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eMedicine Specialties > Emergency Medicine > Infectious Diseases

Tick-Borne Diseases, Ehrlichiosis

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

Updated: Sep 17, 2008

Introduction

Background

In the past 10 years in the United States, 3 emerging tick-borne diseases caused by the obligate intracellular bacteria of the genus Ehrlichia have been recognized. Human monocytic ehrlichiosis (HME) was first described in 1986 and is caused by Ehrlichia chaffeensis. Human granulocytotropic anaplasmosis (HGA), formerly known as human granulocytic ehrlichiosis (HGE), was described in 1993 and is caused by Anaplasma phagocytophilum. Both types have been referred to as spotless Rocky Mountain spotted fever. Ehrlichia ewingii was described in 1999 as an agent of human ehrlichiosis.

Pathophysiology

The hematopoietic system is the main organ system affected. However, the GI, immune, and nervous systems also are involved.

Frequency

United States

Ehrlichiosis is a seasonal disease observed mainly from April to September. In 1999, ehrlichiosis became reportable to the CDC. In 2005, 786 cases of HGA were reported. The 3 states that reported the most cases were New York (221 cases), Minnesota (186 cases), and Wisconsin (155 cases). In 2006, 646 cases of HGA were reported. The 3 states that reported the most cases were New York (235 cases), Minnesota (177 cases), and Wisconsin (49 cases).

In 2005, 506 cases of HME were reported. The 3 states that reported the most cases were New York (85 cases), Oklahoma (79 cases), and New Jersey (64 cases). In 2006, 578 cases of HME were reported. The 3 states that reported the most cases were New York (141 cases), Missouri (73 cases), and New Jersey (67 cases).

International

Human granulocytotropic anaplasmosis has been reported throughout Europe. As of March 2003, 65 cases of confirmed HGA were reported.

Ehrlichia sennetsu causes a mononucleosislike illness in Japan and Malaysia.

Mortality/Morbidity

The total duration of illness for HME and HGA is unknown. No chronic cases have been reported at this time.

  • The HME mortality rate is reported to be 2-5%, while that for HGA is 7-10%.
  • HME has a reported hospitalization rate as high as 60%, while that for HGA is 28-54%.

Sex

Males are affected more than females in HME and HGA. In 2006, the CDC reported that of the 646 cases of HGA, 357 were males and 273 were females (16 cases did not specify sex). HME had a similar distribution, with 337 males and 234 females among the 578 cases in 2006 (7 cases did not specify sex).

  • The incidence rates per 100,000 for males were 0.26 for HGA and 0.24 for HME. For females, the rates were 0.19 for HGA and 0.16 for HME.

Age

  • Cases are reported more frequently in adults than in children. The highest age range is between 40 and 64 years.
  • Elderly patients (>60 y) are more likely than others to develop severe infections and account for most of deaths due to this disease.

Clinical

History

The histories for HME, HGA, and E ewingii infection are similar and may include the following:

  • Tick bites or exposure (>90% in 1 series) (Patients usually present within 1 week of tick bite.)
  • Fevers (>90%)
  • Headaches (>85%)
  • Malaise (>70%)
  • Myalgias (>70%)
  • Rigors (60%)
  • Nausea (40%)
  • Vomiting (40%)
  • Anorexia (40%)
  • Confusion (20%)
  • Rash (10%) (These can occur anywhere on the body, not necessarily at the site of the tick bite.)

Physical

No specific findings that assist in making the diagnosis are evident on clinical examination.

Causes

Target cells for the pathogens are macrophages or granulocytes.

  • In HME, the following ticks may affect the macrophages:
    • Lone-star tick (Amblyomma americanum)
    • American dog tick (Dermacentor variabilis)
  • In HGA, the following ticks may affect the granulocytes:
    • Blacklegged tick (Ixodes scapularis)
    • American dog tick (D variabilis)
  • In E ewingii infection, the Lone-star tick (A americanum) may affect the granulocytes.

Differential Diagnoses

Babesiosis
Erythema Multiforme
Stevens-Johnson Syndrome
Tick-Borne Diseases, Lyme
Tick-Borne Diseases, Rocky Mountain Spotted Fever
Toxic Shock Syndrome

Workup

Laboratory Studies

  • The CBC count in patients with ehrlichiosis may indicate the following:
    • Leukopenia
    • Thrombocytopenia
    • Morulae in peripheral granulocytes (25-80%) but not in monocytes (Morulae are cytoplasmic vacuoles in which Ehrlichia species grow.)
  • Wright staining of blood smears may be performed. Blood smears may only be positive in up to 60% of cases.
  • Mild-to-moderate elevations of aminotransferase levels may be present.

Other Tests

  • Indirect fluorescent antibody test
    • HME is present with a 4-fold increase in the antibody titer (minimum titer, 1:64) or a single high antibody titer (>1:128).
    • HGA is present with a 4-fold increase in the antibody titer (minimum titer, 1:80).
  • Polymerase chain reaction
    • PCR is a research tool available in selected hospitals.
    • The Centers for Disease Control and Prevention perform this test, but submission of samples requires prior approval.

Treatment

Emergency Department Care

Do not delay treatment to wait for confirmatory laboratory results. With a strong suspicion of ehrlichiosis, start antibiotic treatment as soon as possible.

Consultations

Consult an infectious disease specialist, particularly if the patient is a child or is pregnant.

Medication

Antibiotic treatment should begin as soon as the diagnosis is ascertained. Antipyretics may be necessary.

Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.


Doxycycline (Bio-Tab, Doryx, Vibramycin)

Only drug proven to be effective. Inhibits protein synthesis and thus bacterial growth by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Dosing

Adult

Hospitalized patients: 100 mg IV bid
Nonhospitalized patients: 100 mg PO bid

Pediatric

Hospitalized patients: 3 mg/kg/d IV bid
Nonhospitalized patients: 3 mg/kg/d PO

Interactions

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy

Contraindications

Documented hypersensitivity; severe hepatic dysfunction

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Photosensitivity (with prolonged exposure to sunlight or tanning equipment); reduce dose in renal impairment; consider determining drug serum levels in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can permanently discolor teeth; Fanconilike syndrome may occur with outdated tetracyclines

Follow-up

Inpatient & Outpatient Medications

  • Continue doxycycline for 3 days after defervescence, for a minimum of 5-7 days.

Deterrence/Prevention

Deterrence and prevention of ehrlichiosis includes the following:

  • Wear light-colored clothes.
  • Tuck pants into socks.
  • Use insect repellent.
  • Regularly examine the body for ticks.
  • Promptly remove ticks by using forceps. (A feeding period of 3-48 h is required before disease is transmitted.)

Complications

  • Compared with other patients, elderly patients have a higher risk of death.
  • Laboratory test results are necessary to make the diagnosis.
  • An alternative antibiotic for children aged 8 years or younger and for pregnant patients is not available.

Prognosis

  • A favorable outcome is associated with the early use of antibiotics.
  • Many cases of HGA and HME may be subclinical and self-limited.

Miscellaneous

Medicolegal Pitfalls

  • Failure to determine a history of tick bite
  • Failure to consider the diagnosis in patients with flulike symptoms during the summer season

References

  1. 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. Dec 1 1996;125(11):904-8. [Medline].

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

  3. Bakken JS, Krueth J, Wilson-Nordskog C, et al. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA. Jan 17 1996;275(3):199-205. [Medline].

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

  5. CDC. Human Ehrlichiosis. Available at http://www.cdc.gov/ncidod/dvrd/ehrlichia/Index.htm. Accessed September 4, 2008.

  6. 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. Mar 31 2006;55(RR-4):1-27. [Medline].

  7. Dumler JS, Bakken JS. Ehrlichial diseases of humans: emerging tick-borne infections. Clin Infect Dis. May 1995;20(5):1102-10. [Medline].

  8. Fishbein DB, Dawson JE, Robinson LE. Human ehrlichiosis in the United States, 1985 to 1990. Ann Intern Med. May 1 1994;120(9):736-43. [Medline].

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

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

  11. Maeda K, Markowitz N, Hawley RC, et al. Human infection with Ehrlichia canis, a leukocytic rickettsia. N Engl J Med. Apr 2 1987;316(14):853-6. [Medline].

  12. McQuiston JH, McCall CL, Nicholson WL. Ehrlichiosis and related infections. J Am Vet Med Assoc. Dec 15 2003;223(12):1750-6. [Medline].

  13. Ochoa WG, Wedro BC, Firary SA. Images in emergency medicine. Human ehrlichiosis. Ann Emerg Med. Nov 2005;46(5):470, 478. [Medline].

  14. Prince LK, Shah AA, Martinez LJ, Moran KA. Ehrlichiosis: making the diagnosis in the acute setting. South Med J. Aug 2007;100(8):825-8. [Medline].

  15. Schaffner W, Standaert SM. Ehrlichiosis--in pursuit of an emerging infection. N Engl J Med. Jan 25 1996;334(4):262-3. [Medline].

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

  17. Walker DH, Dumler JS. Emergence of the ehrlichioses as human health problems. Emerg Infect Dis. Jan-Mar 1996;2(1):18-29. [Medline].

Keywords

tick-borne disease, ehrlichiosis, Ehrlichia ewingii, Ehrlichia phagocytophila, human granulocytic ehrlichiosis, HGE, human monocytic ehrlichiosis, HME, vector-borne disease, tick-borne disease, Anaplasma phagocytophilum, human granulocytotropic anaplasmosis, HGA

Contributor Information and Disclosures

Author

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.

Medical Editor

Samuel M Keim, MD, Associate Professor, Department of Emergency Medicine, University of Arizona College of Medicine
Samuel M Keim, MD 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, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Jon Mark Hirshon, MD, MPH, Associate Professor, Department of Emergency Medicine, University of Maryland School of Medicine
Jon Mark Hirshon, MD, MPH 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, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Charles V Pollack, Jr, MD, MA, FACEP, Professor, Department of Emergency Medicine, University of Pennsylvania College of Medicine; Chairman, Department of Emergency Medicine, Pennsylvania Hospital
Charles V Pollack, Jr, MD, MA, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians
Disclosure: sanofi-aventis Honoraria Consulting; sanofi-aventis Honoraria Speaking and teaching; Schering-Polugh Honoraria Consulting; Schering-Plough Honoraria Speaking and teaching; The Medicines Company Honoraria Consulting; GlaxoSmithKline Grant/research funds Other

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