Methotrexate induced cutaneous ulceration and altered mental status

A 77-year-old female with a history of rheumatoid arthritis, diabetes mellitus, and asthma presented to an outside hospital with severe oral pain and perioral redness ten days after receiving ciprofloxacin and nitrofurantoin for a urinary tract infection. She was transferred for possible Stevens-Johnson Syndrome and dermatology was consulted. On examination, the patient had altered mental status, ulcerations along the buccal mucosa, clusters of hemorrhagic papules along the upper lip, and vulvar erythema. She reported taking methotrexate weekly and folic acid daily. Given concern for orofacial herpes simplex virus (HSV), she was started on intravenous acyclovir. Over the following days, her mucositis did not improve, and she developed new, non-specific erosions on her back, right arm, chest, and shins. HSV PCR was negative, and her progressively worsening cytopenias, mental status, and skin lesions were together felt to be suggestive of methotrexate toxicity, likely in the setting of concomitant administration of ciprofloxacin. A biopsy was performed that demonstrated interface dermatitis with focal dermoepidermal separation and keratinocyte necrosis. Leucovorin was administered and the patient improved with supportive care. The antiproliferative activity of methotrexate lends itself to numerous adverse effects, the most common of which in dermatology is mucositis but also includes skin ulcers and systemic effects. This case serves to highlight the importance of close medication monitoring with methotrexate administration and coordinated care among specialties. While methotrexate toxicity can have various presentations, unexplained skin ulcers, cytopenias, and mental status changes may be a clue in diagnosing and providing care for affected patients.