The oral cavity in leprosy: what clinicians need to know.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a bacillus that has a tropism for skin and peripheral nerves. Leprosy treatment is based on a multidrug therapy established by the World Health Organization in 1982 and, despite its widespread use, Brazil ranks second worldwide in numbers of cases. Oral involvement in leprosy has been poorly described in the literature, and few studies have shown that although the bacillus is found in mucosa, specific leprosy lesions are rare and affect patients with advanced stages of the disease. This review aimed to assess the literature on oral manifestations in leprosy and the aspects involving oral cavity in leprosy pathogenesis.

Use of anti-PGL-1 antibodies to monitor therapy regimes in leprosy patients

The suitability of IgM antibodies to PGL-1 for monitoring the response to multidrug therapy (MDT) was sequentially tested by ELISA in 105 leprosy patients, and bacterial indexes (BI) were also determined. Patients were divided into 3 groups: group 1, 34 multibacillary (MB) patients treated for 12 months with MDT-MB; group 2, 33 MB patients treated for 24 months with MDT-MB, and group 3, 38 paucibacillary (PB) patients treated for 6 months with MDT-PB. Untreated MB patients exhibited higher antibody levels (mean ± SEM): group 1 (6.95 ± 1.35) and group 2 (12.53 ± 2.02) than untreated PB patients (1.28 ± 0.35). There was a significant difference (P < 0.01) in anti-PGL-1 levels in group 1 patients: untreated (6.95 ± 1.35) and treated for 12 months (2.78 ± 0.69) and in group 2 patients: untreated (12.53 ± 2.02) and treated for 24 months (2.62 ± 0.79). There was no significant difference between untreated (1.28 ± 0.35) and treated (0.62 ± 0.12) PB patients. Antibody levels correlated with BI. The correlation coefficient (Pearson’s r) was 0.72 before and 0.23 (P < 0.05) after treatment in group 1 and 0.67 before and 0.96 (P < 0.05) after treatment in group 2. BI was significantly reduced (P < 0.01) after 12 and 24 months on MDT (group 1: 1.26-0.26; group 2: 1.66-0.36). Our data indicate that monitoring anti-PGL-1 levels during MDT may be a sensitive tool for evaluating treatment efficacy. These data also indicate that the control of leprosy infection can be obtained with 12 months of MDT in MB patients.

Use of anti-PGL-1 antibodies to monitor therapy regimes in leprosy patients.

The suitability of IgM antibodies to PGL-1 for monitoring the response to multidrug therapy (MDT) was sequentially tested by ELISA in 105 leprosy patients, and bacterial indexes (BI) were also determined. Patients were divided into 3 groups: group 1, 34 multibacillary (MB) patients treated for 12 months with MDT-MB; group 2, 33 MB patients treated for 24 months with MDT-MB, and group 3, 38 paucibacillary (PB) patients treated for 6 months with MDT-PB. Untreated MB patients exhibited higher antibody levels (mean +/- SEM): group 1 (6.95 +/- 1.35) and group 2 (12.53 +/- 2.02) than untreated PB patients (1.28 +/- 0.35). There was a significant difference (P < 0.01) in anti-PGL-1 levels in group 1 patients: untreated (6.95 +/- 1.35) and treated for 12 months (2.78 +/- 0.69) and in group 2 patients: untreated (12.53 +/- 2.02) and treated for 24 months (2.62 +/- 0.79). There was no significant difference between untreated (1.28 +/- 0.35) and treated (0.62 +/- 0.12) PB patients. Antibody levels correlated with BI. The correlation coefficient (Pearson's r) was 0.72 before and 0.23 (P < 0.05) after treatment in group 1 and 0.67 before and 0.96 (P < 0.05) after treatment in group 2. BI was significantly reduced (P < 0.01) after 12 and 24 months on MDT (group 1: 1.26-0.26; group 2: 1.66-0.36). Our data indicate that monitoring anti-PGL-1 levels during MDT may be a sensitive tool for evaluating treatment efficacy. These data also indicate that the control of leprosy infection can be obtained with 12 months of MDT in MB patients.

Endocrine dysfunction in leprosy.

Leprosy is still an endemic disease, especially in Third World countries, and, because of migration, it still persists in Europe and the United States. The disease affects the peripheral nerves, skin, and multiple internal organs, making its clinical recognition difficult. In particular, the endocrine manifestations caused by leprosy have been underestimated, even by specialists. The endocrine changes present in leprosy include hypogonadism, sterility, and osteoporosis. In addition, the spectral immune nature of leprosy offers an attractive model to investigate the pathogenetic correlation between the patterns of inflammation in the poles of its spectrum and the hormonal disarrangements observed in this disease. It is important that those involved in leprosy management be aware of the potential endocrine changes and their treatment to address the disease in all of its aspects. In this article, we review the findings on endocrine dysfunction in leprosy, including a survey of the literature and of our own work.

Dipstick assay to identify leprosy patients who have an increased risk of relapse.

Classification of leprosy patients into paucibacillary (PB) and multibacillary (MB) determines the duration of treatment; misclassification increases the risk of relapse because of insufficient treatment if an MB patient is classified as PB. We explored the possibility of using a simple dipstick assay based on the detection of antibodies to the Mycobacterium leprae-specific phenolic glycolipid-I (PGL-I) as a tool for classification of patients into PB and MB for treatment purposes. The sensitivity of the dipstick test for detection of MB patients was 85.1%, the specificity 77.7%. We found that of the 71 dipstick negative PB patients 25 (35.2%) were clinically cured at the end of treatment, compared with only two (9.5%) of the 21 dipstick positive PB patients. Of 170 patients in the study population, nine (5.3%) relapsed within the 5-year follow-up period. Seven were MB patients, all dipstick positive. Two PB patients relapsed, one was dipstick negative and one was dipstick positive. Dipstick positivity is a risk factor for the future development of relapses, especially in those groups of patients who had received a shorter-than-usual course of treatment and the dipstick can be used as an additional, simple tool for classification of patients and for identification of those patients who have an increased risk of relapse.

Production of transforming growth factor-beta 1 (TGF-beta1) by blood monocytes from patients with different clinical forms of leprosy.

In the present study, the concentration of TGF-beta1 secreted by adherent cells isolated from human peripheral blood mononuclear cells (PBMC) and either stimulated with PGL-1 or lipopolysaccharide (LPS) or left unstimulated was determined by ELISA. The cells were isolated from untreated patients with different clinical forms of leprosy and healthy individuals. The adherent cells exhibited spontaneous release of TGF-beta1 in all clinical forms of leprosy and in healthy individuals; however, lepromatous leprosy/borderline leprosy (LL/BL) patients presenting erythema nodosum leprosum (ENL) displayed significantly higher concentrations of TGF-beta1 than either the other patients studied or the controls. These high TGF-beta1 levels were consistently observed when LL/BL ENL cells were stimulated with phenolic glycolipid (PGL-1) or LPS, and even in the absence of a stimulus (P < 0.01). The most significant differences in TGF-beta1 levels were observed when comparing the results in the presence of PGL-1 from ENL with, in order of significance: tuberculoid leprosy (TT) patients (P < 0.001), LL/BL patients without ENL (P < 0.01), healthy individuals (P < 0.01) and borderline-borderline/borderline-tuberculoid (BB/BT) patients with reversal reaction (RR) (P < 0.01). The BB/BT patients produced equivalent levels of TGF-beta1 compared with LL/BL patients without ENL, for all types of stimuli (P > 0.05). In contrast, TT patients produced the lowest levels of TGF-beta1 among all the subjects studied (both patients and healthy controls), especially following PGL-1 stimulation (P < 0.001, and P < 0.05, respectively). In conjunction with our previous data regarding TGF-beta1 expression in dermal lesions, it appears that TGF-beta1 probably plays different roles in leprosy: (i) to mediate a suppressive action locally, associated with the presence of PGL-1, and (ii) to induce proinflammatory effects when secreted systemically by monocytes, thereby acting as a modulatory cytokine in the acute inflammatory reactions of ENL and associated with the Th2 immune response in multibacillary forms of leprosy.

Lucio's phenomenon: clinical and therapeutic aspects.

We report four cases of necrotizing reactions of the Lucio's phenomenon type, an entity rarely observed in Brazil despite the high prevalence of leprosy. Clinical, histopathological and therapeutic aspects are described and compared to those reported in the literature for cases classified as diffuse, non-nodular lepromatous leprosy with Lucio's phenomenon.

The use of bone scintigraphy to detect active Hansen's disease in mutilated patients.

Mutilation of extremities was very frequent in patients affected by leprosy in the past; although it is now much less common, it is still seen, mainly in patients with long-term disease. In general, mutilation of the nose and ears is caused by the bacillus and mutilation of the hands and feet a consequence of chronic trauma. Leprosy must be chronically treated and any decision to interrupt therapy is based on laboratory tests and biopsy. Scintigraphy is a non-invasive procedure which could be of great value in to determining disease activity. We studied eight patients (five males and three females, aged 64-73 years) who presented with mutilation of the nose (2), ear (1), feet (3) or foot and hand (2). Conventional three-phase bone scintigraphy (750 MBq) and X-ray examinations of the affected areas were performed in all patients. Bone scintigraphy was abnormal in four patients (the presence of bacilli was confirmed by biopsy in two of them), and normal in the other four. In all patients except for the one with ear mutilation, radiography only showed the absence of bone. We conclude that bone scintigraphy is very useful to determine disease activity in cases of mutilation caused by leprosy. It seems to be superior to conventional radiography and may enable bone biopsies to be avoided.

Detection of transforming growth factor-beta 1 in dermal lesions of different clinical forms of leprosy.

Immunohistochemical studies were performed to determine the presence and distribution of polypeptide transforming growth factor (TGF)-beta 1, a cytokine with macrophage-suppressing activity, in skin biopsies from 41 patients with different clinical forms of leprosy. We used an anti-TGF-beta 1 polyclonal antibody and the avidinbiotin-peroxidase (ABC complex) method. The results demonstrated that the lesions of the lepromatous and borderline lepromatous forms presented intense cytoplasm staining for TGF-beta 1 in the cells of the dermal infiltrate. A reaction of moderate intensity was observed in the cells of granulomas from borderline borderline cases, whereas no detectable immunoreaction was observed in granuloma cells from the tuberculoid and borderline tuberculoid forms. Considering that in the lepromatous leprosy form Mycobacterium leprae multiplies in the cytoplasm of macrophages and the lesions are diffuse and consist of poorly differentiated young macrophages, we believe that these alternations may be explained at least in part by the presence of TGF-beta 1 in the dermal infiltrate. Production of the cytokine may be induced by the presence of the bacillus itself and of its constituents, causing a mechanism of parasite evasion. Similarly, the absence of TGF-beta 1 in tuberculoid leprosy, which progresses with a specific immune response to M. leprae, may explain the intense differentiation of macrophage cells with the formation of well defined epithelioid granulomas capable of eliminating most of the bacilli.

Correlation between TNF production, increase of plasma C-reactive protein level and suppression of T lymphocyte response to concanavalin A during erythema nodosum leprosum.

The complex symptoms observed in lepromatous leprosy patients with reactive episodes of the erythema nodosum leprosum (ENL) type are associated with different serum components actively participating in the acute inflammatory reaction. Among them are the tumor necrosis factor (TNF) and the acute-phase protein C-reactive protein (CRP). TNF and CRP were found at significantly more elevated concentrations in the serum of patients with ENL, with a positive correlation of about 95% when compared with patients with nonreactive lepromatous leprosy (L) or tuberculoid leprosy (T) or with control individuals. Furthermore, in another series of experiments CRP had a specific and significant suppressive action on concanavalin A (ConA)-induced lymphoproliferation in cultures from patients and controls, the reduction being more marked (75%) in patients with ENL. By extrapolation from its known actions, production of TNF may have a number of potential consequences for the immunobiology of ENL. Thus, TNF may cause direct injury to compromised cells, facilitating mononuclear cell activation and production of cytokines such as interleukin-1 and interleukin-6, and upregulating hepatocyte expression of CRP. Both CRP and TNF in high serum concentrations have the ability to enhance the acute inflammatory process in ENL, favoring increased macrophage activation and phagoctyosis, and contributing to the elimination of damaged cells and bacilli, as well as in the reduction of T-suppressor cells, with a consequent improvement in the immunologic response of ENL patients.

Renal transplantation in leprosy patients.

We report four cases of leprosy in renal transplant recipients, two of whom had the disease before transplantation and no signs of relapse even in the presence of immunosuppressive drugs. The other two cases presented with lepromatous and borderline (dimorphous) leprosy 5 months and 5 years after transplantation, respectively. The disease of the last patient was controlled with sulfone even in the presence of immunosuppressive drugs, but the mechanism whereby the first patient rapidly developed lepromatous leprosy is unclear, even though he was a home contact of a patient with lepromatous leprosy (his wife). In view of the data presented here, we do not contraindicate renal transplantation in patients with leprosy who frequently suffer changes in renal function. We believe that renal function should be periodically evaluated in patients with borderline and lepromatous leprosy.

Anti-PGL1 levels in leprosy patients and their contacts.

1. We determined the anti-PGL1 levels of 402 individuals from the Ribeirão Preto region since the phenolic glycolipid (PGL1) is a specific Mycobacterium leprae antigen. This group consisted of 47 leprosy patients (26 with the lepromatous form, 16 with the tuberculoid form and 5 with the borderline form), 12 tuberculosis patients, 19 leprosy contacts, and 324 healthy blood donors from the Hemocenter of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. Anti-PGL1 levels were detected by ELISA. 2. Anti-PGL1 levels were normal in patients with tuberculoid and borderline leprosy, in tuberculosis patients and in almost all of the healthy blood donors. Patients with untreated lepromatous leprosy had elevated anti-PGL1 levels while most patients under treatment (9/16) had normal anti-PGL1 levels. Only 3% of blood donors (10/324) had elevated anti-PGL1 levels, but when these individuals were submitted to clinical and bacilloscopic examination no signs of disease were found. To complete the clinical investigation, these 10 subjects were submitted to the Mitsuda reaction which was negative in 3 of them. All of these 10 subjects are being monitored, since they may be at risk to develop leprosy. 3. On the basis of the present data, it seems that ELISA is a potentially important assay for the detection and chemotherapy of subclinical leprosy, permitting the control of epidemic centers of the disease.