Erythema Nodosum

Introduction

Erythema nodosum gets attention to us as it is the most frequent panniculitis seen in the dermatology office, it is related to a immunologic hypersensitivity reaction. Beyond treating underlying triggers, therapeutic options of EN consist mainly of NSAIDs,symptomatic care, potassium iodide, and colchicine.

We present here the last review found in Pubmed about this pathology, it is an article from the Dermatology Therapy Journal published on July 2010.

The Article

EN is the most common form of panniculitis. It classically presents as tender, warm, erythematous subcutaneous nodules on the bilateral pretibial areas. Although it can occur in both sexes and at any age, it has a predilection for young women, particularly during the second through the fourth decades of life.  The female to male ratio has been reported as 4–5 : 1. EN has also been reported to occur in anatomic locations other than the shins, especially on the thighs and extensor forearms.

Ulceration or suppuration of lesions of EN is exceedingly rare, although it has been reported in a case associated with Crohn’s disease. Moreusually, individual nodules last approximately 2 weeks and then slowly involute without scarring. New crops of lesions can continue to arise for as long as 6 weeks. Occasionally, if subcutaneous hemorrhage has occurred, the lesions of EN resolve with a bruise-like hyperpigmentation and are then sometimes termed erythema contusiforme.

EN is often accompanied by systemic symptoms including fever, malaise, arthritis, and arthralgias. These symptoms can comprise a prodrome as early as 1–3 weeks before the lesions appear. Arthralgias and rheumatoid factor-negative arthritis have been reported to persist for up to 2 years after the resolution of EN lesions.

Pathophysiology

EN is generally regarded as a type IV delayed hypersensitivity response to a variety of antigens. This nonspecific subcutaneous reaction pattern is commonly idiopathic; a trigger is not identified in one third to one half of cases . The most common infectious cause and the most common cause in children is streptococcal upper respiratory infections (Lancefield Group A, Streptococcus pyogenes), accounting for 28–44% of cases

Depending on the patient’s signs and symptoms, a reasonable laboratory and radiologic workup might include antistreptolysin O or anti-DNase B levels, a chest X-ray, stool cultures, a tuberculin skin test, and a urine pregnancy test. In the absence of specific symptoms or positive findings, further studies are probably not cost–effective.

Skin biopsy may be of great benefit in diagnosing clinically atypical cases of EN. As for all panniculitides, a deep incisional biopsy with a generous sample of the subcutaneous fat gives the greatest chance of a definitive diagnosis. Histopathologically, EN is the prototypical septal panniculitis. Neutrophils frequently predominate in early lesions, and increased circulating neutrophils in the peripheral blood may promote production of reactive oxygen intermediates and resulting tissue damage. Indeed, many of the therapeutic options discussed below may be effective through their actions on neutrophils.

Therapeutic Options

The primary treatment for EN is to remove the underlying trigger, if possible. Potential causative drugs should be discontinued based on risk–benefit assessment and consultation with the prescribing physician. Underlying infections or malignancies should receive appropriate treatment. Beyond these steps, the mainstay of treatment is symptomatic, as most cases are self-limited and will resolve spontaneously. Patients should be cautioned that up to 2 months may elapse before they stop developing new lesions. Recurrences occur in 33–41% of cases and are more likely if the etiology is unknown.

Nonsteroidal anti-inflammatory drugs. The first-line therapy is nonsteroidal anti-inflammatory drugs (NSAIDs), including salicylic acid derivatives.

Rest, elevation, and compression.  Bed rest and regular elevation of the legs are highly recommended adjuvant treatments. Some of the pain of EN is likely caused by the pressure of edema on surrounding tissues. In the present authors’ experience, raising the legs above the level of the heart for at least 30 minutes twice daily can mitigate the discomfort.

Potassium iodide.  Potassium iodide (KI) is a time-honored therapy in the arsenal of the dermatologist. First discovered in the 19th century as a treatment for thyroid disease, today, it is used to treat a variety of dermatologic conditions, including EN and nodular vasculitis. The mechanism of action of KI is not entirely known, but there is evidence that it inhibits neutrophil chemotaxis as well as significantly suppresses neutrophils’ ability to generate toxic oxygen intermediates.

Colchicine.  Colchicine has proved to be useful in the treatment of EN, particularly for lesions that occur in the setting of Behçet’s disease. Reported successful doses are between 1 and 2 mg per day, divided into twice daily dosing. For unclear reasons, women are more likely to respond to colchicine than men.

A plant-derived alkaloid, colchicine’s anti-inflammatory activity is thought to partly derive from its ability to arrest microtubule polymerization, resulting in impaired neutrophil chemotaxis. There is also new evidence that colchicine suppresses inflammasome-driven caspase-1 activation, blocks adhesion of neutrophils to endothelium by decreasing expression of L-selectin, and inhibits neutrophilic production of superoxide anions.

References

Gilchrist H, Patterson JW. Erythema nodosum and erythema induratum (nodular vasculitis): diagnosis and management. Dermatol Ther. 2010 Jul-Aug;23(4):320-7.

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