Infectious Disease · PANCE / PANRE

Rocky Mountain Spotted Fever (RMSF)

Tick-borne rickettsial vasculitis with fever, headache, and centripetal petechial rash — empiric doxycycline at first suspicion saves lives.

Also known as: RMSF, Rickettsia rickettsii, spotted fever rickettsiosis

Overview

Acute systemic illness caused by Rickettsia rickettsii, an obligate intracellular gram-negative coccobacillus, transmitted by Dermacentor variabilis (American dog tick, eastern US), D. andersoni (Rocky Mountain wood tick, western US), and Rhipicephalus sanguineus (brown dog tick, Arizona).

Epidemiology

Despite the name, most US cases occur in the South Atlantic and Central states (North Carolina, Tennessee, Oklahoma, Arkansas, Missouri). Peak May-September. Case-fatality up to 20-25% untreated, <1% with early doxycycline. Children and immunocompromised at highest risk.

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Risk factors

Outdoor exposure in endemic regions during warm months
Tick attachment (transmission can occur within 6-10 hours)
Contact with dogs in tick-endemic areas
G6PD deficiency associated with fulminant disease

Pathophysiology

Rickettsia rickettsii invades vascular endothelial cells, multiplying intracellularly and spreading cell-to-cell via actin-based motility. The resulting widespread small-vessel vasculitis causes increased vascular permeability, microhemorrhage (petechial rash), tissue edema, hypovolemia, and end-organ damage (encephalitis, ARDS, AKI, DIC).

Clinical presentation

Symptoms

Abrupt fever, severe headache, myalgia, malaise (2-14 days post-tick bite)
Nausea, vomiting, abdominal pain (can mimic acute abdomen)
Rash appears day 2-5: blanching macules → maculopapular → petechial; starts at wrists/ankles → spreads centripetally to trunk; involves palms and soles in ~50%
Confusion, lethargy, focal neuro deficits in severe disease

Signs / physical exam

Petechial rash on wrists/ankles, palms/soles (~half of patients; appears late)
Conjunctival injection, periorbital edema
Hypotension, oliguria in advanced disease
Hepatosplenomegaly, jaundice

Classic findings

Fever + headache + centripetal rash (wrists/ankles spreading inward, including palms/soles) in a summer outdoor exposure — but rash may be absent or appear late in 10-20%; DO NOT wait for rash to treat.

Differential diagnosis

Meningococcemia — Rapidly progressive petechiae/purpura, hypotension, meningitis; blood culture; treat empirically with ceftriaxone + doxycycline overlap until clarified
Ehrlichiosis/anaplasmosis — Tick-borne, similar prodrome, rash less common; leukopenia, thrombocytopenia, elevated LFTs; same doxycycline coverage
Measles — Cough, coryza, conjunctivitis, Koplik spots; rash starts on face and spreads caudally
Secondary syphilis — Rash includes palms/soles but not petechial; positive RPR
Drug reaction (TEN, DRESS) — Recent drug exposure, mucosal involvement, eosinophilia; biopsy
Idiopathic thrombocytopenic purpura (ITP) — Isolated thrombocytopenia, no fever, no systemic illness
Viral exanthem (enterovirus, parvovirus) — Usually self-limited; less toxic appearance; supportive care

Diagnostic workup

Diagnostic criteria

Clinical diagnosis with serologic confirmation. Treatment should NEVER be delayed for laboratory confirmation.

Labs

CBC (thrombocytopenia, normal or low WBC), CMP (hyponatremia, elevated LFTs, elevated Cr)
Coags (prolonged PT/PTT in severe disease)
Rickettsia rickettsii IgM and IgG indirect immunofluorescence assay (IFA) — paired acute and convalescent (2-4 weeks later) titers, 4-fold rise diagnostic
Skin biopsy with immunohistochemistry/PCR — highest sensitivity within 24 hours of rash onset
Blood PCR — variable sensitivity; useful early

Imaging

CXR if respiratory symptoms (pulmonary edema/ARDS)
CT/MRI brain for altered mental status or focal deficits

Diagnostic algorithm

flowchart TD
  A[Fever + headache<br/>summer + outdoor exposure] --> B{Tickborne illness<br/>suspected?}
  B -->|Yes| C[Start doxycycline<br/>do NOT delay for labs]
  C --> D[Obtain: CBC, CMP,<br/>IFA serology, skin bx if rash]
  D --> E{Rash develops?}
  E -->|Yes| F[Centripetal pattern,<br/>palms/soles → RMSF likely]
  E -->|No rash| G[Consider ehrlichiosis,<br/>anaplasmosis — doxy covers all]
  D --> H[Continue doxy<br/>≥3 days after afebrile]

Empiric management of suspected tickborne rickettsial illness — initiate doxycycline first, confirm later.

Treatment

First-line

Doxycycline 100 mg PO/IV BID for all ages — including children <8 (CDC and AAP — benefit far exceeds tooth discoloration risk for short courses)
Treat for at least 3 days after defervescence; typical course 5-7 days
Pediatric dosing: 2.2 mg/kg/dose BID up to 100 mg

Second-line / adjunct

Chloramphenicol — only for confirmed doxycycline allergy or pregnancy (debated; doxycycline preferred in pregnancy if severe)
Avoid sulfonamides — may worsen rickettsial illness
Fluoroquinolones and beta-lactams ineffective

Complications

Encephalitis with seizures, coma, focal deficits
ARDS, myocarditis, AKI requiring dialysis
DIC with gangrene of digits/extremities (amputation in survivors)
Permanent neurologic sequelae (hearing loss, paralysis, cognitive impairment) in delayed-treatment survivors
Death (mortality 20-25% untreated, <1% if doxycycline within 5 days of symptom onset)

PANCE pearls

Triad of fever, headache, and rash is present in <50% at initial presentation — treat empirically based on exposure and clinical picture.
Mortality climbs sharply when doxycycline is delayed beyond day 5 of illness — never withhold for serology.
Doxycycline is the drug of choice in children regardless of age (CDC 2017 update).
Hyponatremia, thrombocytopenia, and transaminitis form a useful early laboratory triad.
Tick avoidance: permethrin-treated clothing, DEET on skin, daily tick checks, prompt removal with fine forceps at skin level.

References

CDC 2016 — Diagnosis and Management of Tickborne Rickettsial Diseases (MMWR Recommendations and Reports)
AAP Red Book — Doxycycline use in children — Rocky Mountain Spotted Fever and other tickborne rickettsioses
IDSA — Guidelines for selected rickettsial diseases

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