Methotrexate Mechanism — SCE Dermatology MCQ

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ModerateDermatopharmacologyMethotrexate MechanismSCE Dermatology

A 35-year-old man has psoriasis and is starting Methotrexate. His dermatologist explains that Methotrexate works differently in psoriasis than in cancer. In dermatological doses, what is the primary mechanism?

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Correct answer: D — At low doses (7.5-25 mg/week), Methotrexate acts primarily as an anti-inflammatory/immunomodulatory agent through adenosine release (AICAR accumulation) rather than through antifolate cytotoxicity

At dermatological doses (7.5-25 mg weekly), Methotrexate's primary mechanism is anti-inflammatory rather than cytotoxic. Low-dose MTX causes accumulation of AICAR (aminoimidazole carboxamide ribonucleotide), which promotes extracellular adenosine release. Adenosine is a potent anti-inflammatory mediator that suppresses T-cell activation, reduces pro-inflammatory cytokine production (TNF-alpha, IL-1, IL-6), and promotes anti-inflammatory pathways. This explains why low-dose weekly MTX is effective in inflammatory conditions (psoriasis, RA, eczema) without causing the severe myelosuppression seen with high-dose cancer chemotherapy. The antifolate/cytotoxic mechanism contributes at higher doses. Folic acid supplementation reduces side effects without significantly impacting anti-inflammatory efficacy.

Reference: BAD 2016 MTX; Pharmacology Review