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Clinical and histopathological activity in paucibacillary leprosy patients after fixed-duration multidrug therapy.

In 37 clinically-diagnosed borderline-tuberculoid (BT) leprosy patients skin biopsies were done prior to starting multidrug therapy (MDT) and at the end of 6 months therapy. Clinical and histopathological activity, graded as active, resolving and inactive, were studied at the end of 6 months of MDT. Of the 37 clinically-diagnosed BT patients 24 could be confirmed by histopathology as having BT leprosy, while the other 13 biopsies showed features of indeterminate (I) leprosy. After 6 months of MDT, out of the 24 histopathologically-confirmed BT patients, 4 (17%) showed clinical activity and 8 (33%) showed histopathological activity. Of the 13 histopathologically-diagnosed indeterminate cases all were clinically inactive but histological activity persisted in 3 cases (23%). Out of the 37 clinically-diagnosed BT patients 3 showed both clinical and histopathological activity at the end of MDT. This study emphasizes the importance of performing histopathological examinations on leprosy patients undergoing research studies for the confirmation of diagnosis and for proper classification of the disease. The histopathological activity that outlasts the MDT may be due to the bacillary fragments that persist but clinical activity coupled with histopathological activity seen in 3 patients at the end of 6 months may foreshadow a relapse and these patients and others like them need to be followed up for longer durations.

Adolescent↗

[Leprosy in Africa. Current status and epidemiological significance].

The introduction briefly describes the pathogenesis, classification, diagnosis and modern treatment possibilities. In Africa leprosy is considered endemic. The World Health Organization estimates the total number of cases at 3.5 million. Over the last 20 years, however, the recorded number of cases has decreased dramatically. Increasing mobility on the part of the population, relocation from countryside to the cities, and a tendency towards urbanization are introducing a new dimension to leprosy distribution and the fight against the disease in Africa. Despite the not-inconsiderable financial, material and human resources that have so far been made available--mostly from outside the country--only a small percentage of the presumptive number of leprosy sufferers are receiving an adequate, modern combination therapy. This means that leprosy continues to represent a serious public and individual health problem in Africa.

Adolescent↗

A study of incidence of Australia antigen and derangements in liver function tests in leprosy.

The present study was conducted in 50 patients of various subtypes of leprosy (Lepromatous, Tuberculoid, Borderline borderline) and 25 healthy control, for detection of Australia antigen and various liver function tests (serum protein, cholesterol, alkaline phosphates, SGOT, SGPT, bilirubin and liver biopsy) to see incidence of Australia Antigen and derangement in liver function. It was concluded that incidence of Australia antigen in study and control group was zero. Total serum protein and serum globulin was increased in lepromatous leprosy. A/G ratio was reversed in 34.3% and 50% in lepromatous and tuberculoid leprosy respectively. Granulomatous hepatitis was seen in 66.66% and 50% cases of lepromatous and tuberculoid leprosy respectively. No relationships was established between hepatic lesion, Australia antigen and liver function test.

Adolescent↗

Leprosy in low endemic areas of India: an appraisal and suggested measures for control.

Prevalence of leprosy in the low endemic areas of India is described based on the observations of patients attending an Urban Leprosy Centre in the Union Territory of Delhi from the neighbouring states. The rising incidence in these so-called low to moderate endemic places is closely linked to factors related to urbanisation, movement of people in search of employment, etc., which necessitate fresh surveys in these areas. A significant number of leprosy patients attending the Centre were irregular (37.7%) in therapy and many absconded after the initial visit (35.3%), the reasons for which are discussed. These figures are compared to that from similar low endemic areas and known high endemic parts of the country. Suitable modifications to the control programme in these areas are suggested under the purview of the National Leprosy Eradication Programme.

Adolescent↗

An immunohistochemical and morphological study of amyloidosis complicating leprosy in Malaysian patients.

Congo red screening of tissue blocks from 37 consecutive autopsies on leprosy patients revealed 7 cases of systemic amyloidosis, indicating a prevalence rate of 19%. 5 were males and 2 females. All were ethnic Chinese. Their ages ranged from 52 to 85 years with a mean of 69 years. Six had lepromatous leprosy while the remaining 1 had tuberculoid leprosy. In all 7 cases, the amyloid was AA in type, being permanganate-sensitive and immunoreactive with anti-human AA protein antiserum. Hepatic deposition was limited to blood vessels, a pattern typical of AA (secondary) amyloidosis. With regard to renal involvement, 4 showed a predominantly vascular pattern of infiltration while 3 exhibited the more ominous glomerular pattern. Three died of chronic renal failure and 2 of congestive cardiac failure attributable to renal and cardiac amyloidosis respectively. One patient succumbed to septicaemia and the remaining 1 to acute myocardial infarction. AA amyloidosis remains a serious and significant complication of leprosy among Malaysians.

Aged↗

Enthesopathy in leprosy.

OBJECTIVE: To determine whether patients with leprosy have enthesopathy at the calcaneus of plantar fascia. METHODS: In a radiographic study of over 3 years, we investigated the presence and location of enthesophytes in patients with leprosy compared to healthy age and sex matched controls with no evidence of bone or joint disease. RESULTS: Calcaneus enthesopathy occurred significantly more frequently in patients with leprosy than in controls, but no difference in the location of enthesophytes was found between the 2 groups. Calcaneus spurs were detected more frequently in lepromatous patients than in tuberculoid patients. CONCLUSION: Enthesitis is a manifestation of leprosy and may be more common in lepromatous than in tuberculoid patients.

Adult↗

Skeletal manifestations of leprosy: analysis of 137 patients from different clinical settings in the pre- and post-modern treatment eras.

This study was conducted to further characterize the nature of leprosy-related bone alterations, to develop a hypothesis of their pathophysiology, and to define the impact of treatment on bone damage. Radiographs of 60 patients under care at the Carville, Louisiana leprosy hospital were compared with 50 from the early (before availability of effective treatment) part of this century and with 27 from the Toronto (Ontario, Canada) leprosy clinic. Two-thirds of lesions were so severe that distal digital tufts had been lost to whittling, resorption, or fragmentation. Fifty percent were felt to be pathognomonic for the changes of leprosy. Resorption, fragmentation, and malaligned fractures are highly suggestive of leprosy, while diaphyseal whittling appears specific when medullary sclerosis or wavy diaphyseal borders are present. Medicinal intervention appeared to be of limited benefit for bone damage; perhaps greater attention to joint/bone protection (as recommended in diabetes management) will prove helpful. Environmental adjustment to minimize injury risk and daily limb examination for injury are recommended.

Journal Article↗

Liver in leprosy: histological and biochemical findings.

The histological findings and their correlation with biochemical functions of the liver in 240 leprosy patients are presented. In 21% with tuberculoid leprosy and in 62% with lepromatous leprosy leprous granulomata were found in the liver. A significant prevalence of granulomatous lesions in the liver among patients with tuberculoid and borderline-tuberculoid leprosy of less than one year's duration suggests that bacillaemia occurs early in all forms of leprosy.There was a direct correlation between bacterial index and the presence of acid-fast bacilli in the liver. Of 50 patients with negative skin smears seven had acid-fast bacilli at liver biopsy. From none of these liver homogenates were acid-fast bacilli grown on culture in Löwenstein-Jensen medium.The alterations in liver functions were more consistently seen when acid-fast bacilli were associated with the presence of leprous granulomatous lesions. The acid-fast bacilli were found to persist even after one to five years of specific antileprosy therapy and after the bacilli in the skin had cleared up. This may explain the relatively frequent recrudescence or relapse of the bacillated types of leprosy when specific antileprosy therapy is stopped soon after bacterial negativity is attained on skin smears.

Biopsy↗

Novel HLA Class I Alleles Associated with Indian Leprosy Patients.

Convincing results on HLA Class II associations have been reported, however data on HLA class I association are limited and inconsistent from studies in Leprosy. We present here the HLA A, B, and C allele distribution by molecular high resolution PCR-SSOP technique in 32 leprosy patients compared with the 67 controls, from the same ethnic background. The significant results from the present study were a significant increase in frequency of HLA A*0206, A*1102, B*4016, B*5110, Cw*0407, and Cw*0703 was observed when compared to controls. A striking decrease in the frequency of HLA A*0101, Cw*04011, and Cw*0602 leprosy patients was observed when compared to the controls. Further haplotype A*1102-B*4006-Cw*1502 was significantly increased among the lepromatous leprosy patients when compared to the controls. It seems that HLA class I alleles play vital roles in disease association/pathogenesis with leprosy among Indians.

Journal Article↗

Autoantibodies in lepromatous leprosy.

Lepromatous leprosy patients often develop erythema nodusum leprosum (ENL) reactions mainly during treatment of the disease. Hence, this study sought to investigate correlation between the prevalence of certain autoantibodies and ENL reactions in these patients. The patients included in the study were fifty patients with lepromatous leprosy and a similar number of normal controls. Sera were collected from the patients and normal controls and the prevalence of circulating rheumatoid factor antinuclear and antismooth muscle antibodies was determined. The prevalence of autoantibodies was increased in lepromatous leprosy as compared with normal controls. The prevalence of these autoantibodies were affected differently by the ENL reactions. ENL lepromatous leprosy showed a slight decrease in prevalence of antinuclear and antismooth muscle antibodies, whereas there was a slight increase in the prevalence of rheumatoid factor in ENL lepromatous leprosy. The levels of serum immunoglobulins tended to show a decline towards ENL lepromatous patients compared with the uncomplicated lepromatous patients. The significance of these finding is discussed in relation to their possible role in the pathogenesis of ENL reaction. It is concluded that some of these autoantibodies and immunoglobulins may be utilized during ENL reactions in the formation of immune complexes.

Journal Article↗

[Reactional status of leprosy].

Reactional leprosy is studied according to its clinical forms A) Lepromatous a) Acute lepromatization: encroaching and invasive nature; the patient becomes more and more lepromatous ; bad prognosis. b) Erythema nodosum: "contusiform dermatitis"; variable prognosis not so bad as it is in the preceding case; allergic nature and its evolution is usually detained and therapeutics efficient. c) Erythema multiform. d) Lucio's phenomenon: vascular lesions and consequently necrosis as a complication of the "erythema necrotisans" (beautiful leprosy). B) Tuberculoid Reactional tuberculoid is the only one in this benign type, the Mitsuda's test must always be positive and prognosis consequently good. C) Dimorphous or "Borderline" whose Mitsuda's test is mostly negative, sometimes positive, but not stable. The lesions may stimulate the tuberculoid leprids but they invade mucous membranes, are impregnated by pigmentation, may present the Unna's band, and other characteristics of the Lepromatous type. Are associated (fever, asthenia and emaciation). Prognosis not very good, because of the possibility of lepromatization, according to its tendency. Evolution slower and frequent relapses. Besides there are nodular lesions. Pathogeny 1) Perifocal allergic reaction (Jadassohn). Similar to epituberculosis and Herxheimer reaction. 2) Septicemia. Sensitized tissues inside or outside the lesions, are invaded by the bacilli and so the allergic reaction takes place. Even without culture resources, Mycobacterium leprae has been found in the blood by direct examination. 3) Autoimmunization (Waldenstrom, Matthews and Trantman, 1965). Based upon the similarity between both humoral syndromes, in leprosy reactions and collagenous, diseases, as to: hypergammaglobulins, hypercryoproteins, antigammaglobulins, serological reactions (Wassermann, Kahn, Kline, VDRL) positives, Antistreptolysin O, protein C reactive, antinuclear factors, latex and Wadler-Rose test positives (rheumatoid tests) lowering of complement. If leprosy reaction is like this, it should be the less agressive of the autoimmune diseases. a) Its eruptions are cyclic not of long standing duration, as a general rule. b) Its prognosis has been recognized as good, except lately, because of the use of corticoid therapy which has been fatal, in many cases. After some years the leprosy reaction cures spontaneously. Treatment (see article)

Erythema Multiforme↗

Freeze-etching study of human and murine leprosy bacilli.

Morphologic features of the electron transparent zone (ETZ) material around human and murine leprosy bacilli were examined by a freeze-etching technic. The ETZ around human leprosy bacilli is composed of spherical droplets of hydrophobic material. These are always liquid at body temperature and they never show crystalline lamellar structure even at the temperature of liquid nitrogen. The ETZ around murine leprosy bacilli is composed of ribbon-like or membranous crystalline structures. This material is solid and crystalline at the body temperature of mice, and this solid material is the chief cause of the random arrangement of murine leprosy bacilli inside the cytoplasm of murine lepra cells. This crystalline structure has also been observed around murine leprosy bacilli grown on cell-free culture media.

Cell-Free System↗

Preliminary taxonomic studies on the leprosy bacillus.

Antigens extracted from leprosy bacilli obtained from infected human and armadillo tissues have been examined by immunodiffusion analysis with serum samples from lepromatous patients and with immune sera raised in rabbits. Using the best combinations of serum and antigen extracts, 12 antigenic constituents were found in the leprosy bacilli. Six of these were antigens common to all mycobacteria and nocardiae, 4 were specific to the leprosy bacillus and the position of 2 could not be determined. Groups ii and iii antigens (i.e. those associated with the slow growing and fast growing subgenera of mycobacteria) were not found in theleprosy bacillus, suggesting some relationship with M. vaccae and similar strains, in which these antigens are also missing. Lymphocyte transformation tests performed on lymph node cells of mice infected or immunized with leprosy bacilli also showed the leprosy bacillus to have a closer relationship with M. vaccae than with other mycobacteria.

Animals↗

Pitfalls in the cytological classification of borderline leprosy in the Ridley-Jopling scale.

This is a blinded, retrospective, correlative study of classification of leprosy by cytomorphology, clinical examination, and bacterial density. One hundred consecutive adequate aspirates from skin lesions of leprosy were studied. The Ridley-Jopling (R-J) five-group classification system was used. May-Gruenwald-Giemsa (MGG) and Ziehl-Neelsen (Z-N) stains were employed. Complete clinical, cytological, and bacteriological concordance was found in 88 patients. One-step mismatch in classification was seen in 12 patients with cytomorphological features of borderline-borderline (BB/mid-borderline) leprosy. Cytomorphological features of BB leprosy in aspirates from skin lesions should alert the cytopathologist to the possibility that the bacteriological index (BI) may vary widely. Appropriate steps must be taken to ensure accurate reporting of BI.

Azure Stains↗

In situ demonstration of Mycobacterium leprae antigens in leprosy lesions using monoclonal antibodies.

Cryostat sections of skin and nerve lesions of leprosy were stained with monoclonal antibodies recognising Mycobacterium leprae antigens and indirect immunofluorescence. In both the tuberculoid and lepromatous lesions, PGL1, 55-65-kDa, 17-kDa protein antigens and cross-reactive non-protein antigens were present. 65-kDa antigens were seen mainly in the skin lesions of lepromatous leprosy. The infiltrates in both the skin and nerve granulomas of tuberculoid and lepromatous leprosy showed membranous staining with monoclonal antibodies recognising PGL1 and 55-65-kDa antigens. Bacilli in the lesions and the cells in the lymph node granulomas of patients with tuberculosis or the infiltrates in the lesions of tinea corporis or sections of normal skin did not show any staining with these monoclonal antibodies. These results confirm that M. leprae antigens are present and are expressed on the infiltrating cells of leprosy lesions.

Antibodies, Bacterial↗

Restoration of defective cytokine activity within lepromatous leprosy lesions.

Immunohistological studies of tuberculoid leprosy lesions (TT-lesions) showed a dense, well organized granuloma consisting of a central area with epitheloid and giant cells containing interferon-gamma (IFN-Gamma) and CD3+, CD4+ T helper/inducer (Th/i) cells, a considerable proportion of which expressed the interleukin-2-receptor (IL-2 R). This central area was surrounded by round cells which consisted mainly of CD3+/CD8+ T cytotoxic/suppressor (Tc/s) lymphocytes. The overlying keratinocytes (KC) were strongly positive for HLA-DR antigens on the surface, indicating high intralesional IFN-Gamma activity. In contrast, lepromatous leprosy lesions (LL-lesions) showed a disorganized infiltrate composed by foamy cells and round cells, the latter mainly expressing the CD3+/CD8+ phenotype. IFN-Gamma activity could not be detected within the lesions. The KC overlying the infiltrate were consistently negative for HLA/DR reactivity pointing to a defective intralesional IFN-Gamma production in LL patients. Two out of four patients with LL leprosy could be sensitized with dinitrochlorobenzene (DNCB). The eliciting of DNCB skin reactions within the LL-lesion led to the recruitment of new infiltrating cells; the resulting infiltrate resembled a local reversal towards the tuberculoid pole of leprosy.

CD4-Positive T-Lymphocytes↗

Expression of cyclooxygenase type 2 in lepromatous and tuberculoid leprosy lesions.

BACKGROUND: Leprosy is an infectious disease with two polar forms, tuberculoid leprosy (TL) and lepromatous leprosy (LL), which are dominated by T-helper (Th) 1 and Th2 cells, respectively. High concentrations of prostaglandin E2 produced by the inducible enzyme cyclooxygenase type 2 (COX-2) in LL could inhibit Th1 cytokine production, contributing to T-cell anergy. OBJECTIVES: To compare the COX-2 expression in LL and TL. METHODS: Skin biopsies from 40 leprosy patients (LL, n = 20; TL, n = 20) were used to determine by immunohistochemistry and automated morphometry the percentage of COX-2 immunostained cells. RESULTS: Most COX-2-positive cells were macrophages; their percentages in the inflammatory infiltrate located in the papillary dermis, reticular dermis and periadnexally were significantly higher in LL than TL (P < 0.001 by Student's t-test). CONCLUSIONS: The high expression of COX-2 in LL may be related to high prostaglandin production contributing to T-cell anergy.

Biopsy↗

Expression of transforming growth factor-beta isoforms and their receptors in lepromatous and tuberculoid leprosy.

Leprosy is an infectious disease with two polar forms, tuberculoid leprosy (TT) and lepromatous leprosy (LL), that are characterized by strong cell-mediated immunity (CMI) and CMI anergy, respectively. Transforming growth factor-beta (TGF-beta) belongs to a family of pleiotropic cytokines (TGF-beta1, TGF-beta2 and TGF-beta3) that participate in the control of cell differentiation and proliferation, as well as tissue repair. This cytokine family is unique because it suppresses CMI. In this study, we compared the expression of the three TGF-beta isoforms and their receptors in skin biopsies from LL and TT patients (LL = 20; TT = 20) using immunohistochemistry and automated morphometry. The percentage of cells immunostained for the three TGF-beta isoforms and cells positive for the three TGF-beta receptors in the inflammatory infiltrate located in the papillary dermis, reticular dermis and periadnexal tissue were significantly higher in LL than that in TT, with macrophages being the most common and strongest immunoreactive cells. Some lymphocytes, fibroblasts, keratinocytes and epithelial cells from sweat glands and hair roots were also positive. In situ reverse-transcription polymerase chain reaction corroborated the capacity of these cells to synthesize TGF-beta1 and TGF-beta receptor 2. This high expression of TGF-beta isoforms and their receptors could contribute to CMI anergy and other clinical characteristic features of leprosy, like skin atrophy.

Biopsy↗