Brief Reports

Brief reports of new clinical or laboratory observations, cases of unusual importance, and new developments in medical care will be considered for publication in this section. Manuscripts must be typed double-spaced. Text length must not exceed 750 words; not more than ten references and one figure or table can be used. See "Information for Readers and Authors" for form of references. Manuscripts should include an abstract of not over 150 words. Reports will be reviewed by consultants when, in the opinion of the editors, such review is needed. The Editor reserves the right to shorten reports and to make changes in style.

Carbamazepine-Induced Aseptic Meningitis Lynn T. Simon, MD; Benjamin Hsu, MD; and Bruce T. Adornato, MD Annals of Internal Medicine. 1990;112:627-628.

Carbamazepine is a drug increasingly used in a number of conditions including seizure disorders, trigeminal neuralgia, peripheral neuropathy, and occasionally psychiatric illness. We report a case of aseptic meningitis as an adverse effect of carbamazepine. The only previous report of this association is in a patient with the Sjogren syndrome. Case Report A 50-year-old man with a history of bipolar illness, hypertension, diabetes, and right hemiparesis from a previous stroke presented to the Palo Alto Veterans Affairs Hospital on 8 May 1989 with confusion, leftsided myoclonus, temperature of 39 °C, and a diffuse erythematous maculopapular rash. The cerebrospinal fluid showed 33 x 106/L leukocytes, with 0.02 neutrophils, 0.85 lymphocytes, and 0.13 mononuclear cells; glucose, 161 mmol/L (serum, 358 mmol/L); and protein, 65 g/L. Cultures for bacteria, fungi, and acid-fast bacteria were negative and a cerebrospinal VDRL test was nonreactive. A Westergren sedimentation rate was 43 mm/h and a peripheral leukocyte count was 9.7 x 109/L with 0.04 eosinophils. The patient's medications at that time were lithium carbonate, 300 mg three times daily; disulfiram, 250 mg daily; and carbamazepine, 100 mg three times daily. The carbamazepine had been started 2.5 months earlier for management of mania. He had been taking disulfiram for From Stanford University School of Medicine, Stanford, California. For current author addresses, see end of text.

8 years to treat alcoholism. At admission the lithium level was 0.85 mmol/L, and carbamazepine, 3.7 /xmol/L. An electroencephalogram was diffusely slow without focal or paroxysmal abnormalities. All medications were withdrawn and the patient's rash, fever, myoclonus, and mental status improved within 2 days. A presumptive diagnosis of a viral meningitis was made and the patient was discharged on 16 May on his regular medications, lithium, disulfiram, and carbamazepine. Three days later the patient returned with a temperature of 38 °C, a confluent erythematous rash, confusion, and myoclonus. The cerebrospinal fluid showed 14 x 106/L leukocytes with 0.89 lymphocytes and 0.11 mononuclear cells; glucose, 80 mmol/L (serum, 189 mmol/L); and protein, 34 g/L. The peripheral leukocyte count was 9.9 x 109/L with 0.16 eosinophils, which later increased to 0.30 eosinophils with a leukocyte count of 8.0 x 109/L. A carbamazepine level was 6.1 /xmol/L and a lithium level was 1.62 mmol/L. When carbamazepine was withdrawn, all symptoms resolved within 2 days. The patient was discharged on lithium, 300 mg three times daily, and disulfiram, 250 mg daily, without return of symptoms. Discussion Our patient developed an allergic reaction with fever, rash, peripheral eosinophilia, and an aseptic meningitis manifested by confusion, myoclonus, and a cerebrospinal fluid pleocytosis. The administration of carbamazepine was temporally related to the patient's symptoms, which abated with withdrawal of carbamazepine and recurred with its readministration. The most frequently reported side effects of carbamazepine include hematologic, dermatologic, and hepatic abnormalities in addition to common complaints of drowsiness, loss of coordination, diplopia, and vertigo, which are usually transient and dose related (1). To our knowledge, only one previous report (2) has been published of aseptic meningitis caused by carbamazepine. The patient had the Sjogren syndrome and received carbamazepine to treat trigeminal neuralgia. An ibuprofen-related meningitis has been reported in patients with systemic lupus erythematosus (3) and mixed connective tissue disease (4). Our patient was not known to suffer from connective tissue disease, had negative antinuclear-antibody and rheumatoid factors, and denied use of ibuprofen or other nonsteroidal anti-inflammatory agents. Alternative explanations for this patient's symptoms are unlikely. Although disulfiram has many side effects and interactions with other drugs, we do not feel this agent was primarily responsible for this patient's symptoms. He had been taking disulfiram for many years without a similar reaction. The interaction of disulfiram with phenytoin is well recognized (5) but has not been

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found to significantly alter carbamazepine levels (6) or produce other adverse reactions when used with carbamazepine. However, we cannot exclude that this patient's aseptic meningitis was caused by a combination of these two drugs. Although it is possible that our patient suffered from a viral meningitis with recrudescence, the temporal relationship of carbamazepine therapy, peripheral eosinophilia, and myoclonus makes this very unlikely. Myoclonus has been reported in association with an encephalitis; however, it has also been reported with the use of tricyclic antidepressants (7). Carbamazepine is structurally related to the tricyclic compounds and myoclonus has also been observed with carbamazepine therapy (8). The myoclonus in our patient was most likely caused by a toxic effect of carbamazepine because it recurred with the meningitis and eosinophilia. Thus, although rarely reported, carbamazepine may cause aseptic meningitis. With the increasing number of neurologic and psychiatric (9) indications for its use, this unusual adverse reaction may become recognized more frequently. Reprints are not available. Current Author Addresses: Dr. Simon: 1112 Dupont Circle, Louisville, KY 40207. Dr. Hsu: Division of Dermatology, UCLA, 10833 LeConte Avenue, Los Angeles, CA 90024. Dr. Adornato: 1101 Welch Road, Suite C5, Palo Alto, CA 94304.

References 1. Pellock, JM. Carbamazepine side effects in children and adults. Epilepsia. 1987;28:S64-70. 2. Hilton E, Stroh EM. Aseptic meningitis associated with administration of carbamazepine. J Infect Dis. 1989;159:363-4. 3. Widener HL, Littman BH. Ibuprofen-induced meningitis in systemic lupus erythematosus. JAMA. 1978;239:1062-4. 4. Bernstein RF. Ibuprofen-related meningitis in mixed connective tissue disease. Ann Intern Med. 1980;92:206-7. 5. Kutt H. Interactions of antiepileptic drugs. Epilepsia. 1975;16:393402. 6. Krag B, Dam M, Angelo H, Christensen JM. Influence of disulfiram on the serum concentration of carbamazepine in patients with epilepsy. Acta Neurol Stand. 1981;63:395-8. 7. Lippman S, Moskovitz R, OTuama L. Tricyclic-induced myoclonus. Am J Psychiatry. 1977;134:90-1. 8. Aguglia U, Zappia M, Quattrone A. Carbamazepine-induced nonepileptic myoclonus in a child with benign epilepsy. Epilepsia. 1987; 28:515-8. 9. Ballenger JC. The use of anticonvulsants in manic-depressive illness. J Clin Psychiatry. 1988;49(Suppl):S21-5. © 1990 American College of Physicians

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15 April 1990 • Annals of Internal Medicine • Volume 112 • Number 8

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Carbamazepine-induced aseptic meningitis.

Brief Reports Brief reports of new clinical or laboratory observations, cases of unusual importance, and new developments in medical care will be con...
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