S. De Schepper

Effect of vitiligo on self-reported health-related quality of life

Background  Vitiligo is a pigmentary disorder affecting at least 1% of the total population. Although the disease does not produce direct physical impairment, it may considerably influence the psychological well‐being of the patients. It has been suggested that patients suffer from low self‐esteem, poor body image and a poor quality of life. The majority of the studies on the psychosocial impact of vitiligo were conducted in the U.S.A. and England.

New insights in segmental vitiligo: case report and review of theories

Segmental vitiligo and generalized vitiligo are in general considered to be separate entities. The aetiopathogenesis of segmental vitiligo remains unclear, although several hypotheses have been put forward including mainly neuronal mechanisms. The typical association with other autoimmune diseases, as seen in generalized vitiligo, seems to be significantly less in segmental vitiligo, although recent insights point towards a possible immune‐mediated overlap between the two subtypes. In this article, we describe a case with simultaneous presence of segmental vitiligo, alopecia areata, psoriasis and a halo naevus. To our knowledge, this is the first case with this exceptional combination. This concomitant presence could support the involvement of a shared autoimmune‐mediated process, and may provide new insights into the pathogenesis of segmental vitiligo and direct future research. In the light of this remarkable case, different possible aetiopathogenetic mechanisms leading to the clinical presentation of segmental vitiligo are discussed and a new three‐step theory is proposed.

The many faces of interleukin‐17 in inflammatory skin diseases

Interleukin (IL)‐17 is an emerging target for inflammatory skin disorders. Given the remarkable success of its therapeutic inhibition in psoriasis, the pathogenic role of this cytokine is being explored in other immune‐mediated diseases. Interestingly, IL‐17 is linked to particular skin conditions where its activation coincides with disease flares. The leading hypothesis for its contribution to proinflammatory signalling cascades is driving inflammasome activation. However, IL‐17 stimulation also releases a range of noninflammasome‐related cytokines from human skin. Furthermore, a role in cytotoxic responses and an important interplay with the microbiome is hypothesized. While treatment failure would be surprising in neutrophilic dermatoses, the picture might be more complex in lymphocyte‐mediated conditions. Nonetheless, increasing insights into the pathogenesis suggest that beneficial responses are also probable in the latter conditions. Study of this pathway in the skin reveals some intriguing aspects of the IL‐17‐related immunological network.

The distribution pattern of segmental vitiligo: clues for somatic mosaicism

Background  Segmental vitiligo is characterized by a unilateral and localized distribution. So far, the underlying mechanism is still an enigma.

Serum plakophilin-3 autoreactivity in paraneoplastic pemphigus.

Summary Background  Paraneoplastic pemphigus (PNP) is a malignancy‐associated autoimmune disease in which circulating autoantibodies recognize various polypeptides that constitute the desmosomes and hemidesmosomes of epithelial structures.

Halo naevi with associated vitiligo-like depigmentations: pathogenetic hypothesis.

Background  In analogy with melanoma‐associated leucoderma, halo naevi may trigger in some patients the development of additional depigmentations which are in distribution, extent and prognosis not in accordance with classic vitiligo.

Adventitious shoot regeneration and appearance of sports in several azalea cultivars

Shoots can be regenerated from leaf explants of most azalea (Rhododendron simsii) cultivars using a two-step protocol with a callus induction and a regeneration phase. This procedure is unsuccessful for a few cultivars, because of excessive callus production. In most such cases, shoot regeneration could be obtained in one step, starting from petioles as explants. Flower colour variations (the induction of sports) were frequently observed after regeneration. This phenomenon offers prospects for the enlargement of the commercial assortment but can also be used for the study of gene regulation processes in flower colour variegation.

Genetic and epigenetic aspects of somaclonal variation: flower colour bud sports in azalea, a case study

Bud sporting is the consequence of sudden variations in gene expression of somatic cells, leading to the occurrence of phenotypically altered shoots on plants. This phenomenon can be observed in most vegetatively propagated plant species and finds its origin in genetic as well as epigenetic events. In azalea the frequent occurrence of flower colour sports is appreciated as a valuable additional source of variation; more than half of the commercial assortment consists of flower colour bud sports. However, when clonal uniformity is desired for registration (Distinctness Uniformity Stability, DUS) and mass propagation, this somaclonal variation is perceived as a hindrance. Insight into the molecular mechanism(s) underlying the induction of bud sporting might improve breeding strategies, towards the appropriate choice of cultivars in hybridisation experiments. The complex beauty of sport phenotypes clearly indicates interactions within and between genetic and epigenetic mechanisms. Therefore, using azalea somaclonal variation as a model, a review of the literature on various genetic and epigenetic phenomena that regulate or influence gene expression, as well as on the links that exist between them is presented.

Cessation of spread as a treatment objective in vitiligo : perception from the patients' point of view

DEAR EDITOR, Vitiligo is an acquired condition resulting from the progressive loss of melanocytes. It is known that the unpredictable nature of vitiligo and its tendency to progress can be psychologically overwhelming. In our previous clinical observational trials and during clinical practice we noticed frequently that disease stability is relevant for many patients. Therefore, we wanted to evaluate the perception of disease impact, the general treatment motivation and the treatment motivation if disease stabilization would be the outcome. The second aim was to evaluate whether clinical variables might influence the impact of the disease and motivation for treatment. This was a monocentre observational trial conducted at the Department of Dermatology of Ghent University Hospital. Between August 2009 and March 2015, we recruited in a consecutive manner 864 patients with nonsegmental vitiligo. The study was approved by the local ethics committee. Data were taken by history using a standardized questionnaire. Special attention was given to the questions with respect to the general treatment motivation (motivation A) and motivation for treatment if this could induce cessation of spread/ disease stability (motivation B). Patients were asked to score for both questions their motivation on a scale from 0 to 10. Statistical analyses were performed using SPSS 22.0 (IBM, Armonk, NY, U.S.A.). All values are expressed as median (interquartile range, IQR). For all tests, P-values of less than 0 05 were considered to indicate statistical significance. Adjustment for possible confounding factors was performed using a multivariate regression model. In total, 864 patients with nonsegmental vitiligo were enrolled in this study, including 400 men and 464 women (Table 1). The general motivation score for treatment (motivation A) was collected for 814 patients. Motivation to treat if stabilization could be achieved (motivation B) was available for 365 patients. The impact score was measured in 849 patients with vitiligo. The majority of included patients under treatment (68 4%) were using topical treatments (82 2%), followed by ultraviolet B (UVB) treatment (17 8%). A high number (87 6%) of patients with vitiligo reported a strong general motivation (motivation A) for treatment (score ≥ 7) (Fig. 1a). Only 3 5% mentioned a poor motivation (score < 4). Patients receiving UVB treatment and having dark skin phototypes displayed a significantly higher motivation for treatment (P = 0 019 and P = 0 008, respectively). The general motivation to treat was the highest during the first 2 years of the disease (P = 0 001). There was a drop in general treatment motivation in the age group of 11– 20 years (P = 0 036). The motivation to treat decreased slightly if disease stabilization was proposed as the treatment goal (motivation B). Still, 84 1% of patients mentioned a motivation score ≥ 7 if stable disease could be attained. Only 5 7% of patients seemed not to be willing to treat in this setting (motivation score < 4). The motivation for treatment to achieve disease stabilization was also the highest in the first 2 years of the disease (P = 0 013) and remained stable afterwards. There was a negative correlation between a higher body surface area (BSA) and motivation to treat if stabilization would be the outcome (P < 0 001) (Fig. 1b). In patients with a BSA of more than 10%, cessation of disease progression was a less important motivation for treatment (mean motivation B score BSA < 10% vs. BSA > 10%: 8 49 vs. 7 22; P = 0 001). There was a wide difference in reported impact scores of the patients (Fig. 1c–h). An impact score from 0 to 3 was found in 30 6% of patients, a score of 4–7 in 40 0% of patients and a score from 8 to 10 in 29 4% of patients. As

Biomarkers of disease activity in vitiligo : a systematic review

The pathophysiology of vitiligo is complex although recent research has discovered several markers which are linked to vitiligo and associated with disease activity. Besides providing insights into the driving mechanisms of vitiligo, these findings could reveal potential biomarkers. Activity markers can be used to monitor disease activity in clinical trials and may also be useful in daily practice. The aim of this systematic review was to document which factors have been associated with vitiligo activity in skin and blood. A second goal was to determine how well these factors are validated in terms of sensitivity and specificity as biomarkers to determine vitiligo activity. Both in skin (n=43) as in blood (n=66) an adequate number of studies fulfilled the predefined inclusion criteria. These studies used diverse methods and investigated a broad range of plausible biomarkers. Unfortunately, sensitivity and specificity analyses were scarce. In skin, simple histopathology with or without supplemental CD4 and CD8 stainings can still be considered as the gold standard, although more recently chemokine (C-X-C motif) ligand (CXCL) 9 and NLRP1 have demonstrated a good and possibly even better association with progressive disease. Regarding circulating biomarkers, cytokines (IL-1β, IL-17, IFN-γ, TGF-β), autoantibodies, oxidative stress markers, immune cells (Tregs), soluble CDs (sCD25, sCD27) and chemokines (CXCL9, CXCL10) are still competing. However, the two latter may be preferable as both chemokines and soluble CDs are easy to measure and the available studies display promising results. A large multicenter study could make more definitive statements regarding their sensitivity and specificity.