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Epithelioid granuloma in the iris of a lepromatous leprosy patient; an unusual finding.

This case report depicts a case of histopathologically confirmed polar lepromatous (LL) leprosy with a bacterial index of 4+. He experienced recurrent episodes of erythema nodosum leprosum (ENL) in the first 5 years after diagnosis. Skin smears became negative after 6 years of dapsone monotherapy and have remained negative since that time. At 23 years after diagnosis, the patient had developed cataracts and underwent intracapsular cataract extractions with broad-based iridectomies. In one of the iris specimens, histopathologic examination revealed a focal granuloma composed of epithelioid cells. Subsequently a lepromin skin test showed a positive Mitsuda reaction with a borderline tuberculoid histopathology. This clearly illustrates the immunological upgrading of a polar lepromatous patient, perceived first in the iris tissue.

Adult↗

Role of paucibacillary leprosy in the transmission of disease.

The objective of this study was to establish that paucibacillary leprosy also carried increased risk of infection to the community. All members of 100 families with an index paucibacillary case were clinically, bacteriologically and immunologically examined. The "comparison" group was sampled from suspect register. Fifty-six cases occurred among 944 contacts of index paucibacillary cases; of these, four were multibacillary and 52 were paucibacillary. In the "comparison" group, two contacts out of 760 developed paucibacillary leprosy. This difference, between the two groups, was statistically significant. All the 56 cases in the index case families were under 20 years of age; and 50 of them were aged under 15 years. Male/female ratio was 2.1:1. Of the 56 cases, 28 shared the same bed with the index patient, 20 shared the same room and eight lived in the same house. Lepromin positivity rate was higher in "comparison" families (92.2%) than in index case families (74.6%), the difference being statistically significant (x = 6.09, P < 0.001). Contacts of index case families, therefore, were immunologically at higher risk than contacts of "comparison" families.

Adolescent↗

Patients presenting with defined areas of sensory loss--a preliminary study.

Thirty patients presenting with circumscribed areas of clearly demonstrable hypoesthesia were chosen from amongst those attending this Institute. Their history and clinical features were recorded, lepromin test was done for reading at four weeks, and peripheral part of the hypoesthetic area was biopsied for histopathology and immunostaining. The subjects were predominantly adult males with the symptomatic sites limited to the extremities. On routine histopathological examination of the symptomatic sites, the diagnosis of leprosy, using defined criteria, could be made in six cases (20%). Immunostaining of the remaining sections showing either no pathology or a nonspecific pathology revealed the presence of mycobacterial antigen in five of the 24 cases (20.83%). Overall, leprosy could be diagnosed in 11 of the 30 cases studied (36.66%). This study shows that leprosy may be an important cause of circumscribed areas of sensory deficit.

Adolescent↗

Mycobacterium leprae: atypical and unclassified.

Once M. leprae is grown on artificial media in the test tube, it might prove to have a great variety of characteristics quite different to those expected from our knowledge of M. leprae isolated from the susceptible host. The cultures might be slow or fast growing, pigmented or colorless, pathogenic for the armadillo, or not; they might produce limited disease in the foot pad of mice, or the contrary. The in vitro M. leprae culture might or might not provoke a lepromine reaction; the culture might grow at a lower or higher temperature. It is well documented that mycobacteria show great differences in elasticity and adaptability to cultivation conditions. It is absolutely certain that once grown in a test tube, M. leprae will behave as an atypical species. However, each individual culture of M. leprae obtained in vitro will have the same drug sensitivity pattern as in the lepromatous leprosy patient from whom it was cultivated.

Adaptation, Physiological↗

Kveim-test in patients suspected of sarcoidosis and in leprosy patients in a geographical area not yea investigated.

The Kveim-test was studied in a geographical area (São Paulo, Brazil) not yet investigated, and leprosy patients were also tested. One hundred and forty seven patients from a general hospital who had had the possibility of sarcoidosis, as a differential diagnosis, were tested with Kveim suspension. Another group of 13 patients with clinical and histological diagnosis of leprosy (10 with tuberculoid leprosy lepromin-positive and 3 with indetermined leprosy) was also tested with Kveim suspension. Sixteen Kveim-tests (10 per cent) with sarcoid granulomatous reaction revealed histologically were considered positive. Three patients with sarcoidosis for more than 3 years gave negative Kveim-test. Four patients with positive Kveim-test had respectively lymphosarcoma, Crohn's disease, lung fibrosis and concurrent tuberculosis infection. Nine positive Kveim-tests (5.6 per cent) were coincident with sarcoidosis. Thirteen leprosy patients (ten tuberculoid) gave negative Kveim-test.

Adolescent↗

Comparison of PCR mediated amplification of DNA and the classical methods for detection of Mycobacterium leprae in different types of clinical samples in leprosy patients and contacts.

Traditional staining and microscopic examination techniques for the detection of Mycobacterium leprae, DNA amplification by polymerase chain reaction (PCR) of a 531-bp fragment of the M. leprae specific gene encoding the 36-kDa antigen, and serodiagnosis with M. leprae specific antigens (PGL-1 and D-BSA) were compared on different clinical specimens (serum samples, slit-skin smears, biopsies and swabs) from 60 leprosy patients attending the Sanatorium of Fontilles. Patients were divided into groups; (i) 20 multibacillary patients (MB) with positive bacteriological index (BI) by conventional methods and on WHO multidrug therapy (MDT); (ii) 30 MB patients with negative BI and completed minimum 2 years treatment MDT; (iii) 10 paucibacillary (PB) patients who had completed 6 months MDT at least 8 years ago. Control groups included four non-leprosy patients for PCR methods and 40 health control patients and 10 tuberculosis patients for serological methods. In the multibacillary BI positive group, there was a good correlation between all methods. All tests were negative in the paucibacillary group, although only a few patients were tested and all had been treated many years ago. One must be cautious concerning the diagnostic potential of these techniques in this type of leprosy. We also studied different combinations of leprosy diagnosis methods to determine the potential risk in a leprosy contact individuals group. The prevalence of antibodies to M. leprae antigens in serum was measured, together with the presence of M. leprae DNA in the nose and lepromin status in a group of 43 contacts of leprosy patients (12 household and 31 occupational) to evaluate the maintenance of infection reservoirs and transmission of the disease. Only two individuals were found to form a potential high risk group.

Adult↗

Comparison between anti-PGL-I serology and Mitsuda reaction: clinical reading, microscopic findings and immunohistochemical analysis.

The lepromin test, serum IgM antibodies against Mycobacterium leprae and in situ observations of T cell subsets in biopsies of Mitsuda reaction using monoclonal antibodies were performed on 44 untreated leprosy patients belonging to various classifications of the disease. The Mitsuda reaction was accessed clinically and histologically after 28 days. Clinical reading and histological analysis of Mitsuda reaction showed good agreement. The high positivity in clinical reading correlated with compact granulomas in histology. There is a graduation of Mitsuda reaction that follows the immunological spectrum of the disease. The histological study of Mitsuda reaction is valuable to confirm the immunological condition in doubtful clinical reaction. Anti-PGL-I IgM levels correlated with disease classification, increasing from the tuberculoid towards the lepromatous pole of the disease spectrum. There was an inverse correlation between serum IgM antibody levels and clinical and histological reading of Mitsuda reaction. There were no statistical difference in quantities and distribution of CD4+ and CD8+ T cells in all Mitsuda reactions. The pattern of cellular content of Mitsuda reaction could not be related to the T cells.

Adolescent↗

Histopathological monitoring of an immunotherapeutic trial with Mycobacterium w.

Immunotherapeutic trials with Mycobacterium w (M. w.) on multibacillary patients are in progress at two large hospitals in New Delhi. A total of 380 patients so far have been inducted into the trial. The histopathological profile of the initial 87 patients (52 in the vaccine group, 35 in the control group) who have now completed 2 years of treatment are presented in this report. The vaccine group received multidrug therapy (MDT) and eight intradermal injections of M. w. every 3 months; the control group had MDT with starch injections as a placebo. Skin biopsies were taken at induction and thereafter at every 6 months. The results show a significantly higher proportion of biopsies with histopathological upgrading and/or clearance of dermal granuloma among the vaccinated cases. The number of patients becoming bacteriologically negative was higher in the vaccine group. There was no increase in the degree of neural inflammation in the biopsies showing upgrading. The lepromin site biopsy in patients who converted to positivity after vaccination showed epithelioid cell granulomas as did the biopsies from the nodules developing at the vaccination sites. The histopathological observations confirm the additional immunotherapeutic effect of M. w. used along with standard MDT therapy.

Analysis of Variance↗

Leprosy and HIV co-infection in five patients.

In a retrospective study, five patients are reported who suffered from a Mycobacterium leprae/HIV co-infection and were treated for their HIV infection with HAART. In four patients, this revealed their leprosy and induced a type I leprosy reaction. Two patients who were lepromin negative at diagnosis were retested after about 1 year of anti-retroviral treatment, and found to be positive.

AIDS-Related Opportunistic Infections↗

Lepromatous leprosy: a review and case report.

Leprosy is a contagious and chronic systemic granulomatous disease caused by Mycobacterium leprae (Hansen s bacillus). It is transmitted from person to person and has a long incubation period (between two and six years). The disease presents polar clinical forms (the multibacillary lepromatous leprosy and the paucibacillary tuberculoid leprosy), as well as other intermediate forms with hybrid characteristics. Oral manifestations usually appear in lepromatous leprosy and occur in 20-60% of cases. They may take the form of multiple nodules (lepromas) that progress to necrosis and ulceration. The ulcers are slow to heal, and produce atrophic scarring or even tissue destruction. The lesions are usually located on the hard and soft palate, in the uvula, on the underside of the tongue, and on the lips and gums. There may also be destruction of the anterior maxilla and loss of teeth. The diagnosis, based on clinical suspicion, is confirmed through bacteriological and histopathological analyses, as well as by means of the lepromin test (intradermal reaction that is usually negative in lepromatous leprosy form and positive in the tuberculoid form). The differential diagnosis includes systemic lupus erythematosus, sarcoidosis, cutaneous leishmaniasis and other skin diseases, tertiary syphilis, lymphomas, systemic mycosis, traumatic lesions and malignant neoplasias, among other disorders. Treatment is difficult as it must be continued for long periods, requires several drugs with adverse effects and proves very expensive, particularly for less developed countries. The most commonly used drugs are dapsone, rifampicin and clofazimine. Quinolones, such as ofloxacin and pefloxacin, as well as some macrolides, such as clarithromycin and minocyclin, are also effective. The present case report describes a patient with lepromatous leprosy acquired within a contagious family setting during childhood and adolescence.

Aged↗

IgM antibodies to native phenolic glycolipid-I in contacts of leprosy patients in Venezuela: epidemiological observations and a prospective study of the risk of leprosy.

In a randomized, double-blind vaccine trial in Venezuela, about 29,000 contacts of leprosy patients have been vaccinated with either a mixture of heat-killed Mycobacterium leprae and BCG or BCG alone, and are being re-surveyed annually to detect new cases of leprosy. All contacts had a serum sample collected at the time of entry into the trial, and 13,020 of these sera have been analyzed for antibodies to phenolic glycolipid-I (PGL-I). Antibody levels have been related to various characteristics of the contacts and to their risk of developing leprosy in the following 4 years. A strong association was found between PGL-I antibody level and the risk of developing leprosy, in spite of possible modification of the incidence rate induced by vaccination. Antibody levels were higher in females than in males, and declined progressively with age. Household contacts had higher levels than did non-household contacts, and levels were higher in individuals from the state in Venezuela which has the highest incidence of the disease. No substantial differences were found in antibody levels between contacts of multibacillary and paucibacillary patients, which may in part reflect the influence of treatment, and there was no clear association with the presence of BCG or lepromin scars or with skin-test responses to PPD and leprosy soluble antigen. The assay of antibodies to PGL-I seems unlikely to provide a sensitive or specific test for infection with M. leprae, and measuring PGL-I antibody levels as a screening procedure to identify those at high risk of developing leprosy is unlikely to be particularly useful in most leprosy control programs. Such assays may be useful for the epidemiological monitoring of changes in the intensity of infection with M. leprae in a community and for the study of carefully defined groups of contacts during some phases of control programs.

Adolescent↗

Epidemiological significance of indeterminate leprosy--a hospital based study.

An epidemiological analysis of 100 cases of indeterminate leprosy attending the Department of Dermatology and Venereology of Medical College Hospital, Trivandrum, is presented. It was found that indeterminate leprosy formed 13.23% of all cases of leprosy and 1.3% of all out-patients attending this department. Only 27% of patients with indeterminate leprosy were below 15 years of age. There was a predominance of males especially over 20 years of age. There was no history of contact with leprosy in any of the patients with indeterminate leprosy. All patients with indeterminate leprosy came for hypopigmented patches, suspecting leprosy. Majority had the disease for more than 6 months. Single lesion on the outer aspect of extremity was the most common presentation. The lepromin test was positive in only 2% of patients with indeterminate leprosy, while it was positive in 80% of control subjects. Three cases of dapsone resistance were suspected in this series. The epidemiological significance of the findings is discussed.

Adolescent↗

Four-year follow-up results of a WHO-recommended multiple-drug regimen in paucibacillary leprosy patients in Malawi.

An evaluation of a World Health Organization-recommended multidrug therapy (WHO/MDT) in 499 paucibacillary leprosy patients is described. Patients were followed for 48 months after completion of treatment. Overall relapse rates after treatment were found to be 6.5 per 1000 person years (95% confidence interval 3.4-11.4). There were 12 relapses. A relative lack of cell-mediated immunity, as suggested by number of lesions, clinical classification and lepromin test results, and poor compliance with the dapsone component of WHO/MDT, appeared to be associated with a marginally increased risk of relapse. Severe type 1 reactions after completion of treatment occurred in 17 (3.5%) patients, 15/17 during the first 12 months of follow-up. Overall, 12 (2.5%) patients developed new disabilities during or after WHO/MDT.

Adolescent↗

Pathology of dual Mycobacterium leprae and simian immunodeficiency virus infection in rhesus monkeys.

Three rhesus monkeys were experimentally inoculated with sooty-mangabey-derived Mycobacterium leprae and were inadvertently infected with the simian immunodeficiency virus (SIV) as well. They died of an immunodeficiency syndrome, and at autopsy all had lesions caused by M. leprae. One monkey was inoculated twice with M. leprae, initially with an inoculum from a sooty mangabey that was not infected with SIV and, subsequently, with an inoculum from a mangabey that was SIV infected. The monkey did not develop clinical lesions and became strongly lepromin skin test (LST) positive after the first inoculation, but became infected with both agents and LST negative following the second inoculation. These observations suggest that SIV-infected rhesus monkeys have an increased susceptibility to M. leprae infection and, by analogy, imply that HIV-infected human beings may have an increased susceptibility as well.

Animals↗

In situ identification of activated Ta1+ T lymphocytes in human leprosy skin lesions.

Using a monoclonal antibody, anti-Ta1, that identifies antigen-activated T lymphocytes in vitro, we sought to identify activated T lymphocytes in leprosy skin lesions. Greater numbers of Ta1 positive T lymphocytes were observed in tuberculoid leprosy, lepromin skin tests, and reversal reactions as compared with lepromatous leprosy or erythema nodosum leprosum (ENL) (p less than 0.001). With a double-staining technique, we found that the majority of these activated T lymphocytes were of the helper/inducer phenotype. No differences of Ta1 positive lymphocytes were observed in the peripheral blood. The defective cell-mediated immune response in lepromatous and ENL patients correlates with, and may be related to the failure of T-helper/inducer activation or proliferation in the presence of Mycobacterium leprae.

Antibodies, Monoclonal↗

T & B lymphocytes in the spectrum of leprosy.

The percentage of T & B lymphocytes were estimated in 52 leprosy patients by 'E' and 'EAC' rosette techniques. The mean % values for 'T' lymphocytes were significantly lower in lepromatous group as compared with that of tuberculoid and borderline groups. Also, a significant difference was observed in the mean % values of T & B lymphocytes of the borderline and tuberculoid patients and of the normal control group. These findings were correlated with skin smears and lepromin testing.

Adult↗

[Delayed cutaneous response to different antigens in household contacts of leprosy patients and controls].

The delayed type hypersensitivity (DTH) response to PPD, candidin and histoplasmin, and Mitsuda reaction (MR) in household contacts (HC) of multibacillary (HCM) and paucibacillary (HCP) leprosy patients, and non exposed controls was studied. Intradermal tests with 0.1 ml. of each antigen were performed and read after 48 hours. Late nodular reaction to ML (MR) was evaluated at the 21st day post-challenge. As we had formerly demonstrated, MR was depressed in HCM. Interestingly, this reaction was also depressed in HCP to a lesser magnitude. HCM had a lower DTH response to histoplasmin in relation to PPD and candidin when persons were simultaneously challenged with the three antigens. According to these results we conclude that: a), HCM have a depression in late lepromin reaction; b), in HCP the depression in MR is of a lower magnitude. We hypothesize that in healthy contacts of bacilliferous patients an active mechanism of immunosuppression to mycobacterial antigens may be produced. Alterations in the skin response to histoplasmin is discussed.

Female↗

Clinical and histopathological observations on pure neuritic leprosy.

Pure neuritic leprosy is a well accepted clinical entity. In the absence of skin lesions there is a greater possibility of missing the diagnosis of leprosy due particularly to a wide variety of pure neural manifestations that may mimic other peripheral neuropathies. Histopathological studies of pure neuritic leprosy have received less attention for ethical reasons and limitations of surgery. Classification of pure neuritic leprosy poses problems since the histological spectrum (e.g. Ridley-Jopling scale) is based chiefly on the skin picture. Review of the past literature shows conflicting reports about comparability of the skin and nerve pictures. This paper presents clinical and histopathological observations on twelve patients of pure neuritic leprosy, the interesting observations being that all the patients showed lepromin positivity and a narrower histological spectrum, ranging from TT to BB only.

Adolescent↗