AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Ehrlichiosis is an infection of white blood cells that affects various mammals, including mice, cattle, dogs, deer, horses, sheep, goats, and humans.

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, such as morulae, are visible in the cytoplasm of infected mononuclear phagocytic cells after 5-7 days. The type of ehrlichiosis that develops varies and depends on the infecting species and the type of leukocyte infected. Human granulocytic anaplasmosis (HGA; also known as human granulocytic ehrlichiosis [HGE]) is caused by species that infect granulocytes, including Ehrlichia ewingii and Anaplasma phagocytophilum. In contrast, human monocytic ehrlichiosis (HME) is caused by species that infect monocytes or macrophages, including Ehrlichia chaffeensis and the Ehrlichia equi/E equi cluster.

Pathophysiology

The pathophysiology of ehrlichiosis is not completely understood. Like Rickettsia species, Ehrlichia organisms gain access to the blood via a bite from an infected tick. Amblyomma americanum (Lone Star tick) is the principle tick vector of E chaffeensis and is the primary vector of human monocytic ehrlichiosis. Species that cause human granulocytic anaplasmosis may be transmitted from Ixodes persulcatus ticks and possibly Dermacentor variabilis (dog tick/wood tick).

The major antigenic determinants of Ehrlichia are surface membrane proteins. These antigenic proteins are complex and consist of both thermolabile and thermostable components. In terms of kilodalton (kD) molecular weight, the key protein bands associated with human monocytic ehrlichiosis are the 27-, 29-, and 44-kD bands. The major antigenic determinants associated with human granulocytic anaplasmosis include the 40-, 44-, and 65-kD bands.

Frequency

United States

The distribution of ehrlichiosis in the United States mirrors the tick distribution and appropriate mammalian vectors (eg, white-footed mouse, white-tailed deer). Ehrlichiosis occurs where mammalian hosts are in contact with the appropriate tick vector (ie, A americanum, D variabilis, Ixodes ticks). Hundreds of cases of human monocytic ehrlichiosis and human granulocytic anaplasmosis have been reported, but ehrlichiosis is not a reportable disease; therefore, many more cases go unreported.

Most cases of ehrlichiosis in the United States occur in the states of California and Texas and the southeast and northeast regions of the country, with some cases occurring in the north central states west of the Great Lakes.

International

Ehrlichiosis occurs essentially worldwide, and the frequency parallels the distribution of the appropriate tick vectors for the transmission of Ehrlichia bacteria and the mammalian hosts.

Mortality/Morbidity

The great majority of cases of ehrlichiosis are asymptomatic. Most cases present as mild-to-moderate acute febrile illnesses. In immunocompromised hosts, ehrlichiosis may be severe, manifesting as a Rocky Mountain spotted fever (RMSF)–like illness that may be fatal.

Sex

Ehrlichiosis is more common in males, with a male-to-female ratio of 4:1.

Age

Ehrlichiosis occurs in all age groups but is most common in young adults. For information on pediatric ehrlichiosis, see the article Ehrlichiosis in eMedicine Pediatrics: General Medicine volume.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Clinical manifestations of ehrlichiosis usually begin 5-14 days after the tick bite.
• Patients with ehrlichiosis usually present with severe headache, myalgias, and fever. Shaking chills are often present.
• Nausea and vomiting are common.
• Abdominal pain is uncommon and is typically mild.
• Skin rash due to ehrlichiosis is rare, in contrast to RMSF.

Physical

• In contrast to RMSF, rash is rare in ehrlichiosis. When present in ehrlichiosis, the rash is maculopapular rather than petechial. Also in contrast to RMSF, ehrlichiosis does not cause vasculitis.
• Physical findings due to ehrlichiosis are minimal. Some patients develop slight hepatomegaly.
• Lymphadenopathy is observed in less than 25% of cases, and splenomegaly is not common.
• Patients with severe ehrlichiosis may develop thrombocytopenia or disseminated intravascular coagulation (DIC), which can result in hemorrhage into the skin.

Causes

• Ehrlichia are obligate intracytoplasmic bacteria that infect mononuclear cells and granulocytes.
• Ehrlichia resemble Rickettsia and are tiny (0.2-2 µm) gram-negative organisms that divide by binary fission and multiply within the cytoplasm of infected white blood cells.
• Clusters of Ehrlichia (called morulae) multiply in the vacuoles of cells, forming large mulberry-shaped aggregates.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.
• 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.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Patients who are moderately-to-severely ill may be hospitalized for diagnosis and therapy.

Consultations

• An infectious disease specialist should be consulted for any patient with an acute febrile illness and a recent history of tick exposure.
• A hematologist should be consulted if hemorrhagic manifestations are present.

Diet

• Diet is as usual.

Activity

• Activity may be altered depending on the severity of illness.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The preferred drug for both human monocytic ehrlichiosis (HME) and human granulocytic anaplasmosis (HGA) is doxycycline. In contrast to RMSF, chloramphenicol is not effective in ehrlichiosis. Although experience is limited, in vivo data suggest that rifampin may be useful in patients who are unable to take doxycycline (eg, children <8 y, pregnant females). Fluoroquinolones may be useful against Ehrlichia, but experience is limited.

Drug Category: Antibiotics

Empiric antimicrobial therapy should cover the most likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Deterrence/Prevention

• In endemic ehrlichiosis areas, proper precautions should be taken when traveling through tick-infested wooded areas by minimizing exposed areas of skin with proper clothing and diethyltoluamide (DEET).
• After returning from wooded and/or tick-infested areas, individuals should check themselves carefully for ticks. If found, ticks should be removed carefully and a physician should be consulted.

Prognosis

• Ehrlichiosis carries an excellent prognosis in healthy hosts.
• Ehrlichiosis carries an estimated mortality rate of 1-5%. The likelihood of mortality is much greater in immunocompromised hosts.

Patient Education

• Educate patients in endemic ehrlichiosis areas to take proper precautions when traveling through wooded and/or tick-infested areas (see Deterrence/Prevention).
• For excellent patient education resources, visit eMedicine's Bites and Stings Center. Also, see eMedicine's patient education article Ticks.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Clinicians should remember that doxycycline is the preferred antimicrobial agent for all treatable tick-borne infectious diseases.
• Avoid using chloramphenicol in patients with possible ehrlichiosis because it is ineffective in both human monocytic ehrlichiosis (HME) and human granulocytic anaplasmosis (HGA).

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Oct 16, 2008