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The Jarisch-Herxheimer Reaction in Leptospirosis: Possible Pathogenesis and Review Jon S. Friedland and David A. Warrell
From the Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom
The importance of treating leptospirosis with penicillin is emphasized by two case reports and a review documenting the occurrence of the Jarisch-Herxheimer reaction (JHR) in patients with this bacterial infection. The JHR is significant both as a cause of morbidity and mortality and as an indication of the therapeutic efficacy of penicillin. The possible etiology of the JHR is discussed, and comparisons with the changes occurring in septic shock are made; a study of either condition facilitates the understanding of the other. Tumor necrosis factor is hypothesized to playa key role in both. Current treatment ofthe JHR consists of general clinical support. Specific measures such as oxpentifylline therapy may play a role in the future.
[4, 5]. The dispute over the efficacy of antibiotics in leptospirosis has lasted 40 years. Initial views were conflicting [6], but the use of penicillin was often favored [7, 8]. An uncontrolled study of 84 patients showed that penicillin reduced the duration of fever and ameliorated symptoms [9]. Kocen confirmed this result and suggested that penicillin may reduce the incidence of jaundice and renal failure [10]. Other investigators were unable to show any benefit from treatment with penicillin or other antibiotics [11, 12]. The use of doxycycline has been advocated, but no conclusions can be drawn because only 15 patients were in the treatment arm of a controlled study of this drug [13]. Recently, a prospective randomized study
Received 14 February 1990; revised 25 May 1990. Reprints and correspondence: Dr. Jon Friedland, Department of Communicable Diseases, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, United Kingdom. Reviews of Infectious Diseases 1991;13:207-10 © 1991 by The University of Chicago. All rights reserved. 0162-0886/91/1302-0002$02.00
of 79 subjects [14] indicated that penicillin-treated patients recovered no more quickly than controls; the deaths of one treated patient and three controls did not represent a statistically significant difference. The number of very ill patients involved in this study is unclear. A randomized, placebocontrolled, double-blind study involving severely ill patients with leptospirosis from Manila has finally shown penicillin to be effective [15]. Although no patients died or required dialysis, penicillin markedly shortened the duration of illness and hastened the recovery of renal function. This trial did not include any reported instances of JHR. We present two recent cases of leptospirosis followed by JHR and review the possible pathogenesis of and the therapy for JHR.
Case Reports Case 1. A 51-year-old man presented to the emergency room after a day of rigors, diarrhea, and vomiting and 4 days of malaise, fever, arthralgia, and increasing myalgia. He was unable to walk. A week earlier he had repaired a manhole cover to the sewers. He was febrile (37.9°C) and jaundiced and had an enlarged cervical lymph node and injected conjunctivae. His pulse rate was 1001min, and his blood pressure was 100170 mm Hg. Urine output was good, but renal function was impaired, with blood urea at 18 mmol/L (normal, 2.5-6.7 mmol/L) and serum creatinine at 735 ILmol/L (normal, 70-150 umol/L). The white blood cell count was raised to 11.2/mm3 • Liver function was deranged, with bilirubin at 80 ILmol/L (normal, 3-17 ILmol/L) and aspartate aminotransferase at 74 lUlL (normal, 10-35 lUlL). The level of C-reactive protein (CRP) was 26.9 mg/dL (normal,
The Jarisch-Herxheimer Reaction in Leptospirosis: Possible Pathogenesis and Review Jon S. Friedland and David A. Warrell
From the Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom
The importance of treating leptospirosis with penicillin is emphasized by two case reports and a review documenting the occurrence of the Jarisch-Herxheimer reaction (JHR) in patients with this bacterial infection. The JHR is significant both as a cause of morbidity and mortality and as an indication of the therapeutic efficacy of penicillin. The possible etiology of the JHR is discussed, and comparisons with the changes occurring in septic shock are made; a study of either condition facilitates the understanding of the other. Tumor necrosis factor is hypothesized to playa key role in both. Current treatment ofthe JHR consists of general clinical support. Specific measures such as oxpentifylline therapy may play a role in the future.
[4, 5]. The dispute over the efficacy of antibiotics in leptospirosis has lasted 40 years. Initial views were conflicting [6], but the use of penicillin was often favored [7, 8]. An uncontrolled study of 84 patients showed that penicillin reduced the duration of fever and ameliorated symptoms [9]. Kocen confirmed this result and suggested that penicillin may reduce the incidence of jaundice and renal failure [10]. Other investigators were unable to show any benefit from treatment with penicillin or other antibiotics [11, 12]. The use of doxycycline has been advocated, but no conclusions can be drawn because only 15 patients were in the treatment arm of a controlled study of this drug [13]. Recently, a prospective randomized study
Received 14 February 1990; revised 25 May 1990. Reprints and correspondence: Dr. Jon Friedland, Department of Communicable Diseases, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, United Kingdom. Reviews of Infectious Diseases 1991;13:207-10 © 1991 by The University of Chicago. All rights reserved. 0162-0886/91/1302-0002$02.00
of 79 subjects [14] indicated that penicillin-treated patients recovered no more quickly than controls; the deaths of one treated patient and three controls did not represent a statistically significant difference. The number of very ill patients involved in this study is unclear. A randomized, placebocontrolled, double-blind study involving severely ill patients with leptospirosis from Manila has finally shown penicillin to be effective [15]. Although no patients died or required dialysis, penicillin markedly shortened the duration of illness and hastened the recovery of renal function. This trial did not include any reported instances of JHR. We present two recent cases of leptospirosis followed by JHR and review the possible pathogenesis of and the therapy for JHR.
Case Reports Case 1. A 51-year-old man presented to the emergency room after a day of rigors, diarrhea, and vomiting and 4 days of malaise, fever, arthralgia, and increasing myalgia. He was unable to walk. A week earlier he had repaired a manhole cover to the sewers. He was febrile (37.9°C) and jaundiced and had an enlarged cervical lymph node and injected conjunctivae. His pulse rate was 1001min, and his blood pressure was 100170 mm Hg. Urine output was good, but renal function was impaired, with blood urea at 18 mmol/L (normal, 2.5-6.7 mmol/L) and serum creatinine at 735 ILmol/L (normal, 70-150 umol/L). The white blood cell count was raised to 11.2/mm3 • Liver function was deranged, with bilirubin at 80 ILmol/L (normal, 3-17 ILmol/L) and aspartate aminotransferase at 74 lUlL (normal, 10-35 lUlL). The level of C-reactive protein (CRP) was 26.9 mg/dL (normal,
