What is the appropriate management for a patient presenting with bilateral knee pain, swelling, fever, headache, neck pain, and a rash spreading up to the thighs?

Red Flag Assessment: Suspected Tickborne Rickettsial Disease

This patient requires immediate empiric treatment with doxycycline for presumed tickborne rickettsial disease (TBRD), specifically Rocky Mountain Spotted Fever (RMSF) or ehrlichiosis, given the constellation of bilateral joint pain, fever, headache, neck pain, and ascending rash—do not wait for confirmatory testing. 1

Critical Clinical Recognition

This presentation represents a medical emergency requiring immediate action:

• Fever, headache, neck pain, and rash spreading from lower to upper extremities is the classic progression pattern for RMSF, where rash typically begins on ankles, wrists, or forearms and spreads centripetally 1
• Bilateral knee pain with ankle swelling in the context of systemic symptoms suggests either early disseminated infection or inflammatory arthralgia associated with TBRD 1
• The combination of fever, headache, and neck pain mimics meningococcal disease, necessitating empiric coverage for both conditions when neither can be excluded 1

Immediate Management Algorithm

Step 1: Empiric Antibiotic Therapy (Start Immediately)

Initiate doxycycline immediately without waiting for laboratory confirmation:

• Doxycycline is the treatment of choice for all suspected TBRD regardless of patient age 1
• If meningococcal disease cannot be ruled out based on clinical presentation, add intramuscular ceftriaxone to cover possible Neisseria meningitidis 1
• The risk-benefit ratio strongly favors early treatment, as delayed therapy significantly increases morbidity and mortality in RMSF 1

Step 2: Diagnostic Evaluation (Concurrent with Treatment)

Obtain the following tests immediately, but do not delay treatment:

• Complete blood count with differential: Look for leukopenia, thrombocytopenia (present in up to 94% of ehrlichiosis cases), or increased immature bands 1
• Comprehensive metabolic panel: Check for hyponatremia and elevated hepatic transaminases, which are particularly suggestive of ehrlichiosis 1
• Blood cultures: Obtain before antibiotics if meningococcal disease is in the differential 1
• Cerebrospinal fluid analysis if neck stiffness is prominent: Expect pleocytosis (usually <100 cells/µL) with either polymorphonuclear or lymphocytic predominance, moderately elevated protein (100-200 mg/dL), and normal glucose in TBRD 1

Step 3: Risk Stratification for Hospitalization

Hospitalize if any of the following are present (at least 50% of TBRD patients require hospitalization):

• Evidence of organ dysfunction 1
• Severe thrombocytopenia 1
• Mental status changes 1
• Petechial or purpuric rash (indicates advanced disease) 1
• Inability to tolerate oral medications 1

Key Diagnostic Pitfalls to Avoid

Rash Timing and Characteristics

• Most patients with RMSF do NOT have rash when first seeking care during the first 2-4 days of illness 1
• Rash typically appears 2-4 days after fever onset, meaning early presentations may lack this "classic" finding 1
• The rash can be completely absent in up to 20% of RMSF cases, so absence of rash does not exclude the diagnosis 1
• When present, the rash evolves from blanching pink macules to maculopapules, and may progress to petechiae by day 5-6 of illness 1

Laboratory Findings

• Normal white blood cell count does NOT exclude TBRD: Leukopenia is more common than leukocytosis in ehrlichiosis 1
• Thrombocytopenia and hyponatremia are particularly useful clinical features when present, but their absence does not exclude TBRD 1
• Serologic testing provides supportive diagnostic information but should never delay empiric treatment 1

Distinguishing from Meningococcal Disease

Critical differences that may help differentiate (though empiric treatment for both may be necessary):

• CSF glucose: Very low glucose (<20-30 mg/dL) and gram-negative diplococci on Gram stain suggest meningococcal disease rather than TBRD 1
• Neutrophilic pleocytosis in CSF can occur in both conditions, making reliable distinction difficult 1
• When in doubt, treat empirically for both conditions with doxycycline PLUS ceftriaxone 1

Epidemiologic History (Obtain After Treatment Initiated)

While treatment should never be delayed, obtain detailed exposure history:

• Recent tick exposure or outdoor activities in endemic areas 1
• Geographic location and season (RMSF is more common in southeastern and south-central United States) 1
• Note that absence of recalled tick bite does not exclude TBRD, as many patients do not recall exposure 1

Prognosis and Follow-up

• Early treatment with doxycycline dramatically improves outcomes 1
• Delayed treatment significantly increases risk of severe complications including organ dysfunction and death 1
• Patients should be monitored closely for clinical response within 24-48 hours of initiating therapy 1
• If no improvement occurs within 48-72 hours, reconsider the diagnosis and broaden antimicrobial coverage 1