Mycophenolate Mechanism — SCE Dermatology MCQ

Correct answer: D — Inosine monophosphate dehydrogenase (IMPDH) inhibitor — selectively inhibiting lymphocyte proliferation by blocking the de novo purine synthesis pathway

The correct answer is D, Inosine monophosphate dehydrogenase (IMPDH) inhibitor, selectively inhibiting lymphocyte proliferation by blocking the de novo purine synthesis pathway. Mycophenolate mofetil is a prodrug of mycophenolic acid, which reversibly inhibits IMPDH, the rate-limiting enzyme in de novo guanosine nucleotide synthesis. T and B lymphocytes lack an effective purine salvage pathway and are therefore disproportionately dependent on de novo synthesis, giving mycophenolate relative selectivity for lymphocyte suppression compared with agents that block purine synthesis in all dividing cells. This selective mechanism explains why it is chosen as a third-line systemic option in eczema when methotrexate (hepatotoxicity risk) and ciclosporin (nephrotoxic and hypertensive) are contraindicated, as in this patient with liver disease and hypertension. Why the other options are wrong: E. Calcineurin inhibitor: this describes ciclosporin and tacrolimus, which block calcineurin-mediated IL-2 transcription in T cells, not the mechanism of mycophenolate. B. JAK inhibitor: JAK inhibitors (such as baricitinib or upadacitinib, used in atopic dermatitis) block Janus kinase signalling downstream of cytokine receptors; mycophenolate has no JAK activity. C. Folate antagonist: this is the mechanism of methotrexate, which inhibits dihydrofolate reductase, impairing pyrimidine and purine synthesis via a folate-dependent route, distinct from mycophenolate's direct IMPDH blockade. A. PDE4 inhibitor: phosphodiesterase-4 inhibition (as with apremilast or topical crisaborole) raises intracellular cAMP to reduce inflammatory mediator release, an unrelated pathway to purine synthesis. Key point: Mycophenolate mofetil is selective for lymphocytes because it inhibits IMPDH in the de novo purine synthesis pathway, on which lymphocytes (unlike most cells) are uniquely reliant.

Reference: BNF, Mycophenolate mofetil, Indications and dose (off-label use in severe refractory eczema), available at https://bnf.nice.org.uk/drugs/mycophenolate-mofetil/