A 38-year-old man presents with a 5-year history of well-demarcated erythematous plaques with silvery scales over the extensor surfaces of elbows and knees, along with pitting of nails. Lesions worsen in winter. What is the drug of choice for initiating systemic therapy in this patient with moderate plaque psoriasis?

Explanation

## First-Line Systemic Agent for Moderate Plaque Psoriasis **Key Point:** Methotrexate is the gold-standard first-line systemic agent for moderate-to-severe plaque psoriasis, offering rapid onset of action, proven efficacy, and a well-established safety profile in dermatology. ### Mechanism of Action Methotrexate acts as a folate antagonist, inhibiting dihydrofolate reductase and suppressing T-cell proliferation and inflammatory cytokine production (TNF-α, IL-6, IL-8). It also reduces keratinocyte proliferation. ### Dosing & Monitoring - **Starting dose:** 7.5–10 mg once weekly (oral or IM) - **Escalation:** Increase by 2.5–5 mg every 4–8 weeks up to 15–25 mg/week based on response - **Onset:** 4–8 weeks; peak effect at 12–16 weeks - **Monitoring:** CBC, LFTs, renal function at baseline and every 8–12 weeks ### Clinical Advantages - Rapid and sustained response in 70–80% of patients - Cost-effective and widely available - Can be combined with topical agents or biologics - Suitable for patients with psoriatic arthritis (dual benefit) **High-Yield:** Methotrexate is preferred over acitretin and cyclosporine as first-line because it has the best efficacy-to-risk ratio, lower teratogenicity risk than acitretin, and fewer long-term safety concerns than cyclosporine. ### Contraindications & Precautions - Pregnancy (teratogenic) — requires effective contraception in women of childbearing age - Active infection, severe hepatic or renal disease - Bone marrow suppression - Concurrent use with NSAIDs increases toxicity **Clinical Pearl:** Folic acid 1 mg daily (on non-methotrexate days) reduces toxicity without compromising efficacy. [cite:Griffiths & Barker Rook's Textbook of Dermatology Ch 35]