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Title: A prospective study of borderline leprosy reactions
Author: Barnetson, Ross St Clair
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1977
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Leprosy is still one of the most important diseases in the world today: it afflicts 15 million people and is the most important cause of deformity in man. The causative organism, Mycobacterium leprae (M. leprae) has an affinity for skin and nerve and is remarkably nontoxic; therefore, most of the clinical manifestations are due to the host response. The nerve destruction with consequent deformity, which is the most important complication of the disease, usually occurs during borderline leprosy reactions. Surprisingly there has been little research into this type of reaction, though it seems likely that they result from an increase in cell-mediated immunological reactivity. This thesis describes a prospective study of 83 patients who attended the Addis Ababa Leprosy Hospital with borderline leprosy, the purpose of which was to clarify the mechanisms involved in borderline leprosy reactions. Seventeen of the 83 patients developed reactions during the period of follow up (between one and two years) and the clinical, histological and immunological findings were compared in this group of patients with those patients who did not develop reactions. It was observed that in the reaction patients there was a significant rise in lymphocyte transformation (LT) responses to both 'whole'and 'sonicated' preparations of M. leprae, confirming that these reactions are due to an increase in cell-mediated immunity to mycobacterial antigens. However it was found that in those patients who presented with reactions involving the skin alone, there was a very marked rise in the responses to whole M. leprae (and a smaller rise in response to sonicated M. leprae) whereas those who had reactions involving nerve alone had a rise in LT responses only to sonicated M. leprae. Those with involvement of skin and nerve in the reaction had a marked rise in responses to both antigens. The reason for this remains obscure, but it seems likely that bacillary membrane antigens are associated with 'skin' reactions, and cytoplasmic antigens with 'nerve' reactions; it is possible that this results from different handling of the bacilli by macrophages in skin and Schwann cells in nerve. There were two other findings of considerable importance related to the mechanisms which might be involved in reactions. Firstly, bacilli were often found in dermal and peripheral nerves without surrounding chronic inflammatory infiltrate, though there was marked granulomatous response in skin. It seems likely that this is of importance as sudden 'immune recognition' of bacilli in nerve tissue might account for the increased cell-mediated reactivity that occurs in this type of reaction. Secondly, autologous plasma, which is normally suppressive to LT responses to phytohaemagglutinin in leprosy, developed an augmenting effect during reaction. it is possible that plasma factors normally act as a form of 'brake' mechanism preventing delayed hypersensitivity reactions but during reaction this effect is lost. Probably the most important observation of the study in the short term was the effect of dapsone on reactions. It has always been taught that dapsone should be given initially at low dosage in an attempt to prevent reactions: however, there have been no published reports to support this hypothesis. In a study of 68 patients it was found that of those receiving dapsone 5 mg daily, 11 patients developed reactions whereas only 3 of those receiving 50 mg daily did so. This would suggest that dapsone in higher dosage does not predispose to borderline leprosy reactions, and indeed, may prevent them. When those patients who did not develop reactions were studied it was found that those with borderline tuberculoid (BT) leprosy had significantly higher LT responses to whole and sonicated M. leprae than those with borderline lepromatous (BL) leprosy. However, there was considerable variation in both groups. Those patients with inflamed skin lesions had higher responses in both BT and BL patients than those with non-inflamed lesions, and indeed, those with BL leprosy and inflamed skin lesions had higher responses than those with BT leprosy with non-inflamed lesions. This would suggest that the LT test in leprosy reflects the degree of delayed hypersensitivity rather than that of protective immunity, and that as in tuberculosis, the two phenomena are not necessarily related. Thus some of the mechanisms involved in borderline leprosy reactions and the immune response in leprosy have been clarified, and it is hoped that as a result of this study reactions in some patients will be prevented. It is also hoped that the encouraging results of the study will stimulate further research into these reactions to minimise the morbidity of leprosy in the future.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available