Phototherapy and Biologics for Psoriasis

Phototherapy - Sunbeams & Skin

• Mechanism: Immunomodulatory (↓T-cell activity), antiproliferative (↓keratinocyte turnover).
• Types:
  • NB-UVB (Narrowband UVB): 311-313 nm. First-line. Good efficacy, safer profile (children, pregnancy).
  • PUVA (Psoralen + UVA): Psoralen (oral/topical) + UVA (320-400 nm). Highly effective for severe cases. Higher risk.
• Indications: Moderate-severe widespread plaque, guttate, or palmoplantar psoriasis.
• Adverse Effects (AEs):
  • NB-UVB AEs: Erythema, pruritus, xerosis, long-term photoaging.
  • PUVA AEs: Nausea, phototoxicity, ↑ Squamous Cell Carcinoma (SCC) risk, cataracts. 📌 PUVA: Psoralens Used, Very Aware of SCC.

⭐ NB-UVB is preferred for maintenance therapy due to its lower cumulative toxicity and reduced long-term skin cancer risk.

Biologics Intro & Screening - Psoriasis Precision Strikes

• What: Engineered proteins targeting specific immune mediators (cytokines, receptors). "Precision strikes."
• Indications: Moderate-severe plaque psoriasis, psoriatic arthritis; unresponsive/contraindicated to conventional systemic therapies.
• Broad Classes: TNF-α, IL-17, IL-23, IL-12/23 inhibitors.
• Pre-treatment Screening (Mandatory):
  • Tuberculosis: IGRA (preferred) or TST; Chest X-ray. Treat latent TB.
  • Viral Hepatitis: HBsAg, Anti-HCV, HIV.
  • Labs: CBC, LFTs, KFTs, lipid profile.
  • Exclude: Active serious infection, demyelinating disorders, mod-severe CHF (NYHA Class III/IV), current/recent malignancy.

⭐ All patients MUST be screened for latent TB (IGRA or TST & CXR) before initiating biologic therapy due to significant reactivation risk.

TNF-α Inhibitors - Tumour Necrosis Takedown

• Mechanism: Bind TNF-α, block receptor interaction.
• Key Drugs:
  • Etanercept (fusion protein).
  • Infliximab (chimeric mAb).
  • Adalimumab (human mAb).
• ⚠️ Adverse Effects:
  • ↑ Infection risk (TB reactivation; screen prior).
  • Demyelinating disorders.
  • Drug-induced lupus.
  • Worsening heart failure.
  • Malignancy.
• 📌 Mnemonic: "ETA IN ADA" (Etanercept, Infliximab, Adalimumab).

⭐ Screening for latent TB (Mantoux/IGRA) is mandatory before starting TNF-α inhibitors due to reactivation risk.

Interleukin Inhibitors - Cytokine Cascade Control

• Target key cytokines: IL-12, IL-23, IL-17.
• IL-12/23 Inhibitor (p40 subunit):
  • Ustekinumab: Psoriasis, psoriatic arthritis. 45/90mg SC 0, 4 wks, then q12w.
• IL-17 Inhibitors (IL-17A/IL-17RA): Rapid onset.
  • Secukinumab (IL-17A): 300mg SC (load, then monthly).
  • Ixekizumab (IL-17A): 80mg SC (load, then q2-4w).
  • Brodalumab (IL-17RA): ⚠️ Suicidal ideation risk.

    ⭐ Brodalumab (IL-17RA blocker) has a black box warning for suicidal ideation/behavior.

• IL-23 Inhibitors (p19 subunit): Selective.
  • Guselkumab: 100mg SC q8w (post-load).
  • Risankizumab: 150mg SC q12w (post-load).
  • Tildrakizumab: 100mg SC q12w (post-load).
• TB screening essential pre-treatment.

Biologic Management - Navigating Advanced Care

• Pre-treatment: Screen for latent TB (QuantiferON-TB Gold/Mantoux), HBV, HCV.
• Monitoring: Watch for infections. Regular CBC, LFTs. Evaluate response (e.g., PASI 75).
• Choice Factors: Severity (PASI), type (PsA), comorbidities (IBD, demyelination, CHF), patient preference, prior therapy.
• Vaccinations: Inactivated vaccines 2-4 weeks prior. Live vaccines strictly contraindicated during therapy.

⭐ All patients must be screened for latent tuberculosis before initiating biologic therapy due to risk of reactivation.

High-Yield Points - ⚡ Biggest Takeaways

• NB-UVB (311 nm) is preferred phototherapy; safer than PUVA.
• PUVA (Psoralen + UVA) increases SCC risk; requires eye protection.
• Biologics target: TNF-α (infliximab), IL-12/23 (ustekinumab), IL-17 (secukinumab), IL-23p19 (guselkumab).
• Screen for latent TB, Hepatitis B/C, HIV before starting biologics.
• TNF-α inhibitors: Risk of TB reactivation, demyelination, worsening heart failure.
• IL-17 inhibitors: Risk of candidiasis, may worsen IBD.
• Ustekinumab targets p40 subunit of IL-12/IL-23.