ENLIST 1: An International Multi-centre Cross-sectional Study of the Clinical Features of Erythema Nodosum Leprosum

Abstract

Erythema nodosum leprosum (ENL) is a severe multisystem immune mediated complication of borderline lepromatous leprosy and lepromatous leprosy. ENL is associated with skin lesions, neuritis, arthritis, dactylitis, eye inflammation, osteitis, orchitis, lymphadenitis and nephritis. The treatment of ENL requires immunosuppression, which is often required for prolonged periods of time and may lead to serious adverse effects. ENL and its treatment is associated with increased mortality and economic hardship. Improved, evidence-based treatments for ENL are needed; however, defining the severity of ENL and outcome measures for treatment studies is difficult because of the multiple organ systems involved. A cross-sectional study was performed, by the members of the Erythema Nodosum Leprosum International STudy (ENLIST) Group, of patients with ENL attending seven leprosy referral centres in Brazil, Ethiopia, India, Nepal, the Philippines and the United Kingdom. We systematically documented the clinical features and type of ENL, its severity and the drugs used to treat it. Patients with chronic ENL were more likely to be assessed as having severe ENL. Pain, the most frequent symptom, assessed using a semi-quantitative scale was significantly worse in individuals with “severe” ENL. Our findings will determine the items to be included in a severity scale of ENL which we are developing and validating. The study also provides data on the clinical features of ENL, which can be incorporated into a definition of ENL and used for outcome measures in treatment studies.

A Systematic Review of Immunological Studies of Erythema Nodosum Leprosum

“…Individuals with ENL present crops of painful, erythematous skin nodules with systemic symptoms of fever and malaise (6). ENL is a multisystem disorder and other organ involvement includes iritis, arthritis, lymphadenitis, orchitis, and neuritis (6).…”

“…High doses of clofazimine are also commonly used (6). Treatment often lasts for many months or years.…”

New therapeutics for leprosy

“…The management of ENL has changed little since the report by Sheskin of the effectiveness of thalidomide in six patients in 1965 . Patients with ENL continue to be treated with prolonged courses of corticosteroids, thalidomide and clofazimine . The degree of immunosuppression required is often profound and severe adverse effects including deaths attributable to corticosteroids are common …”

“…The median age of individuals affected by ENL is 32 years and managing ENL in women of childbearing potential is particularly challenging due to the teratogenic effects of thalidomide. Apremilast is contraindicated in pregnancy and so acceptable, effective methods of preventing conception are still required.…”

Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles

“…Leprosy immune reactions are systemic inflammatory complications that commonly occur when introducing a treatment. However, these reactions may also occur at any time during the disease course and can relapse intermittently over several years 1,2 . Leprosy immune reactions are classified by the World Health Organization (WHO) as type 1 (T1R or reverse reaction) and type 2 (T2R or erythema nodosum leprosum) and are manifested by multibacillary (MB) patients 1,2 .…”