Pemphigus Vulgaris

Pemphigus vulgaris (PV) is a life threatening autoimmune intraepidermal blistering disease caused by IgG autoantibodies against desmoglein 3 (mucosal dominant) and desmoglein 1 (mucocutaneous), with loss of keratinocyte adhesion (acantholysis).

• Incidence is 1 to 5 per million per year, higher in Ashkenazi Jewish, Mediterranean and South Asian people. Onset is between 40 and 60 years. HLA-DRB1*04:02 and DQB1*05:03 are the strongest associations.
• Triggers: drugs with thiol groups (penicillamine, captopril), rifampicin, NSAIDs, and rarely infections. Paraneoplastic pemphigus is a separate disorder.
• Untreated mortality is nearly 75%; with treatment it is about 5%, mainly from infection and therapy complications.

• Painful oral erosions (buccal mucosa, palate, gingiva) often precede skin disease by months.
• Flaccid blisters that rupture to leave painful erosions on skin, scalp, trunk, axillae and groin. Nikolsky sign positive and Asboe-Hansen sign present.
• Pharyngeal, laryngeal, oesophageal, conjunctival and genital involvement. Hoarseness, dysphagia, weight loss.
• Superinfection (Staphylococcus, HSV) and fluid and protein loss in extensive disease.

• Biopsy of an early blister edge: suprabasal acantholysis with a "tombstone" appearance of basal cells.
• Perilesional direct immunofluorescence: intercellular IgG and C3 in a "fishnet" pattern (gold standard).
• Serum anti-desmoglein 1 and 3 ELISA (titres correlate with activity); indirect immunofluorescence on monkey oesophagus.
• Baseline before therapy: HbA1c, lipids, bone density, hepatitis B and C, HIV, TB screen, TPMT, and ENT or oesophageal assessment if symptomatic.
• Exclude pemphigus foliaceus, paraneoplastic pemphigus, bullous pemphigoid, erosive lichen planus, SJS, herpetic stomatitis.

• First line (moderate to severe): rituximab 1000 mg IV on days 1 and 15 (or 500 mg at month 12 and 18 as maintenance), with prednisolone 0.5 to 1 mg/kg/day tapered over 3 to 6 months. This achieves complete remission in about 90% and reduces cumulative steroid dose.
• Premedicate rituximab (paracetamol, chlorphenamine, hydrocortisone 100 mg IV); check hepatitis B serology.
• Mild disease: prednisolone 0.5 mg/kg with or without steroid sparing agents.
• Adjuvants: azathioprine 2 to 3 mg/kg (check TPMT), mycophenolate mofetil 1 to 1.5 g twice daily, methotrexate 10 to 25 mg weekly, dapsone 100 mg, cyclophosphamide pulses in refractory disease.
• Refractory or severe: IVIG 2 g/kg over 3 to 5 days monthly, immunoadsorption, plasmapheresis.
• Supportive care: Pneumocystis prophylaxis (co-trimoxazole 960 mg three times weekly), calcium and vitamin D with bisphosphonate, PPI, glucose and BP monitoring, topical clobetasol for erosions, antiseptic baths, mouth rinses with lidocaine and dexamethasone, nutrition, wound care, and low dose HSV prophylaxis if recurrent.
• Monitor anti-Dsg titres. Relapse is common during taper.