Tuberculoid leprosy: An in vivo microvascular evaluation of cutaneous lesions.

Tuberculoid leprosy (TT) is characterized by cutaneous lesions called plaques. Although microvascular ultrastructure of TT patients' skin is well-documented, little is known about functional aspects of their microcirculation. We aimed, for the first time, to evaluate, in vivo, the microcirculation of TT cutaneous lesions. Seven TT patients, males, under treatment were included in the study. The spectral analysis of frequency components of flowmotion (endothelial, sympathetic, myogenic, cardiac and respiratory) was performed using laser Doppler flowmetry (LDF). Endothelial dependent and independent vasodilatations were assessed by LDF associated to acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis, respectively. Vessel density (VD), perfused vessel density (PVD), proportion of perfused vessels (PPV%), microvascular flow index (MFI) and flow heterogeneity index (FHI), reflecting tissue perfusion and oxygenation, were evaluated through sidestream dark field (SDF) imaging. All microvascular analysis were performed in TT lesions and in healthy skin in the contralateral limb of the same patient, used as control skin. VD, PVD and PPV% and MFI were significantly lower in the cutaneous lesion compared to contralateral healthy skin. The contribution of different frequency components of flowmotion, endothelial dependent and independent vasodilatations and FHI were not statistically different between control skin and cutaneous lesion. Our results suggest that TT cutaneous lesions have a significant impairment of tissue perfusion, which may aggravate peripheral nerve degeneration caused by Mycobacterium leprae infection.

Mandating nerve biopsy: A step towards personalizing therapy in pure neuritic leprosy.

Pure neuritic leprosy (PNL) accounts for 5% to 10% of leprosy patients who usually present with asymmetrical neuropathy in the absence of lepra bacilli on slit-skin smears. However, nerve biopsies in PNL lack appropriate categorization in current immunologic terms. We aimed to classify nerve biopsies according to the immune spectrum of leprosy and assess the role of histologic classification of nerve biopsies in treating PNL. Patients from two tertiary care referral centres were enrolled in this incident case study. Patients presenting with mononeuropathy and multiple mononeuropathies presumably with leprosy, without skin lesions, underwent nerve biopsy and slit-skin smear examination. Amongst 78 patients with mononeuropathy, 38 were diagnosed with leprosy on nerve biopsy. Leprosy was classified as tuberculoid in 16, lepromatous in 5 and borderline in 17 patients. Lepra bacilli were present in 15 biopsies. On comparing histologic subtypes with number of nerves involved clinically, a significant number of cases with single nerve involvement showed multibacillary (BB, BL or LL) histology and vice versa. Nerve biopsy helps in diagnosing patients presenting with PNL and aids in classifying it to customize the treatment for best results. Current treatment recommendations for PNL from WHO and National Leprosy Eradication Program are based on clinical assessment only, which are likely to result in inconsistent treatment and possibly relapse in cases where histomorphology shows disparity. Inclusion of nerve biopsy to guide therapy in patients with PNL is suggested.

Induction and treatment of anergy in murine leprosy.

Leprosy is a disease consisting of a spectrum of clinical, bacteriological, histopathological and immunological manifestations. Tuberculoid leprosy is frequently recognized as the benign polar form of the disease, while lepromatous leprosy is regarded as the malignant form. The different forms of leprosy depend on the genetic and immunological characteristics of the patient and on the characteristics of the leprosy bacillus. The malignant manifestations of lepromatous leprosy result from the mycobacterial-specific anergy that develops in this form of the disease. Using murine leprosy as a model of anergy in this study, we first induced the development of anergy to Mycobacterium lepraemurium (MLM) in mice and then attempted to reverse it by the administration of dialysable leucocyte extracts (DLE) prepared from healthy (HLT), BCG-inoculated and MLM-inoculated mice. Mice inoculated with either MLM or BCG developed a robust cell-mediated immune response (CMI) that was temporary in the MLM-inoculated group and long-lasting in the BCG-inoculated group. DLE were prepared from the spleens of MLM- and BCG-inoculated mice at the peak of CMI. Independent MLM intradermally-inoculated groups were treated every other day with HLT-DLE, BCG-DLE or MLM-DLE, and the effect was documented for 98 days. DLE administered at a dose of 1.0 U (1 × 10(6) splenocytes) did not affect the evolution of leprosy, while DLE given at a dose of 0.1 U showed beneficial effects regardless of the DLE source. The dose but not the specificity of DLE was the determining factor for reversing anergy.

Primary neural leprosy: systematic review.

The authors proposed a systematic review on the current concepts of primary neural leprosy by consulting the following online databases: MEDLINE, Lilacs/SciELO, and Embase. Selected studies were classified based on the degree of recommendation and levels of scientific evidence according to the "Oxford Centre for Evidence-based Medicine". The following aspects were reviewed: cutaneous clinical and laboratorial investigations, i.e. skin clinical exam, smears, and biopsy, and Mitsuda's reaction; neurological investigation (anamnesis, electromyography and nerve biopsy); serological investigation and molecular testing, i.e. serological testing for the detection of the phenolic glycolipid 1 (PGL-I) and the polymerase chain reaction (PCR); and treatment (classification criteria for the definition of specific treatment, steroid treatment, and cure criteria).

Primary neural leprosy: systematic review / Hanseníase neural primária: revisão sistemática

The authors proposed a systematic review on the current concepts of primary neural leprosy by consulting the following online databases: MEDLINE, Lilacs/SciELO, and Embase. Selected studies were classified based on the degree of recommendation and levels of scientific evidence according to the “Oxford Centre for Evidence-based Medicine”. The following aspects were reviewed: cutaneous clinical and laboratorial investigations, i.e. skin clinical exam, smears, and biopsy, and Mitsuda's reaction; neurological investigation (anamnesis, electromyography and nerve biopsy); serological investigation and molecular testing, i.e. serological testing for the detection of the phenolic glycolipid 1 (PGL-I) and the polymerase chain reaction (PCR); and treatment (classification criteria for the definition of specific treatment, steroid treatment, and cure criteria).

Os autores propuseram-se a realizar uma revisão sistemática em conceitos atuais sobre a hanseníase neural primária, consultando as seguintes bases bibliográficas on-line: MEDLINE, Lilacs/SciELO e Embase. Os estudos selecionados foram classificados conforme o grau de recomendação e o nível de evidência científica de acordo com o “Oxford Centre for Evidence-based Medicine”. Os seguintes temas foram revisados: investigações clínica e laboratorial cutâneas, ou seja, exame, esfregaço e biópsia de pele e reação de Mitsuda; investigação neurológica (anamnese, eletroneuromiografia e biópsia de nervo); investigação sorológica e testes moleculares, ou seja, testes sorológicos para detecção de um glicolipídio fenólico e reação de cadeia de polimerase (PCR) e tratamento (critérios de classificação para definição de tratamento específico, tratamento com esteroides e critérios de cura).

[Diagnosis and treatment of leprous neuropathy in practice]. / Diagnostic et traitement de la neuropathie lépreuse en pratique.

Leprosy still affects 240,000 persons every year in the world. It is a particularly common cause of neuropathy and severe disabilities in developing countries. With increasing migration, new cases of leprosy are regularly diagnosed in developed countries, where it still remains rare and so underestimated. Cutaneo-nevritic leprosy is the most frequent form of leprosy. It may be diagnosed by the clinical features and the cutaneous histology and bacteriology. Neuritic leprosy without obvious skin lesions is reported in 5 to 15% of leprosy patients. It must be suspected in persons from areas of endemic disease presenting with nerve thickening and associated nerve deficit. Nerve biopsy is essential for diagnosis. However search for bacilli in cutaneous samples may be of great help and avoid nerve biopsy. Acute and severe neuritis occurs during reactional states, reversal reaction (Type 1) and erythema nodosum leprosum (Type 2). Multidrug therapy is advocated. The treatment of acute neuropathy needs a supplementary medical and sometimes surgical treatment.

Great auricular nerve involvement in leprosy: scope for misdiagnosis.

Three patients with neuritis of the great auricular nerve (GAN) have been reported. Two patients seen by physicians and an otolaryngologist had prominent and tender cord along the neck with facial edema and history of fainting attack in one, and erythema and hyperaesthesia of the ear in the other simulating vascular occlusion, which were confirmed to be leprosy in Type 1 reaction by the dermatologist. In the third, cold abscess in the nerve that had persisted after anti-leprosy treatment was mistaken as tuberculous cervical lymphadenitis by a surgeon since aspiration had revealed acid-fast bacilli. The probable reasons for misdiagnosis include rarity of involvement of the GAN and its proximity to main blood vessels, and the need for careful interpretation of laboratory results.

Estudo terapêutico comparando a associação de rifampicina, ofloxacina e minociclina com a associação rifampicina, clofazimina e dapsona em pacientes com hanseniase multibacilar / Therapeutical study comparing the association of rifampin, ofloxacine e minocycline with a association rifampin, clofazimine e dapsone in patients with bacillus leprosy

O presente trabalho comparou dois esquemas terapêuticos em pacientes com hanseniase multibacilar. O grupo l, que recebeu o tratamento convencional (PQT-MB), foi denominado grupo de controle. O grupo 2, denominado de grupo teste, recebeu a associação de rifampicina 600mg, mais ofloxacina 400mg, mais minociclina 100mg (ROM), administrado sob supervisão, uma vez por mês. A duração total do tratamento nos dois grupos foi de dois anos. Na avaliação inicial foram realizados: exame clinico, baciloscopio e histologico. A baciloscopia e a biopsia foram repetidas no final do primeiro ano e novamente no final do segundo ano de tratamento. A avaliação clinica foi realizada mensalmente por ocasião da administração da dose supervisionada. No grupo 1 foram avaliados 14 pacientes. O indice baciloscopio (IB) antes do tratamento variou de 2 a 4,8. No grupo 2 foram estudados 12 pacientes. O IB antes do tratamento nesse grupo variou de m1,6 a 4,8. Ambos os grupos apresentavam lesões cutâneas que os caracterizavam como pertencentes ao pólo vichoviano. Histologicamente apresentavam quadro de hanseniase virchoviana ativa, exceto um paciente do grupo 2. Ao final do primeiro ano de tratamento estavam todos clinicamente melhorados, o indice baciloscopio diminuido e com quadro histologico em regressão. Essa tendencia de melhora se mantinha e na avaliação do finanl do segundo ano todos estavam clinicamente, baciloscopidamente e histologicamente ainda melhores. A análise estatistica dos parametros, baciloscopio e histologico, mostrou que não houve diferença estatisticamente significativa entre os grupos estudados, sendo, portanto os dois esquemas equivalentes. A ocorrência de reação tipo 2(eritema nodoso hansenico-ENH) foi igual nos dois grupos. no primeiro grupo 1, todos apresentaram pigmentação cutânea devido a clofazimina. Os resultados, portanto, demonstraram que o esquema com administração mensal de rifampicina, mais ofloxacina, mais minociclina tem eficácia e segurança equivalenteao esquema convencional. Além disso, tem a vantagem de não acarretar pigmentação cutânes, ser totalmente supervisionado, podendo ser utilizado como esquema alternativo.

O paciente com suspeita de hanseníase primariamente neural / The patient with suspicion of primarily neural leprosy

The author presents the definition of primarily neural leprosy, describes it clinically and exposes the differentiation among the similar neuropathies. The main causes of mononeuropathies, multiple mononeuropathies and polineuropathies that can be misinterpreted as leprosy were discussed. The role of nerve biopsy in the diagnosis confirmation and its prevailing findings were presented. And finally, there were suggestions of the procedures for health workers when facing these patients on the field.

Algorithms as guides for the prevention of permanent nerve damage in leprosy patients.

The responsibility for treating leprosy patients is being passed on to the general medical and health care services, predominantly located in primary health care centres. It therefore becomes necessary for the staff of these services to have clear guidelines on what they should do to prevent permanent nerve damage and its consequences when they come across a leprosy patient with neuritis or nerve function deficit. Six algorithms to help achieve this purpose are presented in this article.

An evaluation of clinical and histopathological status in paucibacillary leprosy patients after completion of sixed duration therapy

The presente study was carried out involving 25 patients with paucibacillary leprosy who attended the outpatient department of dermatology of Father Muller's Medical College Hospital during the period January 2001 to March 2002. All the patients were examined clinically and histopathologically at the beginning and at the end of six months of MDT and relevant data recorded. Clinicopathological correlation with histopathological classification before MDT was 72% and 68% at the end of MDT in our study. At the end of treatment 4 (16%) cases were clinically active and 8 (32%) were histopathologically active. The study showed that active cases were siginificantly reduced as a result of MDT, both clinically and histopatologically. The histopathological activity that outlasts MDT may be due to the bacillary fragments that persist; but clincial activity coupled with histopathological activity seen in 2 patients at the end of 6 months of MDT was possibly an indicator of relapse and these patients and similar others need to be follewed up for a longer duration. Is this study, resolution of granuloma and clinical activity after completion of MDT were assessed

[Leprosy simulating other diseases]. / Lepra simulando otras enfermedades.

The low current prevalence of leprosy in Spain together with the diversity of its clinical expression make the detection of this disease difficult. Three native and three imported cases are here reported. Different specialists mistook this disease for other entities: familial polyneuropathy, autoimmune disease, tuberculosis, cutaneous mycosis, and cutaneous sarcoidosis. Lepra is a very polymorphic disease and its diagnosis is based on finding cutaneous hypoesthesic lesions, neural thickening and presence of acid-fast bacilli (in cutaneous specimens or nasal exudates).

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

A longitudinal study of immunologic reactivity in leprosy patients treated with immunotherapy.

More than 150 leprosy patients treated with multidrug therapy (MDT) plus immunotherapy (IMT) with a mixture of heat-killed Mycobacterium leprae plus live BCG were studied in relation to humoral and cell-mediated immune responses. Many previously had received prolonged sulfone monotherapy. Patients received 2 to 10 doses of IMT in a period of 1 to 3 years, depending upon their clinical form of leprosy. The patients were followed up for 5 to 10 years with repeated determinations of antibody levels to phenolic glycolipid-I; lymphoproliferative (LTT) responses to soluble extract of M. leprae, to whole bacilli and to BCG, skin-test responses and bacterial indexes (BIs). After MDT plus IMT there was a statistically significant decrease of antibody levels in the multibacillary (MB) group. The BI decreased proportionally to the ELISA results. LTT increased to M. leprae antigens, especially to soluble extract, in a high percentage of these patients (34% of LL patients positive). Lepromin positivity in MB patients increased from 5% initially positive to 75% at the cut-off during this follow up. These results show substantial early and persistent cell-mediated reactivity to M. leprae in many MB patients treated with MDT-IMT, confirming and expanding previously published data.