Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations.

BACKGROUND: Guidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology. OBJECTIVE: To produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD. METHODS: A multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group supported guideline development by performing systematic evidence reviews, facilitating guideline processes, and holding focus groups with patient and family partners. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed rating the certainty of evidence and strength of recommendations. Evidence-to-decision frameworks, subjected to public comment, translated evidence to recommendations using trustworthy guideline principles. RESULTS: The panel agreed on 25 recommendations to gain and maintain control of AD for patients with mild, moderate, and severe AD. The eAppendix provides practical information and implementation considerations in 1-2 page patient-friendly handouts. CONCLUSION: These evidence-based recommendations address optimal use of (1) topical treatments (barrier moisturization devices, corticosteroids, calcineurin inhibitors, PDE4 inhibitors [crisaborole], topical JAK inhibitors, occlusive [wet wrap] therapy, adjunctive antimicrobials, application frequency, maintenance therapy), (2) dilute bleach baths, (3) dietary avoidance/elimination, (4) allergen immunotherapy, and (5) systemic treatments (biologics/monoclonal antibodies, small molecule immunosuppressants [cyclosporine, methotrexate, azathioprine, mycophenolate, JAK inhibitors], and systemic corticosteroids) and UV phototherapy (light therapy).

Targeted Combined Endpoint Improvement in Patient and Disease Domains in Atopic Dermatitis: A Treat-to-Target Analysis of Adults with Moderate-to-Severe Atopic Dermatitis Treated with Upadacitinib.

A treat-to-target approach was recently developed to guide systemic treatment for adults with atopic dermatitis (AD). Recommendations outlined criteria for a 3-month initial acceptable treatment target and a 6-month optimal target, evaluated using global assessment of patient-reported disease severity, as well as Eczema Area and Severity Index, itch assessed on an 11-point numerical rating scale, Dermatology Life Quality Index, or Patient-Oriented Eczema Measure. Achievement of these targets with once-daily upadacitinib (15 mg and 30 mg) monotherapy was evaluated using integrated adult data from the Measure Up 1 and 2 phase 3 studies. Among the 852 patients treated with upadacitinib 15 mg or 30 mg, the 3-month initial acceptable target was achieved by >80%, >78%, and ≥87% of patients, and the 6-month optimal target was achieved by ≥53%, >61%, and >73% of patients at weeks 2, 16, and 52, respectively. Achievement of all 6 individual criteria for each of the target goals also increased over time. These findings suggest that upadacitinib 15 mg and 30 mg may help improve standards of care in patients with moderate-to-severe AD by achieving 6-month target goals at 16 weeks and as early as 2 weeks for most patients.

Analysis of Reddit Reveals JAK Inhibitor Questions Among Atopic Dermatitis Patients.

Reddit is a popular social media website that is increasingly being used as a source of health information and discussion, especially among the younger population. We analyzed the subreddit "eczeJAKs" (a group whose "about" statement is: "Janus Kinase Inhibitors for Th2 Dermatitis"), and found many gaps in patient knowledge, showing areas for future improvement.  J Drugs Dermatol. 2024;23(4):7787.     doi:10.36849/JDD.7787R2.

Attenuation of Atopic Dermatitis in Newborns, Infants, and Children With Prescription Treatment and Ceramide-Containing Skin Care: A Systematic Literature Review and Consensus.

BACKGROUND: Atopic dermatitis (AD) typically starts in infancy and early childhood. The chronic skin disorder is associated with recurrent flares, pruritus, and genetic predisposition. Daily use of moisturizers that contain lipids, such as ceramides, reduces the rate of AD flares and the need for topical steroid treatment. We aimed to provide insights on AD attenuation to tailor AD prescription therapy, skin care, and maintenance treatment to improve pediatric patients with AD and families. METHODS: A panel of 6 pediatric dermatologists and dermatologists who treat neonates, infants, and children developed a consensus paper on AD attenuation for pediatric patients. The modified Delphi process comprised a face-to-face panel meeting and online follow-up to discuss the systematic literature search results and draw from clinical experience and opinion of the panel to adopt and agree on 5 statements.  Results: Understanding the functional properties of newborn and infant skin, discussing skincare product use with parents, and recommending tailored prescription and skincare routines can improve newborn, infant, and children’s skin health. Studies on the prophylactic application of moisturizers initiated in early infancy suggest moisturizers may delay rather than prevent AD, especially in high-risk populations and when used continuously. Increasingly there is evidence that moisturizer application reduces the severity of AD and extends the time to flares, which may help attenuate the atopic march. The protective effect of skin care for AD has been observed in studies where its daily use is ongoing; these beneficial effects may be lost in less than 1year after cessation. It is therefore important to emphasize that skin care should be routinely used when counseling patients and caregivers.  Conclusion: Healthcare providers can improve patient outcomes in atopic-prone infants and children by providing instructions regarding the daily benefits of applying skin care with gentle cleansers and moisturizers. Using gentle cleansers and moisturizers containing barrier lipids from birth onward may delay AD occurrence and mitigate severity in predisposed infants.J Drugs Dermatol. 2024;23(3): doi:10.36849/JDD.7894.

Appearance Dissatisfaction and Body Dysmorphic Disorder in the Dermatology Patient.

Dermatologists routinely see patients with inflammatory skin conditions and aesthetic concerns that involve substantial psychological comorbidity. However, most dermatologists do not receive formal training in this area, and many are unsure how to best help treat certain patients holistically. Body dysmorphic disorder (BDD) is a common and distressing psychiatric condition that disproportionately impacts dermatology patients, including patients living with chronic inflammatory skin conditions such as acne and atopic dermatitis. BDD is characterized by preoccupation with nonexistent or minimally noticeable flaws in physical appearance that cause clinically significant distress or impairment in functioning. Adolescent populations may be particularly vulnerable to clinically significant body image dissatisfaction, including BDD, due to the high prevalence of acne and the pervasive role of social media platforms. The rise of social media may exacerbate body image issues through repetitive exposure to idealized and often unrealistic beauty standards. Though screening questionnaires can assist dermatologists in recognizing BDD, dermatologists must collaborate with mental health providers to provide comprehensive care to vulnerable patients, including adolescents.J Drugs Dermatol. 2024;23(7):545-550.  doi:10.36849/JDD.8156.

Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms.

BACKGROUND: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear. OBJECTIVE: We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. METHODS: As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence. RESULTS: Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings. CONCLUSIONS: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.

Topical treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD prescription topical treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT databases to September 5, 2022, for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using 7 groups-group 1 being most potent. This review is registered in the Open Science Framework (https://osf.io/q5m6s). RESULTS: The 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty evidence, pimecrolimus improved 6 of 7 outcomes-among the best for 2; high-dose tacrolimus (0.1%) improved 5-among the best for 2; low-dose tacrolimus (0.03%) improved 5-among the best for 1. With moderate- to high-certainty evidence, group 5 TCS improved 6-among the best for 3; group 4 TCS and delgocitinib improved 4-among the best for 2; ruxolitinib improved 4-among the best for 1; group 1 TCS improved 3-among the best for 2. These interventions did not increase harm. Crisaborole and difamilast were intermediately effective, but with uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus. CONCLUSIONS: For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective.

Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD systemic treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna). RESULTS: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.

Safety of topical medications in the management of paediatric atopic dermatitis: An updated systematic review.

AIM: New topical agents have been developed for the treatment of atopic dermatitis (AD) in recent years. This systematic review is intended to synthesize the clinical trial literature and concisely report the updated safety and adverse effects of topical medications used to treat atopic dermatitis in children. METHODS: A systematic search of Cochrane Library, Embase, PubMed and ClinicalTrials.gov from inception to March 2022 was conducted for trials of topical medications used to treat AD in patients <18 years (PROSPERO #CRD42022315355). Included records were limited to English-language publications and studies of ≥3 weeks duration. Phase 1 studies and those that lacked separate paediatric safety reporting were excluded. RESULTS: A total of 5005 records were screened; 75 records met inclusion criteria with 15 845 paediatric patients treated with tacrolimus, 12 851 treated with pimecrolimus, 3539 with topical corticosteroid (TCS), 700 with crisaborole and 202 with delgocitinib. Safety data was well reported in tacrolimus trials with the most frequently reported adverse events being burning sensation, pruritus and cutaneous infections. Two longitudinal cohort studies were included, one for tacrolimus and one for pimecrolimus, which found no significant increased risk of malignancy with topical calcineurin inhibitor (TCI) use in children. Skin atrophy was identified as an adverse event in TCS trials, which other medications did not. Systemic adverse events for the medications were largely common childhood ailments. CONCLUSION: Data discussed here support the use of steroid-sparing medications (tacrolimus, pimecrolimus, crisaborole, delgocitinib) as safe options with minimal adverse events for managing paediatric AD, although a larger number of TCI studies reported burning and pruritus compared to TCS studies. TCS was the only medication class associated with reports of skin atrophy in this review. The tolerability of these adverse events should be considered when treating young children. This review was limited to English-language publications and the variable safety reporting of trial investigators. Many newer medications were not included due to pooled adult and paediatric safety data that did not meet inclusion criteria.

Corticosteroid exposure and cumulative effects in patients with eczema: Results from a patient survey.

BACKGROUND: Individuals with eczema may have substantial lifetime corticosteroid exposure, increasing the risk of corticosteroid-related side effects. OBJECTIVE: To conduct a patient survey evaluating corticosteroid exposure and its cumulative effects in individuals with eczema. METHODS: The multinational online survey was conducted between November 5, 2020, and January 11, 2021. Participants were aged 18 years or older and a patient (n = 1889) or a caregiver of a child (n = 271) diagnosed with having eczema by a medical professional. RESULTS: All participants reported using corticosteroids. Average duration of topical corticosteroid (TCS) use was 15.3 years in adults and 3.6 years in children; 75% used TCS 1 to 2 times a day and 50% applied TCS 15 to 30 days/mo. Frequency and duration could not be determined by varying prescription TCS potencies. Oral corticosteroid use was reported by 36% of the participants (23% for eczema), with a lifetime average of 8.4 courses in adults and 8.1 courses in children. Corticosteroids for non-eczema atopic conditions were reported by 49% of the participants. In participants using TCS, 83% of adults and 64% of children experienced worsening symptoms over time. Development of new symptoms and conditions increased with a greater number of corticosteroid treatments and longer duration of TCS use but may have been owing to eczema progression. Symptoms consistent with topical steroid withdrawal syndrome after TCS discontinuation were reported by many participants. CONCLUSION: Reported substantial corticosteroid exposure throughout their lifetime eczema experience placed participants at risk of negative outcomes. Corticosteroids are a critical component of eczema treatment for many patients. However, careful corticosteroid prescribing practices and monitoring are needed to avoid side effects. When possible, corticosteroid-sparing strategies should be explored.

Practical management of ocular surface disease in patients with atopic dermatitis, with a focus on conjunctivitis: A review.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that can significantly decrease quality of life. AD is commonly associated with comorbidities including ocular surface disease (OSD). Conjunctivitis is the most common OSD associated with AD and can increase in incidence with use of monoclonal antibody biologics that target the type 2 inflammatory pathway. The objective of this review is to raise awareness of comorbid OSD in AD patients that dermatologists may encounter, with a focus on conjunctivitis, and equip dermatologists to address mild ocular concerns. We provide background on the subtypes and pathogenesis of comorbid OSD in AD patients and describe OSD associated with type 2 inflammation-inhibiting AD biologics. We also discuss screening and diagnosis, recommended treatment options for dermatologists, and when to refer to an eye care specialist. This multispecialty approach aims to support the overall health of AD patients and provide optimal patient care.

Individual Article: A Novel 3-Step Over-the-Counter Eczema Regimen Improves Eczema Severity, Itch, and Life Quality: Randomized Study.

BACKGROUND: Eczema, or atopic dermatitis (AD), is a chronic relapsing skin disease associated with unpredictable flares of erythema, rash, and pruritus. AD arises from a combination of immune system dysregulation and abnormal skin barrier function. Skin barrier support with proper skincare regimens have a central role in management. METHODS: This was a multi-center, 12-week in-use study of a skincare regimen in children and adults with mild-to-moderate eczema (6-16) on the Patient-Oriented Eczema Measure (POEM), and ≥2 flares within 3 months prior to screening. The regimen included Itch Relief Gel, Eczema Soothing Lotion, and Flare Relief Cream. Efficacy assessments included POEM, ItchyQuant, Eczema Area and Severity Index (EASI), Quality of Life and digital photography, along with gathering of adverse events and cutaneous tolerability. RESULTS: 34 subjects completed the study. In 12 weeks, mean POEM scores improved from 9.7 to 5.3, and EASI scores improved by 17.9% (P<0.05 vs baseline). Additionally, mean ItchyQuant scores showed that pruritus was significantly improved from 5.4 at baseline to 2.7 at week 12 (P<0.05). The number of flares decreased from 4.2 to 3.2 after 12 weeks of regimen application (P<0.05 vs 12 weeks before baseline). Quality-of-life measures also showed improvement in both children and adults from baseline (P<0.05). There were no related adverse events, the regimen was well tolerated, and participants had positive perceptions of the regimen. CONCLUSIONS: 12-week use of this OTC skincare regimen resulted in significant improvements in EASI, POEM, and ItchyQuant scores, a reduced number of flares, and improved quality of life. J Drugs Dermatol. 2023;22:10(Suppl 2):s21-26.

Burden, Control, and Treatment of Moderate to Severe Atopic Dermatitis in 2021: A United States Patient Survey Study.

BACKGROUND: Recent data on unmet needs in the treatment of moderate to severe atopic dermatitis (AD) in the US are not available. OBJECTIVE: To describe disease control, quality of life (QoL), and treatment satisfaction in a United States population with moderate-to-severe AD. METHODS: Cross-sectional 2021 survey conducted among US patients recruited to an online survey from Kantar e-profiles, their panel partners, and Global Perspectives. Adults with self-reported, physician-diagnosed AD completed the primary survey. Of those reporting moderate to severe AD, a subset, including patients who “strongly disagreed,” “somewhat disagreed,” or were “neutral” on the statement “my eczema is adequately controlled” (“inadequately controlled”) with varying experience with approved biologic treatment (dupilumab), completed a second, enriched survey. Outcome measures evaluated included self-reported disease control and severity and validated measures including Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD), Dermatology Life Quality Index (DLQI), Recap of Atopic Eczema (RECAP), and Treatment Satisfaction Questionnaire for Medication (TSQM-9). RESULTS: Of 3,285 patients who participated in the primary survey, 1,935 self-reported moderate-to-severe AD, 979 (51%) of whom reported inadequate control. A total of 371 completed the enriched survey, leading to an analytic sample with 87 controlled patients and 284 inadequately controlled patients (178/284 inadequately controlled patients never received dupilumab, 23 previously received it, and 83 were currently receiving it). Mean RECAP, PO-SCORAD, and DLQI scores were significantly worse (P<0.01) for inadequately controlled vs controlled patients: 7.26 vs 13.9; 38.3 vs 26.9; and 9.9 vs 7.0, respectively. Mean TSQM-9 scores for inadequately controlled vs controlled patients were significantly worse across all domains—effectiveness, convenience, and global satisfaction (P<0.01): 45.5 vs 69.5, 62.3 vs 72.5, 48.3 vs 69.3, respectively. CONCLUSIONS AND RELEVANCE: This study found about half of the patients had inadequate control of their disease. This may partially be due to underuse of systemic biologics in eligible patients. There remains an unmet need for additional education on current and new systemic biologics that could allow patients to achieve better AD control, improved QoL, and greater overall treatment satisfaction. J Drugs Dermatol. 2023;22(2):119-131. doi:10.36849/JDD.7071.

Dermatology in Contemporary Times: Building Awareness of Social Media's Association With Adolescent Skin Disease and Mental Health.

BACKGROUND: The contribution of psychological disorders to the burden of skin disease has been poorly explored in adolescent patients. The review aims to provide insights into the psychological, social, occupational, and social medias' association with acne, atopic dermatitis (AD), and aesthetics in adolescent patients. METHODS: The project used a modified Delphi process comprising face-to-face discussions followed up online.  The systematic literature search results informed the 14 draft statements. During an expert panel meeting, the draft statements underwent the panel's evaluation at a workshop, followed by a plenary discussion adopting five statements using evidence from the literature coupled with the panel's opinions and experiences.  Results: Studies reported an association between poor sleep, social impairment, and mental health disorders, including body dysmorphic disorder (BDD) with acne or AD in adolescents with acne or AD. Education for patients and parents may improve self-management skills and self-responsibility, promoting better outcomes for acne and AD. The use of certain types of social media can contribute to unrealistic expectations regarding the outcomes of cosmetic procedures. Social media use may also be associated with, and potentially contribute to unrealistic appearance expectations and certain mental health conditions. However, social media use may have benefits, such as connection, diversity, social support, increased self-esteem, safe identity experimentation, and an increased opportunity for self-disclosure.  Conclusions: The association with negative life events, BDD, suicidal ideation, depression, and anxiety are thought to be high for adolescent patients with acne or AD. Using social media for information has both positive and negative aspects. Awareness of the risks and benefits of receiving health information about dermatological disease among adolescents needs to be improved through the education of patients and clinicians. Action-oriented items need to be developed to help dermatologists address these issues in clinical practice.Rieder EA, Andriessen A, Cutler V, et al. Dermatology in contemporary times: building awareness of social media's association with adolescent skin disease and mental health. J Drugs Dermatol. 2023;22(8):817-825. doi:10.36849/JDD.7596.

The Skin Barrier and Moisturization: Function, Disruption, and Mechanisms of Repair.

BACKGROUND: The anatomic layers of the skin are well-defined, and a functional model of the skin barrier has recently been described. Barrier disruption plays a key role in several skin conditions, and moisturization is recommended as an initial treatment in conditions such as atopic dermatitis. This review aimed to analyze the skin barrier in the context of the function model, with a focus on the mechanisms by which moisturizers support each of the functional layers of the skin barrier to promote homeostasis and repair. SUMMARY: The skin barrier is comprised of four interdependent layers - physical, chemical, microbiologic, and immunologic - which maintain barrier structure and function. Moisturizers target disruption affecting each of these four layers through several mechanisms and were shown to improve transepidermal water loss in several studies. Occlusives, humectants, and emollients occlude the surface of the stratum corneum (SC), draw water from the dermis into the epidermis, and assimilate into the SC, respectively, in order to strengthen the physical skin barrier. Acidic moisturizers bolster the chemical skin barrier by supporting optimal enzymatic function, increasing ceramide production, and facilitating ideal conditions for commensal microorganisms. Regular moisturization may strengthen the immunologic skin barrier by reducing permeability and subsequent allergen penetration and sensitization. KEY MESSAGES: The physical, chemical, microbiologic, and immunologic layers of the skin barrier are each uniquely impacted in states of skin barrier disruption. Moisturizers target each of the layers of the skin barrier to maintain homeostasis and facilitate repair.

Bleach baths for atopic dermatitis: A systematic review and meta-analysis including unpublished data, Bayesian interpretation, and GRADE.

BACKGROUND: Bleach bathing is frequently recommended to treat atopic dermatitis (AD), but its efficacy and safety are uncertain. OBJECTIVE: To systematically synthesize randomized controlled trials (RCTs) addressing bleach baths for AD. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and GREAT from inception to December 29, 2021, for RCTs assigning patients with AD to bleach vs no bleach baths. Paired reviewers independently and in duplicate screened records, extracted data, and assessed risk of bias (Cochrane version 2) and GRADE quality of evidence. We obtained unpublished data, harmonized individual patient data and did Frequentist and Bayesian random-effects meta-analyses. RESULTS: There were 10 RCTs that enrolled 307 participants (median of mean age 7.2 years, Eczema Area Severity Index baseline mean of means 27.57 [median SD, 10.74]) for a median of 6 weeks (range, 4-10). We confirmed that other trials registered globally were terminated. Bleach baths probably improve AD severity (22% vs 32% improved Eczema Area Severity Index by 50% [ratio of means 0.78, 95% credible interval 0.59-0.99]; moderate certainty) and may slightly reduce skin Staphylococcal aureus colonization (risk ratio, 0.89 [95% confidence interval, 0.73-1.09]; low certainty). Adverse events, mostly dry skin and irritation, along with itch, patient-reported disease severity, sleep quality, quality of life, and risk of AD flares were not clearly different between groups and of low to very low certainty. CONCLUSION: In patients with moderate-to-severe AD, bleach baths probably improve clinician-reported severity by a relative 22%. One in 10 will likely improve severity by 50%. Changes in other patient-important outcomes are uncertain. These findings support optimal eczema care and the need for additional large clinical trials. TRIAL REGISTRATION: PROSPERO Identifier: CRD42021238486.

Biologics and Small Molecule Inhibitors: an Update in Therapies for Allergic and Immunologic Skin Diseases.

PURPOSE OF REVIEW: Biologics and small molecule inhibitors (SMIs) are a rapidly growing class of highly efficacious therapies in the treatment of chronic immunologic and allergic conditions. With precision targeting of inflammatory signaling molecules, these new agents selectively modulate the immune system to treat a variety of conditions. Dermatologic diseases, including atopic dermatitis and psoriasis, are of particular interest due to the growing number of new biologics and SMIs in recent years. This review serves to summarize and evaluate the recent literature regarding biologics and SMIs. RECENT FINDINGS: Currently approved biologics for AD achieve clear or almost clear skin in less than 40% of patients treated. Several biologics that are still under investigation for AD have shown better efficacy in phase III trials with similar safety profiles. Recently approved SMIs for AD also demonstrate a high degree of efficacy, but safety profiles may limit their use. Psoriasis has several highly efficacious biologics on the market; however, only one SMI is currently available. Additional SMIs for psoriasis have completed phase III trials and demonstrated high efficacy. This article evaluates recent literature on biologics and small molecule inhibitors for AD and psoriasis.

Efficacy, Safety, and Applications of Skin Protectants.

The skin barrier is essential for protection against allergens, irritants, and pathogens and is intimately involved in a variety of inflammatory conditions. As such, approaches to treating these inflammatory skin conditions could involve the repair and protection of the skin barrier. This form of treatment can be delivered in the form of skin protectants, though their protective value remains questionable. Evidence suggests that skin protectants could form an additional layer of protection against harmful substances that could penetrate the skin barrier. However, although several studies support the efficacy of skin protectants, others suggest potentially aggravating effects instead. The range of active ingredients included in skin protectant formulas varies widely, which could account for these observed differences. While the use of skin protectants could prove beneficial in populations at higher risk of exposure to irritants, their effectiveness may be hindered by a lack of proper adherence. The findings gathered from the existing literature on skin protectants appear promising, though further investigation must be conducted to better understand their protective effects against conventional barrier repair approaches. J Drugs Dermatol. 2022;21(9):977-982. doi:10.36849/JDD.6705.

Supplement Article: The Role of Epidermal Barrier Dysfunction and Cutaneous Microbiome Dysbiosis in the Pathogenesis and Management of Acne Vulgaris and Rosacea.

BACKGROUND: Dysregulation of either the cutaneous microbiome (CM) or epidermal barrier function (EBF) is thought to play an increasingly important role in acne vulgaris (AV) and rosacea pathogenesis. OBJECTIVE: To review the literature regarding epidermal barrier dysfunction (EBD) and cutaneous dysbiosis in AV and rosacea and provide clinical pearls for dermatologists. METHODS: A Medline literature search was performed for relevant literature regarding EBD and dysbiosis and either AV or rosacea. An expert consensus panel was then convened to discuss article merits and distill findings into clinical pearls. RESULTS: Final review included 138 articles. Puberty may alter natural stratum corneum lipid ratios, instigating and/or exacerbating EBD in AV. Patients with severe AV have an abundance of virulent Cutibacterium acnes phylotype IA1. EBD may manifest as classic signs of rosacea and improve with treatment. While several microbial populations are dysregulated in rosacea, the effect from any singular species is unclear. Current AV and rosacea treatment regimens may mitigate inflammation but may also indiscriminately damage CM and EBF. Physiologic moisturizers and cleansers that harness pre-/pro-/postbiotics may have a role in restoring CM, EBF, and potentially improving dermatosis severity. LIMITATIONS: Limited prospective clinical trial data especially regarding over-the-counter (OTC)/non-prescription skincare products. CONCLUSION: Appropriately developed prescription and OTC preparations may selectively influence the microbiome and potentially maintain/restore EBF. By understanding this relationship, dermatologists will be better able to educate patients on the importance of appropriate skin care.J Drugs Dermatol. 2022;21:9(Suppl 2):s5-14.

Efficacy and safety of crisaborole in patients with mild-to-moderate atopic dermatitis and other atopic comorbidities.

Background: Crisaborole is a nonsteroidal anti-inflammatory phosphodiesterase 4 inhibitor that is approved for the treatment of patients with mild-to-moderate atopic dermatitis (AD); however, the efficacy and safety of crisaborole in patients with AD and other atopic comorbidities have not been investigated. Objective: This post hoc pooled analysis of the pivotal phase III studies (CrisADe CORE 1 and CORE 2) assessed the efficacy and safety of crisaborole versus vehicle in patients aged ≥ 2 years with mild-to-moderate AD and other atopic comorbidities. Methods: Patients with mild-to-moderate AD and a medical history of asthma, allergic rhinitis, or food allergies were identified. Efficacy assessments included the proportion of patients who achieved Investigator's Static Global Assessment (ISGA) success at day 29, ISGA clear or almost clear at day 29, and improvement in the Severity of Pruritus Scale score at week 4. Safety was assessed via treatment-emergent adverse events (TEAEs). Results: This analysis included 1522 patients (crisaborole, 1016; vehicle, 506); 26.2, 15.9, and 16.5% had a medical history of asthma, allergic rhinitis, and food allergies, respectively. The mean age was 12.2 years. A significantly greater proportion of patients treated with crisaborole achieved ISGA success at day 29 compared with patients treated with vehicle for most subgroups analyzed. Furthermore, a significantly greater proportion of patients treated with crisaborole achieved ISGA clear or almost clear at day 29 across all subgroups and demonstrated improvement in the Severity of Pruritus Scale score at week 4 versus patients treated with vehicle in most of the subgroups. Overall, most TEAEs were mild or moderate in severity; the most common treatment-related TEAE in patients with atopic comorbidities was application-site pain (crisaborole, 5.1%; vehicle, 1.7%). Conclusion: Crisaborole was efficacious and well tolerated in patients with mild-to-moderate AD and other atopic comorbidities, which suggested that crisaborole should be considered for the management of AD in this population. Clinical Trials NCT02118766 (CrisADe CORE 1) and NCT02118792 (CrisADe CORE 2), www.clinicaltrials.gov.