DESCRIPTION

• Erythema nodosum (EN) is characterized by multiple symmetric, nonulcerative tender nodules on the extensor surface of the lower extremities, 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
    • Behçet 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)

Pediatric Considerations

Typically, EN begins 2–3 wk after onset of S. pharyngitis.

[Outline]

• DESCRIPTION
• ETIOLOGY

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
  • Behçet 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
  • Behçet syndrome
  • Lipodystrophies
  • Leukemic infiltration of fat
  • Panniculitis associated with steroid use, cold, and infection

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

Pediatric Considerations

• 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)
  • Do not exceed 4 g/24 h
• 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

• Potassium iodide
• Steroids

[Outline]

• INFORMATION
• PRE-HOSPITAL
• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

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.

[Outline]

• DISPOSITION
• FOLLOW-UP RECOMMENDATIONS

• 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.

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

[Outline]

• ICD9
• ICD10

• 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. Andrew's 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.

Herbert G. Bivins