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TICK- AND MITE-BORNE SPOTTED FEVERS is a topic covered in the Harrison's Manual of Medicine.

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Caused by R. rickettsii, RMSF has the highest case–fatality rate of all rickettsial diseases.

  • In the United States, the prevalence is highest in the south-central and southeastern states. Most cases occur between May and September.
  • A rare presentation of fulminant RMSF is seen most often in male black pts with G6PD deficiency.
  • RMSF is transmitted by different ticks in different geographic areas—e.g., the American dog tick (Dermacentor variabilis) transmits RMSF in the eastern two-thirds of the United States and in California, and the Rocky Mountain wood tick (D. andersoni) transmits RMSF in the western United States.


Rickettsiae are inoculated by the tick after ≥6 h of feeding, spread lymphohematogenously, and infect numerous foci of contiguous endothelial cells. Increased vascular permeability, with edema, hypovolemia, and ischemia, causes tissue and organ injury.

Clinical Manifestations

The incubation period is ~1 week (range, 2–14 days). After 3 days of nonspecific symptoms, half of pts have a rash characterized by macules appearing on the wrists and ankles and subsequently spreading to the rest of the extremities and the trunk.

  • Lesions ultimately become petechial in 41–59% of pts, appearing on or after day 6 of illness in ~74% of all cases that include a rash. The palms and soles become involved after day 5 in 43% of pts but do not become involved at all in 18–64%.
  • Pts may develop hypovolemia, prerenal azotemia, hypotension, noncardiogenic pulmonary edema, renal failure, hepatic injury, and cardiac involvement with dysrhythmias. Bleeding is a rare but potentially life-threatening consequence of severe vascular damage.
  • CNS involvement—manifesting as encephalitis, focal neurologic deficits, or meningoencephalitis—is an important determinant of outcome. In meningoencephalitis, CSF findings are notable for pleocytosis with a mononuclear cell or neutrophil predominance, increased protein levels, and normal glucose levels.
  • Laboratory findings may include increased plasma levels of acute-phase reactants such as C-reactive protein, hypoalbuminemia, hyponatremia, and elevated levels of creatine kinase.


Without treatment, the pt usually dies in 8–15 days; fulminant RMSF can result in death within 5 days. The mortality rate is 3–5% despite the availability of effective antibiotics, mostly because of delayed diagnosis. Survivors of RMSF usually return to their previous state of health.


Within the first 3 days, diagnosis is difficult, since only 3% of pts have the classic triad of fever, rash, and known history of tick exposure. When the rash appears, RMSF should be considered.

  • Immunohistologic examination of a cutaneous biopsy sample from a rash lesion is the only useful diagnostic test during acute illness, with a sensitivity of 70% and a specificity of 100%.
  • Serology, most commonly the indirect immunofluorescence assay (IFA), is usually positive 7–10 days after disease onset, and a diagnostic titer of ≥1:64 is usually documented.


  • Doxycycline (100 mg bid PO or IV) is the agent of choice for both children and adults but not for pregnant women and pts allergic to this drug, who should receive chloramphenicol.
  • Treatment is given until the pt is afebrile and has been improving for 2 or 3 days.

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Loscalzo, Joseph, et al., editors. "TICK- and MITE-BORNE SPOTTED FEVERS." Harrison's Manual of Medicine, 19th ed., McGraw Hill Inc., 2017. harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623253/all/TICK__AND_MITE_BORNE_SPOTTED_FEVERS.
TICK- AND MITE-BORNE SPOTTED FEVERS. In: Loscalzo J, Jameson JL, Longo DL, et al, eds. Harrison's Manual of Medicine. 19th ed. McGraw Hill Inc.; 2017. https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623253/all/TICK__AND_MITE_BORNE_SPOTTED_FEVERS. Accessed April 23, 2019.
TICK- AND MITE-BORNE SPOTTED FEVERS. (2017). In Loscalzo, J., Jameson, J. L., Longo, D. L., Hauser, S. L., Fauci, A. S., & Kasper, D. L. (Eds.), Harrison's Manual of Medicine. Available from https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623253/all/TICK__AND_MITE_BORNE_SPOTTED_FEVERS
TICK- and MITE-BORNE SPOTTED FEVERS [Internet]. In: Loscalzo J, Jameson JL, Longo DL, Hauser SL, Fauci AS, Kasper DL, editors. Harrison's Manual of Medicine. McGraw Hill Inc.; 2017. [cited 2019 April 23]. Available from: https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623253/all/TICK__AND_MITE_BORNE_SPOTTED_FEVERS.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - TICK- AND MITE-BORNE SPOTTED FEVERS ID - 623253 ED - Loscalzo,Joseph, ED - Jameson,J Larry, ED - Longo,Dan L, ED - Hauser,Stephen L, ED - Fauci,Anthony S, ED - Kasper,Dennis L, BT - Harrison's Manual of Medicine UR - https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623253/all/TICK__AND_MITE_BORNE_SPOTTED_FEVERS PB - McGraw Hill Inc. ET - 19 DB - Harrison's Manual of Medicine DP - Unbound Medicine ER -