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      Serological responses to prednisolone treatment in leprosy reactions: study of TNF-α, antibodies to phenolic glycolipid-1, lipoarabinomanan, ceramide and S100-B

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          Abstract

          Background

          Corticosteroids have been extensively used in the treatment of immunological reactions and neuritis in leprosy. The present study evaluates the serological response to steroid treatment in leprosy reactions and neuritis.

          Methods

          Seven serological markers [TNF-α, antibodies to Phenolic glycolipid-1 (PGL-1 IgM and IgG), Lipoarabinomannan (LAM IgG1 and IgG3), C2-Ceramide and S100 B] were analyzed longitudinally in 72 leprosy patients before, during and after the reaction. At the onset of reaction these patients received a standard course of prednisolone. The levels of the above markers were measured by Enzyme linked immunosorbent assay (ELISA) and compared with the individuals own value in the month prior to the reaction and presented as percentage increase.

          Results

          One month before the reaction individuals showed a varying increase in the level of different markers such as TNF-α (53%) and antibodies to Ceramide (53%), followed by to PGL-1 (51%), S100B (50%) and LAM (26%). The increase was significantly associated with clinical finding of nerve pain, tenderness and new nerve function impairment. After one month prednisolone therapy, there was a fall in the levels [ TNF-α (60%), C2-Ceramide (54%), S100B (67%), PGL-1(47%) and LAM (52%)] with each marker responding differently to steroid.

          Conclusion

          Reactions in leprosy are inflammatory processes wherein a rise in set of serological markers can be detected a month before the clinical onset of reaction, some of which remain elevated during their action and steroid treatment induces a variable fall in the levels, and this forms the basis for a variable individual response to steroid therapy.

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          Most cited references23

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          Leprosy now: epidemiology, progress, challenges, and research gaps.

          Leprosy continues to be a challenge to health worldwide, with about 250,000 new cases being detected every year. Despite widespread implementation of effective multidrug therapy, leprosy has not been eliminated. A third of newly diagnosed patients have nerve damage and might develop disabilities, although the proportion varies according to several factors, including level of self-care. Women who develop leprosy continue to be especially disadvantaged, with rates of late diagnosis and disability remaining high in this subgroup. Leprosy was not a specified disease in the Millennium Development Goals, but improvements in the other areas they cover, such as education and levels of poverty, will help leprosy patients and services. We review data and make recommendations for research on diagnosis, treatment, and prevention, such as further use of molecular analysis of the Mycobacterium leprae genome, implementation of BCG vaccination, and administration of chemoprophylaxis to household contacts. We also suggest development of tools for early diagnosis and detection of infection and nerve damage, and formulation of strategies to manage the chronic complications of leprosy, such as immune-mediated reactions and neuropathy. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Global leprosy situation, 2010.

            (2010)
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              The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in north India.

              The aim of this study was to find predictors of neuropathy and reactions, determine the most sensitive methods for detecting peripheral neuropathy, study the pathogenesis of neuropathy and reactions and create a bank of specimen, backed up by detailed clinical documentation. A multi-centre cohort study of 303 multibacillary leprosy patients in Northern India was followed for 2 years. All newly registered MB patients requiring a full course of MDT, who were smear positive and/or had six or more skin lesions and/or had two or more nerve trunks involved, were eligible. A detailed history was taken and physical and neurological examinations were performed. Nerve function was assessed at each visit with nerve conduction testing, warm and cold detection thresholds, vibrometry, dynamometry, monofilaments and voluntary muscle testing. Because the latter two are widely used in leprosy clinics, they were used as 'gold standard' for sensory and motor impairment. Other outcome events were type 1 and 2 reactions and neuritis. All subjects had a skin biopsy at registration, repeated at the time of an outcome event, along with a nerve biopsy. These were examined using a variety of immunohistological techniques. Blood sampling for serological testing was done at every 4-weekly clinic visit. At diagnosis, 115 patients had an outcome event of recent onset. Many people had skin lesions overlying a major nerve trunk, which were shown to be significantly associated with an increased of sensory or motor impairment. The most important adjusted odds ratios for motor impairment were, facial 4.5 (1.3-16) and ulnar 3.5 (1.0-8.5); for sensory impairment they were, ulnar 2.9 (1.3-6.5), median 3.6 (1.1-12) and posterior tibial 4.0 (1.8-8.7). Nerve enlargement was found in 94% of patients, while only 24% and 3% had paraesthesia and nerve tenderness on palpation, respectively. These increased the risk of reactions only marginally. Seven subjects had abnormal tendon reflexes and seven abnormal joint position sense. In all but one case, these impairments were accompanied by abnormalities in two or more other nerve function tests and thus seemed to indicate more severe neuropathy. At diagnosis, 38% of a cohort of newly diagnosed MB leprosy patients had recent or new reactions or nerve damage at the time of intake into the study. The main risk factor for neuropathy found in this baseline analysis was the presence of skin lesions overlying nerve trunks. They increased the risk of sensory or motor impairment in the concerned nerve by 3-4 times. For some nerves, reactional signs in the lesions further increased this risk to 6-8 times the risk of those without such lesions. Patients with skin lesions overlying peripheral nerve trunks should be carefully monitored for development of sensory or motor impairment.
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                Author and article information

                Contributors
                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central
                1476-511X
                2014
                28 July 2014
                : 13
                : 119
                Affiliations
                [1 ]CODEWEL Nireekshana ACET India, Narayanaguda, Hyderabad 500029 AP, India
                [2 ]Department of Microbiology, Government Institute of Science, Madame Cama Road, Mumbai, India
                [3 ]London School of Hygiene & Tropical Medicine, London, UK
                [4 ]Department of Neurology and Clinical Neurophysiology, St. Elisabeth Hospital, Tilburg, The Netherlands
                [5 ]The Leprosy Mission Hospital, Naini, Allahabad, UP, India
                [6 ]Miraj Civil Hospital, Miraj, Maharashtra, India
                [7 ]Blue Peter Public Health & Research Centre (BPHRC), Hyderabad, AP, India
                [8 ]Mahavir Medical Research Center, 37/165, BhagwanMahavir Marg, AC Guards, Masab Tank, Hyderabad, AP, India
                [9 ]The Leprosy Mission Hospital, Faizabad, UP, India
                [10 ]Leprosy Unit, Royal Tropical Institute, Amsterdam, The Netherlands
                Article
                1476-511X-13-119
                10.1186/1476-511X-13-119
                4124507
                25070345
                05b26989-558d-462b-a255-5e3150c6461b
                Copyright © 2014 Raju et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 9 June 2014
                : 18 July 2014
                Categories
                Research

                Biochemistry
                leprosy,tnf-α,corticosteroids,prednisolone,pgl-1,s-100b,lam,ceramide
                Biochemistry
                leprosy, tnf-α, corticosteroids, prednisolone, pgl-1, s-100b, lam, ceramide

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