Erythema Nodosum

Is this cellulitis—or something else?

NAOMI G. JOHANSEN, MD
Tampa, Fla
JAMES CLICK, MD
Brigham and Women’s Hospital
BARBARA B. WILSON, MD
University of Virginia

Dr Johansen is a dermatologist in Tampa, Florida, Dr Click is a senior resident at Brigham and Women’s Hospital in Boston, and Dr Wilson is associate professor of dermatology at the University of Virginia School of Medicine in Charlottesville.

KIRK BARBER, MD, FRCPC––Series Editor: Dr Barber is a consultant dermatologist at Alberta Children’s Hospital and clinical associate professor of medicine and community health sciences at the University of Calgary in Alberta.

erythema nodosumCase: A 16-year-old girl has had multiple red, tender nodules over the anterior surfaces of her lower extremities for about 2 weeks. The lesions have been accompanied by arthralgia of the ankles and knees.

The patient has been otherwise healthy and is taking no medications. She denies trauma to the area. Her past medical history and family and social histories are unremarkable.

The erythematous to violaceous nodules are about 2 cm in diameter. Edema of the ankles is noted. Other physical findings are normal.

Is this cellulitis—or something else?

(Answer on next page.)

Answer: Painful nodules and ankle edema are typical of erythema nodosum.

This teenage girl has erythema nodosum (EN), the most common panniculitis, or inflammation of subcutaneous fat.1 Her rash is characteristic of EN in that the lesions are round to ovoid, 2 to 6 cm in diameter, and located on the extensor surfaces of the lower extremities—although the lesions may also arise on the forearms and trunk. That the patient is a girl is also characteristic of EN, which shows a predilection for women, with a 3 to 6:1 ratio of females to males affected. The condition has been reported in virtually all age groups; however, the peak age range is in the third to fourth decade.

This patient did not report having malaise, arthralgias, and low-grade fever before the rash onset; however, such a prodrome precedes the eruption in the majority of patients. The lesions evolve from firm and erythematous papules to blue or purple nodules and eventually fade over several weeks, as was the case in this girl, and her lesions resolved without residual scarring or ulceration. In some patients, the condition lasts 6 months or more and has the potential to recur for years. Edema of the ankles frequently accompanies the nodules.

EN is thought to be the result of a hypersensitivity reaction. Although about half of all cases are idiopathic, EN is associated with a number of diseases, including sarcoidosis, inflammatory bowel disease, and infection.2 The most commonly related infection is strep throat; however, fungal infections (eg, histoplasmosis, coccidiomycosis, and blastomycosis), tuberculosis, and other infections can accompany EN.3,4 Thus patients with a diagnosis of EN require further evaluation that includes a complete history and physical examination, antistreptolysin-O titer or throat culture, tuberculin skin test, and chest radiograph.

Rarely an underlying malignancy, such as lymphoma, may be associated with EN. Drugs reported to cause EN include oral contraceptives, sulfonamides, and bromides.
EN is diagnosed clinically. When the presentation is atypical or the diagnosis is in question, an excisional or deep punch biopsy may be performed. A normal punch biopsy may not provide adequate subcutaneous tissue for analysis. Histologically, septal fibrosis is observed in the subcutaneous fat, granulomatous inflammation, and a lymphohistiocytic infiltrate.

Treatment of EN is primarily directed at any underlying condition. Bed rest and leg elevation may provide some relief of symptoms, especially if lower extremity edema is significant. Additional benefit may be obtained using NSAIDs, compressive dressings, and systemic corticosteroids. If the cause is unknown and lesions are persistent, a supersaturated solution of potassium iodide can be titrated until a clinical response is achieved.5