CASE SHEET - PEMPHIGUS VULGARIS

PATIENT PROFILE

PRESENTING COMPLAINTS

1. Painful blisters over the body - 6 weeks
2. Painful erosions in the mouth - 8 weeks
3. Difficulty in chewing and swallowing - 6 weeks
4. Raw, weeping areas over skin after blisters rupture - 4 weeks

HISTORY OF PRESENTING ILLNESS

• Intake of penicillamine, captopril, or other ACE inhibitors
• Exposure to pesticides (fogo selvagem)
• Drug allergies
• Similar illness in family
• Any malignancy

PAST HISTORY

• No history of similar illness in the past
• No history of diabetes mellitus, hypertension, tuberculosis, or asthma
• Not a known case of any autoimmune disorder

PERSONAL HISTORY

• Diet: Vegetarian
• Appetite: Reduced (due to painful oral erosions)
• Sleep: Disturbed (due to pain)
• Bowel & Bladder: Normal
• Smoking: Non-smoker
• Alcohol: Non-alcoholic

FAMILY HISTORY

• No similar illness in family members
• No family history of autoimmune disorders

DRUG HISTORY

• Not on any long-term medications
• No history of intake of drugs known to trigger pemphigus (penicillamine, rifampicin, nifedipine, captopril, penicillin, gold salts)

GENERAL PHYSICAL EXAMINATION

• Patient is conscious, cooperative, and oriented
• Moderately built, moderately nourished
• Pallor: Mild (due to chronic disease)
• Icterus: Absent
• Cyanosis: Absent
• Clubbing: Absent
• Lymphadenopathy: Mild bilateral cervical lymphadenopathy (reactive, due to secondary infection)
• Oedema: Absent
• Dehydration: Mild (due to fluid loss from extensive erosions)
• Temperature: 37.8°C (low-grade fever due to secondary infection)
• Pulse: 90/min, regular
• Blood Pressure: 110/70 mmHg
• Respiratory Rate: 18/min
• Weight: 62 kg

DERMATOLOGICAL EXAMINATION

A. Distribution of Lesions

• Face (perioral region, cheeks)
• Scalp
• Neck
• Trunk (chest, back - most severely affected)
• Axillae (bilateral)
• Groin (bilateral)
• Oral mucosa

B. Primary Lesions

• Blisters (Bullae): Multiple, thin-walled, flaccid bullae of varying sizes (0.5 to 4 cm), arising on apparently normal or slightly erythematous skin. Contents are clear/serous, some hemorrhagic.
• Most notably on the back: Large confluent areas of denuded skin with a few intact blisters at the periphery.

C. Secondary Lesions

• Erosions: Raw, moist, painful erosions resulting from ruptured bullae. Erosions show a tendency to spread peripherally.
• Crusting: Shallow crusts overlying healing erosions; no deep scarring.
• Post-inflammatory hyperpigmentation in areas of healed lesions.
• No scarring on healing.

D. Special Signs

E. Mucosal Examination

• Oral cavity: Multiple painful erosions involving buccal mucosa, palate, gingiva, tongue, and lips. Erosions are ragged with no tendency to heal. Lips show fissured, hemorrhagic crusts at vermilion border. Offensive mouth odour present.
• Conjunctiva: Not involved (no conjunctival erosions)
• Genitalia: Not involved

F. Hair and Nails

• Hair: Thinning noted over scalp (approximately 5% of PV patients; temporary hair loss possible)
• Nails: No periungual involvement

SYSTEMIC EXAMINATION

• Cardiovascular System: S1 S2 heard, no murmurs
• Respiratory System: Air entry bilateral, vesicular breath sounds
• Abdomen: Soft, non-tender, no organomegaly
• Central Nervous System: Higher functions intact, no focal deficits

PROVISIONAL DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

INVESTIGATIONS

Routine

Specific Investigations

• Site: Perilesional skin / base of fresh intact bulla (using Asboe-Hansen manoeuvre to extend bulla)
• Expected finding: Suprabasal acantholysis with intraepidermal blister formation. "Tombstone row" of basal keratinocytes at floor of blister. Acantholytic (Tzanck) cells - rounded keratinocytes with lost intercellular bridges in blister cavity.

• Sample: Perilesional skin (4 mm punch biopsy)
• Expected finding: "Chicken wire" / "fishnet" pattern of intercellular IgG deposits throughout the epidermis. C3 may also be present. Staining is uniform, not granular.

• Substrate: Monkey oesophagus or guinea pig lip
• Expected finding: Intercellular IgG on epithelial cell surfaces
• Titre correlates with disease activity

• Anti-Dsg3 antibody: Positive (mucosal involvement)
• Anti-Dsg1 antibody: Positive (cutaneous involvement - correlates with mucocutaneous disease)
• Antibody titre can be used to monitor disease activity and treatment response

• Sample: Scraping from floor of fresh erosion
• Expected: Acantholytic (Tzanck) cells - large, rounded keratinocytes with hyperchromatic nucleus, lost intercellular bridges (non-specific, supportive)

DIAGNOSIS

• Clinical features (flaccid bullae, positive Nikolsky sign, mucosal erosions)
• Histopathology (suprabasal acantholysis, tombstone row, Tzanck cells)
• DIF (intercellular IgG "chicken wire" pattern)
• ELISA: Anti-Dsg1 and Anti-Dsg3 positive

PATHOGENESIS (Summary)

• Dsg3 is predominantly expressed in the lower epidermis and mucosa. Anti-Dsg3 alone causes mucosal erosions.
• Dsg1 is expressed throughout the epidermis. Anti-Dsg1 + Anti-Dsg3 together cause mucocutaneous disease (full pemphigus vulgaris).

TREATMENT

General Measures

1. Admit to ward (if extensive disease)
2. Barrier nursing to prevent secondary infection
3. Wound care: Gentle daily cleansing of erosions with saline, silver sulfadiazine 1% cream application to denuded areas
4. Oral hygiene: Antiseptic mouthwash (0.12% chlorhexidine) for oral erosions
5. Nutritional support: High-protein diet; IV fluids if dehydrated; albumin infusion if severely low
6. Pain management: Analgesics; topical lidocaine gel for oral lesions
7. Prophylaxis: Co-trimoxazole (trimethoprim-sulfamethoxazole) for Pneumocystis jirovecii prophylaxis if on high-dose immunosuppression

Specific Medical Treatment

First-Line: Systemic Corticosteroids

• Prednisolone 1-1.5 mg/kg/day orally (started as initial control dose)
• Continue until new blister formation stops and existing lesions begin healing
• Gradual tapering: 25% dose reduction every 2-4 weeks once disease controlled
• Pulse therapy (for severe/resistant cases): IV methylprednisolone 1 g/day for 3-5 days

Steroid-Sparing Adjuvant Agents (to reduce cumulative steroid dose)

Biologics (for Moderate-to-Severe / Refractory Disease)

• Rituximab (anti-CD20 monoclonal antibody): 1000 mg IV x 2 doses 2 weeks apart (rheumatoid arthritis protocol), or 375 mg/m² IV weekly x 4 doses (lymphoma protocol). Now considered first-line for severe disease by many experts. The Ritux 3 trial (Lancet, 2017) demonstrated superiority of rituximab + short-term prednisone vs prednisone alone.
• Intravenous Immunoglobulin (IVIG): 2 g/kg over 3-5 days; used in combination with rituximab in severe cases

Topical Treatment

• Potent topical corticosteroids (clobetasol propionate) for localised lesions
• Silver sulfadiazine cream for extensive denuded areas (antibacterial + wound healing)

Monitoring

• New blister count (Pemphigus Disease Activity Index - PDAI)
• Anti-Dsg ELISA titres - correlate with disease activity; negative DIF predicts sustained remission
• Bone density (DEXA scan) - due to long-term corticosteroid use
• Blood glucose, blood pressure, weight - steroid side effects
• CBC, LFT, renal function - monitoring for immunosuppressant toxicity

COMPLICATIONS

From Disease

• Secondary bacterial infection (most common) leading to sepsis
• Fluid and electrolyte imbalance (hyponatraemia, hypoalbuminaemia)
• Malnutrition (due to painful oral erosions)
• Respiratory compromise (if laryngeal/tracheal mucosa involved)
• Oesophagitis dissecans superficialis (sloughing of oesophageal mucosa)

From Treatment (Corticosteroid Side Effects)

• Cushing's syndrome
• Osteoporosis and vertebral fractures
• Hyperglycaemia / steroid-induced diabetes
• Hypertension
• Opportunistic infections (bacterial, fungal - especially Candida, Pneumocystis)
• Peptic ulcer disease
• Cataract / Glaucoma
• Adrenal suppression

PROGNOSIS

• Prior to corticosteroids: Mortality was ~75% (from sepsis, malnutrition, fluid loss)
• With treatment: Mortality has fallen to approximately 5-10%; most deaths now from treatment complications rather than disease itself
• Mucocutaneous type (anti-Dsg1 + anti-Dsg3) generally has a more protracted course than mucosal-dominant type
• Reversion of DIF to negative predicts sustained remission after drug withdrawal
• Rituximab-treated patients have high rates of long-term complete remission

DISCHARGE ADVICE / PATIENT EDUCATION

1. Continue all medications as prescribed; do not stop steroids abruptly
2. High-protein, calcium-rich diet; avoid spicy/hard foods until oral erosions heal
3. Avoid triggers: UV exposure, trauma, heat; use sun protection
4. Avoid drugs that may trigger pemphigus (penicillamine, captopril)
5. Regular follow-up every 4 weeks initially, then every 3 months
6. Watch for signs of secondary infection - report immediately
7. Carry a steroid card; alert any new physician about current medications
8. Bone protection: Calcium 1000 mg/day + Vitamin D 800 IU/day supplementation

REFERENCES

• Fitzpatrick's Dermatology, 9th Ed, Chapter 52 - Pemphigus
• Andrews' Diseases of the Skin, 13th Ed, Chapter 21 - Pemphigus Vulgaris
• Robbins & Kumar Basic Pathology, Chapter 22 - Pemphigus Vulgaris and Pemphigus Foliaceus
• Dermatology, 2-Volume Set, 5th Ed (Bolognia) - Chapter 29 - Pemphigus

VIVA / LONG CASE QUESTIONS AND ANSWERS

Q1. What is pemphigus? How is it classified?

Q2. What is the autoantigen in pemphigus? What is the desmoglein compensation hypothesis?

• Pemphigus Vulgaris: Dsg3 (mucosal type) and Dsg1 + Dsg3 (mucocutaneous type)
• Pemphigus Foliaceus: Dsg1 only

• Dsg3 is abundant in the lower epidermis and throughout oral mucosa
• Dsg1 is expressed throughout the epidermis but is absent/minimal in oral mucosa

Q3. What is Nikolsky sign? In which conditions is it positive?

• Pemphigus (all types) - true Nikolsky
• Staphylococcal Scalded Skin Syndrome (SSSS)
• Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis (TEN)
• Bullous impetigo
• Linear IgA dermatosis

• Bullous Pemphigoid
• Dermatitis Herpetiformis
• Epidermolysis Bullosa (non-acquired types)

Q4. Describe the histopathology of pemphigus vulgaris.

1. Suprabasal acantholysis - loss of cohesion between keratinocytes just above the basal cell layer, creating a cleft/blister within the epidermis
2. "Tombstone row" - basal keratinocytes remain attached to the basement membrane, appearing like a row of tombstones at the blister floor
3. Acantholytic (Tzanck) cells - free-floating, rounded keratinocytes with enlarged hyperchromatic nuclei and lost intercellular bridges within the blister cavity
4. Blister contents - serous fluid, acantholytic cells, occasional eosinophils and neutrophils
5. Dermal changes - mild perivascular infiltrate of lymphocytes and eosinophils

Q5. Describe the immunofluorescence findings in pemphigus vulgaris.

Q6. How do you differentiate Pemphigus Vulgaris from Bullous Pemphigoid?

Q7. What are the scoring systems used in pemphigus?

Q8. What is paraneoplastic pemphigus?

• Severe, painful, refractory oral and conjunctival erosions (hallmark)
• Polymorphous skin lesions (blistering + lichenoid + erythema multiforme-like)
• Autoantibodies against multiple plakin family proteins: periplakin, envoplakin, desmoplakin I & II, BP230, and Dsg1/3
• Bronchiolitis obliterans (pulmonary involvement) is a major cause of mortality
• DIF: Intercellular IgG + linear BMZ IgG
• Poor prognosis; mortality >90% in some series

Q9. What drugs cause pemphigus?

• P - Penicillamine (most common - thiol drug)
• C - Captopril / ACE inhibitors
• B - Beta-lactam antibiotics (penicillin, cephalosporins)
• R - Rifampicin
• I - Immune checkpoint inhibitors (pembrolizumab, nivolumab)
• N - Nifedipine
• G - Gold salts

Q10. What is Fogo Selvagem?

Q11. What is Pemphigus Vegetans?

• Neumann type: Starts as PV-like bullae that heal with hypertrophic/vegetating plaques covered with pustules, especially in intertriginous areas (axillae, groin, scalp); more severe
• Hallopeau type (pyodermite végétante): Primary pustular lesions that evolve to vegetating plaques; milder course with higher remission rate

Q12. Outline the treatment of pemphigus vulgaris.

• Prednisolone 1-1.5 mg/kg/day + adjuvant (azathioprine or MMF)
• Continue until no new lesions for 2 weeks and 80% of old lesions healed

• Slow taper of prednisolone (25% reduction every 4-6 weeks)
• Maintain adjuvant agent

• Lowest effective dose of prednisolone (ideally ≤10 mg/day)
• Continue adjuvant

• Aim for complete clinical and immunological remission (DIF negative)
• Trial of drug withdrawal after 2 years of sustained remission

• Rituximab 1000 mg IV x 2 (Day 1 and Day 15) + short-course prednisolone
• Superior long-term remission with fewer steroid side effects (Ritux 3, Lancet 2017)

CERTIFICATE OF CLINICAL EXAMINATION

• Student Name: ______________________
• Reg. No.: ______________________
• Clinical Posting: Dermatology, Venereology & Leprosy
• Date: 14 / 07 / 2026
• Examined by: ______________________
• Signature of Guide/Examiner: ______________________
• Marks: ________ / ______