Basics
Description
- Erythema nodosum (EN) is characterized by multiple symmetric, nonulcerative tender nodules on the extensor surface of the lowerextremities, typically in young adults.
- Peak incidence in 3rd decade
- More common in women (4:1)
- Nodules are round with poorly demarcated edges and vary in size from 1 to 10 cm.
- Skin lesions are initially red, become progressively ecchymotic appearing as they resolve over 3-6 wk.
- Lesions are caused by inflammation of the septa between SC fat nodules (septal panniculitis).
- Spontaneous regression of lesions within 3-6 wk
- Major disease variants include:
- EN migrans (usually mild unilateral disease with little or no systemic symptoms)
- Chronic EN (lesions spread via extension, and associated systemic symptoms tend to be milder)
Etiology
- Immune-mediated response
- 30-50% of the time etiology is idiopathic
- Often a marker for underlying disease; specific etiologies include:
- Drug reactions:
- Oral contraceptives
- Sulfonamides
- Penicillins
- Infections including:
- Streptococcal pharyngitis
- Mycobacterium tuberculosis (TB)
- Atypical mycobacteria
- Coccidioidomycosis
- Hepatitis
- Syphilis
- Chlamydia
- Rickettsia
- Salmonella
- Campylobacter
- Yersinia
- Parasites
- Leprosy
- Systemic diseases:
- Sarcoidosis
- Inflammatory bowel disease
- Beh §et disease
- Connective tissue disorders
- Malignancies such as lymphoma and leukemia
- Catscratch disease
- HIV infection
- Rarely can be caused by vaccines for hepatitis and TB (BCG)
Typically, EN begins 2-3 wk after onset of S. pharyngitis.
Diagnosis
Signs and Symptoms
- Tender erythematous nodules symmetrically distributed on extensor surface of lower legs
- Lesions occasionally occur on fingers, hands, arms, calves, and thighs.
- In bedridden patients, dependent areas may be involved.
- Fever, malaise, leukocytosis, arthralgias, arthritis, and unilateral or bilateral hilar adenopathy with any form of the disease
History
- General symptoms may precede or accompany the rash:
- Fever
- General malaise
- Polyarthralgias
- GI symptoms with EN may be a marker for:
- Inflammatory bowel disease
- Bacterial gastroenteritis
- Pancreatitis
- Beh §et disease
- A history of travel is important, as there are regional variations in etiology.
Physical Exam
- A careful exam is important, as underlying etiology varies by region.
- Lesions are most common on the pretibial area but may occur on the thigh, upper extremities, neck and, rarely, the face.
- Absence of lesions on the lower extremities is atypical, as are ulcerated lesions.
- Lower-extremity edema may occur.
- Adenopathy should be evaluated.
Essential Workup
Careful history and physical exam directed at detecting precipitating cause
Diagnosis Tests & Interpretation
Lab
- CBC
- Throat culture/ASO titer
- ESR
- Appropriate chemistry tests
- Liver function tests
- Serologies for coccidioidomycosis in endemic regions
- TB skin testing in endemic regions
Imaging
CXR: Hilar adenopathy may be evidence of sarcoidosis, coccidioidomycosis, tuberculosis, or other fungal infections.
Diagnostic Procedures/Surgery
Definitive diagnosis made by deep elliptical biopsy and histopathologic evaluation (punch biopsy may be inadequate): Usually indicated for atypical cases or when TB is being considered
Differential Diagnosis
- EN migrans and chronic EN
- Any type of panniculitis can resemble EN.
- Differences can be determined histopathologically.
- Other disorders include:
- Periarteritis nodosum
- Migratory thrombophlebitis
- Superficial varicose thrombophlebitis
- Scleroderma
- Systemic lupus erythematosus
- α1-antitrypsin deficiency
- Beh §et syndrome
- Lipodystrophies
- Leukemic infiltration of fat
- Panniculitis associated with steroid use, cold, and infection
Treatment
- Rare in children, S. pharyngitis is the most likely etiology.
- Catscratch disease should be considered.
Pre-Hospital
Maintain universal precautions
Initial Stabilization/Therapy
Airway, breathing, and circulation (ABCs); IV, oxygen, monitoring as appropriate
Ed Treatment/Procedures
- Treatment should be directed at underlying disease.
- Supportive therapies include rest and analgesics.
- Corticosteroids and potassium iodide may hasten resolution of symptoms.
- Systemic corticosteroids are contraindicated in the presence of certain underlying infections such as TB or coccidioidomycosis, which may disseminate with their use.
- Potassium iodide is contraindicated in hyperthyroid states.
Medication
- Aspirin: 650 mg PO q4-6h PRN (peds: contraindicated)
- Ibuprofen: 400-800 mg PO q8h (peds: 5-10 mg/kg PO q6h)
- Indomethacin: 25-50 mg PO q8h
- Potassium iodide/SSKI (used for resistant disease; contraindicated in hyperthyroidism): 900 mg PO daily for 3-4 wk
- Systemic corticosteroids (prednisone): 40 mg/d PO; duration determined by primary physician
First Line
- Rest/supportive care
- NSAIDs
- Treatment of underlying disease
Second Line
Follow-Up
Disposition
Admission Criteria
Dictated by the severity of symptoms and the etiologic agent
Discharge Criteria
- Nontoxic patients, able to take PO fluids without difficulty
- Scheduled follow-up should be arranged.
Issues for Referral
- EN is usually self-limited and resolves in 3-6 wk.
- Atypical cases may need excisional biopsy.
- Steroid and potassium therapy needs primary physician monitoring.
Follow-Up Recommendations
- Follow-up to assess for resolution with primary care physician or dermatologist.
- Evaluation of underlying etiology may require specialist referral.
Pearls and Pitfalls
- EN is usually idiopathic but may be the 1st sign of systemic disease.
- Lesions may recur if underlying disease is not treated.
- Atypical and chronic lesions may indicate an alternative diagnosis and need biopsy.
- Patients taking potassium or steroids need close follow-up.
Additional Reading
- Gilchrist H, Patterson JW. Erythema nodosum and erythema induratum (nodular vasculitis): Diagnosis and management. Dermatol Ther. 2010;23(4):320-327.
- James JD, Berger TG, Elston DM. Andrews Disease of the Skin: Clinical Dermatology, 10th ed. Philadelphia, PA: WB Saunders; 2006.
- Mert A, Kumbasar H, Ozaras R, et al. Erythema nodosum: An evaluation of 100 cases. Clin Exp Rheumatol. 2007;25:563-570.
- Sarret C, Barbier C, Faucher R, et al. Erythema nodosum and adenopathy in a 15-year-old boy: Uncommon signs of cat scratch disease. Arch Pediatr. 2005;12:295-297.
- Schwartz RA, Nervi SJ. Erythema nodosum: A sign of systemic disease. Am Fam Physician. 2007;75:695-700.
Codes
ICD9
- 017.10 Erythema nodosum with hypersensitivity reaction in tuberculosis, unspecified
- 695.2 Erythema nodosum
ICD10
- A18.4 Tuberculosis of skin and subcutaneous tissue
- L52 Erythema nodosum
SNOMED
- 32861005 Erythema nodosum (disorder)
- 74610006 Tuberculous erythema nodosum (disorder)
- 76097009 Erythema nodosum migrans (disorder)
- 69688007 Erythema nodosum, chronic form (disorder)
- 240360007 Yersinia erythema nodosum (disorder)
- 240411003 Erythema nodosum leprosum (disorder)
- 297940005 Drug-induced erythema nodosum (disorder)
- 78223000 Coccidioidomycosis with erythema nodosum (disorder)