Leprosy: A great imitator.

In recent years, advances in medical diagnosis and treatment have greatly attracted our attention, whereas some rare diseases, such as leprosy, have not found a place in the medical education curriculum; their existence may even be forgotten. Although the prevalence and incidence rates for leprosy have been significantly reduced as a result of the control strategies of the World Health Organization, new cases still appear. A total of 214,783 new cases were reported from 143 countries during 2016, corresponding to the global new-case detection rate of 2.9 per 100,000 population. Leprosy proves to be a very interesting model due to its immunologic properties. It joins with syphilis, mycosis fungoides, cutaneous tuberculosis, and sarcoidosis as one of the great imitators. The diagnosis of leprosy can be simple and practical, but considering the diagnosis of leprosy in the differential diagnosis is the first requisite again.

Reading of the Mitsuda test: comparison between diameter and total area by means of a computerized method.

The Mitsuda test is a skin test based on the individual's immune response through late and highly specific hypersensitivity reaction to the Mycobacterium leprae bacillus. A negative reaction identifies individuals who present a higher risk of becoming ill if exposed to M. leprae and, if they become ill, to develop the virchowian form of disease. The Mitsuda test reading is performed by means of a millimeter ruler. The dermatoscopy is a method that has not been used in the evaluation of cutaneous tests, although its use has increased in several areas. The study aimed to compare the results between the standardized reading and the total area of the Mitsuda test obtained by a computerized method which was structured by the association of digital dermatoscopy, the Dermatology Web system and the Image Tool 3.0 software. Data collection was performed at the Dermatology Outpatient Clinic of the Eduardo de Menezes Hospital, in Belo Horizonte, from November 2015 to August 2016. The sample consisted of 100 leprosy domiciliary contacts. There was an excellent agreement between the Mitsuda test (diameter and area), with a coefficient greater than 80%, and an excellent correlation with the Spearman's correlation coefficient (0.936). The intraclass correlation coefficient indicated a low (0.219) but significant agreement between the two measurements. In conclusion, there is a significant correlation between the standardized reading and the total area of the Mitsuda test. Digital dermoscopy can be an alternative instrument of evaluation, allowing the computerization and recording of the Mitsuda test.

Leprosy. An update: definition, pathogenesis, classification, diagnosis, and treatment.

Leprosy is a chronic granulomatous disease caused by the bacillus Mycobacterium leprae. It primarily affects the skin and peripheral nerves and is still endemic in various regions of the world. Clinical presentation depends on the patient's immune status at the time of infection and during the course of the disease. Leprosy is associated with disability and marginalization. Diagnosis is clinical and is made when the patient has at least 1 of the following cardinal signs specified by the World Health Organization: hypopigmented or erythematous macules with sensory loss; thickened peripheral nerves; or positive acid-fast skin smear or skin biopsy with loss of adnexa at affected sites. Leprosy is treated with a multidrug combination of rifampicin, clofazimine, and dapsone. Two main regimens are used depending on whether the patient has paucibacillary or multibacillary disease.

Survey to identify Mycobacterium leprae-infected household contacts of patients from prevalent regions of leprosy in Colombia.

Leprosy in Colombia is in the post-elimination phase; nevertheless, there are regions of this country where the incidence is still around 3-4/100,000. Early detection of leprosy patients is a priority for achieving control and elimination of leprosy; however, the clinical exam is not very sensitive and thus, the majority of patients are diagnosed only when they demonstrate lesions, and damage to the nerves and skin has already occurred. The goal of the present study was to identify Mycobacterium leprae infection and immune responses in household contacts (HHC) of leprosy patients from three prevalent regions of Colombia. Clinical examination, the Mitsuda test, evaluation of IgM anti-PGL-I in the serum, the bacillar index (BI), and polymerase chain reaction (PCR) from nasal swabs (NS) were performed for 402 HHC of 104 leprosy patients during a cross-sectional survey. Positive titers for IgM anti-PGL1 were found for 54 HHC, and PCR-positive NS for 22. The Mitsuda reaction was negative for 38 HHC, although three were positive for IgM anti-PGL-1 titers. The data document that leprosy transmission among HHC is still occurring in a non-endemic country.

Survey to identify Mycobacterium leprae-infected household contacts of patients from prevalent regions of leprosy in Colombia

Leprosy in Colombia is in the post-elimination phase; nevertheless, there are regions of this country where the incidence is still around 3-4/100,000. Early detection of leprosy patients is a priority for achieving control and elimination of leprosy; however, the clinical exam is not very sensitive and thus, the majority of patients are diagnosed only when they demonstrate lesions, and damage to the nerves and skin has already occurred. The goal of the present study was to identify Mycobacterium leprae infection and immune responses in household contacts (HHC) of leprosy patients from three prevalent regions of Colombia. Clinical examination, the Mitsuda test, evaluation of IgM anti-PGL-I in the serum, the bacillar index (BI), and polymerase chain reaction (PCR) from nasal swabs (NS) were performed for 402 HHC of 104 leprosy patients during a cross-sectional survey. Positive titers for IgM anti-PGL1 were found for 54 HHC, and PCR-positive NS for 22. The Mitsuda reaction was negative for 38 HHC, although three were positive for IgM anti-PGL-1 titers. The data document that leprosy transmission among HHC is still occurring in a non-endemic country.

Immediate hypersensitivity to rifampicin in 3 patients: diagnostic procedures and induction of clinical tolerance.

BACKGROUND: Desensitization with drugs may be indicated in some clinical situations. Apart from large experiences with beta-lactam antibiotics and cotrimoxazole in HIV infection, experience with other drugs is limited. Rifampicin may elicit exanthema and urticaria, and their pathomechanisms are not known in detail. Since therapy with rifampicin may be indispensable in mycobacterial infections or against multiresistant Staphylococcus aureus, desensitization may be indicated in some patients. OBJECTIVE: Report of immediate hypersensitivity to rifampicin and description of diagnostic and desensitization procedures. METHODS: We report 3 patients with immediate urticarial reactions to rifampicin. Diagnostic procedures included skin and in vitro tests (specific IgE, lymphocyte transformation test, LTT, and CAST). The non-irritant cutoff concentration was evaluated in 24 volunteers. A 7-day desensitization procedure was used. RESULTS: Only intradermal tests at a dilution of at least 1:10,000 (concentration of rifampicin approximately 0.006 mg/ml) were true positive, whereas in vitro tests (IgE, LTT and CAST) did not correctly identify hypersensitive patients. Two patients had positive accidental reexposure. All patients were successfully desensitized with rifampicin according to a slow 7-day protocol. CONCLUSIONS: Rifampicin rarely elicits immediate hypersensitivity symptoms which may be diagnosed by intradermal skin tests. In vitro tests did not contribute to the diagnosis. Therefore, an IgE-mediated mechanism remains to be proven. Desensitization with rifampicin using different protocols has been reported. In our 3 cases, clinical tolerance to rifampicin was achieved using a 7-day protocol.

Infection by Mycobacterium leprae of household contacts of lepromatous leprosy patients from a post-elimination leprosy region of Colombia

The Leprosy Control Program of Antioquia, (post-elimination leprosy state of Colombia), had registered by 1999, 56 lepromatous leprosy patients and their household contacts (HHC). Our interest was to detect Mycobacterium leprae infection in these HHC. Clinical examination, acid-fast bacillary staining (AFB) in nasal secretions, and slit skin samples, IgM anti-PGL-I in serum and Lepromine A (Mitsuda) reactivity were tested. Two hundred forty eight HHC were studied, 49 percent were male. After clinical examination, two HHC were diagnosed as multi bacillary patients; 13 percent showed positive IgM anti-PGL-I titers; Mitsuda reaction (> 4 mm) was positive in 59 percent; AFB was negative in all samples, except in the two new patients. HHC were classified according to test results.Group 1: two new multi bacillary patients. Group 2: 15 HHC seropositive, Mitsuda-negative. Group 3: 13 HHC seropositive, Mitsuda-positive. Group 4: 130 HHC seronegative, Mitsuda-positive. Group 5: 88 HHC seronegative, Mitsuda-negative. These results are an indication that the transmission of the infection is still happening in a region considered in the post elimination phase. The two new patients represent an infection source for others contacts, and groups 2 and 3 are infected HHC that could develop the disease in future. Follow up of high risk population is necessary to achieve real elimination of leprosy.

Infection by Mycobacterium leprae of household contacts of lepromatous leprosy patients from a post-elimination leprosy region of Colombia.

The Leprosy Control Program of Antioquia, (post-elimination leprosy state of Colombia), had registered by 1999, 56 lepromatous leprosy patients and their household contacts (HHC). Our interest was to detect Mycobacterium leprae infection in these HHC. Clinical examination, acid-fast bacillary staining (AFB) in nasal secretions, and slit skin samples, IgM anti-PGL-I in serum and Lepromine A (Mitsuda) reactivity were tested. Two hundred forty eight HHC were studied, 49% were male. After clinical examination, two HHC were diagnosed as multi bacillary patients; 13% showed positive IgM anti-PGL-I titers; Mitsuda reaction (> or = 4 mm) was positive in 59%; AFB was negative in all samples, except in the two new patients. HHC were classified according to test results. Group 1: two new multi bacillary patients. Group 2: 15 HHC seropositive, Mitsuda-negative. Group 3: 13 HHC seropositive, Mitsuda-positive. Group 4: 130 HHC seronegative, Mitsuda-positive. Group 5: 88 HHC seronegative, Mitsuda-negative. These results are an indication that the transmission of the infection is still happening in a region considered in the post elimination phase. The two new patients represent an infection source for others contacts, and groups 2 and 3 are infected HHC that could develop the disease in future. Follow up of high risk population is necessary to achieve real elimination of leprosy.

Estudo Comparativo entre reação de mitsuda e fenotipagem HLA em pacientes hansenianos

Neste estudo propôs-se comparar o teste intradérmico de Mitsuda e os alelos HLA-DR2 /HLA -DR3 e HLA-DQ1 relacionados com as formas clínicas da hanseníase, visando contribuir para o delineamento de nova metodologia no auxílio prognóstico desta doença. Foram estudados 176 pacientes hansenianos (50 HT, 50 HV e 76 HD). A tipificação do HLA-DR e HLA -DQ foi determinada pela técnica de PCR/SSP e a reação de Mitsuda pela intradermorreação com leitura em 28 dias. Na forma HT os resultados demonstraram que a reação de Mitsuda foi positiva em todos os pacientes, sendo 16% positivo1+, 68% positivo2+ e 16% positivo3+. O diâmetro de induração variou entre 4,0 a 18,0mm, com valor médio de 7,5mm. A especificidade HLA-DR2 esteve presente em 28% dos pacientes deste grupo (24% HLA-DRB1*15 e 4% HLA-DRB1*16). A especificidade HLA-DR3 esteve presente em 16% dos pacientes (8% HLA-DRB1*17 e 8% HLA-DRB1*18), 2% apresentaram os alelos HLA-DR2 e HLA-DR3 simultâneamente, totalizando 46% da amostra estudada com o marcador. A forma HV apresentou a reação de Mitsuda negativa em todos os pacientes estudados. A especificidade do HLA-DQ1 esteve presente em 74% dos pacientes (34% HLA-DQB1*05, 28% HLA-DQB1*06 e 12% HLA-DQB1*05 e HLA-DQB1*06). No grupo HD, o padrão de leitura da reação de Mitsuda resultou em negativo em 48,7%, duvidoso 5,2%, positivo 1+ 30,3% e positivo 2+ 15,8%. O diâmentro da induração variou entre negativo a 7,5mm com valor médio de 2,4mm. Com relação aos alelos HLA, não foi possível realizar a comparação, por não se ter verificado após estudo de associação, nenhum alelo relacionado ao grupo HD. Realizou-se também análise não estratificada dos pacientes de acordo com a resposta ao teste de Mitsuda. Oitenta e cinco pacientes foram positivos para o teste de Mitsuda e destes, 43,5% possuíam o alelo HLA-DR2 ou HLA-DR3. Noventa e um pacientes tiveram reação de Mitsuda negativa, destes 65,9% apresentaram o alelo HLA-DQ1. Os dados obtidos neste estudo permitiram ...

Estudo Comparativo entre reação de mitsuda e fenotipagem HLA em pacientes hansenianos / Comparative study between the mitsuda test and the HLA phenotype in leprosy patients

Neste estudo propôs-se comparar o teste intradérmico de Mitsuda e os alelos HLA-DR2 /HLA -DR3 e HLA-DQ1 relacionados com as formas clínicas da hanseníase, visando contribuir para o delineamento de nova metodologia no auxílio prognóstico desta doença. Foram estudados 176 pacientes hansenianos (50 HT, 50 HV e 76 HD). A tipificação do HLA-DR e HLA -DQ foi determinada pela técnica de PCR/SSP e a reação de Mitsuda pela intradermorreação com leitura em 28 dias. Na forma HT os resultados demonstraram que a reação de Mitsuda foi positiva em todos os pacientes, sendo 16% positivo1+, 68% positivo2+ e 16% positivo3+. O diâmetro de induração variou entre 4,0 a 18,0mm, com valor médio de 7,5mm. A especificidade HLA-DR2 esteve presente em 28% dos pacientes deste grupo (24% HLA-DRB1*15 e 4% HLA-DRB1*16). A especificidade HLA-DR3 esteve presente em 16% dos pacientes (8% HLA-DRB1*17 e 8% HLA-DRB1*18), 2% apresentaram os alelos HLA-DR2 e HLA-DR3 simultâneamente, totalizando 46% da amostra estudada com o marcador. A forma HV apresentou a reação de Mitsuda negativa em todos os pacientes estudados. A especificidade do HLA-DQ1 esteve presente em 74% dos pacientes (34% HLA-DQB1*05, 28% HLA-DQB1*06 e 12% HLA-DQB1*05 e HLA-DQB1*06). No grupo HD, o padrão de leitura da reação de Mitsuda resultou em negativo em 48,7%, duvidoso 5,2%, positivo 1+ 30,3% e positivo 2+ 15,8%. O diâmentro da induração variou entre negativo a 7,5mm com valor médio de 2,4mm. Com relação aos alelos HLA, não foi possível realizar a comparação, por não se ter verificado após estudo de associação, nenhum alelo relacionado ao grupo HD. Realizou-se também análise não estratificada dos pacientes de acordo com a resposta ao teste de Mitsuda. Oitenta e cinco pacientes foram positivos para o teste de Mitsuda e destes, 43,5% possuíam o alelo HLA-DR2 ou HLA-DR3. Noventa e um pacientes tiveram reação de Mitsuda negativa, destes 65,9% apresentaram o alelo HLA-DQ1. Os dados obtidos neste estudo permitiram concluir que a utilização isolada da tipificação HLA não constitui uma ferramenta adequada para auxílio no prognóstico da doença, embora o emprego em conjunto das duas metodologias poderão complementar o diagnóstico da hanseníase

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.

Comparative study of Mitsuda reaction to nude mouse and armadillo lepromin preparations using nine-banded armadillos.

In 14 nine-banded armadillos the Mitsuda response to nude mouse-derived lepromin (lepromin-nu/nu) was compared to that of armadillo-derived lepromin (lepromin-A) by injecting the reagents intradermally into either side of the abdomen of the animal and examining the biopsies from the sites after 12 days. The histopathologic responses to both antigens were found to be similar, whether the animal was Mitsuda-negative (lepromatous) or Mitsuda-positive (tuberculoid). It is pointed out that armadillos are good experimental models for leprosy, and their use can replace humans in experimental studies.

Reatividade da lesäo cutânea de hanseníase a imunógenos epicutâneo e intradérmico / Rectivity of the leprous cutaneous by intradermic and epicutaneous immunogens

FUNDAMENTOS - Foram observados dois pacientes de doenças imunes da pele, cuja extensäo foi delimitada pela lesäo cutânea de hanseníase, sugerindo comportamentos imunológicos diferentes entre área afetada e a pele sadia do mesmo paciente. OBJETIVOS - Verificar experimentalmente, pelo teste epicutâneo com DNCB e intradêrmico com candidina, se na lesäo cutânea da hanseníase TT e BT existem modificaçöes da imunidade celular em relaçäo à pele aparentemente normal do mesmo paciente. MÉTODOS - Foram selecionados 39 voluntários portadores de hanseníase TT e BT. Em 26, foi aplicado DNCB epicutâneo e, em 13, candidina intradérmica. Os resultados desses testes foram avaliados por: resposta clínica, estudo histopatológico e exame imuno-histoquímico dos componentes celulares das reaçöes. RESULTADOS - A resposta clínica à aplicaçäo epicutânea de DNCB na lesäo de hanseníase TT e BT foi maior do que na pele sadia do mesmo paciente. Näo houve diferença com a aplicaçäo intradérmica de candidina nesses locais. As CL apresentaram diminuiçäo de número nos locais de aplicaçäo de DNCB, permanecendo esse número inalterado nos locais testados com candidina. CONCLUSOES - A lesäo cutânea de hanseníase (TT e BT) responde de modo mais intenso ao imunógeno aplicado por via epicutânea do que a pele sadia do mesmo paciente. Sugere-se que a hanseníase (TT e BT) interfira na reatividade da pele ao nível da lesäo cutânea e que as células de Langerhans näo participem dessa reatividade