Category: signaling
Topical anti-inflammatory pharmacology for atopic + inflammatory skin diseases (atopic dermatitis, psoriasis, contact dermatitis, lichen, vitiligo). Three primary mechanistic classes: (1) Topical corticosteroids (TCS) — GR agonists with potency stratified by class (super-potent class I clobetasol → class VII low-potency hydrocortisone-topical). GR → transrepression of NF-κB target cytokines + induction of anti-inflammatory genes (lipocortin-1, IκBα). Side effects: skin atrophy, striae, telangiectasia, HPA suppression with prolonged + high-potency use; tachyphylaxis. (2) Topical calcineurin inhibitors (TCI) — tacrolimus-topical 0.03/0.1%, pimecrolimus 1%. FKBP12-calcineurin complex blocks NFAT → ↓IL-2 + ↓IL-4 + ↓IL-13. Steroid-sparing alternative, especially in atopic dermatitis on face/folds. Original FDA boxed warning for theoretical malignancy risk has eased. (3) PDE4 inhibitors — crisaborole 2% — cAMP elevation → ↓pro-inflammatory cytokines. Steroid-sparing, mild atopic dermatitis. (4) Topical JAK inhibitors — ruxolitinib-topical (Opzelura, atopic dermatitis + vitiligo) — JAK1/2 inhibition → ↓IFN + IL-4 + IL-13 signaling. Strategy: highest-potency steroid burst → step-down → maintenance with steroid-sparing TCI / PDE4 / JAKi to avoid TCS adverse effects. Cross-links: [[glucocorticoid_receptor_signaling]] (TCS mechanism), [[calcineurin_nfat_t_cell_activation]] (TCI mechanism), [[jak_stat_signaling]] (JAKi), [[asthma_th2_eosinophil_inflammation]] (atopic march).