Clinical and histopathological evaluation of the effect of addition of immunotherapy with Mw vaccine to standard chemotherapy in borderline leprosy.

This study reports detailed analysis of clinical parameters and clearance of granuloma in borderline leprosy patients treated with immunotherapy and chemotherapy. It aims to assess the additive effect of immunotherapy (Mwvaccine) with standard MDT on clinical status of untreated borderline leprosy cases and on granuloma fraction of untreated borderline leprosy cases. Patients attending the OPD were serially recruited in two groups. A total of 150 cases in one treatment (trial) group (Mw vaccine plus MDT) and 120 cases in another treatment (control) group (MDT only) of border line leprosy have been included. After the formal written consent, detailed clinical examination, charting, smear examination of all untreated borderline patients of both groups was done, biopsies were taken from the active lesions of all patients of both groups at start of therapy and every six month thereafter till the completion of therapy. The same procedure was repeated every six months during the follow-up period. Standard MDT was given to all the patients of both groups according to type of disease. Mw vaccine 0.1 ml (0.5 x 10(9) bacilli) was injected intra-dermally at the start of therapy and every six months in addition to chemotherapy to the treatment group. The BT cases were followed up after 6 doses of MDT and 2 doses of Mw vaccine, and, the BB, BL cases were followed up after 24 doses of MDT plus 5 doses of Mw vaccine. Clinically, greater and faster improvement was observed in all the clinical parameters, faster attainment of smear negativity and two episodes of lepra reaction occurred in cases treated with combined chemotherapy and immunotherapy, as compared to controls (chemotherapy alone) wherein clinical improvement was slower in all parameters, slower attainment of smear negativity in bacillary index and seven showed the occurrence of reactions, histipathologically in addition to more rapid clearance of granuloma in immunotherapy treated group, a significant finding was an increase in the epithelioid cells population in this group. This suggests a possible immunoactivation of the macrophages especially in BB/BL immunotherapy group. Overall comparison of regression induced by chemotherapy alone with that induced by combined chemotherapy and immunotherapy shows a greater reduction in clinical parameters as well as granuloma fraction in BT cases as well as in BB/BL cases. This trial shows the potential usefulness of this approach of addition of immunotherapy to standard chemotherapy in borderline leprosy cases which leads to in faster recovery from disease reduced chances of reactions and faster granuloma clearance. Such information is expected to be useful in improving the immunotherapeutic approaches for treatinggranulomatous conditions in general and in leprosy in particular.

Histopathological lesions of apparently normal skin in leprosy patients.

This study was carried out on 50 patients with different clinical types of leprosy 38 males (76 % and 12 females (24%), ages ranged from 14 -70 years with a mean age +/- SD 49.22 +/- 12.97 years. Mean disease duration was 5.65 years +/- SD = 9.27 selected to study a group of leprosy patients and compare the clinical parameters with histopathological findings and bacteriologic status of the skin to evaluate the relevance of their patients. Patients were subjected to full medical history taking including disease duration, type and duration of previous or current therapies. Complete clinical examination, for the determination of the clinical type of leprosy. Skin slit smear (SSS) and skin biopsies were taken and examined after staining for histopathological assessment and Acid fast bacilli (AFB). SPSS package version (statistical Package for Social Sciences) was used for data analysis. The biopsy of normally looking skin showed classic histopathological features of leprosy in more than half of the cases (26 cases, 52%). The histopathological types of leprosy diagnosed in such cases were as follows: indeterminate leprosy (IL) in 4 cases (15.38%), Tuberculoid leprosy (TL) in 2 cases (7.69%), Borderline tuberculoid (BT) in 4 cases (15.38), Borderline Borderline (BB) i.e Query in 8 cases (30.76%), Borderline Lepromatous (BL) in 7 cases (26.92%) and Lepromatous leprosy (LL) in a patient (3.84%). Other 24 cases showed either no evidence of leprosy in (9 cases, 37.5%), or query findings (in the form of sweat gland changes either alone or in combination with thickened nerves and superficial and deep perivascular lymphohistiocytic infiltrate) in 15 cases (62.5%). Histopathology of skin lesion biopsies showed TL in 3 cases (6%), BT in 8 cases (16%), BB in 8 cases (16%), BL in 14 cases (28%), LL in 12 cases (24%) and leprosy in reaction in 5 cases (10%). In 16 cases (32%), histopathological type of leprosy detected by microscopical examination of biopsies from skin lesions differed from that diagnosed by clinical examination.

Perfil clinico-epidemiológico dos casos de hanseníase atentidos no Hospital Universitário em Campo Grande, Mato Grosso do Sul, de janeiro de 1994 a julho de 2005 / Clinical-epidemiological profile of leprosy patients assisted at the University Hospital of Mato Grosso do Sul Federal University, Campo Grande, MS, from January 1994 to July2005

Estudo descritivo, realizado a partir da coleta de dados de 192 fichas de notificação e controle da hanseníase, do total de pacientes atendidos no período de janeiro de 1994 a julho de 2005, no Ambulatório do Hospital Universitário da Universidade Federal de Mato Grosso do Sul, com o objetivo de traçar o perfil epidemiológico da hanseníase no grupo de pacientes estudados e gerar subsídios à política de controle da hanseníase. As variáveis estudadas constam da ficha de notificação e controle da hanseníase. Observou-se a predominância de casos no sexo masculino (62,5%); na faixa etária de 40 a 59 anos (45,8%); multibacilares (67,2%); da forma clinica dimorfa (35,9%) e virchowiana (27,6%). Setenta e três (73%) por cento dos casos foram avaliados em relação à incapacidade ao inicio do tratamento, encontrando-se 66,7% desses casos sem nenhum problema com as mãos, pés ou olhos e 33,3% com incapacidade ou deformidade ao início do tratamento.

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.

Reacao tipo 1 pós alta / Type 1 reaction after the discharge

E apresentado um caso de hanseniase pre-dimorfa tratada com PQT/PB/OMS com alguma melhora na ocasiao da alta. Um ano apos, a area de anestesia que apresentava no dorso do pe direito se estendeu pela panturrilha ate o cavo popliteo. Seis anos depois paciente retorna ao Centro de Saude com lesoes em placa quase planas roseo-hipocromicas anestesicas no tronco e pe esquerdo. Uma biopsia de uma lesao do abdome mostrou um quadro histopatologico compativel com reacao tipo 1 e baciloscopia igual a +++. Oa autores discutem a possibilidade dos bacilos estatem em um estado de persistencia e nao terem sido destruidos pelas drogas utilizadas. Segundo eles, apos a alta houve progressao dos bacilos pelos nervos determinando alteracoes no seu microambiente e consequentemente causando aumento da area anestesica sem serem reconhecidos ainda pelo sistema imune. Quando 6 anos depois eles se multiplicaram e foram finalmente reconhecidos pelas defesas do organismo, foram em parte destruidos, e deram lugar ao aparecimento de antigenos que desencadearam uma reacao de hipersensibilidade (reacao tipo 1). Os autores chamam a atencao que esses fatos tem que ser levados em consideracao no tratamento de pacientes nessas condicoes porque a resposta ao tratamento dos casos paucibacilares e diferente dos casos virchovianos

Lepra dimorfa lepromatosa localizada / Localized borderline lepromatous leprosy

Presentamos el caso de una mujer de 24 años, que consultó por una única placa eritematosa en la pierna derecha; el resto de la piel era normal. Daba la impresión de ser una lesión de lepra tuberculoide, pero tenía un índice baciloscópico elevado. La baciloscopía en el resto de la piel y las mucosas fue negativa. La evidencia histológica de lepra dimorfa lepromatosa fue notable. El caso se diagnosticó como lepra dimorfa lepromatosa localizada, una forma de presentación infrecuente de la lepra multibacilar. Este trabajo informa el caso de una paciente con lepra dimorfa lepromatosa limitada a un sitio del tegumento. Se destaca la importancia de realizar baciloscopía y biopsia en todos los casos de lepra (AU)

Paciente com reacao tipo I e tipo II e dez anos de seguimento / Type I and type II reactions in a patients with ten years of follow-up

Relata-se o caso de um individuo do sexo masculino, de 52 anos de idade, que desde 20 anos atras vinha apresentando sinais e sintomas de hanseniase multibacilar, mas so procurou tratamento apos 5 anos, quando apresentava manifestacoes de Eritema Nodoso Hansenico (ENH - Reacao tipo 1) inclusive com comprometimento articular. Instalado o tratamento (PQT/MB) o paciente passou a apresentar episodios de ENH, que se continuaram apos a alta medicamentosa alternando-se ou em concomitancia com episodios de reacao tipo 1 (reacao reversa) o que definiu como dimorfo. Assim permaneceu quase 10 anos, tendo apresentado, por algum tempo, esplenomegalia e sinais de hiperesplenismo. So melhorou, quando a deteccao de bacilos viaveis levou a reinstalacao da PQT. A discussao do caso ressalta alguns aspectos interessantes desta evolucao: 1) a demora no diagnostico leva pacientes dimorfos a adquirirem caracteristicas virchovianas com rica baciloscopia (virchovianos sub-polares); 2) estes pacientes tem maior possibilidade de albergarem bacilos persistentes que eventualmente se multiplicam e estimulam reacoes tipo I; 3) a alternancia de reacoes tipo 1 e tipo 2 pode indicar a participacao da imunidade celular no desencadeamento do ENH, onde a reacao granulomatosa romperia os infiltrados especificos regressivos, expondo antigenos intracelulares. Frente ao estado de hipersensibilidade humoral, haveria deposicao de complexos imunes e desencadeamento de reacao inflamatoria aguda; 4) a alta da PQT nao significa cura da hanseniase.

Prevalencia de olho seco em portadores de hanseniase do Hospital de Dermatologia Sanitaria de Goiania / ?

Objetico: Determinar a prevalencia de olho seco em portadores de hanseniase do Hospital de Dermatologia Sanitaria de Goiania, comparando-se a um grupo controle. Desenho: Estudo de prevalencia. Material e metodos: A amostra do presente estudo inclui 70 portadores de hanseniase, do Hospital de Dermatologia Sanitaria de Goiania, e 30 individuos no grupo controle, da Fundacao Banco de Olhos de Goias, ambos localizados em Goiania-GO. Foram realizados exeme oftalmologico e testes de Schirmer I, break-up time (BUT) e rosa bengala em todos estes individuos em uma unica avaliacao. Resultados: Quarenta e quatro (63,0%) portadores de hanseniase eram do sexo masculino e 22 73,3%) individuos do grupo controle, do sexo feminino (p=0,001). A idade medica dos hansenianos foi de 61,1+-12,5 anos e no grupo controle, 55,7+-9,6 anos. Quinze (21,4%) hansenianos e quatro (13,3%) individuos deo grupo controle apresentaram diagnostico de olho seco (p=0,429) A forma virchowiana (74,2%) da hanseniase foi a mais prevalente e o olho seco (66,7%) foi mais frequente nesta forma clinica da doenca. Conclusao: A prevalencia de olho seco nos portadores de hanseniase foi semelhante a encontrada nos individuos do grupo controle

Utility of fine-needle aspiration cytology in the classification of leprosy.

The role of fine-needle aspiration cytology (FNAC) in the diagnosis of benign skin lesions has been restricted primarily to the evaluation of bacteriologic and morphologic indices in leprosy. This study was undertaken to evaluate the efficacy of FNAC in the diagnosis and classification of lepromatous lesions. Aspirates of 94 newly diagnosed cases of leprosy were studied, and the bacterial load was determined by modified Ziehl-Neelsen (ZN) stain. A skin biopsy was taken from the same site at the same sitting. Frozen and paraffin sections stained with hematoxylin-eosin (H&E) and ZN stains were examined from the biopsy specimen. In 61 of 94 cases (64.9%), the aspirates were satisfactory. Both diagnosis and classification of leprosy were possible in 40 of these 61 cases; the rest of the aspirates showed nonspecific chronic inflammation. The 39 cases of leprosy where a biopsy was available from the same site were classified on FNAC into tuberculoid (TT and BT), lepromatous (LL and BL), and midborderline (BB) subtypes. Taking the histologic diagnosis and Ridley-Jopling classification to be the gold standard, a strong concordance in tuberculoid leprosy cases (18 of 20 cases, 90%) and in lepromatous cases (15 of 16 cases, 93.7%) was observed. Midborderline cases of leprosy posed a problem, and a correct cytohistological correlation was observed in only one of the three cases.

Histological changes in the nerve, skin and nasal mucosa of patients with primary neuritic leprosy.

Primary neuritic leprosy (PNL) presents as a peripheral neuropathy with no visible skin patches and skin smears negative for acid fast bacilli. The pathogenesis of PNL is poorly understood. The aim of the study was to document the histological changes in the nerve, apparently normal skin and nasal mucosa in PNL and to study its significance to the pathogenesis of leprosy lesions. The study is based on a cohort of 208 PNL patients registered at the Schieffelin Leprosy Research and Training Centre, Karigiri. All patients had a nerve biopsy, 196 had a skin biopsy and 39 had a nasal mucosal biopsy. The findings reveal that PNL patients exhibit a spectrum of disease histologically in the nerve ranging from lepromatous to tuberculoid leprosy with a significant proportion (46%) manifesting a multibacillary leprosy histology. Findings in the apparently normal skin and nasal mucosa reveal that there are widespread changes due to leprosy in tissues such as the skin and nasal mucosa even when the disease appears clinically confined to a few nerves. PNL may be an early stage in the pathogenesis of the disease before the appearance of skin lesions. The number of nerves enlarged and lepromin status did not give any clue to the nature of underlying disease.

Progression of acral bone resorption in multibacillary leprosy.

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.

Lepra indeterminada: una fase de transición en la evolución de la enfermedad / Undetermined leprosy: transition in disease evolution

Se efectúa una revisión de la clasificación de la forma indeterminada de la lepra, sus características clínico-histológicas y evolutivas. La misma es considerada como una forma incial de la enfermedad que frecuentemente cura en forma espontánea, sin tratamiento. Sin embargo, en algunos casos puede evolucionar hacia las otras formas clínicas discapacitantes de la enfermedad, siendo importante su diagnóstico y tratamiento precoz. Se describen los últimos estudios realizados para llegar a un diagnóstico de certeza de esta forma inicial (PCR, Inmunoperoxidasas), y los estudios predictivos de su evolución hacia otras formas clínicas (dosaje de AC séricos, reacción de la lepromina). El diagnóstico temprano de la lepra indeterminada, sin discapacidades, es uno de los objetivos de los Programas de Control, para la eliminación de la enfermedad (AU)

Lepra indeterminada: una fase de transición en la evolución de la enfermedad / Undetermined leprosy: transition in disease evolution

Se efectúa una revisión de la clasificación de la forma indeterminada de la lepra, sus características clínico-histológicas y evolutivas. La misma es considerada como una forma incial de la enfermedad que frecuentemente cura en forma espontánea, sin tratamiento. Sin embargo, en algunos casos puede evolucionar hacia las otras formas clínicas discapacitantes de la enfermedad, siendo importante su diagnóstico y tratamiento precoz. Se describen los últimos estudios realizados para llegar a un diagnóstico de certeza de esta forma inicial (PCR, Inmunoperoxidasas), y los estudios predictivos de su evolución hacia otras formas clínicas (dosaje de AC séricos, reacción de la lepromina). El diagnóstico temprano de la lepra indeterminada, sin discapacidades, es uno de los objetivos de los Programas de Control, para la eliminación de la enfermedad

Borderline--tuberculoid leprosy: clinical and immunological heterogeneity.

The authors analysed some immunological criteria in leprosy patients diagnosed as borderline tuberculoid by the presentation of different grades of skin lesions as well as different grades of nerve involvement. Only 50% of the patients presented a single skin lesion and 58% had none or only one affected nerve. Nineteen patients (39.6%) showed a positive lepromin reaction (induration > or = 5 mm). Patients with a positive skin test had a greater number of skin lesions when compared with patients with a negative lepromin test. Fifty-seven percent of the patients were found to be positive using a lymphoproliferation test (LTT) in response to Mycobacterium leprae antigens. Positive LTT results did not correlate with the number of skin lesions, but patients unresponsive to LTT had a lesser extent of nerve involvement. Four out of 18 patients (22%) released high IFN gamma levels in PBMC culture stimulated by M. leprae. (mean U/ml +/- SD = 142 +/- 72). All of these 4 patients presented only one skin lesion, although three of them had more than one affected nerve. Nineteen out of 21 patients (90.5%) showed no anti-PGL-1 antibodies in their serum. The low levels of anti-PGL-1 antibodies among these patients confirmed their tuberculoid background even in those with multiple skin lesions. These findings seem to attribute an important role to IFN gamma in restraining the spreading of the infection in the skin, but IFN gamma may have an opposite effect on the nerves. The potential pathological effects of IFN gamma during the delayed type of hypersensitivity can be related to its ability to synergise with other inflammatory cytokines such as TNF alpha, IL-1 beta, and others.

Multibacillary nerve histology in clinically diagnosed borderline tuberculoid leprosy patients.

The classification of leprosy into multibacillary (MB) and paucibacillary (PB) patients in almost all clinics is entirely dependent on clinical examination. In a study of 21 patients clinically classified as borderline tuberculoid (BT) and, therefore, belonging to the PB group, skin smears and skin and nerve biopsies were examined. Four patients did not have any histopathological evidence of leprosy. Skin smears showed that 1 patient was positive for acid-fast bacilli (AFB), 2 skin biopsies belonged to the borderline lepromatous (BL) category and showed AFB in their lesions, and AFB were present in 10 nerve biopsies classified as BL. It is possible that reported relapses among PB patients may be in those patients with demonstrable AFB in the lesions, including nerves. A careful follow-up study of this particular group of patients after PB multidrug therapy is suggested to resolve this question.