N. van Geel

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.

Guidelines for the management of vitiligo: the European Dermatology Forum consensus.

The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental and nonsegmental vitiligo has been developed by the members of the Vitiligo European Task Force and other colleagues. It summarizes evidence‐based and expert‐based recommendations (S1 level).

Quality of life and stigmatization profile in a cohort of vitiligo patients and effect of the use of camouflage.

Background: Few studies have paid attention to the effects of treatment interventions on the psychosocial consequences of vitiligo. Objectives: To quantify and analyse the psychosocial benefit of the use of camouflage in vitiligo patients. Patients and Methods: 78 vitiligo patients completed the Dermatology Life Quality Index (DLQI) and an adapted stigmatization questionnaire, and 62 of them completed the DLQI after at least a 1-month use of camouflage. Results: The initial mean overall DLQI score (n = 78) is 6.9 (SD 5.6). The mean global stigmatization score is 38%. Disease extent and disease severity are strong predictors of the DLQI (p < 0.0001). Vitiligo on the face/head/neck substantially affects the DLQI, independently of degree of involvement. The mean DLQI score before and after use of camouflage (n = 62) is 7.3 (SD 5.6) and 5.9 (SD 5.2; p = 0.006). Mainly the high-scoring items ‘feelings of embarrassment and self consciousness’ and ‘choice of clothing’ improve. Predictors of improvement are higher DLQI scores (p = 0.0005) and higher total severity scores (p = 0.03). Conclusions: Camouflage can be recommended, particularly in patients with higher DLQI scores or self-assessed disease severity. Patients with minor involvement of the face benefit from camouflage.

Surgical Techniques for Vitiligo: A Review

Although the treatment of vitiligo has improved during the last decade, therapy is still not satisfying for many patients. This is probably due to the fact that the aetiopathogenesis is unknown. Several treatment modalities, such as PUVA, UVB and local corticosteroids are currently used in the treatment of active vitiligo. However, these treatments usually induce incomplete repigmentation. Surgical methods intended to repigment leucoderma are an interesting therapeutic option if patients have stable disease. Two types of surgical techniques are available: tissue grafts and cellular grafts, with in between autologous cultured epithelial grafts. Tissue grafts are full-thickness punch grafts, split-thickness grafts and suction blister grafts. With tissue grafts, only a limited surface area can be treated but with good results in the majority of cases. Cellular grafts include non-cultured keratinocytes/melanocytes and cultured melanocytes. The exact success rate of repigmentation with cellular grafts is still unknown, since only a small number of studies have been published. Starting from autologous cellular suspensions, epithelial grafts of various compositions can be cultured in vitro. They can be used for larger areas. The purpose of this review is to describe the applications of different surgical techniques used to treat recalcitrant vitiligo.

Clinical significance of Koebner phenomenon in vitiligo

Background  The clinical significance of Koebner phenomenon (KP) in vitiligo with respect to disease activity and course is still debatable. Recently, a new classification was introduced for the assessment of KP.

Long-term results of noncultured epidermal cellular grafting in vitiligo, halo naevi, piebaldism and naevus depigmentosus.

Background  Several surgical techniques are available for the treatment of stable leucoderma. The use of noncultured epidermal cellular grafting was introduced in 1992. Data on long‐term follow‐up regarding stability of the repigmented area, time to achieve the final repigmentation, colour matching, reaction to sun exposure and patient satisfaction with treatment have been reported only a few times previously.

Immune reactions in benign and malignant melanocytic lesions: lessons for immunotherapy

Spontaneous regression of benign and malignant melanocytic lesions can be a visible sign of immunosurveillance. In this review, we discuss different immune reactions against melanocytic lesions: halo nevus, Meyerson’s nevus, regression in melanoma and melanoma‐associated depigmentation. These entities present with particular clinical aspects, histology and evolution. In all entities, a melanocyte‐specific T‐cell reaction has been assumed but a different degree of melanocyte destruction is present. A focus on the immune responses in melanocytic lesions reveals several aspects of an adequate skin immunity and may help to identify the key points in the immune destruction of melanocytes. These insights can add to the knowledge of how to optimize immunotherapeutic strategies in melanoma.

Characterization of the in vivo immune network of IDO, tryptophan metabolism, PD-L1, and CTLA-4 in circulating immune cells in melanoma

In melanoma, both the induction of immunosuppression by tumor cells and the inflammatory antitumor response can induce an upregulation of counter-regulatory mechanisms such as indoleamine 2,3-dioxygenase (IDO), programmed death-ligand 1 (PD-L1) and CTLA-4+ regulatory T-cells (Tregs) in the tumor microenvironment. Even though these immunosuppressive mediators are targets for immunotherapy, research investigating their expression in the peripheral blood is lacking. We therefore, performed flow cytometry on PBMCs of stage I–IV melanoma patients. IDO expression was detected in plasmacytoid dendritic cells (pDC) and monocytic myeloid-derived suppressor cells (mMDSC), and increased in advanced disease stage (p = 0.027). Tryptophan breakdown confirmed the functional activity of IDO and was linked with increased PD-L1+ cytotoxic T-cells (p = 0.009), relative lymphopenia (p = 0.036), and a higher mDC/pDC ratio (p = 0.002). High levels of circulating PD-L1+ cytotoxic T-cells were associated with increased CTLA-4 expression by Tregs (p = 0.005) and MDSC levels (p = 0.033). This illustrates that counter-regulatory immune mechanisms in melanoma should be considered as one interrelated signaling network. Moreover, both increased PD-L1+ T-cells and CTLA-4 expression in Tregs conferred a negative prognosis, indicating their in vivo relevance. Remarkably, circulating CTLA-4, IDO, and pDC levels were altered according to prior invasion of the sentinel lymph node and IDO expression in the sentinel was associated with more IDO+ PBMCs. We conclude that the expression of IDO, PD-L1, and CTLA-4 in the peripheral blood of melanoma patients is strongly interconnected, associated with advanced disease and negative outcome, independent of disease stage. Combination treatments targeting several of these markers are therefore likely to exert a synergistic response.

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.

Peritumoral indoleamine 2,3‐dioxygenase expression in melanoma: an early marker of resistance to immune control?

Indoleamine 2,3‐dioxygenase (IDO) is an emerging immunomodulating factor in cancer. IDO expression in tumour‐negative sentinel lymph nodes (SLNs) of patients with melanoma has a negative prognostic value.