Dermatology · PANCE / PANRE

Erythema Nodosum

Septal panniculitis presenting as tender erythematous nodules on the anterior shins.

Also known as: EN, septal panniculitis, erythema contusiforme

Overview

Acute, self-limited septal panniculitis characterized by symmetric, tender, erythematous, ill-defined subcutaneous nodules typically on the anterior shins. It represents a hypersensitivity reaction to a wide range of antigenic triggers rather than a primary skin disease.

Epidemiology

Most common form of panniculitis. Peak incidence 20-40 years; female predominance 3-5:1. Up to 50% of cases are idiopathic. Geographic variation reflects underlying infectious triggers (e.g., coccidioidomycosis in the southwestern US, tuberculosis worldwide).

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Risk factors

Infections: streptococcal pharyngitis (most common identifiable cause in children and adults), tuberculosis, coccidioidomycosis, histoplasmosis, Yersinia, Salmonella, Mycoplasma, HIV, hepatitis B/C, EBV
Sarcoidosis (Löfgren syndrome triad: EN, bilateral hilar lymphadenopathy, arthralgias/fever)
Inflammatory bowel disease (Crohn > ulcerative colitis)
Drugs: oral contraceptives, sulfonamides, penicillins, bromides, iodides
Pregnancy
Behçet disease, lymphoma/leukemia (rarely)

Pathophysiology

A delayed-type hypersensitivity reaction to circulating antigens leads to immune complex deposition and neutrophilic inflammation within the connective tissue septa of subcutaneous fat. The septa widen and become infiltrated, while fat lobules remain relatively spared — the defining feature of septal panniculitis. Miescher radial granulomas (small histiocytic aggregates around central clefts) are characteristic on biopsy.

Clinical presentation

Symptoms

Sudden eruption of painful, tender, warm, erythematous nodules — typically over 1-2 weeks
Symmetric distribution on anterior shins, occasionally extending to thighs, forearms, or trunk
Prodromal or accompanying constitutional symptoms: low-grade fever, malaise, arthralgias
Lesions evolve through bruise-like color changes ('erythema contusiforme') over weeks and resolve without scarring

Signs / physical exam

1-5 cm poorly demarcated, deep, tender erythematous nodules
No ulceration (an important negative)
Joint tenderness or effusion (especially ankles) — common with Löfgren syndrome
Lymphadenopathy or hepatosplenomegaly if infectious or sarcoid trigger

Classic findings

Tender bilateral shin nodules in a young woman after streptococcal pharyngitis or sarcoidosis.

Differential diagnosis

Erythema induratum (nodular vasculitis) — Lobular panniculitis with vasculitis; tender nodules on posterior calves; often ulcerate; classically tuberculin-associated
Cellulitis — Unilateral, warm, expanding erythema with systemic signs; not nodular; responds to antibiotics
Thrombophlebitis — Linear cord along a vein, palpable thrombosed vessel, often after IV access; Doppler diagnostic
Cutaneous polyarteritis nodosa — Painful subcutaneous nodules with livedo reticularis on lower extremities; medium-vessel vasculitis on biopsy
Subcutaneous fat necrosis (post-trauma) — Localized nodules at site of trauma; lobular panniculitis with foamy macrophages
Lupus panniculitis — Indurated plaques, often on proximal limbs or face; lobular panniculitis with lymphocytic infiltrate

Diagnostic workup

Diagnostic criteria

Diagnosis is clinical when classic tender shin nodules accompany a recognized trigger. Deep incisional or excisional biopsy (punch biopsies often inadequate) showing septal panniculitis without vasculitis confirms the diagnosis when atypical features are present.

Labs

CBC, ESR, CRP (often markedly elevated)
ASO titer and throat culture for group A streptococcus
PPD or interferon-gamma release assay (IGRA) for tuberculosis
Hepatitis B and C, HIV serology
Stool studies for Yersinia / Salmonella in patients with GI symptoms
Pregnancy test in reproductive-age women
Medication review for hormonal contraceptives, sulfas, etc.

Imaging

Chest x-ray — essential to screen for sarcoidosis (bilateral hilar adenopathy of Löfgren syndrome) and pulmonary tuberculosis or coccidioidomycosis
Further imaging (chest CT, abdominal imaging) driven by clinical findings

Diagnostic algorithm

Trigger Category	Examples	Clue / Screen
Infection	Group A strep, TB, coccidioides, Yersinia, EBV, HIV	Throat culture, ASO, PPD/IGRA, geography-guided serologies
Sarcoidosis (Löfgren)	EN + hilar adenopathy + ankle arthritis	Chest x-ray, ACE level, serum calcium
IBD	Crohn disease > UC	GI symptoms, CRP/fecal calprotectin, colonoscopy
Drugs	OCPs, sulfonamides, penicillins, bromides, iodides	Temporal medication review
Pregnancy	Often resolves postpartum	β-hCG
Malignancy	Lymphoma, leukemia (rare)	CBC with smear; further workup if atypical
Idiopathic	~50% of cases	Diagnosis of exclusion

Common triggers of erythema nodosum and their initial screening tests.

Treatment

First-line

Identify and treat the underlying trigger (e.g., antibiotics for streptococcal infection, treatment of TB or sarcoidosis, stopping offending drug)
NSAIDs (naproxen, ibuprofen, indomethacin) for pain and inflammation — mainstay of symptomatic therapy
Bed rest, leg elevation, compression stockings
Avoid potential triggers (e.g., switch hormonal contraception if temporally associated)

Second-line / adjunct

Potassium iodide (SSKI) 300-900 mg/day for persistent or severe disease — avoid in pregnancy and thyroid disease
Colchicine 0.6 mg twice daily, particularly for Behçet-associated EN
Systemic corticosteroids (prednisone) for severe, debilitating, or recurrent disease only after excluding infection
Hydroxychloroquine, dapsone, or TNF inhibitors for chronic/recurrent idiopathic EN refractory to other therapy

Complications

Recurrence in 5-15% of patients
Chronic dull post-inflammatory hyperpigmentation
Rarely, persistence beyond 6 months ('chronic EN' or EN migrans) requires re-evaluation for occult disease
Complications of the underlying condition (TB, sarcoidosis, IBD) drive prognosis more than the panniculitis itself

PANCE pearls

Always obtain a chest x-ray — sarcoidosis (especially Löfgren syndrome: EN + bilateral hilar adenopathy + ankle arthritis + fever) carries an excellent prognosis and resolves spontaneously.
Streptococcal infection is the most common identifiable trigger in many populations; check ASO titer.
Lesions never ulcerate — ulceration should prompt reconsideration of the diagnosis (erythema induratum, vasculitis, infection).
Punch biopsies often miss the panniculus; deep incisional biopsy through fat is needed if histology is required.
Septal panniculitis without vasculitis is the histologic signature; lobular panniculitis points to other diagnoses.
Symptomatic therapy with NSAIDs and rest is sufficient for most patients; lesions resolve over 3-8 weeks without scarring.

References

BAD/AAD reviews — Schwartz RA, Nervi SJ. Erythema nodosum: a sign of systemic disease (Am Fam Physician 2007; updated reviews)
Löfgren original description — Löfgren S. Primary pulmonary sarcoidosis: clinical course and prognosis (Acta Med Scand 1953)
Mert et al. — Erythema nodosum: an evaluation of 100 cases (Clin Exp Rheumatol 2007)

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