eMedicine Specialties > Infectious Diseases > Bacterial Infections

Ehrlichiosis: Differential Diagnoses & Workup

Author: Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Contributor Information and Disclosures

Updated: Feb 5, 2009

Differential Diagnoses

Babesiosis
Malaria
Meningitis
Rocky Mountain Spotted Fever
Typhoid Fever

Other Problems to Be Considered

Ehrlichiosis is a difficult infectious disease to diagnose because it manifests as an acute undifferentiated febrile RMSF-like illness with few to no physical findings. Most patients who are diagnosed with RMSF without rash probably have ehrlichiosis.

Ehrlichiosis has the same distribution as RMSF and is transmitted by the same tick species (eg, Amblyomma, Dermacentor). Both RMSF and ehrlichiosis manifest as acute, febrile, undifferentiated infectious diseases. However, RMSF causes physical findings that ehrlichiosis does not, including bilateral periorbital edema, edema of the dorsum of the hands and feet, and conjunctival suffusion. The petechial rash of RMSF is absent in ehrlichiosis.

Laboratory findings associated with RMSF and ehrlichiosis are similar (eg, thrombocytopenia, lymphopenia, increased levels of serum transaminases, atypical lymphocytes). However, neutropenia is more common in ehrlichiosis than in RMSF.

Because most patients with ehrlichiosis present with fever and a severe headache, meningitis may be included in the differential diagnoses. Patients with ehrlichiosis do not have nuchal rigidity, as opposed to patients with aseptic or bacterial meningitis. The cerebral spinal fluid (CSF) profile in patients with ehrlichiosis is normal, in contrast to patients with viral or bacterial meningitis.

Other differential diagnostic possibilities include typhoid fever, malaria, and babesiosis. All of these infectious diseases manifest as acute, undifferentiated, febrile illnesses with a paucity of physical signs. The diagnosis of typhoid fever and malaria are suggested by an appropriate epidemiologic profile and/or travel history. Exposure to large Dermacentor ticks would suggest RMSF, whereas exposure to small Ixodes ticks would suggest the possibility of babesiosis.

Co-infections of various tick-borne pathogens transmitted by the same vector are uncommon, but they do occur.

Workup

Laboratory Studies

  • The diagnosis of human monocytic ehrlichiosis (HME) or human granulocytic anaplasmosis (HGA) rests on (1) a single elevated immunoglobulin G (IgG) immunofluorescent antibody (IFA) Ehrlichia titer or (2) demonstration of a 4-fold or greater increase between acute and convalescent IFA Ehrlichia titers.
  • Ehrlichiosis may also be diagnosed by demonstrating characteristic morulae in the cytoplasm of leukocytes. Morulae are diagnostic of ehrlichiosis and occur more frequently in human granulocytic anaplasmosis than in human monocytic ehrlichiosis.
  • The infecting organism is extremely difficult to culture from blood. Detection of the organism with polymerase chain reaction (PCR) is possible, but only a few laboratories are currently capable of performing this assay.1
  • The microbiology laboratory should be alerted to look carefully in the blood smear for cytoplasmic inclusions (morulae), which, if found, are diagnostic of ehrlichiosis.
  • Nonspecific laboratory tests in patients with acute febrile illnesses may suggest various tick-borne infectious diseases, including ehrlichiosis.
  • A complete blood cell (CBC) count should be obtained for possible neutropenia, lymphocytopenia, and/or thrombocytopenia. Anemia is not a typical feature of ehrlichiosis and, if present, is not a hemolytic anemia, as in babesiosis.
  • Atypical lymphocytes have been reported in patients with ehrlichiosis. The erythrocyte sedimentation rate (ESR) is variably elevated in ehrlichiosis.
  • Serum transaminases should be evaluated because they are frequently mildly elevated in ehrlichiosis, as well as in other tick-borne transmitted infectious diseases.
  • DIC may be diagnosed in patients with a cutaneous bleeding diathesis who have thrombocytopenia and in whom schistocytes are observed in the peripheral smear.
  • If other infectious diseases are suspected, appropriate tests should be obtained to rule out these diagnoses. If co-infection with RMSF or babesiosis is suspected, appropriate serology should be obtained to diagnose each of these infectious diseases.

Other Tests

  • Lumbar puncture (LP) may be necessary in patients with fever and severe headache to rule out meningitis.

Histologic Findings

The method of attachment of Ehrlichia to white blood cells is not understood. However, after intracellular multiplication in mononuclear phagocytic cells, the cells burst, releasing ehrlichial cells into the circulation and infecting other white blood cells.

Ehrlichia are obligate intracytoplasmic bacteria that infect mononuclear cells and granulocytes. Ehrlichia, which are tiny (0.2-2 µm) gram-negative organisms that resemble Rickettsia, divide by binary fission and multiply within the cytoplasm of infected white blood cells. Clusters of Ehrlichia multiply in host cell vacuoles to form large mulberry-shaped aggregates called morulae. Ehrlichia inclusion bodies (morulae) are visible in the cytoplasm of infected mononuclear phagocytic cells after 5-7 days.

More on Ehrlichiosis

Overview: Ehrlichiosis
Differential Diagnoses & Workup: Ehrlichiosis
Treatment & Medication: Ehrlichiosis
Follow-up: Ehrlichiosis
Multimedia: Ehrlichiosis
References
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Further Reading

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Keywords

ehrlichiosis, human monocytic ehrlichiosis, HME, human granulocytic anaplasmosis, HGA, human granulocytic ehrlichiosis, HGE, spotless Rocky Mountain spotted fever, Ehrlichia, Ehrlichia chaffeensis, E chaffeensis, Erlichia ewingii, E ewingii, Anaplasma phagocytophilum, A phagocytophilum, morulae

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Contributor Information and Disclosures

Author

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Thomas J Marrie, MD, Chair, Professor, Department of Medicine, Division of Infectious Diseases, University of Alberta College of Medicine
Thomas J Marrie, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, Canadian Infectious Disease Society, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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