Rocky Mountain spotted fever (RMSF)

Introduction

Tick-borne infection caused by Rickettsia rickettsii characterized by sudden onset of fever, severe headache, myalgia & characteristic rash.

Etiology

• etiologic agent: Rickettsia rickettsii
• transmitted through bite of infected tick or inoculation through abrasion with thick feces or body fluids
• exposure to ticks occurs in tick-infested areas or in association with dogs who bring the tick to the patient
• the American dog tick Dermacentor variabilis endemic east of the Rocky Mountains is the most commonly identified tick

Epidemiology

• 95% of patients become ill between April 11 & Sept. 30
• occurs only in western hemisphere
• cases reported in all states except Vermont & Hawaii
• North Carolina, South Carolina, Oklahoma & Tennessee account for 48% of cases in US
• 600 cases reported annually in US
• only 60% of patient remember recent tick bite (within 2 weeks)
• ticks transmitting Rickettsia rickettsii
  • Dermacentor andersoni (wood tick), western USA
  • Dermacentor variabilis (dog tick)
    • eastern 2/3 & areas of west coast USA
  • Rhipicephalus sanguineus, Mexico
  • Amblyomma cajennense, Mexico, Central & South America

Pathology

• H&E: necrotizing vasculitis
• direct immunofluorescence microscopy: R rickettsii-specific antigen within endothelial cells
• pathophysiology:
  • initial replication of R rickettsii in endothelial cells
  • followed by hematogenous dissemination
  • organisms attach to vascular endothelial cells
  • R rickettsii spreads from endothelial cell to endothelial cell forming a network of infected endothelial cells
  • rash results from extravasation of blood after vascular necrosis
  • cases of severe infection of brain & lung have a high mortality

Clinical manifestations

• incubation period: 3-14 days, mean: 7 days after tick bite
• prodrome: anorexia, irritability, malaise, feverish feeling
• onset of symptoms is generally abrupt
  • fever (94%), up to 40 degrees C
  • severe headache (86%)
  • generalized myalgia, especially back & legs (83%)
  • arthralgia
  • rigors
  • photophobia
  • nausea with vomiting
  • dyspnea, cough
• rash
  • 14% have rash on day 1, 49% have rash within 3 days, 20% have rash after 5 days, 10-13% have no rash
  • early lesions: 2-6 mm, pink, blanchable macules
  • in 1-3 days, macules evolve to red papules
  • in 2-4 days lesions become hemorrhagic (petechiae-like)
  • necrosis of the skin & underlying tissue may occur, especially fingers, toes, ears, scrotum
  • distribution: generally rash begins on wrists, forearms & ankles; later appears on palms & soles; within 6-18 hours rash spreads centripetally to arms, thighs, trunk & face (distribution distinguishes from ehrlichiosis)
• variant presentations
  • spotless fever (13%), diagnosis often missed
  • abdominal syndrome, may mimick acute abdomen
  • thrombotic thrombocytopenic purpura

* image

Laboratory

• complete blood count (CBC):
  • anemia, thrombocytopenia
• comprensive metabolic panel
  • elevated serum transaminases
  • hyponatremia may be noted
• serology
  • immunofluorescent antibody (IFA) or ELISA for IgM & IgG anti-Rickettsial antibodies
  • 4-fold increase in titer between acute & convalescent titers is diagnostic
  • a titer of > 64 is detectable between days 7-10 of illness
• skin biopsy for immunocytochemistry or Rickettsia rickettsii DNA or Rickettsia rickettsii RNA facilitates diagnosis during acute infection
• see ARUP consult

Complications

• extensive cutaneous necrosis secondary to DIC, with gangrene of extremities requiring amputation
• hypotensive shock
• hepatomegaly, splenomegaly, GI hemorrhage, altered consciousness, transient deafness, incontinence, oliguria, secondary bacterial infections of the lung, ear, parotid gland
• death
  • associated with old age, delay in treatment & treatment with chloramphenicol
  • untreated fatality is 20-23%; if treated within 5 days of presentation, fatality is 3%, 6% if > 40 years of age
  • death generally occurs within 5-15 days
• long-term sequelae
  • neurologic: paraparesis; hearing loss; peripheral neuropathy; bladder & bowel incontinence; cerebellar, vestibular & motor dysfunction; language disorders
  • disability from limb amputation
  • scrotal pain following cutaneous necrosis

Differential diagnosis

• meningococcemia
  • nuchal rigidity, DIC, palpable purpura, petechiae
• disseminated gonococcal infection
• secondary syphilis
• Staphylococcus aureus septicemia
• toxic shock syndrome
• typhoid fever
• leptospirosis
• other Rickettsial infections
  • ehrlichiosis
    • macules, papules & petechiae (1/3)
    • rash: central distribution, peripheral sparing
    • may be no rash
      • most patients with Rock Mountain spotted fever have rash
    • leukopenia
    • leukocyte or monocyte intracytoplasmic inclusions (morulae)
  • murine typhus
  • epidemic typhus
  • rickettsialpox
• viral exanthem
  • measles
  • varicella
  • rubella
  • enterovirus
• adverse cutaneous drug reaction
• immune complex vasculitis
• idiopathic thrombocytopenic purpura
• thrombotic thrombocytopenic purpura
• Kawasaki's syndrome

Management

• empiric treatment if Rocky Mountain Spotted fever suspected
  • treatment within 5 days of presentation reduces mortality from 20% to 6%
  • do not withhold or discontinue treatment based on serologic testing
• doxycycline 100 mg PO/IV BID
  • drug of choice in adults & children > 8 years
  • contraindicated in pregnant women
• tetracycline 25-40 mg/kg/day divided QID
• chloramphenicol if pregnant, 50-75 mg/kg/day divided QID
• supportive therapy
  • shock
  • acute renal failure
  • respiratory failure
  • prolonged coma
• prognosis: in uncomplicated cases, defervescence generally occurs within 48-72 hours of initiating therapy

More general terms

• rickettsial spotted fever; tick typhus

Additional terms

• Rickettsia rickettsii
• tick bite