Erythema nodosum

Erythema nodosum is the most frequent clinicopathologic variant of panniculitis. The process is a cutaneous reaction that may be associated with a wide variety of disorders, including infections, sarcoidosis, rheumatologic diseases, inflammatory bowel diseases, medications, autoimmune disorders, pregnancy, and malignancies. Histopathologically, erythema nodosum is the stereotypical example of a mostly septal panniculitis with no vasculitis. The composition of the inflammatory infiltrate in the septa varies with age of the lesion. Treatment of erythema nodosum should be directed to the underlying associated condition, if identified.     

Erythema nodosum

Erythema nodosum (EN) is the most common form of panniculitis. It is characterized by the presence of rounded or oval, slightly raised, nonulcerative painful red nodules in the skin and subcutaneous fatty tissue, 1 to 6 cm in diameter, sometimes coalescing. They tend to be symmetrical in distribution and are usually located bilaterally on the lower extremities, particularly on the anterior tibial surface, although they may also involve the ankles, the lower parts of the thighs, and the forearms.     

Erythema nodosum

Erythema nodosum is the most frequent clinicopathologic variant of panniculitis. The process is a cutaneous reaction that may be associated with a wide variety of disorders, including infections, sarcoidosis, rheumatologic diseases, inflammatory bowel diseases, medications, autoimmune disorders, pregnancy, and malignancies. Erythema nodosum typically manifest by the sudden onset of symmetrical, tender, erythematous, warm nodules and raised plaques usually located on the lower limbs. Often the lesions are bilaterally distributed. At first, the nodules show a bright red color, but within a few days they become livid red or purplish and, finally, they exhibit a yellow or greenish appearance, taking on the look of a deep bruise. Ulceration is never seen, and the nodules heal without atrophy or scarring. Histopathologically, erythema nodosum is the stereotypical example of a mostly septal panniculitis with no vasculitis. The septa of subcutaneous fat are always thickened and variously infiltrated by inflammatory cells that extend to the periseptal areas of the fat lobules. The composition of the inflammatory infiltrate in the septa varies with age of the lesion. In early lesions edema, hemorrhage, and neutrophils are responsible for the septal thickening, whereas fibrosis, periseptal granulation tissue, lymphocytes, and multinucleated giant cells are the main findings in late stage lesions of erythema nodosum. A histopathologic hallmark of erythema nodosum is the presence of the so-called Miescher's radial granulomas, which consist of small, well-defined nodular aggregations of small histiocytes arranged radially around a central cleft of variable shape. Treatment of erythema nodosum should be directed to the underlying associated condition, if identified. Usually, nodules of erythema nodosum regress spontaneously within a few weeks, and bed rest is often sufficient treatment. Aspirin, nonsteroidal antiinflammatory drugs, such as oxyphenbutazone, indomethacin or naproxen, and potassium iodide may be helpful drugs to enhance analgesia and resolution. Systemic corticosteroids are rarely indicated in erythema nodosum and before these drugs are administered an underlying infection should be ruled out.     

Erythema nodosum

Erythema nodosum (EN) has been known since 1798,¹ when it was considered to be a clinical entity. In the latter half of the 19th century, “rheumatism” was regarded as the principal cause and tuberculosis as a minor causative factor of EN. During the first four decades of the present century, tuberculosis was reported to be the cause of EN in over 90% of adult patients, but in the 1940s and 50s, sarcoidosis, streptococcal, and other infections, and some other causes, were suggested.² During the last 15–20 years, a variety of factors have been found to trigger EN; however, despite thorough investigations, no evident cause for EN can be found in 10–30% of cases (Fig. 1).     

Erythema nodosum

Erythema nodosum is the most common and, in its classic form, the most easily recognized cause of inflammatory nodules on the legs. It is characterized by inflammatory, tender, nonulcerating, nonscarring nodules that are typically multiple and bilateral. The rather characteristic clinical presentation can be attributable to one of many causes or associated with a wide spectrum of systemic diseases. Diagnosis, evaluation, and treatment are discussed.     

Erythema nodosum migrans

During 1963-1971 at the University Central Hospital, Helsinki, 438 patients with erythema nodosum (EN) were seen. Of these 56 were diagnosed erythema nodosum migrans (ENmi), which is considered only a clinical variation of EN. Only 3 of these patients were men. The mean duration of the eruption was 4.5 months. The number of nodules varied from 1 to 8. In 40 patients they were unilateral. No scarring resulted. Patients' general health was good. Fever and artholgia were rare.1 In half the ENmi cases no other disease or condition could be associated with the eruption. Of conditions possibly triggering the EN, pregnancy was recorded in 40 percent; streptococcal infections and sarcoidosis were next in frequency. The number of oral contraceptive users among EN patients was 2 1/2 times as high as expected based on sales figures. (According to the sales statistics 16 percent of women of fertile age in Finland take this medication while 40 percent of women of fertile age with EN were taking oral contraceptions at onset of the eruption. ) This supports the view that female sex hormones may influence the host response to various agents.     

Erythema nodosum in Singapore

A retrospective study was carried out of all patients presenting with erythema nodosum over a 3-year period (1994-1997) at the National Skin Centre, Singapore. There were 75 patients, aged 4-70 years with a peak (40%) in the 21-30-year-old age group; 65 were female and 10 were male, giving a female to male ratio of 6.5 : 1. Precipitating factors included viral respiratory tract infections and streptococcal pharyngitis in 20 cases (26%), tuberculosis in two cases (3%), pregnancy in three cases (4%) and miscellaneous conditions: Behcet's syndrome (two cases), gonorrhoea (one case), varicella (one case) and cat-scratch disease (one case). The cause was unknown in 45 cases (60%). The pattern of erythema nodosum in Singapore is similar to that reported in the Western literature except that sarcoidosis and inflammatory bowel disease are uncommon associations.     

Erythema nodosum in Sweet's syndrome

A 36-year-old man had Sweet's syndrome associated with plaques on the legs that were typical of erythema nodosum both clinically and histologically. To our knowledge, true erythema nodosum has not previously been recognized as part of Sweet's syndrome.     

Erythema nodosum associated with sporotrichosis

Case 1 A 34‐year‐old woman had ulcerated lesion 2 cm in diameter on the right leg of 2 months’ evolution. She also presented painful erythematous nodules on lower limbs accompanied by arthralgia appearing 1 month after the initial lesion ( Figure 1a ). The patient reported having been scratched on the right leg by a cat with sporotrichosis 15 days before the initial symptoms. Examination of the ulcerated lesion showed growth of Sporothrix schenckii, and histological investigation of one nodule showed a mononuclear inflammatory infiltrate in the hypodermis with a predominantly septal distribution, negative upon culture for fungi ( Figure 1b ). Radiographic examination of left ankle showed increased soft tissue, while other ancillary tests were normal. The patient was treated with itraconazole 100 mg/day for 4 months, with regression of Erythema nodosum (EN) on day 20.

Figure Figure 1  Open in figure viewer PowerPoint (a) Ulcerated lesions on right calf and erythematous nodules on lower limbs. (b) Histopathology of one lower limbs nodule, displaying small granuloma in the subcutaneous cellular tissue (HE, 4 ×)