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Infectious Disease And Microbiology – Erythema Nodosum
Erythema nodosum is the most common form of panniculitis, characterized by inflammatory, tender nodules that typically appear on the lower extremities, especially the shins. It represents a reactive process rather than a primary infection and is often associated with a wide range of underlying conditions.
Epidemiologically, erythema nodosum most frequently affects individuals between 18 and 34 years of age and is more common in females. The annual incidence in hospitalized patients has been estimated at 52 cases per million people, with an overall prevalence of about 2.4 per 1,000 population per year. Seasonal clustering has been observed, particularly in cases associated with sarcoidosis, with peaks in late summer and early autumn.
Genetic predisposition has been suggested, especially in sarcoidosis-associated cases, where specific human leukocyte antigens such as HLA-B8 and HLA-DR3 have been implicated.
Pathophysiologically, erythema nodosum is considered a type IV delayed hypersensitivity reaction to various antigens. This immune-mediated process leads to inflammation of the subcutaneous fat, particularly affecting the septa between fat lobules.
The etiology is diverse and includes infectious and noninfectious causes. Among infectious triggers, streptococcal infections (especially group A beta-hemolytic streptococci) are the most common. Other bacterial causes include tuberculosis, brucellosis, and cat-scratch disease. Viral causes include cytomegalovirus, Epstein–Barr virus, HIV, hepatitis B, and herpes simplex virus. Fungal infections such as histoplasmosis and coccidioidomycosis, as well as protozoal infections like toxoplasmosis and amebiasis, have also been implicated.
Noninfectious causes include medications (e.g., sulfonamides and oral contraceptives), malignancies (such as lymphoma and leukemia), and systemic diseases including sarcoidosis, inflammatory bowel disease, Behçet’s disease, lupus erythematosus, and Sjögren’s syndrome. Pregnancy is another recognized trigger. In many cases, however, no cause is identified (idiopathic erythema nodosum).
Clinically, patients present with the sudden onset of painful, erythematous nodules, most commonly on the shins, ankles, and knees. These lesions may be accompanied by systemic symptoms such as fever, fatigue, and joint pain. The nodules evolve over time, changing from bright red to purplish and eventually yellow-green, resembling bruises. Importantly, they do not ulcerate and heal without scarring.
On physical examination, the nodules are tender and raised initially, later becoming flatter as they resolve. They are most commonly located on the anterior lower legs but may also appear on the arms, neck, or face in rare cases.
Diagnosis is largely clinical but supported by investigations aimed at identifying the underlying cause. Laboratory tests include complete blood count, inflammatory markers (ESR), antistreptolysin O titers, throat cultures, and PCR for streptococcal infection. Tuberculosis testing and urinalysis may also be performed. Imaging such as chest X-ray is useful, particularly to detect sarcoidosis (e.g., bilateral hilar lymphadenopathy) or tuberculosis.
Additional diagnostic procedures may include stool studies for gastrointestinal symptoms, skin biopsy (which shows characteristic “Miescher’s radial granulomas”), and further investigations such as colonoscopy or lung biopsy depending on suspected underlying disease.
The differential diagnosis includes other forms of panniculitis such as erythema induratum of Bazin, superficial thrombophlebitis, Lyme disease, and systemic lupus erythematosus.
Management is primarily supportive, as erythema nodosum is usually self-limiting and resolves within a few weeks. Treatment should focus on addressing the underlying cause when identified. Symptomatic relief can be achieved with nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin or naproxen. In more severe cases, corticosteroids (e.g., prednisone) may be used after excluding infections and malignancy. Other therapies, including potassium iodide, hydroxychloroquine, colchicine, or biologics like infliximab, may be considered in specific cases.
General supportive measures include bed rest, leg elevation, and compression therapy to reduce discomfort and inflammation.
The prognosis is generally excellent, with most cases resolving within 3–4 weeks. Recurrence is uncommon but may occur, particularly in idiopathic cases or those associated with recurrent infections.
Complications are rare but may include unusual manifestations such as optic neuritis during acute episodes.
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