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Erythema Nodosum

BASICS

DESCRIPTION

  • Delayed-type IV hypersensitivity panniculitis affecting subcutaneous fat.
  • Presents with multiple, bilateral, erythematous, tender nodules usually on the anterior shins.
  • Lesions evolve color like bruises, no ulceration (unlike erythema induratum).
  • Common prodrome: fever, weight loss, arthralgia.
  • Usually self-limited, remitting spontaneously within weeks to months without scarring.
  • Divided into acute (common) and chronic (rare).
  • Pediatric variant often limited to palms/soles, unilateral, shorter duration.
  • May recur during pregnancy.

EPIDEMIOLOGY

  • Most frequent in women aged 18-34 years.
  • Incidence 1-5 per 100,000 per year.
  • Female predominance (6:1).
  • Geographic variation based on associated disorders prevalence.

ETIOLOGY AND PATHOPHYSIOLOGY

  • Idiopathic: up to 55%.
  • Infectious causes (44%):
  • Most common: streptococcal pharyngitis
  • Others: mycobacteria, mycoplasma, chlamydia, coccidioidomycosis, Campylobacter, rickettsiae, Salmonella, 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%): fungal infections, viral/chlamydial, malignancies, Sweet syndrome, COVID-19 and SARS-CoV-2 vaccine.

RISK FACTORS

  • Underlying infections, systemic diseases, drug exposures as above.

DIAGNOSIS

HISTORY

  • Prodrome 1-3 weeks prior: fever, malaise, weight loss, cough, arthralgia.
  • Tender, erythematous nodules mainly on shins.
  • May have headache, chills, fatigue.
  • Systemic symptoms may precede skin lesions.

PHYSICAL EXAM

  • Warm, tender, erythematous nodules and plaques on anterior shins; may extend proximally or to other sites.
  • Nodules 1-10 cm, poorly demarcated.
  • Color changes resemble bruises (erythema contusiformis).

DIFFERENTIAL DIAGNOSIS

  • Nodular vasculitis/erythema induratum (ulcerative).
  • Superficial thrombophlebitis.
  • Cellulitis.
  • Weber-Christian disease.
  • Lupus panniculitis.
  • Cutaneous polyarteritis nodosa.
  • Sarcoidal granulomas.
  • Cutaneous T-cell lymphoma.
  • Infectious panniculitis (various organisms).

DIAGNOSTIC TESTS

  • Labs: ESR/CRP often elevated, CBC mild leukocytosis.
  • Throat culture, ASO titer, blood/stool cultures as indicated.
  • Tuberculin skin test.
  • CXR to evaluate for sarcoidosis or TB.
  • Biopsy rarely necessary except atypical or chronic cases.
  • Histology: septal panniculitis without vasculitis, early neutrophilic infiltrate, Miescher radial granulomas (histiocytes with stellate clefts), late fibrosis and giant cells.
  • Cutaneous ultrasound may show mixed lobular/septal panniculitis.

TREATMENT

GENERAL MEASURES

  • Usually self-limited within 1-2 months.
  • Supportive: mild compression, leg elevation for pain relief.
  • Discontinue causative drugs.
  • Treat underlying disorder if identified.

MEDICATION

First Line

  • NSAIDs:
  • Ibuprofen 400 mg q4-6h (max 3200 mg/day)
  • Indomethacin 25-50 mg TID
  • Naproxen 250-500 mg BID
  • Caution: GI effects, fluid retention, renal insufficiency, CV risk, interactions with diuretics and β-blockers.

Second Line

  • Potassium iodide 400-900 mg/day divided for 3-4 weeks (monitor thyroid function, pregnancy class D).
  • Corticosteroids for severe/refractory cases: prednisone 1 mg/kg/day for 1-2 weeks (side effects: hyperglycemia, hypertension, weight gain, mood changes, osteoporosis).
  • Colchicine (Behçet disease-associated EN): 0.6-1.2 mg BID (GI upset common).

ONGOING CARE

  • Elevate legs, consider elastic support stockings during ambulation.
  • Monitor monthly or per underlying disease course.

PATIENT EDUCATION

  • Lesions resolve in weeks to months, unlikely to scar.
  • Joint symptoms may persist.
  • Avoid causative drugs and exposures.

PROGNOSIS

  • Lesions resolve in 2 weeks on average; total course 6-12 weeks.
  • Recurrences possible, especially in sarcoidosis, streptococcal infections, pregnancy, oral contraceptive use.

COMPLICATIONS

  • Dependent on underlying condition.
  • EN lesions themselves typically do not cause complications.

REFERENCES

  1. Chowaniec M, Starba A, Wiland P. Erythema nodosum—review of the literature. Reumatologia. 2016;54(2):79-82.
  2. Laborada J, Cohen PR. Tuberculosis-associated erythema nodosum. Cureus. 2021;13(12):e20184.
  3. Schwartz RA, Nervi SJ. Erythema nodosum: a sign of systemic disease. Am Fam Physician. 2007;75(5):695-700.
  4. Xie Y, Yin B, Shi X. Erythema nodosum following SARS-CoV-2 vaccine. J Eur Acad Dermatol Venereol. 2022;36(10):e752-e753.

CODES

  • ICD10 L52 Erythema nodosum
  • ICD10 A18.4 Tuberculosis of skin and subcutaneous tissue

CLINICAL PEARLS

  • EN presents as erythematous patches with palpable underlying nodularity.
  • Evaluation for systemic causes essential despite high rate of idiopathic cases.
  • Presence of hilar adenopathy is not specific for sarcoidosis.
  • In Hodgkin lymphoma patients, EN may herald recurrence.