> Table of Contents > Rocky Mountain Spotted Fever
Rocky Mountain Spotted Fever
Ginny H. Lee, MD
Alison Southern, MD, MS, FACEP
image BASICS
  • Rocky Mountain spotted fever (RMSF) is a potentially fatal tick-borne systemic small vessel vasculitis caused by the bacterium Rickettsia rickettsii.
  • RMSF is the most common and lethal rickettsial disease in the United States.
  • Typically characterized by fever, headache, and myalgias followed by a centripetal (moving inward from the extremities toward the trunk) rash
  • System(s) affected: cardiovascular, musculoskeletal, skin, CNS, renal, hepatic, and pulmonary
  • In the United States, the incidence of RMSF increased from <2 cases per million persons in 2000 to >8 per million in 2008 (1).
  • Reported in all states except Hawaii, Alaska, and Maine
  • North Carolina, Tennessee, Oklahoma, Arkansas, and Missouri account for ˜60% of cases. RMSF also found in areas of Canada and in Central and South America (2).
  • Predominant age: All ages are susceptible; highest prevalence in children 5 to 9 years of age (2,3).
  • Predominant sex: male > female, likely due to increased outdoor exposures (3,4).
  • Peak incidence occurs with tick exposure, typically in late spring and summer (3).
In the United States, about 2,000 cases are reported annually (2).
  • <0.1% of ticks carry virulent Rickettsial species.
  • Infected ticks include the American dog tick, Dermacentor variabilis in the eastern United States; the Rocky Mountain wood tick, Dermacentor andersoni in the western United States; and the Brown dog tick, Rhipicephalus sanguineus in the southwest (1,2).
  • An adult tick releases Rickettsia rickettsii from its salivary glands after 6 to 10 hours of feeding (1).
  • Rickettsiae proliferate inside endothelial cells by binary fission and invade contiguous vascular endothelial cells, causing a small-vessel vasculitis and the characteristic rash.
  • Increased vascular permeability leads to edema, hypovolemia, and hypoalbuminemia, with subsequent end-organ injury.
  • Platelets are consumed locally due to vascular injury, but coagulopathy or disseminated intravascular coagulation (DIC) is rare (4).
  • Incubation time: 2 to 14 days; median 4 to 7 days
  • Transplacental transmission of infection has not been demonstrated.
  • RMSF can rarely be caused by direct inoculation of tick blood into open wounds or conjunctivae.
  • Known tick bite, engorged tick, or presence of tick for >20 hours; likelihood of infection increases with duration of tick attachment
  • Crushed tick during its removal
  • Accumulated outdoor exposure or residence in a wooded area
  • Contact with outdoor pets or wild animals
In known tick-prone areas (2,4,5)
  • Limit time spent in tall grasses, open areas of low bushy vegetation, and wooded areas.
  • Cover exposed skin; wear a hat, long sleeves, pants and closed-toed shoes.
  • Use DEET-containing insect repellents on exposed skin. Permethrin can be used on clothing.
  • “Tick checks”: Carefully inspect the entire body after possible exposure, especially the scalp, neck, and axillae. Ticks are commonly hidden by hair. Closely inspect legs, groin, external genitalia, and waistlines.
  • Remove attached ticks in their entirety with finetipped tweezers. Grasp the tick close to the skin and gently pull upward. If mouth-parts separate, try to remove gently. Nail polish, petrolatum jelly, and heating do not aid in tick removal. Wear gloves if possible.
  • Wash hands and site of bite thoroughly after tick removal to avoid potential mucosal inoculation.
  • Prophylactic antibiotic treatment is not recommended.
Delay in presentation and initiation of therapy increases risk of long-term sequelae and mortality.
On days 3 to 4, a centripetal rash usually forms (80% of adults), involving the palms and soles, spreading centrally to arms, legs, and trunk. The rash typically starts as an erythematous, macular, or maculopapular exanthem; 50% become petechial or purpuric; blanchable.
  • 20% never develop the “classic” rash, delaying diagnosis and resulting in a more severe outcome. Rash can be difficult to visualize on dark-skinned patients.
  • Rash may be variable in appearance. Do not rely solely on the presence or absence of the typical rash for diagnosis.
  • In severe cases, the rash can involve the entire body and mucosal membranes and may progress to necrotic or gangrenous lesions.
  • The rash is not associated with pruritus or urticaria; when present, this makes RMSF less likely.
  • Hepatosplenomegaly (12-16%)
  • Lymphadenopathy (27%)
  • Viral exanthems (e.g., measles, rubella, roseola)
  • Meningoencephalitis (viral meningitis or encephalitis, bacterial meningitis)
  • Meningococcemia
  • Typhus
  • Ehrlichiosis
  • Lyme disease
  • Leptospirosis
  • Toxic shock syndrome
  • Adenovirus infection
  • Drug reaction or serum sickness
  • Mononucleosis
  • Kawasaki disease
Diagnosis is often clinical in patients with exposure history in an endemic area. Retrospective confirmation by serology. Do not delay treatment awaiting serology.
Initial Tests (lab, imaging)
  • Specific laboratory diagnosis
    • Serum indirect fluorescent antibody (IFA): Titer of >1:64 is diagnostic. A 4-fold increase of acute and convalescent titers confirms an active case of RMSF (1).
    • Antibodies usually develop 7 to 10 days after onset of symptoms; optimal time for testing, therefore, is 14 to 21 days after symptom onset. Do not delay treatment.
    • Early treatment may limit antibody formation.
    • Seropositivity increases with age in endemic states. Positive spotted fever group Rickettsia antibody does not necessarily signify an acute infection.
  • Nonspecific laboratory changes (incidence) (4)
    • WBC count: variable and frequently normal
    • Thrombocytopenia (32-52%)
    • Hyponatremia, mild (19-56%)
    • P.929

    • Anemia, mild (5-24%)
    • Azotemia (12-14%)
    • Elevated AST (36-62%)
    • Coagulation derangements are uncommon, despite vascular damage.
    • CSF is usually normal; some patients may have mononuclear pleocytosis, elevated protein, and normal glucose.
  • Other than occasional nonspecific pneumonic infiltrates on chest radiograph, imaging procedures are rarely helpful.
Diagnostic Procedures/Other
Skin biopsy can offer definitive diagnosis. A 3-mm punch biopsy is sufficient to perform a rapid direct fluorescent antibody (DFA) test (sensitivity 70%, specificity 100%). Electron microscopy (EM) can also identify rickettsiae within endothelial cells. Western immunoblotting confirms the specific spotted fever group species (1,2,4).
Test Interpretation
  • Rickettsiae can be demonstrated within endothelial cells by DFA or EM.
  • Petechiae due to the vasculitis may be seen on various organ surfaces (e.g., liver, brain, or epicardium).
  • Secondary thromboses and tissue necrosis may be seen.
First Line
Doxycycline is the treatment of choice in both adults and children (1,2,3,4).
  • Untreated rickettsial infections have a high rate of morbidity and mortality. Other antibiotics are considerably less effective.
  • The ONLY contraindication to doxycycline is severe allergy.
  • For adults: 100 mg PO or IV q12h for 7 to 10 days, treat for at least 3 days after the fever resolves.
  • For children weighing <45 kg (100 lbs): 2.2 mg/kg/dose (max 200 mg) q12h for 7 to 10 days, treating for at least 3 days after fever resolves; those ≥45 kg, refer to adult dosing (4)
  • Fever should subside within 24 to 72 hours with early treatment; may take longer if patient is severely ill.
  • If patient has no response to doxycycline, consider an alternate diagnosis. Rickettsial resistance to doxycycline has NOT been documented.
  • Side effects of doxycycline
    • Dyspepsia. Take medication with food and water. Avoid dairy products, iron preparations, or antacids, as they may inhibit drug absorption.
    • Photosensitivity may occur. Minimize sun exposure and use sunscreen.
    • Risk of dental staining in children <8 years old is minimal if short courses are administered.
Second Line
  • Chloramphenicol: 50 mg/kg/day IV divided q6h (4 g/day max); same dose in renal failure
    • Associated with aplastic anemia and an increased case mortality
  • Fluoroquinolones have not been evaluated clinically in RMSF, but they have shown in vitro activity against R. rickettsii.
  • Sulfa-containing drugs may worsen tick-borne infections and are contraindicated.
Pregnancy Considerations
  • Doxycycline is appropriate for this life-threatening infection in pregnancy if suspicion is high, despite the potential risk to fetal bones/teeth.
  • Chloramphenicol may be considered during the first 2 trimesters but should be avoided in the 3rd trimester due to potential for gray baby syndrome.
  • Consider infectious disease consult.
  • Report cases of RMSF to public health authorities.
Patients with neurologic injury or loss of limbs caused by gangrene may require prolonged physical and cognitive therapy.
Admission Criteria/Initial Stabilization
  • CNS dysfunction
  • Nausea/vomiting preventing oral antibiotic therapy
  • Immunocompromised patients
  • Specific acute organ failure
  • Failure of oral pain management
  • ICU placement for acutely ill patients with shock
IV Fluids
Aggressive fluid resuscitation and electrolyte management may be required in critically ill patients.
Discharge Criteria
  • Resolution of fever
  • Ability to take oral therapy and nutrition
  • Hospitalize patients with moderate to severe disease
  • Patients with mild disease may be treated as outpatients. Close follow-up is important to identify complications.
  • Infection does not confer lifelong immunity.
Patient Monitoring
  • Outpatients should be seen every 2 to 3 days until symptoms resolve.
  • Follow up CBC, electrolytes, LFTs if clinically indicated.
Consider nutritional supplementation if intake is poor.
  • Prognosis is closely related to timely administration of appropriate antibiotics. Treatment before day 5 of illness can prevent morbidity and mortality (6).
  • When treated promptly, prognosis is usually excellent with resolution of symptoms over several days and no sequelae.
  • If complications develop, course may be more severe and long-term sequelae (especially neurologic sequelae) more likely (6).
  • Children aged 5 to 9 years and elderly >70 years are at higher risk of morbidity and/or mortality (4,6).
    • Black males with G6PD deficiency are at highest risk for fulminant RMSF, in which death can occur within 5 days (4).
1. Lin L, Decker CF. Rocky Mountain spotted fever. Dis Mon. 2012;58(6):361-369.
2. Pujalte GG, Chua JV. Tick-borne infections in the United States. Prim Care. 2013;40(3):619-635.
3. Dahlgren FS, Holman RC, Paddock CD, et al. Fatal Rocky Mountain spotted fever in the United States, 1999-2007. Am J Trop Med Hyg. 2012;86(4): 713-719.
4. Woods CR. Rocky Mountain spotted fever in children. Pediatr Clin North Am. 2013;60(2):455-470. doi:10.1016/j.pcl.2012.12.001.
5. Minniear TD, Buckingham SC. Managing Rocky Mountain spotted fever. Expert Rev Anti Infect Ther. 2009;7(9):1131-1137.
6. Botelho-Nevers E, Raoult D. Host, pathogen and treatment-related prognostic factors in rickettsioses. Eur J Clin Microbiol Infect Dis. 2011;30(10):1139-1150.
A77.0 Spotted fever due to Rickettsia rickettsii
Clinical Pearls
  • Diagnosis of RMSF requires a high index of clinical suspicion. Painless tick bites often go unnoticed, and some patients may never develop a rash.
  • Treatment should begin immediately in suspected cases. Doxycycline is indicated for treatment of RMSF in both adults AND children. The only absolute contraindication is severe allergy to the drug.
  • Lab testing is nonspecific and frequently normal.
  • Although prevalence is highest in central and southeastern United States, cases have been reported in almost all states.