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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
- Erythema nodosum most commonly occurs after an infection. The latency period may be from several days to several weeks.
- Various infections have been suspected of being triggering factors.
- Streptococcal tonsillitisSore Throat and Tonsillitis
- Viral upper respiratory tract or pharyngeal infections
- Mononucleosis Mononucleosis
- Pneumonia, particularly if caused by Chlamydia pneumoniae Pneumonia or Mycoplasma pneumoniae Mycoplasma Pneumoniae Infections
- Bacterial intestinal infections, particularly yersiniosis Yersiniosis, salmonellosis Diarrhoeal Diseases Caused by Microbes
- Herpes infections Herpes Simplex Infection of the Skin
- Consider local prevalence: lung tuberculosis, particularly if a primary infection Diagnosing Tuberculosis, environmental mycobacterial infections Pulmonary Diseases Caused by Environmental Mycobacteria, HIV infection HIV Infection, viral hepatitis Viral Hepatitis
- Erythema nodosum has also been linked to some infections that are extremely rare in many industrialized countries (in tourists coming from endemic areas or in immigrants), such as endemic deep fungal infections Deep Endemic Mycoses (histoplasmosis, coccidioidomycosis (valley fever), blastomycosis), leprosy (erythema nodosum leprosum), melioidosis Bacterial Diseases in Warm Climates
- Drugs
- Various drugs, such as combined oral contraceptives or NSAIDs, antimicrobial medication, such as sulfamethoxazole or amoxicillin, injectable gold and iodine, have been suspected of triggering erythema nodosum.
- There is usually a temporal association with the initiation of drug treatment; the latency period may be long.
- In patients with autoimmune diseases, erythema nodosum may appear before other symptoms of the underlying disease, during the acute initial phase or during an exacerbation of chronic disease.
- Pregnancy
- Malignancies
- In about 50% of cases, the aetiology remains unknown.
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]