Atopic Eczema — SCE Dermatology MCQ

Correct answer: D — Calcineurin (via binding to FKBP-12), blocking T-cell activation and inflammatory cytokine production

The correct answer is D: Calcineurin (via binding to FKBP-12), blocking T-cell activation and inflammatory cytokine production. Tacrolimus is a macrolide that enters T cells and binds the cytosolic immunophilin FKBP-12; this complex then binds and inhibits the phosphatase calcineurin, preventing dephosphorylation and nuclear translocation of NFAT. Without nuclear NFAT, transcription of IL-2 and other pro-inflammatory cytokine genes is switched off, suppressing T-cell activation and the cutaneous inflammatory cascade driving atopic eczema. This calcineurin-inhibitor mechanism, distinct from corticosteroids, explains why topical tacrolimus does not cause skin atrophy and is licensed for eczema unresponsive to, or intolerant of, conventional therapy, including sensitive sites such as the face and flexures. Why the other options are wrong: E. JAK kinases: this is the mechanism of oral or topical JAK inhibitors (eg baricitinib, topical ruxolitinib/delgocitinib), which block cytokine receptor signalling downstream of JAK-STAT pathways, not calcineurin/NFAT signalling used by tacrolimus. A. Cyclooxygenase-2: COX-2 inhibition is the mechanism of NSAIDs, reducing prostaglandin synthesis; tacrolimus has no effect on the arachidonic acid pathway. C. Dihydrofolate reductase: this is the target of methotrexate, which impairs purine/pyrimidine synthesis and lymphocyte proliferation, an entirely separate immunosuppressive pathway from calcineurin inhibition. B. Phosphodiesterase-4: PDE4 inhibition (eg crisaborole, apremilast) raises intracellular cAMP to reduce cytokine release, a different enzyme target unrelated to the calcineurin-NFAT axis blocked by tacrolimus. Key point: Tacrolimus binds FKBP-12 to inhibit calcineurin, halting NFAT-driven cytokine transcription, which distinguishes it mechanistically from JAK, PDE4, COX-2 and dihydrofolate reductase inhibitors used elsewhere in dermatology.

Reference: electronic medicines compendium (emc), Protopic 0.1% Ointment Summary of Product Characteristics, section 5.1 Pharmacodynamic properties, https://www.medicines.org.uk/emc/product/1608/smpc