Discuss the topical and systemic therapies in psoriasis.

Topical Therapies

Topical therapies are the first-line treatment for mild to moderate psoriasis. They are applied directly to the affected skin and aim to reduce inflammation and slow down skin cell turnover.

• Corticosteroids: These are the most commonly used topical agents. They reduce inflammation and itching. Available in various potencies (class 1-7), the choice depends on the location and severity of psoriasis. Prolonged use can lead to skin atrophy, telangiectasia, and striae.
• Vitamin D Analogues (Calcipotriol, Calcitriol): These agents normalize skin cell growth and reduce inflammation. They are often used in combination with corticosteroids. Side effects include skin irritation and hypercalcemia (rare).
• Retinoids (Tazarotene): These are vitamin A derivatives that normalize skin cell growth and reduce inflammation. They can cause skin irritation, redness, and photosensitivity.
• Coal Tar: A traditional treatment, coal tar reduces inflammation, itching, and scaling. It has an unpleasant odor and can stain clothing.
• Salicylic Acid: A keratolytic agent that helps remove scales and improve penetration of other topical medications.
• Calcineurin Inhibitors (Tacrolimus, Pimecrolimus): These are immunosuppressants used for psoriasis in sensitive areas like the face and skin folds. They carry a black box warning regarding potential malignancy, though the risk is considered low.

Systemic Therapies

Systemic therapies are used for moderate to severe psoriasis or when topical therapies are insufficient. They affect the entire body and have a greater potential for side effects.

• Methotrexate: A folate antagonist that suppresses the immune system and reduces skin cell proliferation. It requires regular monitoring of liver function and blood counts.
• Cyclosporine: An immunosuppressant that inhibits T-cell activation. It can cause nephrotoxicity and hypertension, requiring careful monitoring.
• Acitretin: An oral retinoid that normalizes skin cell growth. It is teratogenic and requires strict contraception measures.
• Apremilast: A phosphodiesterase 4 (PDE4) inhibitor that reduces inflammation. It is generally well-tolerated but can cause diarrhea and nausea.
• Biologic Therapies: These are genetically engineered proteins that target specific components of the immune system.
  • TNF-α inhibitors (Etanercept, Infliximab, Adalimumab): Block tumor necrosis factor-alpha, a key inflammatory cytokine.
  • IL-17 inhibitors (Secukinumab, Ixekizumab, Brodalumab): Block interleukin-17, another important inflammatory cytokine.
  • IL-23 inhibitors (Guselkumab, Risankizumab, Tildrakizumab): Block interleukin-23, a cytokine involved in psoriasis pathogenesis.

Comparison of Systemic Therapies

Therapy	Mechanism of Action	Common Side Effects	Monitoring
Methotrexate	Folate antagonist, immunosuppression	Nausea, fatigue, liver toxicity	Liver function tests, CBC
Cyclosporine	T-cell inhibition	Nephrotoxicity, hypertension	Renal function tests, blood pressure
Acitretin	Retinoid, normalizes skin cell growth	Teratogenicity, hyperlipidemia	Pregnancy test, lipid profile
Apremilast	PDE4 inhibitor, reduces inflammation	Diarrhea, nausea	None routinely required
Biologics	Target specific immune pathways	Injection site reactions, increased risk of infection	Screening for latent TB, monitoring for infections