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).
Keep reading — start your free trial
You've read your 2 free diagnosis previews. Create your free account to unlock the full Erythema Nodosum outline — plus all 514 diagnoses, 5,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
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 |
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)
Practice Dermatology questions on FirstPassPA
Turn this outline into retention. 5,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
Start studying free → Browse all 514 diagnosesEducational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.