Iltefat Hamzavi

Revised classification/nomenclature of vitiligo and related issues: the Vitiligo Global Issues Consensus Conference

During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global importance for vitiligo clinical research. As suggested by an international panel of experts, the conference focused on four topics: classification and nomenclature; definition of stable disease; definition of Koebner’s phenomenon (KP); and ‘autoimmune vitiligo’. These topics were discussed in seven working groups representing different geographical regions. A consensus emerged that segmental vitiligo be classified separately from all other forms of vitiligo and that the term ‘vitiligo’ be used as an umbrella term for all non‐segmental forms of vitiligo, including ‘mixed vitiligo’ in which segmental and non‐segmental vitiligo are combined and which is considered a subgroup of vitiligo. Further, the conference recommends that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably. The conference also endorsed the classification of KP for vitiligo as proposed by the VETF (history based, clinical observation based, or experimentally induced). Lastly, the conference agreed that ‘autoimmune vitiligo’ should not be used as a separate classification as published evidence indicates that the pathophysiology of all forms of vitiligo likely involves autoimmune or inflammatory mechanisms.

Impact of Long-Wavelength UVA and Visible Light on Melanocompetent Skin

The purpose of this study was to determine the effect of visible light on the immediate pigmentation and delayed tanning of melanocompetent skin; the results were compared with those induced by long-wavelength UVA (UVA1). Two electromagnetic radiation sources were used to irradiate the lower back of 20 volunteers with skin types IV-VI: UVA1 (340-400 nm) and visible light (400-700 nm). Pigmentation was assessed by visual examination, digital photography with a cross-polarized filter, and diffused reflectance spectroscopy at 7 time points over a 2-week period. Confocal microscopy and skin biopsies for histopathological examination using different stains were carried out. Irradiation was also carried out on skin type II. Results showed that although both UVA1 and visible light can induce pigmentation in skin types IV-VI, pigmentation induced by visible light was darker and more sustained. No pigmentation was observed in skin type II. The quality and quantity of pigment induced by visible light and UVA1 were different. These findings have potential implications on the management of photoaggravated pigmentary disorders, the proper use of sunscreens, and the treatment of depigmented lesions.

Effects of Visible Light on the Skin

Electromagnetic radiation has vast and diverse effects on human skin. Although photobiologic studies of sunlight date back to Sir Isaac Newton in 1671, most available studies focus on the UV radiation part of the spectrum. The effects of visible light and infrared radiation have not been, until recently, clearly elucidated. The goal of this review is to highlight the effects of visible light on the skin. As a result of advances in the understanding of skin optics, and comprehensive studies regarding the absorption spectrum of endogenous and exogenous skin chromophores, various biologic effects have been shown to be exerted by visible light radiation including erythema, pigmentation, thermal damage and free radical production. It has also been shown that visible light can induce indirect DNA damage through the generation of reactive oxygen species. Furthermore, a number of photodermatoses have an action spectrum in the visible light range, even though most of the currently available sunscreens offer, if any, weak protection against visible light. Conversely, because of its cutaneous biologic effects, visible light is used for the treatment of a variety of skin diseases and esthetic conditions in the form of lasers, intense pulsed light and photodynamic therapy.

Randomized Control Trial for the Treatment of Hidradenitis Suppurativa with a Neodymium‐Doped Yttrium Aluminium Garnet Laser

BACKGROUND Hidradenitis suppurativa (HS) is a chronic suppurative condition for which there is limited efficacy of medical and surgical treatments. OBJECTIVE To assess whether the 1,064‐nm neodymium‐doped yttrium aluminium garnet (Nd:YAG) laser is an effective treatment for HS. MATERIALS AND METHODS Prospective, randomized, controlled study for patients with stage II to III HS disease (n=22). A series of 3 monthly laser sessions were performed. Treatment response was measured before each laser session and 1 month after the completion of laser treatment (HS Lesion, Area, and Severity Index (HS‐LASI) scale). A modification was made to include symptoms (erythema, edema, pain, and purulent discharge; modified HS‐LASI, 0‐3 scale). RESULTS The percentage change in HS severity after 3 months of treatment was –65.3% over all anatomic sites, −73.4% inguinal, −62.0% axillary, and −53.1% inframammary. For all anatomic sites combined and each individual anatomic site, the change in HS severity from baseline to month 3 was statistically significant at the treated sites (p<.02 for modified HS‐LASI and HS‐LASI) but not at the control sites (p>.05 for modified HS‐LASI and HS‐LASI). CONCLUSIONS The long‐pulse Nd:YAG laser is effective for treatment of HS. The effectiveness of Nd:YAG laser, a hair epilation device, supports the primary follicular pathogenesis of the condition. The authors have indicated no significant interest with commercial supporters.

A Systematic Review of Treatments for Hidradenitis Suppurativa

OBJECTIVES To conduct a systematic review of the effectiveness of various modalities to treat hidradenitis suppurativa (HS) and to establish recommendations on its appropriate management. DATA SOURCES MEDLINE, Cochrane, and PubMed databases. STUDY SELECTION English-language prospective, retrospective, and case studies describing at least 4 patients with HS. DATA EXTRACTION Data quality and validity were addressed by multiple reviewers using independent extraction. DATA SYNTHESIS Studies were categorized as treatments using antibiotics, biological agents, laser surgery, excisional surgery, or miscellaneous modalities. Of 62 publications included in the review, 4 studies met criteria to be assigned the highest grade for quality of evidence. CONCLUSIONS Shown to be effective treatments for HS were a clindamycin-rifampin combination regimen, a course of infliximab, monthly Nd:YAG laser sessions, and surgical excision and primary closure with a gentamicin sulfate-collagen sponge. Most therapies used to treat HS were supported by limited or weak scientific evidence. A treatment approach is presented based on the evidence and on clinical experience at the Follicular Disorders Clinic, Department of Dermatology, Henry Ford Hospital, Detroit, Michigan. This review emphasizes the need for large randomized controlled trials to evaluate treatment options for HS.

Afamelanotide and Narrowband UV-B Phototherapy for the Treatment of Vitiligo: A Randomized Multicenter Trial

IMPORTANCE Narrowband UV-B (NB-UV-B) phototherapy is used extensively to treat vitiligo. Afamelanotide, an analogue of α-melanocyte-stimulating hormone, is known to induce tanning of the skin. OBJECTIVE To evaluate the efficacy and safety of combination therapy for generalized vitiligo consisting of afamelanotide implant and NB-UV-B phototherapy. DESIGN, SETTING, AND PARTICIPANTS This study was performed in 2 academic outpatient dermatology centers and 1 private dermatology practice. We enrolled men and women 18 years or older with Fitzpatrick skin phototypes (SPTs) III to VI and a confirmed diagnosis of nonsegmental vitiligo that involved 15% to 50% of total body surface area. Vitiligo was stable or slowly progressive for 3 months. Patients were randomized to combination therapy (n = 28) vs NB-UV-B monotherapy (n = 27). After 1 month of NB-UV-B phototherapy, 16 mg of afamelanotide was administered subcutaneously to the combination therapy group monthly for 4 months while NB-UV-B phototherapy continued; the other group continued to receive NB-UV-B monotherapy. INTERVENTIONS Narrowband UV-B monotherapy vs combined NB-UV-B phototherapy and afamelanotide. MAIN OUTCOMES AND MEASURES Response on the Vitiligo Area Scoring Index and Vitiligo European Task Force scoring system. RESULTS Response in the combination therapy group was superior to that in the NB-UV-B monotherapy group (P < .05) at day 56. For the face and upper extremities, a significantly higher percentage of patients in the combination therapy group achieved repigmentation, and at earlier times (face, 41.0 vs 61.0 days [P = .001]; upper extremities, 46.0 vs 69.0 days [P = .003]). In the combination therapy group, repigmentation was 48.64% (95% CI, 39.49%-57.80%) at day 168 vs 33.26% (95% CI, 24.18%-42.33%) in the NB-UV-B monotherapy group. Notable adverse events included erythema in both groups and minor infections and nausea in the combination therapy group. Comparison between Fitzpatrick SPTs showed patients with SPTs IV to VI in the combination therapy group had improvement in the Vitiligo Area Scoring Index at days 56 and 84 (P < .05); no significant difference was noted in patients with SPT III. CONCLUSIONS AND RELEVANCE A combination of afamelanotide implant and NB-UV-B phototherapy resulted in clinically apparent, statistically significant superior and faster repigmentation compared with NB-UV-B monotherapy. The response was more noticeable in patients with SPTs IV to VI. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01430195.

The Efficacy of Afamelanotide and Narrowband UV-B Phototherapy for Repigmentation of Vitiligo

BACKGROUND Vitiligo is characterized by depigmented patches of skin due to loss of cutaneous melanocytes. Many recent studies have demonstrated defects in the melanocortin system in patients with vitiligo, including decreased circulating and lesional skin levels of α-melanocyte-stimulating hormone (α-MSH). Afamelanotide is a potent and longer-lasting synthetic analogue of naturally occurring α-MSH. OBSERVATIONS We describe the preliminary results of 4 patients with generalized vitiligo who developed repigmentation using afamelanotide in combination with narrowband UV-B (NB-UV-B) phototherapy. Patients were treated 3 times weekly with NB-UV-B and starting in the second month received a series of 4 monthly implants containing 16 mg of afamelanotide. Afamelanotide induced faster and deeper repigmentation in each case. All patients experienced follicular and confluent areas of repigmentation within 2 days to 4 weeks after the initial implant, which progressed significantly throughout treatment. All patients experienced diffuse hyperpigmentation. CONCLUSIONS We propose that afamelanotide represents a novel and potentially effective treatment for vitiligo. The combined therapy of NB-UV-B and afamelanotide appears to promote melanoblast differentiation, proliferation, and eumelanogenesis. Further studies are necessary to confirm these observations.

Paradoxical Hypertrichosis After Laser Therapy: A Review

BACKGROUND Laser hair removal is a safe and effective procedure for the treatment of unwanted body hair but is not exempt from side effects. A rare but significant adverse effect with this treatment modality is paradoxical hypertrichosis. OBJECTIVE To evaluate the potential etiologies, risk factors, related laser types, and treatment options for the development of excess hair after laser therapy. MATERIALS AND METHODS An analysis of previously published case studies and review articles along with our own experience was used to gather information regarding this phenomenon. RESULTS Paradoxical hypertrichosis has a low incidence, ranging from 0.6% to 10%, and most commonly occurs on the face and neck. All laser and light sources have the potential to cause hair induction, especially in individuals with darker skin types (III–VI); with dark, thick hair; and with underlying hormonal conditions. Possible causes include the effect of inflammatory mediators and subtherapeutic thermal injury causing induction of the hair cycle. Treatment for paradoxical hypertrichosis is laser therapy of the affected area. CONCLUSIONS Paradoxical hypertrichosis is a rare side effect of laser hair removal; the pathogenesis of this event remains widely unknown. We recommend further large‐scale studies to investigate this effect. The authors have indicated no significant interest with commercial supporters.

Incidence of nonmelanoma skin cancer in a cohort of patients with vitiligo

BACKGROUND Nonmelanoma skin cancer (NMSC) incidence in patients with vitiligo has not been studied. OBJECTIVE We sought to quantify the incidence of NMSC in patients with vitiligo. METHODS A cohort of 477 patients with vitiligo and no history of NMSC seen in an outpatient academic center between January 2001 and December 2006 was established. All charts for patients with vitiligo were reviewed for incident NMSC, and histopathology verified. Age-adjusted (2000 US Standard Million) incidence rates were calculated and compared to US rates. RESULTS Six patients with NMSC were identified; all were Caucasian (>61 years). Age-adjusted incidence rates were: basal cell carcinoma, male 1382/100,000; basal cell carcinoma, female 0; squamous cell carcinoma, male 465/100,000; squamous cell carcinoma, female 156/100,000. Except for basal cell carcinoma in females, all rates were higher than US rates but not statistically significant. LIMITATIONS Comparison incidence rates from the general patient population during the same time period were unavailable. CONCLUSION Health care providers should be aware of the possible risk of NMSC in Caucasian patients with vitiligo.

Developing core outcome set for vitiligo clinical trials: international e‐Delphi consensus

1 Centre of Evidence Based Dermatology, University of Nottingham, Nottingham,UK 2 Department of Dermatology, Ghent University Hospital, Ghent, Belgium3 Department of Dermatology, Henry Ford Hospital, Detroit, MI, USA4 Department of Dermatology, Yamagata University School of Medicine,Yamagata, Japan 5 Department of Dermatology, Osaka University, Osaka, Japan6 Dermatology Department, Al-Minya University, Al-Minya, Egypt 7 Departmentof Dermatology and Venereology, Ain Shams University, Cairo, Egypt8 Department of Dermatology, Ibn Sina University Hospital, Rabat, Morocco9 Mohammed V Souissi University, Rabat, Morocco 10 Department ofDermatology, University of Bordeaux National Reference Centre for Rare SkinDiseases H^opital St-Andr e, Bordeaux, France 11 Department of Medicine,Division of Dermatology, University of Massachusetts Medical School,Worcester, MA, USA 12 Department of Dermatology, Pontifcia UniversidadeCatœlica do Paranffi, Curitiba, Brazil 13 Department of Dermatology, University ofTexas Southwestern Medical Center, Dallas, TX, USA 14 National Skin Centre,Singapore City, Singapore 15 Department of Dermatology, Kaohsiung MedicalUniversity, Kaohsiung City, Taiwan 16 Department of Dermatology, KinkiUniversity Faculty of Medicine, Osaka-Sayama, Japan 17 Vitiligo Light Clinic,Riyadh, Saudi Arabia 18 Department of Dermatology, Cairo University, Kasr AlAiny Hospital, Cairo, Egypt 19 Departments of Pathology, Microbiology andImmunology/Oncology Institute, Loyola University Chicago, Chicago, IL, USA20 Department of Dermatology, Dongguk University Ilsan Hospital, Gyeonggi-do,Korea 21 Department of Dermatology, PGIMER, Chandigarh, India 22 Departmentof Dermatology, San Gallicano Dermatologic Institute IRCCS, Roma, ItalyCORRESPONDENCE Khaled Ezzedine and Viktoria Eleftheriadou, e-mails: khaled.ezzedine@chu-bordeaux.fr; viktoria.eleftheriadou@nottingham.ac.uk