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.

Fig. 1

Clinical features of erythema nodosum (EN). a Erythematous tender nodules bilaterally on the shins. b Bruise-like appearance “erythema contusiformis”

Fig. 2

Erythema nodosum (EN) histopathological features. Hematoxylin and eosin staining. a A predominantly septal panniculitis, at × 5 magnification. b Lymphohistiocytic infiltrate with the presence of neutrophils and giant multinucleated cells at × 100 magnification

Fig. 3

Approach to the diagnosis of patients with erythema nodosum. ASO antistreptococcal O titers, GAS group A streptococci, ICBD International Criteria for Behçet’s Disease, ISG International Study Group, RADT rapid antigen detection tests, TB tuberculosis