Loy, Monika

Lutz, Hans

Pusterla, Nicola

Weber, Rainer

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253CID 1998;26 (January) Correspondence2. Chesney PJ, Bergdoll MS, Davis JP, Vergeront JM. The disease spectrum, borreliosis. The authors described a 22-year-old man who presentedepidemiology, and etiology of toxic-shock syndrome. Annu Rev Micro- with fever, headache, myalgia, arthralgia, conjunctivitis, fatigue, andbiol 1984;38:315–38. erythema migrans after he had been camping in forests in Slovenia.3. Reingold AL, Hargrett NT, Dan BB, Shands KN, Strickland BY, Broome Because of the presence of leukopenia and thrombocytopenia, a diag-CV. Nonmenstrual toxic shock syndrome. A review of 130 cases. Annnosis of ehrlichiosis was considered, but serological tests to detectIntern Med 1982;96:871–4.antibodies to Ehrlichia equi and Ehrlichia phagocytophila and micro-4. Kain KC, Schulzer M, Chow AW. Clinical spectrum of nonmenstrual toxicscopic examination of blood smears were negative. However, theshock syndrome (TSS): comparison with menstrual TSS by multivariatepresence of antibodies to Borrelia burgdorferi was documented. Thediscriminant analyses. Clin Infect Dis 1993;16:100–6.patient was treated with tetracyclines and recovered quickly.5. Cone LA, Woodard DR, Byrd RG, Schulz K, Kopp SM, Schlievt PM. Arecalcitrant, erythematous, desquamating disorder associated with toxin- Nadelman et al. [2] challenged the assertion of Gu¨nthard et al. [1,producing staphylococci in patients with AIDS. J Infect Dis 1992;165: 3], arguing that a negative serology for E. equi does not exclude638–43. coinfection with Ehrlichia and that unusual clinical manifestations or6. Verbon A, Fisher CJ Jr. Severe recalcitrant erythematous desquamating laboratory findings following tick bites are not necessarily due to thedisorder associated with fatal recurrent toxic shock syndrome in a patientprotean manifestations of Lyme borreliosis but may be caused bywithout AIDS. Clin Infect Dis 1997;24:1274–5.coinfection with B. burgdorferi and the agents of human granulocytic7. Schlossberg D. A possible pathogenesis for recurrent toxic shock syndrome.ehrlichiosis (HGE), babesiosis, or tick-borne encephalitis.Am J Obstet Gynecol 1981;141:348–9.We recently had the opportunity to follow the patient of Gu¨n-8. Davis JP, Osterholm MT, Helms CM, et al. Tristate toxic-shock syndromethard almost 2 years after his illness. He had been completely healthystudy. II. Clinical and laboratory findings. J Infect Dis 1982;145:441–8. since he was treated for acute Lyme disease. In addition, he clearlyremembered that he had been bitten by several ticks in Slovenia.Reprints or correspondence: Dr. Annelies Verbon, Department of Internal Three stored serum samples (kindly provided by Dr. O. Pe´ter, Sion,Medicine, F4-260, Academic Medical Center, Meibergdreef 9, 1105 AZ Am-Switzerland) and one specimen obtained during the current follow-sterdam, the Netherlands.up were examined for antibodies to E. phagocytophila by indirectClinical Infectious Diseases 1998;26:252–3immunofluorescence, as previously described [4]. We found sero-q 1998 by The University of Chicago. All rights reserved.1058–4838/98/2601–0083$03.00 conversion and reconversion of antibodies to E. phagocytophila, sug-gesting that the patient had been coinfected with the agent of HGEand with B. burgdorferi (table 1). It is well accepted that the causativeagent of HGE is immunologically closely related to E. phagocytophilaFever, Leukopenia, and Thrombocytopenia in a Patientand E. equi, and thus these antigens (but not the Ehrlichia chaffeensiswith Acute Lyme Borreliosis Were Due to Humanantigen) are useful in serological testing for HGE [6].Granulocytic EhrlichiosisTicks of the genus Ixodes (the likely vector of HGE) are prevalentin Europe and are known to transmit Lyme borreliosis and the Euro-SIR—Gu¨nthard et al. [1] raised the question whether leukopenia,thrombocytopenia, and hepatitis may be associated with acute Lyme pean tick-borne encephalitis virus. In addition, seroepidemiologicalTable 1. Laboratory values for a 22-year-old man who was bitten by a tick in Slovenia.No. of days after tick biteParameter 7 9 12 21 90 620Leukocytes (1109/L) 2.2 3.3 ND 4.3 ND NDThrombocytes (1109/L) 98 140 ND 228 ND NDC-reactive protein (mg/L)* 59 16 ND ND ND NDAspartate aminotransferase (U/L)† 96 61 ND 16 ND NDAlanine aminotransferase (U/L)† 91 109 ND 51 ND NDIgG and IgM antibodies toBorrelia burgdorferi ‡ Negative ND Positive Positive ND NDIgM antibodies to B. burgdorferi ‡ Borderline ND Positive Positive ND NDAntibodies to European tick-borneencephalitis virus Negative ND ND Negative Negative NDAntibodies to Ehrlichia equi andEhrlichia phagocytophila ‡ Negative ND ND Negative Negative NDTiter of antibodies toE. phagocytophila§ 20 ND 80 ND 80 20NOTE. ND  not done.* Normal level, 10.† Normal level, 40.‡ Data are from [1,3].§ Data are from methods previously described [4,5]; titers of 80 are considered negative.254 Correspondence CID 1998;26 (January)Referencesdata from Switzerland [7], Norway, the United Kingdom, and Swedenhave suggested that HGE may be prevalent in Europe. Investigators1. Gu¨nthard HF, Pe´ter O, Gubler J. Leukopenia and thrombocytopenia in ain Slovenia recently provided serological and molecular evidence ofpatient with early Lyme borreliosis. Clin Infect Dis 1996;22:1119–20.HGE in their country [8]. Furthermore, a newly discovered species2. Nadelman RB, Strle F, Horowitz HW, Agger WA, Wormser GP. Leukope-of Ehrlichia in dogs in Switzerland was shown to have a 100%nia, thrombocytopenia, and Lyme borreliosis: is there an association?sequence homology of the 16S rRNA gene with that of the agent of[letter]. Clin Infect Dis 1997;24:1027–8.HGE [9]. Thus, it can be hypothesized that HGE occurs in Europe,3. Pe´ter P, Gubler J, Gu¨nthard HF. Reply [letter]. Clin Infect Dis 1997;24:although there have not been any reports of microscopic detection of 1028–9.the organism in humans. 4. Pusterla N, Wolfensberger C, Lutz H, Braun U. Serological testing on theThe methods for diagnosing HGE have yet to be improved. The occurence of bovine ehrlichiosis in the Cantons Zu¨rich, Schaffhausen,clinical manifestation of ehrlichiosis is a nonspecific febrile illness. Thurgau, St. Gallen and Obwalden. Schweiz Arch Tierheilkd 1997 (inThe sensitivity of microscopic examination for detecting Ehrlichia in press).5. Pusterla N, Wolfensberger C, Gerber-Bretscher R, Braun U, Lutz H. Com-granulocytes or monocytes is low [10], and molecular diagnosis isparison of indirect immunofluorescence for Ehrlichia phagocytophilaavailable only in research laboratories. Serological tests to detectand E. equi in horses. Equine Vet J 1998 (in press).antibodies to the agent of HGE are currently not standardized and6. Dumler JS, Asanovich KM, Bakken JS, Richter P, Kimsey R, Madiganare not commercially available; furthermore, negative serological testsJE. Serologic cross-reactions among Ehrlichia equi, Ehrlichia phagocy-do not exclude the presence of ehrlichiosis. We believe that the failuretophila, and human granulocytic Ehrlichia. J Clin Microbiol 1995;33:of Gu¨nthard et al. [1, 3] to detect antibodies reacting with E. equi1098–103.and E. phagocytophila on days 21 and 90 could be explained by a7. Brouqui P, Dumler JS, Lienhard R, Brossard M, Raoult D. Human granulo-somewhat lower diagnostic sensitivity of the tests used. We have cytic ehrlichiosis in Europe. Lancet 1995;346:782–3.used an assay that has been extensively validated in 2,557 serum 8. Petrovec M, Furlan SL, Zupanc TA, et al. Human disease in Europe causedsamples from cattle [4], 1,645 serum samples from horses [5], and by a granulocytic Ehrlichia species. J Clin Microbiol 1997;35:1556–9.in 1,515 human serum samples (N. Pusterla, unpublished data). 9. Pusterla N, Huder J, Wolfensberger C, Litschi B, Parvis A, Lutz H. Granu-Epidemiological and clinical evidence is growing that HGE is locytic ehrlichiosis in two dogs in Switzerland. J Clin Microbiol 1997;35:2307–9.also prevalent in Europe. Suspicion of HGE (or dual infections10. Bakken JS, Krueth J, Wilson-Nordskog C, Tilden RL, Asanovich K,with HGE and Lyme borreliosis), based on a patient’s history andDumler JS. Clinical and laboratory characteristics of human granulo-clinical presentation and the pathognomonic laboratory pattern,cytic ehrlichiosis. JAMA 1996;275:199–205.including leukopenia, thrombocytopenia, and elevation of transam-inases [10], is crucial because it has major therapeutic implications.HGE requires treatment with tetracyclines and does not respondReprints or correspondence: Dr. Rainer Weber, Division of Infectious Dis-to b-lactam antibiotics [10].eases and Hospital Epidemiology, Department of Internal Medicine, UniversityHospital of Zurich, CH-8091 Zurich, Switzerland.Rainer Weber, Nicola Pusterla, Monika Loy, and Hans LutzDivision of Infectious Diseases and Hospital Epidemiology, Department Clinical Infectious Diseases 1998;26:253–4of Internal Medicine, University Hospital of Zurich; and Department of q 1998 by The University of Chicago. All rights reserved.1058–4838/98/2601–0084$03.00Veterinary Internal Medicine, University of Zurich, Zurich, Switzerland

Fever, Leukopenia, and Thrombocytopenia in a Patient with Acute Lyme Borreliosis Were Due to Human Granulocytic Ehrlichiosis

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