A. Organisms

1. Caused by rickettsial organisms, family Anaplasmataceae
   1. Coccobacillus shape
   2. Obligate intracellular bacteria
2. Species
   1. Monocytic: Ehrlichia chaffeensis
   2. Granulocytic: E. equi, Anaplasma phagocytophilum
   3. Uncommon granulocytic: E. ewingii [2]
   4. E. sennetsu - cause of Sennetsu fever (mononucleosis like illness) in East Asia
   5. E. canis

B. Monocytic Ehrlichosis [4,5]

1. Most commonly caused by E. chaffeensis
   1. Lone Star Tick (Ambyomma americanum) is probable vector
   2. Mainly in Central and southeastern USA but widespread, also Africa, Europe [6]
   3. Most common cause of ehrlichosis in USA
   4. Male : Female 2:1
2. Symptoms [3]
   1. Fever, chills, malaise, severe headache, myalgia, arthralgia
   2. Less common: anorexia, pharyngitis, lymphadenopathy, rash
   3. Confusion present in 20% of cases, cough in 30%
   4. Preceding tick bite may not have been noticed
   5. Often mistaken for Lyme Disease, "flu" or another rickettsial illness
   6. Unusual mimic of vasculitis [1]
3. Laboratory Abnormalities
   1. Mild thrombocytopenia, lymphopenia most common
   2. Mild liver function test (LFT) abnormalities common
   3. Abnormal PTT (normal PT), elevated FDP (FSP), LDH usually abnormal
4. Diagnosis
   1. Diagnosis may be made by serology
   2. Morulae may be seen on buffy coat smears (insensitive test)
   3. Culture is slow and not widely available
5. Treatment
   1. Tetracyclines: doxycycline 100mg po bid
   2. Fever abates within 48 hours, other symptoms and signs over 3-7 days
   3. Continue treatment for 2 weeks (also reduces risk of Lyme Disease)
   4. Trimethoprim-sulfamethoxazole (Bactrim®, Septra®) may exacerbate symptoms

C. Granulocytic Ehrlichosis [10]

1. Demographics
   1. Majority of patients are in Wisconsin and Minnesota [7]
   2. Increasing reports from Nantucket, Massachusetts, and Westchester, New York [8]
   3. Usual vector is Ixodes scapularis ticks, which can also transmit Lyme Disease
   4. May also be transmitted by Dermatacentor variabilis (American Dog Tick)
   5. Concern for concommitent infection with babesia and/or Lyme agent
2. Etiologic Agents
   1. A. phagocytophilum (majority) and E. equi (majority) are most common
   2. Some patients have E. ewingii [2]
   3. Patients seldom have serological cross-reaction with usual human ehrlichia specias
   4. Organism can now be cultured in human neutrophil-like cells [8,9]
   5. Polymerase chain reaction (PCR) can also be used for identification [2,8]
   6. Serology is also very useful for convalescent (but not acute) diagnosis
3. Symptoms and Signs [7]
   1. Fever (100%), malaise, myalgias, arthralgia, chills, rigors
   2. Headache (85%), Nausea or Anorexia or Vomiting (~35%)
   3. Typically with leukopenia (average WBC 3-4K), anemia, thrombocytopenia (60-100K/µL)
   4. Immature neutrophil forms prominent in nearly all patients (usually >15%)
   5. Leukocytic inclusions
   6. Myositis can occur but is not very common [10]
   7. May progress to sepsis syndrome; death ~1% (may be higher in some populations)
4. Treatment
   1. Doxycycline 100mg po or iv bid for 2-3 weeks is very effective
   2. Erythromycin does not appear to be effective
   3. Cephalosporins are probably second line, with some efficacy [8]
   4. No response to sulfa drugs, quinolones
   5. Symptoms generally improve within 24-72 hours after begining antibiotics

D. Differential Diagnosis [1]

1. Broad differential since presentations are nonspecific
2. Multiorgan syndromes including toxic shock syndrome, meningococcemia, sepsis
3. Lyme Disease
4. Endocarditis
5. Typhoid fever
6. Rocky mountain spotted fever
7. Tuleremia
8. Babesiosis
9. Q Fever

References

1. Stone JH, Dierberg K, Aram G, Dumler JS. 2004. JAMA. 292(18):2263
2. Buller RS, Arens M, Hmiel SP, et al. 1999. NEJM. 341(3):148
3. Yawetz S and Mark EJ. 2001. NEJM. 345(22):1627 (Case Record)
4. Medoff G and Murray PR. 1998. Am J Med. 104(6):600
5. Dawson JE, Warner CK, Standaert S, Olson JG. 1996. Arch Intern Med. 156(2):137
6. Standaert SM, Dawson JE, Schaffner W, et al. 1995. NEJM. 333(7):420
7. Backken JS, Krueth J, Wilson-Ordskog C, et al. 1996. JAMA. 275(3):199
8. Aguero-Rosenfeld ME, Horowitz H, Wormser G, et al. 1996. Ann Intern Med. 125(11):904
9. Goodman JL, Nelson C, Vitale B, et al. 1996. NEJM. 334(4):209
10. Heller HM, Telford SR III, Branda JA. 2005. NEJM. 352(13):1358 (Case Record)