Tick-borne intracellular bacterial infections of leukocytes; cause fever, leukopenia, thrombocytopenia, and transaminase elevation responsive to doxycycline.
Also known as: anaplasmosis, Anaplasma phagocytophilum, human granulocytic anaplasmosis, HGA, ehrlichiosis, Ehrlichia chaffeensis, human monocytic ehrlichiosis, HME
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Risk factors
- Outdoor activity in endemic regions during tick season
- Tick bite or tick attachment
- Age >50 years (more severe disease)
- Immunocompromised state including HIV, transplant, splenectomy
- Co-infection with Lyme disease or babesiosis (anaplasmosis)
- Occupational exposure: hunters, forestry, military training in endemic areas
Pathophysiology
Tick-injected bacteria infect target leukocytes (granulocytes for Anaplasma, monocytes for Ehrlichia), replicate intracellularly within membrane-bound morulae, and cause systemic cytokine activation. The result is fever, hematologic suppression, hepatocellular injury, and in severe disease, multiorgan failure.
Clinical presentation
Symptoms
- Sudden onset of fever, chills, severe headache, myalgias, malaise 1-2 weeks after tick exposure
- Nausea, vomiting, abdominal pain
- Cough, sore throat (less common)
- Confusion, photophobia in severe disease
- Rash uncommon in anaplasmosis (<10%); occurs in approximately 30% of ehrlichiosis cases (maculopapular, sometimes petechial)
- Children with HME may have rash more frequently than adults
Signs / physical exam
- Fever, often >38.9 C
- Hepatosplenomegaly may be present
- Lymphadenopathy occasionally
- Meningismus and altered mental status in severe disease
- Rash (truncal or extremity, rarely palms/soles) in some ehrlichiosis patients
Classic findings
Febrile patient from endemic region with recent tick exposure and the laboratory triad of leukopenia, thrombocytopenia, and elevated transaminases. Morulae within neutrophils (anaplasmosis) or monocytes (ehrlichiosis) on peripheral blood smear are pathognomonic when present.
Differential diagnosis
- Rocky Mountain spotted fever (RMSF) — Rash on wrists/ankles spreading centrally, headache, GI symptoms; Rickettsia rickettsii; treat empirically with doxycycline
- Lyme disease — Erythema migrans rash, arthritis; co-infection common with anaplasmosis
- Babesiosis — Hemolytic anemia, intraerythrocytic parasites; co-infection with anaplasmosis common
- Viral hepatitis — LFT elevation, hepatitis serologies
- Acute leukemia — Cytopenias, blasts on smear
- Influenza or other viral syndrome — Seasonality, respiratory symptoms; PCR
- Sepsis — Blood cultures, source identification
Diagnostic workup
Diagnostic criteria
Diagnosis based on compatible clinical syndrome with positive PCR, morulae on smear, or seroconversion. Treatment should not be delayed pending confirmation.
Labs
- CBC with peripheral smear: leukopenia, thrombocytopenia, sometimes mild anemia; morulae within granulocytes or monocytes
- AST and ALT elevation (2-5x upper limit common)
- PCR on whole blood — most sensitive in the first week of illness (preferred diagnostic test)
- Serology: IFA for Anaplasma and Ehrlichia; 4-fold rise in titers between acute and convalescent samples confirms diagnosis (retrospective)
- BMP, LFTs, coagulation studies (severe cases)
- Concurrent testing for Lyme disease and babesiosis given shared tick exposure
Imaging
- Generally not required
- Chest imaging if respiratory failure
- Head imaging if mental status changes (exclude alternative cause)
Treatment
First-line
- Doxycycline 100 mg PO or IV BID for 7-14 days (typically 10-14 days; for anaplasmosis alone 10 days; for ehrlichiosis at least 3 days after defervescence) — first-line for all ages including children
- Doxycycline is the treatment of choice EVEN IN CHILDREN under 8 — short courses do not stain teeth significantly and benefit outweighs risk; CDC and AAP endorse this for tick-borne rickettsial diseases
- Empirical therapy should be initiated based on clinical suspicion in endemic exposure; defervescence typically within 24-48 hours of starting doxycycline
- Supportive care: IV fluids, transfusion as needed
- Evaluate for and treat coexisting Lyme disease or babesiosis
Second-line / adjunct
- Rifampin for pregnant patients or doxycycline-intolerant patients with anaplasmosis (limited evidence for ehrlichiosis — doxycycline strongly preferred even in pregnancy in some severe cases)
- Chloramphenicol historically used but not recommended as first-line (poor efficacy compared with doxycycline, marrow toxicity)
- Report cases to state and local health departments — nationally notifiable
Complications
- ARDS, shock, multiorgan failure
- Meningoencephalitis (more common in ehrlichiosis)
- Coagulopathy, DIC
- Acute kidney injury
- Rhabdomyolysis
- Opportunistic infection complicating prolonged hospitalization in severe disease
- Mortality 0.5-1% for anaplasmosis, up to 3% for ehrlichiosis even with treatment
PANCE pearls
- Triad of fever + leukopenia/thrombocytopenia + elevated LFTs in a patient with tick exposure should prompt empirical doxycycline.
- Doxycycline is recommended even in young children for suspected tick-borne rickettsial disease — short courses are safe.
- Defervescence within 48 hours of doxycycline supports the diagnosis and is itself nearly pathognomonic.
- Morulae on smear are uncommon but specific — look in granulocytes for Anaplasma and in monocytes for Ehrlichia.
- Co-infection with Lyme disease or babesiosis is common with anaplasmosis (shared Ixodes vector) — test for all three when one is suspected.
References
- CDC — Diagnosis and Management of Tickborne Rickettsial Diseases (CDC MMWR Recommendations and Reports, Biggs et al. 2016)
- IDSA — IDSA guidance on Lyme disease and tick-borne co-infections (2020)
- AAP — American Academy of Pediatrics Red Book — doxycycline for rickettsial diseases in children
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