What is the workup for Erythema Nodosum (EN)?

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From the Guidelines

The workup for erythema nodosum should begin with a thorough history and physical examination, focusing on identifying potential triggers, as the diagnosis is typically clinical and biopsy is rarely needed 1. The physical examination should include a total body skin examination with attention to examining all mucous membranes, as well as a complete review of systems to rule out any other etiology of the skin problem, such as an infection, an effect of another drug, or a skin condition linked to another systemic disease 1. Key aspects of the physical examination include:

  • Evaluating all skin surfaces and mucous membranes (eyes, nares, oropharynx, genitals, and perianal area) for signs of infection, inflammation, or other skin conditions
  • Assessing for lymphadenopathy, and facial or distal-extremity swelling, which may be signs of DIHS/DRESS
  • Checking for pustules or blisters or erosions in addition to areas of dusky erythema, which may feel painful to palpation Laboratory tests should include complete blood count, erythrocyte sedimentation rate, C-reactive protein, antistreptolysin O titer, and tuberculin skin test or interferon-gamma release assay to evaluate for potential underlying causes such as infection or inflammation 1. Additional tests may include throat culture, stool studies for enteric pathogens, and serology for fungal infections depending on clinical suspicion 1. Treatment focuses on addressing the underlying cause while providing symptomatic relief with NSAIDs like ibuprofen (400-800mg three times daily) or naproxen (500mg twice daily), and for severe cases, systemic corticosteroids like prednisone (20-40mg daily with taper) may be considered 1. Elevation and compression stockings can help reduce pain and swelling, and potassium iodide (400-900mg daily in divided doses) can be effective for persistent cases. Most cases resolve within 3-6 weeks, but recurrence is possible, and the pathophysiology involves a delayed hypersensitivity reaction causing inflammation in the subcutaneous fat, resulting in the characteristic tender, erythematous nodules typically on the anterior shins.

From the Research

Erythema Nodosum Workup

The workup for erythema nodosum involves a comprehensive history and physical examination, as well as various laboratory tests and diagnostic procedures. The goal of the workup is to identify any underlying systemic disease or condition that may be causing the erythema nodosum.

Laboratory Tests

Some of the laboratory tests that may be included in the workup for erythema nodosum are:

  • Complete blood count with differential 2, 3
  • Erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) level 2, 3, 4
  • Testing for streptococcal infection, such as throat culture, rapid antigen test, antistreptolysin-O titer, and polymerase chain reaction assay 2, 3
  • Biopsy, which may be deep incisional or excisional, to visualize the subcutaneous fat and septa 2
  • Platelet levels, which may be elevated in patients with underlying systemic disorders 4

Diagnostic Evaluation

The diagnostic evaluation for erythema nodosum may also include:

  • Chest radiography to rule out tuberculosis or other pulmonary diseases 2, 3
  • Stool cultures to rule out gastrointestinal infections 2
  • Purified protein derivative test to rule out tuberculosis 2
  • Testing for other underlying conditions, such as sarcoidosis, inflammatory bowel disease, or cancer, based on the patient's history and physical examination results 2, 5, 6

Risk Stratification

Patients with erythema nodosum should be stratified by risk for tuberculosis and other underlying systemic diseases, and further evaluation and testing should be tailored to the individual patient's needs 2.

Key Findings

Some key findings that may indicate an underlying systemic disorder in patients with erythema nodosum include:

  • Non-pretibial localization of lesions 4
  • Elevated platelet levels 4
  • Presence of systemic symptoms, such as fever or weight loss 5, 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Erythema nodosum: a sign of systemic disease.

American family physician, 2007

Research

Erythema nodosum.

World journal of pediatrics : WJP, 2018

Research

Erythema Nodosum: A Practical Approach and Diagnostic Algorithm.

American journal of clinical dermatology, 2021

Research

Erythema nodosum: the underlying conditions.

Clinical rheumatology, 2000

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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