Serum immunoglobulin (Ig) G responses to a variety of mycobacterial antigens were measured in children from the UK, in children with tuberculosis from Hyderabad, India and Dhaka, Bangladesh, classified according to whether the disease was disseminated or localized, and in non-tuberculous controls. Anti-lipoarabinomannan (LAM) IgG responses in UK children showed a marked trough between 6 months and 3 years coincident with the reported peak incidence of disseminated tuberculosis. Geometric mean IgG responses to sonicates of slow-growing mycobacteria (rich in LAM) in 36 children with disseminated tuberculosis were markedly lower than in 99 children with localized tuberculous lesions (for Mycobacterium scrofulaceum P < 0.01, for M. tuberculosis P < 0.01, and for M. vaccae P < 0.01). Responses to purified LAM were also lower in the disseminated tuberculosis group (P < 0.05) but there was no difference between the groups in their response to mycobacterial 65 kDa protein. Multiple regression analysis showed that the reduced response to sonicated mycobacterial antigens and to LAM in children with disseminated disease was independent of age, nutritional status, skin test reactivity, duration of previous symptoms, and city of origin. There was no evidence for sequestration of antibody to immune complexes. These findings are compatible with the hypothesis that children with low levels of antibody to sonicated mycobacterial antigen and to LAM, or those who cannot mount an antibody response, are predisposed to dissemination. A role for antibody in preventing disseminated forms of tuberculosis in childhood has implications for the development of improved vaccines and for the optimum timing of vaccination with bacille Calmette-Guérin.

Various types of lasers have been demonstrated to be effective in the treatment of vitiligo. The mode of action of these lasers is just as varied as the purpose of intervention. Many clinicians are not aware of the unique opportunity these lasers offer to improve the outcomes of vitiligo treatment. To date, no clear overview exists of the use of lasers in vitiligo treatment. Thus, the aim of this review is to discuss the various types of lasers and provide an overview of the evidence for their efficacy. We found good evidence from a systematic review that the excimer laser is effective, induces repigmentation rates comparable to NB‐UVB and has improved outcomes when combined with calcineurin inhibitors. Ablative lasers are commonly used for tissue graft or melanocyte–keratinocyte cell graft transplantation. They provide safe, fast and uniform denudation of the epidermis with propitious repigmentation outcomes. We found conflicting evidence from two systematic reviews regarding the efficacy of fractional ablative lasers for improving outcomes of NB‐UVB therapy, a systematic review including only fractional ablative lasers provided evidence for efficacy. Q‐switched nanosecond lasers have shown to be safe and effective for inducing depigmentation, although recurrence is common, and most studies were small and retrospective. Despite proven efficacy and safety, laser treatments are relatively expensive and suited for limited body surface areas and selected cases. Each type of laser has benefits and risks associated and should, therefore, be individually chosen based on location, extent, activity and type of vitiligo.

Background The treatment of non‐segmental vitiligo (NSV) remains a challenge. Current treatments often achieve suboptimal clinical results. To improve these treatment results, several new therapies are being developed and investigated. There is, however, little evidence on the actual need for novel therapies. Objective To assess patients’ perspective on current and novel therapies for vitiligo. Methods A prospective questionnaire study was conducted in a large cohort of vitiligo patients that consecutively visited the outpatient clinic of the Amsterdam University Medical Centre between April 2017 and January 2019. Patients were requested to fill in a digital questionnaire on patient characteristics, disease burden, quality of life, efficacy and satisfaction of current treatments and aspects regarding new treatments. Results A total of 325 vitiligo patients completed the questionnaire (60% response rate). Of the respondents, 94% believed that new and improved treatments are needed and 86% would be willing to participate in clinical trials investigating a new therapy. Sixty‐nine per cent would agree on taking weekly injections if it led to effective treatment results. Of the patients that had received therapy before, 49% reported that the current treatments were not effective and 50% was not satisfied with the current treatments. Sixty‐seven per cent of the patients experienced facial lesions as an extreme burden, whereas this was, 25%, 12% and 10% for lesions on the hands, trunk and feet, respectively. The emotional burden score was significantly higher in dark skin types compared with light skin types (respectively, 8 vs 5, U P < 0.05). Conclusion There is a substantial need for new vitiligo therapies. A considerable number of patients in our study are dissatisfied with current treatments and are emotionally burdened by the disease. Moreover, the vast majority demands novel treatments and is willing to participate in clinical trials.

Mounting evidence shows that the PD-1/PD-L1 axis is involved in tumor immune evasion. This is demonstrated by anti-PD-1 antibodies that can reverse tumor-associated PD-L1 to functionally suppress anti-tumor T-cell responses. Since type I and II interferons are key regulators of PD-L1 expression in melanoma cells and IFNγ-producing CD8 + T cells and IFNα-producing dendritic cells are abundant in vitiligo skin, we aimed to study the role of PD-1/PD-L1 signalling in melanocyte destruction in vitiligo. Moreover, impaired PD-1/PD-L1 function is observed in a variety of autoimmune diseases. It is, therefore, hypothesized that manipulating PD-1/PD-L1 signalling might have therapeutic potential in vitiligo. The PD-1 + T cells were abundantly present in situ in perilesional vitiligo skin, but expression of PD-L1 was limited and confined exclusively to dermal T cells. More specifically, neither melanocytes nor other epidermal skin cells expressed PD-L1. Exposure to IFNγ, but also type I interferons, increased PD-L1 expression in primary melanocytes and fibroblasts, derived from healthy donors. Primary human keratinocytes only showed increased PD-L1 expression upon stimulation with IFNγ. More interestingly, melanocytes derived from non-lesional vitiligo skin showed no PD-L1 upregulation upon IFNγ exposure, while other skin cells displayed significant PD-L1 expression after exposure. In a vitiligo skin explant model, incubation of non-lesional vitiligo skin with activated (IFNγ-producing) T cells from vitiligo lesions was previously described to induce melanocyte apoptosis. Although PD-L1 expression was induced in epidermal cells in these explants, this induction was completely absent in melanocytes. The lack of PD-L1 upregulation by melanocytes in the presence of IFNγ-producing T cells shows that melanocytes lack protection against T-cell attack during vitiligo pathogenesis. Manipulating PD-1/PD-L1 signalling may, therefore, be a therapeutic option for vitiligo patients.

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Stabilized vitiligo resistant to conventional therapy (e.g. segmental vitiligo) and piebaldism lesions can be treated with autologous cellular grafting techniques, such as non-cultured cell suspension transplantation (NCST) and cultured melanocyte transplantation (CMT). These methods are preferred when treating larger surface areas due to the small amount of donor skin needed. However, the donor to recipient expansion ratios and outcomes reported in studies with cellular grafting vary widely, and to date, no overview or guideline exists on the optimal ratio. The aim of our study was to obtain an overview of the various expansion ratios used in cellular grafting and to identify whether expansion ratios affect repigmentation and colour match. We performed a systematic literature search in MEDLINE and EMBASE to review clinical studies that reported the expansion ratio and repigmentation after cellular grafting. We included 31 eligible clinical studies with 1591 patients in total. Our study provides an overview of various expansion ratios used in cellular grafting for vitiligo and piebaldism, which varied from 1:1 up to 1:100. We found expansion ratios between 1:1 and 1:10 for studies investigating NCST and from 1:20 to 1:100 in studies evaluating CMT. Pooled analyses of studies with the same expansion ratio and repigmentation thresholds showed that when using the lowest (1:3) expansion ratio, the proportion of lesions achieving >50% or >75% repigmentation after NCST was significantly better than when using the highest (1:10) expansion ratio (v 2 P = 0.000 and v 2 P = 0.006, respectively). Less than half of our included studies stated the colour match between different expansion ratios, and results were variable. In conclusion, the results of our study indicate that higher expansion ratios lead to lower repigmentation percentages after NCST treatment. This should be taken into consideration while determining which expansion ratio to use for treating a patient.

Introduction: Treatment of non-segmental vitiligo (NSV) remains a challenge. Efficacy of NB-UVB treatment may increase with more frequent use or in combination with topical agents. Currently, data on the most effective treatment regimen lacking. Our objective is to retrospectively compare NB-UVB treatment regimens for non-segmental vitiligo. Methods: Patients with NSV treated with NB-UVB therapy were included in two time periods. Group I received NB-UVB therapy twice a week (conventional treatment) and group II received NB-UVB thrice a week, combined with topical agents (intensified treatment). Patients completed a questionnaire regarding the degree and onset of repigmentation, satisfaction and side effects. Results: Repigmentation scores did not differ significantly between the two groups. Onset of repigmentation in the first three months seemed higher in group II, but this difference was not significant (23.4% vs 51.1%; p ¼ .11). In both groups the majority of the patients were moderately to very satisfied (group I: 70.2% group II: 73.3%). The occurrence of adverse effects was comparable.Conclusions: This study indicates that conventional and intensified treatment for NSV seem to be comparable. The intensified treatment might be more effective to speed up the onset of repigmentation, but larger prospective studies are needed to objectify these findings. ARTICLE HISTORY

Dear Editor, Narrow-band ultraviolet B (NB-UVB) is a widely used treatment for non-segmental vitiligo (NSV). It is frequently combined with topical therapy (such as calcineurin inhibitors and/or corticosteroids), due to the superiority of combination therapy above monotherapy. [1][2][3][4] In cases of rapidly spreading vitiligo, systemic steroids in an oral minipulse (OMP) scheme are often added to this therapy to arrest