Erythema Nodosum – Causes, Symptoms, Diagnosis, Treatment and Ongoing care
- A delayed-type hypersensitivity reaction to infectious agents, medications, or malignancies, or in the setting of autoimmune disorders, presenting as a subcutaneous panniculitis
- Clinical pattern of multiple, bilateral, erythematous, tender subcutaneous nodules that undergo a characteristic pattern of color changes, similar to that seen in bruises. Unlike erythema induratum, the lesions of erythema nodosum do not typically ulcerate.
- Occurs most commonly on the shins, less commonly on the thighs and forearms
- May be accompanied by fever and arthralgias
- Often idiopathic but may be associated with a number of clinical entities
- Usually remits spontaneously in weeks to months without scarring or atrophy
- Synonym(s): Dermatitis contusiformis
May have repeat outbreaks during pregnancy
- Predominant age: 20–30 years
- Predominant sex: Female > Male (3:1).
Varies geographically depending on the prevalence of disorders associated with erythema nodosum
- Idiopathic: 37–60%
- Bacterial: Streptococcal infections (most common cause in children), tuberculosis, leprosy, tularemia, gonorrhea, Yersinia enterocolitica,Campylobacter, Salmonella, Shigella
- Drugs: Sulfonamides, amoxicillin, oral contraceptives, bromides
- 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, after radiation therapy
Commonly Associated Conditions
- Increasingly tender and aching nodules on the legs, usually over the shins.
- Fever, malaise, chills, fatigue
- Eruptions often preceded by symptoms of pharyngitis or upper respiratory infection
- 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.
- May occur on any area with subcutaneous fat
- Diameter usually 2–6 cm, but may rarely be larger
Diagnostic Tests & Interpretation
Diagnosis is usually clinical.
- Erythrocyte sedimentation rate (ESR). May be elevated or normal.
- Complete blood count (CBC): Mild leukocytosis
- Antistreptolysin titers may be 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.
CXR for hilar adenopathy or infiltrates related to sarcoidosis or tuberculosis
Deep incisional skin biopsy including subcutaneous fat; rarely necessary except in atypical cases with ulceration, duration greater than 12 weeks or a presentation that does not include skin lesions.
- Septal panniculitis without vasculitis.
- Neutrophilic infiltrate in septa of fat tissue early in course.
- Actinic radial (Miescher’s) granulomas, consisting of collections of histocytes around a central stellate cleft, may be seen (3).
- Fibrosis, paraseptal granulation tissue, lymphocytes, and multinucleated giant cells predominate late in course.
- Nodular vasculitis or erythema induratum (warm ulcerating calf nodules)
- Superficial thrombophlebitis
- Septic emboli
- Weber-Christian disease (violaceous, scarring nodules)
- Lupus panniculitis
- Cutaneous polyarteritis nodosa
- Sarcoidal granulomas
- Cutaneous T-cell lymphoma
- Erythema nodosum leprosum (clinically similar to EN but shows vasculitis on histopathology)
All medications listed as treatment for erythema nodosum are off-label uses of the medications. There are no FDA-approved medications for erythema nodosum.
- Medication usually more effective in acute than in chronic disease
- Condition often self-limited
- Nonsteroidal anti-inflammatory drugs (NSAIDs):
- Ibuprofen: 400 mg po q4–6 hours (not to exceed 3200 mg per day)
- Indomethacin: 25–50 mg po t.i.d.
- Naproxen (Naprosyn): 250–500 mg po b.i.d.
- Aspirin: 325 mg 1–2 tablets po q4–6 hours (not to exceed 12 tablets a day); use enteric-coated tablets to decrease GI upset.
- Active or recent peptic ulcer disease
- History of hypersensitivity to NSAIDs
- 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 is 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.
- Potassium iodide 400–900 mg/d divided 2–3×/day × 3–4 weeks (for persistent lesions). Need to monitor for hypothyroidism with prolonged use. Pregnancy Class D.
- Corticosteroids for severe, refractory cases in which an infectious workup is negative. Prednisone 1mg/kg/d for 1–2 weeks often helps resolve the lesions (4). Potential side effects include hyperglycemia, hypertension, weight gain, mood changes, bone loss, osteonecrosis, myopathy.
- Recent reports of improvement with colchicine 0.6–1.2 mg b.i.d.
- Hydroxychloroquine, thalidomide and cyclosporine may also be used.
- 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.
Complementary and Alternative Medicine
Vitamin B12 replacement. A single case report of resolution of lesions with B12 replacement in a patient who had B12 deficiency and erythema nodosum (5).
Occasionally, admission may be needed for the antecedent illness (e.g., tuberculosis).
- Keep legs elevated.
- Elastic wraps or support stockings may be helpful when patients are ambulating.
Monthly follow-up or as dictated by underlying disorder
- Lesions will resolve over a few weeks to months.
- No scarring is anticipated.
- Joint aches and pains may persist.
- <20% recur.
- Individual lesions resolve generally within 2 weeks.
- Total time course of 6–12 weeks but may vary with underlying disease.
- Joint aches and pains may persist for years.
- Lesions do not scar.
- Recurrences in 12–14% of patients: Occurs over variable periods, averaging several years; seen most often in sarcoid, streptococcal infection, pregnancy, and oral contraceptive use
- Vary according to underlying disease
- None expected from lesions of erythema nodosum
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2. Bartyik K, Várkonyi A, Kirschner A, et al. Erythema nodosum in association with celiac disease. Pediatr Dermatol. 2004;21:227–30.
3. Schwartz RA, Nervi SJ et al. Erythema nodosum: a sign of systemic disease.Am Fam Physician. 2007;75:695–700.
4. Requena L, Yus ES et al. Erythema nodosum. Dermatol Clin. 2008;26:425–38, v
5. Volkov I, et al. Successful treatment of chronic erythema nodosum with vitamin B12. J Am Board Fam Pract. 2005;18:6.
González-Gay MA, García-Porrúa C, Pujol RM, et al. Erythema nodosum: a clinical approach. Clin Exp Rheumatol. 2001;19:365–8.
Habif T. Clinical Dermatology, 4th ed. St. Louis, MO: CV Mosby, 2004.
Requena L, et al. Erythema nodosum. Dermatol Online J. 2002;8:4.
Wolff K, et al., eds. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York: McGraw-Hill Professional, 2007.
695.2 Erythema nodosum
32861005 erythema nodosum (disorder)
- Lesions of erythema nodosum appear to be erythematous patches, but when palpated, their underlying nodularity is appreciated.
- Erythema nodosum in the setting of hilar adenopathy may be seen with multiple etiologies and does not exclusively indicate sarcoidosis.
- In patients with a history of Hodgkin lymphoma, erythema nodosum may be a warning of impending recurrence.