II. Epidemiology

  1. Rocky Mountain Spotted Fever is the most common Rickettsial Disease in the United States
    1. Up to 6000 cases per year of RMSF and related Rickettsial spotted fevers (see below)
    2. RMSF is the most lethal of Tick Borne Illnesses (5-10% mortality)
  2. Bimodal age distribution
    1. Ages 5 to 9 years old (highest mortality)
    2. Age over 40-60 years old
  3. Timing
    1. Most common April to September (90% of cases)
  4. Endemic area (only occurs in Western Hemisphere)
    1. Central America
    2. South America
    3. North America
      1. Occurs in all states except Maine, Hawaii, Alaska
      2. Midwest
      3. Atlantic coast and south central states (account for 60% of cases in U.S.)
        1. North Carolina
        2. Oklahoma
        3. Arkansas
        4. Tennessee
        5. Missouri
  5. Other similar Rickettsial spotted fevers
    1. Respond to similar antibiotics as those used in Rocky Mountain Spotted Fever
    2. In U.S.
      1. Rickettsial Pox (R. akari in North America)
      2. American Boutonneuse fever (R. parkeri in southeast U.S.)
      3. Finders Island Spotted Fever (R. honei in northwest U.S. as well as Australia and southeast Asia)
    3. Non-U.S.
      1. Mediterranean Spotted Fever or Boutonneuse Fever (R. connori in the Mediterranean)
      2. Queensland Tick Typhus (R. australis in australia)
      3. African Tick BiteFever (R. africae in africa)
      4. Siberian Tick Typhus (R. sibirica in China)

III. Pathophysiology

  1. Transmission
    1. Tick to human transmission
      1. Transmission may occur as early as 2 hours after Tick Bite
      2. Tick engorgement need not be present for transmission to have occurred
    2. Person to person transmission does not occur
    3. Tick Bite (Ixodidae tick)
      1. Wood tick (Dermacentor andersoni) is vector in Western U.S.
      2. Dog tick (Dermacentor variabilis) is vector in Southern and Eastern U.S.
    4. Other ticks transmitting spotted fever group Bacteria
      1. Rhipicephalus
      2. Amblyomma Maculatum (Gulf Coast Tick)
  2. Rickettsia rickettsii is causative organism
    1. Gram Negative Bacteria
    2. Small pleomorphic organism
    3. Obligate intracellular Parasite
  3. Infects blood vessel walls
    1. Infects endothelial cells and Smooth Muscle Cells,
    2. Spreads through Lymphatic System
    3. Secondary multiorgan Small Vessel Vasculitis ensues (especially involving skin and Adrenal Glands)
    4. Results in increased vascular permeability and decreased osmotic pressure

IV. Presentation: Classic

  1. Classic presentation in <18% of patients
  2. Initial
    1. Recent Tick Bite in endemic areas
    2. Fever and flu-like illness in spring and summer
    3. Headache
  3. Later (day 6)
    1. Erythematous, Macular rash (transitions to Petechiae)

V. Symptoms (follows 5-7 day incubation)

  1. Fever
  2. Frontal Headache
  3. Myalgias (back and leg Muscles)
  4. Malaise
  5. Nausea or Vomiting
  6. Abdominal Pain (especially in children)

VI. Signs: Rash (occurs in 90-95% of patients)

  1. Onset in first week of illness (follows fever by 2-5 days)
  2. Characteristics
    1. Initial: Pink blanching Macules 1 to 4 mm in diameter
    2. Later: Macules transition to Papules and Petechiae (seen in 40-50% of patients)
    3. Final: Coalesce into large Ecchymoses and ulcerations (eschar may form)
  3. Distribution: Centripetal Rash - peripheral to central spread
    1. Onset: Wrists and ankles
    2. Next: Spreads distally to palms and soles (may be only rash in as many as 40% of patients)
    3. Next: Spreads proximally into upper arms and legs
    4. Later: Trunk, axilla, buttocks, neck
    5. Face is typically spared

VII. Diagnosis

  1. Missed diagnosis initially in up to 75% of cases
    1. Delayed onset of rash until day 6 makes initial diagnosis more difficult
    2. Start empiric management immediately on suspicion
  2. Based on clinical findings
    1. Do not rely on rash or Thrombocytopenia to make diagnosis
  3. Specific testing is for confirmation only
    1. Skin biopsy with immunofluorescent Rickettsia stain
    2. RickettsiaSerology

IX. Labs

  1. Complete Blood Count
    1. White Blood Cell Count normal or slightly decreased (Leukopenia)
    2. Thrombocytopenia
  2. Liver Function Test abnormalities
    1. Serum Bilirubin increased (Hyperbilirubinemia)
    2. Liver transaminases increased
      1. Aspartate Aminotransferase (AST) increased
      2. Alanine Aminotransferase (ALT) increased
  3. Renal Function tests (Serum Creatinine and Blood Urea Nitrogen)
    1. Acute Renal Failure is a late finding
  4. Serum Sodium
    1. Hyponatremia
  5. Cerebrospinal Fluid (indicated for associated neurologuc changes)
    1. CSF Pleocytosis with monocytic predominance

X. Diagnosis

  1. Skin Punch Biopsy with immunofluorescent stain for Rickettsia
    1. Used for confirmation, not for diagnosis
    2. Test Sensitivity: 60%
    3. Test Specificity: Very high
  2. Rickettsia Serology
    1. Positive 7 to 10 days after symptom onset
    2. Used for confirmation, not for diagnosis
    3. IgG increases 4 fold from baseline when re-tested 2-4 weeks later

XI. Management

  1. Start empiric treatment immediately when diagnosis suspected
    1. Do not delay treatment for diagnostic testing
    2. Treatment delayed >5 days after onset increases mortality by 3 fold
    3. Treatment is ideally started before rash onset (typically develops day 6)
  2. Antibiotic Course
    1. Minimum course: 7 days
    2. Continue antibiotics until afebrile for 3 days
  3. Antibiotics
    1. Doxycycline for 7 days
      1. Adult: 100 mg oral or IV twice daily
      2. Child (<45 kg) 2.2 mg/kg (max 100 mg) twice daily
        1. Children of any age and pregnant women should be treated with Doxycycline despite dental risks
        2. Only effective treatment available for a condition with high risk for mortality
    2. Chloramphenicol (only if Doxycycline contraindicated)
      1. Dose: 12.5 mg/kg orally four times daily for 7 days
      2. Higher mortality than with Doxycycline

XIII. Prognosis

  1. Untreated: 20-25% Mortality within 7 to 15 days (median 7 days)
  2. Treated: 4-5% Mortality
  3. Children have a higher mortality rate than adults
  4. G6PD is associated with complications and poor outcome

XV. Resources

  1. CDC Rocky Mountain Spotted Fever
    1. http://www.cdc.gov/ncidod/dvrd/rmsf

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