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.”