Erythema nodosum leprosum (ENL) or type 2 lepra reactions complicate lepromatous leprosy and borderline lepromatous leprosy. We report an 11-year retrospective case record analysis of 481 outpatients with borderline lepromatous and lepromatous leprosy at the Dhoolpet Leprosy Research Center in Hyderabad, India.. The overall prevalence of ENL was 24%, 49.4% among cases of lepromatous leprosy (LL) and 9% among cases of borderline lepromatous (BL) leprosy. Logistic regression analysis identified LL (odds ratio [OR] = 8.4, 95% confidence interval [CI] = 4.6-15.4, P or = 4+ (OR = 5.2, 95% CI = 2.1-12.9, P = 0.001) as major risk factors. The average patient with ENL was male, 34.7 years of age, and had multiple episodes of ENL (mean = 3.1) over an 18.5-month period. Three types of ENL were identified: single acute ENL, multiple acute ENL (repeated discrete episodes), and chronic ENL (continuous episodes). Acute single ENL is rare, accounting for only 8% of cases. Chronic ENL accounted for 62.5% of the cohort. Chronic ENL was of longer duration and more severe. An age > or = 35 years was a risk factor for developing chronic ENL. Patients with chronic ENL were more compliant with multi-drug therapy, especially during the first six doses of multi-drug therapy. Distinguishing these different types of ENL would be useful for patient management and developing improved treatment of these debilitating reactions. Improved strategies for treatment and management of these reactions need to be developed.

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Clinical course of erythema nodosum leprosum: an 11-year cohort study in Hyderabad, India.

Leprosy or Hansen's disease is a chronic infectious disease caused by the Mycobacterium leprae. The skin and nervous manifestations of the disease present a singular clinical picture that is easily recognized. After India, Brazil still is the second country with the greatest number of cases in the world. Around 94% of the known cases and 94% of the new cases reported in America, come from Brazil. The disease presents itself in two well-defined stable and opposite poles (lepromatous and tuberculoid) and two unstable groups (indeterminate and dimorphic). The spectrum of presentation of the disease may also be classified as: tuberculoid tuberculoid (TT), borderline tuberculoid (BT), borderline borderline (BB), borderline lepromatous (BL) and lepromatous lepromatous (LL). The finding of acid fast bacillus in tissue is the most useful method of diagnosis. The effective treatment of leprosy includes the use of specific therapy, suppression of lepra reactions, prevention of physical incapacity, and physical and psychosocial rehabilitation. Chemotherapy with rifampin, dapsone and clofazimine have produced very good results and the control of the disease in Brazil in the foreseeable future is likely.

Leprosy in Brazil

The type of leprosy that affects an individual depends on the immune response mounted against the organism This leads to a spectrum of disease which may be complicated by immunological phenomena called reactions Antimicrobial chemotherapy is effective in treating the Mycobacterium leprae infection but up to 30% of individuals with borderline disease experience Type 1 reactions (T1Rs) T1Rs are immunologically mediated episodes, localised in skin and nerves, which are a major cause of nerve function impairment Nerve function impairment may result in disability and deformity We review the frequency and features of Type 1 reactions The data from the limited number of randomised controlled trials of treatment are discussed These four randomised controlled trials were all conducted in south Asia The accepted treatment of T1Rs is with oral corticosteroids but there is no consensus about the dose or duration of treatment due to the lack of data One randomised controlled trial showed that patients treated with a 5 month course of prednisolone (total dose 231 g) were less likely to need additional prednisolone than those treated with a 3 month course of prednisolone (total dose 294 g) This study did not use nerve function as an outcome measure The improvement in nerve function impairment with steroid treatment is highly variable, with 33-73% of nerves recovering fully Optimal steroid regimes and alternative treatments need to be identified if the disability associated with leprosy is to be minimised Search strategy Papers for this review were identified by repeated searches of the Cochrane Clinical Trials Register, PubMed and LILACS with various combinations of the following search terms 'leprosy', 'lepra', 'reaction', 'steroids', 'corticosteroids', 'reversal', 'Type 1', 'Hansen*' Searches were complete to the end of November 2008

Leprosy type 1 (reversal) reactions and their management.

Erythema nodosum leprosum (ENL) is an immune-mediated complication of leprosy presenting with inflammatory skin nodules and involvement of multiple organ systems, often running a protracted course. Immune complex production and deposition as well as complement activation have long been regarded as the principal aetiology of ENL. However, new data show that cell-mediated immunity is also important. We have performed a critical analysis of studies on the pathology of ENL. Our main findings are as follows. ENL is characterised by an inflammatory infiltrate of neutrophils with vasculitis and/or panniculitis. There is deposition of immune complexes and complement together with Mycobacterium leprae antigens in the skin. Changes in serum levels of Igs indicate a transient, localised immune response. The major T-cell subtype in ENL is the CD4 cell, in contrast to lepromatous leprosy where CD8 cells predominate. The cytokines TNFalpha and IL-6 are consistently found whilst IL-4 is low or absent in ENL lesions, indicating a T(H)1 type response. Keratinocyte 1a and intercellular adhesion molecule-1 (ICAM-1) have been shown to be present in the epidermis in ENL, which is evidence of a cell-mediated immune response. Co-stimulatory molecules such as B7-1 have also been studied but further work is needed to draw strong conclusions. We also highlight potential areas for future research.

Towards understanding the pathology of erythema nodosum leprosum.

Erythema nodosum leprosum (ENL, Type 2 reactions) complicates lepromatous and borderline lepromatous leprosy and can affect many organ systems, often with irreversible damage The reactions commonly occur in the 2 years after starting treatment and often run a recurrent or chronic course, sometimes for many years Even with WHO multi-drug therapy about 30% of LL patients experience ENL We review drug management of ENL focussing on data from controlled trials and other studies The treatment of ENL is difficult because high doses of steroids may be required for prolonged periods and do not always control the inflammation The paradox of ENL is that it can be a life-threatening disorder and requires control with immunosuppression which may itself pose life-threatening risks for patients Treatment with thalidomide provides an effective alternative to steroid therapy, gives better long-term control and avoids the adverse effects of prolonged steroid therapy Controlled clinical trials have demonstrated that thalidomide rapidly controls ENL and is superior to aspirin and pentoxifylline However, thalidomide is teratogenic when taken in early pregnancy and is unavailable in many leprosy endemic countries We discuss the role of thalidomide in treating ENL, the complications encountered and risk reduction strategies that can be used These include good patient selection and counselling, close supervision and adequate access to appropriate contraception Further research is needed to improve the understanding and treatment of this severe and debilitating complication of leprosy Topics for research include: i The development of validated tools to measure the severity and/or activity of ENL ii A detailed assessment of the neurotoxic effects of thalidomide when used to treat ENL iii A well designed trial comparing thalidomide with prednisolone iv The development of a safe and effective alternative to both steroids and thalidomide

The role of thalidomide in the management of erythema nodosum leprosum.

It is well known that reactions are commonplace occurrences during the course of leprosy disease. Stigmatization may even be attributable to reactions which are also responsible for the worsening of neural lesions. A cohort of 162 newly-diagnosed baciloscopically positive patients from the Leprosy Care Outpatient Clinic of the Oswaldo Cruz Foundation (FIOCRUZ) was selected for this study. While 46% of the multibacillary (MB) patients submitted to the 24 fixed-dose multidrug therapy (MDT) regimen suffered reactions during treatment, it was found that all MBs were susceptible and that constant attention and care were required at all times. Fourteen per cent were classified as BB, 52% as BL, and 33% as LL. None of the variables under study, such as, sex, age, clinical form, length of illness, length of dermatological lesions, baciloscopic index (BI), or degree of disability proved to be associate with reaction among the patients studied. Reversal Reaction (RR) occurred in 45%, and Erythema Nodosum Leprosum (ENL) occurred in 55%. Among BB patients who developed reactions (15 patients), 93% presented RR; while among the LL patients who developed reactions (34 patients), 91% presented ENL. Likewise, ENL was very frequent among those with disseminate lesions, while RR was most often observed in patients with segmentary lesions. RR was also most likely to occur during the initial months of treatment. It was demonstrated that the recurrence rate of ENL was significantly higher than that of RR. Neither grade of disability nor BI was shown to be associated with RR and ENL reaction. However, the RR rate was significantly higher among patients showing BI 3.

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de Matos Hj

Papers

Reactional states in multibacillary hansen disease patients during multidrug therapy