Psoriasis Study Guide

📖 Core Concepts Psoriasis – chronic, non‑contagious autoimmune skin disease; hyperproliferative keratinocytes produce erythematous plaques with silvery scales. Key cytokine axis – Th17 cells → IL‑17 / IL‑22 drive keratinocyte proliferation; TNF‑α amplifies inflammation. Clinical types – Plaque (≈90 %); guttate (post‑streptococcal); pustular; inverse; erythrodermic. Koebner phenomenon – new lesions appear at sites of skin trauma. Severity assessment – Body‑Surface‑Area (BSA) ≤ 10 % → mild; >10 % or PASI > 10 → moderate‑severe. Psoriasis Area and Severity Index (PASI) – combines erythema, induration, scaling (0‑4 each) with affected area (0‑6) → total 0‑72. Dermatology Life Quality Index (DLQI) – 10 questions, 0‑30; higher = greater life‑impact. 📌 Must Remember Epidemiology: 2–4 % worldwide; equal sex distribution; peak onset 15‑25 yr. Nail involvement: up to 45 % of skin‑psoriasis patients. Psoriatic arthritis: affects ≈30 % of psoriasis patients. Genetics: PSORS1 (chr 6) accounts for 35‑50 % hereditary risk; concordance in identical twins ≈70 %. Triggers: skin injury, infections (esp. streptococcal), stress, alcohol, smoking, obesity, abrupt steroid withdrawal. Topical first‑line: high‑potency corticosteroid ± vitamin D analogue (synergy). Phototherapy: NB‑UVB (311‑313 nm) ≈ PUVA efficacy; risk of skin cancer with long‑term use. Systemic first‑line for severe disease: methotrexate or ciclosporin; biologics after failure of non‑biologic systemic agents. Biologic targets: TNF‑α, IL‑12/23 (p40), IL‑23 (p19), IL‑17A. Contraindications: oral steroids → rebound flares; anti‑TNF in chronic HBV/HIV; etanercept has low neutralizing‑antibody risk. Comorbidities: 2.2‑fold ↑ cardiovascular events, 1.5‑fold ↑ type 2 diabetes, 28‑55 % depression prevalence. 🔄 Key Processes Immune activation cascade Trauma/infection → dendritic cells release IFN‑α → present antigens to naïve T cells. Differentiation to Th1 & Th17 → secrete IFN‑γ, IL‑17, IL‑22. IL‑17/IL‑22 → keratinocyte hyperproliferation (cell cycle 3‑5 days). Keratinocytes release neutrophil‑attracting cytokines → pustule formation (pustular type). Phototherapy mechanism NB‑UVB induces pyrimidine dimers → interrupts keratinocyte DNA replication and reduces Th17 cytokine expression. Biologic therapeutic algorithm Mild → topical → phototherapy (if refractory). Moderate‑severe → non‑biologic systemic (methotrexate, ciclosporin) → if inadequate/contraindicated → biologic (TNF‑α → IL‑12/23 → IL‑23 → IL‑17). 🔍 Key Comparisons Plaque vs. Guttate → Plaque: raised red patches with silvery scales, chronic; Guttate: drop‑shaped papules, often post‑streptococcal, acute. TNF‑α inhibitor (infliximab) vs. Etanercept → Infliximab: monoclonal antibody, higher potency, risk of neutralizing antibodies; Etanercept: fusion protein, decoy receptor, lower antibody formation. NB‑UVB vs. PUVA → NB‑UVB: 311‑313 nm, no psoralen, lower carcinogenic risk; PUVA: psoralen + UVA, higher SCC risk. Methotrexate vs. Ciclosporin → Methotrexate: antimetabolite, hepatic monitoring; Ciclosporin: calcineurin inhibitor, nephrotoxic & hypertensive risk. ⚠️ Common Misunderstandings “Psoriasis is contagious.” – False; it is autoimmune, not infectious. “Topical steroids cure psoriasis.” – They control flares but do not cure; long‑term use limited to 8 weeks. “All biologics are equally safe in pregnancy.” – Safety not established; many are avoided when pregnancy is planned. “PUVA is always safer than NB‑UVB.” – PUVA has higher cumulative UV dose and greater SCC risk. 🧠 Mental Models / Intuition “Cytokine waterfall” – Picture a waterfall where dendritic cells splash IFN‑α, spawning Th17 “rocks” that cascade IL‑17/IL‑22 downstream, flooding the epidermis with rapid keratinocyte growth. “Severity ladder” – BSA ≤ 10 % → stay on the first rung (topicals); climb higher → phototherapy → systemic → biologics at the top. 🚩 Exceptions & Edge Cases Neutralizing antibodies develop against infliximab, adalimumab, etc.; not seen with etanercept. Pustular psoriasis on palms/soles (palmoplantar) may require systemic therapy even if BSA < 10 %. Erythrodermic psoriasis → life‑threatening, mandates systemic/biologic therapy regardless of PASI. 📍 When to Use Which Mild, localized plaques → high‑potency topical steroid ± vitamin D analogue. Moderate disease (>10 % BSA) or refractory to topicals → NB‑UVB phototherapy. Severe plaque or erythrodermic disease → start methotrexate or ciclosporin; if contraindicated or failure → TNF‑α inhibitor. Psoriatic arthritis present → add NSAIDs → DMARDs (methotrexate, sulfasalazine) → consider TNF‑α or IL‑17 biologic. History of chronic HBV or HIV → avoid anti‑TNF agents; prefer IL‑17/IL‑23 inhibitors if needed. 👀 Patterns to Recognize Post‑streptococcal guttate flare → sudden papular eruption on trunk/extremities in children. Koebner sign → new plaques at sites of scratches, tattoos, or surgical scars. Auspitz’s sign – pinpoint bleeding when scales are removed → classic plaque psoriasis. Pustular lesions with surrounding erythema → think pustular or palmoplantar pustular type; may signal systemic involvement. 🗂️ Exam Traps “Biologics cure psoriasis” – they control disease; relapse common after discontinuation. “PUVA is safer than NB‑UVB for cancer risk” – opposite; PUVA carries higher SCC risk. “Oral corticosteroids are first‑line for severe disease” – they are contraindicated due to rebound flares. “All patients with psoriasis need routine blood work” – only those on systemic/biologic agents require monitoring. “Psoriasis prevalence is higher in African Americans” – actually lower; highest in people of European descent.