Erythema nodosum

Signs and symptoms

Pre-eruptive phase

The first signs of erythema nodosum are often flu-like symptoms such as a fever, cough, malaise, and aching joints. Some people also experience stiffness or swelling in the joints and weight loss.

Eruptive phase

Erythema nodosum is characterised by 1 – nodules (rounded lumps) below the skin surface, usually on the shins. These subcutaneous nodules can appear anywhere on the body, but the most common sites are the shins, arms, thighs, and torso. Each nodule typically disappears after around two weeks, though new ones may continue to form for up to six or eight weeks. Joint pain and inflammation sometimes continue for several weeks or months after the nodules appear.

Less common variants of erythema nodosum include:

• Ulcerating forms, seen in Crohn's disease
• Erythema contusiforme, when a subcutaneous hemorrhage (bleeding under the skin) occurs with an erythema nodosum lesion, causing the lesion to look like a contusion (bruise)
• Erythema nodosum migrans (also known as subacute nodular migratory panniculitis), a rare form of chronic erythema nodosum characterized by asymmetrical nodules that are mildly tender and migrate over time.

File:EN-TBC.PNG|Erythema nodosum lesion in a person with light skin and tuberculosis File:A single EN.JPG|A single lesion of erythema nodosum File:Erythema Nodosum.jpg|Several lesions of erythema nodosum in an individual with dark skin

Causes

EN is associated with a wide variety of conditions.

Idiopathic

About 30–50% of EN cases are idiopathic (of an unknown cause).

Infection

Infections associated with EN include:

• Streptococcal infection which, in children, is by far the most common precipitant
• Several granulomatous mycobacterial infections including tuberculosis, leprosy, and M. avium complex
• Mycoplasma pneumoniae
• Histoplasma capsulatum
• Yersinia
• Lymphogranuloma venereum (LGV), caused by the bacteria Chlamydia trachomatis
• Epstein-Barr virus
• Coccidioides immitis (Valley fever)
• Cat scratch disease

Autoimmune

Autoimmune disorders associated with EN include:

• Behçet's disease

Immune-mediated/Idiopathic granulomatous diseases

• Crohn's disease
• Sarcoidosis

Pregnancy

Pregnancy may be associated with EN.

Medications

Medications associated with EN include:

• Omeprazole
• Sulfonamides
• Oral contraceptives
• Penicillins
• Bromides
• Hepatitis B vaccination

Cancer

Cancers associated with EN include:

• Non-Hodgkin's lymphoma (NHL)
• Carcinoid tumours
• Pancreatic cancer

EN may also be due to excessive antibody production in lepromatous leprosy leading to deposition of immune complexes.

There is an association with the HLA-B27 histocompatibility antigen, which is present in 65% of patients with erythema nodosum.

A useful mnemonic for causes is SORE SHINS (Streptococci, OCP, Rickettsia, Eponymous (Behçet), Sulfonamides, Hansen's Disease (Leprosy), IBD, NHL, Sarcoidosis.

Pathophysiology

Erythema nodosum is probably a delayed hypersensitivity reaction to a variety of antigens. Although circulating immune complexes have been demonstrated in patients with inflammatory bowel disease, they have not been found in idiopathic or uncomplicated cases.

Diagnosis

Erythema nodosum is diagnosed clinically. A biopsy can be taken and examined microscopically to confirm an uncertain diagnosis. Microscopic examination usually reveals a neutrophilic infiltrate surrounding capillaries that results in septal thickening, with fibrotic changes in the fat around blood vessels. A characteristic microscopic finding is radial granulomas, well-defined nodular aggregates of histiocytes surrounding a stellate cleft.

Additional evaluation should be performed to determine the underlying cause of erythema nodosum. This may include a complete blood count (CBC), erythrocyte sedimentation rate (ESR), antistreptolysin-O (ASO) titer and throat culture, urinalysis, intradermal tuberculin test, and a chest x-ray. The ESR is typically high, the C-reactive protein elevated, and the blood showing an increase in white blood cells.

The ESR is initially very high and falls as the nodules of erythema nodosum. The ASO titer is high in cases associated with a streptococcal throat infection. A chest X-ray should be performed to rule out pulmonary diseases, in particular sarcoidosis and Löfgren syndrome.

Treatment

Erythema nodosum is self-limiting and usually resolves itself within 3–6 weeks. A recurring form does exist, and in children, it is attributed to repeated infections with streptococcus. Treatment should focus on the underlying cause. Symptoms can be treated with bed rest, leg elevation, compressive bandages, wet dressings, and nonsteroidal anti-inflammatory agents (NSAIDs). NSAIDs are usually more effective at the onset of EN versus with chronic disease.{{cite web |url=https://www.lecturio.com/concepts/erythema-nodosum/| title=Erythema Nodosum |access-date= 21 July 2021}}

Potassium iodide can be used for persistent lesions whose cause remains unknown. Corticosteroids and colchicine can be used in severe refractory cases. Thalidomide has been used successfully in the treatment of Erythema nodosum leprosum, and it was approved by the U.S. FDA for this use in July 1998. According to a 2009 meta-analysis, there is some evidence of benefit for both thalidomide and clofazimine in the treatment of erythema nodosum leprosum.

Epidemiology

Erythema nodosum is the most common form of panniculitis. It is most common in the ages of 20–30, and affects women 3–6 times more than men.

Eponym

The term, Subacute Migratory Panniculitis of Vilanova and Piñol, was named after the two Catalan dermatologists who provided a brief description and explanation of the disease, Xavier Montiu Vilanova (1902–1965) and Joaquin Aguade Piñol (1918–1977), in 1954, and was named in 1956.

References

References

1. "Erythema Nodosum".
2. Pedro-Pons, Agustín. (1968). "Patología y Clínica Médicas". Salvat.
3. (April 2012). "Information for Families Erythema nodosum". GOSH NHS Foundation Trust.
4. Fitzpatrick, Thomas B.. (2005). "Fitzpatrick's color atlas and synopsis of clinical dermatology". McGraw-Hill.
5. (2007). "Erythema nodosum: A sign of systemic disease". American Family Physician.
6. (2010). "Erythema nodosum and erythema induratum (nodular vasculitis): Diagnosis and management". Dermatologic Therapy.
7. (March 2017). "Dermatology: 2-Volume Set". Mosby.
8. William D. James. (2011). "Andrews' Diseases of the skin: clinical dermatology.". Saunders/ Elsevier.
9. (2009). "Erythema Nodosum: An Experience of 10 Years". Scandinavian Journal of Infectious Diseases.
10. (2021). "Tuberculosis-Associated Erythema Nodosum". Cureus.
11. (2015). "Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases".
12. (August 2007). "Erythema Nodosum, Mycobacterium avium Lymphadenitis, and a 15-mm Mantoux Test". Pediatric Infectious Disease Journal.
13. (1984). "[Erythema nodosum and Crohn's disease]". Medicina Cutanea Ibero-latino-americana.
14. (15 April 2002). "Cutaneous sarcoidosis: a dermatologic masquerader.". American Family Physician.
15. (1997). "Erythema nodosum: 112 cases. Epidemiology, clinical aspects and histopathology". Schweizerische Medizinische Wochenschrift.
16. (2007-03-01). "Erythema nodosum: a sign of systemic disease". American Family Physician.
17. (1990). "Hepatitis B vaccine associated with erythema nodosum and polyarthritis". BMJ.
18. (2009). "Robbins and Coltran Pathological Basis of Disease". Saunders/Elsevier.
19. Cunha, Burke A.. (1999). "Infectious disease pearls". Hanley & Belfus.
20. (2014). "Get Ahead! SURGERY 100 EMQs for Finals". Taylor & Francis.
21. (2006). "Inflammatory Bowel Disease Characteristics Among African Americans, Hispanics, and Non-Hispanic Whites: Characterization of a Large North American Cohort". The American Journal of Gastroenterology.
22. (2000). "Erythema nodosum: Etiologic and predictive factors in a defined population". Arthritis & Rheumatism.
23. (2005). "A double-blind trial of depot corticosteroids in Behcet's syndrome". Rheumatology.
24. (2001). "A double-blind trial of colchicine in Behçet's syndrome". Arthritis & Rheumatism.
25. (2002). "The Schizophrenic Career of a 'Monster Drug'". Pediatrics.
26. (20 June 2005). "THALIDOMIDE". Chemical & Engineering News Archive.
27. (8 July 2009). "Interventions for erythema nodosum leprosum". Cochrane Database of Systematic Reviews.
28. {{EMedicine. article. 1081813. Subacute Nodular Migratory Panniculitis (Vilanova Disease)
29. (1978). "In memoriam Joaquin Piñol Aguadé, 1918--1977". Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und Verwandte Gebiete.