Erythema Nodosum

Erythema nodosum (EN) is an inflammatory condition characterised by inflammation of subcutaneous fat tissue, resulting in painful red/blue lumps or nodules. These nodules typically appear symmetrically on both shins, thighs, arms, and occasionally elsewhere. In young people aged 12–20 years, it is relatively common and often resolves spontaneously within 30 days. While a variety of conditions can cause it, 20 to 50% of cases remain idiopathic.

Overview

Signs and Symptoms

Pre-eruptive Phase

Initial signs often include flu-like symptoms such as fever, cough, malaise, and aching joints. Some individuals may experience stiffness or swelling in the joints and weight loss.

Eruptive Phase

EN is characterised by 1–2-inch (25–51 mm) nodules under the skin surface, predominantly on the shins but also on the arms, thighs, and torso. These nodules usually disappear after about two weeks, though new ones can form for up to six or eight weeks. Initially red, hot, and firm to the touch, the nodules gradually become softer and smaller until they disappear, generally healing without scarring. Joint pain and inflammation may continue for several weeks or months after the nodules appear.

Variants of EN include:

• Ulcerating forms, seen in Crohn's disease
• Erythema contusiforme, where subcutaneous haemorrhage makes the lesion resemble a bruise
• Erythema nodosum migrans, a chronic form with asymmetrical, mildly tender, migrating nodules.

Causes

EN can be associated with various conditions:

Idiopathic

About 30–50% of cases have no identifiable cause.

Infection

Infections linked to EN include:

• Streptococcal infection (most common in children)
• Tuberculosis, leprosy, and other mycobacterial infections
• Mycoplasma pneumoniae, Histoplasma capsulatum, Yersinia, and others
• Epstein-Barr virus, Valley fever, and cat scratch disease

Autoimmune and Immune-mediated Diseases

Conditions like Behçet's disease, Crohn's disease, and sarcoidosis are associated with EN.

Pregnancy

EN can sometimes be associated with pregnancy.

Medications

Medications such as omeprazole, sulfonamides, oral contraceptives, penicillins, bromides, and hepatitis B vaccination can trigger EN.

Cancer

Cancers such as non-Hodgkin's lymphoma, carcinoid tumours, and pancreatic cancer can be associated with EN.

Pathophysiology

EN is likely a delayed hypersensitivity reaction to various antigens. While circulating immune complexes are seen in inflammatory bowel disease patients, they are not found in idiopathic or uncomplicated cases.

Diagnosis

EN is primarily diagnosed clinically. Biopsy and microscopic examination can confirm uncertain cases, revealing a neutrophilic infiltrate around capillaries and fibrotic changes in the fat. Additional evaluations include full blood count (FBC), erythrocyte sedimentation rate (ESR), antistreptolysin-O (ASO) titer, throat culture, urinalysis, tuberculin test, and chest x-ray. Typically, ESR and white blood cells are elevated.

Treatment

EN is self-limiting, usually resolving within 3–6 weeks. Treatment focuses on addressing the underlying cause. Symptomatic treatments include bed rest, leg elevation, compressive bandages, wet dressings, and nonsteroidal anti-inflammatory agents (NSAIDs). Persistent lesions may be treated with potassium iodide, while severe cases may require corticosteroids or colchicine. Thalidomide and clofazimine have shown benefits in treating erythema nodosum leprosum.

Epidemiology

EN is the most common form of panniculitis, predominantly affecting individuals aged 20–30 years and women more frequently than men.

Eponym

The term "Subacute Migratory Panniculitis of Vilanova and Piñol" is named after Catalan dermatologists Xavier Montiu Vilanova and Joaquin Aguade Piñol, who described the disease in the mid-20th century.

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Self-assessment MCQs (single best answer)

What is the most common age range for erythema nodosum (EN)?

Which of the following infections is most commonly associated with erythema nodosum in children?

Which medication is NOT typically associated with causing erythema nodosum?

What type of hypersensitivity reaction is erythema nodosum thought to be?

In the pre-eruptive phase of erythema nodosum, which symptom is NOT commonly observed?

Which of the following is a variant of erythema nodosum characterised by subcutaneous haemorrhage?

What is the typical duration for erythema nodosum to resolve spontaneously?

Which diagnostic test is NOT typically used in the evaluation of erythema nodosum?

Which treatment is NOT commonly used for symptomatic relief of erythema nodosum?

What is the term "Subacute Migratory Panniculitis of Vilanova and Piñol" associated with?