Methotrexate-induced exacerbation of urticarial vasculitis: an unusual adverse reaction

Sir, Systemic immunosuppressive treatments, principally azathioprine, are reported to be effective in some patients with urticarial vasculitis.1,2 We report a case in which methotrexate (MTX), a well‐established antiproliferative and immunosuppressant agent, paradoxically caused an exacerbation of vasculitis. A girl then aged 14 was first admitted as an inpatient in 1979, with a life‐long history of urticarial eruptions. During her admission, routine physical urticaria challenge testing,3 placebo‐controlled oral food additive and drug challenge testing, and autologous serum intradermal testing for autoimmune chronic urticaria4 were negative. Full blood count, urine analysis, complement profile, autoimmune screen and protein electrophoresis were normal. Urticaria persisted for the intervening years, during which time numerous treatments, including a variety of antihistamines, intravenous immunoglobulin, cyclosporin, colchicine and azathioprine, failed to control the disorder. The patient returned to the clinic for investigation of two severe attacks of widespread discoid urticarial plaques in 1996, at age 32 years. She was otherwise well and on no regular medication apart from hormone replacement therapy for primary ovarian failure. On clinical reassessment, examination showed firm red papules and nodules measuring up to 20 mm in diameter, predominantly on the upper and lower limbs (Fig. 1a). These were extremely tender, itchy and painful with a burning quality, but faded after several days, leaving residual pigmentation. Biopsy of an acute lesion showed evidence of urticarial vasculitis, with a neutrophilic and eosinophilic perivascular infiltrate, endothelial cell swelling and nuclear dust.