VESICULO-BULLOUS

LESIONS OF ORAL
CAVITY
Resource faculties:
Dr. Jyotsna Rimal Presenter:
Additional Professor and HOD Abhinaya luitel
Dr. Iccha Kumar Maharjan
JR 1I
Associate Professor
Department of Oral Medicine and Radiology
1
 2
• Definition
• General features of vesiculo-bullous lesions
• Classifications
CONTENTS

• Structure of an epithelium.
• Structure of dermo-epidermal junction.
• Causes
• Individual lesions
• Summary
• Conclusion
• References
 3
DEFINITION

• Vesicle (vesicule, vesicula): elevated blisters containing clear fluid

that are under 1 cm in diameter.

• Bullae: elevated blisters containing clear fluid that are over 1 cm in

diameter.
 4
GENERAL FEATURES OF VESICULO-BULLOUS
LESIONS

• Vesicular lesions are more common, compared to bullous lesions.

• Most vesicular lesions are infectious in nature and present
constitutional symptoms.
• Some bullous lesions can be lethal.
• Most bullous lesion involve both skin and mucous membrane.
• Vesiculo-bullous lesions may appear singularly or in clusters.
 5
• Fluid filled lesions may be intra-epithelial or sub-epithelial in location.
• Small multiple vesicles often coalesce to form bullae.
• Generally vesiculo-bullous lesions are short lived.
• Vesiculo-bullous lesions rupture to leave erosive, ulcerative or
desquamative areas.
• Most vesiculo-bullous lesions are painful after rupture.
 CLASSIFICATION: CLINICAL
PRESENTATION
Predominantly (not exclusively)
vesicular lesions:
• Herpes simplex virus (HSV) infection
(primary herpetic gingiva-stomatitis)
• Varicella (chicken pox)
• Herpes zoster (shingles)
• Hand, foot and mouth disease
• Herpangina
• Dermatitis herpeteformis
6
 Predominantly (not exclusively)
bullous lesions:
• Pemphigus vulgaris
• Bullous pemphigoid
• Benign mucous membrane
pemphigoid
• Bullous lichen planus
• Erythema multiforme and Steven
Johnson syndrome (SJS)
• Bullous impetigo
• Epidermolysis bullosa
• Linear immunoglobulin A disease
(LAD)
 7
HISTOPATHOLOGY
Intra-epithelial vesiculo-bullous  Sub-epithelial vesiculo-
lesions bullous lesions

• HSV infection • Bullous pemphigoid

• Varicella infection • Cicatricial pemphigoid

• Hand, foot and mouth disease • Epidermolysis bullosa

• Pemphigus • Dermal erythema multiforme

• Epidermolysis bullosa • Dermatitis herpeteformis

• Mucoasal erythema multiforme • LAD

• Angina Bullosa Hemorrhagica
 DURATION 8

Acute:  Chronic:
• HSV infection
• Chicken pox • Pemphigus
• Herpes zoster • Bullous pemphigoid
• Herpangina • Cicatricial
• Hand, foot and mouth pemphigoid
disease
• Bullous lichen planus
• Erythema multiforme
• LAD
 9
STRUCTURE OF AN EPITHELIUM

1- Filaments.
2- Desmosome.
3- Hemidesmosome.
4- Basal cell layer
 10
STRUCTURE OF DERMO-EPIDERMAL JUNCTION
 11
CAUSES
 12
PRIMARY HERPES SIMPLEX INFECTION

• Patient do not have immunity due to previous contact with virus.

• Intimate contact with individual who has active or recurrent HSV
lesions.
Herpein; to creep or crawl
• Asymptomatic shedders in saliva secretions.
Coined: Hippocrates, 400
BC
• Majority caused by HSV 1
• Incidence of primary HSV infection vary according to socioeconomic
group.
 • Intraoral: 13

• Clinical features
• Common in children
• Incubation period: 5-7 days
• Negative past history of
herpes
• Prodrome: fever, headache,
malaise, myalgia, nausea, • Inflamed posterior pharyngeal wall
vomiting • Lymph node: submandibular, cervical
nodes palpable and tender
 14
Recrudescent oral HSV infection:
• 8-10% of patient following dental treatment
• Usually systemic signs and symptoms not present
• Triggers: fever, UV radiation, trauma, stress,
menstruation
• Prodrome: itching, tingling, burning
• Papules, vesicles, ulcers, crusting, resolution
• Intraoral: hard palate, attached gingiva, dorsum tongue
 15
HSV in immunocompromised patients:
• Patient under chemotherapy, organ transplantation, AIDS
• Atypical appearing ulcer that may be several centimeter in
size
• Lasts for weeks or months if undiagnosed or untreated.
• Presence of satellite ulcers.
 16
Extraoral lesions:
• Herpetic whitlow: May occur during treatment of infected patient.

Stern and
collaborators, 1959

• Herpetic gladiatorum: Mat herpes, skin lesions.

Shelling and Kibrick,

1964
 17
Differential diagnosis:
• Coxsackievirus infections, hand-foot-and-mouth disease
(ulcers are not clustered and gingiva not involved)
• Necrotising ulcerative gingivitis (widespread and diffuse rather
than localized)

• Recurrent apthous ulcer (history)

• Traumatic ulcer (history)
• CMV infection, fungal infection, neutropenia (biopsy, culture
and blood test)
Investigations 18

• Cytology: Wright, Giemsa (Tzanck preparation),

Papanicolaou stain for multinucleated giant
cells, intra-nuclear inclusions, syncytium or
ballooning degeneration 3M

• Viral isolation: isolation and neutralization of

virus in tissue culture.
 19
• Antibody titer: initially elevated IgG, several weeks later IgM titre
(seroconversion).

• Polymerase chain reaction (PCR): most sensitive method, does not

require viable virus or infected cells for detection. Also, real-time
detection allows for PCR to be carried out promptly, and it may be used
to discriminate HSV types. Detection of viral DNA by PCR is considered
the test of choice for HSV diagnosis
 20

• Management: pain control, supportive care, definitive treatment

Anesthetics: Mucopain,
Deltagel, Zytee
Analgesics: Tantum, Zuben,
Topical: 5% acyclovir, 3%
penciclovir cream 3-6 times/
day
10% Docosanol cream,
5times/day for 10 days
 21

a US Food and drug administration treatment recommendations

b Recommendations from the centers for disease control and
prevention
22
 23

VZV (CHICKEN POX)

• Primary infection with VZV

• Becomes latent in dorsal root ganglia of cranial nerves.
• Reactivation causes herpes zoster infection (HZI), (shingles)
• The incidence of HZI increases with age and the degree of
immunosuppression.
1888, Von Bokay: relation between VZV and
HZV
1954, Weller: VZV isolated from vesicular fluid of
chicken pox and HZI
 24

Clinical features:
• Common in first two decade
• Incubation period: 2-3 weeks
• Prodromal symptoms: fever, headache, chills, malaise
• Lesion begin in trunk and face and spread centrifugally
• Pruritic maculopapular rash followed by “dew-drop” like vesicles.
• vesicles turn cloudy and pustular, burst, and scab, with the crusts
falling off after 1 to 2 weeks
 25
Orofacial manifestations:
• Primary VZV presents as minor acute
ulcers.
• Recurrent VZV:
• V1: herpes zoster opthalmicus,
• V2: midface and upper lip
• V3: lower face and lower lips
 26
 Extraoral :

• HZI (shingles)

• Prodromal symptoms

• Crops of vesicles in dermatomal, “zosteriform

pattern”

• Heal in 2-4 weeks.

• Zoster sine eruptione or zoster sine herpete: no

dermatomal lesions.
Complications: 27
VZV
• Cerebellar ataxia,
encephalitis, pneumonia,
myocarditis, hepatitis
HZI
• Post herpetic neuralgia,
acute retinal necrosis
• Ramsay hunt syndrome,
type 2 Neurologist, James Ramsay
Hunt
 28

Differential diagnosis:
• Pulpitis (pain at prodromal symptoms, before appearance of vesicles)
• HSV (culture)
• Acute Necrotising ulcerative periodontitis (involvement)
• Osteoradionecrosis (history of exposure to radiation and
bisphosphonate)
 29

Investigations:
• Cytology: smear with stanadard laboratory stain for multinucleated
giant cells. Direct fluorescent antibody testing.
• Viral isolation: viral culture stands the gold-standard
• Antibody titer: zoster sine eruption
• PCR
30
 31

KRB, SSE. Postherpetic

neuralgia-pathogenesis,
treatment, and prevention. N
Engl J Med. 1996 Jul
4;335(1):32-42
 32
Management: pain control, adequate hydration, supportive care,
definitive treatment

Anesthetics: Mucopain,
Deltagel, Zytee
Analgesics: Tantum, Zuben,
Topical: 5% acyclovir, 3%
penciclovir cream 3-6 times/
day
10% Docosanol cream,
5times/day for 10 days
 33
Varicella zoster: As described for herpes simplex

Stoopler ET, Greenberg MS. Update on herpesvirus infections. Dent Clin North Am
2003;47(3):517–32.
Stoopler ET. Oral herpetic infections (HSV 1-8). Dent Clin North Am 2005;49(1): 15–29,
vii.
Cohen JI. Clinical practice: herpes zoster. N Engl J Med 2013;369(3):255–63.
 34

Seth JS, , Michael D, Deborah P, Management of Herpes Zoster (Shingles) and Postherpetic
Neuralgia. Am Fam Physician. 2000 Apr 15;61(8):2437-2444.
 35
HAND, FOOT AND MOUTH DISEASE

• Coxsackie virus (CV) A 16, Enterovirus (EV) 71

• C VA4–7, C VA9, C VA10, CVA24, C VB2, and C VB5, Echovirus 18,
have also been implicated
• HFM disease, as with many CV infections, including herpangina, tends
to be seasonal (usually summer), occurs in epidemic clusters with high
transmission rates.
• Associated with severe central nervous system disease (such as
meningitis and brainstem encephalitis), paralysis, pulmonary edema,
and death
Clinical features: 36

• Usually afflicts children younger than 10 years in

summer.
• low-grade fever and sore mouth
• 75 to 100% of patients have a skin rash,
especially on the hands and feet (dorsal, palms
and soles) and 30% on the buttocks.
• The rash is first red and macular and then
becomes vesicular
Intra-oral: 37
• Sore mouth and throat.
• Begin as erythematous macules that become vesicles and quickly
break down to ulcers.
• Usually located on the tongue, hard and soft palate, and buccal
mucosa
 38
HERPANGINA

• Herpangina derives from Herpes, meaning “Vesicular eruption,” and

Angina, meaning “Inflammation of the throat.”
• CVA (serotypes 1–10, 16, and 22) are the most common viruses
isolated from this disease.
• C VB1–5, echoviruses, and E V71 have also been identified in this
condition
 Intra-oral: 39
• Sore throat and pain on swallowing.
Clinical features:
• Erythema of the oropharynx, soft palate,
• Under 10 are usually
and tonsillar pillars.
afflicted
• Small vesicles form, rapidly break down
• Outbreaks as epidemics
to 2 to 4 mm ulcers, persist for 5 to 10
in summer.
days
• Fever, headache, and
• Lymphonodular pharyngitis, a variant of
myalgia that usually last
herpangina is associated with C VA10.
only 1 to 3 days.
• Sore throat, diffuse small nodules in the
oropharynx
 40

Differential diagnosis:

• Primary HSV infection ( lesions on palms and soles and posterior oral cavity)
• Streptococcal throat infection (purulent exudates)
 41

Investigations:

• Viral culture: throat or faeces (CV A9, A16 grow readily), inoculation
into new born mice
• Antibody titer: serum IgM can be detected early on but is not serotype
specific
 42
• Skin biopsies: intraepidermal vesicles with a mixed lymphocytic and
neutrophilic infiltrate, degeneration of epidermal cells, and dermal edema.

• Eosinophilic nuclear inclusions and intracytoplasmic picornavirus

particles are seen in the surrounding dermal vessels.
• Lymphonodular pharyngitis shows hyperplastic lymphoid nodules
Cutaneous infection, Dermatology, Dermatopathology, Viral infections. Neil Coleman,
October 3, 2011
Management: 43
• CV infections are self-limiting (unless complications arise or the patient is
immunocompromised)
• Management is directed toward control of fever and mouth pain, supportive
care, and limiting contact with others to prevent spread of the infection.
• Ensure adequate fluid intake to prevent dehydration. Cold liquids are
generally preferable. Spicy or acidic substances may cause discomfort.
• Fever may be treated with antipyretics. Pain may be treated with standard
doses of acetaminophen or ibuprofen. Anesthetics may also be applied to
the oral cavity via mouthwashes or sprays
 44
• Keep the person or child cool. Remove clothes or use light cotton clothes or
bedding. Open windows or use a fan in the room where appropriate. Do not
cold-sponge a child who has a fever.
• If child goes to day care or school, talk to the staff about when your child
can return.
• Wash your hands frequently. It is especially important after you touch a
blister or change the diaper of an infected child.
• Don't let your child share toys or give kisses while he or she is infected.
• Effective antiviral agents for CV are not available

Center for disease control and prevention, 24/7, saving lives: protecting
people
1995-2015 Healthwise, Incorporated. Healthwise, Healthwise for every
health decision
 45
DERMATITIS HERPETEFORMIS 1884, L.A Duhring

• Occurs in 2nd to 3rd decade with male predilection

• Cutaneous manifestations of celiac disease.
• Pathology unclear: tissue transglutaminase appears as dominant
auto-antigen in intestine, skin and mucosa
• Gluten enteropathy can be severe in 2/3rd of patients
• Severe cases: dysphagia, weakness, diarrhea, weight loss
Clinical features: 46
• Bilateral symmetric pruritic papules, vesicles
primarily in extensor surface of extremities.
• Face and oral cavity, occasionally affected
• Clusters of vesicles or papules arise and resolve
followed by hyperpigmentation
• Intraorally painful ulcers preceded by collapse of
ephemeral vesicles or bullae.

Dermatitis herpetiformis, disease of teeth and oral cavity,

2004
 47
Differential diagnosis

• Bullous Pemphigoid (histopathology)

• Erythema Multiforme (acute, inflammatory)
• Linear Immunoglobulin A disease (histopathology)
 48
Investigations:
• Histopathology: focal aggregates of neutrophils and eosinophils
among deposits of fibrin at apices of dermal pegs

• Immunofluorescence: Direct immunofluorescence show IgA and C3 at

dermal papillary apices
Dermpedia.org
Treatment: 49
Gluten free diet
• Reduces the requirement for medication to control DH
• Improves associated gluten-sensitive enteropathy
• Enhances nutrition and bone density
• May reduce the risk of developing other autoimmune conditions
• May reduce the risk of intestinal lymphoma
Oral dapsone: usually reduces itch within 3 days.
• 25 mg to 300 mg daily

Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Dermatitis Herpeteformis,Updated by Dr Shendy
Engelina, Core Medical Trainee, Northampton General Hospital, UK, February 2016.
Emiliano Antiga, Marzia Caproni. The diagnosis and treatment of dermatitis herpetiformis. Clin Cosmet Investig
Dermatol. 2015; 8: 257–265
 PEMPHIGUS 50
Pemphix, Pemphig:
Bubble
• Autoimmune, potentially life threatening, causing blisters and erosions of
the skin and mucous membranes.
• Occurs more frequently among Ashkenazi Jews, strong association with
HLA -DR4 and DQ8 haplotypes.
• The DR6 and DQ5 haplotypes are more common in non-Jewish patients
• Desmoglein 1 (DSG1), a glucoprotein adhesion molecule in skin, whereas
desmoglein 3 (DSG3) is chiefly in mucosal epithelium.
True Pemphigus: McBride (1777) and Wichmann (1791)
 51
• The immune reaction against these glycoproteins causes a loss of
cell-to-cell adhesion, resulting in the separation of cells and the
formation of intraepithelial bullae

• There are 0.1 to 0.5 cases reported each year per 100,000
population, with the highest incidence occurring in the 5th and 6th
decades of life

• The major variants of pemphigus are Pemphigus Vulgaris (PV),

pemphigus foliaceus, paraneoplastic pemphigus (PNPP), and drug-
related pemphigus
 52
• Pemphigus vegetans is a variant of PV, and pemphigus erythematosus is
of pemphigus foliaceus.
• In pemphigus foliaceus, the blister occurs in superficial granular cell layer
whereas in PV, the lesion is deeper, just above the basal cell layer.

• Mucosal involvement is not a feature of foliaceus and erythematous

forms, where the antibodies are only directed against DSG1
• Drugs associated with drug-induced pemphigus include d-penicillamine
and captopril.
 53
Antigens targeted by autoantibodies and
corresponding forms of pemphigus
Antigens Forms of Pemphigus
Desmoglein 3 Mucosal Pemphigus vulgaris
Desmoglein 3, 1 and probably Mucocutaneous Pemphigus
4 vulgaris
Desmoglein 1 Pemphigus Foliaceous
Desmoglein 3, 1 and plakin Paraneoplastic pemphigus
proteins
Adapted from Etlin DA, Dent Clin North Am 2005; 49: 110
 54
PEMPHIGUS VULGARIS
Etiology and pathogenesis Derived from mass
of common people
• Accounts for over 80% of cases
• Binding of IgG autoantibodies to DSG 3, a transmembrane
glycoprotein adhesion molecule present on desmosomes and finally
breaks the connection between epithelial cells, resulting in blisters
and desquamation
• Mucosal involvement have antibodies primarily against DSG 3, skin
and mucosal involvement will have antibodies against both DSG3
and DSG1
• Coexistence: particularly myasthenia gravis
 55
Clinical manifestations:
• Thin-walled bulla arising on normal skin or mucosa.
• Bulla rapidly breaks, continues to extend peripherally, leaving large
areas denuded of skin
• Bulla spread +ve, Nikolsky sign +ve
Oral findings: 56
• Begin as the classic bulla on a noninflamed base; more frequently, the clinician
sees shallow irregular ulcers because the bullae rapidly break.
• Epithelium peels in irregular pattern, leaves denuded base
• Edges of the lesion continue to extend peripherally
• lesions start on the buccal mucosa, often in areas of trauma along the occlusal
plane.
• Palate and gingiva are other common sites.
 57

Differential diagnosis:
• Recurrent apthous ulcer (individual lesions heal and recur, round
and symmetric)
• Mucous membrane pemphigoid (histopathology)
• Bullous pemphigoid (Nikolsky sign negative)
• Erosive lichen planus (localized erosive areas, histopathology)
 58
Investigations
• Biopsy

• Electron microscopy: the earliest epithelial changes as a loss of

intercellular cement substance; this is followed by a widening of
intercellular spaces, destruction of desmosomes, and, finally, cellular
degeneration resulting in the classic suprabasilar bulla,
• Direct immunofluorescence: 59

• Indirect immunofluorescence:
 60

• Titer of the antibody has been related to the level of clinical

disease.

• An enzyme linked immunosorbent assay has been

developed that can distinguish anti-DSG1 antibodies from
anti-DSG3 in serum samples of patients with PV
 Management 61

Topical therapy:
• For multiple oral erosions, ‘corticosteroid mouthwashes are practical, for
example, soluble betamethasone sodium phosphate 0.5 mg, dexamethasone
0.5mg tablet dissolved in 10 mL water may be used up to four times daily, holding
the solution in the mouth for about 5 min.
• Isolated oral erosions could be treated with application of triamcinolone
acetonide 0.1% in adhesive paste or clobetasol 0.05% gel.
• Topical cyclosporine (100 mg/ m1) in oral pemphigus has been described and
may be of some benefit but is expensive.
 62

Systemic therapy:
• Initial, Prednisolone 1-2 mg/kg/day.
• Maintenance, prednisolone : 1-1.5mg/kg/day
• It is recommended to give concomitant calcium supplements to all patients on
corticosteroids

• Depending upon the response and or tolerance of medication, adjuvant

(immunosuppressive) therapy may be substituted or added to corticosteroid
therapy, in an attempt to spare or reduce prednisone dose and its associated
complications
 63
Adjuvant therapy

• Azathioprine 2.5mg/kg/day (TPMT deficient: 0.5mg/kg/day)

• Mycophenolate mofetil: 2-3.5gm/day
• Methotrexate: 10-25mg/week
• Dapsone: 7.5mg/kg/day upto 200mg/day
• Biologic agents: Rituximab, Infliximab, Etanercept (not
approved for use in Pemphigus, under trial)

International pemphigus and pemphigoid foundation, last update: Dec 22, 2016
Grando SA. New approaches to the treatment of pemphigus. J Investig Dermatol Symp Proc 2004;9(1):84–91
Arash A, Shirin L. The Management of Oral Pemphigus Vulgaris with Systemic Corticosteroid and Dapsone. J
Dent Res Dent Clin Dent Prospects. 2008 Winter; 2(1): 33–37.
 64
PEMPHIGUS VEGETANS

• Accounts for 1 to 2% of pemphigus cases, is a relatively benign variant

of PV
• Two forms: Neumann and Hallopeau type.
• Neumann type: more common, and early lesions are similar to those
seen in PV, with large bullae and denuded areas. These areas attempt
healing by developing vegetations of hyperplastic granulation tissue.
• Hallopeau type: less aggressive, pustules are the initial lesions,
followed by verrucous hyperkeratotic vegetations.
 65

Oral findings

• lesions may be lace-like ulcers with a purulent surface on a red base

or have a granular or cobblestone appearance
• Oral lesions that are associated with inflammatory bowel disease and
resemble pemphigus vegetans both clinically and histologically are
referred to as pyostomatitis vegetans.
 66

Investigations:
• Biopsy results of the early lesions of pemphigus vegetans show
suprabasilar acantholysis.
• In older lesions, hyperkeratosis and pseudoepitheliomatous
hyperplasia become prominent.
• Immunofluorescent study shows changes identical to those seen in PV
Management:
• Treatment is the same as that for PV.
 67
PEMPHIGUS FOLIACEUS

• Autoimmune diseases is high in the epidermis, either in the granular

layer or just beneath the stratum corneum.
• Antibody binding may have a direct effect on the function of the
desmosomal cadherins in the upper epidermis, causing detachment of
keratinocytes.
• Desmoglein-l is present but only weakly expressed in mucosae
accounting for the lack of mucosal involvement in pemphigus
foliaceus.
 68
Clinical features:
• Scattered, scaly lesions involving the 'seborrhoeic' areas:
scalp, face, chest and upper back. Blistering may not be
obvious because the cleavage is superficial and the small
flaccid blisters rupture easily.
• Oral lesions are uncommon.
 69
Histology

Management: same as that for

PV
 70
PARANEOPLASTIC PEMPHIGUS

• Severe variant of pemphigus associated with an underlying neoplasm,

most frequently non-Hodgkin’s lymphoma, chronic lymphocytic
leukemia, or thymoma.
• Castleman disease and Waldenström macroglobulinemia are also
associated with cases of PNPP.
• The damage to the epithelium in PNPP is due to both an autoimmune
reaction with epithelial cells and cell-mediated cytotoxicity.
Clinical findings: 71
• severe blistering and erosions of mucous
membranes and skin.
• Onset is often rapid, and oral and conjunctival
lesions are both common and often severe.
• Unlike EM or TEN , the lesions of PNPP
continue to progress over weeks to months.
• Progressive pulmonary involvement occurs in up
to 40% of patients with PNPP
 72

Oral manifestations
• Oral lesions are the most common
manifestation of PNPP.
• These are frequently extensive and
painful.
• The lesions are frequently inflamed
and necrotic, with large erosions
covering the lips, tongue, and soft
palate
 73

Differential diagnosis:

• Drug reaction (history of drug intake)

• Lichen planus (histopathology)
• Erythema multiforme (histopathology)
• Pemphigus (histopathology)
• Pemphigoid (histopathology)
 74
Investigations:

• Histopathology:
• DIF
• IIF
 75
Management:
• PNPP secondary to localized tumors such as Castleman disease improve
with the surgical removal of the tumor.
• PNPP resulting from lymphoma have a poor prognosis and usually die
within 2 years from a combination of the underlying disease, respiratory
failure, and extensive mucocutaneous involvement.
• Use of a combination of prednisone and immunosuppressive drug therapy
may help control the severity of the skin lesions, but the oral, conjunctival,
and pulmonary disease is frequently resistant to treatment
 76

SUBEPITHELIAL BULLOUS DERMATOSES

• Group of mucocutaneous blistering diseases that are characterized by

an autoimmune reaction that weakens a structural component of the
basement membrane
• Include bullous pemphigoid, mucous membrane pemphigoid, linear IgA
disease, epidermolysis bullosa aquisita, and chronic bullous dermatosis
of childhood
• Recent research into pathologic mechanisms is defining the specific
antigens in the basement membrane complex involved in triggering the
autoantibody response.
 BULLOUS PEMPHIGOID (BP) 77

• An autoimmune disease caused by the binding of autoantibodies to

specific antigens in lamina lucida region on the hemidesmosomes of
epithelial basal cells.
• These antigens are glycoproteins referred to as bullous pemphigoid
antigens, BP 180 and BP 230.
• Binding of antibody to antigen activates both leukocytes and
complement, causing localized damage to the basement membrane,
resulting in vesicle formation in the subepithelial region
 78

• It is self-limiting and may last from a few months to 5

years.
• BP may be a cause of death in older debilitated
individuals.
• BP has occasionally been reported in conjunction with
other diseases, particularly multiple sclerosis and
malignancy, or drug therapy, particularly diuretics
 79

Clinical manifestations
• Occurs chiefly in adults over the age of 60 years
• Characteristic skin lesion of BP is a blister on an inflamed base that
chiefly involves the scalp, arms, legs, axilla, and groin
• Pruritis is a common feature of the skin lesions, which may initially
present as macules and papules.
• Unlike pemphigus, BP is rarely life threatening since the bullae do not
continue to extend at the periphery to form large denuded areas,
 80
Oral findings
• The oral lesions of BP are smaller, form slowly, and are less painful.
• Desquamative gingivitis has also been reported as the most common
manifestation and gingival lesions may be the only site of oral
involvement.
• Gingival lesions consist of generalized edema, inflammation, and
desquamation with localized areas of discrete vesicle formation.
 81

Differential diagnosis:

• Erosive lichen planus (white lines)

• Pemphigus (Nikolsky +ve, more extensive erosion of mucosa)
• Cicatricial pemphigoid (Nikolsky +ve)
 82

Investigations:

• Histopathology:
• DIF
• IIF
• The salt-split test
 83
• For Localized BP:
• Use potent topical steroids. As elderly people have low tolerance for standard
regimens of oral corticosteroids, topical corticosteroid therapy is effective for both
moderate and severe bullous pemphigoid, and is superior to oral corticosteroid
therapy for extensive disease.
• For Extensive BP:
• Topical steroids
• Higher doses of oral steroids, 0.75 mg/kg prednisolone
• Topical/Oral steroids plus systemic treatments like Immunosuppresants
 84
MUCOUS MEMBRANE PEMPHIGOID (MMP, CICATRICAL
PEMPHIGOID)

• Chronic autoimmune subepithelial disease resulting in mucosal blistering,

ulceration, and subsequent scarring.
• Primary lesion occurs when autoantibodies directed against proteins in the
basement membrane zone, acting with complement (C3) and neutrophils,
cause a subepithelial split and subsequent vesicle formation.
• Ten different basement membrane antigens have been identified in cases of
MMP
 85

Dent Clin N Am 57 (2013) 611–

630
 86

Clinical manifestations:
• patients over the age of 50, twice as frequently in women
• Any mucosal surface, most frequently involve the oral mucosa.
• The conjunctiva is the second most common site of involvement and
can lead to scarring and symblepharon, ankyloblepharon
• Corneal damage is common, progressive scarring leads to blindness
in close to 15% of patients.
• Lesions may also affect the genital mucosa, causing pain and sexual
87
dysfunction.
• Laryngeal involvement causes pain, hoarseness, and difficulty in
breathing, whereas esophageal involvement may cause dysphagia,
which can lead to debilitation and death in severe cases.

• Skin lesions, usually of the head and neck region, are present in 20 to
30% of patients.
Oral findings: 88

• Desquamative gingivitis is the most common manifestation and may

be the only manifestation
• Lesions may present as intact vesicles of the gingival or other mucosal
surfaces, but more frequently appear as nonspecific-appearing
erosions
 89

Dent Clin N Am 57 (2013) 611–

630
 90
Differential diagnosis:

• Bullous pemphigoid (Nikolsky sign –ve)

• Erosive lichen planus (histopathology)
• Pemphigus (histopathology)
 91
Investigations:
• Histopathology
• DIF

• However, cases of MMP have also been identified where the antigen is
present on the dermal side of the split. This latter antigen has been
identified as epiligrin (laminin 5), an adhesion molecule that is a
component of the anchoring filaments of the basement membrane
 92

• MMP associated with epiligrin has been reported to carry a higher

risk of association with an underlying malignancy, but the evidence
for this is not conclusive
• Only 10% of MMP patients demonstrate positive IIF for circulating
antibasement membrane zone antibodies.
 93
Management

• Large randomized controlled clinical trials in MMP are not

available. Treatment should be individualized depending on the
severity of disease, age, general health, medical history, and any
contraindications to the use of systemic medications.
• Collaboration of multidisciplinary specialists involving oral
medicine experts, dermatologists, ophthalmologists,
otolaryngologists, and gastroenterologists will improve patient
outcome.
 94

Dent Clin N Am 57 (2013)

611–630
 95

Topical therapy: Desquamative lesion

Application may be facilitated by the placement of a resilient vacuum-

formed occlusive splint that covers the involved gingiva
• Triamcinolone 0.1% ointment
• 0.1 mL/cm3 triamcinolone, 10 mg/mL: Intralesional
 96

Dent Clin N Am 57
(2013) 611–630
 97
ERYTHEMA MULTIFORME (EM)
Ferdinand Von Hebra,
1866
• Acute, self-limiting, inflammatory mucocutaneous disease that
manifests on the skin and often oral mucosa, although other mucosal
surfaces, such as the genitalia, may also be involved
• EM minor: 10% of skin involvement and there is minimal to no mucous
membrane involvement
• EM major: extensive skin involvement, with the oral mucosa and other
mucous membranes affected.
 98

• Historically, fulminant forms of EM were labeled Stevens-

Johnson syndrome (SJS) and toxic epidermal necrolysis
[TEN (Lyell disease)]
• EM is etiopathogenetically distinct from those two latter
conditions, and they are discussed separately.
 99
Etiology and pathogenesis

• EM is a hypersensitivity reaction, and the most common inciting factors are

infection, particularly with HS V, or drug reactions to NSAIDS or anticonvulsants.
• Cases of oral EM precipitated by benzoic acid, a food preservative, have been
reported.

• HS V antigens incite a T cell–mediated delayed-type hypersensitivity reaction that

generates interferon-c, with the amplified immune system recruiting more T cells to
the area.
• Cytotoxic T cells, natural killer cells, and/or cytokines destroy the epithelial cells
 100

Dent Clin N Am 57 (2013)

583–596
 101
Clinical findings:
• Age: 20 and 40 years, with 20% occurring in children.
• Recurrent EM: average of 6 episodes a year (range 2–24)
• Prodromal symptoms: fever, malaise, headache, sore throat, rhinorrhea, and cough
• Classic skin lesion: central blister or necrosis with concentric rings of variable color
around it called typical “target” or “iris” lesion.
• Variants are called “atypical target” lesions.
Oral findings: 102
• The most commonly affected sites are the lips (36%), buccal mucosa (31%), tongue
(22%), and labial mucosa (19%)
• Irregular bullae, erosions, or ulcers surrounded by extensive areas of inflammation,
mild erythema and erosion to painful ulcerations
• When severe, ulcers may be large and confluent, causing difficulty in eating,
drinking, and swallowing, and patients with severe EM may drool blood-tinged saliva
• Severe crusting and bleeding of the lips are common
 103

Differential diagnosis:
• Primary HSV gingivostomatitis (culture positive for HS V and do
not usually present with the typical skin rash, smaller lesion)
• Pemphigus, pemphigoid (chronic, slowly progressive)
• Recurrent apthous ulcer (more discrete)
• Paraneoplastic pemphigus (associated with malignancy)
 104
Investigations:
• No specific laboratory tests that are useful, and the diagnosis is made
primarily on clinical findings
• Histopathology:
 105
Management
Mild EM
• Treatment of mild disease (limited oral and cutaneous involvement), should
be focused on symptomatic relief using topical anti-inflammatory,
anesthetic, or analgesic agents. Some of the drugs that can be used are
as follows:
• Fluocinonide 0.05% or other topical steroid agents need to be applied to
involved areas 2 to 3 times per day
• Mouthwash containing equal parts of viscous lidocaine 2%,
diphenhydramine (12.5 mg/5 mL), and an aluminum hydroxide and
magnesium hydroxide mixture as a swish-and-spit, up to 4 times per day.
Severe EM 106
• The most commonly used steroid is oral prednisone 40 to 60 mg per day,
which is tapered over 2 to 4 weeks
• Recurrence and supportive care
• Continuous antiviral therapy, Acyclovir (400 mg twice daily), valacyclovir
(500 mg twice daily), or famciclovir (250 mg twice daily).
• Supportive care should be provided in the form of a liquid diet, intravenous
fluids, electrolytes, and nutritional support
Adjuvants: Dapsone 100-150mg/day, Azathioprine 100-150mg/day or
mycophenolate mofetil 1000mg BD
Dent Clin N Am 57 (2013) 583–596
STEVENS JOHNSON SYNDROME (SJS) AND TOXIC 107
EPIDERMAL NECROLYSIS (TEN)
Steven and Johnson,
1922
• Studies support the concept that SJS is a less severe variant of TEN and
separate clinically and etiopathogenetically from EM
• Arise on the chest rather than the extremities on erythematous and
purpuric macules; these lesions are called “atypical targets.”
• SJS is much more likely to be associated with medication use and
Mycoplasma pneumoniae infection
• The more common inciting drugs include antibacterial sulfonamides,
anticonvulsants, oxicam NSAIDs, and allopurinol.
 108
Clinical manifestations
• Mucosal surfaces of the eye, genitalia, and
mouth are almost always severely affected by
SJS/TEN, always with skin involvement
• Prodromal symptoms: fever, nausea, vomiting,
malaise, sore throat, rhinitis
Oral findings
• Extensive oral ulceration with hemorrhagic
crusts on the vermilion.
• Resemble oral lesions of paraneoplastic
pemphigus.
 109
• Histopathology:
Management: 110
• No standardized guidelines for treatment of SJS/TEN. Recognition and
prompt discontinuation of the offending agent is a priority.
• Use of all drugs should be stopped as quickly as possible, especially those
taken within 8 weeks before the onset of TEN symptoms.
• Ophthalmologic consultation is imperative. Ocular lubricants and elimination
of new lid adhesions should be a priority.
• Patients with TEN benefit greatly from admission to a burn unit where
dressings, fluid and electrolyte replacement, and antibiotics are best
administered. Otherwise, protein loss, electrolyte imbalance, and infection
can result in death up to 60% of cases
 111
• The use of systemic steroids is controversial
• If used, should be in the range of 100 mg prednisolone and discontinued within
48 hours once the disease stops progressing.
• Counsel the patient about avoiding the responsible drug in the future.
• In the future, treatments tailor-made to the pathogenesis may be available,
such as antibodies against CD95 or FasL, the ligand that results in apoptosis
or keratinocytes

Garcia-Doval I, LeCleach L, Bocquet H, Otero XL, Roujeau JC. Toxic epidermal necrolysis and Stevens-Johnson
syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol 2000;136:323–7.
McGee T, Munster A. Toxic epidermal necrolysis syndrome: mortality rate reduced with early referral to a regional
burn unit. Plast Reconstr Surg 1998;102:1018–22.
Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, et al. Inhibition of toxic epidermal necrolysis by
blockade of CD95 with human intravenous immunoglobulin. Science 1998;282:490–3.
 112
BULLOUS LICHEN PLANUS

• Rarest form of oral lichen planus

• Supposed to be immunologically induced degeneration of
basal cell layer
• Exact etiology is still unclear
 113
Clinical features:
• Female predominance in 4th-7th decade of life
Oral findings:
• Commonly affects posterior buccal mucosa and lateral
border of tongue
• Bulla with white striae are characteristic, bulla rupture to
leave erosive areas
• Burning sensation with pain is present
 114
Differential diagnosis:
• Bullous pemphigoid (histopathology)
• Pemphigus vulgaris (Nikolsky +ve)
Investigations:
• Histopathology:
• Management: 115
• Oral mini pulse therapy
• Betamethasone 5 mg orally on two consecutive days in a week for three
months.
• Followed by tapering of the dose of betamethasone by 0.5 mg every two
weeks over the next ten weeks
• Others:
• Tab prednisolone 10 mg 4 times a day for 10 days and then gradual
tapering.
• Tab levamisole150 mg once daily for 3 days
Patil A, Prasad S, Ashok L, Sujhata GP. Oral bullous lichen planus: Case report and review of management.
Contemp Clin Dent. 2012 Jul-Sep; 3(3): 344–348
•Maloth
Benzydamine 0.15% oral rinse
KN, Sunitha K. Bullous Lichen Planus treated with Oral Minipulse Therapy: A Rare Case Report. J Clin
Diagn Res. 2014 Dec; 8(12): ZD17–ZD19
 116
ANGINA BULLOSA HEMORRHAGICA

Clinical features:
• Middle aged patient.
• Blood filled blisters rupture to form erosions and heal within a
week.
• Commonly affect soft palate.
• No history of blood disorders or mucosal blistering disorders.
• Associated with burning sensation while eating.
 117

Differential diagnosis: Subepithelial blistering disorders

Histopathology:
• Subepithelial blister usually blood filled.
• Inflammatory infiltrate in lamina propria
Management:
• Only symptomatic management.
• Anti-inflammatory, antibiotics or antiseptics may be
Beguerie JR, Gonzalez S. Angina Bullosa Hemorrhagica: Report of 11 Cases. Dermatol Reports. 2014 Feb 17;
6(1): 5282
required.
Yip HK. Angina bullosa haemorrhagica: a case report and a concise review. Gen Dent. 2004 Mar-Apr;52(2):162-
4
 LINEAR IMMUNOGLOBULIN A DISEASE (LAD) 118

Etiology and pathogenesis:

• Subepithelial disease characterized by the deposition of IgA rather
than IgG in the basement membrane
• The cause of the majority of cases is unknown, but reported cases
have been drug induced or associated with systemic diseases,
including hematologic malignancies, or connective tissue diseases,
such as dermatomyositis
• Antigens associated with LAD are heterogeneous and may be found
in either the lamina lucida or lamina densa of the basement
membrane Tadeusz Chorzelski, 1979
Clinical manifestations: 119
• Characterized by pruritic papules and blisters at
sites of trauma such as the knees and elbows.
• Other patients have bullous skin lesions. Oral
mucosa and conjunctiva are also commonly
involved. String of pearl
Oral findings:
• Oral lesions are common in LAD and may be seen
in up to 70% of patients.
• Blisters and erosions of the mucosa frequently
accompanied by desquamative gingivitis,
 120
Differential diagnosis:
• MMP (Nikolsky +ve)
• DH (celiac disease)
Investigations:
• Histopathology
• DIF
• IIF: usually negative, but when positive, it
will demonstrate circulating IgA antibodies
against a basement membrane antigen.
 121

Management:
• Topical corticosteroid 0.1% three times a day for 3 months, oral prednisolone
1-2mg/kg/day gradually tapering the dose for three months.
• Dapsone 100mg/day is a drug of choice if corticosteroids do not work.
• Mycophenolate mofetil 1 gm/day can be other drug of choice.
• Severe cases may require a combination of systemic corticosteroids and
immunosuppressive drug therapy
Francesca A, Stefano, Rolando C, Sarah M, Davide F, Michele S. A Rare Case of Desquamative Gingivitis due to
Linear IgA Disease: Morphological and Immunofluorescence Features. In vivo 21: 1093-1098 (2007)
Passos L, Rabelo RF, Matsuo C. Linear IgA/IgG bullous dermatosis - successful treatment with dapsone and
mycophenolate mofetil. An Bras Dermatol. 2011;86(4):747-50.
Regan EO, Bane A, Flint S. Linear IgA Disease Presenting as Desquamative GingivitisA Pattern Poorly Recognized in
Medicine. Arch Otolaryngol Head Neck Surg. 2004;130(4):469-472
 122

CHRONIC BULLOUS DISEASE OF CHILDHOOD (CBDC)

• Subepithelial blistering disorder, chiefly affects children below 5

years.
• Deposition of IgA antibodies in the basement membrane zone,
which are detected by DIF on the epidermal side of salt-split
skin or mucosa.
1901, Bowen described First 6 cases
 123
Clinical manifestations:
• Lesion is cluster of vesicles and bullae on an inflamed
base.
• The genital region is commonly involved, conjunctival,
rectal, and oral lesions may also be present.
• self-limiting and resolves prior to puberty
Oral findings:
• Oral mucosal involvement is present in up to 50% of
cases,
• Blisters and erosions of the mucosa frequently
accompanied by desquamative gingivitis
• Lesions of the perioral skin are common
 Diagnosis and management: 124
• Diagnosis is made by biopsy, DIF, IIF

• This disease is self-limiting, and the lesions characteristically heal within 2

years.
• As with LAD, the lesions are responsive to corticosteroid or dapsone
therapy.
Mintz EM, Morel KD. Treatment of chronic bullous disease of childhood. Dermatol Clin.2011 Oct;29(4):699-700
Li JF,•Mancini
Systemic corticosteroids
AJ. Treatment may Dermatosis
of Linear IgA Bullous be required for severe
of Childhood cases Mofetil. Arch
With Mycophenolate
Dermatol. 2003;139(9):1121-1124
 125
EPIDERMOLYSIS BULLOSA

Etiology and pathogenesis Ferdinand Ritter Von Hebra, 1870

• Inherited mucocutaneous disorder due to defective collagen

metabolism, are group of genodermatosis
• Blisters arise spontaneously or on mild trauma
• Inherited forms must be differentiated from Epidermolysis bullosa
aquisita which is an autoimmune disorder
• Inheritance may be dominant or recessive (more severe and
agrgessive)
 126
Classification:

• Epidermolysis bullosa simplex (epidermolytic): Intraepidermal

cleavage is seen. Suprabasal and Basal epidermolysis bullosa
simplex.
• Junctional epidermolysis bullosa (lamina lucidolytic): Intralamina
lucida, Herlitz and Others
• Dystrophic epidermolysis bullosa (dermolytic): Sublamina densa
cleavage. Dominant dystrophic and Recessive dystrophic
• Kindler syndrome: Mixed
 127

Clinical features and oral findings:

Epidermolysis bullosa simplex:

• Presence of multiple vesicles or bullae at birth or after birth
• Common site affected are hand and feet, oral mucosa is rare
• Self-limiting.
• Heal in week or 10 days
 128

Junctional epidermolysis bullosa:

• Severe form that occurs at birth and death occurs in first

three months
• Hoarse, cry, cough, breathing difficulty, Skin sheds.
• Oral, ocular, pharyngeal and genital mucosa may be involved
• Oral lesions manifest as bullae followed by erosions
 129

Dystrophic epidermolysis bullosa:

• Dominant form occurs at birth and adolescent

• Initially it is generalized, with age lesion confines
• Bullae on feet, ankles, knees and elbows
• Dystrophic nails, palmar plantar hyperkeratosis, hypertrichosis
• Milia may be seen on face, oral involvement is limited
• Recessive form is seen at birth or neonates 130
• Bulla ruptures, erosive areas and heal by extensive scarring,
“club like fists”
• Nail may be absent or defective
• Bulla in the oral mucosa which ruptures to leave erosive areas
• Extensive scarring of oro-pharyngeal and esophageal tissues
may lead to hoarseness of voice, difficulty feeding, swallowing
• Congenitally missing teeth, malformed or hypoplastic teeth are
seen
 131
EPIDERMOLYSIS BULLOSA AQUISITA (EBA)
Elliot, 1895

• EBA have IgG autoantibodies directed against type VII collagen, a

component of the anchoring fibrils of the basement membrane.
• There are two forms of EBA: the classic form, which results in a lesion
of the basement membrane with little inflammation, or the inflammatory
form, which includes a significant infiltration of neutrophils.
• EBA can resemble BP or MMP with widespread skin lesions or primary
involvement of the oral mucosa, genital mucosa, conjunctiva, and larynx
132
 133
Management:
• The treatment is similar as described for MMP and LAD
• The classic form of the disease tends to be resistant to treatment, whereas
the inflammatory form often responds well to dapsone.
• Some patients with an inadequate response to dapsone have obtained
remission with colchicine.
• Systemic corticosteroids and immunosuppressive drugs are often required
to control the lesions in severe widespread EBA
 BULLOUS IMPETIGO 134

Etiology and pathogenesis:

• Bacterial infection (staphylococcus aureus, group II, type 71) that

affects superficial skin
• Some cases caused by streptococcus pyogenes have been reported
• Common in infants and young children.
• If present in adult may be associated with HIV-1
• Exotoxin is directed towards epidermal desmoglein 1
 135

Types:
• Bullous: staphylococcal toxin is responsible
• Non-bullous: host response to staphylococcus is
responsible
 136
Clinical features and oral findings:

• Common in 2-5 years

• Small to large, painless fragile bullae in extremities, axilla and trunk
with burning or itching sensation
• Serous clear yellow fluid turns cloudy and dark yellow in 3-4 days
• Bullae ruptures to leave thin, light brown, varnish or honey like crust
• Collarette is present 137
• When various parts are involved: “staphylococcal scalded skin
syndrome

Investigation:
• Histopathology
Management: 138
• Self limiting
• Resolves in 2 weeks
 139

Adams HH, Banvard C, Juckett G. Impetigo: diagnosis and treatment. Am fam

physician. 2014 aug 15;90(4):229-235
Cole C, Gazewood J. Diagnosis and treatment of impetigo. Am fam
physician. 2007 mar 15;75(6):859-864.
 140

SUMMARY

• Vesiculo-bullous lesions of oral cavity present themselves in various

forms.
• Beginning right from short lasting vesicle or bullae, they end up in
erosion, ulceration or desquamative lesions.
• They can be primarily vesicular or bullous, intra or sub epithelial and
acute or chronic.
 141
• Individual lesions as described above have their own etiopathogenesis,
clinical presentation and management.
• Except for those with viral etiology, corticosteroids remain the mainstay
of treatment.
• Immunosuppressant can be used as steroid sparing agents especially in
case of auto-immune diseases.
• Till date there is no standard or universally accepted management for
oral form of any vesiculo-bullous disease. Researches are going on in
this field leading to evidence based practice.
 142
CONCLUSION

• Three pieces of information in particular help the clinician rapidly

categorize a patient’s disease and simplify the diagnosis: the length of
time the lesions have been present (acute or chronic lesions), the past
history of similar lesions (primary or recurrent disease), and the number
of lesions present (single or multiple).
• With knowledge of basic dermatology, a complete review of systems
should be obtained for each patient, including questions regarding the
presence of skin, eye, genital, and rectal lesions.
Dew drop like vesicle is a clinical manifestation of: 143

a. Primary Herpes simplex

b. Recurrent herpes simplex
c. Varicella zoster
d. Herpes Zoster
Antigen associated with mucosal pemphigus vulgaris is:
a. Desmoglein 1
b. Desmoglein 3
c. Desmoglein 4
d. Desmoglein 1,3 and plakin protein
 144
String of pearl is the clinical feature of:
a. LAD
b. EM
c. MMP
d. EBA
One of the following is not the feature of Hallopeau type pemphigus
vegetans:
a. Pustular
b. Less aggressive
c. Hyperkeratotic vegetations
d. More common
 145

Auto-antigens against type VII collagen in MMP in present in:

a. Lamina lucida
b. Lamina densa
c. Hemidesmosomes
d. Desmosomes
 REFERENCES 146
• Greenberg MS, Glick M. Burket’s Oral Medicine Diagnosis and Treatment. 10th edition. Ontario: BC Decker Inc;
2003
• Warnakulasuriya S, Tilakarantne WM. Oral Medicine and Pathology: A guide to diagnosis and management. 1st
edition. New Delhi: Jaypee; 2014

• Prabhu SR. Textbook of Oral Medicine. 1st edition. Oxford University Press
• Khanna N. Illustrated synopsis of dermatology and sexually transmitted diseases. 4th edition. Delhi: Elsevier;
2014
• Scuibba JJ. Autoimmune Oral Mucosal Diseases: Clinical, Etiologic, Diagnostic, and Treatment Considerations.
Dent Clin N Am. 2011; 55: 89–103

• Wright JT, Fine JD, Johnson L. Hereditary epidermolysis bullosa: oral manifestations and dental management.
Pediatr Dent. 1993;15: 242-47
• Dag C, BezginT, Ozalp N. Dental Management of Patients with Epidermolysis Bullosa. OHDM. 2014; 13(3):
623-27
• Samim F, Auluk A, Zed C, Williams PM. Erythema Multiforme: A Review of Epidemiology, Pathogenesis,
Clinical Features, and Treatment. Dent Clin N Am. 2013; 57: 583–596
 147
• Diagnosis and Management of Unusual Oral Mucosal Diseases and Disorders in Periodontal Practice. American
Academy of Periodontology. Philadelphia Pennsylvania: October1, 2013
• Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology. 3rd edition. Philadelphia:
Saunders; 2014

• Harman KE, Albert S, Black MM. Guidelines for the management of pemphigus vulgaris. British Journal of
Dermatology. 2003; 149: 926–937
• Dwyer DE, Cunningham Al. Herpes simplex and varicella–zoster virus infections. MJA Practice Essentials. 2002;
177: 267-73
• Angierio F, Benedicenti S, Crippa R et al., A Rare Case of Desquamative Gingivitis due to Linear IgA Disease:
Morphological and Immunofluorescence Features. In vivo. 2007; 21: 1093-1098
• Passos L, Rabelo RF, Matsuo C. Linear IgA/IgG bullous dermatosis - successful treatment with dapsone and
mycophenolate mofetil. An Bras Dermatol. 2011; 86(2): 333-5
• Sollecito TP, Parisi E. Mucous membrane pemphigoid. Dent Clin N Am. 2005; 49: 91–106
• Xu HH, Werth VP, Parrisi E, Sollecito TP. Mucous Membrane Pemphigoid. Dent Clin N Am. 2013; 57: 611–630

• DeRossi SS, Ciarrocca KN. Lichen planus, lichenoid drug reactions, and lichenoid mucositis. Dent Clin N Am.
2005; 49: 77–89
 148
• Rai A, Arora M, Naikmasur V et al., Oral Pemphigus Vulgaris: Case Report. Ethiop J Health Sci. 2015; 25(4): 367-
72
• Ettlin DA. Pemphigus. Dent Clin N Am. 2005; 49: 107–125

• Rimal J, Sumanth KN, Ongole R, George T, Chatterjee S. A rare presentation of oral pemphigus vulgaris as
multiple pustules. Kathmandu University Medical Journal. 2007; 5(20): 541-545
• Lim GFS, Cusack CAR, Kist JM. Perioral Lesions and Dermatoses. Dent Clin N Am. 2014; 58: 401–435
• Dubinsky RM, Kabbani H, Chami E. Practice Parameter: Treatment of postherpetic neuralgia. American Academy
of Neurology. 2004; 2(2): 959-65
• Kost RG, Straus SE. Post herpetic neuralgia- pathogenesis, treatment and prevention. The New England Journal
of Medicine. 1996; 335(1): 32-42
• Balasubramaniam R, Kuperstein AS, Stoopler ET. Dent Clin N Am. 2014; 58: 265–280
• Erugula SR, Singaraju DK, Govada J et al., Vesiculobullous lesions of oral cavity. IAIM. 2016; 3(11): 154- 163
• Baykal C, Yazganoglu KD. Dermatological diseases of nose and ears: An illustrated guide. 2010
• Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 3rd edition. Philadelphia:
Saunders; 2014
149
 150

Incidence of pemphigus

• 0.09-1.8 %

Kanwar AJ, Vinay K. Treatment of pemphigus: An Indian perspective. Indian J Dermatol Venereol
Leprol 2014;80:285-8
Kanwar AJ, De D. Pemphigus in India. Indian J Dermatol Venereol Leprol 2011;77:439-49
 151
Behavioral
therapy
• Relaxation training:
Diaphragmatic breathing: patient learns to breathe by expanding the
lungs fully, while keeping the shoulders and chest relaxed, allowing the
abdomen to expand thus increasing oxygen intake.
Progressive muscle relaxation (PMR): engaging in a combination of
muscle tension and relaxation exercises of specific muscles or muscle
groups throughout the body. The patient is typically instructed to engage
in the tension/relaxation exercises in a sequential manner until all areas
of the body have been addressed.
 152
Autogenic training (AT): self-regulatory relaxation technique in which a
patient repeats a phrase in conjunction with visualization to induce a
state of relaxation. This method combines passive concentration,
visualization, and deep breathing techniques.
Visualization/Guided imagery: encourages patients to use all of their
senses in imagining a vivid, serene, and safe environment to achieve a
sense of relaxation and distraction from their pain and pain-related
thoughts and sensations
 153

• Operant behavioral therapy:

Graded activation: Patients are instructed to safely break the cycle of

inactivity and deconditioning by engaging in activity in a controlled and
time-limited fashion.
Time contingent medication schedules: Psychologists can institute time-
contingent medication schedules to reduce the likelihood of dependence
on pain medications for attaining adequate control over pain.
 154

• Hypnosis
state of highly focused attention during which alteration of
sensations, awareness and perception can occur.
Hypnosis has been an effective technique for helping patients in
acute pain associated with burns, dental work, and
uncomfortable medical procedures

Golden AB. A muntidisciplinary approach to non-pharmacologic pain management. JAOA. 2002; 102
(3).
Roditi D, Robinson ME. The role of psychological interventions in the management of patients with
chronic pain. Psychol Res Behav Manag. 2011; 4: 41–49
 155

Interaction between mycophenolate mofetil

• Both being immunosuppressant drug, they exhibit
synergistic action, further weaken the immune system and
increase the risk of infection.
 156

Location of Desmoglein
Hemidesmosomal proteins desmoglein 1 and 3 differ in location in skin and
mucous membrane.
Skin: Dsg 1 is expressed throughout epidermis but more in superficial layer
while Dsg 3, more predominantly in basal layer.
Mucosa: Both Dsg are expressed equally but Dsg 1 is located much lower
level than Dsg 3.

Coleman WB, Tsongalis GJ. Essential concepts in molecular pathology. 1st edition. China.
Elsevier; 2010.
 157

Gluten free diet

• Rice
• Oats
Wheat
• Pulses
Barley
• Gluten free products are also available Rye
158

Nikolsky sign Bulla spread sign

Pemphigus vulgaris Pemphigus
MMP BP, MMP
TEN DH, EBA
SSSS SJS and TEN
 159
• Alcohol should be avoided during use of levamisole. It causes dizziness,
nausea, vomiting and GI upset.
• Crust: Hard but brittle external coat or covering. It is formed by surface
deposits of serum, pus, cellular debris and bacterial deposits. (Merriam
Webster Medical Dictionary)
• Salt split technique: To differentiate Pemphigoids from EBA. Punch
biopsy samples are incubated in 5 mL of NaCl (1 mol/L) at 4ºC for 24 h.
The epidermis is then teased from the dermis with the use of a fine
forceps. The specimen is then processed and treated with IgG and
C conjugates as in DIF.
DA,3 RR, BC. Salt split technique: a useful tool in the diagnosis of subepidermal bullous disorders. Indian J
Dermatol. 2010 Oct-Dec; 55(4): 334–336
Arvind Babu R S, Chandrasekar P, Chandra K L, Reddy G S, Kumar K K, Ramana Reddy B V.
Immunofluorescence and its application in dermatopathology with oral manifestations: Revisited. J Orofac Sci
2013;5:2-8
 Rationale behind doing indirect 160
immunofluorescence
• High specificity: positive and negative samples produce a large difference in
signal strength. Each bound antibody shows a typical fluorescence pattern
depending on the location of the individual antigens.
• The entire antigen spectrum of the original substrate is available, thus allowing
the detection of a large number of antibodies and achieving a higher detection
rate.
• Immunofluorescence enables simultaneous detection of antibodies against
several biochemically different antigens on one single biological substrate.
• The indirect immunofluorescence test is the analytical method of choice when it
would be too difficult or too complicated to prepare the test antigens individually
Arvind Babu R S, Chandrasekar P, Chandra K L, Reddy G S, Kumar K K, Ramana Reddy B V.
for enzyme immunoassays.
Immunofluorescence and its application in dermatopathology with oral manifestations: Revisited. J Orofac Sci
2013;5:2-8
 161

Can be stored at room temperature for 5

days
Arvind Babu R S, Chandrasekar P, Chandra K L, Reddy G S, Kumar K K, Ramana Reddy B V.
Immunofluorescence and its application in dermatopathology with oral manifestations: Revisited. J Orofac Sci
2013;5:2-8
Michel B. Milner Y. David K. Preservation of tissue-fixed immunoglobulins in skin biopsies of patients with lupus
erythematosus and bullous diseases. A preliminary report. J. Invest. Dermatol. 1972; 59: 449-452
 162
Symblepharon: differential
diagnosis

• Ocular cicatricial • Porphyria cutanea tarda

pemphigoid • Rosacea
• Stevens-Johnson • Epidemic keratoconjunctivitis
syndrome • Xeroderma pigmentosum
• Trauma • Squamous papilloma of the
• Conjunctival burns conjunctiva
• Atopic keratoconjunctivitis
 163
Rationale behind combining immunomodulator and
steroid
• Immunomodulators are natural or synthetic substances that help to
regulate or normalize the immune system, modulate the immune
reaction and decrease inflammatory replication
• The benefits of immunomodulators stem from their ability to stimulate
natural and adaptive defense mechanisms, such as cytokines, which
enables the body to help itself.
• The natural immunomodulators act to strengthen weak immune systems
and to moderate immune systems that are overactive
• An immunomodulators should be given along with a steroid to spare 164
side effect and speed the rejuvenating process. For these reasons these
drugs come under the category of steroid sparing drugs
• Firstly, It may be used in patients who fail to obtain a remission or who
experience serious adverse effects secondary to glucocorticoid therapy.
• Second, it may be used concomitantly with glucocorticoid therapy to
decrease the total dose of glucocorticoid needed and, hence, the
adverse effects. The concomitant use of adjuvant therapy allows the
glucocorticoid dose to be tapered rapidly. Patients are maintained on the
“steroid-sparing” agent for 18–24 months
SN, SA, AJ, PS. Immunomodulators in oral lesions. Research Journal of Pharmaceutical, Biological and Chemical
Sciences. 2016; 7(2)
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Drugs having Staph aureus coverage

• Penicillinase resistant penicillin: cloxcillin, dicloxacillin,

flucloxacillin, methicillin, nafcillin.
• First gen cephalosporins: cephalexin, cefazolin.
• Clindamycin, erythromycin, lincomycin.
• MRSA: vancomycin, clindamycin, lincomycin,
 166
Drugs causing erythema multiforme

• Oxicam NSAIDs: piroxicam, tenoxicam

• Sulfonamides: sulfamethoxazole, sulfasalazine,
sulfadiazine
• Anticonvulsants: carbamazepine, phenytoin,
phenobarbital
• Trimethoprim- sulfonamide combination
• Allopurinol
• Penicillins
 167
Typical and atypical target lesions
• A target lesion is a round skin lesion with three concentric colour zones:
Darker centre with a blister or crust
Ring around this that is paler pink and raised due to oedema (fluid
swelling)
Bright red outermost ring
• Atypical target lesions show just two zones and / or an indistinct border.
In erythema multiforme, these lesions are raised (papular)
Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN), they
are flat (macular)
 168
Genodermatoses

• Inherited genetic skin conditions often grouped into three

categories: chromosomal, single gene, and polygenetic.
• Xeroderma pigmentosum
• Epidermolysis Bullosa
• Incontinentia pigmenti
• Ichthyosis
• Restrictive dermopathy
• Palmoplantar keratoderma
• Ectodermal dysplasia
• Neurofibromatosis
• White sponge nevus
• Keratosis follicularis