Elsevier

Dermatologic Clinics

Volume 26, Issue 4, October 2008, Pages 425-438
Dermatologic Clinics

Erythema Nodosum

https://doi.org/10.1016/j.det.2008.05.014Get rights and content

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.

Section snippets

Etiology

Erythema nodosum may be associated with a wide variety of disease processes and its observation must always be followed by a search for underlying etiology. A review of the literature reveals that the list of etiologic factors that can lead to erythema nodosum is long and varied, including infections, drugs, malignant diseases, and a wide group of miscellaneous conditions (Box 1).1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32

Pathogenesis

Erythema nodosum is considered to be a hypersensitivity response to a wide variety of inciting factors. The variability of possible antigenic stimuli that can induce erythema nodosum indicates that this disorder is a cutaneous reactive process and that the skin has limited responses to different provoking agents. Erythema nodosum probably results from the formation of immune complexes and their deposition in and around venules of the connective tissue septa of the subcutaneous fat. Circulating

Clinical features

Erythema nodosum can occur at any age, but most cases appear between the second and fourth decades of the life, with the peak of incidence between 20 and 30 years of age, probably because of the high incidence of sarcoidosis at this age.136 Several studies have demonstrated that erythema nodosum occurs three to six times more frequently in women than in men,137 although the gender incidence before puberty is approximately equal.124 Racial and geographic differences of incidence vary depending

Laboratory anomalies

Because the list of possible etiologic factors in erythema nodosum is extensive, a rational, cost-effective, diagnostic approach in patients with erythema nodosum is desirable. A complete clinical history should be elicited in all patients, with reference of previous diseases, medications, foreign travel, pets and hobbies, and familial cases.

Initial evaluation should include complete blood count, determination of the sedimentation rate, antistreptolysin O titer, urinalysis, throat culture,

Histopathology

Histopathologically, erythema nodosum is the stereotypical example of a mostly septal panniculitis with no vasculitis. The septa of subcutaneous fat are always thickened and infiltrated by inflammatory cells that extend to the periseptal areas of the fat lobules. Usually, a superficial and deep perivascular inflammatory infiltrate predominantly composed of lymphocytes is also seen in the overlying dermis. The composition of the inflammatory infiltrate in the septa varies with age of the lesion.

Prognosis

Most cases of erythema nodosum regress spontaneously in 3 to 4 weeks. More severe cases need about 6 weeks. Relapses are not exceptional, and they are more common in patients with idiopathic erythema nodosum and erythema nodosum associated with nonstreptococcal or streptococcal upper respiratory tract infections. Complications are uncommon. A patient developed retrobulbar optic nerve neuritis during the acute episode of erythema nodosum,166 and another patient with chronic hepatitis C had

Treatment

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 and nonsteroidal anti-inflammatory drugs, such as oxyphenbutazone, 400 mg per day,168 indomethacin, 100 to 150 mg per day,169 or naproxen, 500 mg per day,170 may be helpful to enhance analgesia and resolution. If the lesions persist longer, potassium iodide in a

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