Notes · Dermatology · 10 October 2026

Pemphigus vulgaris

Definition

• Pemphigus vulgaris (PV) is an autoimmune intra‑epidermal blistering disease characterized by IgG auto‑antibodies directed against desmoglein‑3 (and often desmoglein‑1), leading to loss of keratinocyte adhesion (acantholysis).
• Clinically presents with flaccid bullae and painful erosions that involve skin and mucous membranes, most commonly the oral cavity.

Epidemiology

• Incidence: 0.5–1.5 cases per 100 000 population per year worldwide; slightly higher in Mediterranean, Ashkenazi Jewish, and South‑Asian groups.
• Age: Peak onset 40–60 years; rare in children.
• Sex: Slight female predominance (≈1.5:1).
• Geography (India): Reported incidence 0.1–0.3/100 000; higher in northern states; urban referral centres see ~30–40 new cases/year.

Aetiology / Risk Factors

• Genetic predisposition: HLA‑DRB104, HLA‑DRB114, HLA‑DQ alleles.
• Environmental triggers:
  • Drugs (thiols, phenols, penicillamine, ACE inhibitors, NSAIDs).
  • Infections (HSV, CMV, H. pylori).
  • Physical trauma (Koebner phenomenon).
• Other associations: Thyroid disease, rheumatoid arthritis, lupus erythematosus, and malignancies (rare).

Pathophysiology

• Auto‑antibodies (IgG4 subclass) bind desmoglein‑3 (predominantly mucosal) and desmoglein‑1 (skin) → disruption of desmosomal cadherins → acantholysis.
• “Desmoglein compensation theory”:
  • Mucosal lesions when only Dsg‑3 is targeted (Dsg‑1 compensates in skin).
  • Mucocutaneous disease when both Dsg‑3 and Dsg‑1 are targeted.
• Complement activation and inflammatory cytokines (IL‑1, TNF‑α) amplify keratinocyte damage.
• T‑cell help (Th2 cytokines) drives B‑cell production of pathogenic IgG.

Clinical Features

• Mucosal involvement (≈90%):
  • Painful oral erosions (buccal mucosa, palate, gingiva).
  • Pharyngeal, laryngeal, genital erosions may occur.
• Cutaneous lesions (≈70%):
  • Flaccid bullae <1 cm that rupture easily → erosions with a positive Nikolsky sign.
  • Distribution: scalp, face, trunk, intertriginous areas; sparing of palms/soles.
• Prodromal phase: Nonspecific soreness, burning, or “herpetiform” vesicles.
• Systemic signs: Low‑grade fever, malaise in severe disease.

Investigations

Management (Current Guidelines – 2024)

1. Acute Control

• Systemic corticosteroids:
  • Prednisone 1–1.5 mg/kg/day (max 100 mg) until disease control (usually 2–4 weeks).
  • Taper by 10 % every 2 weeks once lesions are quiescent.
• Adjunctive steroid‑sparing agents (first‑line):
  • Rituximab (anti‑CD20) – 1 g IV on day 1 and day 15 (or 375 mg/m² weekly ×4). Recommended as first‑line in moderate‑severe PV (British Society for Dermatology 2023, updated 2024).
  • Azathioprine 2–2.5 mg/kg/day or Mycophenolate mofetil 1–2 g/day if rituximab unavailable.
• Topical therapy: High‑potency corticosteroid ointment (clobetasol 0.05 %) for limited oral lesions; analgesic mouthwash (lidocaine).

2. Maintenance / Long‑term Therapy

• Rituximab repeat dosing based on B‑cell repopulation or clinical relapse (usually 6–12 months).
• Low‑dose oral steroids (≤10 mg/day) + steroid‑sparing agent for 12–24 months.
• Monitoring: ELISA titers every 3 months; CBC, LFT, renal function every 2–3 months.

3. Management of Refractory Disease

• Intravenous immunoglobulin (IVIG) 2 g/kg over 2–5 days (monthly cycles).
• Cyclophosphamide 1–2 mg/kg/day (reserved for severe, non‑responsive cases).
• Plasmapheresis in life‑threatening pemphigus (e.g., extensive mucosal involvement with airway compromise).

4. Supportive Care

• Infection prophylaxis: Trimethoprim‑sulfamethoxazole for Pneumocystis jirovecii if steroids >20 mg/day >1 month.
• Bone health: Calcium 1 g + Vitamin D 800 IU daily; consider bisphosphonate if steroids >3 months.
• Vaccination: Inactivated vaccines (influenza, hepatitis B) before immunosuppression; avoid live vaccines while on rituximab.

Complications

• Infections: Bacterial (Staph, Strep), fungal (candidiasis), viral (HSV, VZV).
• Medication‑related: Steroid‑induced diabetes, hypertension, osteoporosis, avascular necrosis; azathioprine hepatotoxicity; rituximab infusion reactions.
• Nutritional: Malnutrition due to painful oral lesions → weight loss, anemia.
• Psychosocial: Depression, anxiety, social isolation.
• Rare: Paraneoplastic pemphigus, squamous cell carcinoma in chronic ulcerated areas.

High‑Yield Exam Points

• Desmoglein compensation theory explains mucosal‑only vs. mucocutaneous disease.
• Positive Nikolsky sign is a bedside hallmark of PV (also seen in toxic epidermal necrolysis).
• DIF “fish‑net” pattern is diagnostic; differentiate from bullous pemphigoid (linear BMZ).
• Rituximab is now first‑line for moderate‑severe PV (2023‑24 BSG/ICD guidelines).
• Oral lesions precede skin lesions in >90 % of cases – a key clue in history taking.
• Tzanck smear shows acantholytic cells but cannot differentiate pemphigus from Hailey‑Hailey disease.
• Steroid‑sparing agents are essential to reduce long‑term corticosteroid morbidity.
• ELISA anti‑Dsg‑3 >20 U/mL correlates with active disease; falling titres predict remission.

Practice questions

1. A 45‑year‑old woman presents with painful oral erosions for 3 weeks and flaccid bullae on the trunk that rupture easily. Tzanck smear shows acantholytic cells. Which immunofluorescence finding is most characteristic?
Answer: Direct immunofluorescence showing intercellular IgG and C3 in a “fish‑net” pattern – diagnostic of pemphigus vulgaris.

2. According to the 2024 British Society for Dermatology guideline, the preferred first‑line systemic therapy for moderate‑severe pemphigus vulgaris is:
A) High‑dose oral prednisolone alone
B) Azathioprine monotherapy
C) Rituximab combined with low‑dose steroids
D) Cyclophosphamide
Answer: C — Rituximab combined with low‑dose steroids is recommended as first‑line for moderate‑severe PV.

3. Which of the following statements best explains why palm and sole skin are usually spared in pemphigus vulgaris?
A) They lack desmoglein‑3 expression.
B) They have a thick stratum corneum that prevents antibody penetration.
C) Desmoglein‑1 predominates and compensates for loss of desmoglein‑3.
D) High keratinocyte turnover neutralizes auto‑antibodies.
Answer: C — Desmoglein‑1 predominates in palm/sole epidermis and compensates for desmoglein‑3 loss, preventing blister formation.

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