Basics
Description
Two common clinically described infections are human monocytic ehrlichiosis (HME), caused by Ehrlichia chaffeensis, and human granulocytic anaplasmosis (HGA), caused by Anaplasma phagocytophilum. Human ehrlichiosis can be caused by 2 other Ehrlichia species in the United States: ewingii and muris-like agent.
Epidemiology
- HME typically occurs in the midwest, south central, and southeastern United States, mirroring the pattern of Rocky Mountain spotted fever (RMSF). In addition, it has been found in Europe, South America, Asia, and Africa.
- HGA typically occurs in the north central, northeastern United States, and northern California, similar to Lyme disease. Most patients are infected during April through September, the months of greatest tick and human outdoor activity.
- A second peak of HGA occurs from late October to December.
General Prevention
- Avoid tick-infested areas.
- Clothes should cover arms and legs.
- Use tick repellents, but with caution in young children.
- A thorough body search should always be done after returning from a tick-infested area:
- If a tick is found, the area should be cleaned with a disinfectant, and the tick should be removed immediately.
- To remove the tick, grasp the tick at the point of origin with forceps, staying as close to the skin as possible.
- Applying steady, even pressure, slowly pull the tick off the skin. After the tick has been removed, clean the skin with a disinfectant.
- Instruct parents to seek medical attention only if symptoms develop.
- No vaccine is available.
Pathophysiology
- Obligate intracellular, pleomorphic, gram-negative bacteria.
- Transmission to humans by a tick vector
- Incubation period from 2 to 21 days
- HME infects monocytes and macrophages, whereas HGA infects neutrophils.
- The bacteria reside and divide within cytoplasmic vacuoles of circulating leukocytes, called morulae.
- There is overinduction of the inflammatory and immune response, resulting in clinical manifestations of disease, including multiorgan system involvement.
Etiology
- HME is transmitted by Amblyomma americanum, the Lone Star tick. The white-tailed deer is the major reservoir.
- HGA is transmitted by Ixodes scapularis, the black-legged or deer tick, or the Western black-legged tick (Ixodes pacificus). Small mammals such as the white-footed mouse are the major reservoirs.
- Congenital infection is very rare but has been described in case reports.
Diagnosis
- Classic presentation: fever, headache, and myalgias, followed by the development of a progressive leukopenia, thrombocytopenia, and anemia
History
- History of tick bite or exposure to wooded areas that are endemic for tick-borne diseases is helpful but is not always present.
- Fever, severe headache, chills, and myalgias
- Complaints of abdominal pain, vomiting, anorexia, and diarrhea may be present.
- Cough and sore throat are often described.
Physical Exam
- Fever is described in all children.
- A pleomorphic rash occurs in ~66% of pediatric patients with HME:
- Rash is described as macular, maculopapular, petechial, erythematous, vesicular, or a combination of these.
- Usually distributed on the trunk and extremities; spares palms, soles, and face
- Mental status change due to meningoencephalitis
- Cardiac murmur (II/VI systolic ejection murmur at the left lower sternal border)
- Hepatosplenomegaly
- Conjunctival or throat injection
Diagnostic Tests & Interpretation
Lab
- CBC with differential (with smear)
- Thrombocytopenia, <150,000/mm3 (77-92% incidence)
- Lymphopenia, <1,500/mm3 (75%) with HME
- Neutropenia, <4,000/mm3 (58-68%) with HGA
- Anemia, hematocrit <30% (38-42%)
- Intracytoplasmic morulae within leukocytes (20-60%), more common with HGA
- Electrolytes with BUN and creatinine: hyponatremia (33-65%)
- Liver function tests: elevated alanine aminotransferase, >55 U/L (90%)
- Coagulation labs, type and cross, as indicated
- CSF
- Leukocytosis, with an average cell count of 100/mm3
- Lymphocytic predominance
- Elevated protein and borderline low glucose (less common in children, more common in adults)
- Microbiology cultures are negative.
- Intraleukocytoplasmic Ehrlichia microorganisms (morulae) have been described on CSF smears.
- Serum studies
- Acute and convalescent antibody titers of Ehrlichia (a 4-fold rise or fall is considered positive) obtained 2-4 weeks apart
- An acute antibody titer of ≥1:128 is considered diagnostic.
- Polymerase chain reaction is also available for both HME and HGA.
- The detection of intraleukocytoplasmic Ehrlichia microcolonies (morulae) on blood or bone marrow monocytes or granulocytes is diagnostic but is not present in all patients.
Diagnostic Procedures/Other
- Bone marrow biopsy is not necessary to diagnose the ehrlichiosis but may be carried out amid concern for other hematologic diseases.
- Bone marrow is usually hypercellular, but normocellularity and hypocellularity have also been found.
Alert
- Failing to consider the diagnosis of ehrlichiosis or a delay in treatment pending confirmatory serum titers increases morbidity and mortality.
- Thus, treatment should be started if infection is suspected based on history, physical, and initial laboratory data.
- Alternative diagnoses should be considered in children who do not rapidly improve with doxycycline.
- Simultaneous infections have been documented with HGA and Lyme disease.
Differential Diagnosis
- Tick-borne infection
- RMSF
- Tularemia
- Relapsing fever
- Lyme disease
- Colorado tick fever
- Babesiosis
- Other infections
- Toxic shock syndrome
- Kawasaki disease
- Meningococcemia
- Pyelonephritis
- Gastroenteritis
- Hepatitis
- Leptospirosis
- Epstein-Barr virus
- Influenza
- Cytomegalovirus
- Enterovirus
- Streptococcus pharyngitis
- Miscellaneous
- Leukemia
- Idiopathic thrombocytopenia purpura
- Hemolytic uremic syndrome
Treatment
Medication
First Line
- Doxycycline, either PO or IV
- Drug of choice regardless of age of child who is severely ill
- Dose: 4.4 mg/kg/day divided q12h (max dose 200 mg q12h)
- Treatment duration: minimum 5-10 days. Continue for 3-5 days after defervescence, longer if there is CNS involvement.
Second Line
- Rifampin has been reported to be an effective antibiotic for children <8 years of age who are less toxic and are experiencing an HGA infection.
- Dose: 20 mg/kg/day divided q12h for 5-10 days
- This is also the drug of choice for pregnant mothers.
- Unlike Lyme disease, neither amoxicillin nor ceftriaxone has been shown to be effective for the treatment of ehrlichiosis.
Additional Treatment
General Measures
- Volume and BP medications as needed
- Intubation for respiratory failure
- Dialysis for renal failure
- Platelets for thrombocytopenia
- Packed red blood cells for anemia
- Fresh frozen plasma, cryoprecipitate, and vitamin K for DIC
- Antifungal or antibiotics for secondary infections
Ongoing Care
Prognosis
- >60% of patients are hospitalized.
- Case fatality rate for HME is 2-5%; for HGA, 7-10%.
- Elevated BUN and creatinine have been associated with a more severe course.
- Children appear to have an excellent outcome: Blood, renal, and liver abnormalities resolve in 1-2 weeks after initiating antibiotics.
- Cognitive and behavioral problems have been reported.
- Neuropathy has been described.
Complications
- Neurologic
- Headache, described as severe
- Mental status changes
- Seizures
- Coma
- Focal neurologic findings
- Cognitive learning deficits
- Hematologic
- Disseminated intravascular coagulation (DIC)
- Thrombocytopenia
- Leukopenia
- Lymphopenia
- Anemia
- GI
- Hemorrhage
- Elevated liver enzymes
- Hepatosplenomegaly
- Respiratory
- Pulmonary hemorrhage
- Interstitial pneumonia
- Pleural effusions
- Noncardiogenic pulmonary edema
- Infectious
- Fungal superinfection
- Nosocomial infections
- Opportunistic infections
- Renal
- Renal failure
- Proteinuria
- Hematuria
- Cardiac
Additional Reading
- Dhand A, Nadelman RB, Aguero-Rosenfeld M, et al. Human granulocytic anaplasmosis during pregnancy: case series and literature review. Clin Infect Dis. 2007;45:589-593. [View Abstract]
- Havens NS, Kinnear BR, Mat ³ S. Fatal ehrlichial myocarditis in a healthy adolescent: a case report and review of the literature. Clin Infect Dis. 2012;54:e113-e114. [View Abstract]
- Schutze GE, Buckingham SC, Marshall GS, et al. Human monocytic ehrlichiosis in children. Pediatr Infect Dis J. 2007;26:475-479. [View Abstract]
- Dumler JS, Madigan JE, Pusterla N, et al. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. Clin Infect Dis. 2007;15:S45-S51. [View Abstract]
Codes
ICD09
- 082.40 Ehrlichiosis, unspecified
- 082.41 Ehrlichiosis chafeensis [E. chafeensis]
- 082.49 Other ehrlichiosis
ICD10
- A77.40 Ehrlichiosis, unspecified
- A77.41 Ehrlichiosis chafeensis [E. chafeensis]
- A77.49 Other ehrlichiosis
SNOMED
- 77361002 Ehrlichiosis (disorder)
- 359747000 Human ehrlichiosis due to Ehrlichia chaffeensis (disorder)
- 13906002 Anaplasmosis (disorder)
- 85708001 Human anaplasmosis due to Anaplasma phagocytophilum (disorder)
FAQ
- Q: If a tick is removed from my child, should antibiotics be started?
- A: No. Antibiotics should be started if a child becomes symptomatic because prophylactic use of antimicrobial agents will not prevent the development of disease.
- Q: What is the most common chief complaint in children with ehrlichiosis?
- A: Intense, unremitting headache and fever are the most common features.