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ALLOPURINOL INDUCED MENINGITIS
0022-5347/00/1646-2028/0 THE JOURNAL OF UROLOGY® Copyright © 2000 by AMERICAN UROLOGICAL ASSOCIATION, INC.®
Vol. 164, 2028, December 2000 Printed in U.S.A.
ALLOPURINOL INDUCED MENINGITIS DAVID A. DUCHENE, CHRISTOPHER P. SMITH
AND
RICHARD A. GOLDFARB
From the Department of Urology, Baylor College of Medicine, Houston, Texas KEY WORDS: allopurinol, meningitis
The xanthine oxidase inhibitor allopurinol is commonly prescribed in urology. Although generally well tolerated by patients, many adverse reactions, including fatalities, have been reported.1, 2 To our knowledge we report the first case of aseptic meningitis due to allopurinol administration. CASE REPORT
A 60-year-old white man presented with a temperature of 103.8F (39.9C), shaking chills, nausea, headache, neck stiffness and severe back pain. History was significant for recurrent uric acid stones initially treated with extracorporeal shock wave lithotripsy in March 1999 and then with laser lithotripsy in July. After the latter procedure, the patient was discharged home on levofloxacin and began preventative treatment with acetazolamide and allopurinol. He was readmitted to the hospital the day of discharge with a temperature of 104.0F (40.0C), presumably due to a partially treated urinary tract infection. The patient had taken the initial 300 mg. allopurinol orally only a few hours earlier. Broadspectrum antibiotics were given, and the allopurinol and acetazolamide were discontinued. An extensive fever evaluation was negative. The patient recovered from this acute episode and was doing well at scheduled followup in August. At that time he was restarted on allopurinol and acetazolamide. Soon after taking 300 mg. allopurinol orally, the patient returned to the hospital and was diagnosed with a drug reaction (versus possible urosepsis). During hospitalization, the patient became confused and agitated. Neurology was consulted to evaluate the altered mental status, persistent headache and neck pain. Infectious disease and internal medicine services were also consulted. White blood count was 9,500/mm.3 (normal 4,300 to 10,800) with 85% neutrophils (normal 45% to 74%). Urine and blood cultures were negative. Chest radiograph and computerized tomography of the head, abdomen and pelvis were normal. Electroencephalogram showed a slow occipital rhythm and diffuse slowing of background activity, which indicated a diffuse disturbance in brain function. Cerebrospinal fluid analysis revealed protein 149 mg./dl. (normal 25 to 50), glucose 62 mg./dl. (normal 40 to 70), 33 red blood cells/ml. (normal 0 to 5) and 74 white blood cells/ml. (normal less than 5) with 53% neutrophils (normal 0%), 29% lymphocytes (normal 60% to 70%), 6% monocytes (normal 30% to 50%), 1% eosinophils (normal 0% to 7%) and 11% basophils (normal 0% to 2%). Cerebrospinal fluid venereal disease research laboratory and cryptococcal screen was nonreactive with no acid-
fast bacilli present. Cerebrospinal fluid culture and antigens for group B streptococci, group B Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae and Escherichia coli were negative. Test results were consistent with an aseptic meningitis syndrome caused by allopurinol drug reaction. The patient was asymptomatic and afebrile after allopurinol was discontinued, and was discharged home in good condition. DISCUSSION
Approximately 2% of hospitalized patients will have adverse reactions to allopurinol with severe hypersensitivity reactions occurring in 0.4%.2 The most common adverse reactions are relatively benign and consist of maculopapular skin rashes, hives, itching, drowsiness, headache, indigestion, unusual hair loss or drug fever. However, life threatening, severe hypersensitivity reactions may occur and generally present with a clinical picture of worsening renal function, acute hepatocellular injury, skin lesions, fever, eosinophilia and leukocytosis.1, 2 Our patient had aseptic meningitis due to allopurinol. Drug induced aseptic meningitis is a complication in which numerous other drugs, namely nonsteroidal anti-inflammatory agents, certain antibiotics, radiographic agents and muromonab-CD3, have also been associated.3 The pathogenesis of adverse reactions to allopurinol is thought to involve a combination of immunological processes, genetic predisposition and accumulation of the drug.1 It is noteworthy that while most adverse reactions occur in patients receiving a total dose of more than 2 gm. allopurinol, our patient had aseptic meningitis after cumulative ingestion of only 600 mg. allopurinol.2 Our case emphasizes that allopurinol has serious side effects in certain patients and should only be prescribed for appropriate indications. The indications in urology include recurrent uric acid renal calculi, recurrent calcium oxalate renal calculi when associated with hyperuricuria and prevention of acute urate nephropathy in patients receiving cytotoxic therapy for malignancies.
Accepted for publication July 21, 2000.
2028
REFERENCES
1. Arellano, F. and Sacristan, J. A.: Allopurinol hypersensitivity syndrome: a review. Ann Pharmacother, 27: 337, 1993 2. McInnes, G. T., Lawson, D. H. and Jick, H.: Acute adverse reaction attributed to allopurinol in hospitalized patients. Ann Rheum Dis, 40: 245, 1981 3. Marinac, J. S.: Drug- and chemical-induced aseptic meningitis: a review of the literature. Ann Pharmacother, 26: 813, 1992
Vol. 164, 2028, December 2000 Printed in U.S.A.
ALLOPURINOL INDUCED MENINGITIS DAVID A. DUCHENE, CHRISTOPHER P. SMITH
AND
RICHARD A. GOLDFARB
From the Department of Urology, Baylor College of Medicine, Houston, Texas KEY WORDS: allopurinol, meningitis
The xanthine oxidase inhibitor allopurinol is commonly prescribed in urology. Although generally well tolerated by patients, many adverse reactions, including fatalities, have been reported.1, 2 To our knowledge we report the first case of aseptic meningitis due to allopurinol administration. CASE REPORT
A 60-year-old white man presented with a temperature of 103.8F (39.9C), shaking chills, nausea, headache, neck stiffness and severe back pain. History was significant for recurrent uric acid stones initially treated with extracorporeal shock wave lithotripsy in March 1999 and then with laser lithotripsy in July. After the latter procedure, the patient was discharged home on levofloxacin and began preventative treatment with acetazolamide and allopurinol. He was readmitted to the hospital the day of discharge with a temperature of 104.0F (40.0C), presumably due to a partially treated urinary tract infection. The patient had taken the initial 300 mg. allopurinol orally only a few hours earlier. Broadspectrum antibiotics were given, and the allopurinol and acetazolamide were discontinued. An extensive fever evaluation was negative. The patient recovered from this acute episode and was doing well at scheduled followup in August. At that time he was restarted on allopurinol and acetazolamide. Soon after taking 300 mg. allopurinol orally, the patient returned to the hospital and was diagnosed with a drug reaction (versus possible urosepsis). During hospitalization, the patient became confused and agitated. Neurology was consulted to evaluate the altered mental status, persistent headache and neck pain. Infectious disease and internal medicine services were also consulted. White blood count was 9,500/mm.3 (normal 4,300 to 10,800) with 85% neutrophils (normal 45% to 74%). Urine and blood cultures were negative. Chest radiograph and computerized tomography of the head, abdomen and pelvis were normal. Electroencephalogram showed a slow occipital rhythm and diffuse slowing of background activity, which indicated a diffuse disturbance in brain function. Cerebrospinal fluid analysis revealed protein 149 mg./dl. (normal 25 to 50), glucose 62 mg./dl. (normal 40 to 70), 33 red blood cells/ml. (normal 0 to 5) and 74 white blood cells/ml. (normal less than 5) with 53% neutrophils (normal 0%), 29% lymphocytes (normal 60% to 70%), 6% monocytes (normal 30% to 50%), 1% eosinophils (normal 0% to 7%) and 11% basophils (normal 0% to 2%). Cerebrospinal fluid venereal disease research laboratory and cryptococcal screen was nonreactive with no acid-
fast bacilli present. Cerebrospinal fluid culture and antigens for group B streptococci, group B Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae and Escherichia coli were negative. Test results were consistent with an aseptic meningitis syndrome caused by allopurinol drug reaction. The patient was asymptomatic and afebrile after allopurinol was discontinued, and was discharged home in good condition. DISCUSSION
Approximately 2% of hospitalized patients will have adverse reactions to allopurinol with severe hypersensitivity reactions occurring in 0.4%.2 The most common adverse reactions are relatively benign and consist of maculopapular skin rashes, hives, itching, drowsiness, headache, indigestion, unusual hair loss or drug fever. However, life threatening, severe hypersensitivity reactions may occur and generally present with a clinical picture of worsening renal function, acute hepatocellular injury, skin lesions, fever, eosinophilia and leukocytosis.1, 2 Our patient had aseptic meningitis due to allopurinol. Drug induced aseptic meningitis is a complication in which numerous other drugs, namely nonsteroidal anti-inflammatory agents, certain antibiotics, radiographic agents and muromonab-CD3, have also been associated.3 The pathogenesis of adverse reactions to allopurinol is thought to involve a combination of immunological processes, genetic predisposition and accumulation of the drug.1 It is noteworthy that while most adverse reactions occur in patients receiving a total dose of more than 2 gm. allopurinol, our patient had aseptic meningitis after cumulative ingestion of only 600 mg. allopurinol.2 Our case emphasizes that allopurinol has serious side effects in certain patients and should only be prescribed for appropriate indications. The indications in urology include recurrent uric acid renal calculi, recurrent calcium oxalate renal calculi when associated with hyperuricuria and prevention of acute urate nephropathy in patients receiving cytotoxic therapy for malignancies.
Accepted for publication July 21, 2000.
2028
REFERENCES
1. Arellano, F. and Sacristan, J. A.: Allopurinol hypersensitivity syndrome: a review. Ann Pharmacother, 27: 337, 1993 2. McInnes, G. T., Lawson, D. H. and Jick, H.: Acute adverse reaction attributed to allopurinol in hospitalized patients. Ann Rheum Dis, 40: 245, 1981 3. Marinac, J. S.: Drug- and chemical-induced aseptic meningitis: a review of the literature. Ann Pharmacother, 26: 813, 1992