A 52-year-old woman presents with painful blisters on the oral mucosa and skin of the chest and abdomen for 3 weeks. Histopathology shows intraepidermal acantholysis with suprabasal clefting. Direct immunofluorescence reveals IgG and C3 deposits in an intercellular pattern. What is the drug of choice for initial management of pemphigus vulgaris?

Explanation

## First-Line Treatment of Pemphigus Vulgaris **Key Point:** Systemic corticosteroids (prednisolone or methylprednisolone) are the gold standard and first-line treatment for pemphigus vulgaris, regardless of disease severity or extent. ### Rationale for Systemic Corticosteroids 1. **Immunosuppressive mechanism**: Corticosteroids suppress antibody production against desmoglein 3 (and desmoglein 1 in mucocutaneous disease), the primary pathogenic autoantigen in pemphigus vulgaris. 2. **Rapid disease control**: They achieve clinical remission faster than any steroid-sparing agent alone. 3. **Evidence-based**: Established as first-line in all major dermatology textbooks and international guidelines. ### Typical Initial Dosing - **High-dose induction**: Prednisolone 1–1.5 mg/kg/day (typically 40–60 mg/day) for 4–6 weeks until new blister formation ceases. - **Gradual taper**: Once disease control is achieved, slow tapering over months to minimize relapse. - **Steroid-sparing agents**: Azathioprine, mycophenolate mofetil, or rituximab are added after 2–4 weeks to allow steroid dose reduction and prevent long-term toxicity. ### Role of Adjunctive Agents | Agent | Role | Timing | | --- | --- | --- | | Azathioprine | Steroid-sparing | Added at week 2–4 of corticosteroid therapy | | Mycophenolate mofetil | Steroid-sparing | Alternative to azathioprine | | Rituximab (anti-CD20) | Severe/refractory cases | Reserved for corticosteroid-resistant disease | | Topical corticosteroids | Adjunctive only | For localized lesions; never monotherapy | **High-Yield:** The combination of systemic corticosteroids + azathioprine is superior to corticosteroids alone in reducing cumulative steroid dose and improving long-term outcomes [cite:Dermatology Textbook]. **Clinical Pearl:** Oral involvement (painful erosions) is present in >90% of pemphigus vulgaris cases at presentation and often precedes skin lesions; this mandates early systemic therapy, not topical treatment alone. **Warning:** Topical corticosteroids or tacrolimus alone are ineffective for systemic pemphigus vulgaris and delay appropriate treatment, increasing morbidity and mortality risk.