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Ehrlichiosis Workup

  • Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD  more...
 
Updated: Sep 18, 2015
 

Approach Considerations

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

Buffy coat examination may reveal morulae, which are diagnostic characteristics of HME/HGA. Morulae are observed in the cytoplasm of neutrophils in patients with HGA and in monocytes in patients with HME. Only a minority of patients with HME have detectable morulae.

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Lab 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.[1]

Ehrlichiosis may also be diagnosed by demonstrating characteristic morulae in the cytoplasm of leukocytes. Morulae are diagnostic of ehrlichiosis and occur more frequently in HGA than in HME. The microbiology laboratory should be alerted to look carefully in the blood smear for them.

The infecting organism is extremely difficult to culture from blood. Detection of the organism with polymerase chain reaction (PCR) assay is possible.[11]

A complete blood cell (CBC) count should be obtained for possible neutropenia, relative lymphopenia, and/or thrombocytopenia. Anemia is not a 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 minimally/moderately elevated in ehrlichiosis.

Elevated C-reactive protein (CRP) levels are common in the first week of illness and typically resolve by the end of the second week.

Serum transaminases are frequently mildly elevated in ehrlichiosis, as well as in other tick-borne infectious diseases. Abnormal liver enzymes are found in 86% of patients.

If other infectious diseases are suspected, appropriate tests should be obtained to rule out these diagnoses. If coinfection with RMSF or babesiosis is suspected, appropriate serology should be obtained to diagnose each of these infectious diseases.

Microscopic examination (by an experienced microbiologist) of blood smears stained with eosin-azure type dyes, such as Wright-Giemsa stain, may reveal morulae in the cytoplasm of leukocytes. As many as 20% of patients with HME and 20-80% of patients with HGA may have morulae in the first week of infection. A negative result should not be taken as proof of no infection.

Hyponatremia (< 130 mEq/L) is found in 40% of patients.

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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, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa

Disclosure: Received research grant from: Pfizer;GlaxoSmithKline;AstraZeneca;Merck;American Academy of Pediatrics<br/>Received income in an amount equal to or greater than $250 from: Sanofi Pasteur;Astra Zeneca;Novartis<br/>Consulting fees for: Sanofi Pasteur; Novartis; Merck; Astra Zeneca.

Samuel M Keim, MD, MS Professor and Chair, Department of Emergency Medicine, University of Arizona College of Medicine

Samuel M Keim, MD, MS is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Public Health Association, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Walid Abuhammour, MD, MBA, FAAP Professor of Pediatrics, Michigan State University College of Medicine; Director of Pediatric Infectious Disease, Department of Pediatrics, Al Jalila Children's Hospital

Walid Abuhammour, MD, MBA, FAAP is a member of the following medical societies: American Medical Association, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP Assistant Professor of Pediatrics, Co-Director of Antimicrobial Stewardship, Medical Director, Division of Pediatric Infectious Diseases and Immunology, Connecticut Children's Medical Center

Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics

Disclosure: Received research grant from: Cubist Pharmaceuticals, Durata Therapeutics, and Biota Pharmaceutical<br/>Received income in an amount equal to or greater than $250 from: HealthyCT insurance<br/>Medico legal consulting for: Various.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jon Mark Hirshon, MD, MPH, PhD Professor, Department of Emergency Medicine, University of Maryland School of Medicine

Jon Mark Hirshon, MD, MPH, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Public Health Association, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Thomas J Marrie, MD Dean of Faculty of Medicine, Dalhousie University Faculty of Medicine, Canada

Thomas J Marrie, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, Association of Medical Microbiology and Infectious Disease Canada, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Acknowledgements

Geofrey Nochimson, MD Consulting Staff, Department of Emergency Medicine, Sentara Careplex Hospital

Geofrey Nochimson, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

References
  1. CDC. Ehrlichiosis. [Full Text].

  2. Chapman AS, Bakken JS, Folk SM, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide for physicians and other health-care and public health professionals. MMWR Recomm Rep. 2006 Mar 31. 55:1-27. [Medline].

  3. Buller RS, Arens M, Hmiel SP, et al. Ehrlichia ewingii, a newly recognized agent of human ehrlichiosis. N Engl J Med. 1999 Jul 15. 341(3):148-55. [Medline].

  4. Aguero-Rosenfeld ME, Horowitz HW, Wormser GP, et al. Human granulocytic ehrlichiosis: a case series from a medical center in New York State. Ann Intern Med. 1996 Dec 1. 125(11):904-8. [Medline].

  5. Bakken JS, Dumler JS, Chen SM, et al. Human granulocytic ehrlichiosis in the upper Midwest United States. A new species emerging?. JAMA. 1994 Jul 20. 272(3):212-8. [Medline].

  6. Heilpern KL. Update: human ehrlichiosis--Maryland and Wisconsin, 1994. Ann Emerg Med. 1998 Jul. 32(1):108-10. [Medline].

  7. Lovrich SD, Jobe DA, Kowalski TJ, Policepatil SM, Callister SM. Expansion of the midwestern focus for human granulocytic anaplasmosis into the region surrounding la crosse, wisconsin. J Clin Microbiol. 2011 Nov. 49(11):3855-9. [Medline].

  8. Pritt BS, Sloan LM, Johnson DK, Munderloh UG, Paskewitz SM, McElroy KM, et al. Emergence of a new pathogenic Ehrlichia species, Wisconsin and Minnesota, 2009. N Engl J Med. 2011 Aug 4. 365(5):422-9. [Medline].

  9. Strle F. Human granulocytic ehrlichiosis in Europe. Int J Med Microbiol. 2004 Apr. 293 Suppl 37:27-35. [Medline].

  10. Hamburg BJ, Storch GA, Micek ST, Kollef MH. The importance of early treatment with doxycycline in human ehrlichiosis. Medicine (Baltimore). 2008 Mar. 87(2):53-60. [Medline].

  11. Everett ED, Evans KA, Henry RB, McDonald G. Human ehrlichiosis in adults after tick exposure. Diagnosis using polymerase chain reaction. Ann Intern Med. 1994 May 1. 120(9):730-5. [Medline].

  12. Cunha BA, Chandrankunnel JG, Hage JE. Ehrlichia chaffeensis human monocytic ehrlichiosis with pancytopenia. Scand J Infect Dis. 2012 Jun. 44(6):473-4. [Medline].

  13. Nayak SU, Simon GL. Myocarditis after trimethoprim/sulfamethoxazole treatment for ehrlichiosis. Emerg Infect Dis. 2013 Dec. 19(12):1975-7. [Medline]. [Full Text].

  14. Sachdev SH, Joshi V, Cox ER, Amoroso A, Palekar S. Severe life-threatening Ehrlichia chaffeensis infections transmitted through solid organ transplantation. Transpl Infect Dis. 2014 Feb. 16(1):119-24. [Medline].

  15. Schotthoefer AM, Meece JK, Fritsche TR. A clinical, diagnostic, and ecologic perspective on human anaplasmosis in the Upper Midwest. WMJ. 2014 Jun. 113(3):107-14; quiz 115. [Medline].

  16. St Clair K, Decker CF. Ehrlichioses: anaplasmosis and human ehrlichiosis. Dis Mon. 2012 Jun. 58(6):346-54. [Medline].

  17. Watson ME Jr, Storch GA, Dunne WM Jr, Burnham CA. A 2-year-old female with Fever and rash. J Clin Microbiol. 2011 Jul. 49(7):2389, 2784. [Medline]. [Full Text].

 
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Female Lone Star tick, Amblyomma americanum, found in the southeastern and Midatlantic United States. It is a vector of several zoonotic diseases, including human monocytic ehrlichiosis and Rocky Mountain spotted fever. Courtesy of the CDC/Michael L. Levin, PhD.
Map of the United States showing the distribution of the Lone Star Tick, which is the principle vector for ehrlichiosis.
Established and reported distribution of anaplasmosis vectors Ixodes scapularis and Ixodes pacificus, by county, in the United States from 1907-1996. Courtesy of the Division of Vector-Borne Infectious Diseases at the Centers for Disease Control and Prevention.
Anaplasmosis incidence by age. Courtesy of the Centers for Disease Control and Prevention.
Ehrlichiosis incidence by age. Courtesy of the Centers for Disease Control and Prevention.
Table. Characteristics of HME Versus HGA
  Human monocytic ehrlichiosis (HME) Human granulocytic anaplasmosis (HGA)
Cell type Affected Monocytes Granulocytes
Organism E chaffeensis A phagocytophilum
Vector Amblyomma americanum (Lone Star tick) Ixodes scapularis (black-legged tick), Ixodes pacificus (Western black-legged tick) in California, Ixodes ricinus in Europe, and probably Ixodes persulcatus in parts of Asia
Location Southeastern and south-central United States Wisconsin and Minnesota, less active in New York and Connecticut, also California
Rash 30% of adults, 60% of children Rare
Prognosis ~3% mortality < 1% mortality
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