Psoriatic flare after the concomitant administration of L-methylfolate and methotrexate

DHFR: dihydrofolate reductase MTHFR: methylenetetrahydrofolate reductase INTRODUCTION Psoriasis is a chronic disease that causes erythematous patches with silver plaques and scales, often drastically affecting the quality of life of those afflicted by this disease. Psoriasis is a hyperproliferative disease, which is thought to be the result of a dysregulated immune system, specifically overactive T lymphocytes, which release excess proinflammatory cytokines and result in hyperproliferation of keratinocytes. Treatment for psoriasis ranges from topical corticosteroids to systemic agents such as biologic immune suppressants. One such systemic agent, methotrexate, has been used to treat moderate to severe psoriasis for more than 40 years. Methotrexate inhibits key steps in the metabolism of folic acid, a vitamin that contributes to numerous metabolic pathways necessary for cell survival. Folate or folinic acid is a B vitamin that is consumed in leafy greens or dietary supplements. These vitamins are necessary for crucial methylation reactions such as those seen in the synthesis of nitrogenous bases in DNA and RNA and to methylation reactions necessary for the production of amino acids and essential neurotransmitters. Metabolism of folic acid begins with its reduction into dihydrofolate and then tetrahydrofolate by dihydrofolate reductase (DHFR). Next, serine hydroxymethyltransferase converts tetrahydrofolate into 5,10 methylene tetrahydrofolate, which is converted to the metabolically active 5-methyl tetrahydrofolate (L-methylfolate) by methylenetetrahydrofolate reductase (MTHFR). Both the DHFR and the MTHFR genes are subject to numerous genetic differences that contribute to a variable rate of folate metabolism in the general population. Of note,