• Clinical pattern of multiple, bilateral, cutaneous, tender, and somewhat painful inflammatory, nonulcerating, and nonscarring eruptions that undergo characteristic color changes ending in temporary bruise-like areas
• Occurs most commonly on the extensor surface of the shins, less common on thighs and forearms
• Often idiopathic, but may be seen as a response to a variety of clinical entities
• Usually subsides in 3–6 weeks without scarring or atrophy
• Synonym(s): Dermatitis contusiformis

ALERT
Pediatric Considerations
Incidence equal, male and female

Pregnancy Considerations
May have repeat outbreaks during pregnancy

• Predominant age: 20–30 years
• Predominant sex: Female > Male (3:1)

Incidence
Unknown

Prevalence
Unknown

See “Etiology.”

• Idiopathic: 37–60%
• Bacterial: Streptococcal infections (most common cause in children), tuberculosis, leprosy, Yersinia enterocolitica, tularemia, Campylobacter, salmonella, Shigella, gonorrhea
• Sarcoid
• Drugs: Sulfonamides, oral contraceptives, bromides
• Pregnancy
• Deep fungal: Dermatophytes, coccidioidomycosis, histoplasmosis, blastomycosis
• Viral/Chlamydial: Infectious mononucleosis, lymphogranuloma venereum, paravaccinia
• Enteropathies: Ulcerative colitis, Crohn disease, Behçet disease (1), celiac disease (2)
• Malignancies: Lymphoma/leukemia, sarcoma, post radiation therapy

See “Etiology.”

History

• Fever, malaise, chills, fatigue
• Increasingly tender and aching patches on the legs, mainly below the knee.
• Eruptions often preceded by symptoms of pharyngitis or other upper respiratory infection
• Headache
• Arthralgias (rare)

Physical Exam

• Initially warm, tender, brightly erythematous nodules, which may be raised, on anterior shins. Lesions become bluish and fluctuant, gradually fading to yellowish resembling a bruise.
• Can also occur on any area with subcutaneous fat
• Diameter 1–15 cm

Lab

• Elevated ESR
• CBC: Mild leukocytosis
• Antistreptolysin titers maybe elevated.
• Throat culture (usually negative because the infection typically resolves before lesions appear)
• Stool culture and leukocytes, if indicated
• Skin testing for mycobacteria, if indicated
• Drugs that may alter lab results: Antecedent antibiotics may affect cultures.

Imaging
CXR for hilar adenopathy or infiltrates related to sarcoidosis or tuberculosis

Diagnostic Procedures/Other
Deep skin excisional biopsy including subcutaneous fat; rarely necessary.

Pathological Findings

• Septal panniculitis
• Neutrophilic infiltrate in septa of fat tissue, early in course
• Fibrosis, paraseptal granulation tissue, lymphocytes, and multinucleated giant cells predominate late in course
• Lower dermis/subcutis involvement and septal fibrosis may occur.

• Superficial thrombophlebitis
• Cellulitis
• Septic emboli
• Erythema induratum (ulcerating calf nodules)
• Nodular vasculitis (warm, ulcerating nodules)
• Weber-Christian disease (violaceous, scarring nodules)
• Lupus panniculitis
• Cutaneous polyarteritis nodosa
• Sarcoidosis granulomata
• Cutaneous T-cell lymphoma
• Erythema nodosum leprosum

First Line

• Medication usually more effective after initial onset vs. with chronic disease
• Condition often self-limited
• NSAIDs:
  • Indomethacin: 75–150 mg/d, divided t.i.d.
  • Naproxen (Naprosyn): 500–1,000 mg/d, divided b.i.d.
  • Aspirin: 325 mg 8–12 times per day; use enteric-coated to decrease GI upset. Titrate to blood levels.
• Contraindications:
  • Active or recent peptic ulcer disease
  • History of hypersensitivity to NSAIDs
• Precautions:
  • GI upset/bleeding
  • Fluid retention
  • Dose reduction in elderly, especially those with renal disease, diabetes, or heart failure
  • May mask fever
  • NSAIDs may elevate liver function tests
• Significant possible interactions:
  • May blunt antihypertensive effects of diuretics and β-blockers
  • NSAIDs can elevate plasma lithium levels.
  • Caution advised with naproxen or any highly protein-bound drug, because it may compete for albumin binding and elevate levels
• NSAIDs can cause significant elevation and prolongation of methotrexate levels.

Second Line

• Potassium iodide 400–900 mg/d, divided 2–3 times a day for 3–4 weeks (for persistent lesions)
• Corticosteroids for severe, refractory cases
• Recent reports of improvement with colchicine 0.6–1.2 mg b.i.d.

General Measures

• Mild compression bandages and leg elevation may reduce pain. (Wet dressings, hot soaks, and topical medications are not useful.)
• Discontinue potentially causative drugs.
• Treat underlying disease.

Admission Criteria
Occasionally admission may be needed for the antecedent illness, e.g., TB.

Vitamin B₁₂ replacement trial (3)

• Bed rest, keep legs elevated
• Elastic wraps or support stockings may be helpful if patients want to be up and around.

Patient Monitoring
Monthly follow-up or as dictated by underlying disorder

No restrictions

• Lesions will resolve over a few months.
• No scarring is anticipated.
• Joint aches and pains may persist.
• <20% recur

• Individual lesions resolve over 3–6 weeks.
• Total time course of 6–12 weeks, but may vary with etiologic disease, if present
• Joint aches and pains may persist for years.
• Lesions do not scar.
• ≥1 recurrences in 12–14% of cases:
  • Occur over variable periods, averaging several years
• Seen most often with sarcoid, streptococcal infection, pregnancy, and oral contraceptives

• Vary according to underlying disease
• None expected from lesions of erythema nodosum

Fitzpatrick TB, et al., eds. Dermatology in General Medicine, 5th ed. New York: McGraw-Hill, 1999.

Gonzalez-Gay MA, et al. Erythema nodosum: A clinical approach. Clin Exp Rheumatol 2001;19:365–368.

Habif T. Clinical Dermatology, 4th ed. St. Louis, MO: CV Mosby, 2004.

Hannuksela M. Erythema nodosum. Clin Dermatol 1986;4:88–95.

Requena L, et al. Erythema nodosum. Dermatol Online J 2002;8:4.

695.2 Erythema nodosum

32861005 erythema nodosum (disorder)

• Löfgren syndrome (erythema nodosum and hilar adenopathy) is seen with multiple etiologies and does not exclusively indicate sarcoid.
• The clinical variant of erythema nodosum migrans (subacute nodular migratory panniculitis) is often unilateral with nodules fewer in number, smaller in size, and longer lasting that extend radially by division into smaller nodules.
• In patients with a history of Hodgkin lymphoma, erythema nodosum is a warning of impending recurrence.

Lewis C. Rose, MD

Figure 23-6

Erythema nodosum. These tender nodules occurred during pregnancy and resolved postpartum.

1. Psychos DN, et al. Erythema nodosum: Underlying conditions. Clin Rheumatol 2000;19:212.  [PMID:10870657]
2. Bartyik K, et al. Erythema nodosum in association with celiac disease. Pediatr Dermatol 2004;21(3):227–230.  [PMID:15165200]
3. Volkov I, et al. Successful treatment of chronic erythema nodosum with vitamin B12. J Am Board Fam Pract 2005;18:6.