Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the International Vitiligo Task Force Part 1: towards a new management algorithm.

BACKGROUND: The treatment of vitiligo can be challenging and depends on several factors such as the subtype, disease activity, vitiligo extent, and treatment goals. Vitiligo usually requires a long-term approach. To improve the management of vitiligo worldwide, a clear and up-to-date guide based on international consensus with uniform stepwise recommendations is needed. OBJECTIVES: To reach an international consensus on the nomenclature and to develop a management algorithm for the diagnosis, assessment, and treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence of topics included in the algorithms. A survey was utilized to resolve remaining issues among a core group of eight experts. Subsequently, the unanimous recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The algorithms highlight the importance of shared decision-making. Dermatologists are encouraged to provide patients with detailed explanations of the prognosis and expected therapeutic outcomes based on clinical examination. The treatment goal should be discussed and clearly emphasized to patients given the different approaches for disease stabilization and repigmentation. The evaluation of disease activity remains a cornerstone in the tailor-made approach to vitiligo patients. CONCLUSIONS: These new treatment algorithms are intended to guide clinical decision-making in clinical practice. Promising novel therapies for vitiligo are on the horizon, further highlighting the need for reliable outcome measurement instruments and greater emphasis on shared decision-making.

Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations.

BACKGROUND: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. OBJECTIVES: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed. CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

Suspension-associated dislocation of the jaw in hanging.

Hanging is a common type of death, and the role of the medical investigation of such deaths by a forensic pathologist not only requires the determination of the cause of death but providing information to assist in the determination of the manner of death. The forensic pathologist should be well versed in the spectrum of injuries known to be associated with neck compression, to document injuries known to be associated with hanging, but also to identify those that are inconsistent with self-inflicted hanging or that may suggest the involvement of a third party in the death. Comprehensive identification and correct interpretation of external and internal injury are crucial for the appropriate degree of police and coroner/medical examiner investigation. We present two cases of deaths believed to be caused by self-inflicted hanging that were observed to have unexpected unilateral dislocation of the temporomandibular joint identified on routine post-mortem computed tomography, without any evidence of involvement of a third party. This injury was unexplained and had not been previously observed at our Forensic Institute nor was it identified after a review of the published biomedical research literature. Issues regarding the cause of this abnormality, possible mechanisms, and the medicolegal significance of this finding will be discussed.

Recipient-to-Donor Ratios in the Surgical Treatment of Vitiligo, Leukoderma, and Piebaldism: A Retrospective Review.

BACKGROUND: The autologous noncultured melanocyte keratinocyte transplant procedure (MKTP) has emerged as a popular grafting technique with proven efficacy for achieving repigmentation. However, there remains no consensus regarding the optimal recipient-to-donor (RD) ratio required to achieve acceptable repigmentation. In this retrospective cohort study of 120 patients, we sought to examine whether expansion ratios impact the repigmentation success rates following MKTP. RESULTS: A total of 69 patients (mean [SD] age was 32.4 [14.3] years, mean follow-up was 30.4 [22.5] months, 63.8% were male; 55% were dark-skinned individuals [Fitzpatrick IV-VI]) were included. The mean percent change in the Vitiligo Area Scoring Index (VASI) was 80.2 (±23.7; RD of 7.3) in patients with focal/segmental vitiligo (SV), 58.3 (±33.0; RD of 8.2) in those with non-segmental vitiligo (NSV), and 51.8 (±33.6; RD of 3.7) in those with leukoderma and piebaldism. Focal/SV was positively associated with a higher percent change in VASI (parameter estimate: 22.6, p value <0.005). In the SV/focal group, non-white patients had a higher RD ratio compared to White individuals (8.2 ± 3.4 vs. 6.0 ± 3.1, respectively, p value = 0.035). DISCUSSION: In our study, we found that patients with SV were significantly more likely to achieve higher repigmentation rates compared to those with NSV. Although repigmentation rates were higher in the low expansion ratio group than in the high expansion ratio group, we did not observe a significant difference between the two groups. CONCLUSION: MKTP is an effective therapy for restoring repigmentation in patients with stable vitiligo. Therapeutic response of vitiligo to MKTP appears to be influenced by the type of vitiligo, rather than a specific RD ratio.

Dysregulated CD38 expression in blood and skin immune cells of patients with hidradenitis suppurativa.

Background: Hidradenitis suppurativa (HS) is a multifactorial, inflammatory skin disease. Increased systemic inflammatory comorbidities and serum cytokines highlight systemic inflammation as a feature of HS. However, the specific immune cell subsets contributing to systemic and cutaneous inflammation have not been resolved. Objective: Identify features of peripheral and cutaneous immune dysregulation. Methods: Here, we generated whole-blood immunomes by mass cytometry. We performed a meta-analysis of RNA-seq data, immunohistochemistry, and imaging mass cytometry to characterize the immunological landscape of skin lesions and perilesions from patients with HS. Results: Blood from patients with HS exhibited lower frequencies of natural killer cells, dendritic cells, and classical (CD14+CD16-) and nonclassical (CD14-CD16+) monocytes, as well as higher frequencies of Th17 cells and intermediate (CD14+CD16+) monocytes than blood from healthy controls. Classical and intermediate monocytes from patients with HS had increased expression of skin-homing chemokine receptors. Furthermore, we identified a CD38+ intermediate monocyte subpopulation that was more abundant in the immunome of blood from patients with HS. Meta-analysis of RNA-seq data found higher CD38 expression in lesional HS skin than in perilesional skin, and markers of classical monocyte infiltration. Imaging mass cytometry showed that CD38+ classical monocytes and CD38+ monocyte-derived macrophages were more abundant in lesional HS skin. Conclusion: Overall, we report targeting CD38 may be worth pursuing in clinical trials. Key Messages: 3.Monocyte subsets express markers of activation in circulation and HS lesionsTargeting CD38 may be a viable strategy for treating systemic and cutaneous inflammation in patients with HS. Capsule Summary: 4.Dysregulated immune cells in patients with HS express CD38 and may be targeting by anti-CD38 immunotherapy.

Dysregulated CD38 expression in blood and skin immune cells of patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a multifactorial, inflammatory skin disease. Increased systemic inflammatory comorbidities and serum cytokines highlight systemic inflammation as a feature of HS. However, the specific immune cell subsets contributing to systemic and cutaneous inflammation have not been resolved. Here, we generated whole-blood immunomes by mass cytometry. We performed a meta-analysis of RNA-seq data, immunohistochemistry, and imaging mass cytometry to characterize the immunological landscape of skin lesions and perilesions from patients with HS. Blood from patients with HS exhibited lower frequencies of natural killer cells, dendritic cells, and classical (CD14+CD16-) and nonclassical (CD14-CD16+) monocytes, as well as higher frequencies of Th17 cells and intermediate (CD14+CD16+) monocytes than blood from healthy controls. Classical and intermediate monocytes from patients with HS had increased expression of skin-homing chemokine receptors. Furthermore, we identified a CD38+ intermediate monocyte subpopulation that was more abundant in the immunome of blood from patients with HS. Meta-analysis of RNA-seq data found higher CD38 expression in lesional HS skin than in perilesional skin, and markers of classical monocyte infiltration. Imaging mass cytometry showed that CD38+ classical monocytes and CD38+ monocyte-derived macrophages were more abundant in lesional HS skin. Overall, we report targeting CD38 may be worth pursuing in clinical trials.

A model for analyzing clustered occurrence data.

Spatial or temporal clustering commonly arises in various biological and ecological applications, for example, species or communities may cluster in groups. In this paper, we develop a new clustered occurrence data model where presence-absence data are modeled under a multivariate negative binomial framework. We account for spatial or temporal clustering by introducing a community parameter in the model that controls the strength of dependence between observations thereby enhancing the estimation of the mean and dispersion parameters. We provide conditions to show the existence of maximum likelihood estimates when cluster sizes are homogeneous and equal to 2 or 3 and consider a composite likelihood approach that allows for additional robustness and flexibility in fitting for clustered occurrence data. The proposed method is evaluated in a simulation study and demonstrated using forest plot data from the Center for Tropical Forest Science. Finally, we present several examples using multiple visit occupancy data to illustrate the difference between the proposed model and those of N-mixture models.

Importance of and instruction for starting a vitiligo patient support group.

Starting and maintaining a vitiligo support group can appear to be a daunting task. However, with proper planning and organization, the process can become manageable and rewarding. Our guide details the reasons to start a vitiligo support group, how to start a group, how to run a group, and how to promote a group. Legal protections and details regarding retention and funding are also discussed. The authors have extensive experience leading and/or assisting support groups for vitiligo and other disease states and we also sought out other current vitiligo support leaders for their valuable insights. Previous research has found that support groups for various medical conditions may have a protective effect and membership can build resilience among participants as well as foster a sense of hope regarding their disease. Further, groups can provide a network for those living with vitiligo to connect with, uplift, and learn from one another. These groups provide the opportunity to initiate lifelong connections with those facing similar circumstances and provide members with new insight and coping strategies. Members can share perspectives with one another and empower one another. We encourage dermatologists to provide vitiligo patients with support group information and to consider being involved in, starting, or otherwise supporting them.

A Multi-Centered Case-Control Study of Vitiligo Support Groups and Quality of Life.

BACKGROUND: There is limited research on the association between vitiligo support group membership and patient quality of life (QoL). OBJECTIVES: To explore the association between support groups and QoL in those with vitiligo by evaluating and comparing the QoL of vitiligo support group members and non-support group members. METHODS: Support group members (n=135) and non-support group members (n=129) were recruited from the Global Vitiligo Foundation (GVF), and three academic medical centers respectively. Patients completed the Vitiligo-Specific Quality of Life (VitiQoL) instrument and a demographic survey. RESULTS: Mean VitiQoL scores for support group members were higher than non-support group members (48.6 ± 23.6 vs 33.0 ± 23.8; P-value < 0.0001), highlighting more negatively impacted QoL. Support group members were less likely to be undergoing treatment (27.4% vs 53.5%; P-value = <0.0001) and were more likely to report duration of vitiligo for >20 years (38.5% vs 19.4%; P-value = 0.0007). CONCLUSIONS: Vitiligo support group membership is associated with worse QoL. Individuals with vitiligo who have worse QoL, chronic, and/or untreated vitiligo may be more likely to seek out vitiligo support groups. Support group referral should be considered in the therapeutic management of vitiligo, particularly in patients whose QoL is more significantly impacted, who fail or are who are without access to treatment or have longstanding disease. J Drugs Dermatol. 2021;20(6):672-675. doi:10.36849/JDD.5706.

Inference from single occasion capture experiments using genetic markers.

Accurate estimation of the size of animal populations is an important task in ecological science. Recent advances in the field of molecular genetics researches allow the use of genetic data to estimate the size of a population from a single capture occasion rather than repeated occasions as in the usual capture-recapture experiments. Estimating the population size using genetic data also has sometimes led to estimates that differ markedly from each other and also from classical capture-recapture estimates. Here, we develop a closed form estimator that uses genetic information to estimate the size of a population consisting of mothers and daughters, focusing on estimating the number of mothers, using data from a single sample. We demonstrate the estimator is consistent and propose a parametric bootstrap to estimate the standard errors. The estimator is evaluated in a simulation study and applied to real data. We also consider maximum likelihood in this setting and discover problems that preclude its general use.

Prospective Controlled Trial for the Treatment of Acne Keloidalis Nuchae With a Long-Pulsed Neodymium-Doped Yttrium-Aluminum-Garnet Laser.

BACKGROUND: Acne keloidalis nuchae (AKN) is a chronic scarring folliculitis with limited interventions of both high efficacy and low morbidity. OBJECTIVE: To assess the efficacy of the long-pulsed 1064-nm neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser and topical steroids as a treatment for AKN compared to topical steroids alone. METHODS: We conducted a single-blinded, randomised, within-patient right-left controlled trial (n = 13). Eight monthly laser treatments were performed on the treated half of the scalp, and triamcinolone 0.1% cream was applied to both sides twice daily. Treatment response was measured using a global assessment score (0 to 10). RESULTS: The laser-treated side showed greater improvement in global assessment score. The mean change was -3.2 (-49.2%) on the treated side and -2.2 (-32.8%) on the control side ( P = .144). Papules responded well to laser treatment, while larger plaques and nodules showed limited improvement. In the 10 patients with papules only, the difference in improvement between the treated and control sides was statistically significant (mean change was -3.5 [-59.3%] for the treated side and -1.8 [-29.5%] for the control side, P = .031). LIMITATIONS: This study was limited by a small sample size and a high dropout rate, as well as the lack of a standardised scoring system for AKN. CONCLUSION: The long-pulsed Nd:YAG laser in conjunction with topical steroids shows promising results in the treatment of AKN, particularly the papular component, and is well tolerated by patients.

Estimating the size of an open population using sparse capture-recapture data.

Sparse capture-recapture data from open populations are difficult to analyze using currently available frequentist statistical methods. However, in closed capture-recapture experiments, the Chao sparse estimator (Chao, 1989, Biometrics 45, 427-438) may be used to estimate population sizes when there are few recaptures. Here, we extend the Chao (1989) closed population size estimator to the open population setting by using linear regression and extrapolation techniques. We conduct a small simulation study and apply the models to several sparse capture-recapture data sets.

Long-term follow-up of patients undergoing autologous noncultured melanocyte-keratinocyte transplantation for vitiligo and other leukodermas.

BACKGROUND: Persistence of pigmentation after a melanocyte-keratinocyte transplantation procedure (MKTP) is an important consideration for efficacy. OBJECTIVE: We sought to determine long-term repigmentation of MKTP in vitiligo and other leukodermas. METHODS: A retrospective review of electronic medical records was conducted for all MKTPs performed at Henry Ford Hospital between January 2009 and April 2014. Repigmentation was assessed by a 5-point grading scale (poor to excellent) and Vitiligo Area Scoring Index (VASI). RESULTS: One hundred patients had MKTP performed at 236 anatomically-based lesions (ABLs); 63 patients with 157 ABLs had long-term data available (12-72 months; median, 24 months). Segmental vitiligo, nonsegmental vitiligo, and physical leukoderma demonstrated improvement in VASI scores: -75.6 ± 24.6%, -59.2 ± 36.6%, and -32.4 ± 33.5%, respectively. In vitiligo, at 24, 48, and 72 months after MKTP, 53%, 64%, and 53% of ABLs, respectively, maintained >75% repigmentation. Skin phototype, age, and anatomic location of ABLs had no significant effect on the outcome of treatment. LIMITATIONS: Limitations of the study include the retrospective design with uncontrolled, postoperative adjuvant treatments and inconsistent compliance to scheduled follow-up evaluations. CONCLUSIONS: MKTP provides satisfactory long-term repigmentation in the majority of appropriately selected patients with leukoderma. MKTP can maintain repigmentation for at least 72 months.

Quality of Life in a Vitiligo Support Group.

BACKGROUND: No study has examined the impact of vitiligo support group membership on vitiligo patient quality of life (QoL).

OBJECTIVE: We sought to examine the QoL impact of vitiligo support groups by comparing QoL and associated patient characteristics between vitiligo patients who are and are not members of a vitiligo support group.

METHODS: Members of a Henry Ford Hospital-sponsored, Southeast Michigan Vitiligo Support Group were compared to non-member vitiligo patients recruited from a previous study cohort.17 Eligible patients were asked to complete the Dermatology Life Quality Index (DLQI) and a study-specific questionnaire designed to collect relevant patient characteristics.

RESULTS: The mean DLQI scores for the support group members and non-members were similar (7.1 ± 5.4 and 6.0 ± 6.5, respectively; P-value 0.2), despite the support group members reporting more severe overall disease and increased disease severity in exposed portions of the body. The African-American: Caucasian ratio and the prevalence of unemployment were both significantly higher among the support group participants. LIMITATIONS: Small sample size may have limited the study's ability to demonstrate the differences between the support group participants and the controls.

CONCLUSIONS: The similar QoL despite an increased prevalence of poorer QoL indicators among the support group participants suggests a protective effect of support group membership.

J Drugs Dermatol. 2017;16(4):344-350.

Regeneration of pilot-scale ion exchange columns for hexavalent chromium removal.

Due to stricter regulations, some drinking water utilities must implement additional treatment processes to meet potable water standards for hexavalent chromium (Cr(VI)), such as the California limit of 10 µg/L. Strong base anion exchange is effective for Cr(VI) removal, but efficient resin regeneration and waste minimization are important for operational, economic and environmental considerations. This study compared multiple regeneration methods on pilot-scale columns on the basis of regeneration efficiency, waste production and salt usage. A conventional 1-Stage regeneration using 2 N sodium chloride (NaCl) was compared to 1) a 2-Stage process with 0.2 N NaCl followed by 2 N NaCl and 2) a mixed regenerant solution with 2 N NaCl and 0.2 N sodium bicarbonate. All methods eluted similar cumulative amounts of chromium with 2 N NaCl. The 2-Stage process eluted an additional 20-30% of chromium in the 0.2 N fraction, but total resin capacity is unaffected if this fraction is recycled to the ion exchange headworks. The 2-Stage approach selectively eluted bicarbonate and sulfate with 0.2 N NaCl before regeneration using 2 N NaCl. Regeneration approach impacted the elution efficiency of both uranium and vanadium. Regeneration without co-eluting sulfate and bicarbonate led to incomplete uranium elution and potential formation of insoluble uranium hydroxides that could lead to long-term resin fouling, decreased capacity and render the resin a low-level radioactive solid waste. Partial vanadium elution occurred during regeneration due to co-eluting sulfate suppressing vanadium release. Waste production and salt usage were comparable for the 1- and 2-Stage regeneration processes with similar operational setpoints with respect to chromium or nitrate elution.

Biologic Behavior of Hydroxyapatite Used in Facial Augmentation.

INTRODUCTION: The recent finding that shrinkage of key areas of the facial skeleton contributes to the aging appearance of the face has prompted a search for the most appropriate bone-like implant material. Evidence that hydroxyapatite, in granular form, maintains volume in the long term supports its use in the correction of aging, in addition to its use in the correction of inherently deficient areas of the facial skeleton. The biologic response of hydroxyapatite needs to be fully understood for its use to be confidently recommended. MATERIALS AND METHODS: Samples of 'living' hydroxyapatite from the anterior maxilla, zygoma, and mandible of 17 patients were analyzed. These were obtained during revision procedures performed between 6 months and 15 years following original placement on the facial skeleton. RESULTS: Histology showed that in every case, the individual granules were embedded within a mass of collagen that made up about half of the total implant volume. The collagen mass also contained fine elastin, fibroblasts, lymphocytes, occasional granulomas, and vessels. By 2 years, a new compact bone containing osteoblasts and osteocytes was present in all specimens in the deep (osseous) aspect. Bone progressively replaced the original collagen between the granules with a sharply defined transition at the interface. CONCLUSIONS: This study confirmed a two-stage biologic change following onlay placement of hydroxyapatite granules on the facial skeleton, i.e., initial collagen formation with subsequent conversion to bone. This integrates the implant with the host bone which stabilizes the implant position and shape initially and in long term. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors. www.springer.com/00266 .