RESUMEN
Erythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates-a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably contributing to the immunopathogenesis of the disease.
Asunto(s)
Eritema Nudoso/inmunología , Leprostáticos/uso terapéutico , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Receptores de IgG/genética , Talidomida/uso terapéutico , Adolescente , Adulto , Anciano , Biopsia , Eritema Nudoso/diagnóstico , Eritema Nudoso/tratamiento farmacológico , Eritema Nudoso/microbiología , Femenino , Humanos , Lepra Dimorfa/tratamiento farmacológico , Lepra Dimorfa/inmunología , Lepra Dimorfa/microbiología , Lepra Lepromatosa/tratamiento farmacológico , Lepra Lepromatosa/inmunología , Lepra Lepromatosa/microbiología , Masculino , Persona de Mediana Edad , Receptores de IgG/inmunología , Piel/microbiología , Piel/patología , Adulto JovenRESUMEN
Tumor necrosis factor α antagonists are proven to be effective for the treatment of chronic inflammatory conditions, such as psoriasis. A major concern for patients is the risk of acquiring granulomatous infectious diseases caused by the immunosuppressive effects of the drugs. We report a 60-year-old man with psoriasis who underwent infliximab treatment for 2 years and developed secondary leprosy, presenting extensive erythematous and infiltrated plaques on the trunk and limbs with loss of sensitivity (thermal, pain and tactile). The skin lesion biopsy showed perivascular epithelioid granulomas, nodular dermal aggregates of foamy macrophages and bundles of acid-fast bacilli. The clinical picture associated with histopathologic evaluation suggested borderline lepromatous leprosy. Before infliximab treatment, the patient had a positive tuberculin skin test and underwent chemoprophylaxis treatment for latent tuberculosis. Although the tuberculin reactivity suggests a strong correlation with a latent Mycobacterium tuberculosis infection, the possibility of infections by other mycobacteria, such as Mycobacterium leprae, should not be discarded.
Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Lepra Dimorfa/diagnóstico , Lepra Dimorfa/microbiología , Psoriasis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Antituberculosos/uso terapéutico , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Infliximab , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/tratamiento farmacológico , Leprostáticos/uso terapéutico , Lepra Dimorfa/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mycobacterium leprae , Mycobacterium tuberculosis , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/microbiologíaRESUMEN
INTRODUCTION: Leprosy is a chronic disease caused by infection with Mycobacterium leprae, an obligate intracellular parasite. A problem in studying the transmission of leprosy is the small amount of variation in bacterial genomic DNA. The discovery of variable number of tandem repeats (VNTRs) allowed the detection of strain variation in areas with a high prevalence of leprosy. Four genotypes of M. leprae based on three single-nucleotide polymorphism (SNPs) were also discovered to be useful for analysis of the global spread of leprosy. METHODS: In this present study, we examined the allelic diversity of M. leprae at 16 select VNTR and three SNP loci using 89 clinical isolates obtained from patients mainly from the neighbouring states of São Paulo and Rio de Janeiro Brazil. RESULTS AND CONCLUSION: By use of a PCR-RFLP-based procedure that allows the recognition of SNP types 3 and 4 without the need for the more expensive DNA sequencing steps, characterisation of the main M. leprae genotypes was easy. When applied on the study population, it was found that the SNP type 3 is most frequent in these two states of Brazil, and that VNTRs provided further discrimination of the isolates. Two Short Tandem Repeats (STRs) were monomorphic, with the remaining 14 STRs represented by two to 18 alleles. Epidemiological associations with township or state were not evident in this random collection and require further investigations. In phylogenetic trees, branches formed by all 16 STRs clearly separated SNP type 3 organisms from the other types while the allelic patterns of two minisatellite loci 27-5 and 12-5 were highly correlated with SNP type 3. This strain typing study provide the basis for comparison of M. leprae strain types within Brazil and with those from other countries, and informed selection of genomic markers and methods for future studies.
Asunto(s)
Variación Genética , Lepra Dimorfa/microbiología , Lepra Lepromatosa/microbiología , Mycobacterium leprae/genética , Brasil/epidemiología , ADN Bacteriano/química , ADN Bacteriano/genética , Humanos , Lepra Dimorfa/epidemiología , Lepra Lepromatosa/epidemiología , Repeticiones de Minisatélite , Filogenia , Polimorfismo de Nucleótido SimpleRESUMEN
Seven multibacillary leprosy and two suspected cases assisted in different situations during clinical care activities at the university in Rio de Janeiro city are described. All cases presented some difficulties for diagnosis, since they evolved with few or no cardinal signs or symptoms of leprosy. A serological test used as an auxiliary tool was helpful in the diagnosis or exclusion procedure of each case, facilitating academic discussions at the time of case examination. Considering serology and bacilloscopy (skin smear) as the only rapid and relatively cheap available tests for confirmation of atypical MB leprosy, the advantages and disadvantages of their use were discussed. Both tests support the diagnostic procedure and the classification of cases for treatment purposes. The advantage of bacilloscopy is its capacity for diagnosis confirmation. The advantages of serology are: (a) its applicability for direct use by health workers, providing immediate results; (b) the potential for patient participation in the process; and (c) it provides a learning opportunity, allowing for improved teaching of leprosy pathogenesis.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos , Glucolípidos , Lepra Dimorfa/diagnóstico , Lepra Lepromatosa/diagnóstico , Mycobacterium leprae/inmunología , Adulto , Anciano , Antígenos Bacterianos/inmunología , Niño , Diagnóstico Diferencial , Femenino , Glucolípidos/inmunología , Humanos , Inmunoglobulina M/sangre , Lepra Dimorfa/microbiología , Lepra Dimorfa/patología , Lepra Lepromatosa/microbiología , Lepra Lepromatosa/patología , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Piel/microbiología , Piel/patologíaRESUMEN
Sete casos de hanseníase multibacilar (MB) e dois casos com suspeição de hanseníase atendidos em situações distintas do atendimento clínico-dermatológico na Universidade Federal do Rio de Janeiro são descritos. Todos apresentaram dificuldades no diagnóstico visto que não tinham sinais e sintomas cardinais da hanseníase. Um teste sorológico utilizado como ferramenta auxiliar foi útil no processo de diagnóstico ou exclusão de cada caso e facilitou as discussões acadêmicas na hora do exame clínico. A sorologia e baciloscopia de linfa são consideradas como os únicos instrumentos rápidos e de baixo custo para a confirmação de casos MB atípicos, e as vantagens e desvantagens de cada exame são discutidas. Ambos os testes complementam o processo diagnóstico e classificação dos casos para fins terapêuticos. A vantagem da baciloscopia está na sua capacidade de confirmação do diagnóstico. As vantagens da sorologia são: (a) sua aplicabilidade para uso direto por profissionais de saúde no momento da consulta, visto que os resultados são imediatos, (b) a possibilidade da participação dos pacientes no processo, e (c) oferece uma oportunidade para melhor ensino da patogênese da hanseníase.
Seven multibacillary leprosy and two suspected cases assisted in different situations during clinical care activities at the university in Rio de Janeiro city are described. All cases presented some difficulties for diagnosis, since they evolved with few or no cardinal signs or symptoms of leprosy. A serological test used as an auxiliary tool was helpful in the diagnosis or exclusion procedure of each case, facilitating academic discussions at the time of case examination. Considering serology and bacilloscopy (skin smear) as the only rapid and relatively cheap available tests for confirmation of atypical MB leprosy, the advantages and disadvantages of their use were discussed. Both tests support the diagnostic procedure and the classification of cases for treatment purposes. The advantage of bacilloscopy is its capacity for diagnosis confirmation. The advantages of serology are: (a) its applicability for direct use by health workers, providing immediate results; (b) the potential for patient participation in the process; and (c) it provides a learning opportunity, allowing for improved teaching of leprosy pathogenesis.
Asunto(s)
Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos , Glucolípidos , Lepra Dimorfa/diagnóstico , Lepra Lepromatosa/diagnóstico , Mycobacterium leprae/inmunología , Antígenos Bacterianos/inmunología , Diagnóstico Diferencial , Glucolípidos/inmunología , Inmunoglobulina M/sangre , Lepra Dimorfa/microbiología , Lepra Dimorfa/patología , Lepra Lepromatosa/microbiología , Lepra Lepromatosa/patología , Sensibilidad y Especificidad , Piel/microbiología , Piel/patologíaRESUMEN
Six thousand skin biopsy specimens taken from April 1978 to January 2002 under conditions as specified by the National Leprosy Control Program (NLCP), were analyzed to obtain information about the work of the program and contribute to the knowledge of this illness in the Mexico. Six-thousand request forms for histologic exam of the NLCP were reviewed. Sixty-two percent of the requests had all the required information and in 38% one or more data items were omitted. The age range was 2 to 98 yrs with a median of 50 yrs; a small number of cases was observed in the age group of 0 to 14 yrs, and the peak was in the age group of 41 to 50 yrs. Of the 6000 biopsies, 3693 were classified. Polar lepromatous (LL) was the most common form of the disease, in 60.3% of cases. Twice as many cases were multibacillary leprosy (MB) as paucibacillary (PB). MB predominated in males, and PB predominated in females. The Cohen's kappa index (kappa) of clinical-histological agreement was 0.202 (95% CI 0.184-0.219) and showed a poor grade of agreement between clinical and histologic diagnosis, with a level of significance of 0.05 (p <0.001). The results may indicate the end of leprosy in Mexico, a country in which the national goal of elimination was reached in 1994, with a prevalence since the year 2000 of 0.17/10 000.
Asunto(s)
Lepra/epidemiología , Programas Nacionales de Salud , Piel/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Niño , Preescolar , Femenino , Humanos , Lepra/microbiología , Lepra/patología , Lepra/prevención & control , Lepra Dimorfa/epidemiología , Lepra Dimorfa/microbiología , Lepra Dimorfa/patología , Lepra Dimorfa/prevención & control , Lepra Lepromatosa/epidemiología , Lepra Lepromatosa/microbiología , Lepra Lepromatosa/patología , Lepra Lepromatosa/prevención & control , Lepra Tuberculoide/epidemiología , Lepra Tuberculoide/microbiología , Lepra Tuberculoide/patología , Lepra Tuberculoide/prevención & control , Masculino , México/epidemiología , Persona de Mediana Edad , Evaluación de Programas y Proyectos de Salud , Piel/microbiologíaRESUMEN
The relative recurrence risk ratio lambdaR (and particularly the sibling recurrence risk ratio, lambdaS) is often of interest to those wanting to quantify the genetic contribution towards risk of disease or to discriminate between different genetic models. However, estimating lambdaR for complex diseases for which genetic and environmental risk factors are both involved is not straightforward. Ignoring environmental factors may lead to inflated estimates of lambdaR. We present a marginal model which uses a copula function to model the association in cumulative incidence rates between pairs of relatives. This model is applicable to present-state data and allows estimation of risk of disease in a pair of relatives (and hence lambdaR), given measured environmental covariates. We apply the model to leprosy among sibling pairs from the Karonga district, Malawi. If risk factors are ignored, the apparent lambdaS in this population is over 3. Accounting for known nongenetic risk factors reduces it to just under 2.
Asunto(s)
Humanos , Lepra Dimorfa/inmunología , Lepra Dimorfa/microbiología , Lepra Dimorfa/transmisión , Lepra Tuberculoide/inmunología , Lepra Tuberculoide/microbiología , Lepra Tuberculoide/transmisión , Lepra Lepromatosa/inmunología , Lepra Lepromatosa/microbiología , Lepra Lepromatosa/transmisión , Lepra/clasificación , Lepra/inmunología , Lepra/microbiología , Lepra/transmisión , Modelos Estadísticos , Modelos Lineales , Modelos Teóricos , Modelos de Riesgos Proporcionales , Medición de Riesgo/estadística & datos numéricos , Medición de Riesgo/tendencias , Oportunidad Relativa , Riesgo , Vacuna BCG/uso terapéuticoAsunto(s)
Anticuerpos Antibacterianos/inmunología , Anticuerpos Monoclonales/inmunología , Antígenos Bacterianos/análisis , Biopsia , Chaperoninas/análisis , Chaperoninas/inmunología , Células de Schwann/microbiología , Lepra Dimorfa/inmunología , Lepra Dimorfa/microbiología , Hipersensibilidad Tardía/microbiología , Inmunohistoquímica , Lipopolisacáridos/análisis , Lipopolisacáridos/inmunología , Macrófagos/microbiología , Mycobacterium leprae/inmunología , Mycobacterium leprae/aislamiento & purificación , Nervios Periféricos/inmunología , Nervios Periféricos/microbiología , Piel/inmunología , Piel/microbiologíaRESUMEN
Although leprosy became a curable disease after implementation of the Global Strategy for the Elimination of Leprosy (WHO), mutilations and deformities are still commonplace in endemic countries. Hence, it remains important to evaluate the prevalence rate and the risk factors of acral bone resorption in the multidrug therapy (MDT) era. A cohort of 105 newly-diagnosed adult multibacillary leprosy patients admitted for treatment between 1990-1992 was surveyed until 1999. Progression of bone resorption (BR) in cured leprosy patients was observed up to 8 years after release from MDT. Twenty three percent of the patients were found to have acral resorption. BR was found to be associated with male sex, grade of disability at diagnosis with other deformities and with the occurrence of four or more lepra reactions. Patient surveillance after release from MDT continues to be a necessary procedure in individuals with disabilities and recurrent or persistent reactions.
Asunto(s)
Resorción Ósea/etiología , Dedos , Lepra Dimorfa/complicaciones , Lepra Dimorfa/tratamiento farmacológico , Lepra Lepromatosa/complicaciones , Lepra Lepromatosa/tratamiento farmacológico , Adolescente , Adulto , Cuidados Posteriores/métodos , Anciano , Resorción Ósea/diagnóstico por imagen , Brasil/epidemiología , Estudios de Cohortes , Personas con Discapacidad/estadística & datos numéricos , Progresión de la Enfermedad , Femenino , Humanos , Leprostáticos/uso terapéutico , Lepra Dimorfa/clasificación , Lepra Dimorfa/epidemiología , Lepra Dimorfa/microbiología , Lepra Lepromatosa/clasificación , Lepra Lepromatosa/epidemiología , Lepra Lepromatosa/microbiología , Masculino , Persona de Mediana Edad , Prevalencia , Modelos de Riesgos Proporcionales , Radiografía , Recurrencia , Factores de Riesgo , Distribución por Sexo , Factores Sexuales , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Clofazimina/uso terapéutico , ADN Bacteriano/análisis , Dapsona/uso terapéutico , Leprostáticos/uso terapéutico , Lepra Dimorfa/diagnóstico , Lepra Dimorfa/microbiología , Lepra Dimorfa/tratamiento farmacológico , Lepra Tuberculoide/diagnóstico , Lepra Tuberculoide/microbiología , Lepra Tuberculoide/tratamiento farmacológico , Mycobacterium leprae/genética , Mycobacterium leprae/aislamiento & purificación , Quimioterapia Combinada , Reacción en Cadena de la Polimerasa , Rifampin/uso terapéuticoAsunto(s)
Adolescente , Biopsia con Aguja , Niño , Diagnóstico Diferencial , Lepra Dimorfa/diagnóstico , Lepra Dimorfa/microbiología , Lepra Dimorfa/patología , Lepra Tuberculoide/diagnóstico , Lepra Tuberculoide/microbiología , Lepra Tuberculoide/patología , Lepra Lepromatosa/diagnóstico , Lepra Lepromatosa/microbiología , Lepra Lepromatosa/patología , Inmunohistoquímica , Tamizaje Masivo , IndiaRESUMEN
The authors studied the Mitsuda reaction in 37 leprosy patients (18 reactional tuberculoid, 19 reactional borderline cases) and compared the results with clinical findings, histopathology and bacilloscopy. Evaluation of the Mitsuda reaction was carried out on days 30, 60, 90 and 120. Most of the reactional tuberculoid patients showed a Mitsuda reaction of +3 in opposition to the reactional borderline patients who showed only +. Bacilloscopic analysis revealed that in 75% of the reactional tuberculoid cases there were rare or no bacilli; bacilli were present in 95% of the reactional borderline cases. The authors conclude that reactional tuberculoid cases have a greater ability to clear bacilli than reactional borderline cases, and that the Mitsuda reaction is a useful tool for the differentiation between these two types of leprosy.
Asunto(s)
Lepromina , Lepra Dimorfa/diagnóstico , Lepra Tuberculoide/diagnóstico , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Lepra Dimorfa/microbiología , Lepra Dimorfa/patología , Lepra Tuberculoide/microbiología , Lepra Tuberculoide/patología , Masculino , Persona de Mediana EdadRESUMEN
The authors studied the Mitsuda reaction in 37 leprosy patients (18 reactional tuberculoid, 19 reactional borderline cases) and compared the results with clinical findings, histopathology and bacilloscopy. Evaluation of the Mitsuda reaction was carried out on days 30, 60, 90 and 120. Most of the reactional tuberculoid patients showed a Mitsuda reaction of +3 in opposition to the reactional borderline patients who showed only +. Bacilloscopic analysis revealed that in 75% of the reactional tuberculoid cases there were rare or no bacilli; bacilli were present in 95% of the reactional borderline cases. The authors conclude that reactional tuberculoid cases have a greater ability to clear bacilli than reactional borderline cases, and that the Mitsuda reaction is a useful tool for the differentiation between these two types of leprosy.
Asunto(s)
Masculino , Femenino , Humanos , Niño , Adolescente , Adulto , Lepromina , Lepra Dimorfa/diagnóstico , Lepra Dimorfa/microbiología , Lepra Tuberculoide/diagnóstico , Lepra Tuberculoide/microbiologíaAsunto(s)
Biopsia con Aguja , Diagnóstico Diferencial , Fibras Nerviosas/microbiología , Fibras Nerviosas/patología , Granuloma/patología , Lepra Dimorfa/diagnóstico , Lepra Dimorfa/microbiología , Histiocitos/microbiología , Histiocitos/patología , Linfadenitis/diagnóstico , Linfadenitis/microbiología , Ganglios Linfáticos/inervación , Mycobacterium leprae/aislamiento & purificación , Neuritas/diagnóstico , Neuritas/microbiología , Cuello/patología , Sistema Nervioso Periférico/patologíaRESUMEN
Thirty-six, untreated borderline lepromatous/lepromatous (BL/LL) leprosy patients with an initial bacterial index (BI) of 4+ to 6+ were serially allocated to three treatment groups. Group I patients received a slightly modified WHO regimen (rifampin once a month, clofazimine and dapsone daily) and BCG intradermally (i.d.) (0.1 mg/per dose). Group II patients were administered the same MDT and Mycobacterium w (2 x 10(8)) killed bacilli/dose i.d., and Group III received the same MDT with 0.1 ml of distilled water i.d. Vaccination was repeated every 6 months. Biopsies were taken from the local site of vaccination and from a distant site, i.e., the back. The progress was monitored periodically by clinical, histopathological and bacterial (BI, mouse foot pad, ATP) parameters. Twenty-five patients had completed a follow up of more than 2 years. These included: 7 in Group I, 10 in Group II, and 8 in Group III. One patient of the MDT + BCG group who was progressing well dropped out after 28 months. In cases on combined chemotherapy and immunotherapy, no viable bacilli were demonstrable by mouse foot pad and ATP measurement after 6 months (at 12 months or afterward). However, in come of the control cases on MDT alone, viable bacilli could be detected even up to 18 months (by mouse foot pad) and 2 years (by ATP estimation). With 36 months of treatment, the mean BI decreased from 4.64+ to 1.66+ in the group on MDT alone (controls), 4.9+ to 0.08+ in the MDT + BCG group, and 4.75+ to 0 in the MDT+Mycobacterium w group. Compared with the MDT and MDT + BCG groups, the fall in the BI was significantly more in the MDT + Mycobacterium w group at 12, 18, and 24 months. While all of the cases in the Mycobacterium w groups became smear negative by 36 months, it took 42 months for all of the BCG group to achieve negativity. Immunotherapy appears to have a significant effect on the killing and clearance of bacilli and should be considered as an adjunct to chemotherapy, especially in bacilliferous lepromatous cases
Asunto(s)
Humanos , Lepra Dimorfa/microbiología , Lepra Dimorfa/terapia , Lepra Lepromatosa/microbiología , Lepra Lepromatosa/terapiaAsunto(s)
Biopsia , Lepra Dimorfa/complicaciones , Lepra Dimorfa/microbiología , Lepra Dimorfa/patología , Lepra Tuberculoide/complicaciones , Lepra Tuberculoide/microbiología , Lepra Tuberculoide/patología , Lepra Lepromatosa/complicaciones , Lepra Lepromatosa/microbiología , Lepra Lepromatosa/patología , Histiocitos/patología , Infecciones por VIH/complicaciones , Mycobacterium leprae/aislamiento & purificación , Síndrome de Inmunodeficiencia Adquirida/complicacionesRESUMEN
En 30 enfermos de lepra se obtuvieron los datos de daño ocular mediante biomicroscopias y se practicaron biopsias del fondo de saco conjuntival. El objetivo fue establecer una correlación clínico-bacteriológica entre la biopsia conjuntival con la baciloscopia, la clasificación y la evolución de la enfermedad. Las lesiones oculares predominantes fueron la madarosis y el engrosamiento de los nervios corneanos. No se encontró ningún caso de ceguera. La concordancia fue del 46.6 por ciento en un total de 6 biopsias conjuntivales positivas.