Beyond the Booth: Excimer Laser for Cutaneous Conditions.

The excimer laser has emerged as an efficacious treatment modality for many dermatologic diseases. The excimer laser is an alternative to standard narrowband ultraviolet B (NBUVB) phototherapy treatment in patients with limited disease. In comparison to standard NBUVB, the excimer laser requires fewer treatment sessions, has reduced treatment duration, requires a lower cumulative UVB dose, and limits UVB exposure to lesional skin. This review addresses the mechanism, safety, application, and efficacy of the excimer laser for the treatment of these conditions.

Evaluation of a Genetic Risk Score for Diagnosis of Psoriatic Arthritis.

BACKGROUND: Diagnosis of psoriatic arthritis (PsA) can be challenging, resulting in delays that contribute to irreversible joint damage, reduced quality of life, and increased mortality. OBJECTIVE: Use genetic markers to develop and evaluate a PsA genetic risk score (GRS) for its ability to discriminate between psoriasis (PsO) only and PsO with PsA among a psoriatic cohort with full genome-wide genotype data. METHODS: Genome-wide single-nucleotide polymorphism genotyping was performed on 724 psoriatic patients. A set of 11 candidate risk genes previously shown to be preferentially associated with PsO or PsA were selected. To evaluate the cumulative effects of these risk loci, a PsA GRS was developed using an unweighted risk allele count (cGRS) and a weighted (wGRS) approach. Additional analyses included only human leukocyte antigen (HLA) risk alleles. RESULTS: The discriminative power attributable to each GRS was evaluated by calculating the areas under the receiver operator characteristic curve (AUROC). The AUROC for the wGRS is 56.2% versus 54.1% for the cGRS, and the AUROC for the HLA-only wGRS model was 56.9% versus 55.7% for the HLA-only cGRS. CONCLUSION: The AUROC of 56.9% for HLA-only wGRS indicates that this approach has the greatest power in discriminating PsA from PsO among these models. Given that an AUROC of 56.9% is quite modest, this study suggests that using a small number of well-validated genetic loci provides limited predictive power for PsA, and that future approaches may benefit from using a larger number of genetic loci.

Implementation of an Ultraviolet Phototherapy Service at a National Referral Hospital in Western Kenya: Reflections on Challenges and Lessons Learned.

INTRODUCTION: In order to manage skin conditions at a national referral hospital level in Kenya, specialized dermatology services, such as dermatologic surgery, dermatopathology, phototherapy, and sub-specialty care, should be offered, as is typically available in referral hospitals around the world. A Kenyan patient with prurigo nodularis, whose severe itch remitted after phototherapy treatment at the University of California, San Francisco (UCSF), inspired the development of a phototherapy service at Academic Model Providing Access to Healthcare (AMPATH), a partnership in Western Kenya between Moi Teaching and Referral Hospital, Moi University College of Health Sciences, and a consortium of North American academic medical centers. METHODS: Initial project funds were raised through a crowdfunding campaign and fundraising events. A new narrowband ultraviolet B phototherapy unit and replacement bulbs were donated and air shipped to Eldoret, Kenya. A team of dermatologists and phototherapy nurses from UCSF conducted a 2-day training session. US-based dermatologists affiliated with AMPATH provide ongoing support through regular communication and on-site visits. RESULTS: Early in implementation, challenges faced included training clinical staff with limited experience in phototherapy and improving communication between nurses and clinicians. More recent challenges include frequent rotation of specialty clinic nurses in the dermatology clinic, adaptation of phototherapy guidelines to balance patient volume with service delivery capacity, and training assessment of disease activity in darkly pigmented skin. CONCLUSION: Strategies that have been helpful in addressing implementation challenges include: increasing on-site and remote training opportunities for clinicians and nurses, developing a tiered payment schema, educating patients to combat misconceptions about phototherapy, dynamic phototherapy referral guidelines to accommodate service delivery capacity, and prioritizing the engagement of a multidisciplinary team.

Evaluating guselkumab: an anti-IL-23 antibody for the treatment of plaque psoriasis.

The approval of guselkumab marks the entry of the IL-23 inhibitor class into the therapeutic armamentarium for patients with moderate-to-severe plaque psoriasis. This class specifically targets the upstream portion of the type 17 helper T (Th17) axis, which has been implicated as a key driver of the abnormal inflammatory state observed in psoriasis. Guselkumab is highly efficacious, with over 85% of the patients achieving ≥75% reduction in Psoriasis Area and Severity Index from baseline (PASI 75) and over 70% of the patients achieving PASI 90 response in its Phase III clinical trials. Additionally, this medication is well-tolerated, with non-serious infections such as nasopharyngitis and upper respiratory infections (URIs) being the most common adverse events (AEs) reported in its clinical trials. Guselkumab offers yet another effective treatment option in the rapidly growing list of available biological therapies for moderate-to-severe plaque psoriasis.

A review of dupilumab in the treatment of atopic diseases.

Dupilumab is a fully human monoclonal IgG4 antibody directed against the alpha subunit of the IL-4 receptor and prevents the signaling of IL-4 and IL-13, two type 2 cytokines known to be important drivers of atopic diseases. In March of 2017, the United States Food and Drug Administration (FDA) approved dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults that is uncontrolled with topical medications, becoming the first biologic agent approved to treat this chronic skin condition. In October of 2018, Dupilumab received approval by the FDA as an add-on maintenance therapy in patients with moderate-to-severe asthma aged 12 years or older with an eosinophilic phenotype or with oral corticosteroid-dependent asthma. This review summarizes the characteristics of dupilumab and the clinical research that has been published to date, including treatment efficacy and adverse events.

Home phototherapy for patients with vitiligo: challenges and solutions.

Vitiligo is a chronic autoimmune condition involving selective dysfunction and destruction of melanocytes in the skin, hair, or both. The typical presentation is well-demarcated depigmented skin patches. Given vitiligo is the most common cause of depigmentation worldwide and early disease responds best to treatment, prompt diagnosis and proactive management of vitiligo are critical. While a wide variety of treatments has demonstrated variable effectiveness in treating vitiligo, phototherapy remains standard of care because of its proven efficacy and favorable side effect profile. However, many patients with vitiligo are unable to access affordable, consistent, or convenient phototherapy. To address these issues, home-based phototherapy has emerged as a patient-centered alternative. The purpose of this review is to discuss management of vitiligo with a specific focus on access to home-based phototherapy (HBPT) for patients with this condition. Key challenges to HBPT include misperceptions around safety and efficacy, inadequate physician education and training, insurance and financial barriers, and appropriate patient selection. Solutions to these challenges are presented, such as approaches to improve physician education and increasing the evidence surrounding the effectiveness and safety of this treatment for vitiligo. In addition, various practical considerations are discussed to guide dermatologists on how to approach HBPT as a treatment option for patients with vitiligo.

Diagnosis and screening of patients with generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening variant of psoriasis that is characterized by recurrent, acute onset, widely distributed pustular eruptions on inflamed, erythematous skin. It is important to recognize acute GPP as a subtype of psoriasis associated with high morbidity and mortality so therapy can be initiated without delay. Since GPP was first described in 1910 by Leopold von Zumbusch, it has been inconsistently defined, stratified, and diagnosed in the literature. Multiple definitions and diagnostic criteria have been proposed over the years. Recently, formal consensus guidelines on GPP have been published by international groups. This article reviews the current evidence and understanding in the diagnosis and screening of GPP.

Acrodermatitis continua of Hallopeau: clinical perspectives.

Acrodermatitis continua of Hallopeau (ACH) is a rare, sterile pustular eruption of one or more digits. The condition presents with tender pustules and underlying erythema on the tip of a digit, more frequently arising on a finger than a toe. As far as classification, ACH is considered a localized form of pustular psoriasis. The eruption typically occurs after local trauma or infection, but such a history is not always present and various other etiologies have been described including infectious, neural, inflammatory, and genetic causes. The natural progression of ACH is chronic and progressive, often resulting in irreversible complications such as onychodystrophy that can result in anonychia, as well as osteitis that can result in osteolysis of the distal phalanges. Because of the rarity of ACH, there have been no randomized controlled studies to evaluate therapies, resulting in an absence of standardized treatment guidelines. In clinical practice, a wide variety of treatments have been attempted, with outcomes ranging from recalcitrance to complete resolution. In recent years, the introduction of biologics has provided a new class of therapy that has revolutionized the treatment of ACH. Specifically, rapid and sustained responses have been reported with the use of anti-tumor necrosis factor agents like infliximab, adalimumab, and etanercept; IL-17 inhibitors like secukinumab; IL-12/23 inhibitors like ustekinumab; and IL-1 inhibitors like anakinra. Nevertheless, there remains a considerable need for more research into treatment for the benefit of individual patients with ACH as well as for the clinical knowledge gained by such efforts. The purpose of this review is to provide a comprehensive overview of the key features of ACH as well as a discussion of clinical management strategies for this unique and debilitating condition.

Anti IL-17 in psoriasis.

Introduction: Psoriasis is a chronic, immune-mediated disease with significant associated comorbidities. Its pathogenesis is likely multifactorial, however, the interleukin-23/T helper 17 pathway has been identified as a critical axis in its pathogenesis. Interleukin-17A is the primary effector of this pathway and overexpression of IL-17A results in epidermal hyperplasia and an overly robust inflammatory response, resulting in the skin plaques and systemic inflammation seen in psoriasis. Targeted anti IL-17 therapies have demonstrated efficacy in the treatment of moderate-to-severe plaque psoriasis.Areas covered: A PubMed search was conducted for relevant literature. Secukinumab, ixekizumab, and brodalumab are anti IL-17 inhibitors currently approved for the treatment of moderate-to-severe plaque psoriasis. The efficacy and safety data from key phase III clinical trials are reviewed here.Expert opinion: By targeting a key mediator of the interleukin-23/T helper 17 pathway, IL-17 antagonists are an effective treatment for plaque psoriasis. It has demonstrated efficacy and a favorable safety profile in key phase III clinical trials. In addition to efficacy, IL-17 antagonists have also shown long-term maintenance of treatment response and a quick onset of action. The efficacy of IL-17 inhibitors in the treatment of moderate-to-severe psoriasis underscores the importance of the IL-23/Th17 pathway in the pathogenesis of psoriasis.

Tofacitinib in the management of active psoriatic arthritis: patient selection and perspectives.

Tofacitinib is an oral Janus kinase inhibitor approved for the treatment of psoriatic arthritis (PsA). It provides an alternative option for patients who have had an inadequate response and tolerance to other disease modifying antirheumatic drugs (DMARDs). It has demonstrated comparable efficacy to biologics, is effective in the management of treatment resistant disease, and is reported to improve enthesitis, dactylitis, and radiographic progression. Tofacitinib is also associated with an increased risk of serious infections, malignancy, and laboratory abnormalities. There is currently a large armamentarium of therapies for psoriatic arthritis, and choosing among treatments can be challenging. Due to this wide selection, a thorough assessment of psoriatic disease phenotype, patient preference, disease presentation, and comorbidities is critical. This review addresses key considerations in patient selection for the treatment of PsA with tofacitinib.

Emerging Methods to Objectively Assess Pruritus in Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is an inflammatory skin disease with a chronic, relapsing course. Clinical features of AD vary by age, duration, and severity but can include papules, vesicles, erythema, exudate, xerosis, scaling, and lichenification. However, the most defining and universal symptom of AD is pruritus. Pruritus or itch, defined as an unpleasant urge to scratch, is problematic for many reasons, particularly its negative impact on quality of life. Despite the profoundly negative impact of pruritus on patients with AD, clinicians and researchers lack standardized and validated methods to objectively measure pruritus. The purpose of this review is to discuss emerging methods to assess pruritus in AD by describing objective patient-centered tools developed or enhanced over the last decade that can be utilized by clinicians and researchers alike. METHODS: This review is based on a literature search in Medline, Embase, and Web of Science databases. The search was performed in February 2019. The keywords were used "pruritus," "itch," "atopic dermatitis," "eczema," "measurements," "tools," "instruments," "accelerometer," "wrist actigraphy," "smartwatch," "transducer," "vibration," "brain mapping," "magnetic resonance imaging," and "positron emission tomography." Only articles written in English were included, and no restrictions were set on study type. To focus on emerging methods, prioritization was given to results from the last decade (2009-2019). RESULTS: The search yielded 49 results in PubMed, 134 results in Embase, and 85 results in Web of Science. Each result was independently reviewed in a standardized manner by two of the authors (M.S., K.L.), and disagreements between reviewers were resolved by consensus. Relevant findings were categorized into the following sections: video surveillance, acoustic surveillance, wrist actigraphy, smart devices, vibration transducers, and neurological imaging. Examples are provided along with descriptions of how each technology works, instances of use in research or clinical practice, and as applicable, reports of validation studies and correlation with other methods. CONCLUSION: The variety of new and improved methods to evaluate pruritus in AD is welcomed by clinicians, researchers, and patients alike. Future directions include next-generation smart devices as well as exploring new territories, such as identifying biomarkers that correlate to itch and machine-learning programs to identify itch processing in the brain. As these efforts continue, it will be essential to remain patient-centered by developing techniques that minimize discomfort, respect privacy, and provide accurate data that can be used to better manage itch in AD.

Factors Influencing Sleep Difficulty and Sleep Quantity in the Citizen Pscientist Psoriatic Cohort.

INTRODUCTION: Sleep is essential for overall health and well-being, yet more than one-third of adults report inadequate sleep. The prevalence is higher among people with psoriasis, with up to 85.4% of the psoriatic population reporting sleep disruption. Poor sleep among psoriasis patients is particularly concerning because psoriasis is independently associated with many of the same comorbidities as sleep dysfunction, including cardiovascular disease, obesity, and depression. Given the high prevalence and serious consequences of disordered sleep in psoriasis, it is vital to understand the nature of sleep disturbance in this population. This study was designed to help meet this need by using survey data from Citizen Pscientist, an online patient portal developed by the National Psoriasis Foundation. METHODS: Our analysis included 3118 participants who identified as having a diagnosis by a physician of psoriasis alone or psoriasis with psoriatic arthritis. Demographic information, psoriasis severity and duration, sleep apnea status, smoking and alcohol consumption, itch timing, and sleep characteristics were included. Two separate multivariate logistic regression models in STATA were used to determine whether the presence of psoriatic arthritis, age, gender, body mass index, comorbid sleep apnea, psoriasis severity, timing of worst itch, smoking status, or high-risk alcohol consumption were associated with sleep difficulty or low sleep quantity, defined by the American Academy of Sleep Medicine as less than 7 h of sleep per night on average. RESULTS: Results from the multivariate logistic regressions found that sleep difficulty was associated with psoriatic arthritis (OR 2.15, 95% CI [1.79-2.58]), female gender (2.03 [1.67-2.46]), obese body mass index (BMI ≥ 30) (1.25 [1.00-1.56]), sleep apnea (1.41 [1.07-1.86]), psoriasis severity of moderate (1.59 [1.30-1.94]) or severe (2.40 [1.87-3.08]), and smoking (1.60 [1.26-2.02]). Low sleep quantity was associated with obese BMI (1.62 [1.29-2.03]), sleep apnea (1.30 [1.01-1.68]), psoriasis severity of moderate (1.41 [1.16-1.72]) or severe (1.40 [1.11-1.76]), and smoking (1.62 [1.31-2.00]). Sleep difficulty and low sleep quantity were not associated with age, alcohol consumption, or timing of worst itch. CONCLUSION: These results are potentially meaningful in several aspects. We identify an important distinction between sleep difficulty and sleep quantity in psoriatic disease, whereby having psoriatic arthritis and being female are each associated with sleep difficulty despite no association with low sleep quantity. Furthermore, there is conflicting evidence from prior studies as to whether psoriasis severity is associated with sleep difficulty, but this well-powered, large study revealed a strong, graded relationship between psoriasis severity and both sleep difficulty and low sleep quantity. Overall, our results show that both sleep difficulty and low sleep quantity were associated with multiple factors in this analysis of a large psoriatic cohort. These findings suggest that dermatologists may gather clinically useful information by screening psoriatic patients for trouble sleeping and low sleep quantity to identify potential comorbidities and to more effectively guide disease management.

Review of the regulation and safety assessment of food substances in various countries and jurisdictions.

This review compares the regulations, definitions and approval processes for substances intentionally added to or unintentionally present in human food in the following specific countries/jurisdictions: Argentina, Australia, Brazil, Canada, China, the European Union, Japan, Mexico, New Zealand, and the United States. This includes direct food additives, food ingredients, flavouring agents, food enzymes and/or processing aids, food contact materials, novel foods, and nanoscale materials for food applications. The regulatory authority of each target jurisdiction/country uses its own regulatory framework and although the definitions, regulations and approval processes may vary among all target countries, in general there are many similarities. In all cases, the main purpose of each authority is to establish a regulatory framework and maintain/enforce regulations to ensure that food consumed and sold within its respective countries is safe. There is a move towards harmonisation of food regulations, as illustrated by Australia and New Zealand and by Mercosur. The European Union has also established regulations, which are applicable for all member states, to establish a common authorisation procedure for direct food additives, flavourings and enzymes. Although the path for approval of different categories of food additives varies from jurisdiction to jurisdiction, there are many commonalities in terms of the data requirements and considerations for assessment of the safety of use of food additives, including the use of positive lists of approved substances, pre-market approval, and a separation between science and policy decisions. The principles applied are largely reflective of the early work by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) committees and JECFA assessments of the safety of food additives for human and animal foods.