Erythema Nodosum: A Practical Approach and Diagnostic Algorithm

Abstract

Erythema nodosum is the most common form of panniculitis and is characterized by tender erythematous nodules mainly in the lower limbs on the pretibial area. The exact cause of erythema nodosum is unknown, although it appears to be a hypersensitivity response to a variety of antigenic stimuli. Although the etiology is mostly idiopathic, ruling out an underlying disease is imperative before diagnosing primary erythema nodosum. Erythema nodosum can be the first sign of a systemic disease that is triggered by a large group of processes, such as infections, inflammatory diseases, neoplasia, and/or drugs. The most common identifiable causes are streptococcal infections, primary tuberculosis, sarcoidosis, Behçet disease, inflammatory bowel disease, drugs, and pregnancy. We propose a diagnostic algorithm to optimize the initial work-up, hence initiating prompt and accurate management of the underlying disease. The algorithm includes an initial assessment of core symptoms, diagnostic work-up, differential diagnosis, and recommended therapies. Several treatment options for the erythema nodosum lesions have been previously reported; nevertheless, these options treat the symptoms, but not the triggering cause. Making an accurate diagnosis will allow the physician to treat the underlying cause and determine an optimal therapeutic strategy.

Clinicopathological Characteristics Related to Etiologies of Erythema Nodosum: A 10-Year Retrospective Study

“…4 EN is considered a hypersensitivity response to various antigens from a wide range of precipitating factors such as infection, inflammation, neoplasm, and drugs. 1,3,5 Evidence of circulating immune complexes in early lesions supports the suggestion that the antigen, antibody, and complement play a significant role in the pathogenesis, and circulating immune complexes may contribute to tissue injury. However, some authors have reported a lack of circulating immune complexes in uncomplicated EN, and a type IV delayed hypersensitivity reaction has been proposed.…”

“…1 The incidence of EN is approximately one to five per 100,000 persons with a male-to-female ratio of 1:1 in children and 1:5 in adults. 2,3 Although EN can occur in any age group, it is most frequently found in the second to fourth decades of life. 4 EN is considered a hypersensitivity response to various antigens from a wide range of precipitating factors such as infection, inflammation, neoplasm, and drugs.…”

“…However, some authors have reported a lack of circulating immune complexes in uncomplicated EN, and a type IV delayed hypersensitivity reaction has been proposed. 3 EN can be classified according to the etiologies as primary or idiopathic EN and secondary EN when there is an identifiable cause. 6 EN has also been defined histopathologically according to the chronology of lesions as acute and chronic EN.…”

“…6,[9][10][11][12][13][14] Conditions related to secondary EN remain inconclusive and vary according to triggering factors in the study period, ethnic, racial, and geographic differences. 3,6,[9][10][11][12] Regarding the clinical course, both idiopathic and secondary EN can resolve spontaneously within approximately 3-6 weeks without scarring. 6,7 Few studies have shown that idiopathic EN tends to recur more frequently than secondary EN.…”

Leprosy suspect presenting at a chest clinic

“…However, erythema nodosum reaction may occur with streptococcus infection, tuberculosis, sarcoidosis, coccidioidomycosis, ulcerative colitis, Behçet disease, drug reactions and various malignancies, which in our case we found no evidence for. 10…”