The use of lasers in vitiligo, an overview.

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.

Assessing the dynamic changes in vitiligo: reliability and validity of the Vitiligo Disease Activity Score (VDAS) and Vitiligo Disease Improvement Score (VDIS).

BACKGROUND: The assessment of the individual evolution of vitiligo is important for therapeutic decision making in daily practice. A fast, simple and validated physician-reported score to assess clinical changes in depigmentation over time in separate parts (activity and improvement) is currently missing. OBJECTIVE: The main objective of the study was to develop and validate the Vitiligo Disease Activity Score (VDAS) and Vitiligo Disease Improvement Score (VDIS). METHODS: The Vitiligo Disease Activity Score (VDAS) and Vitiligo Disease Improvement Score (VDIS) were evaluated based on a photo set of 66 patients with two different time points. In the first (short) version, only the number of changing body regions was counted based on 15 predefined areas (VDAS15 and VDIS15 ), while in the second (extensive) version the degree of worsening or improvement from +4 to -4 for each body area was added for a more detailed assessment (VDAS60 and VDIS60 ). Content and construct validity were tested. In addition inter-, intrarater reliability and feasibility were evaluated by 7 (test) and 5 (retest) physicians. RESULTS: Evidence for content and construct validity was provided. Overall, VDAS15 , VDIS15 , VDAS60 and VDIS60 demonstrated good to excellent inter-rater reliability [intraclass correlation (ICC): VDAS: range = 0.797-0.900; VDIS: range = 0.726-0.798]. The intrarater reliability ICCs were 0.865 and 0.781 for the VDAS15 and VDIS15 , respectively. Similar results were obtained for the VDAS60 and VDIS60 (ICC = 0.913 and 0.800, respectively). Completion time was short (median: 122 s/patient (first round); 95 s/patient (second round)]. LIMITATIONS: Single tertiary centre mainly of skin phototype 2 to 3. CONCLUSION: The VDAS and VDIS appear to be valid, reliable and feasible instruments to score the evolution of vitiligo lesions. This accommodates the current urgent need for a simple, standardized and practical assessment of vitiligo activity and improvement over time.

Donor to recipient ratios in the surgical treatment of vitiligo and piebaldism: a systematic review.

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 (χ2 P = 0.000 and χ2 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.

Validation of a Patient Global Assessment for extent, severity and impact to define the severity strata for the Self Assessment Vitiligo Extent Score (SA-VES).

BACKGROUND: The Self Assessment Vitiligo Extent Score (SA-VES) is a validated, patient-reported outcome measure to assess the body surface area affected with vitiligo. Information on how to translate the obtained score into extent, severity and impact strata (mild-moderate-severe) is still lacking. Stratification is helpful to define inclusion criteria for trials, enables comparison and pooling of trial results and can be used for epidemiological research. OBJECTIVES: The aim was to develop extent, severity and impact strata for the SA-VES based on validated anchor-based questions. METHODS: In total, 315 patients with vitiligo (non-segmental; age ≥ 16) recruited at the Ghent University Hospital (Belgium) completed a questionnaire that was conducted in cooperation with the Dutch Society for vitiligo patients to ensure content validity. First three anchor questions included in the questionnaire [Patient Global Assessment (PtGA) for vitiligo extent, severity and impact] were assessed for content validity, construct validity and intrarater reliability. Subsequently, the PtGAs were used to stratify the SA-VES based on ROC analysis. RESULTS: For all PtGAs (PtGA extent, PtGA severity, PtGA impact), at least 75% of hypotheses evaluated for construct validity were confirmed. Intrarater reliability of all PtGAs was good to excellent (ICCs PtGA extent: 0.623; PtGA severity: 0.828; PtGA impact: 0.851). The optimal cut-off values of the SA-VES between the three global categories (mild/limited - moderate - severe/extensive) were 1.05% and 6.45% based on PtGA extent, 2.07% and 4.8% based on PtGA severity and 2% and 3.35% based on PtGA impact. CONCLUSION: This study provides the first guide for the interpretation of the numerical output obtained by the SA-VES (vitiligo extent) and enables the translation into a global vitiligo grading for extent, severity and impact. As patients' interpretation of vitiligo extent, severity and impact may vary amongst patients worldwide, future international studies will be required.

Reliability and validity of the Vitiligo Signs of Activity Score (VSAS).

BACKGROUND: The associations between disease activity and several clinical signs in vitiligo have been described, but a widely accepted and validated scoring system is lacking. OBJECTIVES: To validate the Vitiligo Signs of Activity Score (VSAS) for physicians. METHODS: Three visible clinical signs were scored on 15 body locations: confetti-like depigmentation (c), Koebner phenomenon (k) and hypochromic areas/borders (h). The inter- and intrarater reliability of the global VSAS and VSAS subscores (c-VSAS, k-VSAS and h-VSAS) were tested by four and three raters (physicians), respectively. Construct validity and feasibility were evaluated. RESULTS: The VSAS demonstrated good inter-rater reliability, with an intraclass correlation coefficient (ICC) of 0·87 in the first round and 0·90 in the second round. The intrarater reliability ICCs were all ≥ 0·86. The inter-rater reliabilities of the subscores were excellent for c-VSAS and fair for k-VSAS and h-VSAS (ICC 0·83, 0·51 and 0·53, respectively, in the first round). Evidence for construct validity was provided. The completion time by the raters (median 2·18 min per patient) improved during the second round (median 1·33 min per patient). A limitation of the study is the low number of patients, mainly of skin phototypes II-III, from a single tertiary centre. CONCLUSIONS: The VSAS appears to be a valid and reliable instrument to score visible clinical signs linked to disease activity in a standardized way. What is already known about this topic? Evidence exists for a possible link between several visible clinical signs in vitiligo and disease activity. A widely accepted and validated scoring system to quantify these clinical signs is lacking. What does this study add? The Vitiligo Signs of Activity Score (VSAS) underwent preliminary validation and may assist quantification of visible clinical signs linked to disease activity in a standardized way in clinical practice and trials. What are the clinical implications of this work? VSAS may be used for future trials that aim to establish the clinical significance of the specific visible clinical signs in vitiligo in a more controlled setting. Linked Comment: Eleftheriadou. Br J Dermatol 2020; 183:801-802.

Reference method for digital surface measurement of target lesions in vitiligo: a comparative analysis.

BACKGROUND: Objective measurement of target lesions in vitiligo is important for clinical practice and trials, yet no preferred tool has been defined. Reported digital tools have shortcomings related to feasibility aspects and often lack information on validity, reliability and responsiveness. Moreover, studies are not yet based on ultraviolet (UV) photography. OBJECTIVES: To assess the reliability, validity and feasibility of two functions in ImageJ for measurement of target lesions, based on three different types of images including UV pictures. METHODS: Planimetric measurements were performed on photographs with and without UV, and lesion contours on transparent sheets of 52 vitiligo lesions from 10 patients with vitiligo. The ImageJ functions 'wand' and 'threshold' were used by three and four assessors, respectively. Inter- and intrarater reliability, hypothesis testing for construct validity, and feasibility were evaluated. RESULTS: The inter- and intrarater reliability for the 'wand' and 'threshold' functions were excellent [intraclass correlation coefficient (ICC) > 0·9] for measurement on pictures (with or without UV). The highest agreement (ICC > 0·95) and lowest variance were obtained for measurements on transparent sheets. All four hypotheses for construct validity were confirmed for all measurements. Overall, all measurement methods scored satisfactorily for user-friendliness. However, measurements on transparent sheets were preferred and the completion time was significantly faster. CONCLUSIONS: This study confirmed the reliability, validity and feasibility of two functions in ImageJ to measure target lesions in vitiligo. Based on the feasibility and included three-dimensional aspects, transparent sheets measured with the ImageJ 'wand' function can be proposed for future trials as a reference method to investigate the criterion validity of other digital instruments.

UV light set-ups for vitiligo photography, a comparative study on image quality and ease of use.

BACKGROUND: Ultraviolet (UV) light is an essential tool to assess the extent, spreading and staging of vitiligo. Different UV light set-ups are used for vitiligo photography, including the following: (i) hand-held Wood's lamps; (ii) soft boxes with UV lamps; (iii) UV flash attached to the camera; and (iv) high output UV flash. OBJECTIVE: Our objective was to compare UV light set-ups for vitiligo photography regarding image quality and ease of use. METHODS: Patients with vitiligo lesions with unclear borders were included. Two images were made with all four UV set-ups per patient, for a large and a small area. Image quality was scored separately by three blinded vitiligo experts on five criteria: overall quality, clearness of borders, contrast and sharpness and for larger areas the shadows. The two professional medical photographers were asked to score the ease of use for each set-up. RESULTS: A total of 88 photos were assessed from 11 patients. For larger areas, the frequency of a 'good' or 'very good' overall quality rating was 12.1% (Wood's), 6.1% (soft boxes), 15.2% (camera flash) and 78.8% (high output flash). For smaller areas, the score 'good' or 'very good' was given to 54.5%, 3%, 66.6% and 84.8% in the same order. For the shadow criteria, each set-up scored below 40% on a 'good' or 'very good' score. The high output flash was scored as most easy to use by the photographers. CONCLUSION: When comparing four different UV light set-ups for vitiligo photography, we concluded that the UV set-ups strongly influenced the quality scores of the obtained images. The high output flash scored best for both small and large areas and for ease of use. For small areas, Wood's lamp and camera flash were acceptable. All set-ups scored badly for shadows, and more research is needed to find the optimal exposure to avoid shadows.

Clinical visible signs of disease activity in vitiligo: a systematic review and meta-analysis.

Vitiligo is an unpredictable depigmenting disorder for which a static method to assess disease activity is lacking. Presence of certain skin manifestations may be indicative of disease activity. Here, we evaluated the current evidence for an association between clinical signs and reported disease activity in vitiligo. A systematic review and meta-analysis was performed based on a search in PubMed, Embase and Cochrane Library. Literature reporting skin manifestations and disease activity was analysed based on descriptive analyses and, if applicable, odd ratios. Forty-six observational studies were selected and analysed, including 28 case reports. Reported clinical signs in relation to active vitiligo were as follows: Koebner's phenomenon, confetti-like depigmentations, tri- and hypochromic lesions (including poorly defined borders), inflammatory borders/areas, itch and leukotrichia. Based on this search, strong evidence was found for Koebner's phenomenon. Poorly defined borders and confetti lesions are potential markers, although more data are needed to confirm this. Evidence for other skin manifestations was inconclusive, whereas case reports on inflammatory borders were indicative of active disease. Limitations included the lack of randomized controlled trials, large-scale prospective studies and heterogeneity due to inconsistent definitions. This systematic review urges the vitiligo community to come forward with consensus-based definitions as well as a reliable scoring system to assess these clinical signs and to design optimal trials to investigate their true predictive value.

Comparison of methods to estimate the affected body surface area and the dosage of topical treatments in psoriasis and atopic dermatitis: the advantage of a picture-based tool.

BACKGROUND: The accurate determination of the dosage of topical treatments is important given its repercussions on patient adherence and therapeutic efficacy. Up till now, the fingertip unit calculated by the rule of hands is considered the gold standard, although its use is associated with several drawbacks. OBJECTIVE: To compare different methods to estimate the affected body surface area (BSA) and dosage of topical treatments in atopic dermatitis and psoriasis and investigate its reliability, user-friendliness and timing. METHODS: In this study, we compared the reliability of three different methods: (i) the fingertip unit calculated by the 1% hand rule; (ii) a picture-based tool [termed Cutaneous Inflammatory Disease Extent Score (CIDES)]; and (iii) a digital drawing tool. Eleven observers scored 40 patients with psoriasis and eczema to assess the inter-rater and intrarater reliability. Timing was automatically recorded, and user-friendliness was investigated by a questionnaire. RESULTS: An excellent intraclass correlation (ICC) was found for both inter-rater agreement and intrarater agreement for the picture-based tool (ICC = 0.92 and ICC = 0.96, respectively). The ICCs for drawing the area of involvement on a silhouette were 0.89 and 0.93, respectively. Finally, the rule of hands was associated with an increased inter-rater variability although an excellent intrarater agreement was found (ICC = 0.79 and 0.95, respectively). Automated calculation of the amount of topical treatment improved reliability, and CIDES was associated with the least variation. CIDES was considered the preferred method by all observers and was fast to perform (median: 30 s). CONCLUSION: A picture-based method offered the most advantages (in terms of reliability, speed and user-friendliness) to estimate the affected BSA and calculate the dosage of topical treatments.

Critical appraisal of the oxidative stress pathway in vitiligo: a systematic review and meta-analysis.

BACKGROUND: The pathogenesis of vitiligo remains a topic of extensive debate. This is partly due to the moderate efficacy of current treatments. The role of the oxidative stress pathway in vitiligo is a popular although controversial research topic. OBJECTIVE: To clarify the role of the oxidative stress pathway in vitiligo compared to other inflammatory skin disorders and to assess the therapeutic role of antioxidants. METHODS: We conducted a systematic search of the existing literature on the aberrancies of the oxidative stress pathway in vitiligo. Subsequently, the efficacy of both topical and oral antioxidants in clinical trials was investigated. RESULTS: A deregulated oxidative pathway is clearly evident with elevated superoxide dismutase, decreased catalase and increased lipid peroxidation. However, similar results have been obtained in other inflammatory skin diseases such as psoriasis, atopic dermatitis, lichen planus and urticaria. This questions the unique role of oxidative stress in the development of vitiligo. Some isolated successes have been reported with oral ginkgo biloba, polypodium leucotomos and vitamin C and E preparations, while other clinical trials have failed to show reproducible results. The use of topical antioxidants delivers in general no beneficial results. CONCLUSION: The oxidative pathway is affected in vitiligo, but its unique initiating or contributory role in the pathogenesis is less evident. Interesting data support the added value of oral antioxidants in vitiligo although confirmatory studies are missing.

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.

Relevance of congenital melanocytic naevi in vitiligo.

BACKGROUND: Some case reports concerning the concomitant presence of congenital melanocytic naevi (CMN), halo naevi and vitiligo have been published. However, their possible link has never been investigated in a large patient population. OBJECTIVES: To evaluate the relevance of CMN in patients with vitiligo with respect to the presence of halo naevi and some general clinical variables such as age of onset, Koebner phenomenon and body surface area (BSA) involvement. METHODS: In total, 1004 patients with vitiligo (nonsegmental) and 291 control patients were included in this observational study. CMN were scored in size, location and halo formation, and classified into clinical convincing or possible lesions. RESULTS: Convincing CMN were present in 3·3% of the patient population and in 1·0% of the control population. The presence of halo naevi was significantly higher (P = 0·01) and age of onset of vitiligo was significantly lower (P < 0·01) in the presence of CMN. Halo formation around the CMN, as observed in 30·3% of cases, was associated with a higher diameter of the CMN. Patients with congenital naevi had a particular predisposition to having lesions on joints/acral areas and reported more often signs of Koebner phenomenon (P = 0·01). No clear difference in disease activity, BSA involvement, associated autoimmune diseases or treatment response was observed in patients with vitiligo with or without congenital naevi. CONCLUSIONS: This study provides clinical evidence that CMN may influence the age of onset of vitiligo and trigger the development of halo naevi in patients with vitiligo.

Hypochromic vitiligo: delineation of a new entity.

BACKGROUND: Hypochromic vitiligo is a rare entity that has been reported only twice under the term 'vitiligo minor', with an absence of clear delineation. OBJECTIVES: To delineate hypochromic vitiligo through a case series of patients with typical bilateral hypopigmented lesions affecting the face and trunk. METHODS: This is a retrospective multicentric evaluation study conducted in eight departments of dermatology in France, Belgium, Senegal and Saudi Arabia. RESULTS: Twenty-four cases of hypochromic vitiligo were identified. Fourteen were men and 10 women. The mean age at diagnosis was 35·4 years (range 8-66). Strikingly, all patients were dark skinned, with skin types V and VI. The pattern of distribution was highly similar in most of the patients (18 of 24), with involvement of the face and neck area predominating on seborrhoeic areas associated with multiple isolated hypopigmented macules involving predominantly the scalp. The retrospective nature of this study is its main limitation. CONCLUSIONS: Hypochromic vitiligo is not yet part of a conventional classification. The disease seems to be limited to individuals with dark skin types. Hypopigmented seborrhoeic face and neck involvement associated with hypopigmented macules of the trunk and scalp is the hallmark of the disease.

Laser (755 nm) and cryotherapy as depigmentation treatments for vitiligo: a comparative study.

BACKGROUND: Depigmentation therapy can be an option in adults with extensive and refractory vitiligo. Remaining pigmented patches can be removed using depigmentation creams (monobenzyl ether of hydroquinone 20%), laser therapy or cryotherapy. In contrast to cream treatment, laser therapy and cryotherapy are fast and targeted methods, capable of destroying melanocytes selectively on one specific area. Up till now, controlled trials comparing laser and cryotherapy as depigmenting treatment in vitiligo are lacking. MATERIAL AND METHODS: We performed a retrospective comparative study in 22 generalized vitiligo patients. Thirty-one pigmented test regions were exposed to cryotherapy and 20 to 755 nm laser therapy. The mean surface area per test region was 3.55 cm2 and number of treatments per test region was limited to one single session in 84.3% and varied up to four sessions (2.0%). RESULTS: Overall no significant difference in the capacity to induce depigmentations was observed between cryotherapy (46.7%) and laser therapy (42.9%) after one treatment. The percentage of induced depigmentation was significantly different according to the body location (P = 0.005) with best results on the trunk, followed by the arms, face, neck and less on the hands. Variables that positively influenced depigmentation results were a younger age of vitiligo onset (P = 0.012), skin type V (P < 0.001) and clinical presence of Koebner's phenomenon (P = 0.039). Despite initial failure after one treatment, repetitive treatment sessions on eight test areas resulted in successful depigmentation. Side-effects were restricted to cryotherapy and concerned mainly hyperpigmentation in the face. CONCLUSION: To our knowledge, this is the first study comparing head-to-head depigmentation strategies intra- and inter-individually. We could demonstrate that in general laser and cryotherapy are equally effective in inducing depigmentations in generalized vitiligo patients. Retreatment of the same area may be required in case of initial failure.

Classification of segmental vitiligo on the trunk.

BACKGROUND: Segmental vitiligo is characterized by a unilateral and localized distribution. A classification for segmental vitiligo on the face has been proposed, while this is still unavailable for lesions on the trunk. OBJECTIVES: To design a classification for segmental vitiligo lesions on the trunk by evaluating their distribution pattern. METHODS: In this retrospective observational study, the distribution pattern of 106 segmental vitiligo lesions on the trunk was analysed and classified into recurring subtypes. RESULTS: Segmental vitiligo was more frequently observed on the ventral side (85·8%) than the lateral side (52·8%) or the back (36·8%) of the trunk. Based on recurring similarities in distribution patterns, lesions were categorized into six distinct subtypes: types 1, 2 and 3 involved the upper part of the trunk, type 4 and 5 the middle part and type 6 the lower part of the trunk. In total, 67·9% of all segmental vitiligo lesions fitted into these subtypes. The most frequent type of lesion was subtype 3 (22·6%), which showed a characteristic V-shaped pattern on the upper trunk, followed by subtype 5 (17·9%), with a band-like pattern on the lateral side, and subtype 6 (13·2%), with a rectangular depigmentation on the lower abdomen. CONCLUSIONS: Based on our observations we suggest a new classification into six subtypes for segmental vitiligo lesions on the trunk, allowing categorization of the majority of segmental vitiligo patterns on the trunk. This may have important prognostic and diagnostic significance in early developing lesions.

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

BACKGROUND: 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. OBJECTIVES: To analyse the expression pattern of IDO and associated immunological changes in corresponding primary melanomas (PMs), SLNs and metastases. METHODS: In 120 patients with melanoma, PMs with corresponding SLNs (n = 85) and metastases (n = 18) were analysed by immunohistochemical staining for IDO and FoxP3. Tumour-infiltrating lymphocytes (TILs) were scored. IDO expression in stimulated peripheral blood mononuclear cells (PBMCs) was analysed in 27 patients. RESULTS: IDO expression in the sentinel node strongly correlated with endothelial IDO expression in the peritumoral stroma of the corresponding primary (P < 0·001) and metastatic melanoma (P < 0·05). Sentinel IDO positivity was inversely correlated with CD8+ lymphocytes (P = 0·01) and TILs (P = 0·05) in PM. Both IDO expression in the sentinel (P < 0·01) and the PM (P = 0·04) had a negative prognostic effect on overall survival, independent of Breslow thickness, sex, age, ulceration and sentinel invasion. IDO expression by PBMCs after stimulation with cytotoxic T-lymphocyte antigen 4 was not correlated with sentinel IDO expression but tended to correlate with disease stage (P = 0·04). CONCLUSIONS: Endothelial IDO expression is highly consistent in primary, sentinel and metastatic tissues of patients with melanoma, indicating that immune suppression in melanoma is determined very early in the disease course. This supports that IDO expression in melanoma is a marker of antitumour immune response with an independent prognostic value.

Distribution patterns in generalized vitiligo.

BACKGROUND: Vitiligo is a common pigmentation disorder affecting approximately 1% of the world population. Nonetheless, its distribution pattern is not well investigated. OBJECTIVE: The aim of this study was to investigate whether the distribution pattern of vitiligo is dependent on the clinical characteristics. METHODS: A total of 700 generalized vitiligo patients were included in this retrospective observational cohort study. RESULTS: The most important predilection areas were the face (87%), followed by acral areas (76.3%) and extremities (59.7%). In women, joints (P = 0.002) (especially elbows), hips (P < 0.001), trunk (P < 0.001) and body folds (P < 0.001) (especially axillas) were more frequently affected compared to men. In contrast, in men more depigmentations in the beard area and genital area were observed (P < 0.001). Vitiligo at a young age is more prone to be localized at the lower extremities whereas the upper extremities are more susceptible at an older age. In the face, the periocular area is linked to a younger age, in contrast to the perioral area. Acral areas were more frequently affected in patients with autoimmune disorders (in particular thyroid disease) (P = 0.001). CONCLUSION: These results point to important differences in the distribution pattern according to the clinical characteristics. Although in some of these areas Koebner's phenomenon probably plays a role, other differences may represent a specific characteristic vulnerability related to the age, gender or typical association with autoimmune disease.

Clinical profile of generalized vitiligo patients with associated autoimmune/autoinflammatory diseases.

BACKGROUND: The significance of associated autoimmune/autoinflammatory diseases in generalized vitiligo patients with respect to their clinical profile has not yet been completely established. OBJECTIVE: The objective of this study was to evaluate the clinical significance of associated autoimmune/autoinflammatory diseases in generalized vitiligo patients with respect to some general clinical variables, distribution pattern, disease activity and treatment response. METHODS: Seven hundred generalized vitiligo patients were included in this retrospective observational cohort study. RESULTS: Associated autoimmune/autoinflammatory diseases were present in 15.4% of the patient population and were more common in women compared with men, especially concerning thyroid disease. Only vitiligo patients with thyroid disease had clear different clinical characteristics. The percentage of total body surface area involvement was significantly (P = 0.005) higher in the presence of thyroid disease which was more pronounced in women compared with men. Patients with thyroid disease had a particular predisposition to acral and joint depigmentations. No clear differences in disease activity or response to therapy were observed in vitiligo patients with or without autoimmune/autoinflammatory disorders. CONCLUSION: The presence of associated autoimmune/autoinflammatory diseases seems to influence the clinical profile of generalized vitiligo patients. Our results support the hypothesis that in the presence of a thyroid disorder, the disease activity of vitiligo is more extensive, in particular on areas prone to friction.

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. OBJECTIVES: To get an insight into the aetiopathogenesis of segmental vitiligo by comparison with the distribution pattern of dermatoses with a possible mosaic or neurogenic background. METHODS: In this retrospective observational study the distribution pattern of 724 unilateral, linear or band-shaped control lesions was compared with 181 segmental vitiligo lesions. Clinical photographs were used to score similarities according to a defined grading system (scale ranging from 0 for no similarities to 4 for complete similarity). Control lesions were evaluated both individually and after grouping into different cell types. RESULTS: In general, only a minority of cases (36·9%), showed similarities (grade 1-4) between control lesions and segmental vitiligo. Grade 2-4 similarities were seen mainly in segmental lentiginosis (73·7%, P < 0·001). The best grade for correspondence (grade 3-4) was observed significantly more only in segmental lentiginosis (36·8% vs. 3·5%, P<0·001) and epidermal naevus verrucosus (12·5% vs. 3·7%, P=0·008) compared with the other control lesions. The distribution pattern of segmental vitiligo significantly overlapped those of other disorders originating from melanocytes. CONCLUSIONS: Our results demonstrate that the distribution pattern of segmental vitiligo is not entirely similar to any other skin disease, although some mosaic skin disorders have more overlap with segmental vitiligo than others. The remarkable clinical similarity with several cases of mosaic diseases involving melanocytes supports the hypothesis that cutaneous mosaicism may be involved in segmental vitiligo.