Anesth Analg 2003;96:1413-1414
© 2003 International Anesthesia Research Society
PAIN MEDICINE
Large-Dose Intravenous Methotrexate-Induced Cutaneous Toxicity: Can Oral Magnesium Oxide Reduce Pain?
Santhanam Suresh, MD*, ,
Sara Lozono, MD , and
Steven C. Hall, MD*,
Department of *Pediatric Anesthesiology, Children’s Memorial Hospital, and
Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and
Division of Anesthesiology, The Cleveland Clinic Foundation, Cleveland, Ohio
Address correspondence and reprint requests to Santhanam Suresh, MD, Department of Pediatric Anesthesiology, Children’s Memorial Hospital, Box 19, 2300 Children’s Plaza, Chicago, IL 60614. Address e-mail to ssuresh{at}northwestern.edu
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Abstract
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IMPLICATIONS: Chemotherapy for cancer is associated with pain including cutaneous vasculitis. Magnesium, an N-methyl-D-aspartic acid-receptor antagonist, was used successfully to treat an adolescent with pain caused by cutaneous vasculitis secondary to methotrexate therapy.
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Introduction
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Large-dose IV methotrexate is used for management of cancer in children and adolescents (1). Although the major dose-limiting step to the use of systemic methotrexate is myelosuppression, other forms of toxicity can be debilitating. Skin reactions, including cutaneous vasculitis (2), although unusual, can mimic peripheral neuritis. This neuritis can manifest as a sympathetically mediated pain in all extremities and may be refractory to the use of oral and/or IV opioids. We report a case of a teenager who developed cutaneous vasculitis after large-dose IV methotrexate for the management of Burkitt’s lymphoma.
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Case Report
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A 14-yr-old female underwent exploratory laparotomy for an abdominal mass, and a diagnosis of Burkitt’s lymphoma was made. Postoperatively, she was started on large-dose methotrexate. She developed tumor lysis syndrome and subsequent renal failure, for which she was placed on hemodialysis. She recovered completely and her creatinine clearance was normal when a second dose of methotrexate was administered. She was also given leucovorin (3) for decreasing complications of IV methotrexate. She started having a burning sensation in her soles and palm 3 days after initiation of methotrexate treatment. The pain management service was consulted, and her Faces pain scale (4) score was noted to be 4/5 and her visual analog scale score was 8/10. She was started on IV fentanyl patient-controlled analgesia. Despite escalating adjustments to her dose, she continued to have severe pain with mechanical allodynia and hyperalgesia. Except for erythema of the palms and soles, no other cutaneous lesions were identified. A dermatological consultation was obtained and a diagnosis of cutaneous vasculitis secondary to methotrexate was made. A biopsy was not performed because there were no skin lesions noted. The consultant dermatologist excluded drug hypersensitivity and paraneoplastic lesions. A neuropathic component to the pain was entertained and an initial noninvasive method using a topical application of eutectic mixture of local anesthetic was performed with no improvement in symptoms (5). The addition of an N-methyl-D-aspartic acid (NMDA)-receptor antagonist was considered and oral magnesium oxide 100 mg was administered once a day. Two days later, with no further escalation of her fentanyl patient-controlled analgesia, her symptoms were significantly improved. Her visual analog scale score improved to 3/10 and her Faces pain scale score was 2/5. There were no side effects, including diarrhea, from the use of magnesium. The burning sensation decreased and her allodynia and hyperalgesia diminished. She was weaned off the fentanyl and discharged home on oral opioids and magnesium oxide. On follow-up at the Hematology Oncology clinic, she has been pain-free but continues her oral regimen of magnesium and oxycodone with acetaminophen.
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Discussion
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Pain secondary to the adverse effects of chemotherapy including peripheral neuropathy and mucositis has been reported in cancer patients (6). Pain caused by cutaneous vasculitis is a rare but painful condition (7). Large-dose methotrexate and oxaliplatin have been associated with painful dysesthesias and neuropathy (8). Cutaneous vasculitis has been reported with cutaneous hypersensitivity after large-dose methotrexate therapy. Eutectic mixture of local anesthetic cream was applied to decrease the neuropathic component of pain with no relief. This is the first use of oral magnesium in the management of cutaneous vasculitis secondary to methotrexate.
Magnesium is an NMDA antagonist. An excessive activation of the excitatory amino acid pathway, particularly the NMDA receptors, may result in pain that does not respond to opioids. An animal model of neuropathic pain has shown that this amplification of the analgesic effects of small-dose morphine is noticed with co-administration of magnesium (9). Because opioids in general have an unsatisfactory effect on neuropathic pain, the addition of magnesium, an NMDA-receptor antagonist, may have an effect on excitatory amino acids and in particular the NMDA channels thereby decreasing neuropathic pain.
Based on our observation, we theorize that the addition of magnesium potentiated the effect of opioids in this patient. Although this is an anecdotal report, the addition of oral magnesium may be considered in chemotherapy-induced cutaneous vasculitis as an adjunct to opioids for providing pain relief.
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References
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Accepted for publication January 6, 2003.
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Abstract
Introduction
