eMedicine Specialties > Dermatology > Diseases of the Subcutaneous Tissue
Erythema Nodosum
Updated: Jan 22, 2009
Introduction
Background
Erythema nodosum (EN) is an acute, nodular, erythematous eruption that usually is limited to the extensor aspects of the lower legs. Chronic or recurrent erythema nodosum is rare but may occur. Erythema nodosum is presumed to be a hypersensitivity reaction and may occur in association with several systemic diseases or drug therapies, or it may be idiopathic. The inflammatory reaction occurs in the panniculus.
Pathophysiology
Erythema nodosum probably is a delayed hypersensitivity reaction to a variety of antigens; circulating immune complexes have not been found in idiopathic or uncomplicated cases but may be demonstrated in patients with inflammatory bowel disease.1
Frequency
United States
Peak incidence occurs at age 18-34 years. Age and sex distributions vary according to etiology and geographic location.2
International
Rates of erythema nodosum vary according to country. In England, the rate is 2.4 cases per 10,000 per year.
Mortality/Morbidity
In most patients, erythema nodosum resolves without any adverse reactions.
Sex
Women are affected more often than men, with a male-to-female ratio of 1:4.
Age
Erythema nodosum may occur in children and in patients older than 70 years, but it is more common in young adults aged 18-34 years. Age distribution varies with geographic location and etiology.
Clinical
History
The eruptive phase of erythema nodosum begins with flulike symptoms of fever and generalized aching. Arthralgia may occur and precedes the eruption or appears during the eruptive phase. Most lesions in infection-induced erythema nodosum heal within 7 weeks, but active disease may last up to 18 weeks. In contrast, 30% of idiopathic erythema nodosum cases may last more than 6 months. Febrile illness with dermatologic findings includes abrupt onset of illness with initial fever, followed by a painful rash within 1-2 days.
Physical
Pertinent physical findings are limited to the skin and joints.
Primary skin lesions
Lesions begin as red tender nodules (see the image below). Lesion borders are poorly defined, and lesions vary from 2-6 cm. During the first week, lesions become tense, hard, and painful; during the second week, they may become fluctuant, as in an abscess, but do not suppurate or ulcerate. Individual lesions last approximately 2 weeks, but occasionally, new lesions continue to appear for 3-6 weeks. Aching legs and swelling ankles may persist for weeks.
Classic presentation of erythema nodosum with nodular red swellings over the shins.
Distribution of skin lesions
Characteristically, lesions appear on the anterior leg; however, they may appear on any surface.
Color of skin lesions
Lesions change color in the second week from bright red to bluish or livid. As absorption progresses, the color gradually fades to a yellowish hue, resembling a bruise. This disappears in 1 or 2 weeks as the overlying skin desquamates.
Hilar lymph nodes
Hilar adenopathy may develop as part of the hypersensitivity reaction of erythema nodosum. Bilateral hilar lymphadenopathy is associated with sarcoidosis, while unilateral changes may occur with infections and malignancy.
Joints
Arthralgia occurs in more than 50% of patients and begins during the eruptive phase or precedes the eruption by 2-4 weeks. Erythema, swelling, and tenderness occur over the joint, sometimes with effusions. Joint tenderness and morning stiffness may occur. Any joint may be involved, but the ankles, knees, and wrist are affected most commonly. Synovitis resolves within a few weeks, but joint pain and stiffness may last up to 6 months. No destructive joint changes occur. Synovial fluid is acellular, and the rheumatoid factor is negative.
Causes
Currently, the most common cause of erythema nodosum is streptococcal infection in children and streptococcal infection and sarcoidosis in adults.3 Numerous other causes have been reported.4 The causes reported most often in the literature are as follows:
- Bacterial infections
- Streptococcal infections are one of the most common causes of erythema nodosum.
- Tuberculosis was an important cause in the past, but it has decreased dramatically as a cause for erythema nodosum; however, it still must be excluded, especially in developing countries.5,6
- Yersinia enterocolitica is a gram-negative bacillus that causes acute diarrhea and abdominal pain; it is a common cause of erythema nodosum in France and Finland.7,8,9
- Mycoplasma pneumoniae infection may cause erythema nodosum.
- Erythema nodosum leprosum clinically resembles erythema nodosum, but the histologic picture is that of leukocytoclastic vasculitis.
- Lymphogranuloma venereum may cause erythema nodosum.
- Salmonella infection may cause erythema nodosum.
- Campylobacter infection may cause erythema nodosum.
- Fungal infections
- Coccidioidomycosis (San Joaquin Valley fever) is the most common cause of erythema nodosum in the American Southwest. In approximately 4% of males and 10% of females, the primary fungal infection (which may be asymptomatic or involve symptoms of upper respiratory infection) is followed by the development of erythema nodosum. Lesions appear 3 days to 3 weeks after the end of the fever caused by the fungal infection.
- Histoplasmosis may cause erythema nodosum.
- Blastomycosis may cause erythema nodosum.
- Drugs: Sulfonamides and halide agents are an important cause of erythema nodosum. Drugs more recently described to cause erythema nodosum include gold and sulfonylureas. Oral contraceptive pills are implicated in an increasing number of reports.
- Enteropathies: Ulcerative colitis and Crohn disease may trigger erythema nodosum. Erythema nodosum associated with enteropathies correlates with flares of the disease. The mean duration of chronic ulcerative colitis before the onset of erythema nodosum is 5 years, and erythema nodosum is controlled with adequate therapy of the colitis. Erythema nodosum is the most frequent dermatologic symptom in inflammatory bowel diseases, and it is strongly associated with Crohn disease.10
- Hodgkin disease and lymphoma: Erythema nodosum associated with non-Hodgkin lymphoma may precede the diagnosis of lymphoma by months. Reports of erythema nodosum preceding the onset of acute myelogenous leukemia have been published.11
- Sarcoidosis: The most common cutaneous manifestation of sarcoidosis is erythema nodosum. A characteristic form of acute sarcoidosis involves the association of erythema nodosum, hilar lymphadenopathy, fever, arthritis, and uveitis, which has been termed Lofgren syndrome. This presentation has a good prognosis with complete resolution within several months in most patients.
- Behçet disease (associated with erythema nodosum)
- Pregnancy: Some patients develop erythema nodosum during pregnancy, most frequently during the second trimester. Repeated episodes occur with subsequent pregnancies or with the use of oral contraceptives.
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| References |
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References
Nguyen GC, Torres EA, Regueiro M, et al. Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohort. Am J Gastroenterol. May 2006;101(5):1012-23. [Medline].
Mert A, Ozaras R, Tabak F, Pekmezci S, Demirkesen C, Ozturk R. Erythema nodosum: an experience of 10 years. Scand J Infect Dis. 2004;36(6-7):424-7. [Medline].
Hassink RI, Pasquinelli-Egli CE, Jacomella V, Laux-End R, Bianchetti MG. Conditions currently associated with erythema nodosum in Swiss children. Eur J Pediatr. Nov 1997;156(11):851-3. [Medline].
Mert A, Ozaras R, Tabak F, Ozturk R. Primary tuberculosis cases presenting with erythema nodosum. J Dermatol. Jan 2004;31(1):66-8. [Medline].
Kakourou T, Drosatou P, Psychou F, Aroni K, Nicolaidou P. Erythema nodosum in children: a prospective study. J Am Acad Dermatol. Jan 2001;44(1):17-21. [Medline].
Puavilai S, Sakuntabhai A, Sriprachaya-Anunt S, Rajatanavin N, Charuwichitratana S. Etiology of erythema nodosum. J Med Assoc Thai. Feb 1995;78(2):72-5. [Medline].
Bottone EJ. Yersinia enterocolitica: the charisma continues. Clin Microbiol Rev. Apr 1997;10(2):257-76. [Medline].
Labbe L, Perel Y, Maleville J, Taieb A. Erythema nodosum in children: a study of 27 patients. Pediatr Dermatol. Nov-Dec 1996;13(6):447-50. [Medline].
Stolk-Engelaar VM, Hoogkamp-Korstanje JA. Clinical presentation and diagnosis of gastrointestinal infections by Yersinia enterocolitica in 261 Dutch patients. Scand J Infect Dis. 1996;28(6):571-5. [Medline].
Farhi D, Cosnes J, Zizi N, et al. Significance of erythema nodosum and pyoderma gangrenosum in inflammatory bowel diseases: a cohort study of 2402 patients. Medicine (Baltimore). Sep 2008;87(5):281-93. [Medline].
Sullivan R, Clowers-Webb H, Davis MD. Erythema nodosum: a presenting sign of acute myelogenous leukemia. Cutis. Aug 2005;76(2):114-6. [Medline].
Moraes AJ, Soares PM, Zapata AL, Lotito AP, Sallum AM, Silva CA. Panniculitis in childhood and adolescence. Pediatr Int. Feb 2006;48(1):48-53. [Medline].
Requena L, Yus ES. Panniculitis. Part I. Mostly septal panniculitis. J Am Acad Dermatol. Aug 2001;45(2):163-83; quiz 184-6. [Medline].
Marshall JK, Irvine EJ. Successful therapy of refractory erythema nodosum associated with Crohn's disease using potassium iodide. Can J Gastroenterol. Sep 1997;11(6):501-2. [Medline].
Tseng S, Pak G, Washenik K, Pomeranz MK, Shupack JL. Rediscovering thalidomide: a review of its mechanism of action, side effects, and potential uses. J Am Acad Dermatol. Dec 1996;35(6):969-79. [Medline].
Further Reading
Keywords
erythema nodosum, EN, delayed hypersensitivity reaction, erythematous eruption, nodular eruption, panniculus, arthralgia, infection-induced EN, idiopathic EN, red tender nodules, aching legs, swollen ankles, hilar adenopathy, morning stiffness, joint tenderness, synovitis, streptococcal infection, sarcoidosis, tuberculosis
Yersinia enterocolitica, Mycoplasma pneumoniae, leprosy, lymphogranuloma venereum, Salmonella infection, Campylobacter infection, coccidioidomycosis, San Joaquin Valley fever, histoplasmosis, blastomycosis, ulcerative colitis, Crohn disease, enteropathies, chronic ulcerative colitis, lymphoma EN, uveitis, Lofgren syndrome, Behçet disease
