In a 51-year-old adult with painful swelling and erythema of the hands and ankles and a normal comprehensive metabolic panel two weeks ago, what is the appropriate initial evaluation and treatment?

Acute Evaluation and Management of Hand and Ankle Swelling with Erythema

Immediately obtain a complete blood count with differential to screen for myeloproliferative disorders, as erythromelalgia—a condition causing burning pain, erythema, and swelling of the extremities—is frequently associated with thrombocythemia and polycythemia vera, and symptoms often precede the hematologic diagnosis by years. 1, 2

Initial Diagnostic Approach

Critical Red Flags to Exclude First

• Myeloproliferative disorders: Check CBC with differential, as erythromelalgia symptoms precede the diagnosis of polycythemia vera or essential thrombocythemia by a median of 2.5 years 2
• Acute gout: Rapid onset of severe pain reaching maximum intensity within 6-12 hours with overlying erythema is highly suggestive of crystal inflammation 3
• Tick-borne illness: Recent tick exposure with fever, headache, and burning sensations on palms/soles raises suspicion for Rocky Mountain spotted fever, which has 5-10% mortality if untreated and requires immediate empiric doxycycline 4, 5
• Diabetic myonecrosis: In patients with long-standing poorly controlled diabetes, abrupt pain and swelling of extremities (especially lower limbs) may represent this under-diagnosed microvascular complication 6

Key Clinical Features to Assess

For erythromelalgia specifically:

• Burning discomfort, warmth, and dermal erythema of feet and/or hands 1
• Symptoms worsen with heat exposure, dependency, or exercise 1, 2
• Symptoms improve with elevation or cooling of the extremity 1, 2
• Attacks are episodic and can severely limit daily activities 4

For gout:

• Podagra (first metatarsophalangeal joint involvement) has high specificity 3
• Presence of tophi (if visible) permits clinical diagnosis 3
• Hyperuricemia supports but does not confirm diagnosis 3

Recommended Laboratory Workup

1. Complete blood count with differential - Essential to detect thrombocytosis, polycythemia, or immature cells that indicate myeloproliferative syndrome 1, 2
2. Serum uric acid level - Elevated in gout, though normal levels do not exclude acute gout 3
3. Inflammatory markers (ESR, CRP) - If gout suspected with atypical features 3
4. Joint aspiration for crystal analysis - Definitive for gout diagnosis if monosodium urate crystals identified 3

Treatment Recommendations

If Erythromelalgia is Suspected

Initiate aspirin 81 mg daily immediately, as platelet-mediated erythromelalgia responds within hours to low-dose aspirin. 4, 1, 2

• This single daily dose provides dramatic improvement in most patients with either primary or secondary erythromelalgia 2
• Adults with thrombocythemia-related erythromelalgia show marked relief with aspirin therapy 1
• Continue monitoring CBC periodically, as any abnormal hemoglobin, white blood cell count, platelet count, or immature cells should prompt evaluation for underlying hematologic disorder 1, 2

If Acute Gout is Suspected

Start colchicine 0.6 mg orally for acute gout attack, with dosing adjusted for renal function and drug interactions. 7

• Colchicine clearance is reduced by 75% in end-stage renal disease with prolonged half-life (18.8 vs 4.4 hours) 7
• Avoid or reduce dose with strong CYP3A4 inhibitors (cyclosporine increases colchicine levels 259-270%, clarithromycin 227-281%, ketoconazole 101-212%) 7

If Rocky Mountain Spotted Fever Cannot Be Excluded

Do not delay empiric doxycycline if fever and tick exposure are present, as mortality increases dramatically with treatment delay. 5

Common Pitfalls to Avoid

• Never attribute new neurological or burning symptoms to psychiatric medications without first excluding serious medical conditions including neuropathy, erythromelalgia, or tick-borne infections 4
• Do not assume normal CMP two weeks ago excludes current pathology, as erythromelalgia and gout are not detected by routine metabolic panels 1, 2
• Do not overlook myeloproliferative disorders in adults with new-onset erythromelalgia, as the blood disorder may not manifest for years after symptom onset 1, 2
• Avoid assuming all targetoid or erythematous lesions are benign, as Rocky Mountain spotted fever requires immediate treatment 5

Follow-Up Strategy

• If CBC reveals thrombocytosis or polycythemia, refer to hematology for bone marrow evaluation and treatment of underlying myeloproliferative disorder 2
• If aspirin trial is effective, continue therapy and monitor CBC every 3-6 months 1, 2
• If symptoms persist despite aspirin, consider MRI to evaluate for diabetic myonecrosis (if diabetic) or other inflammatory myopathies 6
• Definitive crystal analysis via joint aspiration should be pursued if gout remains in differential 3