What is the likely diagnosis for a 38-year-old female with recurrent nodular swelling and pain at multiple sites on both lower limbs, elevated Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) levels, and no other symptoms?

Likely Diagnosis: Erythema Nodosum

You are most likely dealing with erythema nodosum (EN), which is the most common form of panniculitis presenting as recurrent tender nodules on the lower extremities without overlying skin changes. 1, 2

Clinical Features Supporting This Diagnosis

Your patient's presentation is classic for EN:

• Recurrent nodular swelling with pain at multiple sites on both lower limbs 1, 2
• Self-limited episodes lasting 1-2 days (EN nodules typically resolve spontaneously within weeks) 1
• Absence of redness (EN nodules evolve from bright red to livid/purplish to yellow-greenish, resembling deep bruises, but your patient may be presenting between episodes) 1
• Elevated inflammatory markers (ESR 50, CRP 20) are typical of EN 3, 4
• Female predominance (86% of EN cases are women) 3

Immediate Diagnostic Work-Up Required

Since only 32% of EN cases are idiopathic, you must systematically exclude secondary causes 3:

First-Line Investigations (Order These Now):

• Anti-streptolysin O (ASO) titers - post-streptococcal infection is the leading cause (32% of cases) 3
• Chest X-ray or CT scan - to exclude sarcoidosis (11% of cases) and primary tuberculosis (7% of cases) 3
• Tuberculin skin test (PPD) - primary TB is a significant cause 3
• Complete blood count - secondary EN shows higher leukocyte counts than idiopathic 3

Second-Line Investigations (If Above Negative):

• Mycoplasma serology (3% of cases) 3
• Bartonella serology (3% of cases) 3
• Inflammatory bowel disease screening if GI symptoms present (2% of cases) 3
• Medication review - drugs account for 1% of cases 3

Critical Red Flag: Rule Out Takayasu Arteritis

Given the elevated ESR (50) and recurrent nature, you must actively exclude Takayasu arteritis, as recurrent EN can be the presenting sign of hidden systemic vasculitis. 5

Specific Examination Required:

• Blood pressure in both arms - difference >10 mmHg suggests Takayasu 6
• Palpate all peripheral pulses - diminished brachial/radial pulses 6
• Auscultate for bruits - subclavian or aortic bruits 6
• Check for limb claudication symptoms 6

If Any Vascular Signs Present:

• Urgent vascular imaging (CT or MR angiography) of the aorta and great vessels 6
• Immediate rheumatology referral 6

The combination of recurrent EN with persistently elevated ESR (>40) warrants high suspicion for underlying vasculitis, even without obvious vascular symptoms 5.

Management Strategy

Symptomatic Treatment (Start Now):

• NSAIDs (indomethacin or naproxen) for pain relief 1
• Bed rest during acute episodes 1
• Potassium iodide may enhance resolution 1

Avoid Systemic Corticosteroids:

Do not start corticosteroids until infection is definitively ruled out, as infectious causes (streptococcal, TB, Mycoplasma, Bartonella) account for 45% of secondary EN cases 1, 3

Monitoring Inflammatory Markers

• CRP is superior to ESR for monitoring acute response due to its shorter half-life 4
• ESR is better for chronic inflammatory conditions like sarcoidosis or vasculitis if diagnosed 4
• Recheck ESR/CRP every 4-6 weeks if a chronic inflammatory condition is identified 7

Common Pitfall to Avoid

The absence of visible redness does NOT exclude EN - you may be examining between episodes when nodules have resolved, or the patient may be describing the tender nodules before they become visibly erythematous 1. The recurrent nature, bilateral lower limb distribution, self-limited course, and elevated inflammatory markers are diagnostic even without active lesions at examination.