Erythema Nodosum Workup

Updated: May 11, 2020
  • Author: Jeanette L Hebel, MD; Chief Editor: William D James, MD  more...
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Laboratory Studies

Perform throat culture as part of the initial workup to exclude group A beta-hemolytic streptococcal infection.

Perform erythrocyte sedimentation rates often as part of the initial workup. The rate often is very high.

Antistreptolysin titer is elevated in some patients with streptococcal disease, but normal values do not exclude streptococcal infection. Evaluate titer levels during the initial workup, since streptococcal disease is a common cause of erythema nodosum.

Order stool examination, since along with the appropriate history of gastrointestinal complaints, a stool examination can exclude infection by Yersinia, Salmonella, and Campylobacter organisms.

Order blood cultures according to preliminary indications and findings.


Imaging Studies

Order chest radiographs as part of the initial workup to exclude sarcoidosis and tuberculosis and to document hilar adenopathy.


Other Tests

Intradermal skin tests can be used to exclude tuberculosis and coccidioidomycosis.



Because the diagnosis of erythema nodosum often is clinical, biopsy is reserved for diagnostically difficult cases. Punch biopsies usually are not adequate. Deep skin incisional biopsies are required to sample the subcutaneous tissue adequately. Findings are localized to the subcutaneous tissue.


Histologic Findings

The classic features of erythema nodosum on histopathology include a septal panniculitis with slight superficial and deep perivascular inflammatory lymphocytic infiltrate. [19, 20] The septa of subcutaneous fat usually are thickened. Early-stage lesions demonstrate vascular damage in the septae with neutrophils and eosinophils similar to a leukocytoclastic vasculitis. [21] As lesions evolve, periseptal fibrosis, giant cells, and granulation tissue appear. Miescher granulomas are a hallmark feature of erythema nodosum. Small well-defined nodular aggregates of histiocytes around a central stellate cleft are scattered throughout the lesions. A lymphohistiocytic infiltrate is noted in the septum and in small and medium-sized vessels.