ELISA Test Based on the Phenolic Glycolipid-I (PGL-I) of Mycobacterium leprae: A Reality of a Laboratory from a Non-Endemic Country.

BACKGROUND: Leprosy is a neglected tropical disease caused by Mycobacterium leprae, leading to disabilities if untreated. The ELISA based on phenolic glycolipid I (PGL-I), or its synthetic version ND-O-BSA, is almost universally positive in multibacillary leprosy and thus extensively used in endemic countries. Household contacts with a positive antibody titer have ~6-fold higher probability to develop the disease than those with a negative titer. Thus, the aim of the study was to evaluate the performance of this ELISA in the setting of a non-endemic country. METHODS: We calculate the cut-off using optimized O.D. thresholds, generated by receiver operating characteristics (ROC) curve analysis, testing 39 well-characterized sera obtained from lepromatous leprosy patients with strongly positive ND-O-BSAELISA titer and 39 sera from healthy non-endemic patients never exposed to M. leprae or M. tuberculosis. Indeed, we tested a second set of sera from suspected or confirmed leprosy or household contacts (SLALT group, n=50), and patients with tuberculosis (control group, n=40). RESULTS: We detected 56.4% of SLALT and 22.5% of tuberculosis as positive, consistent with the literature. CONCLUSION: The ELISA based on ND-O-BSA may thus be considered a good option to be used in a non-endemic area as a screening tool in at risk population usually coming to our center.

Is ultraviolet radiation avoidance affecting bone health in melanoma patients?

BACKGROUND: Ultraviolet (UV) radiation has numerous beneficial effects on human health, including stimulating vitamin D and serotonin production and immuno-regulatory activities. Conversely, UV radiation is also classified as a group one carcinogen by the International Agency for Research on Cancer. PURPOSE: To investigated the effects of UV radiation avoidance in melanoma patients in terms of vitamin D levels but also of bone mineral density and trabecular bone microarchitecture. METHODS: We conducted an observational study investigating the effects of UV radiation avoidance in 31 melanoma patients in terms of vitamin D levels but also of bone mineral density and trabecular bone microarchitecture by using dual-energy X-ray absorptiometry scan. Data were compared with two control groups of healthy subjects, who were chronically exposed or not exposed to UV radiation during their lifetime. RESULTS: Melanoma patients had on average slightly lower levels of vitamin D, without reaching statistical significance (P = .135). No significant difference was found across the three groups on T-scores of femoral neck (P = .544), of total hip (P = .617) and of lumbar spine P = .155). No significant difference was found on and trabecular bone score across exposure groups (P = .895). CONCLUSION: UV radiation avoidance does not seem to significantly impact vitamin D levels nor bone health in melanoma patients. Thus, UV protective behavior is advisable for all melanoma patients.

The HLA-Cw6 Dilemma: Is It Really an Outcome Predictor in Psoriasis Patients under Biologic Therapy? A Monocentric Retrospective Analysis.

HLA-Cw6 is one of the most strongly associated psoriasis susceptibility alleles. Data regarding correlation between HLA-Cw6 status and biologic treatment outcomes are divergent. The aim of our study in our cohort of psoriatic patients was to explore if the HLA-Cw6 status influences the response rate to biologic therapies at 16 and 48 weeks. One hundred and one psoriatic patients eligible for biologic therapies were enrolled. HLA-C*06 alleles were detected from their blood samples. The effectiveness of antipsoriatic treatments was reported as 90% Psoriasis Area and Severity Index reduction (PASI90). All biologics showed efficacy at week 16, without significant differences between one another. HLA-Cw6 status did not seem to affect baseline characteristics, or treatment response at week 16. At week 48, IL-12/23 and IL-17 targeting drugs were more effective on Cw6-positive patients than on Cw6-negative patients. Conversely, TNF-targeting drugs seemed to be more effective on Cw6- negative patients than on Cw6-positive patients. The HLA-Cw6 test could well deserve to be integrated into the clinical laboratory work-up supporting the choice of the correct biologic.

Leprosy in Refugees and Migrants in Italy and a Literature Review of Cases Reported in Europe between 2009 and 2018.

Leprosy is a chronic neglected infectious disease that affects over 200,000 people each year and causes disabilities in more than four million people in Asia, Africa, and Latin America. The disease can appear with a wide spectrum of clinical forms, and therefore the clinical suspicion is often difficult. Refugees and migrants from endemic countries affected by leprosy can remain undiagnosed in Europe due to the unpreparedness of clinicians. We retrospectively describe the characteristics of 55 refugees/migrants with a diagnosis of leprosy established in Italy from 2009 to 2018. Continents of origin were Africa (42%), Asia (40%), and South and Central America (18%). The symptoms reported were skin lesions (91%), neuropathy (71%), edema (7%), eye involvement (6%), fever (6%), arthritis (4%), and lymphadenopathy (4%). Seven patients (13%) had irreversible complications. Overall, 35% were relapses and 66% multibacillary leprosy. Furthermore, we conducted a review of 17 case reports or case series and five nationwide reports, published in the same decade, describing 280 migrant patients with leprosy in Europe. In Europe, leprosy is a rare chronic infectious disease, but it has not completely disappeared. Diagnosis and treatment of leprosy in refugees and migrants from endemic countries are a challenge. European guidelines for this neglected disease in this high-risk population would be beneficial.

Specific autoantibodies in dermatomyositis: a helpful tool to classify different clinical subsets.

Autoantibodies are important in the diagnosis of dermatomyositis. They can be divided in two different groups: myositis-associated autoantibodies (MAA) prevailing in overlap syndromes, and myositis-specific autoantibodies (MSA), with diagnostic specificity exceeding 90%. Our purpose was to detect retrospectively the prevalence of the most common MSAs in a group of 19 adult DM patients (13 women, 6 men). A severe DM (SDM), with extensive cutaneous and muscular manifestations, dysphagia, and sometimes pneumopathy, was detected in ten cases. Three patients had a mild DM (MDM), with little muscle and skin impairment, and a short course. Four patients suffered from amyopathic DM (ADM), two from paraneoplastic DM (PDM). Each serum was tested for ANA, ENA, MAAs, MSAs. Myositis-specific autoantibodies were detected in 15 cases. The most frequent was anti-TIF1γ, associated with SDM or PDM in four out of seven cases. Anti-MDA5 antibodies were recorded in a SDM and in a ADM with lung fibrosis. Anti-Mi2 and anti-SRP antibodies were both detected in a MDM and in a SDM, whereas anti-SAE1 in a amyopathic form. Other antibodies (anti-NXP2, -Jo1, -PL7, -PL12, -OJ) were found in single patients with SDM. Our series confirmed that specific autoantibodies could be helpful to classify different clinical subsets, particularly in the case of paraneoplastic forms or association with pneumopathy. Moreover, they can help in predicting the disease evolution and influence therapeutic strategies. A greater number of cases should be useful to highlight the clinical and pathogenic role of these antibodies, and develop a homogeneous protocol for diagnosis and treatment.

Lichen scrofulosorum caused by Mycobacterium leprae: first report.

BACKGROUND: Tuberculides are skin lesions caused by the hematogeneous dissemination of Mycobacterium tuberculosis. Bacilli are rapidly destroyed in the skin and are thus neither visible histologically nor identifiable by culture. Diagnosis depends on previous knowledge of systemic and/or cutaneous tuberculosis. Lichen scrofulosorum (LS), the most uncommon variant of tuberculid, is usually associated with M. tuberculosis infection of lymph nodes or bone but was also reported in association with other mycobacterioses. OBJECTIVES: We report a case of LS in a patient with M. leprae infection. METHODS: In 2008, a 51-year-old woman from the Philippines was diagnosed with tuberculoid leprosy and treated. In 2010 the leprosy was considered to have been cured, and treatment was stopped. In 2011 the patient presented with lesions on the trunk and legs. Biopsy specimens were obtained for histopathologic examination and DNA detection for polymerase chain reaction (PCR). RESULTS: Histopathology in the biopsy from the trunk revealed the dermis to be diffusely occupied by granulomas with perineural and periadnexal disposition. Granulomas were composed of epithelioid cells and lymphocytes. Fite-Faraco staining revealed a few solid acid-fast bacilli within nerve fascicles. Reinfection or the re-reactivation of multibacillary borderline tuberculoid leprosy was diagnosed. Histopathology in the biopsy taken from the leg showed superficial, well-formed granulomas in the vicinity of hair follicles and sweat ducts. No acid-fast bacilli were seen. Analysis by PCR revealed M. leprae DNA in specimens from both the leg and trunk. The clinical features of the papular eruption and the histopathologic findings and concomitant mycobacterial infection with M. leprae led to a diagnosis of LS. Treatment was commenced with dapsone 100 mg/day, clofazimine 50 mg/day and 300 mg/month, and rifampicin 600 mg/day. The lichenoid eruption on the legs disappeared at one month of therapy, whereas the other skin lesions resolved in one year leaving residual hypochromic macules. CONCLUSIONS: Infection with M. leprae may cause LS. The use of PCR in skin biopsies from granulomatous dermatitis of unknown origin can help to identify the responsible agents.

T regulatory cells and plasmocytoid dentritic cells in hansen disease: a new insight into pathogenesis?

Leprosy is characterized by spectrum of histologically different granulomatous skin lesions that reflects the patient's immune response to Mycobacterium leprae. Presence, frequency, and distribution of both CD4+ CD25+ FoxP3+ T regulatory cells (T-regs) and CD123+ plasmacytoid dendritic cells in leprosy have never been investigated. We performed a retrospective immunohistochemical study on 20 cases of leprosy [tuberculoid tuberculoid (TT): 1 patient; borderline tuberculoid (BT): 3 patients; borderline lepromatous (BL): 5 patients; lepromatous lepromatous (LL): 5 patients; borderline borderline in reversal reaction (BB-RR): 1 patient; BT-RR: 2 patients; and erythema nodosum leprosum (ENL): 3 patients]. FoxP3-positive cells were present in 95% of the cases with an average density of 2.9% of the infiltrate. Their distribution was not related to granulomatous structures or special locations. There was no statistical difference of FoxP3 expression between TT, BT, BL, and LL, whereas a statistical significant increment (P = 0.042) was observed in patients affected by reversal leprosy reactions (BT-RR and BB-RR) compared with patients affected by ENL and patients with nonreactional disease forms (BL, LL, BT, TT). CD123 expression was not observed in any of the biopsy specimens evaluated; with the exception of 2 cases of ENL, in which a focal positivity for CD123 was observed. Our results show that plasmacytoid dendritic cells are not involved in the immune response against M. leprae while T-regs are present in leprosy skin lesions. These data raise the question if T-regs have a pathogenetic role in HD as previously demonstrated in Leishmania major and Mycobacterium tuberculosis.

Overexpression of vascular endothelial growth factor and its endothelial cell receptor KDR in type 1 leprosy reaction.

The sites of expression of vascular endothelial growth factor (VEGF) and of KDR, its endothelial cell receptor, were investigated in leprosy reaction Type 1, or reversal reaction (RR), by immunohistochemistry and in situ hybridization. In comparison with nonreactional leprosy, overexpression of both VEGF and KDR was seen in granuloma cells, especially epithelioid and foreign body-type giant cells, the epithelium and the vascular endothelium of RR specimens. In granuloma cells, hybridization for VEGF was stronger than immunostaining, a finding that may reflect the rapid turnover of VEGF in an immunologically dynamic situation such as RR. In the epidermis, double immunohistochemistry revealed VEGF overexpression in CDla-positive dendritic cells. The VEGF may not only be relevant for hyperpermeability and mononuclear cell differentiation (the key morphologic features in the acute, clinically evident phase of RR), but it could also be implicated in RR onset, when dendritic cells are activated in response to antigen stimulation.