Erythema Nodosum

How to Cite This Chapter: Adachi JD, Zimmermann-Górska I. Erythema Nodosum. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed July 18, 2024.
Last Updated: October 31, 2016
Last Reviewed: May 29, 2019
Chapter Information

Definition, Etiology, PathogenesisTop

Erythema nodosum refers to inflammatory nodular lesions in the subcutaneous tissue characterized histologically by septal inflammation. Immune complexes are thought to play a role in the pathogenesis.

Causes of erythema nodosum:

1) Infection: Streptococci, Mycobacterium tuberculosis, Mycobacterium leprae, Yersinia spp, Salmonella spp, Chlamydophila pneumoniae, Neisseria gonorrhoeae, viruses (cytomegalovirus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, HIV), fungi.

2) Drugs: Antibiotics (particularly penicillin), sulfonamides, pyrazole derivatives.

3) Diseases: Sarcoidosis (one of the most frequent causes), inflammatory bowel disease, Sweet syndrome (acute febrile neutrophilic dermatosis), systemic connective tissue diseases (systemic lupus erythematosus, polymyositis/dermatomyositis, systemic sclerosis, systemic vasculitis syndromes).

4) Pregnancy or oral contraceptives.

Clinical Features and Natural HistoryTop

Erythema nodosum occurs mainly in women (~90% of cases). The appearance of lesions is often accompanied by malaise, low-grade or high-grade fever, joint pain, arthritis, symptoms of upper respiratory tract infection, and gastrointestinal symptoms (abdominal pain, diarrhea). Nodules are most commonly located on the anterior lower leg (less frequently on the posterior lower leg), and less often on thighs, buttocks, shoulders, head, and trunk. The lesions are usually from 1 to 5 cm in diameter and may coalesce. Skin over the lesions is erythematous and warm but necrosis never occurs. The nodules are painful, persist for 2 to 9 weeks, and then resolve without scarring. Dark discoloration in the locations of the nodules usually persists for several weeks after they have resolved. Relapses occur in approximately half of the patients, most often in winter and spring.


Diagnostic Tests

1. Blood tests: With the appearance of the nodules, the tests reveal an elevated erythrocyte sedimentation rate (in 60%-85% of patients), leukocytosis with neutrophilia, and elevated serum immunoglobulin (a frequent feature) and aminotransferase levels.

2. Other studies are used depending on the cause. For instance, chest radiographs may reveal features typical for sarcoidosis.

Diagnostic Criteria

Diagnosis is based on clinical features. A skin biopsy is performed in exceptional cases, for instance, when the condition needs to be differentiated from idiopathic panniculitis (Weber-Christian disease).

Differential Diagnosis

Panniculitis, subcutaneous tissue changes directly caused by infection (most commonly staphylococcal), superficial vein thrombosis, cutaneous vasculitis (eg, urticarial vasculitis). Differential diagnosis also includes all the conditions that may cause erythema nodosum (see Definition, Etiology, Pathogenesis, above).


1. Treatment of the underlying condition.

2. Symptomatic treatment: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used if local or systemic symptoms are judged to require treatment; if these are ineffective, short-term glucocorticoids may be used cautiously (note: they may be harmful, eg, in patients with tuberculosis).

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