What's the diagnosis and treatment for a patient presenting with bilateral knee pain, ankle and knee swelling, fever, headache, neck pain, and a spreading rash?

Red Flag: Lyme Disease with Meningitis

The critical red flag in this presentation is Lyme disease with possible meningeal involvement, requiring immediate empiric antibiotic therapy with doxycycline or ceftriaxone before confirmatory testing. This constellation of migratory oligoarthritis (bilateral knee pain progressing to ankle and knee swelling), fever, headache, neck pain (suggesting meningismus), and an ascending rash strongly suggests disseminated Lyme disease 1.

Key Diagnostic Features

Classic Lyme Disease Presentation

• Migratory joint involvement: The progression from bilateral knee pain to ankle and knee swelling over one month represents the typical oligoarticular pattern of Lyme arthritis 1
• Spreading rash: An ascending rash from lower extremities to thighs is consistent with erythema migrans, which can expand centrifugally and may appear weeks after initial tick exposure 1
• Neurologic symptoms: Headache and neck pain suggest early neuroborreliosis (Lyme meningitis), a serious complication requiring urgent treatment 1
• Fever: While not always prominent in Lyme disease, fever combined with meningeal signs indicates systemic dissemination 1

Critical Differentiating Features from Other Causes

Rocky Mountain Spotted Fever (RMSF) would present differently:

• RMSF rash typically begins on wrists/ankles and spreads centripetally (toward trunk), not ascending up the thighs 1
• RMSF rash appears 2-4 days after fever onset, not after one month of joint symptoms 1
• RMSF causes more severe acute illness with rapid progression 1

Kawasaki disease is excluded by:

• Age (typically affects children <5 years) 1
• Lack of conjunctival injection, oral mucosal changes, or extremity erythema/edema 1
• Chronic one-month course inconsistent with Kawasaki's acute presentation 1

Adult-Onset Still's Disease would show:

• Quotidian (daily spiking) fever pattern 1
• Salmon-colored evanescent rash, not a spreading pattern 1
• More prominent systemic features 1

Immediate Management Algorithm

1. Clinical Assessment

• Document tick exposure history: Ask specifically about outdoor activities, geographic location (endemic areas), and any recalled tick bites, though absence doesn't exclude diagnosis 1
• Examine for erythema migrans: Look for expanding erythematous patches with central clearing, though atypical presentations are common 1
• Assess for meningismus: Neck stiffness, photophobia, and severe headache warrant immediate lumbar puncture consideration 1

2. Urgent Laboratory Testing

• Serology: Two-tier testing with ELISA followed by Western blot, though early disseminated disease may be seronegative 1
• Joint aspiration: If large effusion present, aspirate to exclude septic arthritis (synovial fluid in Lyme shows inflammatory pattern with WBC 10,000-25,000/μL) 1, 2
• Lumbar puncture: If meningeal signs present, CSF analysis shows lymphocytic pleocytosis in neuroborreliosis 1

3. Empiric Antibiotic Therapy (Do Not Delay for Test Results)

For Lyme arthritis without neurologic involvement:

• Doxycycline 100 mg PO twice daily for 28 days (first-line) 1
• Alternative: Amoxicillin 500 mg PO three times daily for 28 days if doxycycline contraindicated 1

For suspected neuroborreliosis (with headache/neck pain):

• Ceftriaxone 2 g IV daily for 14-28 days 1
• This patient requires IV therapy given meningeal symptoms 1

Critical Pitfalls to Avoid

Common Diagnostic Errors

• Waiting for serology before treating: Early disseminated Lyme can be seronegative; treat based on clinical presentation in endemic areas 1
• Misinterpreting as viral syndrome: The one-month duration and progressive joint involvement exclude typical viral exanthems 3, 4
• Assuming bilateral joint involvement excludes infection: Lyme arthritis characteristically affects multiple large joints, unlike typical septic arthritis 1

Treatment Considerations

• Inadequate antibiotic duration: Lyme arthritis requires 28 days of oral therapy or 14-28 days IV for neurologic involvement 1
• Missing concurrent tick-borne infections: Consider co-infection with Anaplasma or Babesia if severe systemic symptoms present 1
• Failure to recognize treatment urgency: Delayed treatment of neuroborreliosis can result in permanent neurologic sequelae 1

When to Escalate Care

Immediate infectious disease consultation if:

• Confirmed or suspected neuroborreliosis (this patient qualifies) 1
• Carditis symptoms develop (heart block, chest pain) 1
• Failure to improve after 48-72 hours of appropriate antibiotics 1
• Immunocompromised host 1

Rheumatology referral for:

• Persistent arthritis after completing antibiotic course (post-Lyme arthritis syndrome) 1
• Consideration of anti-inflammatory therapy after infection cleared 1