Erythema Nodosum

Basics

Description

  • A delayed-type IV hypersensitivity reaction to various antigens, or an autoimmune reaction presenting as a panniculitis (1) that affects subcutaneous fat
  • The clinical pattern of multiple, bilateral, erythematous, tender nodules in a typically anterior pretibial distribution that undergo a characteristic pattern of color changes, similar to that seen in bruises. Unlike erythema induratum, the lesions of erythema nodosum (EN) do not typically ulcerate.
  • Occurs most commonly on the shins; less commonly on the thighs, forearms, trunk, head, or neck
  • Often associated with nonspecific prodrome including fever, weight loss, and arthralgia
  • Often idiopathic but may be associated with a number of clinical entities
  • Usually remits spontaneously in weeks to months without scarring, atrophy, or ulceration
  • Uncommon to have recurrences after the initial presentation
  • Divided into acute (more common) and chronic (rare)

Pregnancy Considerations
May have repeat outbreaks during pregnancy

Pediatric Considerations
A rare pediatric variant has lesions only on palms or soles, often unilateral; typically has a shorter duration in children than in adults

Epidemiology

Frequently observed in women aged 18 to 34 years (2)

Incidence

  • 1 to 5/100,000/year
  • Predominant age: 20 to 30 years
  • Predominant sex: female > male (6:1) in adults

Prevalence

  • Varies geographically depending on the prevalence of disorders associated with EN
  • Reported 1 to 5/100,000

Etiology and Pathophysiology

  • Idiopathic: up to 55%
  • Infectious: 44%; streptococcal pharyngitis (most common), mycobacteria, mycoplasma, chlamydia, mycoplasma, coccidioidomycosis, rarely can be caused by Campylobacter spp., rickettsiae, Salmonella spp., psittacosis, syphilis
  • Sarcoidosis: 11–25%
  • Drugs: 3–10%; sulfonamides amoxicillin, oral contraceptives, bromides, azathioprine, vemurafenib
  • Pregnancy: 2–5%
  • Enteropathies: 1–4%; ulcerative colitis, Crohn disease, Behçet disease, celiac disease, diverticulitis
  • Rare causes: <1% (3)
    • Fungal: dermatophytes, coccidioidomycosis, histoplasmosis, blastomycosis, Kerion of Celso
    • Viral/chlamydial: infectious mononucleosis; lymphogranuloma venereum; paravaccinia; HIV; hepatitis B, C
    • Malignancies: lymphoma/leukemia, sarcoma, myelodysplastic syndrome
    • Sweet syndrome
    • Sorafenib, pembrolizumab, dupilumab
    • COVID-19 virus, SARS-CoV-2 vaccine (4)

Risk Factors

See “Etiology and Pathophysiology.”

Commonly Associated Conditions

See “Etiology and Pathophysiology.”

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