1.1.4.1 Erythema Nodosum

Grading & Level of Importance: B

Review:

2026

W. Burgdorf, Munich; A. Salam, J. McGrath, London

Revised by V. del Marmol, Brussels; P. Ortiz-Romero, Madrid; J. White, Brussels

Overview:

ICD-11
Synonyms
Epidemiology
Definition
Aetiology & Pathogenesis
Pathogenesis
Signs & Symptoms
Localisation
Classification
Laboratory & other workups
Dermatopathology
Course
Complications
Diagnosis
Differential Diagnosis
Prevention & Therapy
Special

ICD-11

EB31

Synonyms

Subacute nodular migratory panniculitis.

Epidemiology

2.4/1000 population/year, mostly Spring/Autumn (due to streptococcal infections). F:M = 3-6 : 1. Especially children and adults (20 - 40 years).

Definition

Tissue-reaction pattern with many causes, characterised by painful subcutaneous nodules on the shins, most commonly in women.

Aetiology & Pathogenesis

Specific common causes include:

Streptococcal infections
Hepatitis B
Sarcoidosis
Bowel infections (e.g. Yersinia)
Medications (e.g. penicillins, sulphonamides, oral contraceptives)
Crohn’s disease
Tuberculosis
Other causes such as cat scratch disease and ornithosis.

Pathogenesis

Not well-known. Erythema Nodosum (EN) has been considered a delayed hypersensitivity response to a variety of antigenic stimuli. 30-50% of cases remain idiopathic.

Common causes:

Streptococcal infections
Viral upper respiratory tract infections
Sarcoidosis
Bowel infections (e.g. Yersinia)
Medications (e.g., penicillins, sulphonamides, oral contraceptives)
Crohn’s disease
Tuberculosis
others like, cat scratch disease, ornithosis

Numerous other causes should be considered.

from Daniela Michelle Perez-Garza et al. Erythema Nodosum: A Practical Approach and Diagnostic Algorithm. American Journal of Clinical Dermatology (2021) 22:367–378

Signs & Symptoms

Often prodrome with malaise, fever, joint pain. Then tender, poorly defined subcutaneous erythematous nodules appear, which are warm to the touch. Over time, colour changes from bright red to dark red to yellow-brownish and finally light grey.

There is often a prodrome with malaise, fever, joint pain. Then tender, poorly defined subcutaneous erythematous nodules appear (usually bilateral and symmetric), which are warm to the touch. Over time, the colour changes from bright red to dark red to contusiform (bruise-like) to yellow-brownish and finally light grey.

Localisation

Shins (occasionally thighs, buttocks or arms).

Shins are the most commonly affected area but occasionally the thighs may be affected and rarely buttocks or arms.

Classification

None.

According to cause.

Laboratory & other workups

Blood tests with several serologic markers (rheumatism, streptococci, tuberculosis, yersiniosis, angioconverting enzyme, pancreatic enzymes, antinuclear antibodies), stool culture and radiographic studies may be considered to exclude some of the known causes. Investigation is dictated by the patient’s history and examination findings.

Dermatopathology

Early phase: inflammatory infiltrate of neutrophils in the subcutaneous fat septae, oedema, macrophages and foam cells.

Later phase: granulomatous reaction and finally fibrous septae with scarring of fat tissue. It is in general a septal panniculitis.

The timing of any biopsy should be carefully planned (i.e., not too soon after the appearance of the lesions and not too late afterwards). Erythema nodosum is the prototypic of predominantly septal panniculitis. Characteristically, in the early phase, there is an inflammatory infiltrate of neutrophils in the subcutaneous fat septae, edema, macrophages and foam cells. In the later phase granulomatous reaction and finally fibrous septae and scarring of fat tissue occurs. It is in general a septal panniculitis. Miescher’s granulomas can be present. They are highly characteristic, if not pathognomonic and consist and small collections of macrophages surrounding cleft-like spaces.

Course

EN usually heals spontaneously without scarring within 3-6 weeks, however, after longstanding or relapsing lesions, there may be scarring.

The condition usually heals spontaneously without scarring, however, the eruption may sometimes be longstanding, migrating and/or relapsing. Rarely it may be recurrent depending on the pathogenetic cause. The process usually lasts 3 - 6 weeks.

Complications

Depends on the underlying cause. There are longstanding and migrating subtypes of EN.

Diagnosis

Clinical feature. Occasionally biopsy may be required. A careful search for the underlying disease is needed. Despite investigations, in 25-50% of cases no cause is identified.

Clinical features are usually diagnostic, but as clinical appearance can be undistinguishable from other panniculitis or even panniculitic-like lymphomas, biopsy is mandatory at least in the first flare of lesions. A careful search for the underlying disease is needed. Despite investigations, in 25-50% of cases no cause is identified.

Differential Diagnosis

Erythema nodosum leprosum; erysipelas; urticaria.

Polyarteritis nodosa, nodular vasculitis, other forms of panniculitis e.g., trauma, cold.

Algorithm for clinical and laboratory approach to check diagnosis of erythema nodosum

Prevention & Therapy

Depends on underlying cause. The underlying disease(s) should be treated. Systemic NSAIDs may be helpful. If the clinical symptoms are severe, short-term systemic corticosteroids may be given. Supportive measures: bed rest, heparinoid creams, and compression stockings.

Treat underlying disease and consider the administration of systemic NSAIDs. If the clinical manifestations of erythema nodosum are severe, short-term systemic corticosteroids may be given. Potassium iodide is sometimes used for idiopathic and/or recurrent cases. Supportive measures such as bed rest, heparinoid creams and compression stockings may also be helpful.