Expert Recommendations on Use of Topical Therapeutics for Vitiligo in Pediatric, Adolescent, and Young Adult Patients.

Importance: Evidence-based recommendations for the treatment of vitiligo in pediatric, adolescent, and young adult patients in the US are needed. Objective: To develop evidence- and consensus-based expert recommendations on the diagnosis and treatment of vitiligo in young patients. Evidence Review: A process was developed to produce consensus recommendations addressing questions regarding pediatric vitiligo. A librarian-conducted literature review was performed using articles that met the inclusion criteria: published in English, containing primary data (including meta-analysis) and pediatric-specific data, and analysis of 6 or more patients. Included articles were graded by the Strength of Recommendation Taxonomy criteria and Oxford Centre for Evidence-based Medicine's Levels of Evidence and Grades of Recommendation. Research questions were reviewed on May 9, 2022, through a video conference. One month after the conference, participants participated in an online survey documenting their level of agreement with the generated statements, using a 5-point Likert scale. Findings: Articles on topical corticosteroids and/or topical calcineurin inhibitors (n = 50), topical Janus kinase inhibitors (n = 5), pseudocatalase (n = 2), and microdermabrasion (n = 2) met inclusion criteria. Forty-two recommendations were made on the diagnosis of vitiligo and optimal topical therapeutics, with 33 recommendations obtaining a 70% or greater composite agreement and strong agreement. Topical calcineurin inhibitors twice daily, topical corticosteroids with time limitation due to atrophy risk, and topical ruxolitinib, 1.5%, cream-used off-label for patients younger than 12 years and limited to nonsegmental vitiligo-were identified as evidence-based first-line therapies in the management of pediatric and adolescent patients, with specific guidance on age-based data, minimum therapeutic trial of 6 months or greater, prolonged therapy to prevent recurrence, and the positive benefit of coordinated use of UV therapeutic sources. Conclusions and Relevance: Evidence supports the use of topical calcineurin inhibitors, topical corticosteroids, and topical Janus kinase inhibitors as effective therapeutics for vitiligo in pediatric, adolescent, and young adult patients, with specific decisions on choice of agent based on factors such as site location, body surface area, and age.

Efficacy and Risk Stratification of Janus Kinase Inhibitors in the Treatment of Moderate-to-Severe Atopic Dermatitis.

Recently, 3 oral Janus kinase (JAK) inhibitors-abrocitinib, baricitinib, and upadacitinib-were approved in many regions around the world for the treatment of moderate-severe atopic dermatitis (AD). These JAK inhibitors generally have rapid onset of action and short half-life. Higher doses of abrocitinib and upadactinib even demonstrated superior efficacy to dupilumab. However, JAK inhibitors can be associated with rare serious and potentially life-threatening adverse events. Heterogeneity in study designs and lack of head-to-head studies make safety comparison between JAK inhibitors difficult. Dose reduction and patient selection are the most important considerations for risk mitigation. This narrative review examines the efficacy data for abrocitinib, baricitinib, and upadacitinib from large phase III double-blinded randomized controlled trials in AD and discusses risk stratification for oral JAK inhibitors in AD patients.

Which Clinical Measurement Tools for Atopic Dermatitis Severity Make the Most Sense in Clinical Practice?

Assessment of atopic dermatitis (AD) severity is essential for therapeutic decision making and monitoring treatment progress. However, there are a myriad of clinical measurement tools available, some of which are impractical for routine clinical use despite being recommended for clinical trials in AD. For measurement tools to be used in clinical practice, they should be valid, reliable, rapidly completed, and scored, and easily incorporated into existing clinic workflows. This narrative review addresses content, validity, and feasibility, and provides a simplified repertoire of assessments for clinical assessment of AD based on prior evidence and expert opinion. Tools that may be feasible for clinical practice include patient-reported outcomes (eg, dermatology life quality index, patient-oriented eczema measure, numerical rating scales for itch, pain, and sleep disturbance, AD Control Tool, and patient-reported global assessment), and clinician-reported outcomes (eg, body surface area and investigator's global assessment). AD is associated with variable clinical signs, symptoms, extent of lesions, longitudinal course, comorbidities, and impacts. Any single domain is insufficient to holistically characterize AD severity, select therapy, or monitor treatment response. A combination of these tools is recommended to balance completeness and feasibility.

Evaluation of the protection of sunscreen products against long wavelength ultraviolet A1 and visible light-induced biological effects.

BACKGROUND: Long wavelength ultraviolet-A1 in combination with visible light induces hyperpigmentation, particularly in dark-skin phototypes. This study evaluated the efficacy of four sunscreen formulations in protecting against VL + UVA1 (370-700 nm). METHODS: The test products (A-D) were applied to the back of 12 volunteers, then irradiated with 320 J/cm2 VL + UVA1 (3.5% UVA1 [370-400 nm]). Immediately after irradiation, and at Days 1, 7, and 14, erythema and pigmentation were assessed by investigator global assessment (IGA), colorimetry (Δa* and ΔITA) and diffuse reflectance spectroscopy (DRS)-measured relative dyschromia (area under the curve AUC). Control areas were irradiated without sunscreen. RESULTS: Product D, containing titanium dioxide 11%, iron oxides 1%, and antioxidants, provided the highest and most consistent protection. Compared with unprotected irradiated control, it had statistically significantly less erythema on IGA, DRS (Δoxyhemoglobin), and colorimetry (Δa*) at Day 0; less pigmentation on IGA at all time points, on DRS (relative dyschromia) at Days 7 and 14, and on colorimetry (ΔITA) at Day 0. Product B, containing zinc oxide 12% plus organic UV filters, iron oxides 4%, and antioxidants, also showed some efficacy. CONCLUSION: Of the sunscreens tested, the tinted products provided better protection against VL + UVA1 than the non-tinted products. Since the product with 1% iron oxides was superior to the product with 4% iron oxides, further studies are needed to evaluate whether iron oxide content correlates with better protection.

Comparing Follicular Extension Between Low-Grade and High-Grade Dysplastic Nevi.

ABSTRACT: Dysplastic nevi are an important subset of melanocytic nevi with atypical clinical, histopathologic, as well as genomic features compared with common acquired nevi. Dysplastic nevi are characterized histologically by both cytologic atypia and architectural disorder. The established criteria for cytologic atypia used to distinguish between low-grade and high-grade dysplastic nevi are often subjective, although there is a dearth of more objective, reproducible features of architectural disorder (eg, pagetoid scatter) that have been validated to differentiate between low-grade and high-grade dysplastic nevi. In this study, we sought to determine whether the presence and degree of follicular extension differ between low-grade and high-grade dysplastic nevi. We retrospectively examined the histopathologic features of 90 dysplastic nevi: 60 cases of low-grade dysplastic nevi (average age of 47.2 ± 18.1 years; 62.7% female) and 30 cases of high-grade dysplastic nevi (average age of 47.4 ± 19.8 years; 60.0% female). After examination, 50% of the cases of dysplastic nevi (n = 45) had hair follicles within the lesion, for which the presence and degree of follicular extension was then determined. Low-grade and high-grade dysplastic nevi do not differ significantly regarding the presence of follicular extension, average depth of follicular extension, and confluence of nevus cells along the follicular epithelium. Both low-grade and high-grade dysplastic nevi in our study demonstrated follicular extension that was superficial, that is, above the level of isthmus of hair follicles (insertion of sebaceous gland into hair follicle). Future studies are warranted to confirm these preliminary findings.

Safety of Oral Janus Kinase Inhibitors in the Treatment of Moderate-to-Severe Atopic Dermatitis.

Multiple Janus Kinase (JAK) inhibitors were developed as potential treatments for moderate-to-severe atopic dermatitis (AD). There is a substantial amount of safety data from recent trials of oral JAK inhibitors in patients with AD. However, the vast majority of safety data for oral JAK inhibitors is derived from patients with rheumatoid arthritis and other immune-mediated disorders, and is primarily derived from tofacitinib, a pan-selective JAK inhibitor. This narrative review examines safety data for oral JAK inhibitors from studies in AD and other indications. The available data do demonstrate that rare but serious and life-threatening adverse events can occur with oral JAK inhibitor treatment and should be carefully considered in therapeutic shared decision making.

Systematic review of photodynamic therapy for the treatment of hidradenitis suppurativa.

OBJECTIVE: To perform a systematic review of available literature regarding the use of 5-aminolevulinic acid (ALA) and ALA derivative photodynamic therapy (PDT) in the treatment of hidradenitis suppurativa (HS) and provide recommendations on its use. METHODS: A systematic review was performed of all published studies up to September 1, 2019 from nine databases, including PubMed, that evaluated PDT in the treatment of HS. For each study, quality of evidence and risk of bias was evaluated. Recommendations from the body of evidence were created based on Strength of Recommendation and Taxonomy (SORT) criteria. RESULTS: Eighteen studies met inclusion criteria. The majority of studies had a high risk of bias. Blue light PDT with 20% ALA and red light PDT with 16% methyl aminolevulinate (MAL) demonstrated some benefit based on a small number of poor-quality studies with a high risk of bias (Grade C, level III evidence). The most promising results were for 1%-5% ALA with intralesional diode, with good to complete response in 78%-94% of anatomic sites treated (Grade B, level II evidence). LIMITATIONS: The majority of studies contained high levels of bias, with significant heterogeneity between studies. Conclusions are limited by small samples sizes, lack of randomized controlled trials, and differing protocols. CONCLUSION: Further studies are needed to determine the clinical efficacy of 20% ALA with blue light and MAL with red light. Intralesional diode PDT shows the most promise and warrants further investigation in larger, randomized controlled trials.

Racial disparities in dermatology.

Significant racial/ethnic disparities in dermatologic care and their subsequent impact on dermatologic conditions were recently reported. Contributing factors include socioeconomic factors, gaps in educational exposure, and underrepresentation of minority groups in the dermatologic workforce. In 2021, the American Academy of Dermatology (AAD) announced its three-year plan to expand diversity, equity, and inclusion in dermatology. One way to reduce disparities in dermatology is for every dermatologist, regardless of race or ethnicity, to receive adequate education in diseases, treatments, health equity, and tailored approaches to delivering dermatologic care with cultural humility. In addition, a diverse dermatologic workforce-especially at the level of residency program educators and organizational leaders-will contribute to improved cross-cultural understanding, more inclusive research efforts, and improved treatment approaches for conditions that are more prevalent or nuanced in certain racial/ethnic populations. Finally, the dermatology and broader healthcare community needs to acknowledge and educate ourselves on the health impacts of racism.

Safety and Efficacy of Intense Pulsed Light With Radiofrequency in United States Hidradenitis Suppurativa Patients.

Copy: The combination of intense pulsed light and radiofrequency has been described in German populations to be a noninvasive therapy option for patients with hidradenitis suppurativa, demonstrating significant improvements in the quality of life and reduction in number of inflammatory lesions. OBJECTIVE: To evaluate the efficacy and safety of combination intense pulsed light and radiofrequency therapy in patients with hidradenitis suppurativa in the United States. METHODS: A prospective split body was conducted in the United States on patients with bilateral hidradenitis suppurativa. Subjects received 3 passes of intense pulsed light and radiofrequency per treatment session to a single involved body region on a randomized side of the body at least 2 weeks apart over 9 to 10 treatment sessions. RESULTS: When measured from baseline to final visit, the overall mean difference in Dermatology Life Quality Index was found to be statistically significant (-2.8, P=0.043, n = 9). Patients reported mild discomfort during therapy and no adverse events occurred during or after treatment sessions. CONCLUSIONS: Although statistically significant, the mean difference in Dermatology Life Quality Index in treated patients found in this study did not reach the minimal clinically important difference for inflammatory skin disease. J Drugs Dermatol. 2022;21(4):430-432. .doi:10.36849/JDD.6562.

The suitability of treating atopic dermatitis with Janus kinase inhibitors.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease with significant morbidity and reduced quality of life, especially in patients with moderate-severe AD. Recently, topical and oral Janus kinase (JAK)-inhibitors were investigated as treatments for mild-moderate and moderate-severe AD. However, rare serious adverse-events observed with JAK-inhibitor therapy in AD, rheumatoid arthritis, and other immune-mediated disorders warrant careful consideration. AREAS COVERED: This review examines the efficacy and safety of topical and oral JAK-inhibitors for treatments in AD, and reviews potential applications in AD. EXPERT OPINION: JAK-inhibitors have rapid-onset and robust and durable efficacy, which give them considerable versatility for treating the gamut of AD patients. While the U.S. Food and Drug Administration has only approved upadacitinib and abrocitinib to treat moderate-severe AD refractory to treatment with other systemic medications including biologics, or when use of those therapies is not recommended, oral JAK-inhibitors have the potential to be used both as first-line or second-line systemic therapies in moderate-severe AD. However, oral JAK-inhibitors can lead to laboratory anomalies and rare serious adverse events. All of these important characteristics should be addressed in shared-decision-making conversations, patient counseling, choosing appropriate therapies for patients, and monitoring patients in clinical practice.

The inpatient burden of pyoderma gangrenosum and associated comorbidities in children in the United States.

Pyoderma gangrenosum is an ulcerating inflammatory condition defined pathologically by an abundance of neutrophils in the absence of infection. Often, hospital admission is necessary for rapidly progressing PG for wound care and adequate pain control. However, few large-scaled controlled studies exist examining hospitalizations for PG in the pediatric populations and the associated comorbidities. We sought to determine the prevalence, length of stay (LOS), cost of care, and any risk factors for admission and associated comorbidities in children hospitalized for PG in the U.S. Data were analyzed from the 2002 to 2012 National Inpatient Sample, including a 20% representative sample of all hospitalizations in the United States. The prevalence of hospitalization between 2002 and 2012 ranged from 2 to 11 per million hospitalized children. Hospitalization for PG was associated with older age, female gender, black race/ethnicity, the third quartile for household income, having 2-5 chronic conditions, being admitted to a micropolitan or a non-metro/micropolitan hospital and to a teaching hospital. Hospitalization with vs. without a primary diagnosis of PG was associated with significantly prolonged LOS. The total inflation-adjusted cost of care for hospitalization with a primary diagnosis of PG was $2,202,576; $200,234 per year). The geometric-mean cost of hospitalization was significantly higher in children with vs. without a primary diagnosis of PG. Children hospitalized for PG were found to have higher odds of thyroid disease, inflammatory bowel disease, hematologic malignancy, and other autoimmune disorders. While children are rarely hospitalized for PG, they have prolonged hospitalization, and clinical interventions need to be developed to prevent hospitalization for PG. Further, concomitant workup for other systemic comorbidities is also warranted at the time of diagnosis and throughout disease course.

The value of photomedicine in a global health crisis: Utilizing ultraviolet C to decontaminate N95 respirators during the COVID-19 pandemic.

One early problem during the height of the COVID-19 global pandemic, caused by severe acute respiratory syndrome 2 (SARS-CoV-2), was the shortage of personal protective equipment donned by healthcare workers, particularly N95 respirators. Given the known virucidal, bactericidal, and fungicidal properties of ultraviolet irradiation, in particular ultraviolet C (UVC) radiation, our photomedicine and photobiology unit explored the role of ultraviolet germicidal irradiation (UVGI) using UVC in effectively decontaminating N95 respirators. The review highlights the important role of photobiology and photomedicine in this pandemic. Namely, the goals of this review were to highlight: UVGI as a method of respirator disinfection-specifically against SARS-CoV-2, adverse reactions to UVC and precautions to protect against exposure, other methods of decontamination of respirators, and the importance of respirator fit testing.

Management of inadequate response and adverse effects to dupilumab in atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, skin pain, and sleep disturbances. Currently, dupilumab is the only systemic therapy and biologic medication approved by the United States Food and Drug Administration for moderate-to-severe AD in adults and children. There is a sparsity of literature available on determining treatment failure with dupilumab and the next steps health care providers can take to treat AD. Individual goals and quality of life and not just body surface area should be considered when defining treatment failure. Possible confounding dermatoses also should be ruled out. Early identification of dupilumab-induced adverse events is important. For most patients, dupilumab can be continued while treatment for the adverse event is initiated. Adjusting the frequency of dupilumab dosing also may be considered in some circumstances. Adjuvant therapies, such as methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, or phototherapy can be added but the safety and efficacy of these combination treatments are not known at this time.

Dermatology for the internist: optimal diagnosis and management of atopic dermatitis.

Internists are front-line health care providers that commonly provide the first encounter to patients for dermatological conditions, especially atopic dermatitis (AD). Internists need to be comfortable with managing mild-moderate AD in their practices. Criteria and guidelines established in dermatology literature are available to help the general practitioner diagnose and treat AD. AD is a systemic disease associated with multiple cutaneous and extra-cutaneous comorbidities that warrant screening by internists, especially mental health conditions. Environmental factors may play a role in the development or worsening of AD; however, there is currently no strong evidence to guide specific population- or clinic-based interventions for their avoidance. While food allergies are common in AD patients, the role of food allergens as an exacerbating factor for AD is controversial. Before starting any dietary modifications, careful evaluation should be performed by an allergist. If the patient is not well-controlled despite adequate topical therapies or is experiencing severe/worsening disease, early referral to dermatology is warranted to rule out confounding diagnoses and/or escalation to systemic therapies. Finally, it is important to recognise the racial disparities present in AD and address these when formulating treatment plans.Key messages:Confounding dermatoses, either instead of or in addition to AD, should be considered in treatment-refractory AD, and the appropriate workup may be initiated while awaiting dermatology referral.AD patients have multiple cutaneous and extra-cutaneous comorbidities that warrant screening by internists, especially mental health conditions.

Proceeding report of the Fourth Symposium on Hidradenitis Suppurativa Advances 2019.

The Fourth Annual Symposium on Hidradenitis Suppurativa (SHSA) took place on November 1-3, 2019, at the Westin Book Cadillac Hotel in Detroit, Michigan. This symposium was a joint meeting of the US Hidradenitis Suppurativa Foundation and the Canadian Hidradenitis Suppurativa Foundation. This cross-disciplinary meeting with experts from around the world was an opportunity to discuss the most recent advances in the study of hidradenitis suppurativa (HS) pathogenesis, clinical trials, classification, scoring systems, complementary/alternative medical treatments, diet, pain management, surgical and laser treatment, and ultrasonographic assessment. A special preconference workshop was held on the use of neodymium-doped yttrium-aluminum-garnet laser hair reduction, sinus tract deroofing, and carbon dioxide laser excision with ultrasonographic mapping and tumescent anesthesia for the treatment of HS. The focused workshops on establishing an HS clinic, setting up an HS support group, the Hidradenitis Suppurativa Prospective Observational Registry and Biospecimen Repository, and wound care were held during the meeting. A special program called HS Ambassadors was established for patients who may have questions about the conference presentations, and in addition, a meet and greet for patients and HS Ambassadors was arranged. To facilitate networking between those early in their careers and clinical and research experts, a mentoring reception was held.

Skin and eye protection against ultraviolet C from ultraviolet germicidal irradiation devices during the COVID-19 pandemic.

With the COVID-19 pandemic depleting personal protective equipment worldwide, various methods including ultraviolet C (UVC) germicidal irradiation (UVGI) have been implemented to decontaminate N95 filtering facepiece respirators. These devices pose a risk for UVC exposure to the operator with reported adverse effects generally limited to the eyes and skin. Our hospitals are currently using UVC devices for N95 decontamination with a few reported cases of face and neck erythema from exposure. Because sunscreens are designed and tested for UVA and UVB protection only, their effects on blocking UVC are largely unknown. Therefore, our objective was to determine if various sunscreens, UV goggles, and surgical mask face shields minimize UVC exposure from UVGI devices. Our study clearly demonstrated that healthcare workers responsible for the disinfection of PPE using UVGI devices should always at least utilize clear face shields or UV goggles and sunscreen to protect against side effects of UVC exposure.

The inpatient burden and comorbidities of pyoderma gangrenosum in adults in the United States.

Hospital admission is often necessary for management of pyoderma gangrenosum (PG), including wound care and pain control. No large-scale controlled studies examined the burden of hospitalization for PG. The objective of this study is to determine the prevalence, predictors, outcomes, and costs of hospitalization for PG in United States adults. Data were analyzed from the 2002 to 2012 National Inpatient Sample, including a 20% representative sample of United States hospitalizations. The prevalence of hospitalization for PG increased between 2002 and 2012. Primary admission for PG was associated with age 40-59 years, female sex, black race/ethnicity, second-quartile household income, public or no insurance, and multiple chronic conditions. PG admissions were more likely at teaching and medium or large hospitals. Geometric-mean length and cost of hospitalization were higher in inpatients with vs. without a primary diagnosis of PG. The majority of inpatients with PG were classified with minor (64.4%) or moderate (25.7%) likelihood of dying, but moderate (52.5%) and major (28.7%) loss of function. PG was associated with numerous other health disorders. The limitation of this study is the lack of data on PG treatment. This study demonstrated a substantial and increasing inpatient burden of PG in the United States, with considerable disability and mortality risk, multiple comorbid health disorders, and costs.

The Role of Environmental Exposures in Atopic Dermatitis.

PURPOSE OF REVIEW: Although genetic factors clearly play a role in the development of atopic dermatitis (AD), the recent dramatic increase in the prevalence of AD in low- and middle-income countries is not consistent with only a role of genetic factors. These findings strongly suggest that environmental factors may play an important role in the pathogenesis of AD. RECENT FINDINGS: We reviewed the role of gene-environment studies; in utero exposures including tobacco smoke, alcohol, maternal stress, various digestive supplements, and gestational diabetes; early-life exposures including diet, gut microbiota, antibiotics, and breastfeeding; climate including temperature, ultraviolet radiation exposure, and air pollution; and household products, indoor allergens, water hardness, pH, and skin microbiota and their effects on AD. Environmental factors definitely play a role in the pathogenesis of AD. However, identifying definitive factors continues to be difficult in the setting of conflicting evidence and the complex interactions between genotypes and the environment resulting in a multitude of AD phenotypes. All of the different environmental interactions discussed highlight the importance of intervening on multiple levels in a patient's environment to improve or even prevent AD symptoms. Further, the importance of modifying environmental factors early on in a person's life is demonstrated. When possible, all of these environmental factors should be considered in treating a patient with AD and the appropriate modifications should be made at population and individual levels.

The most recent advances in understanding and managing hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, and debilitating skin disease of the hair follicle unit that typically develops after puberty. HS has a significant negative impact on both the quality of life (QOL) of patients affected by this disease as well as family members and caregivers. However, the pathogenesis of HS is multifactorial and still remains to be fully elucidated, which makes the development of treatments difficult. The last 10 years have seen a surge in HS research, and many new findings have come to light, yet much more remains to be elucidated. Physicians must employ a multidisciplinary approach to maximally address all facets of HS. Clinical characteristics of the disease that differ between females and males as well as across different races and ethnic groups must be considered. Targeted topical, oral, and injectable therapies continue to be developed for HS as a greater understanding of the pathogenesis is reached. However, randomized controlled trials regarding dietary factors that may contribute to HS are needed to meet our patients' growing concerns and questions about the role of diet in HS pathogenesis. Finally, improved outcome measures are needed to standardize HS severity and grading between physicians and clinical trials, and a more diverse representation of HS populations is needed in clinical trials.