A 48-year-old man from Mumbai presents with a 2-month history of recurrent painful oral ulcers and blistering of the palate and buccal mucosa. Over the past 4 weeks, flaccid blisters have appeared on the chest and abdomen, which rupture easily leaving erosions. He denies recent drug use or food allergies. Serum testing reveals positive indirect immunofluorescence with circulating autoantibodies against desmoglein 3 (anti-Dsg3). A skin biopsy from an erosion shows suprabasal acantholysis with preserved basal cell attachment to the basement membrane. What is the most appropriate initial treatment?

Explanation

## Treatment of Pemphigus Vulgaris ### First-Line Therapy **High-Yield:** Systemic corticosteroids are the gold standard initial treatment for pemphigus vulgaris. High-dose oral corticosteroids (prednisolone 1–1.5 mg/kg/day) are required to suppress autoantibody production and achieve disease control. **Key Point:** Topical corticosteroids and antihistamines alone are insufficient for systemic pemphigus vulgaris. They may be used as adjuncts for oral lesions but cannot control the underlying autoimmune process. ### Treatment Algorithm ```mermaid flowchart TD A[Pemphigus Vulgaris Diagnosis]:::outcome --> B[Initiate systemic corticosteroids]:::action B --> C[Prednisolone 1-1.5 mg/kg/day]:::action C --> D{Response in 1-2 weeks?}:::decision D -->|Yes| E[Gradual taper over months]:::action D -->|No| F[Add steroid-sparing agent]:::action F --> G[Azathioprine or Mycophenolate]:::action E --> H[Maintenance therapy]:::action H --> I[Prednisolone 0.5 mg/kg/day or less]:::action ``` ### Steroid-Sparing Agents **Mnemonic: AMMO** (Azathioprine, Mycophenolate, Methotrexate, Others) | Agent | Mechanism | Onset | Typical Dose | |-------|-----------|-------|-------------| | **Azathioprine** | Purine antagonist; inhibits T-cell proliferation | 6–8 weeks | 1–2 mg/kg/day | | **Mycophenolate mofetil** | Selective IMPDH inhibitor; inhibits B-cell proliferation | 4–6 weeks | 1–3 g/day | | **Methotrexate** | Folate antagonist; immunosuppression | 4–6 weeks | 15–25 mg/week | | **Rituximab** | Anti-CD20 monoclonal antibody; B-cell depletion | 2–4 weeks | 375 mg/m² weekly × 4 | **Clinical Pearl:** Rituximab is increasingly used in severe or refractory pemphigus vulgaris and has shown excellent outcomes in clinical trials, but prednisolone remains the initial therapy. ### Rationale for Systemic Corticosteroids 1. **Rapid anti-inflammatory effect:** Suppresses T-cell and B-cell function 2. **Reduces autoantibody production:** Targets the underlying pathogenic mechanism 3. **Achieves remission:** 80–90% of patients achieve clinical remission within 4–8 weeks 4. **Prevents complications:** Prevents secondary infection of erosions and systemic complications **Warning:** Abrupt withdrawal of corticosteroids can precipitate disease flare. Gradual tapering over months is essential. ### Monitoring During Treatment - **Clinical response:** Cessation of new blister formation (1–2 weeks); healing of erosions (2–4 weeks) - **Serological response:** Decline in anti-Dsg3 titers (correlates with clinical improvement) - **Adverse effects:** Screen for hyperglycemia, hypertension, osteoporosis, opportunistic infections **High-Yield:** Early addition of a steroid-sparing agent (azathioprine or mycophenolate) reduces cumulative corticosteroid exposure and long-term toxicity.