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.

Hydrolyzed Rice Protein-Based Formulas, a Vegetal Alternative in Cow's Milk Allergy.

Formulas adapted to infant feeding, although most of the time made from cow's milk proteins, can be made from hydrolyzed rice protein but they must be classified as "formulas for specific medical needs", according to European regulations. The nutritional quality of rice proteins is thus suitable to be used in infant formulas giving that it is supplemented by certain amino acids which can be lacking. Besides, hydrolysis is required to facilitate their water solubility and digestibility. Owing to a low allergenicity of rice and to the absence of the cross-allergy between milk proteins and rice proteins, these formulas are adapted to the diet of children with cow's milk protein allergy (CMPA), which explains their growing use in some countries. However, CMPA, an expanding disorder, has consequences for growth, bone mineralization, and often has an association with allergy to other foods, including cow's milk extensive hydrolysate, so that a surveillance of the adaption of hydrolyzed rice protein formulas (HRPF) to CMPA, the absence of unexpected side effects, and the appropriate response to its various health hazards seems mandatory. This paper analyses the health problem deriving from CMPA, the industrial development of hydrolyzed rice protein formulas, and the limited number of clinical studies, which confirms, at the moment, a good allergic tolerance and safety. The goal is to better advise heath care professionals on their use of HRPFs during CMPA.

A new phototherapy regimen during winter as an add-on therapy, coupled with oral vitamin D supplementation, for the long-term control of atopic dermatitis: study protocol for a multicentre, randomized, crossover, pragmatic trial - the PRADA trial.

BACKGROUND: Atopic dermatitis is a highly prevalent, chronic, relapsing disease in both adults and children. On the severity spectrum, lower-end patients benefit from small amounts of topical anti-inflammatory treatments (TAT), whereas higher-end patients need systemic immunosuppressants; in-between patients are treated with TAT and phototherapy. The major therapeutic challenge in this population is the long-term control of disease activity, and the current TAT-based pro-active strategy does not meet all their needs. Immunosuppressants are used as long-term control add-on treatments, but they are restricted to the most severely affected patients because of safety concerns. In addition, neither immunosuppressants nor other strategies have been properly evaluated in the long term despite long-term control having been acknowledged as one of the most important core outcome domains to be targeted in atopic dermatitis trials. Safe add-on therapies, rigorously evaluated for long-term control of the disease, are therefore needed. Phototherapy and vitamin D supplementation are both good candidates. METHODS: This is a multicenter, national, randomized, superiority, crossover trial testing add-on phototherapy (one winter under spaced sessions of phototherapy and one winter under observation) among subjects receiving standard care (i.e., TAT). On the same population, we will test the long-term control provided by oral supplementation of vitamin D versus placebo in a randomized, superiority, double-blind, parallel-group trial. The primary outcomes are (1) repeat measures of the PO-SCORAD severity score over 1 year and (2) cumulate consumption of TAT (number of tubes) during the winter. They will be tested following a hierarchical testing procedure. The secondary outcomes will be measures repeated over 2 years of investigator-based severity scores, patient-reported severity and quality of life scores, serum vitamin D levels, weeks during which the disease is well-controlled, inter-visit cumulate consumption of TAT, and synthetic patient-reported satisfaction at the end of each winter. DISCUSSION: This study includes two separate 2-year pragmatic trials designed to evaluate the efficacy of vitamin D supplementation and pro-active phototherapy for primary care atopic dermatitis patients receiving TAT on long-term control of disease activity. The experimental design enables the study of both interventions and exploration of the interaction between vitamin D and phototherapy. A pragmatic trial is particularly suited to the assessment of long-term control. This study explores the possibility of new and safe therapeutic strategies for the control of long-term atopic dermatitis, and is an example of efficacy research that is unlikely to be sponsored by industrialists. A potentially effective low-cost therapeutic strategy for long-term control is essential for patients and public health. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02537509 , first received: 1 September 2015.

Quality of life of parents living with a child suffering from atopic dermatitis before and after a 3-month treatment with an emollient.

Atopic dermatitis (AD) can be extremely disabling and may cause psychological problems for affected children and their families. Moisturizers and emollients are important in the baseline daily skin care of patients with AD. To assess the effect of a 3-month, twice-daily treatment with an emollient on the quality of life (QoL) of parents with a child with mild to moderate AD (SCORing Atopic Dermatitis [SCORAD] ≤ 30, a multicenter open trial was performed by eight dermatologists on 191 volunteers. Evaluation by the dermatologist of the child's clinical condition (SCORAD) and of the efficacy and overall safety of the treatment was associated with a QoL questionnaire completed by one parent of the atopic child. A self-assessment of the global QoL and of the efficacy and overall safety was also performed. During the study, mean SCORAD dropped from 28 to 12 (p < 0.001), with good improvement in skin dryness and pruritus criteria. At the same time, the self-assessment of the global parent QoL scores dropped from 4.4 to 2.1 (p < 0.001) with 60%, 48% and 79% favorable parent opinions regarding wellbeing or improvement of the health condition, quality of sleep, and efficacy of the emollient, respectively. This trial revealed the efficacy of the product in improving parent QoL (85% of parents noted improvement in QoL), and its global safety was considered to be very good or good, with 80% favorable opinions in parents' declarative judgements and dermatologists' assessments. The emollient evaluated improves the course of AD and can improve the QoL of patients and their families.

Alternative procedure to allow continuation of dapsone therapy despite serious adverse reaction in a case of dapsone-sensitive erythema elevatum diutinum.

Dapsone has potent anti-inflammatory effects and remains an effective therapy in a variety of skin disorders: cutaneous vasculitis, neutrophilic dermatoses and blistering disorders. However it may cause a severe idiosyncratic reaction compatible with drug-induced DRESS (drug reaction with eosinophilia and systemic symptoms) leading to the discontinuation of the treatment despite its effectiveness. We report a 68-year-old woman who was successfully treated with dapsone for erythema elevatum diutinum. However she developed a hypersensitivity syndrome compatible with DRESS with fever, skin rash and acute hepatitis confirmed in vitro by the presence of circulating dapsone- specific T cells. Dapsone therapy was suspended, leading to a relapse of erythema elevatum diutinum. While alternative therapies were totally ineffective in our patient to improve her skin condition, we proposed a tolerance induction protocol to dapsone with excellent results.

Survey of dermatologists' phototherapy practices for vitiligo.

BACKGROUND: The details of phototherapy practices for vitiligo have been rarely studied. OBJECTIVE: To explore the details of phototherapy practices for vitiligo among dermatologists. METHODS: A self-administered questionnaire about the details of phototherapy practices for vitiligo was distributed to all dermatologists attending a national general dermatology conference in Riyadh, Saudi Arabia, in 2008. RESULTS: Questionnaires were returned by 121 of 140 participants (response rate = 86.4%). The mean age of the respondents was 39.34 ± 9.7 years, and 65% were males. One hundred eight of 110 (98.2%) respondents provided phototherapy to their vitiligo patients. The mean number of vitiligo patients who underwent phototherapy each week per dermatologist's office was 18 ± 2.26. Narrowband ultraviolet B (NB-UVB) was the most common modality chosen to treat generalized vitiligo (84%). Excimer laser was the most common modality used to treat focal and segmental vitiligo (53% and 39%, respectively). Sixty-eight percent of dermatologists administered a fixed starting dose of NB-UVB to all patients, whereas 31% used the minimal erythema dose as a guide. Fifty percent reported that NB-UVB resulted in better color matching with the surrounding skin. Thirty-seven percent favored NB-UVB over psoralen + ultraviolet A for a faster response, and 31% preferred NB-UVB for a pigmentation that is more durable. Forty-seven percent (50/106) of the respondents limited the number of phototherapy sessions to reduce the risks of skin cancer. However, no respondent reported any skin cancer incidence in phototherapy-treated vitiligo patients. CONCLUSION: There is a need for phototherapy guidelines for the treatment of vitiligo in patients with skin of color.

The historical basis of a misconception leading to undertreating atopic dermatitis (eczema): facts and controversies.

The quest for clarifying the pathophysiology of atopic dermatitis (eczema) has lasted for 25 centuries. Yearning to discern the primum movens of atopic dermatitis, physicians aimed to identify the curative therapy. Recent scientific efforts has brought to the light an ever-growing amount of interplaying pathophysiologic factors, including the epidermal barrier, the digestive flora, food, early infections and antigenic stimulations, and innate and adaptive immune response; however, overfocusing on some of these factors, along with misconceptions about the benefit/risk balance of topical therapies, has sometimes led topical therapies being disregarded. Reviewing the history of pathophysiologic concepts, we aim to return topical therapies to the center of the clinical management of atopic dermatitis.

Polyunsaturated fatty acids partially reproduce the role of melanocytes in the epidermal melanin unit.

The incidence rate of melanoma is higher in fair-skinned than in dark-skinned individuals. In negroid skin there is more eumelanin which is present in all skin layers and fewer polyunsaturated fatty acids (PUFA) than in caucasoid skin. The western diet, which is rich in omega-6 polyunsaturated fatty acids, is associated with more proneness to cancer including cutaneous melanoma. To study the respective influence of omega-6 PUFA and low phototype melanocytes on redox status -basal and following UV irradiation-, we used epidermal reconstructs. The addition of polyunsaturated fatty acids as well as the presence of low phototype melanocytes affected basal status similarly except for catalase activity, which decreased significantly in polyunsaturated fatty acid-supplemented reconstructs. Following UV, polyunsaturated fatty acids and low phototype melanocytes increased lipid and protein oxidative damage without affecting direct DNA damage. However, polyunsaturated fatty acids increased epidermal apoptosis whereas low phototype melanocytes decreased it. Since our data suggest that an omega-6 PUFA rich-diet may increase oxidative damage in melanocytes without inducing apoptosis, the long-term net outcome could be cumulated mutations and an increased risk of skin cancer, especially melanoma.