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Clinical Specialist, Internal Medicine Service, University Hospital of La Paz, Paseo de la Castellana, 261 28046, Madrid, Spain, fax 34-913148011, a.borobia{at}gmail.com
Clinical Specialist, Internal Medicine Service, University Hospital of La Paz
Clinical Specialist, Clinical Pharmacology Service, Pharmacology Department, University Hospital of La Paz, School of Medicine, Autonomous University of Madrid, Madrid
Clinical Specialist, Internal Medicine Service, University Hospital of La Paz
Clinical Specialist, Internal Medicine Service, University Hospital of La Paz
Clinical Specialist, Professor, Internal Medicine Service, University Hospital of La Paz
Published Online, April 15, 2008. www.theannals.com, DOI 10.1345/aph.1K634
Case Report. A 76-year-old man with a past history of stable angina pectoris treated with aspirin was transferred to our hospital with a one-week history of fever, dry cough, dyspnea, oliguria, and bilateral edema in lower extremities. Two months earlier the patient had been diagnosed with M. kansasii pulmonary disease and was treated with a combined preparation of isoniazid 50 mg, rifampin 120 mg, and pyrazinamide 300 mg (Rifater). He was taking 5 tablets daily (total daily dose: isoniazid 250 mg, rifampin 600 mg, pyrazinamide 1500 mg). At that time, laboratory parameters included hemoglobin 15.3 g/dL, white blood cell (WBC) count 7540/µL, platelets 232 x 103/µL, serum creatinine 1.1 mg/dL, and urea 56 mg/dL.
On the patient's admission, laboratory data showed acute renal failure (serum creatinine 9.6 mg/dL, urea 168 mg/dL) and thrombocytopenia (platelets 85 x 103/µL). Other results were WBC count 13,300/µL, hemoglobin 13.9 g/dL, and proteinuria, with urine protein 1.5 g/L. Liver enzymes (aspartate aminotransferase and alanine aminotransferase) and coagulation parameters were within reference ranges. Renal ultrasound and Doppler studies did not show any obstructive or vascular cause to explain the acute renal failure. An extensive diagnostic workup yielded no positive results; therefore, an adverse drug reaction was suspected. Rifater was withdrawn and broad-spectrum antimicrobials (linezolid, piperacillin/tazobactam, ethambutol, levofloxacin) were introduced.
Two weeks after Rifater was discontinued, clinical and analytic parameters normalized. With the goal of treating M. kansasii with at least 2 first-line drugs, a controlled trial of rifampin at increasing doses (80 mg the first day, 150 mg the second day, 200 mg the third day) was attempted a week later. The day following reintroduction, a palpable purpura appeared, serum creatinine increased (1.9 mg/dL), and the platelet count dropped (Figure 1). Rifampin was withdrawn on the fourth day; 4 days later, the serum creatinine level returned to within normal limits and skin purpura disappeared. Skin purpura biopsy demonstrated leukocytoclastic vasculitis. Two weeks later, the patient was discharged with normal renal function and platelet count.
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Discussion. The few previously reported cases of acute renal failure due to rifampin have most frequently been associated with intermittent or interrupted treatment.1,2 The deterioration in renal function typically appears acutely after reintroduction of rifampin. However, a few cases have described this adverse reaction as developing with continuous administration of the drug.1,2 Rifampin was not reintroduced in any of these cases; therefore, causal relationship is difficult to establish.
Rifampin-induced renal failure is mediated by mechanisms of hypersensitivity type II or, less frequently, type III. It is hypothesized that anti-rifampin antibodies bind to the I antigen present on the cellular surface of adult erythrocytes, platelets, and renal tubular epithelium. This binding then induces cellular destruction.4,5 Other mechanisms have been described as causes of thrombocytopenia, such as the development of antibodies to the glycoprotein Ib-IX complex on the platelet surface.
This is, to the best of our knowledge, the first reported case of histologically confirmed rifampin-induced leukocytoclastic vasculitis. Iredale et al.3 reported on a patient with a skin lesion suggestive of vasculitis, but there was no histological confirmation.
Use of the Naranjo probability scale indicated a probable relationship between rifampin and acute renal failure, thrombocytopenia, and leukocytoclastic vasculitis.6 This case has been reported to the Spanish Health Authorities (number 07-121).
Footnotes
We gratefully thank E Ramirez Garcia MD PhD and AJ Carcas Sansuan MD PhD, clinical pharmacologists of University Hospital of La Paz, for their comments and suggestions on the manuscript.
References
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