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.

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.

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.

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.

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.

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.

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.

Sunscreen: FDA regulation, and environmental and health impact.

Photoprotection, including the use of sunscreen, has been shown to decrease the development of keratinocyte cancers and melanoma. Due to concerns about the environmental effects of some organic UVR filters, several locations across the world have begun to pass legislation banning the use of these ingredients in sunscreens. Furthermore, the health effects of several organic UVR filters have also been called into question and a recent proposal by the US FDA has resulted in public confusion about the safety of sunscreens. The aim of this article is to discuss FDA regulation of sunscreens and to review the environmental and health effects of oxybenzone and octinoxate. Ultimately, as dermatologists, our recommendations are to continue to encourage people to practice proper photoprotection including photoprotective clothing, staying in the shade while outdoors, and applying sunscreen to exposed areas. For those concerned about the potential environmental and health effects of organic UVR filters, inorganic/mineral UVR filter (namely, zinc oxide and titanium dioxide)-based sunscreens can be used.

Visible light in photodermatology.

Until recently, visible light (VL) had been regarded to be without significant photobiologic effect on the skin. Updated research suggests that this is not the case and the measurable effect of visible light on the skin is being documented in all skin types. Recent studies have demonstrated that in dark-skinned individuals, visible light can induce more intense and longer lasting pigmentation of the skin compared to UVA1. This effect was potentiated when VL was combined with a small percentage of ultraviolet A1 radiation (UVA1). Further, the combination of VL + UVA1 was also able to induce erythema in light-skinned individuals, a novel finding since the erythemogenic spectrum of sunlight had primarily been attributed to ultraviolet B (UVB) and short wavelength UVA (320-340 nm). Based on these findings, VL and UVA1 may also potentially play a role in conditions aggravated by sun exposure such as phototoxicity in light-skinned patients and post-inflammatory hyperpigmentation and melasma, especially in dark-skinned individuals. Currently available organic (chemical) UV filters are not sufficient to protect the skin from the effect of VL. VL is emerging as a key player in photodermatology and additional research is needed on the cutaneous effects of VL, as well as the development of filters and other means of photoprotection against the harmful effects of the VL spectrum. The aim of this manuscript is to review the literature on the cutaneous effects of VL as well as to highlight areas of dermatology where VL may play an important role.

Ultraviolet-C and other methods of decontamination of filtering facepiece N-95 respirators during the COVID-19 pandemic.

During global health emergencies such as the current COVID-19 pandemic, the decontamination of single-use personal protective equipment (PPE) becomes a necessary means to keep up with the growing demand from healthcare workers and patients alike. Many unverified methods are being considered, which can pose the risk of incomplete decontamination and lead to catastrophic results. Several factors come into play when determining the suitability of such methods including the quality of the decontamination technique, the targeted pathogen, cost, ease of installation and use, rate of sterilization, and the surface or material to be sterilized. The germicidal properties of ultraviolet-C are well known. This review will cover the most commonly described methods for the sterilization of N95 respirators, namely, ultraviolet germicidal irradiation, hydrogen peroxide vaporization, microwave-generated steaming, and dry heating. These techniques have been tested previously and have demonstrated efficacy in reducing or inactivating viral and bacterial pathogens, although testing against SARS-CoV-2 specifically has not been done. Moreover, it must be emphasized that proper disposal after a single use is still ideal under normal circumstances.

Spectrum of virucidal activity from ultraviolet to infrared radiation.

The COVID-19 pandemic has sparked a demand for safe and highly effective decontamination techniques for both personal protective equipment (PPE) and hospital and operating rooms. The gradual lifting of lockdown restrictions warrants the expansion of these measures into the outpatient arena. Ultraviolet C (UVC) radiation has well-known germicidal properties and is among the most frequently reported decontamination techniques used today. However, there is evidence that wavelengths beyond the traditional 254 nm UVC - namely far UVC (222 nm), ultraviolet B, ultraviolet A, visible light, and infrared radiation - have germicidal properties as well. This review will cover current literature regarding the germicidal effects of wavelengths ranging from UVC through the infrared waveband with an emphasis on their activity against viruses, and their potential applicability in the healthcare setting for general decontamination during an infectious outbreak.

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.

Associations of pemphigus or pemphigoid with autoimmune disorders in US adult inpatients.

BACKGROUND: The associations and predictors of the gamut of autoimmune conditions in pemphigus and pemphigoid have been examined in few large-scale controlled studies. OBJECTIVE: To examine associations of pemphigus or pemphigoid with autoimmune disorders and related outcomes in adults. METHODS: Data from the 2002-2012 National Inpatient Sample were analyzed, including an ∼20% sample of all US hospitalizations (n = 72,108,077 adults). RESULTS: In multivariable logistic regression models, pemphigus (adjusted odds ratio 1.46, 95% confidence interval 1.30-1.63) and pemphigoid (adjusted odds ratio 1.35, 95% confidence interval 1.24-1.48) were associated with ≥1 autoimmune disorder. Pemphigus was associated with 9 of 29 and pemphigoid with 13 of 32 autoimmune disorders examined in bivariable models. Among pemphigus inpatients, unspecified autoimmune disease, vitiligo, eosinophilic esophagitis, and myasthenia gravis had the strongest effect sizes. Whereas, among pemphigoid inpatients, unspecified autoimmune disease, vitiligo, and chronic urticaria had the strongest effect sizes. There were significant differences of autoimmune comorbidities by age, sex, and race/ethnicity. The estimated excess annual costs of hospital care attributed to autoimmune disorders among inpatients with pemphigus was $2,286,588 and pemphigoid $4,301,681. LIMITATION: Lack of treatment history data. CONCLUSION: Inpatients with pemphigus or pemphigoid had increased odds of multiple cutaneous, extracutaneous, and systemic autoimmune disorders, which were associated with a considerable cost burden.

Association between atopic dermatitis and autoimmune disorders in US adults and children: A cross-sectional study.

BACKGROUND: Little is known about the risk and predictors of autoimmune diseases in children and adults. OBJECTIVE: To determine the prevalence, predictors, and excess costs of autoimmune disease in atopic dermatitis (AD) patients. METHODS: Cross-sectional study of the 2002-2012 National Inpatient Sample, which includes a ∼20% sample of all US hospitalizations (n = 87,053,155 adults and children). RESULTS: The prevalence of autoimmune disease was higher in adults with AD (7.9%, 95% confidence interval [95% CI] 7.3-8.5%) than without AD (5.7%, 95% CI 5.7%-5.8%) and higher in children with AD (2.0%, 95% CI 1.7%-2.3%) than without AD (1.0%, 95% CI 0.9%-1.1%). In multivariable logistic regression models controlling for sociodemographics, adult (adjusted odds ratio 1.45, 95% CI 1.32-1.58) and pediatric (adjusted odds ratio 2.08, 95% CI 1.73-2.50) AD were associated with any autoimmune disorder. In particular, AD was associated with 18 of 32 autoimmune disorders examined in adults and 13 of 24 examined in children, including disorders of the skin, endocrine, gastrointestinal, hematologic, and musculoskeletal systems. AD patients hospitalized with any autoimmune disorder had a higher cost of inpatient care, with $2.5-$50 million excess annual costs. CONCLUSIONS: Adults and children with AD had increased cutaneous and extracutaneous autoimmune disorders, which were associated with a considerable cost burden.

Association between atopic dermatitis and serious cutaneous, multiorgan and systemic infections in US adults.

BACKGROUND: Atopic dermatitis (AD) is associated with barrier disruption, immune dysregulation, and immunosuppressing treatments that can increase the association with an unusual number of infections. OBJECTIVE: To determine whether adults with AD have an unusually large number of serious infections and related outcomes. METHODS: Data from the 2002 to 2012 National Inpatient Sample were analyzed, including an approximately 20% sample of all US hospitalizations (n = 72,108,077 adults). Prevalence of serious infections in hospitalized patients with vs without AD, length of stay, cost of care, and inpatient mortality secondary to serious infections were determined. RESULTS: The prevalence of serious infections expressed as a percentage (95% confidence interval) was higher in adults hospitalized with than in those without AD (42.1% [41.6-42.6] vs 25.4% [25.2-25.6]; P = .0002). In logistic regression models with multiple predictors (multivariable logistic regression models), AD was associated with 32 of 38 infections examined. Associated cutaneous infections included eczema herpeticum (odds ratio [95% confidence interval] adjusted for other predictors: 67.93 [47.93-96.28]), erysipelas (11.15 [9.47-13.1]), and cellulitis (4.53 [4.42-4.64]). Associated respiratory infections included aspergillosis (1.51 [1.21-1.88]) and tuberculosis (1.57 [1.41-1.76]). AD was associated with extracutaneous, multiorgan, and systemic infections, including infectious arthropathy (2.01 [1.84-2.20]), endocarditis (1.25 [1.12-1.39]), encephalitis (1.65 [1.40-1.96]), and methicillin-resistant Staphylococcus aureus infections (3.29 [3.17-3.42]). Patients with AD hospitalized with vs without any serious infection had an increased geometric mean cost of inpatient care ($8,273 [8,126-8,423] vs $7,179 [7,052-7,307]) and length of stay (5.3 days [5.2-5.3] vs 3.9 [3.9-4.0]; P = .0002), with $11 to $228 million excess annual costs from hospitalization with serious infections in adults with AD. CONCLUSION: Adults with AD had increased cutaneous, respiratory, multiorgan, and systemic infections, which were associated with a considerable cost burden.

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.