Case Presentation: A 63 year old female with a past medical history significant for rheumatoid arthritis, COPD, hypertension, hypothyroidism who was admitted with the chief complaint of a rash. It was present for two months and was predominantly distributed on the extremities and gluteal region. It was painful and at times even pruritic. There were sores in her mouth for weeks with anorexia and weight loss due to odynophagia (to solids and liquids). Also endorsed low grade fevers at home upto 100.2°F. Apart from that she had acute diarrhea with occasional hematochezia (which she attributed to hemorrhoids). Therapy with methotrexate and folic acid was initiated approximately 9 years ago and had never encountered any side effects or lab abnormalities. Last dose of methotrexate was a week prior to hospitalization. She did report a recent hospitalization for renal failure approximately two months ago. On examination there were crusted/ulcerated appearing necrotic macular lesions on bilateral upper extremities. There were necrotic ulcers seen on the tips of the fingers and on right great toe. Ulcerated necrotic macules in the gluteal region and posterior aspect of right thigh also seen. Large erosions were seen on the bilateral buccal mucosa, the palate and the lip and oral thrush. Labs showed pancytopenia (white cell count: 1.95 x 109/L, red blood cell count: 2.78 1012/L, platelet count: 101 x 109/L) with neutropenia as well. Macrocytosis was noted and methotrexate level was slightly elevated at 0.06 mcmol/L. A skin biopsy revealed changes consistent with methotrexate induced dermal necrosis. Treatment was initiated with intravenous folic acid and leucovorin following which the pancytopenia resolved and no new skin lesions appeared.

Discussion: This case portrays a case of methotrexate induced toxicity. For the hospitalist this is an important topic to be aware of as methotrexate is frequently used for numerous rheumatological disorders. Cutaneous lesions can be the harbingers of impending methotrexate related adverse effects like pancytopenia. They can be dose-dependent or idiosyncratic and can include: hives, erythematous lesions, nodules, purpuric lesions, blisters, toxic epidermal necrolysis. Our patient developed pancytopenia and cutaneous manifestations of methotrexate toxicity in the form of epidermal necrosis. It was important to exclude infectious etiologies of the rash given the leucopenia and susceptibility to them. Methotrexate levels were not markedly elevated, patient had recently recovered from a renal injury and this attributed to the toxic effects. It undergoes renal excretion hence renal failure predisposes to toxicity. Treatment is discontinuing methotrexate and administering folic acid and leucovorin.

Conclusions: Methotrexate induced skin necrosis is an important complication to recognize as it can be a marker of impending toxic effects like pancytopenia. Should be recognized early and can be treated with leucovorin and high dose folic acid.

IMAGE 1: Ulcerative lesion with central necrosis on the dorsum of the hand.

IMAGE 2: Ulcerative lesion on left posterior thigh.