Initial assessment
In a patient with suspected erythema nodosum, the approach should begin by confirming the presence of erythematous nodules. When present, it is essential to obtain a complete clinical history, including lesion characteristics, temporal evolution and the presence of other associated signs or symptoms. Erythema nodosum is more common in women, with an approximate female-to-male ratio of three to five to one, particularly in the second and third decades of life, although it may occur at any age. In most typical cases, the diagnosis is essentially clinical, with incisional or excisional biopsy reserved for atypical presentations or situations of diagnostic uncertainty.
Clinical features of erythema nodosum
The typical clinical picture is characterised by painful erythematous nodules, usually bilateral and symmetrical, preferentially located in the pretibial region, although the heels, thighs or forearms may also be involved. It is usually a self-limiting condition, lasting between one and six weeks, with lesion resolution resembling that of a bruise. Healing occurs without ulceration, scarring or skin atrophy. Lesions at different stages of evolution may coexist, and recurrences are relatively frequent. Erythema nodosum is often associated with systemic symptoms, such as fever, malaise, headache, abdominal pain, diarrhoea, vomiting, cough, lymphadenopathy, weight loss and arthralgia.
Assessment for secondary aetiology
Once a compatible clinical picture has been confirmed, investigation for a possible secondary aetiology should be undertaken. The first step is to determine whether the patient is taking medication, has undergone radiotherapy or has recently received vaccines, as these exposures may trigger erythema nodosum. Among the drugs most frequently implicated are beta-lactam antibiotics, cephalosporins, sulfonamides, oral contraceptives, gold salts and others. Associated vaccines include tetanus, BCG, hepatitis B, human papillomavirus and typhoid fever. Whenever clinically safe, the suspected agent should be discontinued and the patient reassessed.
Targeted clinical investigation
In the absence of a drug- or vaccine-related cause, the presence of signs or symptoms suggestive of underlying disease should be assessed. Although erythema nodosum is frequently idiopathic, it is essential to exclude secondary causes, particularly streptococcal infections, tuberculosis, sarcoidosis, Behçet disease, inflammatory bowel disease and malignancies. A targeted laboratory and imaging work-up should be performed according to clinical suspicion, including full blood count, inflammatory markers, microbiological studies and appropriate imaging.
Main aetiologies to consider
Streptococcal infection should be considered when there is a recent history of pharyngitis, with lesions appearing two to three weeks after the infectious episode. Tuberculosis should be considered in the presence of prolonged fever, night sweats, weight loss, persistent cough or close contact with known cases, with immunological tests, sputum examination and chest radiography indicated. Sarcoidosis should be suspected in the presence of respiratory symptoms, fatigue, arthralgia and weight loss, and chest radiography should be performed. Behçet disease should be considered when recurrent oral and genital ulcers, uveitis or a positive pathergy test coexist. Inflammatory bowel disease may be suspected in the presence of recurrent diarrhoea and abdominal pain, and stool tests and colonoscopy may be required. When malignancy is suspected, investigation should be guided by the clinical signs present. In women of childbearing potential, pregnancy should always be excluded.
Initial therapeutic approach
When a secondary cause is identified, treatment should be directed at the underlying disease. In the absence of an identifiable aetiology, a diagnosis of idiopathic erythema nodosum is considered. In most cases, treatment is symptomatic, including elevation of the lower limbs and use of compression bandages to relieve pain and oedema. Non-steroidal anti-inflammatory drugs, such as indometacin or naproxen, are effective for pain control, but should be avoided in the context of active inflammatory bowel disease.
Treatment in persistent or specific cases
If lesions persist, potassium iodide may be considered, at doses between three hundred and nine hundred milligrams per day, with gradual reduction. This drug is contraindicated during pregnancy and breastfeeding and should be used with caution in patients with thyroid dysfunction. In patients with erythema nodosum associated with Behçet disease, colchicine is an effective therapeutic option.
Corticosteroid therapy and options in recurrent cases
Systemic or intralesional corticosteroids are rarely used and may be considered only in severe lesions and after rigorous exclusion of active infection or malignancy. In recurrent or refractory situations, other therapeutic options include hydroxychloroquine, minocycline, tumour necrosis factor-alpha inhibitors, thalidomide, ciclosporin and dapsone, usually in a specialist setting.
Follow-up
In persistent or recurrent cases, it is essential to reassess the diagnosis and reconsider biopsy, ensuring a continuous and integrated approach to the patient with erythema nodosum.
