01Approach to the Critical Patient/attcp44

Immediate priorities

›Time-critical recognition and treatment

›RMSF kills without the full triad — treat on suspicion alone

›Classic triad (fever + rash + tick bite) present in minority at initial visit

›~15% never develop rash ("spotless" RMSF)

›Tick bite recalled by only ~50% of patients

›Doxycycline immediately upon clinical suspicion

›Do not await confirmatory serology — results lag clinical need by days to weeks

›Case-fatality rate 20–40% when treatment delayed beyond day 5

›Delay to days 8–9 carries 40–50% mortality

Hemodynamic assessment

›Shock physiology

›Systolic BP < 90 mmHg

›Vasculitis-driven endothelial leak — judicious fluid resuscitation

›Risk of pulmonary edema and ARDS with aggressive fluids

›MAP < 65 mmHg

›Norepinephrine initiation for refractory hypotension

›ICU-level monitoring required

›Tachycardia

›Fever-driven versus myocarditis/arrhythmia

›Continuous cardiac monitoring

Escalation triggers

›Criteria for ICU or resuscitation bay

›Petechial or purpuric rash

›Signifies advanced endothelial injury

›Median onset day 5–6 of illness

›Altered mental status or seizures

›Meningoencephalitis pattern

02History/hx64

Exposure history

›Tick exposure and geographic context

›Outdoor activities in past 3–12 days

›Hiking, camping, yard work, gardening

›Wooded, grassy, shrubby environments

›Geographic risk

›60% of US cases from NC, OK, AR, TN, MO

›Cases throughout North and South America

›Endemic area residence or recent travel

›Seasonal timing

›Peak April–September (spring/summer)

›Year-round cases in some endemic areas

›Tick bite recall

›Absent in ~50% — lack of recall paradoxically linked to higher mortality

›Pet dog ownership increases exposure risk

Symptom characterization

›Core symptoms

›Fever onset

›Sudden onset high fever > 38.9°C

›Chills, rigors

›Incubation period 3–12 days after tick bite

›Shorter incubation (≤5 days) associated with more severe disease

›Headache

›Typically severe

›Photophobia common

›Myalgia and malaise

›Diffuse myalgia

›Fatigue and anorexia

03Physical Exam/exam60

Vital signs

›Fever and hemodynamic profile

›Temperature typically > 39°C

›High fever nearly universal at presentation

›Hypothermia in fulminant/shock state

›Heart rate

›Tachycardia common with fever

›Bradycardia relative to fever suggests myocarditis

›Blood pressure

›Hypotension in late or severe disease

›Widened pulse pressure can precede frank shock

Skin examination

›Full body skin survey

›Distribution pattern

›Wrists, ankles, forearms first

›Palms and soles involvement (classic)

›Centripetal spread to trunk

›Face typically spared

›Rash morphology staging

›Early: blanching pink macules 1–5 mm

›Intermediate: maculopapular, non-blanching

›Late: petechial or purpuric — advanced vasculitis

›Cutaneous necrosis or gangrene

›Fulminant disease indicator

›Digital or acral involvement

›Skin color caveat

›Rash may be difficult to recognize in darker skin tones

›Maintain high suspicion regardless of visible rash

04Differential Diagnosis/ddx48

Cannot-miss diagnoses

›Life-threatening mimics requiring immediate action

›Meningococcemia (ICD-10: A39.4)

›Petechial/purpuric rash, rapid hemodynamic collapse

›Cover empirically with ceftriaxone alongside doxycycline if suspected

›Blood cultures before antibiotics if achievable without delay

›Sepsis from occult bacterial source (ICD-10: A41.9)

›Undifferentiated fever with organ dysfunction

›RMSF can present identically to gram-negative sepsis

›Toxic shock syndrome (ICD-10: A48.3)

›Diffuse erythroderma, hypotension, desquamation

›Staphylococcal or streptococcal source

Tick-borne disease mimics

›Rickettsial and similar tick-borne infections

›Ehrlichiosis (ICD-10: A77.40)

›Rash less common (~30%)

›Leukopenia more prominent

›Also treated with doxycycline

›Anaplasmosis (ICD-10: A77.49)

›Similar to ehrlichiosis

›Inclusions (morulae) in neutrophils

›Lyme disease (ICD-10: A69.20)

›Erythema migrans (target lesion)

›Different rash morphology and distribution

›Relapsing fever borreliosis (ICD-10: A68.1)

›Cyclical fevers

›Absence of characteristic spotted fever rash

05Laboratory Tests/lt53

Initial labs

›Complete blood count

›Thrombocytopenia

›Key finding; platelet count < 150 × 10⁹/L

›Severity correlates with disease progression

›WBC typically normal or mildly elevated with left shift

›Comprehensive metabolic panel

›Hyponatremia

›Due to SIADH or vascular leak

›Sodium < 135 mmol/L common

›Renal function

›Elevated creatinine with acute kidney injury

›BUN elevation reflects renal and catabolic burden

›Liver enzymes

›AST and ALT mildly to moderately elevated

›Hepatitis pattern common

›Coagulation studies

›PT, aPTT, fibrinogen, D-dimer

›DIC screen when thrombocytopenia is severe

›Fibrinogen consumption is ominous

Inflammatory and injury markers

›Severity markers

›LDH and CK

›Elevated in later disease with diffuse tissue injury

›LDH elevation correlates with severity

›Lactate

›>= 2 mmol/L indicates tissue hypoperfusion

›>= 4 mmol/L indicates severe sepsis/shock

06Diagnostic Tests/dt64

Scoring Systems

›No validated scoring system specific to RMSF

›RMSF diagnosis is clinical — treat empirically when suspected

›Clinical prediction rules under development but not yet validated

›Do not rely on scoring tools to withhold empiric therapy

›SOFA score for organ dysfunction severity

›Score >= 2 indicates organ dysfunction

›Use to guide ICU admission and monitoring

›qSOFA for rapid bedside risk stratification

›Respiratory rate >= 22/min

›Altered mental status

›Systolic BP <= 100 mmHg

›Score >= 2 associated with poor outcome in sepsis

Scoring Systems Additional

›Severity stratification framework (clinical, not validated score)

›Early/mild disease features

›Fever and headache, myalgia, early macular rash

›Normal or near-normal labs

›Outpatient doxycycline candidate

›Moderate disease features

›Rash progression, lab abnormalities, GI symptoms

›Close follow-up or observation admission

›Severe disease features

›Petechial rash, AMS, organ dysfunction, shock

›ICU admission

MRI

›MRI brain indications in RMSF

›Meningoencephalitis or focal neurologic deficits

07Disposition/dispo40

Admission indications

›Criteria requiring inpatient management

›Clinical severity markers

›Petechial or purpuric rash

›Altered mental status or neurologic changes

›Organ dysfunction (renal failure, hepatic injury, ARDS)

›Hemodynamic instability or need for IV pressors

›Severe thrombocytopenia (platelet < 50 × 10⁹/L)

›Inability to tolerate oral medications

›Persistent vomiting

›Obtunded or unable to swallow safely

›Host and social factors

›Significant comorbidities or immunosuppression

›Concerns about medication adherence

›Inability to return for follow-up within 24 hours

ICU admission criteria

›ICU-level care indications

›Multi-organ failure

›Vasopressor requirement

›Mechanical ventilation for ARDS

›Renal replacement therapy

›Neurologic compromise

›GCS < 13 or seizures

›Rapidly progressive meningoencephalitis

›DIC with bleeding

›Active hemorrhage with coagulopathy

Discharge criteria

›Safe for outpatient management when

08Treatment/t63

Empiric antibiotic therapy

›First-line treatment — doxycycline

›Adult dosing

›Doxycycline 100 mg PO or IV q12h

›IV preferred for vomiting, obtunded, or severely ill patients

›Duration

›Minimum 5–7 days total

›At least 3 days after defervescence and clinical improvement

›Severe or complicated disease may require longer courses

›Timing mandate

›Start immediately upon clinical suspicion

›Do not await confirmatory serology or rash development

›Fever resolves within 24–48 hours if started in first 4–5 days of illness

›Lack of defervescence at 48 hours should prompt diagnostic reassessment

Contraindicated and alternative agents

›Drug safety in RMSF

›Sulfonamides — absolutely contraindicated

›Worsens disease severity and increases mortality

›Never use trimethoprim-sulfamethoxazole for suspected RMSF

›Chloramphenicol — alternative only

›Use only for true doxycycline allergy or intolerance after ID consultation

›Associated with higher case-fatality rate than doxycycline

›Adult dose: 50–75 mg/kg/day IV divided q6h

›Beta-lactams and macrolides — not effective

›Rickettsia rickettsii is naturally resistant

Supportive care

›Fluid management

›IV fluid resuscitation for hypotension

09Special Populations/sp51

Pregnancy

›RMSF in pregnancy

›Disease severity and fetal risk

›RMSF untreated in pregnancy carries high maternal and fetal mortality

›Vasculitis can cause placental insufficiency

›Fetal loss and preterm delivery reported in severe cases

›Treatment in pregnancy

›Doxycycline is still first-line despite pregnancy

›RMSF mortality risk far exceeds theoretical doxycycline risk to fetus

›Short-course doxycycline acceptable in all trimesters for life-threatening infection

›Consult ID and maternal-fetal medicine for severe cases

›Chloramphenicol use in pregnancy

›Avoid near term — gray baby syndrome risk in neonate

›Second trimester use only if doxycycline truly contraindicated

›Monitoring

›Fetal monitoring in third trimester with severe disease

›ICU-level care for severe or complicated presentations

Geriatric

›RMSF in older adults

›Altered risk profile

›Age >= 40 years associated with higher mortality

›Atypical presentation more common

›Rash may be less prominent or recognized later

›Comorbidity considerations

›Renal dosing adjustment not required for doxycycline at standard doses

›Hepatic dysfunction may alter drug metabolism

›Polypharmacy interactions with doxycycline (antacids, iron reduce absorption)

›Management modifications

10Background/b83

Epidemiology

›Incidence and geographic distribution

›US incidence

›Approximately 4,000–6,000 cases reported annually in the US

›Cases increasing over past two decades

›Significant underreporting likely

›Geographic concentration

›60% of cases in NC, OK, AR, TN, MO

›Cases throughout North and South America

›Brazil and Mexico have high-burden regions

›Seasonal pattern

›Peak April–September

›Year-round cases possible in warm endemic regions

›Mortality and outcomes

›Case fatality rate

›20–40% without treatment

›< 5% with early appropriate doxycycline

›40–50% when treatment delayed to days 8–9

›High-risk groups

›Age < 10 years and >= 40 years

›G6PD deficiency — highest short-term fatality risk

›Alcohol use disorder

›Lack of tick bite recall associated with higher mortality (delayed diagnosis)

›Vector and reservoir

›Primary tick vectors in the US

›Dermacentor variabilis (American dog tick) — eastern US

›Dermacentor andersoni (Rocky Mountain wood tick) — western US

›Rhipicephalus sanguineus (brown dog tick) — increasingly recognized, especially southwestern US

›Transmission

›Tick must be attached 6–10 hours to transmit Rickettsia rickettsii

›Prompt tick removal reduces transmission risk

Pathophysiology

›Mechanism of disease

›Causative organism

›Rickettsia rickettsii — obligate intracellular gram-negative bacterium

›Spotted fever group rickettsia

›ICD-10: A77.0

›Entry and dissemination

›Inoculated via tick saliva during feeding

›Infects endothelial cells of small and medium blood vessels

›Spreads hematogenously and lymphatically

›Endothelial injury cascade

›Direct endothelial cell invasion and destruction

›Inflammatory cytokine release (TNF-alpha, IL-1, IL-6)

›Microvascular leak — protein and fluid extravasation

›Vasculitis in multiple organ systems simultaneously

›Organ-specific consequences

›CNS — meningoencephalitis from cerebral vasculitis

›Lung — non-cardiogenic pulmonary edema, ARDS

›Kidney — renal tubular injury and acute kidney injury

›Skin — petechial rash from microvascular hemorrhage

›Myocardium — myocarditis from cardiac endothelial involvement

›Coagulation — thrombocytopenia from platelet consumption and endothelial damage

Therapeutic Considerations

›Mechanism of doxycycline efficacy

›Mode of action

›Inhibits ribosomal 30S subunit — bacteriostatic

›Penetrates host cells to reach intracellular Rickettsia

›Achieves high intracellular concentrations

›Clinical response benchmark

›Fever resolves within 24–48 hours of doxycycline if started in first 4–5 days

›Failure to defervesce within 48 hours should prompt diagnostic reassessment

›Evidence basis for treatment decisions

›MMWR 2016 CDC guidelines (Biggs et al.)

›Doxycycline first-line for all ages, all presentations

›Empiric treatment before confirmatory testing

›Wilderness Medical Society guidelines 2021

›Tick bite prevention and management recommendations

›No prophylactic antibiotics after asymptomatic tick bite

›IDSA/ASM microbiology laboratory guide 2024

›IFA serology gold standard for confirmation

›PCR as adjunct during acute febrile phase

›Natural history without treatment

›Untreated outcome trajectory

›Initial fever and myalgia evolving over 2–4 days

›Rash appears days 2–4 after fever

›Petechiae signify advanced microvascular injury by days 5–6

›Multi-organ failure and death risk sharply rises after day 5 without treatment

›Long-term sequelae after severe disease

›Neurologic complications

›Cognitive impairment

›Sensorineural hearing loss

›Paraparesis or monoparesis

›Vascular complications

›Limb amputation after gangrene in fulminant cases

›No reliable immunity after infection — reinfection possible

11Patient Discharge Instructions/pdi28

copy discharge instructions

›Discharge instructions for Rocky Mountain Spotted Fever

›Your diagnosis and treatment

›You have been diagnosed with Rocky Mountain Spotted Fever, a serious infection caused by bacteria transmitted by tick bites

›You have been prescribed doxycycline to treat this infection

›Take doxycycline exactly as prescribed — complete the full course even if you feel better

›Take doxycycline with a full glass of water and remain upright for 30 minutes to reduce stomach upset

›Avoid antacids, calcium supplements, iron, and dairy within 2 hours of doxycycline — these reduce absorption

›Expected recovery

›Fever should begin to improve within 24–48 hours of starting doxycycline

›If fever does not improve within 48 hours, return to the emergency department

›Fatigue and muscle aches may persist for several days after fever resolves

›Follow-up required

›Return to your doctor or this emergency department within 24–48 hours

›This is required to ensure you are improving on treatment

›Return to the emergency department immediately if

›Fever is not improving or is worsening after 48 hours on antibiotics

›New rash appears or existing rash spreads, changes color, or develops purple/red spots (petechiae)

›Confusion, difficulty thinking, unusual behavior, or seizures

›Severe headache or neck stiffness

›Shortness of breath or chest pain

›You are unable to keep your antibiotic down due to vomiting

›Decreased urination or swelling of face, hands, or feet

›Any rapid or dramatic worsening of symptoms

›Tick prevention going forward

›Use DEET-based insect repellent on exposed skin and permethrin-treated clothing in tick habitats

›Perform daily tick checks on yourself, children, and pets after outdoor activities

›Remove ticks promptly with fine-tipped tweezers — grasp near skin surface and pull upward steadily

12References/r21

Guidelines and key sources

›Primary guideline reference

›Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and Management of Tickborne Rickettsial Diseases. MMWR Recomm Rep. 2016

›CDC primary guideline for RMSF and other spotted fever rickettsioses

›Doxycycline first-line for all ages including children under 8 years

›Empiric treatment without awaiting confirmatory results

›Gottlieb M, Long B, Koyfman A. Evaluation and Management of RMSF in the Emergency Department. J Emerg Med. 2018

›Emergency department focused review

›Clinical pearls for early recognition and treatment

›Ho BM, Davis HE, Forrester JD, et al. Wilderness Medical Society Clinical Practice Guidelines for Tick-Borne Illness. Wilderness Environ Med. 2021

›Tick prevention and management recommendations

›No prophylactic antibiotics after asymptomatic tick bite

›Miller JM, Binnicker MJ, Campbell S, et al. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update. IDSA/ASM. Clin Infect Dis. 2024

›IFA serology gold standard — acute and convalescent paired samples

›PCR utility during acute febrile phase

›Bejarano JIC, Gonzalez EAL, et al. Epidemiologic Characterization and Risk Factors of RMSF in Children in Northeastern Mexico 2018–2024. Arch Med Res. 2026

›Pediatric RMSF epidemiology and risk factor analysis

›McCormick DW, Nicholson WL. Rickettsial Diseases. CDC Yellow Book. 2025

›Travel medicine reference for rickettsial diseases

›Clinical and epidemiologic summary

›Pace EJ, O'Reilly M. Tickborne Diseases: Diagnosis and Management. Am Fam Physician. 2020

›Primary care and emergency medicine overview of tick-borne illness spectrum

Evidence & Review

Evidence & Review