appearance. It eventually heals
with severe scarring which may distort the soft palate or tongue, perforate
the hard palate or destroy the uvula.

Management:
Serological confirmation of the infection is essential. Tests are either
specific (such as the FTA-ABS) or non-specific as in the VDRL. The
VDRL becomes positive 4-6 weeks after infection and becomes negative
 -19-

only after effective treatment but false positives can result from several
other causes. The FTA-ABS acts as a check against false positive or
negative results, but remains positive despite effective treatment for the life
of the individual.
Antibiotics, particularly penicillin, are the mainstay of treatment but
tetracycline and erythromycin are also effective. Treatment should be by a
specialist and must be continued until non-specific serological reactions
(VDRL) are persistently negative.

Non-infective Stomatitis
Traumatic Ulcers:
Traumatic ulcers are usually caused by a denture and often seen in
the buccal or lingual sulcus. They are tender, have a yellowish floor and red
margins; there is no induration. If caused by the sharp edge of a broken-
down tooth, they are usually on the tongue or buccal mucosa. Occasionally,
a large ulcer is caused by biting the cheek after a dental local anaesthetic.
Traumatic ulcers heal a few days after elimination of the cause. If
they persist for more than 7-10 days, or there is any other cause for
suspicion as to the cause, biopsy should be carried out.

Tramatic ulcer on the lateral aspect of

the tongue related to sharp edge of a
tooth
 -20-

Recurrent Aphthous Stomatitis (Recurrent Aphthae):

Recurrent aphthae constitute one of the most common oral mucosal
diseases and affect 10-25% of the population, but many cases are mild and
accepted with little complaint.

Possible Aetiological Factors for Recurrent Aphthae:

• Genetic predisposition
• Exaggerated response to trauma
• Infections
• Immunological abnormalities
• Gastrointestinal disorders
• Haematological deficiencies
• Hormonal disturbances
• Stress
Clinical Features:

Typical Features of Recurrent Aphthae

• Onset frequently in childhood but peak in adolescence or early
adult life
• Attacks at variable but sometimes relatively regular intervals
• Most patients are other wise healthy
• A few have haematological defects
• Most are non-smokers
• Usually self-limiting
Types of Recurrent Aphthae
• Minor aphthae
- The most common type
- Non-keratinised mucosa affected
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- Ulcers are shallow, rounded, 5-7 mm across with an

erythematous margin and yellowish floor.
- One or several ulcers may be present
- Healing without scar.

• Major aphthae
- Uncommon
- Ulcers are frequently several centimeters across and deep.
- Sometimes mimic a malignant ulcer (indurated base with
everted edges).
- Ulcers may persist for several months
- Keratinized and non-keratinized mucosa affected (tongue
dorsum, soft palate, retromolar area)
- Healing with scar.

• Herpetiform aphthae
- Uncommon
- Non-keratinised mucosa affected
- Ulcers are 1-2 mm across
- Dozens or hundreds may be present
- May coalesce to form irregular ulcers.
- Widespread bright erythema around the ulcers.
 -22-

Minor aphthous ulcer Herpetiform ulcers

Crops of tiny ulcers coalesced

Major aphthous ulcer

Clinical Picture:

- Lesions are confined to oral mucosa (no extraoral

manifestations).

- Prodrome: burning sensation (2-48 hours) with the

appearance of localized erythema

- Ulceration: single or multiple ulcers appear within few

hours. Ulcers are surrounded by erythema and painful. No
tissue tags surround the ulcers (helps to differentiate it
from ulcers due to vesiculo- bullous diseases).
 -23-
- Healing: in minor form it takes 7-14 days, in major
ulcers it may take several months. No scar formation
occurs except in major form.

- Healing is characterized by disappearance of the

surrounding erythema.

Diagnosis and Management:

The most important diagnostic feature is the history of recurrences
of self-healing ulcers at fairly regular intervals. The only other condition
with this history is Behcet's disease.Otherwise, most patients appear well,
but haematological investigation is particularly important in older patients.
Routine blood indices are informative, and usually the most important
finding is an abnormal mean corpuscular volume (MCV).
Check-list for Diagnosis of Recurrent Aphthae:
History: The history is all-important Check for:
o Recurrences
o Pattern? Minor, major or herpetiform
o Onset as child or teenager
o Family history
o Distribution only on non-keratinised
mucosa
o Signs or symptoms of Behcet's disease
(ocular, genital, skin, joint lesions)

Examination: Check for:

o Discrete well-defined ulcers
o Scarring or soft palate involvement
suggesting major aphthae
o Exclude other diseases with specific
appearances. e.g. lichen planus or
vesiculobullous disease
 -24-
Special investigations
Used to exclude underlying conditions especially in patients with
onset in later life. Check for:
o Anaemia, iron, red cell folate and
vitamin B12 status.
o History of diarrhea, constipation or blood
in stools suggesting gastrointestinal
disease, e.g. celiac disease or
malabsorption.

Treatment:

If macro-or microcytosis is present, further investigation is necessary

to find and remedy the cause. Treatment of vitamin B12 deficiency or folate
deficiency is sometimes sufficient to control or abolish aphthae.
Apart from the minority with underlying systemic disease, treatment
is empirical and palliative only. Despite numerous clinical trials, no
medication gives completely reliable relief. Patients should therefore be
made to understand that the trouble may not be curable but can usually be
alleviated and usually resolves eventually of its own accord.
For minor aphthae: treatment is related to the severity.
- In mild cases: Protective topical treatment as orabase
can be used and to relief pain topical anaesthetic or
non-steroidal anti-inflammatory can be used.
Benzydamine hydrochloride mouth wash can also be
used.
- In more severe cases: Potent topical steroid can be
used.
N.B: Corticosteroids are unlikely to hasten healing of existing ulcers,
but probably reduce the painful inflammation. Also, early application before
 -25-
ulcer development can abort the lesion (patients with highly frequent ulcers
can recognize the burning sensation preceding the ulcer)
Triamcinolone dental paste is a corticosteroid in a vehicle which
sticks to the moist mucosa. The corticosteroid is slowly released and has an
anti-inflammatory action.
Tetracycline mouth rinses. For herpetiform aphthae particularly
the contents of a tetracycline capsule (250 mg) can be stirred in a little
water and held in the mouth for 2-3 minutes three times daily. Some
patients like to use this mouth rinse regularly for 3 days each week if they
have frequent ulcers. An antifungal drug may also need to be given to
patients who are susceptible to superinfection by Candida albicans.
Chlorhexidine. A 0.2% solution has also been used as a mouth rinse
for aphthae. Used three times daily after meals and held in the mouth for at
least 1 minute,
Treatment of major aphthae. Major aphthae may some times be so
painful, persistent, and resistant to conventional treatment. Effective
treatments include systemic or intralesional steroids, azathioprine,
cyclosporine colchicines and dapsone.

Behcet's Disease:
Behcet's syndrome was originally defined as a triad of oral aphthae,
genital ulceration and uveitis. However, it is a multisystem disorder with
varied manifestations.
Patients are usually young adult males between 20 and 40 years old.
Patients suffer one of four patterns of disease, namely:
• Mucocutaneous (oral and genital ulceration)
 -26-
• Arthritic (joint involvement with or without mucocutaneous
involvement)
• Neurological (with or without other features) or
• Ocular (with or without other features).

The oral aphthae of Behcet's disease are not distinguishable from

common aphthae. They are the most consistently found feature and
frequently the first manifestation. Behcet's disease should therefore be
considered in the differential diagnosis of aphthous stomatitis.

Diagnosis:

Pathergy Test:
The test is positive if there is an exaggerated response to a sterile
needle puncture of the skin, where such puncture is followed by pustule
formation.

Diagnostic criteria for Behcet's disease

Major Criteria Minor Criteria
• Recurrent oral aphthae • Arthralgia or arthritis
• Genital ulceration • Gastrointestinal lesions
• Eye lesions (uveitis, retinal • Vascular lesions (mainly thrombotic)
vasculitiz ) • Central nervous system involvement
• Skin lesions
(Erythema nodosum,
subcutaneous thrombophlebitis,
hyperirritability of the skin +ve
pathergy test)
 -27-
Treatment:
No specific treatment, but oral lesions can be controlled by:
- Topical or intralesional corticosteroids
- Topical anaesthesia to alleviate pain
- Systemic corticosteroids in resistant cases (40-60 mg
prednisone/day).
- Combination of steroid and immunsuppressive drugs
(e.g. azathioprine).

Reiter’s Syndrome:
Syndrome:
A triad of urethritis, arthritis and conjunctivitis.

Oral manifestations:
1. Painless circinate white lesions that may ulcerate giving
aphthous-like ulcers.

2. Geographic tongue like lesions

3. Purpuric rash in palate

Treatment:
Oral lesions are self limiting

Erythema Multiforme: Hypersensitivity reaction

This is an acute inflammatory mucocutaneous disease but among

dental patients oral lesions are the most prominent or the only ones present

Aetiology and Pathology:

The aetiology is not clear and though the disease may be reaction to
a variety of causes, no convincing mechanism has been proposed.
 -28-
 Infections, particularly herpetic can be triggering factors.
 Drugs, particularly sulphonamides and barbiturates, have also
been implicated, but a positive drug history is also rare. Even
when drugs have been taken, coincidence cannot always be
excluded .
 In most patients no precipitating cause can be found.
The histological appearance
Variable. Widespread necrosis of keratinocytes with eosinophilic
colloid change in the superficial epithelium may progress to intraepithelial
vesicle or bulla formation. However, subepithelial vesiculation is more
frequent Degenerative changes in the epithelium are associated with
infiltration by inflammatory cells which also involve the corium and may
have a perivascular distribution.

Clinical Picture:
All forms of the disease can occur at any age, including very young
children recurrences are common.

Erythema Multiforme Minor:

This accounts for about 80% of cases. The lesions are dull red, flat
or slightly raised maculopapules, which may remain small or may increase
in size to reach a diameter of 1-3 cm in 48 h. typical cases show at least
some target (or iris) lesions. A typical target lesion is less than 3 cm in
diameter, rounded, and has three zones: a central area of dusky erythema or
purpura, a middle paler zone of oedema and an outer ring of erythema with
a well-defined edge. Atypical target lesions have only two of the zones. The
lesions appear in successive crops for a few days and fade in 1-2 weeks,
 -29-
sometimes leaving dusky discoloration. Often the hands are selectively
involved. The kobner phenomenon is not uncommon, there may be
occasional erythematous lesions, erosions or bullae on the mucous
membranes.
Localized vesiculobullous form
This form is intermediate in severity. The skin lesions present as
erythematous macules or plaques, often with a central bulla and a marginal
ring of vesicles. Mucous membranes are quite often involved.

Erythema Multiforme Major-Stevens Johnson Syndrome:

The more severe types of erythema multiforme may include two
distinct syndromes erythema multiforme major (with classical target lesions
and Stevens-Johnson Syndrome, merging into toxic epidermal necrolysis
(atypical target lesions, epidermal necrosis predominating).
The onset is usually sudden, although there may be a prodromal
systemic illness of 1-13 days before the eruption appears. Numerous organs
are affected, changes were found with the following frequency: mouth
100% eyes, skin, male genitalia, anal mucous membrane, bronchitis and
pneumonitis.
The most common change in the eyes is a severe catarrhal or
purulent conjunctivitis, but bulla formation may occur. Corneal ulceration is
frequent. The eye changes often regress completely, and rarely blindness
occurs .
 -30-
The skin lesions are very variable in extent. They may be typical
maculopapular lesions of erythema multiforme, or they may be bullous, or
rarely even pustular.

Oral manifestations:
The oral mucous membrane shows extensive bulla formation
followed by erosions and a grayish-white membrane.
The lips show characteristic haemorrhagic crusting.

Crusted lip lesion Intra-oral lesion

Target (iris) lesions

 -31-

A case with erythema

multiform .Notice the sparing
of the gingiva despite the
extensive lesions in the
neighboring mucosa .Also
notice the bloody crust on the
upper lip.

Management:
Patients should be warned of the possibility of recurrences but that
the disease usually run a limited course.
There is no specific treatment. Systemic corticosteroids may give
symptomatic relief. Antibiotics are usually also given in severe cases with
the idea of preventing secondary infection. Levamisole has also been
reported to be effective. In some cases acyclovir is effective.
N.B.: Mucocutaneous ocular syndromes:
These are a group of diseases that show characteristic oral, skin and
eye lesions.
These diseases include:
1- Behcet’s disease (syndrome)
2- Reiter’s disease (syndrome)
3- Stevens Johnson syndrome.
 -32-
Pemphigus Vulgaris:
Pemphigus is an uncommon autoimmune disease causing vesicles or
bullae on skin and mucous membranes. It is usually fatal if untreated.

Clinical Features:
• Females usually aged 40-60 years are predominantly affected.

• Lesions often first appear in the mouth but spread widely on the
skin.

• Vesicles are fragile and infrequently seen intact in the mouth.

Residual erosions often have ragged edges and are superficial,
painful and tender. Gently stroking the mucosa can cause a
vesicle or bulla to appear (Nikolsky's sign). Also lateral
movement may lead to excessive peeling off of the oral
epithelium.

• Oral lesions show lack inflammatory signs unless secondary

infection occurs.

• Extension of lesions to the vermilion border may lead to the

formation of a crusted lesion.

Progress of the disease is very variable, it may sometimes be

fulminanting with rapid development of widespread oral ulceration, spread
to other sites such as the eyes within a few days, and very soon afterwards
to the skin.
Skin lesions consist of vesicles or flaccid bullae varying from a few
millimeters to a centimeter or so across.
 -33-
The skin also shows Nikolsky’s sign where firm sliding pressure
with a finger will separate normal looking epidermis from the dermis
leading to the formation of a bulla or an erosion.
The bullae at first contain clear fluid which may then become
purulent or haemorrhagic. Rupture of vesicles leaves painful ragged
erosions. Protein, fluid and electrolytes are lost from the raw areas and they
readily become secondarily infected. Without treatment, death usually
follows due to electrolyte imbalance and secondary infection.
Immunosuppressive treatment is usually life-saving.

Flacid skin bullae Peeling off of oral epithelium

Pathology:
Intra epithelial vesicles and bullae are formed. Lesions result from
the destruction of desmosomal junction between prickle cells and basal cells
due to the presence of autoantibodies against desmoglein 3 which is an
attachment molecule in desmosomes. This results in:
 -34-
• Loss of intercellular adherence of suprabasal spinous cells
(acantholysis)
• Formation of clefts immediately superficial to the basal cells.
• The attachment of basal cells with basement membrane is not affected,
though basal cells themselves are separated from each other
(tombstone appearance).
• Extension of clefts to form intraepithelial vesicles (due to filling up of
the clefts with inflammatory exudate).
• Rupture of vesicles to form ulcers
• High titre of circulating antibodies (mainly IgG4 and to lesser extent
IgG1) to epithelial intercellular cement substance (desmoglein 3)
• Binding of antibodies to intercellular substance detectable by
fluorescence microscopy.
• A smear taken from the base of a vesicle or oral erosion (Tzank
preparation) will show acantholytic (Tzank) cells which appear round
with large dark nuclei and little cytoplasm.

Management:
Diagnosis is confirmed by direct immunofluorescence and by the
demonstration of circulating autoantibodies.
60-100 mg/day of predisolone alone or in addition to azathioprine (1-
1.5 mg/kg daily). Azathioprine is given to allow doses of the conrticosteroid
to be lowered and reduce their side-effects. Intralesional steroid application
may help.
 -35-

Mucous Membrane (Cicatricial) Pemphigoid:

Mucous membrane pemphiogoid is an uncommon chronic disease
causing bullae and painful erosions. Skin involvement is uncommon and
often trivial. In stead, mucous membranes all over the body are affected.
The term cicatricial pemphigoid is sometimes used for this group of disease,
but particularly applies to ocular involvement where scarring is prominent
and impairs sight.
Nikolsky's sign is typically positive and a striking clinical finding is
sometimes that the epithelium slides away underneath the edge of a sharp
scalpel when a biopsy is attempted. In the mouth, bleeding into bullae can
cause them to appear as blood bisters. Rupture of erosions leaves raw areas
with well defined margins. Individual erosions persist for some weeks then
slowly heal. Further erosions may develop nearby and this process may
persist for a year or more. Lesions may remain localized to the mouth for
very long periods and may never involve other sites.
Lesions usually favour the palate and gingiva. Desquamative
gingivitis occurs in most cases.

Desquamative Gingivitis:
The term desquamative gingivitis is a clinical description, not a
diagnosis. It is used for conditions in which the gingivae appear red or raw.
Usually the whole of the attached gingival of varying numbers of teeth is
affected
 -36-
Mucous membrane pemphigoid and lichen planus are the most
common causes. The gingivae then appear smooth, red and translucent due
to the thinness of the atrophic epithelium which can be easily stripped off.
In older patients mucous membrane pemphigoid may cause gingival
erosions. Pemphigus vulgaris is another possible causes. In all cases, the
appearances are strikingly different from simple marginal gingivitis, and the
diagnosis should be confirmed by biopsy.

Pathology:
Histologically there is loss of attachment and separation of the full
thickness of the epithelium from the connective tissue at basement
membrane level (subepithelial bulla). Epithelium, though separated,
remains for a time intact and forms the roof of a bulla. The floor of the
bulla is formed by connective tissue alone, infiltrated with inflammatory
cells. The disease is immunologically mediated, and binding of
immunoglobulin or more frequently of complement components along the
basement membrane zone can be demonstrated. Circulating autoantibodies
against laminin and hemides mosomes (components of basement
membrane) are detectable by sensitive techniques.

Management:
The diagnosis is confirmed by biopsy and immunofluorescence
microscopy but it is preferable to obtain an intact vesicle or bulla. Oral
mucous membrane pemphigoid can often be effectively controlled with
topical corticosteroids. Doses are small and without systemic effects.
Because of the possible risk to sight, ocular examination is necessary
if early changes in the eyes are suspected. If the eyes become involved,
systemic corticosteroids have to be given and are effective.
 -37-

Oral Reactions to Drugs:

Drugs:
Many drugs can occasionally cause oral reactions. They are varied in
type but frequently lichenoid or ulcerative. The mechanisms of reactions to
drugs are often obscure.

(A) Local Reaction to Drugs:

Chemical burns. The best-known example is that of aspirin tablets
held against the mucosa close to an aching tooth. This causes superficial
necrosis and a white patch. When the irritant is removed, dead epithelium is
shed and the mucosa heals. Other irritant chemicals are acid etchants, or
phenol dropped on the mucosa.

(B) Systemically Mediated Reactions:

- Depression of marrow function. Drugs may significantly
depress red cell production. Any drug which causes anaemia
might give rise to oral signs. The main example is prolonged
use of phenytoin (for epilepsy) which, in susceptible patients,
can occasionally cause folate deficiency and macrocytic
anaemia. This in turn can cause severe aphthous stomatitis.
Response promptly follows administration of folate, and the
blood picture returns to normal.

- White cell production is depressed by a variety of drugs.

Leucopenia may be severe enough to produce the clinical
picture of agranulocytosis, with necrotizing ulceration of the
gingivae and throat. Drugs which may have this effect include
antibacterials, particularly co-trimoxazole, chloramphenicol,
 -38-
analgesics, phenothiazines and antithyroid agents. When the
main effect is on granulocytes, low-grade oral pathogens,
particularly of the gingival margins, are able to overcome local
resistance and produce necrotizing ulceration.

- Depression of cell-mediated immunity. Immunosuppression by

such drugs as corticosteroids is induced in patients having
organ transplants or with immunologically-mediated diseases.
Viral and fungal infections of the mouth are common in
immunosuppressed patients and can be severe. Recurrences of
childhood viral infections such as measles and chickenpox are
also possible.

- Acute erythema multiforme. Sulphonamides, barbiturates or

other drugs are occasionally implicated, but the mechanisms are
unknown and more frequently there is no evidence of a drug
reaction.

- Toxic epidermal necrolysis: this, which probably represents

the extreme end of the spectrum of erythema multiforme, is one
of the most dangerous and severe types of drug reaction.
Mucosal involvement is common and causes widespread
erosions due to epithelial destruction. Oral ulceration may
precede the dermal changes, and cause the patient to seek
treatment for the extreme soreness of the mouth. Early
diagnosis and treatment is important as the reaction can be
lethal. Metals such as gold salts are important causes but
phenylbutazone, barbiturates and other drugs have also been
implicated.
 -39-
- Fixed drug eruptions. These consist of sharply circumscribed
skin lesions recurring in the same site or sites each time the
drug is given. Many drugs are capable of causing this reaction,
but phenolphthalein, a widely use component of purgatives, is
one of the more common causes. Involvement of the oral
mucous membrane has been described but is exceedingly rare.

- Oral ulcers secondary to cancer chemotherapy: Anticancer

drugs may cause oral ulcers directly or indirectly. Drugs that
cause stomatitis indirectly depress the bone marrow and
immune response, leading to bacterial, viral or fungal infections
of oral mucosa. Others, such as methotrexate, cause oral ulcers
through their direct effect on the replication and growth of oral
epithelial cells by interfering with DNA, RNA and protein
synthesis.

- Oral ulcers secondary to cardiovascular drugs:

Oral ulcerations are among the reactions to beta-adrenergic
blockers and calcium channel blockers. Tongue ulcerations proceeded
by loss of taste have been also reported as a complication of other
groups of cardiovascular drugs. "Scalded mouth syndrome" is reported
as a rare adverse effect.

When oral ulceration occurs , it is very painful ,either aphthous-

like or deep with hyperkeratotic margin . Oral ulcerations resolve
following drug withdrawal and relapse at a re-challenge.
 -40-
RED AND WHITE LESIONS OF THE ORAL MUCOSA
These could be identified into:
• Hereditary white lesions.
- Leukodema
- White sponge nevus
- Hereditary benign intraepithelial dyskeratosis
- Darrier’s disease
• Reactive/inflammatory white lesions:
- Frictional (Traumatic) keratosis
- Chemical injuries of the oral mucosa
- Actinic keratosis (cheilitis)
- Smokeless tobacco-induced keratosis
- Nicotine stomatitis
• Infectious white lesions and white and red lesions:
- Oral hairy leukoplakia
- Candidiasis
- Mucous patches
• Idiopathic "TRUE" leukoplakia
• Erythroplakia
• Oral lichen planus
• Lichenoid reactions
• Lupus erythematosus (systemic and discoid)
• Miscellaneous lesions:
- Oral submucous fibrosis.
- Skin graft.
 -41-

Hereditary White Lesions:

Leukoedema:
Leukoedema is a common mucosal alteration that represents a
variation of the normal condition rather than a true pathologic change.
Features:
It usually has a faint, white, diffuse, and filmy appearance, with
numerous surface folds resulting in wrinkling of the mucosa. It cannot be
scraped off, and it disappears or fades upon stretching the mucosa.
Microscopic examination reveals thickening of the epithelium, with
significant intracellular edema of the stratum spinosum. The surface of the
epithelium may demonstrate a thickened layer of parakeratin.
Treatment:
No treatment is indicated, no malignant change has been reported.

White Sponge Nevus:

The disease usually involves the oral mucosa and (less frequently)
the mucous membranes of the nose, esophagus, genitalia, and rectum. The
lesions of white spongy nevus may be present at birth or may first manifest
or become more intense at puberty.
Features:
Bilateral symmetric white, soft, “spongy”, or velvety thick plaques of
the buccal mucosa. However, other sites in the oral cavity may be involved,
including the ventral surface of the tongue, floor of the mouth, labial
mucosa, soft palate, and alveolar mucosa. The condition is usually
asymptomatic and does not exhibit tendencies toward malignant change.
The characteristic histopathologic features are epithelial thickening,
 -42-
parakeratosis, a peculiar perinuclear condensation of the cytoplasm, and
vacuolization of the suprabasal layer of keratinocytes.

Differential Diagnosis:
• Hereditary benign intraepithelial dyskeratosis.
• Pachyonychia congenital.
• Infections such as candidiasis.
• Traumatic lesions seen in cheek chewing,
• Chemical burns.
• Preneoplastic /neoplastic processes.
This differential diagnosis is best resolved by incisional biopsy.

Treatment:
No treatment is indicated for this benign and asymptomatic condition.

Hereditary Benign Intraepithelial Dyskeratosis:

Features:
1- Oral Lesions:
Thick, corrugated, asymptomatic, white “spongy” plaques involving
the buccal and labial mucosa. Other intraoral sites include the floor of the
mouth, the lateral tongue, the gingiva, and the palate. Generally detected in
the first year of life and gradually increase in intensity until the teens.

2- Eye Lesions
Thick, gelatinous, foamy, and opaque plaques form adjacent to the
cornea. The plaques may exhibit seasonal prominence, with many patients
reporting more-pronounced lesions in the Spring and regression during the
Summer months. Blindness due to corneal vascularization may occur.
 -43-
Histopathologic Features:
Epithelium exhibits marked parakeratin production with thickening
of the stratum spinosum and the presence of numerous dyskeratotic cells
(eosinophilic cells that resemble epithelial pearls).
Treatment:
No treatment is required for the oral lesions. For evaluation and
treatment of the ocular lesions, the patient should be referred to an
ophthalmologist.
Darrier’s Disease: (Keratosis Follicularis)
A genetic disorder characterized by a persistent eruption of
hyperkeratotic papules.

Aetiology:
Darier’s disease is determined by an autosomal dominant gene on
chromosome 12q. However, many cases appear to occur as new mutations.

Pathology:
In the earliest lesions, fissures (lacunae) appear due to acantholysis
above the basal layer; seen in both light and electron microscopy. They later
extend irregularly. Small groups of cells around the lacunae become
separated from their neighbours, enlarge and present a darkly staining
nucleus surrounded by clear cytoplasm and a glistening ring simulating a
membrane. These corps ronds are cells showing premature partial
keratinization (dyskeratosis); they give rise to the grains, small cells with
shrunken cytoplasm, seen in the upper layers of the epidermis.
 -44-
Clinical Features:
Skin Lesions:
The distinctive lesion of Darier’s disese is a firm, rather greasy,
harsh papule, which is skin coloured, yellow-brown or brown. Coalescence
of the papules produces irregular warty plaques or papillomatous masses,
which in the flexures, become vegetating and malodorous. The sites of
predilection are the seborrhoeic areas of the trunk and face, particularly the
scalp margins, forehead, ears and nasolabial furrows.

Oral Lesions:
White umbilicate or cobblestone papules on the palate, tongue,
buccal mucosa, epiglottis, pharyngeal wall, vulva, oesophagus or rectum
may occur, as may hypertrophy of gums. Confluence of the papules may
form patches simulating leukoplakia. Blockage of the salivary glands may
be associated.

Nail Lesions:
Characteristic nail changes are seen:
1- Broad, white, longitudinal bands;
2- Broad, slightly translucent, red, longitudinal bands;
3- A sandwich of red and white longitudinal bands, often with a V-
shaped nick at the free margin of the nail.

Ear Lesions:
The external auditory meatus may be blocked by accumulated
keratotic debris. Most cases of Darier’s disease start before the age of 30
years, and the majority of patients first become aware of lesions between
the ages of 10 and 20 years.
 -45-
Complications:
Patients with Darier’s disease appear to have an increased
susceptibility to herpes simplex infections. There is in addition, an
increased incidence of chronic pyogenic infection. A defect in cell-mediated
immunity has been found.

Treatment:
Many patients with mild disease require no treatment other than a
simple emollient and advice about the effects of sunshine. For those with
more severe disease, retinoids are usually very effective.

Reactive and Inflammatory White Lesions:

Frictional Keratosis:
Clinical Features:
A white plaque with a rough and frayed surface that is clearly related
to an identifiable source of mechanical irritation and that will usually
resolve on elimination of the irritant.
Frictional keratosis is frequently associated with rough or
maladjusted dentures and with sharp cusps and edges of broken teeth.

Histologically:
Such lesions show varying degrees of hyperkeratosis and acanthosis.
Such lesions have never been shown to undergo malignant transformation.

Treatment:
Removal of the offending agent. Biopsies should be performed on
lesions that do not heal after removal of the cause to rule out a dysplastic
lesion.
 -46-

Frictional Keratosis
Cheek Chewing:
White lesions of the oral tissues may result from chronic irritation
due to repeated sucking, nibbling, or chewing of the cheek mucosa.
Most commonly seen in people who are under stress or in
psychological situations in which cheek and lip biting become habitual.
Most patients with this condition are somewhat aware of their habit but do
not associate it with their lesions.

Clinical Features:
The lesions are most frequently found bilaterally on the buccal
mucosa along the plane of occlusion.
The lesions are poorly outlined whitish patches that may be
intermixed with areas of erythema or ulceration.

Histopathologic Picture
Includes hyperparakeratosis and acanthosis. The keratin surface is
usually shaggy and ragged with numerous projections of keratin that
demonstrate adherent bacterial colonies.
 -47-
Treatment and Prognosis:
No treatment is indicated. However, for those desiring treatment and
unable to stop the chewing habit, a plastic occlusal night guard may be
fabricated.

Chemical Injuries of the Oral Mucosa:

Transient nonkeratotic white lesions of the oral mucosa are often a
result of chemical injuries caused by a variety of agents that are caustic such
as aspirin, silver nitrate, formocresol, sodium hypochlorite, dental cavity
varnishes, acid etching materials, and hydrogen peroxide. The white lesions
are attributable to the formation of a superficial pseudomembrane
composed of a necrotic surface tissue and an inflammatory exudates.

Clinical Features:
The lesions are usually located on the mucobuccal fold area and
gingiva but may occur on any mucosal surface exposed to caustic chemical.
The injured area is irregular in shape, white, covered with a
pseudomembrane, and very painful.

Treatment and Prognosis:

The best treatment of chemical burns of the oral cavity is prevention.
The proper use of a rubber dam during endodontic procedures reduces the
risk of iatrogenic chemical burns. A protective emollient agent such as a
film of methyl cellulose may provide relief. However, deep-tissue burns and
necrosis may require careful debridement of the surface, followed by
antibiotic coverage.
 -48-

Chemical burn on the lower lip

Actinic Keratosis (Cheilitis):
Actinic (or solar) keratosis is a premalignant epithelial lesion that is
directly related to long-term sun exposure. These lesions are classically
found on the vermilion border of the lower lip. A small percentage of these
lesions will transform into squamous cell carcinoma. Biopsies should be
performed on lesions that repeatedly ulcerate, crust over, or show a
thickened white area.

Clinical Features:
It appears as a white plaque, oval to linear in shape, usually
measuring <1 cm in size. However, sometimes it becomes extensive. The
surface may be crusted and rough to the touch.

Actinic keratosis
 -49-
Histopathologically:
Basophilic homogenous amorphous alteration of the collagen
(solar elastosis) in the lamina propria. Varying degrees of atypical features
such as increased nucleocytoplasmic ratios , loss of cellular polarity and
orientation, and nuclear and cellular atypia are found within the epithelium.

Treatment and prognosis:

The mainstay of treatment of actinic keratosis is surgery.

Smokeless Tobacco-
obacco-lnduced Keratosis:
Habitually chewing tobacco leaves or dipping snuff results in the
development of a well-recognized white mucosal lesion in the area of
tobacco contact, called smokeless tobacco keratosis, snuff dipper's
keratosis, or tobacco pouch keratosis.

While these lesions are accepted as precancerous, they are

significantly different from true leukoplakia and have a much lower risk of
malignant transformation.

Smokeless tobacco contains several known carcinogens, including

N-nitrosonornicotine (NNN). In addition to its established role as a
carcinogen, chewing tobacco may be a risk factor in the development of
root surface caries. This may be due to its high sugar content and its
association with increased amounts of gingival recession.

Clinical Features:
Most changes associated with the use of smokeless tobacco are seen
in the area contacting the tobacco. The most common area of involvement is
the anterior mandibular vestibule, followed by the posterior vestibule. The
 -50-
surface of the mucosa appears white and is granular or wrinkled in some
cases, a folded character may be seen (tobacco pouch keratosis). Commonly
noted is a characteristic area of gingival recession with periodontal-tissue
destruction in the immediate area of contact.Rarely an erythroplakic
component may be seen.

Smokeless Tobacco-lnduced
Keratosis

Microscopically:
The epithelium is hyperkeratotic and thickened. A characteristic
vacuolization or edema may be seen in the keratin layer and in the
superficial epithelium. Frank dysplasia is uncommon.

Treatment and Prognosis:

Cessation of use almost always leads to a normal mucosal
appearance within 1 to 2 weeks. Biopsy specimens should be obtained from
lesions that remain after 1 month.
 -51-
Nicotine Stomatitis:
Stomatitis:
Nicotine stomatitis (stomatitis nicotina palate, smoker's palate) refers
to a specific white lesion that develops on the hard and soft palate in heavy
cigarette, pipe, and cigar smokers.
The lesion is not considered to be premalignant. Interestingly,
nicotine stomatitis also develops in individuals with a long history of
drinking extremely hot beverages. This suggests that heat, rather than toxic
chemicals in tobacco smoke, is the primary cause.
Reverse smoking (i.e. placing the burning end of the cigarette in the
oral cavity), seen in South American and Asian populations, produces
significantly more pronounced palatal alterations that may be
erythroleukoplakic and that are definitely considered premalignant.
Clinical Features:
The palatal mucosa becomes diffusely gray or white. Numerous
slightly elevated papules with punctuate red centers that represent inflamed
and metaplastically altered minor salivary gland ducts are noted. Lesions
resolve within 2 weeks of cessation of smoking.

Nicotine Stomatitis:
 -52-
Microscopically:
The surface epithelium exhibits hyperkeratosis and acanthosis with
squamous metaplasia and hyperplasia of the salivary ducts as they approach
the surface.
Treatment and Prognosis:
Nicotine stomatitis is completely reversible once the habit is
discontinued. The lesions usually resolve within 2 weeks of cessation of
smoking. A biopsy should be performed on any white lesion of the palatal
mucosa that persists after 1 month of discontinuation of smoking habit.
If patient cannot stop the habit, an acrylic plate is constructed to
cover the palate.

Infectious White Lesions and White and Red Lesions:

Oral Hairy Leukoplakia:

Oral hairy leukoplakia is a corrugated white lesion that usually

occurs on the lateral or ventral surfaces of the tongue in patients with severe
immunodeficiency. The most common disease associated with oral hairy
leukoplakia is HIV infection.
Epstein-Barr virus (EBV) is implicated as the causative agent in oral
hairy leukoplakia.
 -53-
Histopathology:
Examination of the epithelium reveals severe hyperparakeratosis
with an irregular surface, acanthosis with superficial edema, and numerous
koilocytic cells (virally affected "balloon" cells) in the spinous layer. The
characteristic microscopic feature is the presence of homogeneous viral
nuclear inclusions with a residual rim of normal chromatin. The definitive
diagnosis can be established by demonstrating the presence of EBV through
in situ hybridization, electron microscopy, or polymerase chain reaction

Treatment and Prognosis:

The condition usually disappears when antiviral medications such as
zidovudine, or acyclovir are used in the treatment of the HIV infection and
its complicating viral infections.

Oral Hairy Leukoplakia

Oral Candidosis:
Candida species are normal inhabitants of the oral flora of many
individuals, but are present in the mouth of the healthy carrier in a low
concentration. At this concentration, the organism can not usually be
identified by direct microscopic examination of smears from the oral
 -54-
mucosa, and its presence can be demonstrated only by inoculation onto a
selective medium such as Sabouraud’s agar.
The asymptomatic carrier state is affected by a number of known
factors, including the immune status of the host, the strain of Candida, the
local oral environments, smoking, prior use of antibiotics, and the general
health of the host.
The wearing of removable prosthetic appliances is also associated
with higher asymptomatic carrier prevalence rates. Importantly, simple
measures to improve the oral health of the patient will reduce the rate of
Candida colonization of the oral mucosa and denture. Because Candida are
normal oral inhabitants, thrush and other forms of oral candidiasis may be
classified as specific endogenous infections.
Spectrum of oral candidosis:
• Acute candidosis
Thrush (acute pseudomembranous candidosis).
Acute antibiotic stomatitis (acute atrophic or
erythematous)
• Chronic candidosis
Denture-induced stomatitis
Chronic hyperplastic candidosis (candidal leukoplakia)
Median rhomboid glossitis
Chronic mucocutaneous candidosis
Erythematous candidosis
• Angular stomatitis (common to all types of oral candidosis).
 -55-
Important predisposing factors for oral candidosis
• Immunodeficiency (e.g. diabetes mellitus or AIDS) or
immunosuppression (including steroid inhalers, cancer
chemotherapy, and radiotherapy).
• Poor oral hygiene
• Pregnancy
• Anaemia
• Suppression of the normal oral flora by antibacterial drugs
• Xerostomia
• Haematologic malignancies

Acute Pseudomembranous Candidosis (Thrush)

Clinical Features:

Thrush forms generally painless, soft, friable, and creamy coloured

plaques on the mucosa. The distinctive feature is that they can be easily
wiped off, to expose an erythematous mucosa or shallow ulceration. Their
extent varies from isolated small flecks to widespread confluent plaques.
Angular stomatitis is frequently associated as it is with any form of intra-
oral candidosis.

Sometimes a prodrome of bad taste or loss of taste sensation

precedes the appearance of the lesions.
 -56-

Pseudo membranous candidosis

Pathology:
A Gram-stained smear shows large masses of tangled hyphae,
detached epithelial cells and leucocytes. Biopsy shows hyperplastic
epithelium infiltrated by inflammatory oedema and cells, predominantly
neutrophils. Staining with PAS shows many candidal hyphae growing down
through the epithelial cells to the junction of the plaque with the spinous
cell layer.

Management:
Control of any local cause such as topical antibiotic treatment may
alone cause thrush to resolve. If not, a course of nystain or amphotericin
lozenges should allow the oral microflora to return to normal. Failure of
response to topical antifungals such as nystatin suggests immune deficiency.
In immunodeficient patients as in HIV infection, candidosis may respond to
fluoconazole or itraconazole.
 -57-
N.B.:
• Neonatal thrush results from immaturity of the immune
response and infection is probably acquired during passage
through the birth canal.
• Any adult male who develops thrush without apparent cause
should be suspected of having HIV infection. However, any
form of candidosis can be secondary to HIV infection.

Acute Antibiotic Stomatitis:

This can follow overuse or topical oral use of antibiotics, especially
tetracycline, suppressing normal competing oral flora. Clinically, the whole
mucosa is red and sore. Flecks of thrush may be present. Resolution may
follow withdrawal of the antibiotic but is accelerated by topical antifungal
treatment.
Generalized candidal erythema which is clinically similar, can also
be a consequence of xerostomia which promotes candidal infection. It is a
typical complication of Sjogren's syndrome. Nystatin suspension or
miconazole gel held in the mouth is usually effective.

Denture-
Denture-induced Stomatitis:
A well –fitting upper denture cuts off the underlying mucosa from
the protective action of saliva. In susceptible patients, particularly smokers,
this can promote candidosis, seen as a symptomless area of erythema. The
erythema is sharply limited to the area of mucosa occluded by a well-fitting
upper denture or even an orthodontic plate. Similar inflammation is not seen
under the more mobile lower denture which allows a relatively free flow of
saliva beneath it. Angular stomatitis is frequently associated and may form
the chief complaint.
 -58-

Denture-induced Stomatitis

Pathology:
Gram-stained smears show candidal hyphae and some yeast forms
which have proliferated in the interface between denture base and mucosa.
Histologically, there is typically mild acanthosis with prominent blood
vessels superficially and a mild chronic inflammatory infiltrate. The
inflammation is probably a response to enzymes such as phospholipases
produced by the fungus.

Treatment:
To prevent denture-induced stomatitis, denture cleansing that
includes removal of candidal organisms is a necessary and important
factor.Cleansers can be divided into groups according to their primary
components: alkaline peroxides, hypochlorites, acids, disinfectants, and
enzymes.Yeast lytic enzymes and proteolytic enzymes are the most
effective against the infection .
 -59-
Denture soak solution containing benzoic acid completely eradicates
C albicans from the denture surface as it is taken up into the acrylic resin
and eliminates the organism from the internal surface of the prosthesis.
An oral rinse containing 0.12% chlorhexidine gluconate results in
complete elimination of the presence of C albicans on the acrylic resin
surface of the denture and in reduction of palatal inflammation .
A protease-containing denture soak also effectively removes denture
plaque, especially when combined with brushing.
Chlorhexidine oral rinses also may be of some benefit in the control
of oral candidosis
Diet: High-sucrose diets should be avoided.

Median Rhomboid Glossitis.

Erythematous patches of atrophic papillae located in the central area
of the dorsum of the tongue are considered a form of chronic atrophic
candidiasis.

Median Rhomboid Glossitis

 -60-
Chronic Hyperplastic Candidiasis:
Chronic hyperplastic candidiasis (CHC) includes a variety of
clinically recognized conditions in which mycelial invasion of the deeper
layers of the mucosa and skin occurs, causing a prolifertive response of host
tissue.
Candidal leukoplakia is considered a chronic form of oral candidiasis
in which firm white leathery plaques are detected on the cheeks, lips, palate,
and tongue. The differentiation of candidal leukoplakia from other forms of
leukoplakia is based on finding periodic acid-Schiff (PAS)-positive hyphae
in leukoplakic lesions.

Chronic Mucocutaneous Candidiasis:

Persistent infection with Candida usually occurs as a result of a
defect in cell-mediated immunity or may be associated with iron deficiency.
Hyperplastic mucocutaneous lesions, localized granulomas, and adherent
white plaques on affected mucous membranes are the prominent lesions that
identify chronic mucocutaneous candidiasis (CMC).
Two categories of CMC have been described:
(1) Syndrome-associated CMC (further categorized as either familial
or chronic).
(2) Localized and diffuse CMC.

The familial form, candidiasis endocrinopathy syndrome (CES), is a

rare autosomal recessive disorder characterized by an onset of CMC during
infancy or early childhood, associated with the appearance of
hypoparathyroidism, hypoadrenocorticism and other endocrine anomalies.
 -61-
Patients develop persistent oral candidiasis and hyperplastic infections of
the nail folds at an early age.
The other syndrome-associated form is chronic candidiasis
associated with thymoma, which appears with other autoimmune
abnormalities such as myasthenia gravis.
Localized CMC is a variant associated with chronic oral candidiasis
and lesions of the skin and nails. The diffuse variant is characterized by
randomly occurring cases of severe mucocutaneous candidiasis with
widespread skin involvement and development of Candida granulomas.

Management:
Both oral and cutaneous lesions of CMC can be controlled by the
continuous use of systemic antifungal drugs; once treatment is discontinued,
however, the lesions rapidly reappear.

Erythematous Candidosis:
This term applies to red mucosal macules due to Candida albicans
infection in HIV –positive patients. Favoured sites, in order of frequency,
are the hard palate, dorsum of the tongue and soft palate. Treatment with
intraconazole is usually effective.

Angular Stomatitis:
Angular stomatitis is typically caused by leakage of Candida-
infected saliva at the angles of the mouth. It can be seen in infantile thrush
in denture wearers or in association with chronic hyperplastic candidosis. It
is a characteristic sign of candidal infection.
 -62-
Clinically, there is mild inflammation at the angles of the mouth. In
elderly patients with denture-induced stomatitis, inflammation frequently
extends along folds of the facial skin extending from the angles of the
mouth. These folds are due to sagging of the facial tissues with age.
Furrows at the angles of the mouth are made deeper by loss of vertical
dimension and by loss of support to the upper lip by resorption of the
underlying bone. Though establishment of correct vertical dimension and
increasing the thickness of the labial flange of the upper denture can slightly
lessen these furrows, they can rarely be eliminated in this way.
Treatment of intraoral candidal infection alone causes angular
stomatitis to resolve. If there is co-infection with S. aureus, local
application of fusidic acid cream may be required.

Angular Stomatitis
Treatment of Oral Candidiasis:

I) Treatment of underlying predisposing factors (if possible)

II) Antifungal Drugs
- Antifungal antibiotics nystatin and amphotericin B.
- Nystatin for topical use is available as suspension,
 -63-
lozenges and cream (100,000 u).
- Amphotericin B (a topical use is available as
suspension, and lozenges.
- Imidazole derivatives (clotrimazole, miconazole) are
available for topical use (cream, oral gel).
- Systemic therapy includes the use of any one of these
three: ketoconazole, itraconazole, and fluconazole.
- Fluconazole and amphotericin B may be used
intravenously for the treatment of the resistant lesions
of CMC and systemic candidiasis.
The majority of acute oral candida infections respond rapidly to
topical nystatin and will not recur, provided that the predisposing factors
have also been eliminated. Seven to 21 days use of a nystatin rinse three to
four times daily is usually adequate although some resistant cases may
require a second course of treatment. Nystatin in cream form may also be
applied directly to the denture or to the corners of the mouth.
Patients for whom predisposing factors such as xerostomia and
immunodeficiency cannot be eliminated may need either continuous or
repeated treatment to prevent recurrences. The consumption of yogurt two
to three times per week and improved oral hygiene can also help.

Idiopathic “TRUE” Leukoplakia:

Leukoplakia is a white oral precancerous lesion with a recognizable
risk for malignant transformation.
Leukoplakia is currently defined as “a white patch or plaque that
cannot be characterized clinically or pathologically as any other disease”.
 -64-
Etiology:
A number of locally acting etiologic agents, including tobacco,
alcohol, candidiasis, electrogalvanic reactions, and (possibly) herpes
simplex and papillomaviruses, have been implicated as causative factors
for leukoplakia.
Alcohol consumption alone is not associated with an increased risk
of developing leukoplakia, but alcohol is thought to serve as a promoter that
exhibits a strong synergistic effect with tobacco.
Sunlight (specifically, ultraviolet radiation) is well known to be an
etiologic factor for the formation of leukoplakia of the vermilion border of
the lower lip.
Candida albicans is frequently found in histologic sections of
leukoplakia and is consistently (60% of cases) identified in nodular
leukoplakias. The terms “candidal leukoplakia” and “hyperplastic
candidiasis” have been used to describe such lesions. Whether candida
constitutes a cofactor either for excess production of keratin or for
dysplastic or malignant transformation is unknown.

Clinical Features:
Leukoplakia is more frequently found in men, can occur on any
mucosal surface, and infrequently causes discomfort or pain.
- Prevalence increases rapidly with age.
- Approximately 70% of oral leukoplakia lesions are
found on the buccal mucosa, vermilion border of the
lower lip, and gingiva.
 -65-
- Less common on the palate, maxillary mucosa,
retromolar area, floor of the mouth, and tongue.
However, lesions of the tongue and the floor of the
mouth account for more than 90% of cases that show
dysplasia or carcinoma.

Subtypes:

Homogeneous leukoplakia well-defined white patch, that is slightly

elevated and that has a fissured, wrinkled, or corrugated surface. On
palpation, these lesions may feel leathery to “dry, or cracked mud-like”.

Nodular (speckled) leukoplakia the name refers to a mixed red-

and–white lesion in which keratotic white nodules or patches are distributed
over an atrophic erythematous background. This type of leukoplakia is
associated with a higher malignant transformation rate.

Verrucous leukoplakia is a term used to describe the presence of

thick white lesions with papillary surfaces in the oral cavity. These lesions
are usually heavily keratinized and are most often seen in older adults in the
sixth to eighth decades of life. Some of these lesions may exhibit an
exophytic growth pattern.

Proliferative verrucous leukoplakia extensive papillary or

verrucoid white plaques that tend to slowly involve multiple mucosal sites
in the oral cavity and to transform into squamous cell carcinomas over a
period of many years.
 -66-

Homogeneous leukoplakia Nodular (speckled) leukoplakia

Histopathologic Features:
• Highly variable but there is always parakeratosis or orthokeratosis or
both, alternately.
• The epithelium ranges from thinner than normal (atrophic) to much
thicker (acanthotic)
• Most leukoplakias show no dysplastic changes
• A minority display a range of dysplasia from mild to severe and
treatment is planned partly on this basis.
• An inflammatory reaction of lymphocytes and plasma cells is often
present in the underlying connective tissue.

Diagnosis and Management:

If a leukoplakia lesion disappears spontaneously or through the
elimination of an irritant, no further testing is indicated.
For the persistent lesion, however, the definitive diagnosis is
established by tissue biopsy. Adjunctive methods as vital staining with
 -67-
toluidine blue and cytobrush are helpful in selecting the most appropriate
spot for biopsy .
Toluidine blue staining uses a 1% aqueous solution of the dye
which stains dysplastic and malignant cells and resists washing away by
rinsing with 1% acetic acid .
Cytobrush technique utilizes a brush with firm bristles that obtains
individual cells from the full thickness of epithelium for cytologic
examination .
Definitive treatment involves surgical excision although cryosurgery
and laser ablation are often preferred because of their precision and rapid
healing.
Prognosis:
Clinical signs of malignant transformation of leukoplakia include :
Ulceration , erythroplasia , bleeding , induration and lymphadenopathy
After surgical removal long-term monitoring of the lesion site is
important since recurrences are frequent and because additional
leukoplakias may develop.

Erythroplakia:
“Bright red velvety plaque or patch which cannot be characterized
clinically or pathologically as being due to any other condition”. The
majority of erythroplakias (particularly those located under the tongue, on
the floor of the mouth, and on the soft palate and anterior tonsillar pillars)
exhibit a high frequency of premalignant and malignant changes.
 -68-
Although the etiology of erythroplakia is uncertain, most cases of
erythroplakia are associated with heavy smoking, with or without
concomitant alcohol abuse.

Clinical Features:
Erythroplakia occurs predominantly in older men, in the sixth and
seventh decades of life.
Erythroplakias are more commonly seen on the floor of the mouth,
the ventral tongue, the soft palate, and the tonsillar fauces, all prime areas
for the development of carcinoma. Multiple lesions may be present. Almost
all of the lesions are asymptomatic.

Histopathologic Features:
80 to 90% of cases of erythroplakia are histopathologically severe
epithelial dysplasia, carcinoma in situ, or invasive carcinoma.

Differential Diagnosis:
In view of the clinical significance of erythroplakia, its
differentiation from other red inflammatory lesions of the oral mucosa is
critical. Clinically similar lesions may include erythematous candidiasis,
areas of mechanical irritation, denture stomatitis, vascular lesions, and a
variety of nonspecific inflammatory lesions.

Lichen Planus:
Lichen planus is a common chronic inflammatory disease of skin and
mucous membranes. It mainly affects patients of middle age or over. Oral
lesions have characteristic appearances and distribution.

Aetiology:
 -69-
The predominantly T-lymphocyte infiltrate suggests cell-mediated
immunological damage to the epithelium
Clinical Features:

Skin Lesions:
Typical lesions are pruritic, polyangular, planar papules and plaques.
Lesions initially are 2 to 4 mm in diameter, with angular borders, a
violaceous color, and a distinct sheen in cross-lighting. They are usually
symmetrically distributed most commonly on the flexor surfaces of the
wrists, legs, trunk. The face is rarely involved during the acute phase, new
papules may appear at sites of minor skin injury (Koebners phenomenon),
such as a superficial scratch lesions may coalesce or change over time
becoming hyperpigmented, atrophic hyperkeratotic (hypertrophic LP) or
vesiculobullous. If the scalp is affected, patchy scarring alopecia may occur.

Nail Lesions:
Nails are involved in up to 10% of cases. Findings vary in intensity
with nail bed discoloration longitudinal ridging and lateral thinning and
complete loss of the nail matrix and nail with scarring of the proximal nail
fold onto the nail bed.

Oral Lesions:
The oral mucosa is involved in about 50% of cases; oral lesions may
occur in the absence of cutaneous lesions and usually persist for life
Reticulated lacy bluish-white, linear lesions (Wickham’s striae) are a
hallmark of oral LP especially on the buccal mucosae.
Although OLP may occur at any oral mucosal site, the buccal
mucosa is the most common site. OLP is classified as reticular, atrophic or
 -70-
erosive and bullous. Apart from the erosive and bullous forms of the
disorder, reticular OLP is quite frequently a painless lesion that is usually
asymptomatic
The reticular form consists of:
(a) Slightly elevated fine whitish lines (Wickham’s striae) that
produce either a lacelike pattern or a pattern of fine radiating
lines.

(b) Annular lesions. Whitish elevated lesions, or papules, usually

measuring 0.5 to 1.0 mm in diameter, may be seen on the well-
keratinized areas of the oral mucosa. However, large plaque
like lesions may occur on the cheek, tongue, and gingivae, and
these are difficult to distinguish from leukoplakia.

These lesions are asymptomatic or the patient of roughness or

change in colour.
Atrophic lichen planus presents as inflamed areas of the oral
mucosa covered by thinned red-appearing epithelium.
Erosive lesions probably develop as a complication of the atrophic
process when the thin epithelium is abraded or ulcerated. These lesions are
invariably symptomatic, with symptoms that range from mild burning to
severe pain.
Atrophic or erosive lichen planus involving the gingivae results in
desquamative gingivitis. Lichen planus must be distinguished
histologically from other diseases that cause desquamative gingivitis, such
as mucous membrane pemphigoid and pemphigus
 -71-
Bullous lesions are characterized by severe destruction of basal cell
layer which leads to separation of overlying layers forming vesicles or
bullae that soon rupture forming ulcers surrounded by signs of
inflammation. Severe pain characterizes these lesions.
Papular, plaquelike, atrophic, and erosive lesions are very frequently
accompanied by reticular lesions. The affected areas of the oral mucosa are
not bound down or rendered inelastic by lichen planus, and the keratotic
white lines cannot be eliminated by either stretching the mucosa or rubbing
its surface.
Histopathologic Features:

Three features are considered essential for the histopathologic

diagnosis of lichen planus:
(1) Areas of hyperparakeratosis or hyperorthokeratosis.
(2) “liquefaction degeneration” or necrosis of the basal cell layer which
is often replaced by an eosinophilic band.
(3) A dense subepithelial band of lymphocytes. This linear sub-basilar
lymphocytic infiltration is composed largely of T cells.

Isolated epithelial cells, shrunken with eosinophilic cytoplasm and

one or more pyknotic nuclear fragments (Civatte bodies), are often scattered
within the epithelium and superficial lamina propria. These represent cells
that have undergone apoptosis.
 -72-
Immunofluorescent Studies:

Immunofluorescent studies of biopsy specimens from lesions of

lichen planus reveal a number of features that are not seen in hematoxylin-
eosin (H & E)-stained sections:
A shaggy band of fibrinogen in the basement membrane zone in 90
to 100% of cases. Multiple IgM-staining cytoid bodies, usually located in
the dermal papilla or in the peribasalar area.

Oral lesion of lichen planus Skin lesion of lichen planus

(reticular, atrophic & erosive) (polygonal, violacious & flat)

To summarize:
Oral Lichen
Lichen Planus:
Planus: Typical Features
• Females account for at least 65% of patients.
• Patients usually over 40 years.
• Untreated disease can persist for 10 or more years.
 -73-
• Lesions in combination or isolation, comprise:
o Striae.
o Atrophic areas.
o Erosion/ulcers.
o Plaques.
• Common sites are:
o Buccal mucosa.
o Dorsum of tongue.
o Gingiva (infrequently).
• Lesions usually bilateral and often symmetrical.
• Cutaneous lesions are occasionally associated.
• Usually, good response to corticosteroids.

Treatment:
• Asymptomatic lesions require no treatment.

• Corticosteroids have been the most predictable and successful

medications for controlling signs and symptoms.

• Topical medications include high-potency corticosteroids, these are

frequently prescribed as pastes or as gels.

• Erosive lesions may respond to oral dapsone or cyclosporine rinses.

• Systemic steroids are indicated for brief treatment of severe

exacerbations or for short periods of treatment of cases that fail to
respond to topical steroids. Prednisone tablets with dosages varying
between 40 and 80 mg daily for less than 10 days without tapering are
sometimes sufficient. Longer course duration will need tapering of
corticosteroid therapy at the end (when clinical remission is achieved).
 -74-
If treatment with corticosteroids extends for months, antifungal drugs
should be prescribed on monthly basis to avoid the development of oral
candidiasis.

• Intralesional injection of corticosteroid may be used in lesions resistant

to topical and systemic therapy triamcinolone acetonide ampules are
used (weekly regimen).

• Systemically administered dapsone, hydroxychloroquine, azathioprine

and cyclosporine may help in cases resistant to corticosteroids

• Drug combinations could also be used.

Malignant Change in Lichen Planus:

The risk of and possible frequency of malignant change in lichen

planus has long been controversial. Reportedly 1-4% of patients suffer this
complication after 10 years, but there is growing controversy about such
figures. Doubts about the validity of the diagnosis of lichen planus, in
reports of malignant change, have been expressed. Dysplastic lesions, for
example, may have a streaky appearance that has been mistaken for striae.
Also, because lichen planus is so common a disease, the quoted rates for
malignant change would greatly exceed the actual incidence of oral cancer.

Specific risk factors have also not been identified with certainty.

Lichenoid Reactions:
This term is given to lichen planus-like lesions caused by either
systemic drug treatment or those where the histological picture is not
completely diagnostic.
 -75-
Oral lichenoid reactions are most frequently responses to restorative
materials, either amalgam or polymeric. The clinical appearances are
similar or identical to lichen planus or lupus erythematosus but lesions are
localized to mucosa in contact, not just close to, restorations.
Lichenoid reactions are treated in exactly the same way as lichen
planus with withdrawal of drug(s) if possible or removal of restoration.
Thus, the absolute distinction between lichen planus and lichenoid reaction
is not always necessary for treatment.

Lupus Erythematosus:
Lupus erythematosus is an autoimmune connective tissue disease
which has two main forms namely systemic and discoid. Either can give rise
to oral lesions which may appear similar to those of oral lichen planus.

Systemic Lupus Erythematosus:

rythematosus:
Has varied effects. Arthralgias and rashes are most common, but
virtually any organ system can be affected. A great variety of
autoantibodies, particularly antinuclear, is produced.

Pathological features of systemic lupus erythematosus:

Macroscopic:
• Pleurisy.
• Pericarditis.
• Libman-sacks endocarditis.
• Lymphadenopathy.
• Splenomegaly.
• May be none.
 -76-

Microscopic:
• Immunoglobulins and complement at the dermo-epidermal junction
in skin lesions (90%) and uninvolved skin (60%).
• Haematoxylin bodies in the endocardium, renal glomuruli and
elsewhere.
• Periarterial fibrosis of the spleen.
• Wire loop lesions in the kidneys.

Discoid Lupus:
Essentially a skin disease with mucocutaneous lesions
indistinguishable clinically from those of systemic lupus. These may be
associated with arthralgias but rarely, significant autoantibody production.

Clinical Features:
A) Skin Lesions:
Lesions:
1) In DLE:
In DLE the face is most commonly affected and the scalp, ears, nose,
arms, legs and trunk to a lesser extent.
The circumscribed or discoid type is the most frequent, and occurs
particularly on the cheeks, the bridge of the nose, the ears, the side of the
neck and the scalp. Lesions may be bilateral, although not necessarily
symmetrical. They may form a “butterfly rash” on the face.
Alopecia occurs in the scalp lesions in about one-third of patients
and is usually permanent. The eyebrows may be sparse, with erythema of
the eyebrow skin.
 -77-
Other parts of the body may be involved, particularly the dorsa of the
hands and the dorsa and sides of the toes.
Usually, lesions occur as well-defined erythematous patches, varying
in size from few millimeters to 10-15 cm. there is fairly adherent scale in
many cases, and when this is removed its undersurface shows horny plugs
which have occupied dilated pilosebaceous canals (“tin-tack” sign) the
surface may present a dirty, brownish-yellow appearance which is rough to
the touch, because of the follicular plugging. If hyperkeratosis is marked, a
warty lesion with a red, slightly raised edge, results.

2) In SLE:
Cutaneous erythema is the commonest feature, particularly on light-
exposed areas. A butterfly blush or discrete maculopapular eruption with
fine scaling on the butterfly area of the cheeks or elsewhere is also
frequently found. Occasionally, more acute lesions with bulae may follow
exposure to the sun. Bullae may become haemorrhagic.

Cutaneous features of systemic lupus erythematosus.

• Butterfly rash.
• Facial oedema.
• Subacute cutaneous LE.
• Chronic discoid LE.
• Scarring DLE alopecia
• Non-scarring alopecia
• Photosensitivity
• Raynaud’s phenomenon
• Chronic urticaria
• Cutaneous vasculitis Butterfly rash
 -78-
B) Oral Lesions
Lesions:
esions:
Appear in about 20% of cases of systemic lupus, and can rarely be
the presenting sign. Oral lesions occur more commonly in DLE. Typical
lesions are white, often striated, areas, with irregular atrophic areas or
shallow erosions, but the patterns, particularly those of the striae, are
typically far less sharply defined than in lichen planus. They are often
patchy and unilateral and may be in the vault of the palate which lichen
planus typically spares. Lesions can form variable patterns of white and red
areas. oedema and often a hyaline appearance are seen together with
telangiectasia.

Oral lesion of lupus erythematosus

Histopathologic Features:
1) Liquefaction degeneration of basal cell layer.
2) Degenerative changes in the connective tissue (hyalinization,
oedema,..).
 -79-
3) Lupus erythematosus shows more irregular patterns of acanthosis
and lacks the band-like distribution of lymphocytes in the papillary
corium of lichen planus.
4) The inflammatory infiltrate is highly variable in density, typically
extends deeply into the connective tissue, and may have a
perivascular distribution.

Management:
Oral lesions of discoid lupus erythematosus may respond in some
degree to topical corticosteroids. However, oral lesions in acute systemic
lupus erythematosus may not respond to doses of corticosteroids adequate
to control systemic effects of the disease. Under such circumstances,
palliative treatment is needed until disease activity decreases.

Miscellaneous Lesions:
Oral Sumucous Fibrosis:
Fibrosis:
Oral submucous fibrosis (OSF) is a slowly progressive
chronic fibrotic disease of the oral cavity and oropharynx,
characterized by fibroelastic change and inflammation of the
mucosa, leading to a progressive inability to open the mouth,
swallow, or speak. These reactions may be the result of either
direct stimulation from exogenous antigens like Areca alkaloids or
changes in tissue antigenicity that may lead to an autoimmune
response. It occurs almost exclusively in the Indian subcontinent.
The inflammatory response releases cytokines and growth factors
 -80-
that promote fibrosis by inducing the proliferation of fibroblasts,
up-regulating collagen synthesis and down-regulating collagenase
production.
Etiology:

General nutritional and vitamin deficiencies and

hypersensitivity to certain dietary constituents such as chili
peppers, chewing tobacco, habitual use of betel and its constituents
(Areca catechu).
Clinical Features:

The disease first presents with a burning sensation of the

mouth, particularly during consumption of spicy foods. It is often
accompanied by the formation of vesicles or ulcerations and by
excessive salivation or xerostomia and altered taste sensations.
Gradually, patients develop a stiffening of the mucosa, with a
dramatic reduction in mouth opening and with difficulty in
swallowing and speaking. The mucosa appears blanched and
opaque with the appearance of fibrotic bands that can easily be
palpated. Usually involves the buccal mucosa, soft palate, posterior
pharynx, lips, and tongue.

Histologic Features:
Reveals severely atrophic epithelium with complete loss of
rete ridges. Varying degrees of epithelial atypia may be present the
underlying lamina propria exhibits severe hyalinization, with
homogenization of collagen. Cellular elements and blood vessels
are greatly reduced.
 -81-
Treatment and Prognosis:

Oral submucous fibrosis is regarded as a premalignant

condition.
Oral submucous fibrosis is very resistant to treatment. Submucosal
injected steroids and hyaluronidase, are some of the agents that have been
used. In severe cases surgical intervention is the only treatment but the
fibrous bands and other symptoms often recur within a few months to a few
years.
Sin Grafts:
A skin graft may be placed in the mouth to cover a raw area left after
excision of a lesion.
Skin grafts typically appear sharply demarcated smooth and paler
than the surrounding mucosa and occasionally contain hairs . Grafts on the
dorsum of the tongue may become corrugated and less easy to differentiate
from leukoplakia.
 -82-
ORO-FACIAL PIGMENTED LESIONS
ORO-

Classification
1-Melanotic
 Localized
 Diffuse
2-Non melanotic
A- Endogenous
 Lipopigment
 Pigmentation due to RBCs
 Vascular lesions

B- Exogenous
 Black hairy tongue
 Tattoo: Amalgam, graphite tattoo.
 Metallic intoxication: lead, mercury, bismuth.

(1) Melanotic Lesions:

Localized:
Ectodermal alteration e.g. Acanthosis Nigericans.
Increased melanin production:
 Café au lait spots e.g. polyostotic fibrous dysplasia and
multiple neurofibromatosis.
 Smoker’s melanosis
 Lichen planus
 Local irritation.
Melanocyte proliferation:
 Naevi
 -83-
 Melanoma/malignant melanoma
 Lentigo e.g. peutz Jegher’s syndrome
Drug-Induced.

Diffuse:
Racial pigmentation (basilar melanosis)
Metabolic pigmentation
 Hemochromatosis
 Porphyria
 Pellagra
Endocrine
 Addison’s disease
 Hyperpituitrism
Autoimmune
HIV melanosis
Lung/pancreas malignancy
Drug-induced
 Drugs causing melanin formation e.g. ACTH, busulfan.
 Drugs forming complex with melanin e.g. minocyclin.
 Drugs deposited in skin and mucous membrane e.g. silver & gold
Acanthosis Nigericans
Unusual dermatosis characterized by skin hyperkeratosis and
melanin pigmentation and white oral lesion.
 -84-
Types:
1- Benign form
• Associated with insulin resistant diabetes (defect in insulin
receptors). Insulin will bind to receptor for ILGF → growth of
the cells instead of glucose utilization → hyperkeratosis,
acanthosis and papillomatosis.
2- Malignant form
• Internal malignancy releases certain peptides→ stimulate
melanin production.

White intra-oral lesions of acanthosis nigericans Skin lesions

Café au Lait
Lait Spots:
pots:

These lesions have the bright brown colour of coffee and cream that
varies from small to large diffuse macules.

They are found in two rare conditions; neurofibromatosis and

polyostotic fibrous dysplasia.
 -85-

Café au lait spots

(A) Multiple Neurofibromatosis (Von Recklinghausen’s Disease

of Skin):
kin):
It is an inherited autosomal dominant neuroectodermal abnormality
which is characterized by proliferation of fibrous element of nerve sheath,
cafe au lait pigmentation and sometimes Lisch nodules (pigmented iris
hamartomas).

Clinical Features:
(1) Multiple nodules (smooth – painless):
 Sessile or pedunculated, superficial or deep nodules that
mainly affect the trunk. Malignant transformation to
neurogenic sarcoma is common in 5 % of cases. The lesion
may involve the whole body causing cosmetic problem.
 Tongue involvement results in multiple nodules due to
proliferation of fibrous element of lingual nerve. In addition,
macroglossia, scrotal tongue and enlarged fungiform papillae
had been reported.
 -86-

Tongue lesions Skin nodules & café au lait spots

(2) Neurologic manifestation:

 Centrally located lesions within bone cavities are associated
with neurological manifestations such as pain, deafness,
epilepsy, mental retardation and headache.
 Mandibular nerve involvement can be detected
radiographically as radiolucent area and is associated with lip
numbness and pain.
(3) Café au lait pigmentation.
• Six or more café au lait spots (> 5 mm in greatest diameter in
prepubertal individual and >15 mm in greatest diameter in
postpubertal individual )
• Axillary freckles are also seen.

Café au lait pigmentation is the first feature of the disease, appearing

early in childhood.
 -87-
Histological Features:
Lesions are cellular with plump nuclei separated by collagen fibers,
among which mast cells can usually be seen.
Both in café au lait spots and clinically unaffected skin, giant
pigment granules are sometimes found.

Treatment:
Symptomatic. Disfiguring lesions are excised .Surgery is also
indicated when an increase in size and pain suggest malignancy.

(B) Polyostotic Fib

Fibrous
ibrous Dysplasia
Jaffé type
 Unilateral bone involvement
 Most bones are intact
 Skin café au lait spots
 No endocrinal disturbance
Albright syndrome
 Unilateral bone involvement
 Most bones are affected
 Skin café au lait spots
 Endocrinal disturbance is present:affecting:
o Parathyroid
o Thyroid
o Pituitary
o Gonads (precocious puberty)
 -88-
Oral Findings:
Slowly progressive expansion of jaw bone:
Jaw bone is replaced by fibrous tissue and the cortex becomes
thin leading to pathologic fracture
Radiographically the lesion may show one of these patterns:
 Ground glass radio-opaque pattern
 Mottled radiolucent & radio-opaque pattern
 Unilocular or multilocular radiolucencv

Albright
syndrome

Smoker's melanosis
• It is basilar melanosis that occurs in some smokers where
tobacco smoke products stimulate synthesis of melanin.
• It appears as diffuse brown flat macules, mainly on anterior
labial gingiva in cigarette smokers and on palate in pipe
smokers but may also appear on cheek and lip mucosa.

Pigmented lichen planus

 -89-
Lichen planus is dermatologic disease which is characterized by
white papules, erosive and atrophic areas. Rarely erosive or papular form
may be associated with diffuse melanosis.

This increase in melanogenesis may be stimulated by the infiltrate of

T-lymphocytes through the cytokines they produce.

Pigmented lichen planus

Oral melanotic naevi

Benign proliferation of melanocytes which form localized brown to
black patches about 5 or 6 mm across.
Clinical Features:
(i) Nevocellular nevi:
• Junctional nevi:
o Nevus cells maintain their location at the junction of the
epithelium and connective tissue.
 -90-
o They are flat, brown round and oval lesions.
• Compound nevi:
o Nevus cells proliferate down into the connective tissue.
o They are dome-shaped, brown lesions.
• Intradermal/intramucosal nevi:
o Nevus cells are localized in connective tissue.
o They appear as elevated brown nodules.
• Blue nevi
The nevus cells reside deeply in connective tissue. On skin they
appear blue in colour because the overlying vessels dampen the brown
colour of melanin.

Melanoma / Malignant Melanoma:

 Raised, painless, sessile or pedunculated.
 If melanomas become painful, with increased pigmentation,
bleeding or ulceration this may be a sign of malignancy.
 Malignant melanoma is a rare neoplasm of the oral cavity.
 Most commonly found on the palate and anterior labial
gingiva.
 -91-

Malignant Melanoma

Peutz-
Peutz-Jegher’s
Jegher’s Syndrome:
Syndrome:
Definition:
It is an autosomal dominant syndrome that is characterized by
multiple intestinal polyposis and melanotic macules mainly on the face and
oral cavity

Clinical Features:
Brown Pigmentation:
 Multiple melanotic macules appearing as freckles, mainly
perioral, perinasal and perioccular
 Hands and feet are affected .
 Melanotic macules are present intraoral, mainly on palate and
lip. Facial pigmentation may disappear by age but intra oral
lesions do not.
Intestinal Polyposis:
 Polyposis of small intestine may result in abdominal pain,
hemorrhage or intestinal obstruction.
 -92-
 Malignant transformation can occur.
 Intestinal polyps are better to be diagnosed by barium enema

Physiologic Pigmentation:
It is basilar melanosis that evolves in childhood, commonly in dark-
skinned individuals.
It appears as multiple, diffuse flat brown macules, mainly on gingiva,
labial and cheek mucosa.
 -93-

Physiologic(racial) Pigmentation

Haemochromatosis:
Primary:
Disorder of inborn error of iron metabolism secondary to increased
intestinal iron absorption.
Secondary:
Due to increased iron intake or increased destruction of RBCs.
Excess iron is deposited in various tissue and organs:
 In the liver producing liver cirrhosis.
 In the pancreas producing diabetes mellitus.
 In the adrenal gland inducing Addison’s disease.
 In the heart inducing heart failure.
 In the skin producing pigmentation.

Por
Porphyrias:
phyrias:
 -94-
Hereditary diseases caused by abnormalities in the pathway of heme
biosynthesis, resulting in over production of porphyrins and porphyrin
precursors.
Two types are characterized by skin pigmentation:
1) Cutaneous hepatic porphyria “Porphyria cutenea tarda”
Starts as erythema and progresses to vesicles that become confluent
to form bullae, that heal by scar with skin hyperpigmentation.
2) Congenital erythropoietic porphyria:
• Excessive formation of porphyrin in bone marrow leads to its
deposition on the skin producing photosensitivity → vesicular
and bullous reaction on the light exposed skin.
• Vesicles contain serous fluid with red fluorescence.
• Healing is by scars and red brown hyperpigmentation.
• Urine is red in colour.
• Lavender teeth: due to incorporation of porphyrins in decidous
and permanent teeth

Skin lesions of porphyria Lavender teeth

 -95-
Pellagra:
Pellagra:
It is niacin (Nicotinic acid) deficiency.
It progresses through:
• Dermatitis with melanin pigmentation of the exposed skin
surfaces (hands, feet and face).
• Dementia (impaired memory)
• Diarrhea
• Death (if untreated)
Oral Manifestations:

Stomatitis, glossitis, acute necrotizing ulcerative gingivitis,

sialorrhea, angular cheilosis, herpes labialis, deminution of taste sensation.

Dermatitis with melanin pigmentation Oral manifestations of pellagra

Endocrinopathic Pigmentation:
Bronzing of skin and patchy melanosis of the oral mucous membrane
are features of adrenal cortex insufficiency (Addison’s disease) or
hyperfunction of pituitary gland (due to increased ACTH). The
 -96-
oversecretion of ACTH results in melanosis since it is a hormone that have
stimulating properties on melanocytes.

Patchy melanosis of the oral mucsa in Addison's disease

HIV Oral Melanosis::

Melanosis::
HIV positive patients show hyperpigmentation of the nails and
mucous membrane. The etiology is unknown but may be due to the
destruction of adrenal cortex (Addison’s disease).
It appears as diffuse flat brown macules, mainly on buccal and labial

HIV Oral Melanosis

 -97-
(2) Non- Melanotic:
Endogenous pigmentation
Lipopigments
The lipopigment is the colouring matter of the sebum and fatty
tissues.
Lipochrome: “Carotene”
Carotenes are yellow or red fat soluble pigments found in carrots,
tomatoes, sweet potatoes, green leafy plants, milk, body fat and egg yolk.
Carotenes are the precursors of vitamin A .Excessive intake of
carotene results in carotenemia and the resultant yellow colour of skin
isknown as carotenodermia .It also imparts its yellow colour to the oral
mucosa .However, the eyes are spared because carotene is water insoluble
so cannot reach the eye (compare to jaundice).

Yellowish discoloration of oral mucosa due to carotenemia

 -98-
Sebaceous glands:
Yellowish white spots may be seen on the mucous membrane of
lips and/or cheeks due to ectopic collection of sebaceous glands. These are
known as Fordyce’s granules

Fordyce’s granules

Pigmentation Related to RBCs:

RBCs:

Extravasation:
May be due to trauma, bleeding tendency or blood vessel
abnormality. Extravasated RBCs are red in colour then turn brown due to
degradation of Hb into hemosidrin (localized iron overload).
 -99-

Multiple areas of extravasated RBCs

(ecchymosis) in a patient with bleeding
tendency

Petechiae

Petechiae
A smaller than 1 cm diameter deposit of blood or blood pigments in
the extravascular tissues and visible through the skin or mucous membrane.

Ecchymosis
It is a discrete deposit of blood or blood pigments in the extravascular
tissues and visible through the surface of the skin or mucous membrane
which is greater than 1 cm in diameter.
 -100-

Abnormalities of hemoglobin
 Reduced hemoglobin- Heart and lung disease lead to increased
percentage of reduced hemoglobin in arterial blood with cyanosis
(bluish discoloration) of the skin and oral mucosa.
 Sulfhemoglobin- Irreversible combination of sulfonamides with
Hb leads to cyanosis that disappears only when the RBCs
containing the pigment are cleared from the circulation.
 Methemoglobin- Reversible oxidation of Hb forming a brown
color . It is caused by drugs such as nitrites and xylocaine.
 Carboxy hemoglobin- It is formed from inhalation of carbon
monoxide giving a cherry red color. The affinity of Hb to
combine with carbon monoxide is 200 times its affinity for oxygen

Jaundice
Yellow coloration of the sclera , skin and mucous membrane due to
an increase of the yellow pigment bilirubin in the blood & tissue fluid.

Etiology:
 Hemolytic jaundice: Excessive production of bilirubin due to
abnormally increased rate of destruction of RBCs.
 Hepatocellular Jaundice: e.g. Infective hepatitis with wide spread
damage of the liver.
 Extrahepatic (obstructive) Jaundice: Due to obstruction of the
bile duct system by gall stones or by carcinoma of the head of
pancreas.
 -101-

Yellow sclera Yellow color in gigiva

Hemangioma:
Vascular lesions presenting as proliferations of vascular channels are
tumor-like hamartomas. The hemangiomas of childhood are found on the
skin, in the scalp, and within the connective tissue of mucous membranes.
Approximately 85% of childhood-onset hemangiomas spontaneously
regress after puberty.
Depending on the depth of the vascular proliferation within the oral
submucosa the lesion may harbor vessels close to the overlying epithelium
and appear reddish blue or if a little deeper in the connective tissue, a deep
blue.
Most hemangiomas are raised and nodular, some may be flat,
macular and diffuse, particularly on the facial skin, where they are referred
to as port-wine stains. The port-wine hemangioma of facial skin may
concomitantly involve the oral mucosa, where the angioma may continue in
macular fashion or become tumefactive.
 -102-
Most oral hemangiomas are located on the tongue, where they are
multi-nodular and bluish red.
The lip mucosa is another common site for hemangiomas in children;
these tumors are usually localized, blue, and raised. Stain involves the facial
skin. When there is a concurrent history of seizures, the condition represents
encephalo-trigeminal angiomatosis (Sturge-Weber syndrome). Vascular
lesions occur in the brain as well as on the facial skin; skull radiography
may disclose vessel wall calcifications.
Microscopically, a hemangioma may comprise numerous large
dilated vascular channels lined by endothelial cells without a muscular coat;
such lesions are referred to as cavernous hemangiomas.
Patients who require treatment can undergo conventional surgery,
laser surgery, or cryosurgery. Larger lesions that extend into muscles are
more difficult to eradicate surgically, and sclerosing agents such as 1%
sodium tetradecyl sulfate may be administered by intralesional injection.

Hemangioma of the tongue Unilateral portwine stain of face,

(Sturge-Weber syndrome)
 -103-

Kaposi's Sarcoma:
A tumor of vascular origin, rarely encountered in the oral cavity prior
to 1983.
After 1983, oral KS became much more prevalent, being the most
common neoplastic process to accompany HIV infection. The mere
presence of KS lesions in HIV-seropositive subjects constitutes a diagnostic
sign for acquired immunodeficiency syndrome (AIDS).
 Multi-focal smooth, red raised neoplasm, characterized by
proliferation of blood vessels.
 Site: head, neck, tip of nose & intra-orally the palate is commonly
involved in AIDS patient.

Nose lesions Palate lesions

Microscopically, KS lesions show proliferating spindle cells with

mild pleomorphism associated with plump endothelial cells oriented about
small lumina. Erythrocytes is a prominent feature, and hemosiderin granules
are commonly encountered. The more hemosiderin present, the browner the
tumor will appear clinically. The pattern of growth in larger lesions is multi-
nodular .
 -104-
Treatment:
The early plaque or macular stage lesions are painless and do not
require treatment. Nodular lesions may become unsightly and interfere with
mastication; in this situation, therapy may be desirable. Electrocautery is
recommended, intralesional injection of 1% sodium tetradecyl sulfate will
result in necrosis of the tumor; however it is painful. Intralesional injection
of sclerosing agent can also help.

Hereditary Hemorrhagic Telangiectasia:

A genetically transmitted disease, inherited as an autosomal
dominant trait. There may be more than 100 such purple papules on the
vermilion and mucosal surfaces of the lips as well as on the tongue and
buccal mucosa. The facial skin and neck are also involved the nasal mucosa
will reveal similar lesions, and a past history of epistaxis may be a
complaint. Although the differential diagnosis should include petechial
hemorrhages with an attending platelet disorder, petechiae are macular
rather than popular and red or brown rather than purple. Furthermore, HHT
is genetic and should have been noticed in other family members. If any
doubt exists, platelet studies can be ordered to rule out a blood dyscrasia.
Microscopically, HHT shows numerous dilated vascular channels
with some degree of erythrocyte extravasation around the dilated vessels.
There is no treatment for the disease if the patient would like to have
the telangiectatic areas removed for cosmetic reasons, the papules can be
cauterized by electrocautery.
 -105-

Varix

Pathologic dilatation of veins and venules is known as varices or

varicosities .The chief site of involvement in the oral cavity is the ventral
aspect of the tongue where they appear as tortuous blue , red and purple
elevations . They are painless , not subject to rupture and of no clinical
significance .They represent a degenerative change in the adventitia of
venous walls as a result of aging .

Tongue varicosities Varicose veins in the buccal mucosa

Exogenous Pigmentations
 Black hairy tongue
 Tattoo: Amalgam, graphite tattoo.
 Metallic intoxication: lead, mercury, bismuth.
 -106-

Black Hairy Tongue:

Hairy tongue is a relatively common condition of unknown etiology.
The lesion involves the dorsum, particularly the middle and posterior one-
third. Rarely are children affected. The papillae are elongated, sometimes
markedly so, and have the appearance of hairs. The hyperplastic papillae
then become pigmented by the colonization of chromogenic bacteria, which
can impart a variety of colors ranging from green to brown to black.
Various foods, particularly coffee and tea, probably contribute to the diffuse
coloration.
Treatment consists of having the patient brush the tongue and avoid
tea and coffee for a few weeks.

Black Hairy Tongue

Amalgam Tattoo:
Etiology
Amalgam tattoo is due to iatrogenic factors. For example:
 Dentist’s bur loaded with small fragment of amalgam
particles that accumulate during removal of amalgam may
accidentally introduce the metal flecks into the oral mucosa.
 -107-
 Metal particles may fall unnoticed into extraction socket.

Clinical Features
Grey or black macule on gingiva, palate or buccal mucosa.

Management:
Amalgam tattoo is not harmful so its removal is not required.
Biopsy is necessary if the lesion arises at areas distant from any
restoration to exclude melanoma

Amalgam tattoo beside a large Amalgam tattoo due to scratching

proximal restoration the buccal mucosa with a bur laden
with amalgam paticles

Graphite Tattoo:
 It is due to traumatic implantation of graphite from lead
pencil, commonly seen on palate.
 The patient may not recall the injury since the event usually
occurs during grade school.
 -108-
Metallic Intoxication:
High levels of heavy metals or metal salts may result in metallic
intoxication. The exposure of the body to heavy metals may be either:
 Occupational hazard: as workers in lead factories.
 Therapeutic hazard: as certain drugs, that contain salts
of heavy metals (bismuth, gold, mercury).
Clinical Features
1) Systemic symptoms of toxicity including:
 Behavioral changes (eg. Irritability & suicidal attempts in
mercurialism).
 Intestinal pain.
 Neurological disorder (eg hand & foot drop in lead
intoxication , tremors in mercurialism).
 Haematologic disorder (eg. Stippling of RBCs in lead
intoxication).
2) Oral Features:
Oral manifestations of heavy metal intoxication may include
metallic taste, change in the salivary flow (increase or decrease) ,
however, the most common feature is the metallic line formed on the
marginal gingiva :
Grey to black pigmentation that outlines the gingiva like
“eyeliner”. The heavy metal tends to extravasate from vessels in foci of
increased vascular permeability such as inflamed tissue. Thus the free
marginal gingiva is the most commonly affected site.
 -109-

Metallic line formed on the marginal gingiva

Bismuth

This metal was used in the past for the treatment of syphilis. The oral
manifestation is characterized by a narrow blue black line of pigmentation
along the gingival margin ("bismuth line") and gingivostomatitis with
symptoms resembling that of acute necrotizing gingivostomatitis.

Lead

Exposure to lead leads to a condition called "plumbism" or "saturnism".

Exposure may occur through paints, cooking vessels, containers, ointments,
illicit liquor manufactured in car radiators, and tetraethyl lead used as an
antiknock agent in gasoline. Lead has an affinity to the central and
peripheral nervous system. In acute poisoning, demyelination and axonal
degeneration of the nerves occur. Another effect of lead is lead
encephalopathy leading to mental retardation and cerebral palsy. Oral
manifestations are metallic taste, excessive salivation, dysphagia, and a
gray-black line ("lead line") along the gingival margin.

Mercury

Mercurialism (ptyalism) develops due to occupational exposure or

usage of drugs containing mercury. Oral manifestations of mercurialism are
 -110-
increase in flow of thick saliva, metallic taste, and itching sensation of the
mouth. There may be cracking or swelling of the lips and oral ulcerations.

Ingestion of mercurial compounds by children leads to a condition

called acrodynia (Pink's disease). Characterized by peeling of skin, patchy
loss of hair, pruritic maculopapular rashes, severe sweating, irritability,
photophobia with lacrimation, hypertension, insomnia, and gastrointestinal
upset.

Both mercurialism and acrodynia may be accompanied by periosteitis

and loss of alveolar bone leading to teeth mobility and loss .

Mercury intoxication

Silver

Silver pigmentation leads to a condition called argyria. It is

characterized by discoloration of the skin and mucous membrane due to
silver compounds. The skin may turn gray in colour or become cyanotic.
Patient may be very ill.
 -111-
Gold

Gold salts are used in the treatment of rheumatoid arthritis and in some
dermatologic lesions. Inflammation of skin and mucous membrane is a
common feature of toxic reaction.

Arsenic

Arzenism usually occurs due to industrial exposure or poisoning.

Chronic gastritis and colitis are the common clinical symptoms. There may
also be keratosis of the palms and hands, dermatitis, pigmentation, and
ulcerations.

Phosphorus

Phosphorus poisoning leads to periostitis and osteomyelitis of the jaws,

especially the mandible ("phossy jaw")
 -112-

TERMINOLOGY IN ORAL MEDICINE

Clinical Terms:
Symptom

It is defined as any change in the body or its function which is perceptible to

the patient and may indicate a disease.

Sign

It is defined as any change in the body or its function which is perceptible to

a trained observer and may indicate a specific disease.

Tumour

It refers to any swelling affecting organs or tissues of the body due to

reactive, inflammatory, infectious, or neoplastic process.

Hypertrophy

It is an increase in the size of the cells and, with such a change, an increase
in the size of the organ or tissue.

Hyperplasia

It is an increase in the number of the cells in an organ or tissue, which may

then have increased volume.

Oedema

It is the accumulation of excess fluid in the intercellular (interstitial) tissue

spaces or body cavities.

Neoplasm
 -113-
It is an independent uncoordinated new growth of tissue of tissue
potentially capable of unlimited proliferation.

Nodule

It is a solid elevated lesion, varying in size from 0.5 mm to 2 cm. usually

deep seated and involving the lower dermis and subcutaneous fat.

Inflammation

It is defined as the reaction of vascularized living tissue to local injury.

Haematoma

It is a large clot resulting from blood released into the tissue from a ruptured
or injured blood vessel.

Weal

It is an evanescent, oedematous, usually more or less sharply circumscribed

and slightly elevated superficial lesion which appears and disappears
relatively rapidly without leaving permanent changes.

Telangiectasis

It is a condition where there is a visible dilation of the superficial blood

vessel.

Poikiloderma

Refers to a combination of atrophy, telangiectasia, and pigmentary changes,

e.g., radiation dermatitis.

Purpura

Reddish to purple flat lesion caused by extravasation of blood from vessels

into subcutaneous tissues.
 -114-

Petechiae

A smaller than 1 cm diameter deposit of blood or blood pigments in the

extravascular tissues and visible through the skin or mucous membrane.

Ecchymosis

It is a discrete deposite of blood or blood pigments in the extravascular

tissues and visible through the surface of the skin or mucous membrane
which is greater than 1 cm in diameter.

Cyanosis

Increase in the deoxygenated haemoglobin of blood

Embolus

An embolus is a detached intravascular solid, liquid or gaseous mass that is

carried by the blood to a site distant from its point of origin.

Infarction

An infarct is a localized area of ischaemic necrosis in an organ or tissue

resulting from a sudden reduction of either its aterial supply or venous
drainage.

Shock

It is a state of inadequate perfusion of all cells and tissues, which at first

leads to reversible hypoxic injury, but it sufficiently protracted or grave, to
irreversible cell and organ injury and sometimes to the death of the patient.

Necrosis
 -115-
Necrosis is the sum of the morphologic changes that follow cell death in a
living tissue or organ.

Healing

Healing is the repair and replacement of dead or damaged cells by healthy

cells.

Regeneration

Replacement of injured tissue by parenchymal cells of the same type.

Granulation tissue

It is the reparative tissue that is formed on the surface of wounds having

pink, soft granular appearance showing histologically new small blood
vessels and fibroblasts.

Macule

A macule is a circumscribed non-raised area of altered colouration varying

in size from a pinhead to several centimeters, e.g., petechiae, melanin
deposits in addison's disease.

Papule

A papule is a small circumscribed solid elevated area, varying in size from a

pinhead to 5 mm. in surface contour either flat; conical; pointed; circular; or
umblicated, in colour either red, yellow, white or violacious, and in shape
either round or polygonal, e.g., fordyce's granules.

Vesicle

A vesicle is a small circumscribed elevated lesion, varying in size from 2 to

5 mm, with an overlying thin surface, containing an accumulation of fluid
(serum, plasma, or blood).
 -116-
Bulla

It is a large vesicular type of lesion, ranging in size from 0.5 to several

centimeters. eg., pemphigus.

Pustule

It is a vesicular lesion containing purulent material instead of clear fluid,

e.g., pyostomatitis

Crust

Dry products of exudation from lesions occurring on the skin and lips, e.g.,
erythema multiforme.

Burrows

Burrows are short, linear, straight or sinuous lines in the skin, e.g., scabies.

Scale:
Loosened imperfectly cornified parakeratotic superficial layer of skin that is
shed as fine, brawny, dirty white, yellowish keratinous dust or large pearly
white flakes, eg. Psoriasis.

Sinus:
It is a blind tract which connects a cavity lined by granulation tissue to the
epithelial surface.

Fistula:
It is an abnormal condition where there is connection between two
epithelium lined surfaces or organs, e.g. oroantral fistula.

Fistula is often lined by granulation tissue, but it can be epithelialized .

 -117-
Parulis:
It is a mass of granulation tissue which covers the opening of a sinus.

Plaque:
A plaque is a small or large, raised, firm, clearly demarcated area of gray or
white colouration, e.g. leukoplakia.

Erosion:
An erosion is a shallow defect in mucosa representing loss of epithelium
down to but not involving the stratum basale, e.g. erosive lichen planus.

Ulcer:
An ulcer is a defect or break in the continuity of the epithelial component of
skin or mucosa, so that a depression or punched out area exists with
exposure of the underlying connective tissue.

Fissure:
It is a linear, often crusted, tender, painful defect in continuity of the skin,
occurring usually at the mucocutaneous junctions and at sites where there is
considerable elasticity of the skin, e.g. angular cheilitis.

Naevus:
Circumscribed new growth of skin or oral mucosa of congenital origin,
presenting as small, elevated, or flat pigmented lesion.

Pus:
 -118-
It is a liquid usually yellowish in colour formed in certain infections and
composed of tissue fluid containing bacteria and leukocytes.

Pyemia:
It is the presence in the circulation, of infected thrombus which is carried to
various organs where it produces metastatic abscesses or septic infarcts.

Abscess:
It is a localized accumulation of purulent material in the dermis or
subcutaneous tissue, e.g , periapical abscess.

Cellulitis:
Refers to pus tracking through tissue spaces and fascial planes containing
loose subcutaneous tissue, e.g. Ludwig’s angina

Premalignant lesion:
It is a morphologically altered tissue in which cancer is more likely to occur
than its apparently normal counterpart, e.g. leukoplakia.

Premaligant condition:
It is a generalized state associated with a significantly increased risk of
cancer, e.g. oral submucous fibrosis

Leukoplakia:
It is a white patch which can not be removed by scraping and can not be
attributed to any other diagnosable disease.

White lesion:
 -119-
It is a non-specific term used to describe any abnormal area of the oral
mucosa that on clinical examination appears whiter than the surrounding
tissue and is usually slightly raised, roughened, or otherwise of different
texture form adjacent normal tissue.

Keratotic white lesion:

Keratotic white lesions are those lesions which resist rubbing or scraping ,
e.g. leukoplakia.

Non-keratotic white lesion:

Non-keratotic white lesions are those which can be removed by rubbing or
scraping, often leaving raw bleeding surface, e.g. candidiasis.

Hamartoma:
Hamartomas are tumour-like malformations characterized by the presence
of particular histologic tissue in improper proportions or distribution, with a
prominent excess of one type of tissue, e.g. Haemangioma.

Teratoma:
It is a true neoplasm made up of a number of different types of tissue which
are not native to the area in which the tumour occurs, e.g. teratoma of
ovary, which may contain teeth.

Choristoma:
Choristoma refers to microscopically normal cells that are present in
abnormal locations, eg. Rest of pancreatic tissue found in the wall of the
stomach.

Calcification:
 -120-
Deposition of calcium and phosphate ions in tissues in an amorphous and
unorganized manner.

Dystrophic calcification:
Pathologic calcification that occurs in degenerating and dead tissue.

Metastatic calcification:
Precipitation of minerals into normal tissue as a result of higher than normal
levels of ions in the insinuating fluids.

Calcinosis:
Development of calcareous concretions in the subcutaneous and
deepconnective tissue.

Heterotrophic ossification:
Deposition of minerals as organized, well formed bone.

Attrition:
It the physiologic wearing away of tooth material as a result of tooth to
tooth contact.

Abrasion:
It is the pathological wearing away of tooth substance due to some
abnormal mechanical process.

Erosion (Teeth):
It is the loss of tooth substance due to a chemical process that does not
involve bacterial activity.

Aplasia or Agenesis:
 -121-
It is the complete failure of formation of an organ or tissue, e.g. aplasia of
teeth in complete anodontia.

Hypoplasia:
It is the failure of full development of an oragn or tissue, e.g. hypoplasia of
teeth.
 -122-
Atrophy:
It is the disappearance or wasting of tissues or parts of tissues, e.g. atrophy
of lingual papillae.

Histological terms:

Anaplasia:
It is the reversion of the same type of cells from a more highly
differentiated to a less highly differentiated (or more embryonic) type.

Metaplasia:
Metaplasia is a reversible change in which one adult cell type (epithelial or
mesenchymal) is replaced by another adult cell type, e.g. squamous
metaplasia of respiratory epithelium in the bronchioles.

Dysplasia:
Dysplasia is irregular, atypical proliferative change in response to chronic
irritation or inflammation involving epithelial or mesenchymal cells,
principally the former.

Epithelial atypia:
Changes in individual cells in those mucosal lesions that may in time
become malignant are termed epithelial atypia.

Hyperkeratosis:
This condition is characterized by widening or thickening of stratum
corneum.
 -123-
Parakeratosis:
This condition is characterized by widening or thickening of the stratum
corneum in which there is persistence of the nuclei.

Acanthosis:
This condition is characterized by widening and thickening of stratum
spinosum.

Acantholysis:
It refers to separation of cells in the stratum spinosum so that an
intraepithelial split occurs which leads to the formation of an intraepithelial
vesicle.

Dyskeratosis:
This lesion shows abnormal orientation or development of epithelial cells.

Spongiosis:
This term is used to signify intercellular oedema of the epithelium, in which
intercellular bridges of the stratum spinosum become more prominent.

Hydropic degeneration:
It refers to replacement of the nuclei of stratum basale by clear spaces due
to oedema and degeneration of cells.

Ballooning degeneration:
It is characterized by the isolation of a cell from its neighbours, especially
in the lower layers of the epidermis, the withdrawing of its prickles after
 -124-
intracytoplasmic oedema and vacuolization, and the amitotic division of its
nucleus so as to form multinucleated giant cells.

Liquefaction Degeneration:
It refers to obliteration of the line of demarcation of epidermis and dermis
by oedema of the basal cells and subepidermal dermis as well as by the
presence of inflammatory cells at the junction.

Pseudoepitheliomatous Hyperplasia:
In this condition, the retepegs extend far downward, usually accompanied
by acanthosis. The cells are normal in size, shape and chromaticity.

Vascularity:
Increase in the number of capillaries and their engorgement with
erythrocytes.
 White Mucosal Lesions

• Nonpainful • Painful • Nonpainful

• Rough • Rough • Smooth
• Opaque • Opaque • Translucent
• Do not rub off • Rub off • Do not rub off

Surface thickening Surface material Subepithelial change

(see later)

• Curdy, white • Ragged, delicate • Delicate, • Buccal mucosa • Hx of surgery • Hx of betel nut
• Diffuse appearance grainy • Multiple, or other use
• Vague borders • Focal pseudomem- bilateral trauma at • Asian culture
Poor oral hygiene brane • Yellowish location • Limitation of
• • Sharp borders
Diminished host • May be an • Asymptomatic • Asymptomatic tissue movement
• • History of cause
resistance indication of • Static • Static • Progresses
• Heals
• Regresses with cause • Adults
treatment

Fordyce Submucous fibrosis

Pseudomembranous Ulcer (see SCAR
Chemical burn granules
candidiasis ulcerative lesions)

Differential diagnosis of mucosal white lesions characterized by surface material

or submucosal changes [Coleman and Nelson, 1993]

125
 Multiple and Diffuse Red Oral Lesions

Multiple Diffuse

Blanching No blanching

• Small • Linear • Soft palate • Denture or • Tongue • May be enlarged

• Rounded • Ventral tongue • Additional oral habit • Asymptomatic • History of risk
• Located on skin • Asymptomatic lesions • Palate • No bleeding for HIV
• Bleeding • Not prone to (skin) • No tendency infection
• Familial bleeding • Hemorrhage additional • Atrophic (no • Opportunistic
• Older patient tendency lesions papillae) infections
• Anemia • No bleeding • Location • Hairy
• Hx of tendency changes leukoplakia
Hereditary medications, • White, annular • Recurring lung
Lingual varices systemic border infections
Hemorrhagic
Telangiectasia disease, etc, • Weight loss

Bleeding Pressure Benign migratory Kaposi’s

diathesis ecchymosis glossitis sarcoma

Tongue Oropharynx Any area

• Strawberry • Variably • History of • Decreased host

• Atrophic (no
or atrophic painful contact with a resistance
papillae)
tongue new material • Painful
• Burning • History of
• Pharyngitis infectious • Recent onset • White lesions in
• Deficient diet
• Systemic contact • Sore or areas
or absorption
symptoms • Very diffuse burning • Poor oral
• Systemic
• Children • Variable • History of hygiene
findings
systemic other allergic
• Skin rash
symptoms sensitivity

Nutritional
Nonspecific Contact Atrophic
deficiency or Scarlet fever
pharyngitis mucositis candidiasis
anemia

Differential diagnosis of mucosal red lesions [Coleman and Nelson, 1993]

126
 Mucosal Ulcers

Acute onset limited Gradual onset protracted

clinical course clinical course

• Isolated • Multiple • Multiple • Multiple • Multiple • Multiple or

lesions lesions lesions lesions diffuse lesions
• Acute onset
• Vesicles early • Vesicles or • May see • Ulcers or • Tissue
• Short vesicles early
• Acute onset bullae erosions
duration destruction or
• Short duration • Onset in • Acute onset • Gradual onset
(healing) enlargement
(healing) infancy • Recurrence or
• No systemic • Chronic course • Variable onset
• Systemic • Healing and persistence
features recurrence • Progress • Chronic course
features are • Short duration
prominent • May be (change but do • Progress (do
(healing)
(fever, malaise, familial not heal) not heal)
• Systemic
etc.) • May be fatal features absent
• Skin lesions • Systemic
or less may be present features (late)
prominent
Trauma or Generalized
bacterial viral infections
infections
Genetic skin Recurrent viral or Diseases characterized
Autoimmune
diseases idiopathic by tissue destruction
diseases
conditions e.g malignant, T.B.,
Noma

History suggesting toxic medications, severe systemic disease,

immune deficiency, or other compromised condition

Many conditions can produce ulcers or vesicles as a manifestation of physiologic

stress or a toxic state. Severe fever and advanced uremia are examples. In addition,
several conditions described as atrophic red lesions can also produce ulcers when
severe such as contact hypersensitivity, candidiasis, and nutritional deficiencies.

Initial differential diagnosis of oral ulcers [Coleman and Nelson, 1993]

127
 Recurrent Ulcerative Lesions Caused by
Genetic, Infectious, or Idiopathic Conditions

• Multiple lesions
• Vesicles and /or ulcers
• Acute onset with eventual healing
• Chronic or recurrent course
• Systemic features are absent or less prominent

• Muliple lesions • Multiple oral ulcers

• Vesicles or with fibrinous Vesicles early
bullae pseudomembrane Multiple, clustered lesions • Maculopapular
• Onset in infancy and erythematous skin rash
• May be familial halo • Membranous
incidence • Only ulcers (mucous
nonkeratinized patches) of oral
• May be fatal
surfaces affected • Painful • Very painful mucosa
• Rare
• Ulcers are painful • Vesicles leading • Vesicles leading • History of
• No vesicles to ulceration to ulcers chancre 2-10
• Lesions heal within • Only of surfaces • Unilateral in the weeks prior to
a week to 10 days that are distribution of a onset
without scars keratinized (lip, nerve trunk • Regresses 1-2
• Recurrence palate, gingival) • Skin lesions are months later
• Very common • 1-2 weeks common, oral • Occurrence
duration lesions are rare increasing still
• Recurrence • One month uncommon
• Very common duration or more
• Single
Epidermolysis occurrence
bullosa • Unusual in the
mouth Secondary syphilis
Minor aphthous
stomatitis
Secondary herpes
simplex infection CNS and /or
Herpes zoster cardiovascular
degeneration years later
Additional features
(rare)

• Larger, deeper • Painful oral • Painless oral Tertiary syphilis

aphthous ulcers aphthous ulcers aphthous ulcers
• Heal with • Eye lesions • Eye lesions
scarring • Genital ulcers • Urethritis
• Lesions last for • Recurrent • Arthritis
weeks lesions • 30 y/o men
• Lesions almost • Protracted • months duration
always present course • Occasional
recurrence

Major aphthous Behcet’s syndrome Reiter’s syndrome

stomatitis

Differential diagnosis of recurring oral ulcers [Coleman and Nelson, 1993]

128
 Ulcerative Lesions
Caused by Autoimmune Mechanisms

• Multiple lesions
• Ulcers or erosions
• Gradual onset
• Chronic course
• Progress (change but do not heal)
• Skin lesions may be present

• Multiple, painful • Multiple, painful oral • Painful, erythematous oral

oral ulcers ulcers of the buccal • Oral ulcers are
ulcers
mucosa, lip, and/or unusual
• Ulcers persist, often • Gingival typical site
without healing gingival • Bullae leading
• Lesions heal, then recur
• Lesions may exhibit a to ulcers of the
• Nikolsky’s sign • Nikolsky’s sign
white, raised border skin
• Skin lesions usually • Skin lesions are unusual
• Skin lesions are the • Chronic course
present • Eye and genital lesions
typical finding • Elderly people
• Middle to older age may be present
group • May progress in severity • Remissions are
• Middle age or older
• Seldom regresses common
• Progresses to death females
without treatment • Middle age • Seldom leads to
• Remissions are unusual
death
• Seldom leads to death • Seldom leads to death

Bullous
Pemphigus Cicatricial Discoid lupus
pemphigoid
vulgaris pemphigoid erythematosus

Degenerative disease of a major

organ system (kidney, heart,
Systemic lupus etc.) Butterfly facial rash poor
erythematosus extended prognosis

Differential diagnosis of oral ulcers caused by autoimmune diseases [Coleman and Nelson, 1993]

129
 Oral Ulcers

Acute course Protracted or

Recurrent course

Genetic skin diseases

• Isolated • Multiple lesions
• Acute onset • Vesicles early
Autoimmune disease
• Short duration (heal) • Acute onset
• No systemic features • Short duration (heal)
• Systemic features apparent Recurring ulcerative conditions
(fever, malaise, etc.)

• Painful • Nonpainful Destructive oral ulcers

• Obvious cause • Supportive history

Systemic viral
Traumatic • Suppuration Primary syphilis
ulcer (chancre) infections
• Swelling
• Probable
cause

Non specific bacterial infection

• Vesicles • Koplik’s spots • Few oral • Vesicles, ulcers • Vesicles (rare) • Oral ulcers
precede oral (erythematous vesicles, of soft palate or petechiae • Multiple skin
ulcers macules with ulcers • Pharyngitis (common) of lesions
• Affects white centers of • Pruritic skin • Mild fever, the soft palate • Painful
gingiva the buccal vesicular, malaise • Malaise, • Sudden onset
• Painful mucosa) pustular • Children pharyngitis • May exhibit
• Fever and • Fever, malaise, lesions • Mild course • Lymphadenop mild fever,
malaise skin rash • Fever, within a week athy lymphadenopath
• May have • Children malaise early • Protracted y
skin lesions • Epidemic • Children course • Triggered by
• Children • Resolves in 2 • Epidemic • Young adults infections or
Herpangina
under 5 weeks • 2-3 week drugs
• Resolves in course • Limited course
2 weeks, • Young adults
Rubeola • History of contact Mono-Spot • Nonviral, but
(measles) • High-risk lifestyle test clinical course
• HIV test may suggest
Primary herpetic Varicella
viral infection
gingivostomatitis (chicken pox)
Infectious
HIV prodromal mononucleosis
infection (common)
(occurrence) Erythema
multiforme

Severe
Stevens-Johnson
features
syndrome

Differential diagnosis of acute oral ulcers [Coleman and Nelson, 1993]

130
 -131-
References:
Coleman G.C. & Nelson J.F.: Principles of oral diagnosis, Mosby, 1993.

Cawson, R.A & Odell E.W: Cawson’s Essentials of oral pathology & oral
medicine , 7th edition, Churchill Livingstone, 2002.

Pramod J.R.: Essentials of oral medicine, Jaypee, 2003.

Wood N.K & Goaz P.W: Differnetial diagnosis of oral and maxillofacial
lesions, 5th edition, Mosby, 2006.

Greenberg M.S. and Glick M.: Burket’s Oral Medicine. Diagnosis and
treatment , 10th edition, BC Decker Inc, 2003.

Champion R.H., Burton J.L., Burnsr D.A., Breathnach S.M.:

Rook/Wilkinson/Ebling. Textbook of Dermatology. 6th edition. Blackwell
science, 1998.

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