Rocky Mountain Spotted Fever

Rocky Mountain spotted fever (RMSF) is a bacterial infection caused by the obligate intracellular parasite Rickettsia rickettsii. Transmission occurs through an arthropod vector, most commonly the American dog tick (Dermacentor variabilis). Rocky Mountain spotted fever is prevalent in the southeastern United States. Early signs and symptoms of RMSF are nonspecific and include a high fever, severe headache, and rash. The rash is characteristic in that it begins peripherally and moves centrally, and also appears on the hands and soles. A high clinical suspicion is required for diagnosis, and empiric treatment with doxycycline is recommended within 5 days of symptoms onset.

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Rocky mountain spotted fever (RMSF) is an infectious disease caused by the bacteria Rickettsia rickettsii, which is usually transmitted by ticks.


  • Incidence rate (per year): 0–63 cases per million people (state-dependent)
  • Affects all ages, but most common in those aged 40–64 years
  • Higher incidence in Native Americans
  • Most common rickettsial infection in the United States
  • Occurs throughout the United States, but most prevalent in the southeastearn and south-central states
  • Outside the United States: South and Central America
  • Distribution is dependent on the location of the tick vector.
  • Risk factors:
    • Season: more common in spring and early summer
    • Increased tick burden: residency near wooded areas or areas with high grass
Epidemiology of Rocky Mountain spotted fever

Distribution of spotted fever rickettsiosis in the United States, of which RMSF is a type, 2014

Image: “US distribution of spotted fever rickettsiosis” by CDC. License: Public Domain


  • Causative agent is R. rickettsii:
    • Weakly gram negative (poor Gram staining)
    • Obligate intracellular bacterium
  • Route of transmission: tick bite
  • Hosts and vectors:
    • Most common in the United States:
      • American dog tick (Dermacentor variabilis)
      • Rocky Mountain wood tick (Dermacentor andersoni)
    • Central and South America:
      • Brown dog tick (Rhipicephalus sanguineus)
      • Lone star tick (Amblyomma cajennense)
Dermacentor tick

Adult Dermacentor tick

Image: “Adult Dermacentor spp. tick” by Center for Infectious Diseases and Travel Medicine, University Hospital Freiburg, Hugstetter Strasse, Germany. License: CC BY 2.0


  • R. rickettsii are transmitted to human hosts through the bite of an infected tick.
  • During feeding, bacteria are released from tick salivary glands.
  • Rickettsia have a tropism for endothelial cells and adhere to the cells via membrane lipopolysaccharides (LPS) and rickettsial outer membrane proteins (rOmps).
  • Rickettsia are then endocytosed into host cells and cause host cell lysis via:
    • Phospholipase A
    • Protease
    • Free radical–induced lipid peroxidation
  • Rickettsia are then able to spread hematogenously through the blood and lymphatics:
    • Continued replication within vessels causes vasculitis.
    • Widespread vasculitis can result in microhemorrhages and disseminated intravascular coagulation (DIC).

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Clinical Presentation

Symptoms usually occur within 2–14 days of exposure to an infected tick bite. Initial symptoms may be vague and non-specific (fever, generalized malaise). Patients may not be aware of tick exposure.

Classic triad

  • Fever
  • Headache
  • Rash: 
    • Appears 3–5 days after onset of symptoms
    • Starts peripherally on the extremities and then moves centrally
    • Begins as a blanching maculopapular rash and later develops a petechial appearance 
    • Involves the palms and soles (but not always)

Other possible clinical symptoms

  • Arthralgias
  • Abdominal pain (common in children)
  • Nausea and/or vomiting
  • Conjunctivitis 
  • Edema


Complications of untreated infection may include:

  • Encephalitis
  • Pulmonary edema
  • Adult respiratory distress syndrome
  • Arrhythmias
  • Coagulopathy (including DIC)
  • Gastrointestinal bleeding
  • Skin necrosis and gangrene



  • Recent travel to areas with high prevalence
  • Possible tick exposure

Physical exam

  • Rash
  • Pedal edema (especially in children)
  • Conjunctival erythema
  • Meningismus (in cases of central nervous system involvement)
  • Late/severe manifestations:
    • Change in mental status
    • Seizures
    • Gangrene of digits and ears

Laboratory studies

  • Most patients will have normal laboratory findings initially, including normal WBC count.
  • Later abnormalities include:
    • Thrombocytopenia
    • Prolonged partial thromboplastin time (PTT) and prothrombin time (PT)
    • Transaminitis
    • Hyperbilirubinemia
    • Azotemia
  • Definitive tests: 
    • Serology (more common):
      • Immunoglobulin M (IgM) and IgG antibodies appear 7–10 days after illness onset.
      • Seroconversion: 4x increase in IgG antibody levels
    • Polymerase chain reaction (PCR) on a blood sample: low sensitivity
    • Skin biopsy: 
      • Direct immunofluorescence testing or immunoperoxidase staining 
      • Not readily available across the United States
      • 70% sensitive, 100% specific
    • Culture:
      • Difficult to perform
      • Reserved for research purposes
Microscopic image of Rickettsia

Giemsa-stained R. rickettsii in the cells of a tick

Image: “Gimenez stain” by CDC. License: Public Domain



  • Should be started empirically if there is high clinical suspicion
  • Preferably within 5 days of symptom onset
  • 1st line: doxycycline (oral or intravenous)
  • Alternative: chloramphenicol

Supportive care

  • For severe cases requiring hospitalization
  • May include:
    • Mechanical ventilation
    • Dialysis
    • Blood and/or platelet transfusions
    • Anticonvulsant medications


  • Prevention of tick bites
  • Detection and removal of attached ticks
  • Surveillance of symptoms following known tick bites
  • No commercially available vaccines


  • Pre-antibiotic era: 20%–25% mortality (range: 20%–80%)
  • Current mortality is 3%–5%, mostly due to delayed diagnosis and treatment. 
  • Factors associated with increased severity/lethality:
    • Male gender
    • Increasing age
    • Glucose-6-phosphate dehydrogenase deficiency
    • Chronic alcohol abuse
    • African American origin

Differential Diagnosis

  • Meningococcal meningitis: a meningeal infection with Neisseria meningitidis. Fever, headache, and rash are commonly noted in patients with meningococcal meningitis. However, there is usually no history of tick exposure and symptoms do not improve with doxycycline. Diagnosis is established with lumbar puncture. Treatment is usually with ceftriaxone or penicillin.
  • Infectious mononucleosis: a viral infection caused by the Epstein-Barr virus. Initial clinical symptoms of RMSF and infectious mononucleosis are very similar to any viral infection, with malaise and low-grade fever. Mononucleosis can present with a rash but usually spares the palms and soles. Diagnosed with a monospot test. Treatment is largely supportive.
  • Thrombotic thrombocytopenic purpura (TTP): a life-threatening condition caused by defects of von Willebrand factor. Complications of RMSF include thrombocytopenia and disseminated intravascular coagulation (DIC), which can cause a purpuric rash and be mistaken for TTP.  Diagnosis is established with blood work. Treatment involves plasmapheresis and steroids.
  • Measles: a viral infection associated with fever and maculopapular rash. The rash usually starts on the face and then progresses to the trunk and extremities, sparing the palms and soles. Diagnosis is made clinically and confirmed by serology, and treatment is largely supportive.


  1. Riedel, S., Jawetz, E., Melnick, J. L., & Adelberg, E. A. (2019). Jawetz, Melnick & Adelberg’s Medical microbiology (pp. 357–361). New York: McGraw-Hill Education.
  2. Sexton, D., McClain, M. (2020). Clinical manifestation and diagnosis of Rocky Mountain spotted fever. UpToDate, Retrieved January 26, 2020, from
  3. Sexton, D., McClain, M. (2019). Treatment of Rocky Mountain spotted fever. UpToDate, Retrieved January 26, 2020, from
  4. Sexton, D., McClain, M. (2020). Biology of Rickettsia rickettsii infection. UpToDate, Retrieved January 26, 2020, from
  5. Walker DH. Rocky Mountain spotted fever: a seasonal alert. Clin Infect Dis. 1995;20(5):1111. doi: 10.1093/clinids/20.5.1111.

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