L5- Ulcerative and Vesiculobullous lesions II

II. Patients with Recurring Oral Ulcers Burkett s classification for ulcerative and vesiculobullous lesions 2008
• Recurrent aphthous stomatitis (RAS) • Recurrent herpes simplex virus infection
• Bechet syndrome • Recurrent erythema multiform

a. Recurrent aphthous stomatitis

•A disorder characterized by recurring ulcers confined to oral mucosa in pts with no other signs of disease.
• The term “aphthous” is derived from a Greek word “aphtha” which means ulceration
• Affects approximately 20 % of the population
• Age; more seen in teen ages
• Sex: females are more commonly affected
• Site: non-keratinized mucosa, rarely affect keratinized mucosa
• RAS classified into:
→ Minor ulcers: less than 1 cm in diameter, heal without scarring)
→ Major ulcers: Sutton disease; periadenitis mucosa necrotica recurrence, are over 1 cm in diameter and
take longer time to heal and often scar
→ Herpetiform ulcers: recurrent crops of dozens of small ulcers throughout the oral mucosa

Minor aphthous ulcer

Clinical manifestation:
• Prodromal features (24h) with tingling and burning sensation at the site where the lesion will develop
• This is followed by localized area of erythema
• Within hours a white papules forms, the center of which become blanched due to necrosis of the epithelium,
undergo sloughing and ulcer appear that gradually enlarge within 2-3 days
Clinical features
• The individual lesions are shallow, round, symmetric and shallow but no tissue tags are present
• Site: common in non-keratinized mucosa
• Shape: round on lip and cheek, elongated in vestibular sulci, surrounded by erythema
• Healing occurs within a week without scar formation
Major aphthous ulcer
• The ulcer is larger than 1 cm in diameter and deep
• Long duration of healing (more than one month)
• Healing: with scar formation
• Site: anywhere especially soft palate, tonsillar areas and keratinized oral mucosa may be involved
• Margins; raised, shiny and erythematous
• Base: indurated on palpation
• Number: solitary but may be multiple
• Extremely painful and disabling, interfering with speech and eating
• Lesion may last for month and sometimes misdiagnosed as squamous cell carcinoma
 Herpetiform aphthous ulcers
• The least variant of RAS
• Tend to occur in adults
• Patient presents with punctate ulcers scattered over a large portion of the oral mucosa
• Tiny pinhead multiple ulcers (1-2 mm) may coalesce forming irregular ulcers
• The most common sites are: the tongue, and the floor of the mouth
• Healing is much quicker than minor or major aphthous ulcers
Etiology
• It is still not well understood, however, the major factors identified include:
• theories suggest a link between RAS and certain microbial agents as streptococci - Helicobacter pylori
• Either directly involved in the pathogenesis or RAS or serve as antigenic stimuli, which provoke antibody
production that cross react with oral mucosa
Genetic factors
• 40% of patients have a family history and these individuals develop ulcers earlier and are of more severe
nature (Various associations with HLA antigens)
• Recent studies link RAS with genetic factors controlling release pro inflammatory cytokines IL6, IL1B, TNF-α
• Hematological deficiency particularly of serum iron, folate or vitaminB12
• nutritional deficiency as Inflammatory bowel diseases such as Crohn's disease and ulcerative colitis may
present with aphthous like ulceration)
• Immunological abnormalities (either an antibody dependent cell mediated cytotoxicity resulting in localized
ulceration of the oral mucosa, or defect in T helper/ T suppressor ratio)
Recurrence precipitated by:
• Anxiety, psychological increase in students before examinations and decline during vacations)
• Localized trauma to the mucosa
• Upper respiratory tract infection and food allergy
• Hormonal changes, increase premenstrual and decrease during pregnancy
Tobacco
Several studies reveal negative association between smoking, smokeless tobacco and RAS, due to:
• Increased mucosal keratinization; which serves as a mechanical and protective barrier against trauma and
microbes
• Reduced production of tumor necrosis factor alpha (TNF-α) and interleukins 1 and 6
Management According to the severity
In mild cases:
• Topical tetracycline mouth rinse or on gauze sponge
• Use protective emollient as orabase
• Pain relief using topical anesthetic agent
• Nonsteroidal anti-inflammatory e.g., brufen
Steroid preparation include:
• Topical: 4 times daily i.e., Betamethason in orabase or kenalog in orabase applied directly on the lesion 2-3
times a day after meals and at the bedtime
• Avoid using silver nitrate, phenol and other caustics in treatment of RAS
b. Bechet’s disease
• A multi system inflammatory disorder of unknown etiology
• Genetic and immunologic factors are implicated.
• Criteria suggested for diagnosis:
Oral aphthous like ulcers that have occurred at least three times during one year period and two of the
following manifestations:
→ Recurring genital lesions
→ Eye lesions (Retinal vasculitis, conjunctivitis, optic atrophy and keratitis)
→ Skin lesions (erythema nodasum, acneiform like lesions and pustular lesions)
→ Positive pathergy test
It is defined as an inflammatory reaction (a pustule) forming within 24 hours of a needle puncture, scratch
or saline injection
→ Arthritis (occur in 50 % of patients and affect knees and ankles) and CNS involvement are common
Treatment
Systemic corticosteroids + immunosuppressive e.g., cyclosporine, colchicine, azathioprine & prednisone
Mucocutaneous ocular syndromes: Steven Johnson s syndrome – Bechet’s syndrome – Reiter’s syndrome

III. Patients with Chronic Multiple Lesions Burkett s classification for ulcerative and vesiculobullous lesions 2008
1. Pemphigus 4. Erosive lichen planus
2. Bullous pemphigoid 5. Chronic herpes simplex infection
3. Mucous membrane pemphigoid

1. Pemphigus
Major variants of pemphigus are:
• Pemphigus vulgaris (PV) • Pemphigus erythematosus
• Pemphigus vegetans • Paraneoplastic pemphigus (PNPP)
• Pemphigus foliaceus • Drug related pemphigus

Pemphigus Vulgaris
• Most common form of pemphigus accounting for over 80 % of cases
Etiology and pathogenesis: Autoimmune:
Autoantibody (IgG) against prickle cell layer of the epithelium causes destruction of the intercellular
cement substance leading to loss of adhesion between epithelial cells acantholysis) and formation of
suprabasilar bullae
Clinical manifestations
• Older age group of 40 60 years
• Constituinal symptoms of cachexia (loss of weight), nervousness, anemia and generalized pruritis are
usually present
Skin lesions:
• Site: face, neck, axilla, trunk and extremities
• It appears as painless bullae on normally looking skin
• The bullae soon rupture and lesion continue to expand peripherally until large areas of skin become
denuded
• Positive Nikolsky’s sign: Lateral pressure to intact bullae → enlargement by extension to normal surface
• Pressure on normal area leads to formation of new lesions
• It is caused by the pulling away (separation) of the upper layer of epithelium from the basal layer
 Oral Manifestations
• 80-90 % of patients with pemphigus vulgaris develop oral lesions sometime during the course of the
disease; and in 60% of cases oral lesions occurs first
• Oral lesions may begin as thinned walled bullae on a non-inflamed base, break rapidly giving rise to
diffuse erosions
• The lesions start on the buccal mucosa along the occlusal plane, palate and gingiva are other common
sites of involvement
• A thin layer of epithelium peels away in an irregular pattern leaving a denuded base
• Edges of the lesion continue to extend peripherally over a period of weeks until they involve large
portions of the oral mucosa becoming painful
• +ve Nikolsky’s sign; epithelium splits & superficial layers slide away on gentle lateral pressure using
• cotton applicator
• If lesions of the pemphigus vulgaris occur in gingiva, so called Desquamative gingivitis
Diagnosis:
History:
• Older age group
• Chronic lesion of weeks to months
• History of developing painless vesicles that become painful on rupture
Clinical examination:
• Diffuse erosions surrounded by normally looking skin or oral mucosa, +ve Nikolsky’s sign
Laboratory tests:
Cytology:
Fresh lesions scraped with spatula and put on glass slide, by Giemsa stain; If +ve: Acantholytic cells or
Tzank cells are present (round epithelial cells with large deeply stained nuclei)
Biopsy:
• Best taken from intact vesicles and bullae but because these lesions are rare on the oral mucosa
• Biopsy should be taken from advancing edge of the lesion where the areas of characteristic acantholysis
may be found
Direct immunofluorescent antibody test
This is done by incubating lesional or perilesional tissue of the patient with fluorescent conjugated
human antiglobulin to demonstrate the presence of autoantibody attached to the tissue
Indirect immunofluorescent antibody test:
• This is done by incubating normal animal or human mucosa with serum from patient suspected of having
the disease and adding fluorescent conjugated human antiglobulin
• Patients with the disease will have antibodies against intercellular substance that will show up under a
fluorescent microscope
Differential diagnosis
• Erythema multiforme (onset, predisposing, skin, oral, histopathology)
• Lichen planus • Pemphigoids
Treatment
• Systemic corticosteroids: Prednisone 60 100 mg/day to control the acute phase, then reduced to a
maintenance dose since corticosteroids reduce the level of serum immunoglobulin
• Topical corticosteroids: for skin and oral mucosa
• Antifungal should be used for one week for every 4 weeks of steroid therapy
• Systemic antibiotics: To prevent secondary infection
 2. Mucous membrane pemphigoid (Cicatricial Pemphigoid)
• Autoimmune disease; autoantibodies against basement membrane
• Mostly occur on mucous membrane and rarely occurs on skin
• Subepithelial vesicles occurring at any mucosal surface
(oral most common) that may lead to scar
• Involvement of the eye is 2nd most common with corneal damage
• lesions may also be found in: Trachea, larynx and genitals
Oral manifestations
• Oral lesions may appear as non-specific erosions similar to pemphigus but less severe or may appear as
intact bullae
• gingival lesions → desquamative gingivitis

3. Bullous Pemphigoid
• Mostly occur on skin and rare on oral mucosa
• Occur in adult over 60 years, initial defect is sub epithelial in the region of basement membrane
• No acantholysis, no nikolisky sign, occasionally occur as desquamative gingivitis
• lesions are smaller, form more slowly and less painful than those in pemphigus
• Etiology: unknown but circulating Ab against basement mb Ag has been detected

IV. Patients with Single Ulcers Burkett s classification for ulcerative and vesiculobullous lesions 2008
• Traumatic ulcer
• Infectious ulcers: Bacterial: TB and chancre
Deep fungal infection: Histoplasmosis, Blastomycosis, Mucomycosis
• Neoplastic ulceration