Key Facts

Erythema nodosum (EN) is a reactive condition that often signals an underlying disease. The evaluation should focus on identifying the trigger, as EN itself is self-limiting and benign.

Epidemiology

• Most common in young women aged 20–40
• F:M ~5:1
• Annual incidence: ~1–5 per 100,000

Aetiology

• Idiopathic: ~50% of cases
• Infections: streptococcal pharyngitis (most common infective cause), TB, Yersinia, Mycoplasma, Chlamydia, fungal (histoplasmosis, coccidioidomycosis)
• Sarcoidosis: important cause in UK — EN may be presenting feature
• Drugs: OCP, sulfonamides, penicillins
• IBD: Crohn's disease (more than UC)
• Pregnancy
• Behçet's disease: EN-like lesions (pathergy positive)
• Malignancy: lymphoma (rare)

Pathophysiology

• Septal panniculitis: inflammation centred on septa between fat lobules
• Type IV (delayed) hypersensitivity reaction to various antigenic triggers
• Immune complex deposition in septal venules → neutrophilic and granulomatous inflammation
• No vasculitis (distinguishes from polyarteritis nodosa)

Typical Presentation

• Tender, warm, erythematous nodules (1–5 cm) on anterior shins
• Bilateral and symmetrical
• Painful — may be difficult to walk
• Evolve like bruises: bright red → violaceous → brown/yellow ('bruise-like' resolution) — called 'erythema contusiformis'
• Do NOT ulcerate or suppurate
• May occur on thighs, forearms (less commonly)

Associated Features

• Malaise, fever, arthralgia (especially ankles)
• Features of underlying cause (e.g. pharyngitis, respiratory symptoms, GI symptoms)

Löfgren Syndrome (Acute Sarcoidosis)

• Erythema nodosum + bilateral hilar lymphadenopathy (CXR) + polyarthralgia ± fever
• Excellent prognosis — >90% spontaneous resolution

Red Flags

• Persistent/recurrent EN — investigate for underlying cause (sarcoidosis, TB, IBD)
• Ulceration — reconsider diagnosis (PAN, vasculitis)
• Weight loss, lymphadenopathy — exclude malignancy
• Cough, night sweats — TB

Bedside

• Clinical diagnosis: typical presentation often requires no biopsy

Bloods

• CRP/ESR: elevated during acute phase
• FBC: leucocytosis if infective cause
• ASOT (anti-streptolysin O titre): streptococcal trigger
• ACE level: sarcoidosis (elevated in ~60%)
• Calcium: hypercalcaemia in sarcoidosis
• CRP, LFTs: systemic inflammation
• Stool MC&S: if GI symptoms (Yersinia, IBD)

Imaging

• CXR: ALL cases — bilateral hilar lymphadenopathy (sarcoidosis, lymphoma), TB

Biopsy

• Deep incisional or punch biopsy (must include subcutaneous fat): only if diagnosis uncertain or nodules ulcerate
• Histology: septal panniculitis with neutrophilic infiltrate early, granulomatous later; Miescher's radial granulomas

Special Tests

• IGRA or Mantoux: TB screen if CXR abnormal or risk factors
• Throat swab: if preceding pharyngitis
• Pregnancy test: in women of childbearing age

Non-Pharmacological

• Bed rest and leg elevation: reduce pain and swelling; most effective measure
• Compression stockings: supportive
• Address underlying cause: treat streptococcal infection, stop OCP, manage IBD

Pharmacological

• NSAIDs: ibuprofen 400 mg TDS or naproxen 500 mg BD — first-line symptomatic treatment
• Potassium iodide 300–600 mg TDS: second-line — effective but limited availability and GI side effects
• Oral prednisolone 0.5 mg/kg for 1–2 weeks: for severe or refractory EN (only after excluding infection, especially TB)
• Colchicine 500 mcg BD: alternative for recurrent EN

Referral Criteria

• Dermatology: if diagnosis uncertain or recurrent
• Respiratory: if CXR shows hilar lymphadenopathy (sarcoidosis)
• Gastroenterology: if IBD suspected
• Infectious diseases: if TB suspected

• Self-limiting: resolves over 3–6 weeks without scarring
• Recurrence: ~15–30% (usually if underlying cause not addressed)
• Löfgren syndrome: excellent prognosis — >90% spontaneous resolution
• Chronic EN: rare; may occur with persistent underlying disease (sarcoidosis, IBD)
• No malignant potential
• Post-inflammatory hyperpigmentation at nodule sites may persist for months

Causes of Erythema Nodosum — Mnemonic 'SORE SHINS'

Panniculitis Classification