Analysis of HLA-G protein expression in leprosy.

The aim of this study was to evaluate the expression of human leukocyte antigen G (HLA-G) in leprosy. Biopsy and serum samples were collected from 18 patients presenting with leprosy and from healthy controls. Samples were analyzed using immunohistochemistry and ELISA techniques. HLA-G expression was observed in biopsy samples of all patients. The healthy control samples were consistently negative for HLA-G expression. Control plasma samples displayed significantly higher HLA-G expression than those from the patients (p < 0.01). These results are the first demonstration of the expression of HLA-G in leprosy.

Leprosy: Clinical aspects and diagnostic techniques.

Leprosy, also known as Hansen's disease, is a curable infectious disease that remains endemic in >140 countries around the world. Despite being declared "eliminated" as a global public health problem by the World Health Organization in the year 2000, approximately 200,000 new cases were reported worldwide in 2017. Widespread migration may bring leprosy to nonendemic areas, such as North America. In addition, there are areas in the United States where autochthonous (person-to-person) transmission of leprosy is being reported among Americans without a history of foreign exposure. In the first article in this continuing medical education series, we review leprosy epidemiology, transmission, classification, clinical features, and diagnostic challenges.

Position statement: LEPROSY: Diagnosis, treatment and follow-up.

BACKGROUND: Leprosy or Hansen's disease is a chronic infection caused by Mycobacterium leprae (M. leprae) or Mycobacterium lepromatosis (M. lepromatosis). In Europe, most of the leprosy cases are imported. However, occasionally a case is diagnosed in one of the old endemic foci. Leprosy is often not suspected because it is no longer emphasized in the medical curricula. Attention shifted from leprosy to tuberculosis and human immunodeficiency virus infections in the late 20th century, whereby the WHO leprosy programme was toned down in the conviction that leprosy was all but eliminated. The result of unawareness is a harmful doctor's delay. MATERIAL AND METHODS: This paper focusses on clinical diagnosis, complications and treatment based on literature and experience. RESULTS: It mentions the value of laboratory tests in classification, follow-up and detection of relapses. It discusses the etiopathology. CONCLUSION: This is a position statement.

Is the WHO disability grading system for leprosy related to the level of functional activity and social participation?

To investigate the relationship between the WHO disability grading system for leprosy with the limitations to perform daily functional activities and the decrease in social participation in participants with leprosy. Participants with a diagnosis of leprosy were recruited at the dermatology ambulatory clinic of the University Hospital of Sergipe. In order to investigate the association of WHO disability grading system for leprosy with activities of daily living measured with the Screening Activity Limitation and Safety Awareness (SALSA) scale and with the social participation (P-scale), we performed an analysis with the Kruskal-Wallis test and the Spearman coefficient. Thirty-six patients diagnosed with leprosy participated in the study. Most of participants had mild to moderate daily activity limitations and 58% of participants did not have any restriction participation. The findings demonstrated that the WHO grading is associated with the level of activity (P < 0·0001; p = 0·58), but not with the level of participation (P <0·05; p = 0·27). Although the WHO grading system is used in Brazil and worldwide as an epidemiological indicator to explain the burden of leprosy, the results of this study demonstrated that in our sample the WHO grading system was not associated with participation. Participation is a complex construct with the influence of different psychosocial factors. In order to determine social participation damage of infectious diseases such as leprosy, it is necessary to develop new index of classification based on a broader definition of disability. Health professionals should consider the international classification of function and health (ICF) to develop such index.

Leprosy ­ an old infectious disease with unsolved matters. / Lepra Eine alte Infektionskrankheit mit vielen ungeklärten Fragen.

Leprosy is a chronic disease with many clinical manifestations, which affect mainly the skin, the peripheral nerves, mucosa of the upper respiratory tract and the eyes. Although global elimination of leprosy was achieved globally in the year 2000 and the disease is actually rare in most parts of the world, a low but constant number of more than 200,000 new cases are still registered each year. Leprosy is caused by two acid-resistant, slow multiplying Gram-positive bacteria, i. e., Mycobacterium leprae and the recently discovered M. lepromatosis. The transmission routes of these pathogens are not completely understood. All forms of leprosy can be treated with long-lasting antibacterial combination therapy using dapsone and rifampicin and ­ in cases of multibacillar leprosy ­ clofazimin. Using this multi-drug approach, leprosy has been shown to be curable in most cases. However, immunological sequelae (leprosy reactions), which may appear during therapy or even several years later, are frequently difficult to treat. Although leprosy has been eliminated in most countries, its complete eradication is extremely unlikely.

Serum Th1/Th2 and macrophage lineage cytokines in leprosy; correlation with circulating CD4(+) CD25(high) FoxP3(+) T-regs cells.

Not only macrophages, T-helper (Th)1 and Th2, but also CD4(+) CD25(high) FoxP3(+) regulatory T cells (T-regs) are involved in immune response to Mycobacterium leprae. We aimed to evaluate serum interleukin (IL)-1ß and IL-12p70 (macrophage cytokines), interferon-γ (IFN-γ) (Th1 cytokine), IL-4 (Th2 cytokine) and circulating CD4(+) CD25(high) FoxP3(+) T-regs, in untreated leprosy patients. Forty three patients and 40 controls were assessed for the mentioned cytokines using ELISA. Patients were assessed for circulating T-regs using flow cytometry. Patients were subgrouped into tuberculoid (TT), pure neural leprosy (PNL), borderline cases, lepromatous (LL), type 1 reactional leprosy (RL1) and erythema nodosum leprosum (ENL). Serum IL-12p70, IFN-γ and IL-4 were significantly higher in patients versus controls (P < 0.05). Serum IL-4 was highest in LL and lowest in RL1 (P = 0.003). Serum IL-1ß levels was significantly higher in multibacillary versus paucibacillary patients (P = 0.006). Significantly higher T-regs levels was detected in TT, RL1 and PNL, while the lowest levels in ENL(P < 0.001), with significant differences versus controls (P < 0.05). FoxP3 expression% was significantly lower in PNL than other patients and controls (P < 0.05). T-regs/T-effs was lowest in ENL(P < 0.05). IFN-γ correlated positively with T-regs but negatively with IL-1ß (P = 0.041&0.046 respectively), which correlated positively with T-effs%( P = 0.05). IL-4 correlated positively with T-regs FoxP3 expression% (P = 0.009). We concluded that: Circulating T-regs were increased in TT, RL1 and PNL patients, known of relatively high cell-mediated immunity. This finding was supported by low FoxP3 expression (in PNL) and correlation between T-regs count and IFN-γ level. Overproduction of IL-4 in LL may infer liability to develop ENL, with disease progression and immune hyperactivation, marked by deficient T-regs and increased T-regs FoxP3 expression%. IL-1ß probably has a pro-inflammatory role in multibacillary patients as correlated with T-effs%.

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.

[Guidelines for the treatment of Hansen's disease in Japan (third edition)].

ad hoc committee of Japanese Leprosy Association recommends revised standard treatment protocol of leprosy in Japan, which is a modification of World Health Organization's multidrug therapy (WHO/MDT, 2010). For paucibacillary (PB) leprosy, 6 months treatment by rifampicin and dapsone (MDT/PB) is enough. However, for high bacterial load multibacillary (MB) leprosy, 12 months treatment seems insufficient. Thus, (A) For MB with bacterial index (BI) > 3 before treatment, 2 years treatment by rifampicin, dapsone and clofazimine (MDT/MB) is necessary. When BI becomes negative and active lesion is lost within 2 years, no maintenance therapy is necessary. When BI is still positive, one year of MDT/MB is added (3 years in total), followed by maintenance therapy by dapsone and clofazimine until BI negativity and loss of active lesions. (B) For MB with BI < 3 or fresh MB (less than 6 months after the onset of the disease) with BI > 3, 1 year treatment by MDT/MB is necessary. When BI becomes negative and active lesion is lost within one year, no maintenance therapy is necessary. When BI is still positive or active lesion is remaining, additional therapy with MDT/MB for one more year is recommended. Brief summary of diagnosis, purpose of therapy, character of drugs, and prevention of deformity is also described.

[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.

Clinicohistopathological concordance in leprosy - a clinical, histopathological and bacteriological study of 100 cases.

Leprosy is a treatable chronic infectious disease, prevalent in South Asian countries, especially India. Before labeling a patient as a case of leprosy and starting multidrug treatment for particular type, the clinical findings should be correlated and confirmed with histopathological examination and bacteriological index of skin biopsy. Skin biopsy is an important tool in diagnosing leprosy and determining the type of leprosy. In the present study, one hundred untreated clinically diagnosed cases of leprosy were studied according to Ridley-Jopling scale for confirmation of diagnosis and classification of leprosy. The study was done by routine H & E (Haematoxylin & Eosin) staining and Fite-Faraco's staining for acid-fast bacillus. The data pertaining to age, sex, clinical and histopathological classification of the type of leprosy were collected and analyzed. In analyzing the histopathology of a lesion, special attention was given to the following features, viz., invasion of the epidermis with or without erosion, involvement of the sub-epidermal zone, character and extent of granuloma, density of lymphocytic infiltrate epithelioid cells and other cellular elements, nerve involvement and the presence of Mycobacterium leprae. Histological diagnosis of leprosy was established in 98% of clinically diagnosed cases. Clinicohistopathological concordance was maximum in LL(93.75%) followed by BL(87.5%), TT(78.5%), BT(73.8%) and least in IL(27.78%). Overall, it was 60.23%. Indeterminate type of leprosy was diagnosed more on histologythan on clinical evaluation.

Correlation of clinical and histopathological classification of leprosy in post elimination era.

Clinical and histopathological correlative study was carried out in 171 cases of leprosy using the criteria laid down by Ridley and Jopling. There was male preponderance in the study with majority of patients (35.7%) in the age goup of 21-30 years. The overall concordance between the clinical and histopathological diagnosis was 57.3%. Maximum concordance was seen in the polar ends of the spectrum with 76.9% in LL and 75.0% in TT. The concordance rate was lower in the borderline groups with 57.3% in BT, 40.0% in BL and least concordance of 16.7% in BB. However the concordance for IL was higher than the borderline groups with 66.7%. Cases in borderline group are in continuously changing immunological spectrum. Histological classification because of its definitive features gives a better indication than clinical classification for any recent shift of a case in the spectrum. Therefore skin biopsy should be done in all cases for correct classification of leprosy.

Clinico histopathological correlation in leprosy.

INTRODUCTION: Leprosy is a chronic infectious disease caused by M. leprae, which presents in different clinico-pathological forms, depending upon the immune status of the host. Clinical classification gives recognition only to gross appearances of the lesions, whereas the parameters used for the histopathological classification are well defined, precise, and also take into account the immunological features. RESULTS: Of the 182 suspected cases of leprosy which were biopsied, the clinical diagnosis was TT in 32 (17.5%), BT in 70 (38.4%), BB in 5(2.7%), BL in 24 (13.1%), LL in 23 (12.6%), and indeterminate in 28 (15.3%) cases. Of the 182 cases, which were biopsied, only 136 (74.7%) showed histological features consistent with any one type of leprosy. The overall clinicohistological correlation was 74.7 percent. A comparison of the histopathological pattern with that of clinical pattern revealed that the maximum correlation was seen with LL (84.2%), followed by BL (73.3%), BT (64.1%), TT (56%), BB, and IL (50%). CONCLUSION: Because there is some degree of overlap in different types of leprosy, especially the unstable forms, the correlation can be made more accurate by combining clinical and histopathological features.

Childhood leprosy in a tertiary-care hospital in Delhi, India: a reappraisal in the post-elimination era.

OBJECTIVE: To assess the profile and describe the clinical presentations, clinico-histopathological profile, complications and treatment compliance of childhood leprosy at a tertiary care hospital in north-east district of Delhi during 2000-2009. DESIGN: A retrospective institutional study of children less than 14 years of age diagnosed with leprosy and registered in a leprosy clinic during 2000-2009. Demographic, clinical, investigative and treatment data was extracted from a pre-designed proforma. RESULTS: A total of 1790 cases of leprosy were registered during this period, of which 172 (9.6%) were children. The majority of patients (70.3%) were more than 11 years of age with a male preponderance. History of contact was present in 25 (14.5%) patients. Borderline tuberculoid (BT) was the commonest clinical type (70.3%) followed by tuberculoid (TT) seen in 5.8%, mid-borderline (BB) in 1.2%, borderline lepromatous (BL) in 9.9%, lepromatous (LL) in 4.1%, pure neural (PNL) in 4.6% and indeterminate in 4.1% cases. More than half (52.9%) patients had a single lesion. Nerve thickening was detected in 70% cases. Slit skin smears were positive in 34 (19.8%) patients. Eighty-nine (51.7%) children were classified as multibacillary (MB) and 83 (48.3%) as paucibacillary (PB) disease by NLEP criteria. Of the available biopsy records, clinico-histological correlation was observed in 130/151 (86.1%) patients. Lepra reactions were observed in 32 patients (18.6%), Type I in 29 cases and Type II in three cases. Neuritis occurred in 11 (6.4%) and deformities in 22 (12.8%) patients. Thirty-four (19-8%) children defaulted from treatment. Two patients relapsed. CONCLUSIONS: Despite the statistical elimination of leprosy in this region, childhood leprosy cases continue to present in alarming numbers. Our study confirmed that multibacillary disease and the complications of lepra reactions and deformities remain common in children. Early detection, treatment and contact tracing may be important reducing the burden of leprosy in the community. There is a need to continue leprosy control activities with full vigour even in areas where, statistically, it has been eliminated.

A case of leprosy with multiple cranial neuropathy mimicking Melkerson Rosenthal syndrome.

Involvement of cranial nerves is not uncommon in leprosy with trigeminal and facial nerves being commonly affected. Other cranial nerves can also be involved especially in longstanding cases of leprosy towards the lepromatous pole. Herein, we report a case of leprosy with multiple cranial neuropathy mimicking Melkerson Rosenthal syndrome.

[Survey of newly diagnosed Japanese leprosy patients].

We aimed to elucidate the patterns and trends of autochthonous leprosy in Japan from 1964 to 2009, to compare them with the findings from other studies of leprosy in decline. Data on registered leprosy cases in Japan in the period 1964-2009 were analysed with reference to trends in case detection, geographical distribution, age at diagnosis, sex, classification and family history. A consistent decline in leprosy case detection was observed in all areas of the country over the period 1964-2009. Highest incidence was consistently in Okinawa. Autochthonous leprosy has not been reported in anyone born in Japan since 1980. Increasing average age and a shift towards lower latitudes were demonstrated throughout the period. Analyses of data on autochthonous cases revealed patterns similar to those reported in other countries with declining leprosy. Okinawa has had the highest incidence of leprosy in all of Japan since the first national survey in 1900. Several possible explanations include the difference of leprosy control history between Okinawa and the rest of Japan, Okinawa's unique geographical condition, large-scale problem of stigma and discrimination against leprosy patients and delayed improvement of socio-economic conditions.

[Diagnosis of Hansen's disease].

The Leprosy Mailing List (LML) is an e-mailing list open to whoever interested in the field from all over the world. It acts as a forum for exchanging information related to Hansen's disease. It was established in February 2001 in Italy, and the present moderator of the LML is Dr. Salvatore Noto. He and his colleague have recently introduced an atlas for diagnosing Hansen's disease which they brought together information and photos collected through the LML. The atlas is divided into three sections, (1) Introduction, (2) Cardinal signs, and (3) Diagnosis and the clinical spectrum of leprosy, and they are all accompanied with relevant photos. This time, Dr. Noto kindly permitted us to translate the atlas into Japanese to be published in the Japanese Journal of Leprosy and posted in the Japanese Leprosy Association homepage. This article includes the translation and some of the most informative photos. For more information, please refer to the homepage where you will find all photos in the atlas.

Clinicohistopathological correlation in leprosy.

BACKGROUND: Leprosy is a chronic, infectious disease caused by Mycobacterium leprae. It is classified into five groups based on clinical, histological, microbiological and immunological criteria (Ridley and Jopling Classification) . However, a great variation has been observed in the interpretation of histopathological examination ok skin biopsies and clinical presentation of the disease. OBJECTIVE: To correlate clinical diagnosis with histopathological diagnosis of leprosy patients in Nepal. METHODS: A retrospective hospital-based study was conducted among patients with all clinical types of leprosy, classified as per the Ridley-Jopling classification. Skin biopsies were taken from active lesions in all patients and were stained with Hematoxylin and Eosin stain and modified Fite-Ferraco stain for identification of Mycobacterium leprae. The histopathological findings were compared with clinical diagnoses. RESULTS: A total 156 patients were studied, out of which 84 (53.8%) males and 72 (46.1%) females between 8 and 86 years of age. The majority of patients 33 (23.57%) were in the age group of 21-30 years and least affected was children below 10 years 1(0.007%).Overall coincidence of clinical and histopathological diagnoses of classification was seen in 115 cases (80.4%). The maximum correlation (95.2%) was noted in LL patients (p value 0.000049) followed by BT(89.74%), TT (73.2%),BL(72.4%), BB(64.7%). CONCLUSION: Leprosy still continues to be one of the common infectious disease in Nepal and skin biopsy is a useful tool in confirming the clinical diagnosis of leprosy as well as for the therapeutic guide.

The cutaneous infiltrates of leprosy. A transmission electron microscopy study.

The dermal lesions of 18 patients with leprosy have been examined by transmission electron microscopy. The patients exhibited a spectrum of disease from polar lepromatous to polar tuberculoid with intermediate stages in various states of therapy and relapse. The nature and quantities of inflammatory cells and bacteria have been determined by electron microscopy to supplement previous light and fluorescence microscopy studies. Lepromatous leprosy was characterized by many parasitized foam cells containing large, multibacillary vacuoles with intact, osmiophilic Mycobacterium leprae: Bacteria were embedded in an electron-lucent matrix. No extracellular bacteria were evident. Only small numbers of scattered lymphocytes were found. As one approached the borderline state, smaller numbers of bacilli were present as singlets and doublets in small vacuoles of macrophages. The more reactive forms showed increasing bacillary fragmentation, larger numbers of lymphoid cells, and an occasional epithelioid cell. At the tuberculoid end of the spectrum, clear evidence of an exuberant lymphocyte response was evident. Large numbers of T cells with extremely long and complex filipodia were closely associated with epithelioid and multinucleated giant cells. Many of the mononuclear phagocytes appeared nonviable, and areas of necrosis were evident. Bacillary remnants were scarce and the cytoplasm of the epithelioid cells contained occasional dense bodies and many stacks of endoplasmic reticulum and mitochondria. These results suggest that Leu 3a/OKT4 helper cells may be capable of driving the effector function of mononuclear phagocytes. This would lead to a significant microbicidal effect on M. leprae, perhaps through the production of toxic oxygen intermediates.

Nitric oxide metabolites in sera of patients across the spectrum of leprosy.

Leprosy, a chronic infectious disease, caused by Mycobacterium leprae infection, manifests itself as a clinical spectrum depending on the patients' immunological response, finally leading to peripheral nerve damage and deformities in the patients. Nitric oxide (NO) which is known to contribute to pathogenesis of several neurological diseases has been detected in tissues and urine of leprosy patients. This is the first study assessing NO as its stable end products, nitrites and nitrates, in sera of patients across the spectrum of the disease as a possible parameter of prognostic value. Comparison of NO metabolites showed a significant increase in multibacillary patients and patients with type I reactions as compared to healthy control individuals. These levels reduced significantly after treatment. This study has further borne out the utility and reliability of the cadmium-reduction method of estimation of NO metabolites--a relatively inexpensive procedure that lends itself to large-scale screening and follow-up of patients.