> Table of Contents > Rocky Mountain Spotted Fever
Rocky Mountain Spotted Fever
Ginny H. Lee, MD
Alison Southern, MD, MS, FACEP
image BASICS
DESCRIPTION
  • 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
EPIDEMIOLOGY
Incidence
  • 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).
Prevalence
In the United States, about 2,000 cases are reported annually (2).
  • <0.1% of ticks carry virulent Rickettsial species.
ETIOLOGY AND PATHOPHYSIOLOGY
  • 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.
RISK FACTORS
  • 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
GENERAL PREVENTION
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.
image DIAGNOSIS
Delay in presentation and initiation of therapy increases risk of long-term sequelae and mortality.
PHYSICAL EXAM
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%)
DIFFERENTIAL DIAGNOSIS
  • 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
DIAGNOSTIC TESTS & INTERPRETATION
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.
image TREATMENT
MEDICATION
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.
ISSUES FOR REFERRAL
  • Consider infectious disease consult.
  • Report cases of RMSF to public health authorities.
ADDITIONAL THERAPIES
Patients with neurologic injury or loss of limbs caused by gangrene may require prolonged physical and cognitive therapy.
INPATIENT CONSIDERATIONS
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
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
  • 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.
DIET
Consider nutritional supplementation if intake is poor.
PROGNOSIS
  • 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).
REFERENCES
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.
Codes
&NA;
ICD10
A77.0 Spotted fever due to Rickettsia rickettsii
Clinical Pearls
&NA;
  • 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.