What is the diagnosis and management for a patient with a 2-year history of intermittent red painful nodules over the body?

Diagnosis and Management of Intermittent Red Painful Nodules Over the Body

The most likely diagnosis is erythema nodosum, which presents as bilateral, symmetrical, tender erythematous nodules predominantly on the anterior tibial areas, and requires identification of the underlying trigger through targeted workup followed by symptomatic management with NSAIDs and treatment of any identified cause. 1

Clinical Diagnosis

Erythema nodosum is the most common form of panniculitis and presents with characteristic features that distinguish it from other causes of subcutaneous nodules:

• Lesion characteristics: Painful, rounded or oval, erythematous, slightly raised nodules ranging from 1-5 cm in diameter 1
• Distribution: Bilateral and symmetrical lesions located predominantly on the anterior surface of the lower extremities (pretibial areas) 2, 1
• Key distinguishing feature: Nodules do NOT migrate to different locations, unlike gnathostomiasis which shows characteristic migration over days to weeks 3
• Associated symptoms: Often preceded by 1-3 weeks of prodromal symptoms including low-grade fever (60% of cases), malaise (67%), arthralgias (64%), and arthritis (31%) 2, 4

Critical Differential Diagnoses to Exclude

Before confirming erythema nodosum, you must exclude conditions that can mimic this presentation:

• Gnathostomiasis: Presents with migratory subcutaneous nodules that move to different body locations over time, requires travel history to endemic areas (Southeast Asia), and is treated with ivermectin or albendazole 3
• Rosai-Dorfman-Destombes disease (cutaneous RDD): Presents with slow-growing, painless, nonpruritic nodules with coloration varying from yellow to red to brown, typically requires biopsy showing S100-positive histiocytes with emperipolesis 5
• Cutaneous manifestations of systemic histiocytosis: Consider if nodules are painless or have atypical distribution 5

Diagnostic Workup

The diagnosis is primarily clinical, but targeted laboratory evaluation is essential to identify underlying causes:

Initial Screening Tests (Recommended for All Patients)

• Complete blood count with differential 1
• Erythrocyte sedimentation rate and/or C-reactive protein 1
• Throat swab culture and antistreptococcal O titers (streptococcal infection is a common trigger) 1
• Chest radiograph (to evaluate for sarcoidosis, tuberculosis, or malignancy) 1

Additional Testing Based on Clinical Context

• If travel history to endemic areas: Consider serology for gnathostomiasis (Swiss Tropical and Public Health Institute), check for eosinophilia 3
• If systemic symptoms or atypical presentation: Consider biopsy showing septal panniculitis without vasculitis (characteristic of erythema nodosum) 4
• If pregnancy or recent postpartum: Pregnancy itself can be a trigger for erythema nodosum 6
• Individualized testing guided by history: tuberculin skin test, stool studies for inflammatory bowel disease, medication review, autoimmune serologies 1, 4

Common Underlying Causes to Investigate

Approximately 50% of erythema nodosum cases are idiopathic, but you must systematically evaluate for identifiable triggers: 2, 1

• Infections: Streptococcal pharyngitis (most common), tuberculosis, fungal infections 1
• Medications: Oral contraceptives, sulfonamides, halides 2
• Systemic diseases: Sarcoidosis, inflammatory bowel disease (Crohn's disease, ulcerative colitis) 1, 4
• Pregnancy and postpartum period 6
• Malignancy: Maintain oncological vigilance as erythema nodosum may be a paraneoplastic symptom 7

Management Approach

Most cases of erythema nodosum are self-limited and resolve without specific treatment, but symptomatic management improves quality of life:

First-Line Symptomatic Treatment

• Bed rest and leg elevation to reduce discomfort 1
• NSAIDs (nonsteroidal anti-inflammatory drugs) are the first-line pharmacologic treatment for pain management 2, 1

Treatment of Underlying Cause

• Treat any identified underlying condition (e.g., antibiotics for streptococcal infection, discontinue offending medications) 1, 4
• Avoid systemic corticosteroids in idiopathic cases despite their effectiveness, due to the benign nature of erythema nodosum and the risk of disseminating an undiagnosed underlying infection 2
• Consider short-course low-dose corticosteroids only in severe, refractory cases after excluding infectious causes (e.g., prednisone 15 mg/day for 6 days) 6

Important Clinical Pitfalls

• Do not assume idiopathic disease without appropriate workup: A thorough search for underlying causes is essential, as identifying and treating the trigger improves outcomes 7, 1
• Do not use corticosteroids empirically: This can disseminate underlying infections, particularly tuberculosis 2
• Do not confuse with migratory nodules: The fixed, bilateral, symmetrical distribution on anterior tibial areas distinguishes erythema nodosum from gnathostomiasis 3, 1
• Maintain oncological vigilance: Erythema nodosum can be a paraneoplastic manifestation requiring evaluation for underlying malignancy 7

Prognosis

Erythema nodosum typically resolves spontaneously within 3-6 weeks without scarring, even without specific therapy for the causative condition. 4