Immunosuppressive Agents

Corticosteroids - Skin's Mighty Mutes

• Mechanism (MoA): Anti-inflammatory, immunosuppressive, anti-proliferative, vasoconstrictive. Bind cytoplasmic Glucocorticoid Receptors (GR) → modulate gene expression; Inhibit Phospholipase A2 (PLA2) via lipocortin-1 → ↓ Prostaglandins (PGs) & Leukotrienes (LTs).
• Topical Steroid Potency Classification:

  Class	Potency	Examples (0.05% unless stated)
  I	Superpotent	Clobetasol propionate, Halobetasol prop.
  II	Potent	Betamethasone dipropionate, Mometasone furoate (0.1% oint)
  III	Upper Mid	Fluticasone propionate, Triamcinolone acetonide (0.1%)
  IV	Mid-Strength	Mometasone furoate (0.1% cream)
  V	Lower Mid	Desonide, Fluocinolone acetonide (0.01%)
  VI	Mild	Hydrocortisone (1%)
  VII	Least Potent	Hydrocortisone (0.5%)

• Key Indications: Eczema (dermatitis), psoriasis, lichen planus, pemphigoid.
• Topical Side Effects: Skin atrophy, striae, telangiectasias, acneiform eruptions, perioral dermatitis, hypopigmentation. Risk of systemic absorption (↑ with high potency, large area, occlusion).
• Systemic Side Effects: 📌 Cushingoid features (moon facies, buffalo hump), HPA axis suppression, osteoporosis, hyperglycemia, immunosuppression, mood changes.

⭐ Tachyphylaxis (acute tolerance) can occur with continuous prolonged topical steroid use, leading to ↓ efficacy.

TCIs & Methotrexate - Steroid Sparing Stars

• Topical Calcineurin Inhibitors (TCIs)
  • Examples: Tacrolimus, Pimecrolimus.
  • Mechanism: Inhibit calcineurin → ↓ T-cell activation & cytokine release (e.g., IL-2).
  • Uses: Atopic dermatitis (especially face, intertriginous areas), vitiligo.
  • Advantage: No skin atrophy, unlike topical steroids.
  • Side effects: Initial burning/stinging (common, transient), flushing with alcohol.

  ⭐ Black box warning for TCIs: Rare reports of lymphoma and skin malignancies.

• Methotrexate (MTX)
  • Mechanism: Folic acid antagonist; inhibits dihydrofolate reductase → ↓ purine/pyrimidine synthesis.
  • Uses: Psoriasis, psoriatic arthritis, pemphigus vulgaris, mycosis fungoides.
  • Dosing: Weekly (oral, IM, SC). 📌 Mnemonic: MTX = Must Take Xtra (folate).
  • Supplementation: Folic acid (e.g., 5 mg weekly, 24h after MTX) to ↓ toxicity (stomatitis, myelosuppression).
  • Monitoring: CBC, LFTs, renal function tests.
  • Contraindications: Pregnancy (teratogenic), severe liver/kidney disease, active infection.

Azathioprine & MMF - Purine Pathway Players

• Azathioprine (AZA)

  • Prodrug of 6-mercaptopurine (6-MP); inhibits purine synthesis.
  • TPMT testing mandatory. 📌 AZA: "Always Test Purine Metabolism".
  • Dose: 1-3 mg/kg/day.
  • SE: Myelosuppression (esp. low TPMT), hepatotoxicity, GI upset.
  • DDI: Allopurinol (↓ AZA dose 60-75%).

  ⭐ Azathioprine: risk of myelosuppression, especially with low TPMT activity.

• Mycophenolate Mofetil (MMF) / Mycophenolic Acid (MPA)

  • MMF (prodrug) → MPA (active).
  • MOA: Selective IMPDH inhibitor; blocks de novo purine synthesis in lymphocytes. 📌 MMF "Muffles" IMPDH.
  • Dose: MMF 1-2 g/day; EC-MPA 720 mg BID.
  • SE: GI intolerance (diarrhea), leukopenia, teratogenic ⚠️.
  • Adv: More selective than AZA, no TPMT testing required routinely.

Cyclosporine & Biologics - Precision Power

• Cyclosporine: Calcineurin inhibitor; ↓ IL-2, ↓ T-cell activation.
  • Uses: Severe psoriasis, atopic dermatitis, pyoderma gangrenosum.
  • Dose: 2.5-5 mg/kg/day.
  • Side Effects: 📌 "Hairy Gum Bleeder with Bad Kidneys & BP" (Nephrotoxicity, HTN, Hypertrichosis, Gingival hyperplasia). Monitor renal function (Sr. Cr), BP, K+, Mg2+.
• Biologics: Targeted monoclonal antibodies (mAbs) or fusion proteins.
  • Targets: TNF-α (e.g., Infliximab, Adalimumab), IL-17 (e.g., Secukinumab), IL-12/23 (e.g., Ustekinumab), IL-4/13 (e.g., Dupilumab).
  • Screening: Latent TB, Hepatitis B/C before initiation.

⭐ Cyclosporine is highly effective for rapid control of severe psoriasis or atopic dermatitis.

High‑Yield Points - ⚡ Biggest Takeaways

• Topical corticosteroids: Potency guides use; watch for skin atrophy and tachyphylaxis.
• Tacrolimus/Pimecrolimus: Steroid-sparing for atopic dermatitis (face/folds); BBW for lymphoma.
• Methotrexate: For psoriasis/eczema; needs folic acid, monitor LFTs/CBC. Highly teratogenic.
• Azathioprine: TPMT enzyme testing vital before use; risk of myelosuppression. For bullous diseases.
• Cyclosporine: Rapid for severe psoriasis/atopic dermatitis; monitor blood pressure and kidney function.
• Biologics: Targeted for psoriasis; TB screening mandatory pre-treatment_._