Rocky Mountain Spotted Fever

Aka: Rocky Mountain Spotted Fever, RMSF, Rickettsia rickettsii

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II. Epidemiology

  1. Rocky Mountain Spotted Fever (RMSF) 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)
    3. RMSF was the first identified Tick Borne Illness in the U.S.
  2. Bimodal age distribution
    1. Ages 5 to 9 years old (highest mortality)
    2. Age over 40 to 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. South Carolina
        3. Oklahoma
        4. Arkansas
        5. Tennessee
        6. 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. Person to person transmission does not occur
    2. 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
    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 sanguineus (brown dog tick)
      2. Amblyomma Maculatum (Gulf Coast Tick)
    5. Animal hosts
      1. Deer
      2. Rodents
      3. Horses
      4. Cattle
      5. Cats
      6. Dogs
  2. Rickettsia rickettsii is causative organism
    1. See Rickettsiae
    2. Gram Negative Bacteria
    3. Small pleomorphic organism
    4. Obligate intracellular Parasite
  3. Infects blood vessel walls causing an acute multisystem Vasculitis
    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. Risk Factors

  1. Febrile illness in spring or summer
  2. Outdoor exposures including animal exposures in prior 2 weeks
  3. Travel to endemic regions
  4. Male gender
  5. Black men with G6PD (higher risk for fulminant RMSF, fatal by day 5)
  6. Immunosuppression (higher risk for hospitalization and complications)

V. 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 (esp. june, july)
    3. Headache
  3. Later (day 6)
    1. Erythematous, Macular rash (transitions to Petechiae)

VI. Symptoms (follows 5-7 day incubation)

  1. Fever (absent in up to 14% of patients)
  2. Frontal Headache
  3. Myalgias (back and leg Muscles)
  4. Malaise
  5. Nausea or Vomiting
  6. Abdominal Pain (especially in children)

VII. 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
  4. Associated skin findings
    1. Rumpel-Leede Test of Capillary fragility
      1. Petechiae appear distal to a site of applied pressure
    2. Eschar at Tick Bite site
      1. May be present in more severe cases

VIII. Signs: Atypical Presentations

  1. Altered Mental Status
  2. Meningitis
  3. Conjunctivitis
  4. Lymphadenopathy
  5. Periorbital edema (or other Peripheral Edema)
  6. Myocarditis
  7. Hepatosplenomegaly
  8. Jaundice
  9. Arthritis
  10. Vision Loss
  11. Gastrointestinal symptoms (e.g. Abdominal Pain, Nausea, Vomiting)
  12. Pyuria

IX. Diagnosis

  1. Missed diagnosis initially in up to 75% of cases
    1. Only 50% of patients found and removed the causative tick
    2. Delayed onset of rash until day 6 makes initial diagnosis more difficult
    3. Rash absent in up to 15% of adults (5% of children)
    4. Rash may be more difficult to visualize in darker skin
    5. 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

X. Differential Diagnosis

  1. See Purpura Causes
  2. See Febrile Eruption
  3. See Tick Borne Illness
  4. Ehrlichiosis
  5. Mycoplasma pneumonia
  6. Syphilis
  7. Lyme Disease
  8. Coxsachievirus
  9. Mononucleosis
  10. Parvovirus B19
  11. Kawasaki Disease
  12. Leptospirosis
  13. Roseola
  14. Rubeola
  15. Meningococcemia
  16. Toxic Shock Syndrome
  17. Scarlet Fever
  18. Immune Thrombocytopenic Purpura

XI. Labs

  1. Complete Blood Count
    1. White Blood Cell Count normal, Left Shifted or slightly decreased (Leukopenia)
    2. Thrombocytopenia <150,000 (in 30-60% of cases)
    3. Anemia may be present (in up 30% of cases)
  2. Liver Function Test abnormalities
    1. Serum Bilirubin increased (Hyperbilirubinemia)
    2. Liver transaminases increased (38% of cases, at least minor elevations may occur in most patients)
      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
    2. BUN >25 mg/dl (in up to 10% of cases)
  4. Serum Sodium
    1. Hyponatremia <135 mEq/dl (associated with 20-25% of cases, primarily hypovolemic)
  5. Other labs to consider
    1. Cerebrospinal Fluid (indicated for associated neurologuc changes)
      1. CSF Pleocytosis with monocytic predominance
    2. Inflammatory markers (e.g. C-RP)
      1. Non-specific elevations
    3. Serum Creatine Kinase
      1. Positive tests may indicate Myositis or multifocal rhabdomyyonecrosis

XII. Imaging

  1. Chest XRay
    1. May demonstrate Pulmonary Edema or pneumonitis

XIII. Diagnosis

  1. RMSF is a clinical diagnosis
    1. Treat as soon as suspected (do NOT wait for confirmatory diagnostic tests)
  2. Skin Punch Biopsy with immunofluorescent stain for Rickettsia
    1. Used for confirmation, not for diagnosis
    2. Test Sensitivity: 60%
    3. Test Specificity: Very high
  3. Rickettsia Serology (IFA)
    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 (acute vs convalescent titers)
    4. Negative tests do NOT exclude diagnosis
    5. Positive tests do not differentiate between spotted fever groups of Rickettsial infection (most labs)

XIV. 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
        1. Some protocols start with 200 mg IV every 12 hours for the first 72 hours (however has not been studied)
        2. Recommended treatment for all adults (including in pregnancy)
        3. Consult allergy and Immunology specialists in those with severe allergy reported to Tetracyclines
      2. Child (<45 kg or 99 lb) 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. Tetracyclines are the only highly effective treatment available for a condition with high risk for mortality
    2. Chloramphenicol (only if Doxycycline is absolutely contraindicated)
      1. Dose: 12.5 mg/kg orally four times daily for 7 days
      2. Higher mortality than with Doxycycline (primarily had been used before the 1960s)
      3. Avoid in third trimester pregnancy (risk of Gray Baby Syndrome)
  4. Supportive Care
    1. Fluid Resuscitation
      1. Hypotension from Hypovolemia is present in up to 17% of cases
      2. Caution: May require modified fluid infusion rates if significant Hyponatremia
  5. Disposition
    1. Hospitalization (including ICU admission) may be needed (esp. in delayed presentations >5 days)

XV. Complications

  1. Encephalitis (and cerebral edema, Seizures, Ataxia)
  2. Noncardiac Pulmonary Edema and Pulmonary Hemorrhage
  3. Acute Respiratory Distress Syndrome (ARDS, up to 12% of cases)
    1. Mechanical Ventilation required in up to 8% of cases
  4. Acute Renal Failure (from prerenal Azotemia, Acute Tubular Necrosis)
  5. Myocarditis
  6. Cardiac Arrhythmia (7-16% of cases)
  7. Disseminated Intravascular Coagulation (rare)
  8. Gastrointestinal Bleeding
  9. Skin Necrosis

XVI. Prognosis

  1. Prompt treatment results in best outcomes
    1. Untreated: 20-25% Mortality within 7 to 15 days (median 7 days)
    2. Delayed treatment: 4-5% mortality rate
    3. Promptly treated: <1% mortality
      1. Decreased mortality has been associated with the prompt use of Tetracycline Antibiotics since the 1940s
  2. Other risks for increased mortality
    1. Children have a higher mortality rate than adults
    2. G6PD is associated with complications and poor outcome
    3. Delayed presentation >5 days
      1. Higher risk of death at 8-15 days after onset

XVII. Prevention

  1. See Prevention of Vector-borne Infection
  2. Prompt Tick Removal decreases the risk of infection
  3. Prophylactic Antibiotics are not recommended after Tick Bite to prevent RMSF

XVIII. Resources

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

XIX. References

  1. (2016) Sanford Guide to Antibiotics, IOS App accessed 4/14/2016
  2. Kugler (2026) Crit Dec Emerg Med 40(1): 4-12
  3. Chapman (2006) MMWR Recomm Rep 55(RR-4):1-27 [PubMed]
  4. Cunha (2008) Lancet Infect Dis 8(3): 143-4 [PubMed]
  5. Huntington (2016) Am Fam Physician 94(7): 551-7 [PubMed]
  6. Pace (2020) Am Fam Physician 101(9): 530-40 [PubMed]
  7. Thorner (1998) Clin Infect Dis 27:1353-60 [PubMed]

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