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Erythema Nodosum

Essentials

  • There is an underlying reactive immunological process of the subcutaneous adipose tissue (panniculitis).
  • The main symptoms are red, painful nodules primarily on the anterior aspect of the legs.
  • The most common triggering factors include infections (such as streptococcal infection, bacterial intestinal infections), autoimmune diseases (sarcoidosis, inflammatory bowel diseases, rheumatic diseases), various drugs, pregnancy.
  • Triggering factors should be recognized or excluded but they often remain unknown.
  • Treatment is based on treating the aetiological factor and alleviating symptoms.

Prevalence

  • Young adults are most commonly affected.
  • 3-5 times more common in women
  • Geographical differences in the prevalence of the underlying disorders influence the incidence rates.
  • Most cases occur in the winter and spring.

Aetiology

Symptoms and findings

  • There are bilateral indistinctly defined red lesions on the skin, often with underlying nodules tender to palpation.
  • The nodules develop within a few weeks.
  • They are typically situated on the anterior aspect of the legs; more rarely on the ankles, thighs, calves or arms (Images 1 23).
  • The nodules do not usually ulcerate.
  • The disease usually lasts for 1-2 months, and the nodules often assume a bruise-like appearance as they heal (erythema contusiformis).
  • Many patients suffer from fatigue, elevated body temperature, arthralgia, occasionally periarticular swelling and erythema of the ankles, in particular. Inflammatory markers may be slightly elevated.

Differential diagnosis

  • Erysipelas Erysipelas (fever, inflammatory markers significantly elevated)
  • Lymphangitis Lymphangitis
  • Superficial thrombophlebitis Superficial Venous Thrombophlebitis (painful linear induration)
  • Deep vein thrombosis Deep Vein Thrombosis (immobilization, risk factors)
  • Insect bites and stings Insect Stings and Bites (history, itching, sting marks)
  • Urticaria Hives (Urticaria) (migratory skin lesions, itching)
  • Erythema multiforme Erythema Multiforme (cockades, usually in other skin areas, as well)
  • Erythema induratum (on the posterior aspect of the calf, ulceration)
  • Other rarer forms of panniculitis (a heterogeneous group of disorders with inflammation mainly in the subcutaneous adipose tissue)

Workup

  • In a typical case, the diagnosis is clinical.
  • The workup aims at finding any underlying infection or other disease to be able to provide treatment consistent with the aetiology.
  • Any underlying cause will usually cause other symptoms, as well. Good history taking and clinical examination guide further investigations based on clinical suspicion.
    • Ask about any symptoms in family members (streptococci, respiratory viruses), travel (intestinal infections) or use of medication (temporal association with a new drug, such as combined oral contraceptives).
  • If the cause is not clinically evident, laboratory tests and chest X-ray examination can be performed.
  • The workup should be expanded based on clinical considerations and the course of the disease, and specialized care should be consulted, as necessary.

Basic investigations

  • Throat streptococcal culture
  • Basic blood count with platetet count, ESR, CRP, ALT, urinalysis (infections, underlying inflammatory disease)
  • Pregnancy test, serum or urine hCG
  • Faecal calprotectin (inflammatory bowel diseases)
  • Faecal bacteria test/panel with bacterial culture, possibly with nucleic acid detection (bacterial intestinal infection, including, for example, Salmonella, Shigella, Campylobacter, Yersinia, and E. Coli strains that cause gastroenteritis)
  • Chest X-ray (sarcoidosis, tuberculosis)

According to individual judgment

  • Antistreptolysin (a change in the titre or a high titre suggest streptococcal infection)
  • A rapid test for mononucleosis or antibodies to EBV
  • Yersinia antibodies if the patient has unclear abdominal pain, fever
    • Erythema nodosum may be the only postinfectious symptom after yersiniosis Yersiniosis.
  • Pneumonia diagnostics: Chlamydia pneumoniae antibodies and Mycoplasma pneumoniae antibodies if the patient has symptoms of a respiratory infection
  • Antiviral antibodies: HIV antigen and antibodies, HBV antigens and antibodies (HBsAg, HBcAb, and, as necessary, HBcAb IgM), HCV antibodies
  • Tuberculosis tests: tb staining and culture of sputum, three samples
  • Skin biopsy
    • Histopathology may be important in the differential diagnosis of atypical and prolonged cases.
    • For biopsy, a deep fusiform (elliptical) incision is needed to include adipose tissue.

Further investigations in case of unclear or prolonged symptoms

  • Extended diagnosis of infections, investigations for intestinal diseases (such as endoscopies), testing for rheumatic diseases, haematological workup and investigations to exclude malignancy
  • Often done in specialized care.

Treatment

  • The disease usually lasts for 1-2 months. Some patients have relapses but the symptoms are rarely prolonged.
  • Symptomatic treatment is sufficient for many patients: rest, cooling but also hot compresses may relieve the symptoms, compression stockings.
  • Any underlying infection or systemic disease should be treated as far as possible.
  • NSAIDs in 1- to 3-week courses
  • If no triggering factors can be found, 1-2 × 0.5 mg colchicine twice daily (2-4 weeks) or oral glucocorticoid treatment may be considered, such as prednisolone at an initial dosage of 0.5 mg/kg, continued with gradually reduced doses for 2-4 weeks.
  • Potassium iodide has also been used, 1-2 130-mg tablets 3 times daily (for 1-2 weeks). Thyroid function tests must be checked prior to treatment. Hypersensitivity to iodinated contrast medium does not prevent the use of potassium iodide.
  • In recurrent or prolonged cases, other drugs can also be used in courses or for maintenance therapy (usually in specialized care).

Specialist consultation

  • A dermatologist should be consulted in severe, recurring or prolonged clinical cases or if the diagnosis remains unclear.
  • If an underlying systemic disease or more severe infection is diagnosed, consultation of specialized care should be considered.

    References

    • Torralba-Morón Á, Alda-Bravo I. Causes of Erythema Nodosum in Patients Admitted to a Tertiary Care Hospital in Spain. Actas Dermosifiliogr 2020;111(8):683-687. [PubMed]
    • Leung AKC, Leong KF, Lam JM. Erythema nodosum. World J Pediatr 2018;14(6):548-554
    • Chowaniec M, Starba A, Wiland P. Erythema nodosum - review of the literature. Reumatologia 2016;54(2):79-82. [PubMed]
    • Blake T, Manahan M, Rodins K. Erythema nodosum - a review of an uncommon panniculitis. Dermatol Online J 2014;20(4):22376. [PubMed]
    • Gilchrist H, Patterson JW. Erythema nodosum and erythema induratum (nodular vasculitis): diagnosis and management. Dermatol Ther 2010;23(4):320-7. [PubMed]
    • Schwartz RA, Nervi SJ. Erythema nodosum: a sign of systemic disease. Am Fam Physician 2007;75(5):695-700. [PubMed]