Ehrlichiosis
Ehrlichiosis: Excerpt from The 5-Minute Pediatric Consult
Jeffrey P. Louie, MD
Ehrlichiosis - BASICS
Ehrlichiosis - description
Zoonotic infection caused by 4 microorganisms of the genus Ehrlichia:
- The 2 most common clinically described infections are human monocytic ehrlichiosis (HME), caused by Ehrlichia chaffeensis, and human granulocytic ehrlichiosis (HGE), caused by Anaplasma phagocytophila.
- Another organism, Ehrlichia ewingii, has been described and is clinically indistinguishable from HGE.
- A 4th species, Ehrlichia sennetsu, which causes a mononucleosislike syndrome, has been found in Japan and Malaysia.
- The genus Ehrlichia is found within the family Rickettsiaceae.
Ehrlichiosis - 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.
- 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. Once the tick is removed, clean the skin with a disinfectant.
- Instruct parents to seek medical attention only if symptoms develop.
- No vaccine is available.
Ehrlichiosis - epidemiology
- General distribution:
- HGE is typically found in the northern Midwest and coastal regions of the eastern and northeastern US.
- HME is typically found in the southern to southeastern US; found in states where Rocky Mountain spotted fever (RMSF) occurs.
- HGE and HME have been found in California and from Rhode Island to Florida.
- HME and HGE have been found in Europe.
- Most patients are infected during April through September, the months of greatest tick and human outdoor activity.
Ehrlichiosis - incidence
- HME:
- Males are more often infected (57%)
- Average age is 6.7 years (range 7 months to 13.7 years)
- Most infected children reside in rural areas.
- Data from Georgia demonstrated that ehrlichiosis was more common than RMSF, with an incidence of 5.3 per 100,000.
- HGE:
Ehrlichiosis - prevalence
HGE:
- Unknown
- Most infections have occurred in states where Lyme disease is very prevalent: Wisconsin, Minnesota, and Connecticut.
- Congenital transmission has been described.
Ehrlichiosis - pathophysiology
- Obligate intracellular, pleomorphic, Gram-negative bacteria
- Transmission to a human by a tick vector
- Incubation period ranges from 1–21 days
- HME infects mononuclear phagocytes, whereas HGE infects granulocytes.
- The Ehrlichia reside within a leukocyte phagosome (called a morula), where the bacteria divide by binary fission and produce microcolonies.
- The infected cell is destroyed by the morula, thus releasing more organisms into the phagocyte system.
Ehrlichiosis - etiology
- HME and HGE are both carried by tick vectors.
- HME is thought to be transmitted by Amblyomma americanum, the Lone Star tick. The White-tailed deer is the major reservoir.
- The vector for HGE is believed to be Ixodes scapularis, a deer tick, or Dermacentor variabilis, a brown dog tick. Small mammals such as the white-footed mouse are the major reservoirs.
Ehrlichiosis - DIAGNOSIS
Ehrlichiosis - signs & symptoms
- Classic presentation is described as fevers, headache, and myalgias, followed by the development of a progressive leukopenia, thrombocytopenia, and anemia.
- Fevers are found in all children.
- Rash occurs in ~66% of patients and is pleomorphic:
- Described as macular, maculopapular, petechial, erythematous, vesicular, scarlet form, or a combination of these
- Usually distributed on the trunk and extremities
- Chills and myalgia are found in most children.
- Severe headache is often described.
- Abdominal pain, vomiting, anorexia, and diarrhea can be noted.
- Arthralgia
- Cough and sore throat are often described.
Ehrlichiosis - history
History of tick bite or exposure to wooded areas that are endemic for tick-borne diseases is very helpful.
Ehrlichiosis - physical exam
- Mental status changes/irritability
- Nuchal rigidity
- Cardiac murmur (II/VI systolic ejection murmur at the left lower sternal border)
- Hepatosplenomegaly
- Poor perfusion with hypotension (shock) has been described in a few children as a presenting symptom.
- Conjunctival or throat injection
- Rash as described
Ehrlichiosis - tests
Ehrlichiosis - lab
- CBC with differential (with smear):
- Thrombocytopenia, <150,000/mm3 (77–92% incidence)
- Lymphopenia, <1,500/mm3 (75%)
- Neutropenia, <4,000/mm3 (58–68%, and is more suggestive of HGE)
- Anemia, hematocrit <30% (38–42%)
- Intracytoplasmic morulae within leukocytes (10–80%)
- 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
- Microbiology cultures are negative.
- Ehrlichia morulae (intraleukocytoplasmic Ehrlichia micro-organisms) have been described on CSF smears.
- Serum studies:
- Titers for both HGE and HME have been developed.
- Titers are available through state health departments, the Centers for Disease Control and Prevention, or a reference laboratory.
- 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 ≥1:64 is considered diagnostic.
- Polymerase chain reaction has been developed and shows promise.
- The detection of intraleukocytoplasmic Ehrlichia microcolonies (morulae) on peripheral blood monocytes or granulocytes is diagnostic.
Ehrlichiosis - diag proced-surgery
Bone marrow is usually hypercellular, but normocellularity and hypocellularity have also been found.
- Simultaneous infections have been documented with ehrlichiosis and Lyme disease; therefore, in patients diagnosed with ehrlichiosis, Lyme titers should also be measured to determine whether there is a dual infection. One study from Wisconsin documented a 12% coinfection rate.
- Other coinfections with ehrlichiosis have also been documented with either RMSF or babesiosis.
- Failing to consider the diagnosis of ehrlichiosis or a delay in treatment pending confirmatory serum titers
- Alternative diagnoses should be considered in children who do not rapidly improve with doxycycline.
Ehrlichiosis - differencial diagnosis
- Tick-borne infection:
- RMSF
- Tularemia
- Relapsing fever
- Lyme disease
- Colorado tick fever
- Babesiosis
- Other infection:
- Toxic shock syndrome
- Kawasaki disease
- Meningococcemia
- Pyelonephritis
- Gastroenteritis
- Hepatitis
- Leptospirosis
- Epstein-Barr virus
- Influenza
- Cytomegalovirus
- Enterovirus
- Streptococcus throat
- Miscellaneous:
- Leukemia
- Idiopathic thrombocytopenia purpura
- Hemolytic uremic syndrome
Ehrlichiosis - TREATMENT
Ehrlichiosis - 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
Ehrlichiosis - medication
Ehrlichiosis - first line
Doxycycline either PO or IV: Drug of choice regardless of age of child who is severely ill:
- Children < 45.5 Kg: 4.4 mg/kg/d divided q12h for 1 week
- Children > 45.5 Kg: 100 mg q12h for 1 week
- Doxycycline is a tetracycline, and long-term use has been associated with permanent dental staining and enamel hypoplasia. Short courses, such as those for ehrlichiosis, are unlikely to cause noticeable dental staining. Other side effects are photosensitivity, hepatotoxicity, nausea, and pseudotumor cerebri.
- Treatment for a minimum of 5–10 days and should continue for 3 days after defervescence
Ehrlichiosis - second line
- Rifampin has been reported to be an effective antibiotic for children <8 years of age who are less toxic but who are experiencing an HGE infection. The dose is 20 mg/kg/d divided q12h for 5–10 days. This is also the drug of choice for pregnant mothers.
- Unlike with Lyme disease, neither amoxicillin nor ceftriaxone has been shown to be effective for the treatment of ehrlichiosis.
Ehrlichiosis - FOLLOW UP
Ehrlichiosis - prognosis
- >60% of patients are hospitalized.
- Case fatality for HME is 2–5%; for HGE, 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.
Ehrlichiosis - complications
- Neurologic:
- Headache, described as severe
- Mental status changes
- Seizures
- Coma
- Focal neurologic findings
- Cognitive learning deficits
- Hematologic:
- Disseminated intravascular coagulopathy (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:
- Metabolic: Hyponatremia
Ehrlichiosis - bibliography
- Berry DS, Miller S, Hooke JA, et al. Ehrlichial meningitis with cerebrospinal fluid morulae. Pediatr Infect Dis J. 1999;18:552–555.
- Dumler JS, Bakken JS. Ehrlichial diseases of humans: Emerging tick-borne infections. Clin Infect Dis. 1995;20:1102–1110.
- Fichtenbaum CJ, Peterson LR, Weil GJ. Ehrlichiosis presenting as a life-threatening illness with features of the toxic shock syndrome. Am J Med. 1993;95:351–357.
- Jacobs RF, Schultze GE. Ehrlichiosis in children. J Pediatr. 1997;131:184–192.
- Krause PJ, Corrow CL, Bakken JS. Successful treatment of human granulocytic ehrlichiosis in children using rifampin. Pediatrics. 2003:e252–e253.
- Lantos P, Krause PJ. Ehrlichiosis in children. Sem Infect Dis. 2002;13:249–256.
- Nadelman RB, Horowitz HW, Heish T, et al. Simultaneous human granulocytic ehrlichiosis and Lyme borreliosis. N Engl J Med. 1997;337:27–30.
- Nadelman RB, Nowakoski J, Fish D, et al. Prophylaxis with single dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001;345:79–84.
Ehrlichiosis - CODES
Ehrlichiosis - icd9
082.40 Ehrlichiosis
Ehrlichiosis - FAQ
- Q: If a tick is removed from my child, should antibiotics be started?
- A: Unlike with Lyme disease, this has yet to be defined. Antibiotics should be started if a child becomes symptomatic.
- Q: What is the most common chief complaint in children with ehrlichiosis?
- A: Intense, unremitting headache:
In patients with fever, headache, and flulike illness in the spring to early fall, consider the diagnosis.
Laboratory abnormalities of leukopenia, thrombocytopenia, and hepatitis should lead to presumptive therapy until the diagnosis is clear.
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Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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