Erythema Nodosum: A Practical Approach and Diagnostic Algorithm

Daniela Michelle Pérez-Garza; Sonia Chavez-Alvarez; Jorge Ocampo-Candiani; Minerva Gomez-Flores


Am J Clin Dermatol. 2021;22(3):367-378. 

In This Article

Diagnostic Assessment

Because of the extensive number of possible etiologic processes, the diagnostic approach must be cost effective to initiate a specific treatment. Not all patients may need an extensive work-up, this will allow a cost reduction. Investigations should be tailored to diseases suspected from a careful history and physical examination. Systemic symptoms or altered laboratory test results favor secondary EN;[5] however, in symptomatic patients without a disease-specific clinical finding, a complete work-up must be performed to rule out a severe disease. This examination can lead to early diagnosis and prompt treatment, thus preventing the progression of a serious or life-threatening illness.

Diagnosis of EN is based on clinical presentation and histopathological findings. To identify the underlying cause, the initial work-up must contain a detailed medical history and physical examination. Paraclinical studies including a laboratory work-up and radiologic imaging studies might be necessary. We propose a diagnostic algorithm (Figure 3) to assist clinicians in making an accurate and timely diagnosis to initiate appropriate treatment for the underlying condition.

Figure 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

The initial diagnostic work-up should be aimed at identifying common etiologies. Interrogation for disease-specific and non-specific symptoms, such as fever, fatigue, malaise, weight loss, organ-specific symptoms, and any recently used drugs, is necessary. Laboratory tests and imaging must be guided by the clinical findings, the choice of testing should be based on the history and physical examination. However, the etiology may vary depending on other factors such as the race and geographic location of the patient (Table 2), these factors also determine the laboratory tests and imaging studies that must be requested. Based on what has been published in the literature and taking into account the most frequently reported etiological factors of EN (Table 2), we propose a practical diagnostic algorithm.[4–6,19,22,38,39,45,64–66] We suggest that an initial laboratory work-up should include a complete blood count, erythrocyte sedimentation rate, C-reactive protein, antistreptolysin O titer, throat swab culture, and chest radiography. A pregnancy test must be done in all women of child-bearing age. A sputum acid-fast bacilli smear, mycobacterial culture, and tuberculin skin test or interferon-γ release assay must be performed in the TB endemic regions and with abnormal chest x-rays. If diarrhea, abdominal pain, or other gastrointestinal discomfort is present, a stool examination, culture, and coproparasitoscopic stool study must be performed. Mert et al. reported that leukocytosis, an elevated C-reactive protein level, an accelerated erythrocyte sedimentation rate, the presence of prolonged fever, cough, sore throat, diarrhea, arthritis, non-relapsing EN, and an abnormal chest x-ray were predictors of secondary EN, while recurrent EN predicted primary EN.[5,19]

If the initial work-up is inconclusive, further laboratory testing and imaging studies should be performed. No test abnormalities specific to EN have been described. Unfortunately, in most cases, no specific etiology can be found; therefore, these patients are considered as idiopathic or primary EN.