Wade histoid leprosy: histological and immunohistochemical analysis.

Histoid leprosy is a rare multibacillary form that presents with disseminated papule-nodular cutaneous lesions. To study the inflammatory infiltrate of the histoid form and to compare it with other lepromatous forms, we performed histological and immunohistochemical analysis on skin biopsies. Fifteen patients were included for histopathological analysis (10 histoid and five lepromatous) via the haematoxylin-eosin and Ziehl-Neelsen-Faraco stains. Thus, immunohistochemical techniques using immunoperoxidase assay were performed for: anti-BCG, anti-M. leprae, anti-CD8, anti-CD3, anti-CD20, anti-S100, anti-CD1a, anti-CD68 and antivimentin. Spindle cells were present in all histoid patients. A pseudocapsule was observed in half of both studied forms. A comparison using the Ziehl-Neelsen-Faraco stain to evaluate anti-BCG and anti-M.leprae showed no major differences. The CD3+ cells were more pronounced in the histoid form than the lepromatous form. There was greater immunoreactivity toward CD8+ cells in the histoid form, as well as the CD20+ cell count. A similar count of S100+ cells in the epidermis of both leprosy forms was observed. There was a slight increase of dendritic cells in the histoid patients in the superficial and deep dermis. For CD1a marker, we observed expression in the epidermis and superficial dermis in both forms. A diffuse and intense infiltrate of CD68+ cells was also observed in the histoid and lepromatous forms. The high positivity for vimentin did not allow for a positive cell count. We concluded that the activation of both the cellular and humoral response is more pronounced in the histoid form because the T and B cells showed greater infiltration than those in the lepromatous form. The activation of dendritic and Langerhans cells is similar in both forms. The spindle cells likely belong to the macrophage population, thus maintaining phagocytic ability. The quantities of pseudocapsules and bacilli are similar and cannot serve as criteria for diagnosis.

Lower numbers of natural killer T cells in HIV-1 and Mycobacterium leprae co-infected patients.

Natural killer T (NKT) cells are a heterogeneous population of lymphocytes that recognize antigens presented by CD1d and have attracted attention because of their potential role linking innate and adaptive immune responses. Peripheral NKT cells display a memory-activated phenotype and can rapidly secrete large amounts of pro-inflammatory cytokines upon antigenic activation. In this study, we evaluated NKT cells in the context of patients co-infected with HIV-1 and Mycobacterium leprae. The volunteers were enrolled into four groups: 22 healthy controls, 23 HIV-1-infected patients, 20 patients with leprosy and 17 patients with leprosy and HIV-1-infection. Flow cytometry and ELISPOT assays were performed on peripheral blood mononuclear cells. We demonstrated that patients co-infected with HIV-1 and M. leprae have significantly lower NKT cell frequencies [median 0.022%, interquartile range (IQR): 0.007-0.051] in the peripheral blood when compared with healthy subjects (median 0.077%, IQR: 0.032-0.405, P < 0.01) or HIV-1 mono-infected patients (median 0.072%, IQR: 0.030-0.160, P < 0.05). Also, more NKT cells from co-infected patients secreted interferon-γ after stimulation with DimerX, when compared with leprosy mono-infected patients (P = 0.05). These results suggest that NKT cells are decreased in frequency in HIV-1 and M. leprae co-infected patients compared with HIV-1 mono-infected patients alone, but are at a more activated state. Innate immunity in human subjects is strongly influenced by their spectrum of chronic infections, and in HIV-1-infected subjects, a concurrent mycobacterial infection probably hyper-activates and lowers circulating NKT cell numbers.

Comparison of quality of life evaluated by SF-36 and DLQI in multibacillary and paucibacillary leprosy patients from Sao Paulo, Brazil.

BACKGROUND: Dermatological diseases have a negative impact on quality of life (QoL), affecting mental and physical health. Leprosy patients usually present with a worse QoL compared with those affected by other conditions. Reactions, neural damage, and pain are some of the consequences that contribute to the lower QoL. However, due to the wide spectrum of the disease, symptoms vary according to leprosy's subtype. This study aimed to compare the QoL between paucibacillary and multibacillary leprosy patients. Individuals were also compared considering the presence of reactions and a correlation between questionnaires was performed. METHODS: A total of 104 patients with leprosy aged 18 years old and over were selected. QoL was assessed by the Brazilian-Portuguese validated versions of the Medical Outcomes Study 36-item short-form health survey (SF-36) and the Dermatology Life Quality Life Index (DLQI). RESULTS: Multibacillary patients showed a more impaired physical function, worse bodily pain, lower score of SF-36, and higher interference of skin on the performance of daily activities when compared to the paucibacillary group. Individuals without reactions presented lower bodily pain and less effect of the skin on clothing choices compared to those with reactions. The SF-36 domains exhibited weak correlations with most DLQI questions, and the linear regression model showed that 32% of changes in QoL were related to the skin aspect. CONCLUSIONS: Multibacillary leprosy patients have a worse QoL when compared to paucibacillary patients. Reactions played a small role in the QoL of our cohort of patients.

Leprosy reversal reaction as immune reconstitution inflammatory syndrome in patients with AIDS.

We report 2 instances in which reactional borderline leprosy manifested itself as an immune reconstitution phenomenon in patients with acquired immunodeficiency syndrome. We discuss the clinical, laboratory-based, histopathologic, and immunohistochemical characteristics of both patients. Furthermore, we review similar reports from the literature.

Comparison between anti-PGL-I serology and Mitsuda reaction: clinical reading, microscopic findings and immunohistochemical analysis.

The lepromin test, serum IgM antibodies against Mycobacterium leprae and in situ observations of T cell subsets in biopsies of Mitsuda reaction using monoclonal antibodies were performed on 44 untreated leprosy patients belonging to various classifications of the disease. The Mitsuda reaction was accessed clinically and histologically after 28 days. Clinical reading and histological analysis of Mitsuda reaction showed good agreement. The high positivity in clinical reading correlated with compact granulomas in histology. There is a graduation of Mitsuda reaction that follows the immunological spectrum of the disease. The histological study of Mitsuda reaction is valuable to confirm the immunological condition in doubtful clinical reaction. Anti-PGL-I IgM levels correlated with disease classification, increasing from the tuberculoid towards the lepromatous pole of the disease spectrum. There was an inverse correlation between serum IgM antibody levels and clinical and histological reading of Mitsuda reaction. There were no statistical difference in quantities and distribution of CD4+ and CD8+ T cells in all Mitsuda reactions. The pattern of cellular content of Mitsuda reaction could not be related to the T cells.

High expression of myeloid-related proteins 8 and 14 characterizes an inflammatorily active but ineffective response of macrophages during leprosy.

Macrophages are decisive cells for the course of leprosy as they phagocytose Mycobacterium leprae and have the potential to influence the specific immune response. Expression and release of the myeloid-related protein (MRP) 8 and MRP14 (S100A8 and S100A9) characterize a proinflammatory subtype of macrophage that is prominent in, for example, murine infection with lack of a T helper 1 cell response and in certain highly active chronic inflammations of mice and humans. We investigated cutaneous biopsies of the different forms of leprosy (41 untreated patients) including leprosy reaction type 1 (reversal reaction) and type 2 (erythema nodosum leprosum) (n = 18) for expression of MRP8 and MRP14 by subtypes of macrophages. Concomitantly we determined serum levels of MRP8 and MRP14 by sandwich enzyme-linked immunosorbent assay. Expression of MRP8 and MRP14 by CD68-positive macrophages was low in tuberculoid leprosy and rose significantly in borderline tuberculoid leprosy and especially in multibacillary forms, there being expressed by mycobacteria-loaded foam cells. A significant rise of MRP8 and MRP14 expression also occurred in lepra reactions compared to the corresponding non-reactional forms. In type 2 reactions this additional increase was associated with a significant elevation of serum levels. In type 1 it was associated with expression of MRP8 and MRP14 by epitheloid and giant cells, which so far were considered not to express both proteins. In conclusion, we present evidence that the two prominent proteins MRP8 and MRP14 can be re-expressed in vivo by tissue macrophages in chronic infection, that their increased expression is characteristic for a macrophage subtype associated with high inflammatory but low antimycobacterial activity in the absence of a T helper 1 response, and that their significant rise in serum during erythema nodosum leprosum bears diagnostic and pathophysiological relevance.

Anti-phenolic glycolipid-I (PGL-I) determination using blood collection on filter paper in leprosy patients

The authors studied 70 leprosy patients and 20 normal individuals, comparing the traditional sera collection method and the finger prick blood with the conservation on filter paper for specific antibodies against the native phenolic glycolipid-I (PGL-I) from Mycobacterium leprae. The finger prick blood dried on filter paper was eluated in phosphate buffer saline (PBS) containing 0.5 percent gelatin. The classical method for native PGL-I was performed for these eluates, and compared with the antibody determination for sera. It was observed that there is a straight correlation comparing these two methods; although the titles found for the eluates were lower than those obtained for serology. This blood collection method could be useful for investigation of new leprosy cases in field, specially in contacts individuals

Lepra leucomelanodérmica / Leukomelanodermic leprosy

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Leukomelanodermic leprosy

A 39-year-old woman presented with a 6-year history of asymptomatic macules on her back. The patient had no other complaints, and she did not report any case of infectious disease in her family. Examination revealed hyperpigmented macules, presenting irregular edges but with a sharp demarcation, on the midline of the back from the cervical to the lumbar region. Within these hyperpigmented areas, islands of normal appearing skin were observed. There were also some hypopigmented macules on the lateral and posterior aspects of the trunk (Fig. 1). The patient presented thickening of the left ulnar nerve and sensory loss to temperature on the lateral aspect of the left arm. Biopsy specimens were obtained from the hyper- and hypopigmented areas. In the hyperpigmented macule, the biopsy revealed focal areas of hypomelanosis in the epidermis and the presence of melanophages in the superficial dermis, but no acid-fast bacilli were found (Fig. 2a). The Masson-Fontana stain showed an evident pigmentary incontinence (Fig. 2b). The biopsy obtained from the hypopigmented lesion also revealed focal areas of hypomelanosis, but in the superficial dermis an infiltrate of foamy macrophages was observed, as typically found in lepromatous leprosy (Fig. 3a); acid-fast bacilli were found by Fite-Faraco stain. The focal hypomelanosis was confirmed by Masson-Fontana stain (Fig. 3b). Mitsuda's reaction in this patient was negative and slit-skin smears (cutaneous lesion, earlobes, elbows, and knees) were negative for acid-fast bacilli. The patient was treated with multidrug therapy for multibacillary leprosy: rifampin, 600 mg once monthly (supervised), clofazimine, 300 mg once monthly (supervised), dapsone, 100 mg daily, and clofazimine, 50 mg daily, all given for 2 years. After 7 months of treatment, the hypopigmented lesions diminished and the hyperpigmented lesions improved after 2 years of treatment and the sensory loss to temperature was restored.

High expression of myeloid-related proteins 8 and 14 characterizes an inflammatory active but ineffective response of macrophages during leprosy

Macrophages are decisive cells for the course of leprosy as they phagocytose Mycobacterium leprae and have the potential to influence the specific immune response. Expression and release of the myeloid-related protein (MRP) 8 and MRP14 (S100A8 and S100A9) characterize a proinflammatory subtype of macrophage that is prominent in, for example, murine infection with lack of a T helper 1 cell response and in certain highly active chronic inflammations of mice and humans. We investigated cutaneous biopsies of the different forms of leprosy (41 untreated patients) including leprosy reaction type 1 (reversal reaction) and type 2 (erythema nodosum leprosum) (n=18) for expression of MRP8 and MRP14 by subtupes of macrophages. Concomitantly we determined serum levels of MRP8 and MRP14 by sandwich enzyme-linked immunosorbent assay. Expression of MRP8 and MRP14 by CD68-positive macrophages was low in tuberculoid leprosy and rose significantly in borderline tuberculoid leprosy and especially in multibacillary forms, there being expressed by mycobacteria-loaded foam cells. A significant rise of MRP8 and MRP14 expression also occurred in lepra reactions compared to the corresponding non-reactional forms. In type 2 reactions this additional increased was associated with a significant elevation of serum levels. In type 1 it was associated with expression of MRP8 and MRP14 by epitheloid and giant cells, which so far were considered not to express both proteins. In conclusion, we present evidence taht the two prominent proteins MRP8 and MRP14 can be re-expressed in vivo by tissue macrophages in chronic infection, that their increased expression is characteristic for a macrophage subtype associated with high inflammatory but low antimycobacterial activity in the absence of a T helper 1 response, and that their significant rise in serum during erythema nodosum leprosum bears diagnostic and pathophysiological relevance.