International Journal of Medicine and Medical Science Vol. 1(4), pp. 099-101, April, 2009 Available online at http://www.academicjournals.org/IJMMS © 2009 Academic Journals Case Report Methotrexate-induced toxic epidermal necrolysis: A case report I. Tazi*, A. Madani, S. Zafad, M. Harif, A. Quessar and S. Benchekroun Hematology and Pediatric Oncology, Hopital 20 Aout 1953 Casablanca Morocco. Accepted 27 March, 2009 Methotrexate (MTX) is a folic acid antagonist that inhibits the enzyme dihydrofolate reductase resulting in decreased cell levels of tetrahydrofolate. Adverse cutaneous reactions to MTX are usually dose- related and have been mainly reported in patients receiving extremely large doses of chemotherapy. Toxicity can affect multiple organ systems including bone marrow, liver, intestinal tract, kidneys, lungs, skin, and blood vessels, resulting in death in severe cases. In this report we describe the case of a 9 year old boy who developed toxic epidermal necrolysis after high-dose MTX treatment and discuss the important clinical and therapeutic features of this condition. Key words: Methotrexate, skin, toxicity, necrolysis. INTRODUCTION Methotrexate (MTX) is a potent competitive inhibitor of di- hydrofolate reductase (DHFR), a key enzyme in the ge- neration of reduced folates crucial for the biosynthesis of purines and thymidylic acid (Blakley and Benkovic, 1984; Blakley, 1995). Due to its substantial antiproliferative ac- tivity, MTX has been used effectively as a chemothera- peutic agent in the treatment of both hematopoietic and solid-organ neoplasms, particularly acute lymphoblastic leukemia, non-Hodgkin’s lymphoma, Ewing’s sarcoma, and osteosarcoma (Jolivet et al., 1983; Schornagel and McVie, 1983; Sorrentino et al., 1993). However, the use- fulness of MTX as an antitumor agent is limited by the to- xicity for highly proliferative normal cells and tissues of the hematopoietic system and gastrointestinal tract (Mar- golis et al., 1971; Rivera et al., 1985). Toxic epider-mal necrolysis (TEN) is a life-threatening disease charac- terized by extensive destruction of the epidermis. The mortality rate averages 25-30% following septicemia and various metabolic disturbances Fritsch, (2000). The ge- nerally recognized cause of TEN is an adverse drug re- action probably involving specific toxic metabolites (Fritsch and Sidoroff, 2000). We describe in this report a fatal case of high dose methotrexate toxicity. *Corresponding author. E-mail: Tazi_illias@hotmail.com. Case report A 9 year old boy was referred to our department with a 7- month history of fever, vomiting, abdominal pain, edema of the lower limbs and loss of appetite. A diagnosis of Burkkit´s lymphoma was established. The patient was classified as Group C according to the LMB 2001 proto- col. A one-week induction treatment using intrathecal chemotherapy (COPADM) was initiated combining daily doses of cyclophosphamide (1,500 mg/m 2 ), vincristine (2 mg/m 2 ), daunorubicine (60 mg/m 2 ), cytarabin (90 mg/m 2 ), prednisone (300 mg/m 2 ) and MTX (8 g/m 2 ). Twenty four hours after the start of MTX infusion, leu- covorin (15 mg, intravenous) rescue was initiated every 6 h for 3 days. Another preventive measure to prevent MTX toxicity included aggressive intravenous fluid replacement (3 L/m 2 /day) and the addition of sodium bicarbonate to the intravenous fluid to alkalinize the urine. Four days after initiation of this treatment, the child developed pan- cytopenia, fever and sever kidney developed. At onset of pancytopenia, the patient was treated with supportive measures. A septic shock developed 10 days after com- pleting the chemotherapy administration. This episode was treated by intravenous antibiotherapy associating ceftazidim (4 g/d), amikacine (15 mg/Kg/d) and vanco- mycin (2 g/d). Growth factors were administered also. Three days later, the patient developed an erythematous painful swelling on the fingers with subsequent large bulla