Human Granulocytic Ehrlichiosis Presenting with Acute Renal Failure and Mimicking Thrombotic Thrombocytopenic Purpura

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Abstract

We present the case of an elderly female patient presenting with recurrent acute renal failure, fever, altered mental status, abdominal pain, thrombocytopenia and a small number of fragmented red cells on peripheral smear mimicking recurrent thrombotic thrombocytopenic purpura (TTP). Eventually, however, she was diagnosed to have human granulocytic ehrlichiosis (HGE), and after treatment for HGE her clinical and laboratory abnormalities resolved. Ehrlichiosis mimicking TTP, diagnosed at postmortem examination, has been described in a single prior case. As illustrated in this case, there are potential difficulties in diagnosing HGE after plasma exchange, blood transfusion and immunosuppressive therapy. Ehrlichiosis, a potentially curable disease, should be considered in the differential diagnosis of thrombotic microangiopathic disorders.

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Direct cultivation of the causative agent of human granulocytic ehrlichiosis.

J L Goodman, C. Nelson, B. Vitale … (1996)

Human granulocytic ehrlichiosis is a potentially fatal tick-borne infection that has recently been described. This acute febrile illness is characterized by myalgias, headache, thrombocytopenia, and elevated serum aminotransferase levels. The disease is difficult to diagnose because the symptoms are non-specific, intraleukocytic inclusions (morulae) may not be seen, and the serologic results are often initially negative. Little is known about the causative agent because it has never been cultivated. We studied three patients with symptoms and laboratory findings suggestive of human granulocytic ehrlichiosis, including unexplained fever after probable exposure to ticks, granulocytopenia, and thrombocytopenia. Peripheral blood was examined for ehrlichia microscopically and with use of the polymerase chain reaction (PCR). Blood was inoculated into cultures of HL60 cells (a line of human promyelocytic leukemia cells), and the cultures were monitored for infection by Giemsa staining and PCR. Blood from the three patients, only one of whom had inclusions suggestive of ehrlichia in neutrophils, was positive for human granulocytic ehrlichiosis on PCR. Blood from all three patients was inoculated into HL60 cell cultures and caused infection, with intracellular organisms visualized as early as 5 days after inoculation and cell lysis occurring within 12 to 14 days. The identity of the cultured organisms was confirmed by immunofluorescence microscopy, PCR analysis, and DNA sequencing. DNA from the infected cells was sequenced in regions of the 16S ribosomal gene reported to differ between the agent of human granulocytic ehrlichiosis and closely related species, including Ehrlichia equi and E. phagocytophila which cause infection in animals. The sequences from all three human isolates were identical and differed from the strain of E. equi studied in having guanine rather than adenine at nucleotide 84. We describe the cultivation of the agent of human granulocytic ehrlichiosis in cell culture. The ability to isolate this organism should lead to a better understanding of the biology, treatment, and epidemiology of this emerging infection.

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Human granulocytic ehrlichiosis in the upper Midwest United States. A new species emerging?

J. S. Bakken, J Dumler, S Chen … (1994)

To characterize the clinical presentation and course, laboratory findings, and treatment outcome of 12 patients with human granulocytic ehrlichiosis. The 12 patients were male, ranged in age from 29 to 91 years, and contracted their illness in Wisconsin or Minnesota. Cases were recognized by the presence of intracytoplasmic inclusions (morulae) in peripheral neutrophils of patients presenting with temperature of 38.5 degrees C or higher, chills, severe headache, and myalgias. All patients had a complete blood cell count and blood chemistry profile. Blood smears were examined by light microscopy. All available paired serum samples were analyzed for presence of indirect fluorescent antibodies against Ehrlichia chaffeensis, Ehrlichia phagocytophila, and Ehrlichia equi. Blood samples from 12 patients were subjected to polymerase chain reaction analysis using primers specific for the E phagocytophila/E equi group, primers that include the agent identified in our patients, as well as E chaffeensis. Varying combinations of leukopenia, anemia, and thrombocytopenia were found in all but one patient. All 12 patients demonstrated morulae in the cytoplasm of neutrophils, but not in mononuclear white blood cells. Serum assays failed to detect antibodies against E chaffeensis, but eight of 10 patients and seven of 10 patients tested had antibody titers of 1:80 or more for E phagocytophila and E equi, respectively. Polymerase chain reaction products obtained with primers for E phagocytophila, E equi, and the granulocytotropic Ehrlichia revealed that seven patients were infected with the same agent. The results of serological assays or polymerase chain reaction strongly suggest that all 12 patients were infected by E phagocytophila, E equi, or a closely related Ehrlichia species. Two of the 12 patients died. The other 10 patients improved rapidly with oral doxycycline treatment. We believe that all 12 patients have been infected with a granulocytic Ehrlichia species, reflecting a recently described new disease entity. The infective organism appears to be closely related to E phagocytophila and E equi. The geographic domain of human granulocytic ehrlichiosis is currently unknown. This novel granulocytic Ehrlichia species is capable of causing fatal infections in humans. Early detection and treatment with tetracycline drugs appear to offer the best chance for complete recovery.

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Clinical and laboratory characteristics of human granulocytic ehrlichiosis.

J. S. Bakken, J Krueth, C Wilson-Nordskog … (1996)

To characterize the clinical and laboratory features observed in patients with human granulocytic ehrlichiosis (HGE) and evaluate the utility of the diagnostic tools used to confirm the diagnosis. Retrospective case study of 41 patients with laboratory-diagnosed HGE. A total of 228 patients from Minnesota and Wisconsin were evaluated between June 1990 and May 1995. Cases were presumptively identified by a history of an influenzalike illness acquired in an area known to be endemic for ticks. Diagnostic laboratory testing included microscopic examination of Wright-stained peripheral blood smears for presence of neutrophilic morulae, polymerase chain reaction (PCR) analysis of acute-phase blood samples for the Ehrlichia phagocytophila/Ehrlichia equi group DNA, and evaluation of serological responses by indirect immunofluorescent antibody assay (IFA), using E equi as antigen. All patients presented with a temperature of at least 37.6 degrees C, and most had headache, myalgias, chills, and varying combinations of leukopenia, anemia, and thrombocytopenia. Eighty percent of the patients tested demonstrated morulae in the cytoplasm of peripheral blood neutrophils. Only 16 of 37 patients tested by PCR were positive for HGE, whereas serum IFA assays of acute or convalescent blood samples detected antibodies against E equi in 38 of 40 patients tested. Two patients died, and the calculated case fatality rate was 4.9%. Human granulocytic ehrlichiosis is being increasingly recognized in Wisconsin and Minnesota. A more severe illness is associated with increased age, anemia, increased percentage of neutrophils and decreased percentage of lymphocytes in peripheral blood, and presence of morulae in neutrophils. The differential diagnosis for patients who develop an influenzalike illness following a tick bite should include HGE. Microscopic examination of the acute-phase blood smear to detect neutrophilic morulae is currently the quickest and most practical screening method for diagnosing HGE in the upper Midwest.

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Author and article information

Journal

Journal ID (publisher-id): AJN

Journal ID (nlm-ta): Am J Nephrol

Journal ID (doi): 10.1159/issn.0250-8095

Title: American Journal of Nephrology

Publisher: S. Karger AG

ISSN (Print): 0250-8095

ISSN (Electronic): 1421-9670

Publication date Subscription-year: 1999

Publication date (Print): December 1999

Publication date (Electronic): 26 November 1999

Volume: 19

Issue: 6

Pages: 677-681

Affiliations

Divisions of ^aNephrology, ^bInfectious Disease, and ^cHematology, Department of Medicine, Hennepin County Medical Center, Minneapolis, Minn., USA

Article

Publisher ID: 13541 Other ID: Am J Nephrol 1999;19:677–681

DOI: 10.1159/000013541

PubMed ID: 10592363

SO-VID: 085293f8-9b70-4d68-a102-af41bef3848a

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Human Granulocytic Ehrlichiosis Presenting with Acute Renal Failure and Mimicking Thrombotic Thrombocytopenic Purpura

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Karger: Nephrology

Most cited references 4

Direct cultivation of the causative agent of human granulocytic ehrlichiosis.

Human granulocytic ehrlichiosis in the upper Midwest United States. A new species emerging?

Clinical and laboratory characteristics of human granulocytic ehrlichiosis.

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