What is Rocky Mountain spotted fever?

Rocky Mountain Spotted Fever (RMSF)

Rocky Mountain spotted fever is the most severe and potentially fatal tickborne rickettsial illness in the United States, caused by the bacterium Rickettsia rickettsii and transmitted primarily through tick bites. 1

Disease Classification and Causative Agent

RMSF is a life-threatening bacterial infection caused by Rickettsia rickettsii, an obligate intracellular organism in the order Rickettsiales that is transmitted by infected ticks. 1, 2 This pathogen belongs to the spotted fever group (SFG) of rickettsioses, which also includes milder diseases like Rickettsia parkeri rickettsiosis and Rickettsia species 364D rickettsiosis. 1

Geographic Distribution and Epidemiology

• RMSF is reported from all 48 contiguous United States and the District of Columbia, though incidence varies geographically. 1
• The disease occurs most commonly in states from Missouri and Oklahoma east to North Carolina and Virginia. 1, 2
• RMSF has emerged in parts of Arizona with unusually high incidence and case-fatality rates, particularly among children, associated with the brown dog tick (Rhipicephalus sanguineus) as the vector. 1
• Cases also occur in Canada, Mexico, and Central and South America (Costa Rica, Panama, Brazil, Colombia, Argentina). 1
• Disease occurrence is seasonal, corresponding with tick feeding periods, with the majority of cases occurring during spring and summer months (April through September). 1, 3

Clinical Presentation

Early Symptoms (First 3-5 Days)

The classic triad of fever, rash, and reported tick bite is rarely present when patients first seek medical care. 1, 4 Early signs and symptoms are nonspecific and difficult to distinguish from self-limited viral infections. 5

• Fever (>38.5°C) is the most common presenting symptom. 3, 6
• Headache occurs in the majority of patients. 3, 5
• Myalgia (muscle pain) is frequently reported. 3, 5
• Nausea, vomiting, and anorexia are common gastrointestinal symptoms. 5
• Approximately half of patients do not recall tick exposure. 3

Rash Characteristics

• Rash is present in most patients during the course of RMSF, although it typically appears 2-4 days after fever onset. 1, 4
• The rash classically begins on the wrists and ankles, then spreads centrally to involve the trunk. 3
• Rash can be atypical, localized, faint, evanescent, and difficult to recognize in persons with darker pigmented skin. 1
• Rash may be absent in up to 15% of cases. 4, 3
• The rash progresses from macular to petechial in character. 3

Severe Manifestations

RMSF causes disseminated infection of endothelial cells, leading to vasculopathy with potentially life-threatening complications. 5

• Increased vascular permeability, edema, hypovolemia, and hypotension. 5
• Pulmonary edema and acute respiratory distress syndrome (ARDS). 5
• Meningoencephalitis with altered mental status progressing to coma. 7, 5
• Acute tubular necrosis and renal failure. 5
• Cutaneous necrosis and gangrene potentially requiring amputation of digits or limbs. 1
• Disseminated intravascular coagulation (DIC), though rare. 1

Laboratory Findings

Laboratory findings are often within or slightly deviated from reference ranges early in the course of illness and cannot be relied upon to guide early treatment decisions. 1

• Thrombocytopenia (low platelet count) may be present. 1, 3
• Increased immature neutrophils (left shift) are often observed. 1
• Elevations in hepatic transaminase levels (AST, ALT) may occur. 1, 3
• Hyponatremia (low sodium) is frequently present. 1, 3
• Elevated creatine kinase or lactate dehydrogenase indicate diffuse tissue injury. 1
• Anemia and abnormal coagulation tests may develop. 3
• Cerebrospinal fluid may show lymphocytic pleocytosis (usually <100 cells/μL) with moderately elevated protein and normal glucose. 1

Critical Mortality Data

Delay in recognition and treatment is the most important factor associated with risk for death from RMSF. 1, 4 Data from Arizona tribal communities (2002-2011) demonstrates the dramatic impact of treatment timing on outcomes: 1

• Treatment initiated on days 1-2: 0% mortality
• Treatment initiated on day 5: 0% mortality, but 50% required ICU care
• Treatment initiated on day 6: 33% mortality, 100% hospitalization
• Treatment initiated on day 9: 50% mortality, 100% ICU admission

The case fatality rate in Sonora, Mexico reached 44% during 2015-2018, with mean time from symptom onset to doxycycline treatment of 7.9 days. 6

Treatment

Doxycycline is the treatment of choice for RMSF in all patients regardless of age or pregnancy status, and must be initiated immediately upon clinical suspicion without waiting for laboratory confirmation. 1, 4, 8

Dosing Regimens

• Adults: 100 mg orally or intravenously twice daily. 4, 8
• Children: 2.2 mg/kg body weight (not to exceed 100 mg per dose) orally or intravenously twice daily. 4, 8
• Duration: Minimum 5-7 days and until the patient has been afebrile for at least 48-72 hours. 4

Special Populations

• Children under 8 years: Doxycycline is recommended despite traditional concerns about dental staining; the risk of fatal outcome from untreated RMSF far outweighs minimal to nonexistent risk of dental effects from short courses. 4
• Pregnant women: Doxycycline should be used despite typical contraindication in pregnancy, as the risk of fatal RMSF outweighs potential fetal risks. 4, 5
• Doxycycline allergy: Chloramphenicol is the only alternative but is associated with higher mortality risk, limited availability, and requires blood monitoring for hematologic adverse effects. 4, 5

Ineffective Treatments to Avoid

• Fluoroquinolones are associated with delayed fever resolution, increased disease severity, and longer hospital stays. 4
• Sulfonamide antimicrobials are contraindicated as they increase disease severity and mortality. 4
• Beta-lactams, macrolides, aminoglycosides, and rifampin are not effective. 4

Diagnostic Testing Limitations

Antibacterial treatment should never be delayed while awaiting laboratory confirmation, nor should treatment be discontinued based on negative acute phase testing. 1 Serologic antibody testing is typically negative during acute illness and only becomes positive during convalescence (2-4 weeks after symptom onset). 9, 5 PCR testing from whole blood may be necessary for acute diagnosis but results are not immediately available. 9

Prevention

• Wear long-sleeved, light-colored clothing in tick-infested habitats. 10
• Check for tick attachment and remove attached ticks promptly. 10
• Apply topical insect repellent to exposed skin. 10
• Treat clothing with permethrin. 10
• Prophylactic antibiotics are not recommended for asymptomatic patients with recent tick bites. 4