Erythema Nodosum

This is presumed to be a hypersensitivity reaction. It is often a dermatological manifestation of infectious or other disease.

The prevalence is 24 cases per 100,000 per year. It can affect any age but is commonest between the ages of 18 and 35 with women affected 4 times as often as men.¹

The eruptive phase begins with fever, aching and arthralgia whilst a painful rash usually appears within a couple of days.
Lesions begin as red, tender nodules. The borders are poorly defined and they are 2 to 6 cms in diameter.

• Erythema nodosum is often indicative of an underlying infectious disease but a cause is not always found. Some underlying causes are not infectious.
• Streptococcal infection is the commonest underlying cause and so it may be a feature of other diseases including scarlet fever and rheumatic fever although in the UK nowadays the former is uncommon and the latter rare.
• Sarcoidosis is also commonly involved in adults although it is not infectious in origin.
• Tuberculosis must be considered.
• Leprosy can produce a clinical picture of erythema nodosum although the histological picture of the lesions is different.
• Various forms of gastroenteritis, especially Yersinia enterocolitica, Salmonella spp. and Campylobacter spp. can be associated.
• Mycoplasma pneumonia can be associated.
• Fungal infections are less common in the UK but coccidioidomycosis is important in the south-west USA. It may occur in histoplasmosis and blastoplasmosis.
• Sulphonamides are used less often nowadays but other drugs to be implicated include sulphonylureas, gold and oral contraceptives.
• It may correlate with flare up of Crohn's disease or ulcerative colitis.
• It can precede the diagnosis of Hodgkin's disease and non-Hodgkin's lymphoma by months and it can accompany Behçet's syndrome.
• It may occur in pregnancy when it is usually in the second trimester. It is likely to recur in future pregnancies and may occur with oral contraceptives.
• In many cases no cause is found.

Although in many cases it is idiopathic it is important to exclude serious underlying disease:

• A throat swab for streptococcus is the first test although it may well be negative, even with streptococcal disease.
• Anti-streptococcal O (ASO) titre may be more helpful although a normal titre does not exclude infection. A rising titre may be more valuable.
• Serum antideoxyribonuclease B (AntiDNAseB) antibodies and antihyaluronidase levels are more sensitive than ASO titre in cases of recent serious streptococcal skin infection.^4,5
• Arrange a full blood count (FBC), and ESR. ESR is often very high regardless of the aetiology, and C-reactive protein may be more contributory.
• Stool examination for Yersinia spp., Salmonella spp. and Campylobacter spp. may yield results as may blood cultures
• In sarcoidosis calcium is often raised.
• Chest x-ray may show bilateral hilar lymphadenopathy (BHL) in sarcoidosis, unilateral or asymmetrical adenopathy in malignancy, or evidence of pulmonary tuberculosis.
• Excisional biopsy may be helpful where the diagnosis is in doubt.

• Erysipelas
• Erythema induratum (Nodular Vasculitis)
• Insect bites
• Acute urticaria
• Familial Mediterranean fever
• Superficial migratory thrombophlebitis
• Thrombophlebitis

• If an infective aetiology has been discovered then appropriate therapy is in order but it should not be given blind.
• A degree of relief can be obtained with cool compresses and bed rest with elevation of the foot of the bed. Bed rest has been advocated for many years and is anecdotally useful, but the evidence base is lacking.
• NSAIDs are useful and no other drugs are usually needed.⁶ Steroids are beneficial but should be used with caution and may be contraindicated if infection has not been excluded.
• In difficult cases oral potassium iodide may be valuable as may tetracycline, and in erythema nodosum of leprosy thalidomide has seen a resurgence.^7,8

The condition usually resolves within 6 weeks but it may be more protracted especially if the underlying cause remains or when it is idiopathic. Serious complications are unusual unless part of the underlying disease. Chronic or recurrent disease is rare. Lesions heal without atrophy or scarring.²