RESUMO
INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease with major diagnostic and therapeutic difficulties, basically comprising two different conditions: primary and secondary forms. Recent advances regarding molecular diagnosis may be useful to distinguish from one another, especially in sporadic cases starting in early infancy. MATERIALS AND METHODS: In this report, we evaluated three Argentinean patients with clinical suspicion of HLH, but without family history. We excluded mutations in the perforin gene but identified in the three patients a novel homozygous deletion (c. 581_584delTGCC; p.Leu194ProfsX2) in the gene-encoding syntaxin 11 (STX11), causing a premature termination codon. RESULTS AND CONCLUSION: Each parent from the three unrelated families resulted heterozygous for this deletion confirming the diagnosis of familial hemophagocytic lymphohistiocytosis type 4. Patients shared the same single-nucleotide polymorphism profile in STX11 gene, and genotyping at ten microsatellites surrounding this gene support the presence of a single-haplotype block carrying the novel mutation.
Assuntos
Família , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/genética , Proteínas Qa-SNARE/genética , Deleção de Sequência/genética , Argentina , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Infecções , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Neutropenia , Linhagem , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Plantar intrinsic foot muscles provide structure to the foot during walking and thus regulate mechanical foot sole stresses. When paralyzed, for instance in leprosy patients with neuropathy of the distal part of the tibial nerve, there is a high prevalence of plantar ulceration and deformities, especially when muscle weakness goes together with loss of foot sole sensibility. These patients should get immediate care involving education, special footwear and reconstructive surgery before further foot impairment and deformity becomes manifest. Thus far, in leprosy patients little attention is paid to screening of plantar intrinsic muscles activity. This can be done with a new simple and non-invasive method, the Paper Grip Test (PGT). There are two variants for detecting intrinsic muscle weakness of the foot, PGT1 for the great toe and PGT2 for the combined lesser toes. In this study, 517 leprosy patients and 170 healthy volunteers were investigated with the PGT. Sensibility of the foot sole was tested by means of a 10 gram monofilament. Specificity to the PGT1 is found to be about 95.3% which is considered good for physical diagnostic tests. PGT2 is less specific than PGT1. Individual muscle power and understanding of the patient seems to influence the outcome of the test to a certain extent. Sensitivity can only be calculated when the diagnosis is confirmed by electromyography. Especially patients with anesthetic feet, females, older patients and patients with PN-, BB- or LL-types of leprosy appeared to have a higher prevalence of intrinsic foot muscle weakness. All results were analyzed by means of the bivariate Pearson correlation-analysis and proved to be statistically significant (p = < 0.05). It is concluded that the PGT1, more than the PGT2, is a useful screening test on the function of plantar intrinsic foot muscles in leprosy patients in hospitals and during fieldwork in developing countries.
Assuntos
Hanseníase/fisiopatologia , Paralisia/complicações , Paralisia/fisiopatologia , Pé/fisiopatologia , Pé/inervaçãoRESUMO
Aunque se sabe que los casos frotis muy bacilíferos presentan un riesgo elevado de recidivas después de ser dadas de alta de la MDT, los programas de control en el campo sin facilidades para efectuar frotis no disponen de un método alternativo para poder detectarlos. Este estudio presentó una prevalencia significativa de este tipo de casos entre 2.374 casos multibacilares nuevos recientemente detectados por frotis cutáneos en Nepal y análisis retrospectivos de 555 casos nuevos recien detectados, BL y LL sin tratar, para identificar parámetros clínicos y de laboratorio asociados con un frotis cutáneo muy bacilíferos. Mientras que alguno de estos parámetros presentan gran sensibilidad en precedir "casos muy bacilíferos", ninguno presenta simultáneamente elevada sensibilidad y especificidad.
Assuntos
Hanseníase , Hanseníase/classificação , Hanseníase/diagnósticoRESUMO
A DNA vaccine composed of the gene for the common mycobacterial secreted protein antigen 85B was demonstrated to protect the mouse foot pad against infection with Mycobacterium leprae. The protective effect was demonstrated by a 61%-88% reduction in the bacterial number, a protective effect less than that of BCG. The same DNA vaccine has been shown to protect mice against M. tuberculosis infection, and the importance of testing other candidate tuberculosis vaccines for their potential to protect against leprosy is discussed.
Assuntos
Humanos , DNA , Mycobacterium leprae/imunologia , Mycobacterium tuberculosis/imunologiaRESUMO
New tools for the detection of leprosy exposure in a community will be necessary for the eradication of leprosy. Candidate leprosy skin-test antigens derived from the fractionation of the leprosy bacillus into cytoplasmic and cell-wall proteins free of immuno-inhibitory mycobacterial lipoglycans and carbohydrates were used in an overnight blood test to determine whether exposure to leprosy can be detected by the production of the cytokine interferon gamma (IFN-gamma). Strong IFN-gamma responses were detected in leprosy contacts to both skin-test antigens compared with control subjects from the same endemic communities. There was little response in patients with tuberculosis. Responses were greatest in contacts with recent leprosy exposure. The implications of these findings for the application of these reagents in a field trial as skin tests to detect exposure to leprosy are discussed in light of the strong association between overnight IFN-gamma to PPD and the tuberculin skin-test responses previously reported.
Assuntos
Hanseníase/genética , Hanseníase/imunologia , Interferon gama/farmacologia , Interferon gama/uso terapêuticoAssuntos
Antígenos HLA-DR/genética , Antígenos HLA-DR/metabolismo , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Ativação Linfocitária , Dados de Sequência Molecular , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/química , Especificidade da Espécie , Genoma Bacteriano , Hanseníase Tuberculoide/diagnóstico , Hanseníase Tuberculoide/imunologia , Hanseníase Tuberculoide/microbiologia , Linfócitos T/imunologia , Mycobacterium leprae/genética , Mycobacterium leprae/imunologia , Mycobacterium leprae/química , Peptídeos/imunologia , Peptídeos/síntese química , Sequência de AminoácidosRESUMO
A retrospective study of new borderline lepromatous and lepromatous patients reporting for multidrug therapy (MDT) for leprosy at the Anandaban Leprosy Hospital, Kathmandu, Nepal, over an 8-year period was conducted to determine the prevalence of erythema nodosum leprosum (ENL), the time and frequency of reactions, and clinical and laboratory parameters associated with ENL. An overall prevalence of ENL in this cohort of 19% was found. One third of these reactions occurred in patients before MDT was given, one third in the first 6 months and one third after 6 months of treatment. Nearly 1 in 10 of the ENL reactions occurred in patients who had completed 2 years of MDT; 45% of patients with ENL had more than one episode. Data collected at the patients' first presentation was used to identify four major risk factors. Patients with lepromatous disease, skin infiltration or a bacterial index (BI) of > 4+ were at significantly increased risk. Patients older than 40 were at significantly decreased risk of ENL. There was a linear relationship in the risk of ENL with an increasing BI and an inverse relationship to increasing age. These observations should enable clinicians to recognize patients at first presentation who will be likely to develop ENL.
Assuntos
Eritema Nodoso/complicações , Eritema Nodoso/fisiopatologiaRESUMO
A new rapid immuno-chromatographic test card for the detection of antibodies to the Mycobacterium leprae 35-kD protein is described. The new assay is compared in the same group of subjects with a direct enzyme ELISA method for 35-kD antibodies and with assays for anti-phenolic glycolipid-I (PGL-I) antibodies using a standard ELISA as well as the recently described [quot ]dipstick[quot ] method. Good concordance was found between the rapid methods and the corresponding ELISA methods. The detection of untreated paucibacillary leprosy by the 35-kD test card was 59% compared with 27% for the PGL-I dipstick; however, the specificity for the 35-kD test card was 90% compared with 100% for the PGL-I dipstick in an endemic population. The potential application of these new, rapid serologic methods for the diagnosis of leprosy under field conditions is discussed.
Assuntos
Humanos , /imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Mycobacterium leprae/fisiologia , Mycobacterium leprae/genéticaRESUMO
The changes in nerve function tests in 297 new leprosy patients over an average period of 30 months were measured. The impact of type 1 reactions (T1R) on sensory and voluntary muscle function was measured by standard tests. Sensory function was improved in patients with single episodes of cutaneous T1R, but not improved in patients with neural T1R or with multiple episodes of either kind of T1R. Patients over 40 years of age improved less than younger patients, and patients admitted for treatment of T1R improved more than those treated as outpatients. These data point to a need to find better regimens for the treatment of nerve damage in T1R.