Topical steroids or emollients: does order matter?

Topical corticosteroids, topical steroid-sparing agents, and emollients are all used to treat atopic dermatitis. However, there are no formal guidelines dictating the order and timing in which these topical modalities should be applied. Additionally, the order of application may change drug absorption, efficacy, and distribution. This is especially important for patients with atopic dermatitis. These patients have a dysfunctional skin barrier, which can lead to greater systemic absorption of drugs. Moreover, children already have an increased rate of systemic absorption due to a higher ratio of body surface area to body weight. Thus, the order of application of topical regimens is of the utmost importance in pediatric dermatology. This manuscript presents an updated review of the literature with a focus on guiding clinicians toward the best practices from the available resources.

Nonsteroidal Approaches for Atopic Dermatitis: A Clinical Update.

Topical corticosteroids (TCSs) are the most widely used treatment for atopic dermatitis (AD), but they can have adverse effects such as skin atrophy, telangiectasias, and hypopigmentation, especially with prolonged use of higher potency steroids. Many patients also have a fear of using TCSs, known as "corticophobia." With the development of biologics and Janus kinase inhibitors, a nonsteroidal approach to the treatment of AD may be possible and may be preferred by certain patients. Given what is known about these nonsteroidal therapies, we propose a structured treatment ladder and action plan that can guide clinicians and patients on the use of these therapies for the treatment of AD. The ladder divides nonsteroidal medication classes into treatments for exacerbation versus maintenance therapies in an escalating order of increasing potential for adverse effects, both real and perceived. This treatment algorithm proposal paves the way for a potential nonsteroidal approach to managing AD.

Is Food-Triggered Atopic Dermatitis a Form of Systemic Contact Dermatitis?

Food allergy in atopic dermatitis is mediated by complex immune interactions between genetics, diet, environment, and the microbiome. When contact between inflamed skin and food antigens occurs, contact hypersensitivity can develop. Consequently, systemic contact dermatitis (SCD) can occur after ingestion of allergenic foods or food additives in the setting of a Th2 response with CLA-positive T cells, triggering dermatitis where skin resident memory lymphocytes reside. This phenomenon explains food-triggered dermatitis. Atopy patch tests (APTs) detect sensitization to food proteins responsible for SCD, which in turn can be confirmed by oral food challenge with delayed interpretation. We summarize the literature on using APTs to identify foods for oral challenge with dermatitis as an outcome. In dermatitis patients at risk for Th2 skewing based on a history of childhood-onset flexural dermatitis, shared decision-making should include a discussion of identifying and avoiding food and food additive triggers, as well as identifying and avoiding all contact allergens, prior to initiation of systemic therapy for dermatitis.

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.

Atopic Dermatitis: Beyond the Skin and Into the Gut.

Atopic dermatitis (AD) is a common, chronic and recurring inflammatory skin disorder characterized by an intensely pruritic, eczematous dermatitis. The etiology of AD is thought to involve a combination of environmental, genetic, and immunologic factors. Emerging research has investigated factors that may impact individual risk for developing AD, disease severity, and treatment response. One component is the gut microbiome, which is considered to play an essential role in maintaining the homeostasis of several organ systems. The gut microbiome has been described as a major regulator of the "gut-skin axis," yet some studies have yielded conflicting evidence regarding the strength of the association of gut microbiota dysbiosis with AD. This review discusses recent insights into the role of the gut microbiome in AD pathogenesis and its interplay among other complex systems that govern the current assessments of and treatments for AD.

Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: a randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial.

Background: Topical anti-inflammatory therapy is a cornerstone of treatment for atopic dermatitis (AD). However, many unmet needs remain with existing therapies. B244 is a live topical biotherapeutic being tested for the reduction of pruritus and improvement of eczema signs in patients with AD. We aimed to assess the safety and efficacy of B244, compared to vehicle, for patients with mild-to-moderate AD and moderate-to-severe pruritus. Methods: In this randomised, placebo-controlled, double-blind phase 2b trial, adults aged 18-65 years with mild-to-moderate AD and moderate-to-severe pruritus were enrolled across 56 sites in the USA. Patients were randomised 1:1:1 into a low-dose (optical density at 600 nm [OD] 5.0), high-dose (OD 20.0), or vehicle group for the 4-week treatment period and a 4 week follow-up period. Patients were instructed to apply the topical spray twice daily throughout the treatment period. Randomisation was centrally based (random alternating blocks of 6 and 3) and stratified by site. All participants, investigators, and those assessing outcomes were blinded to the treatment group assignments. The primary endpoint was the mean change in pruritus as measured by the Worst Itch Numeric Rating Scale (WI-NRS) at 4 weeks. Safety was tracked throughout the study. Primary efficacy analyses included the modified intent-to-treat (mITT) population, encompassing those who received at least one dose of study drug and attended at least one post-baseline visit. The safety population included all participants who received at least one does of study drug. This study is registered with ClinicalTrials.gov, NCT04490109. Findings: Between June 4, 2020 and October 22, 2021, 547 eligible patients were enrolled. All study endpoints were meaningfully improved with B244 compared to vehicle. The WI-NRS score was reduced by 34% (-2.8 B244 vs -2.1 placebo, p = 0.014 and p = 0.015 for OD 20.0 and OD 5.0), from a baseline score of >8. B244 was well tolerated with no serious adverse events (SAEs); treatment-emergent adverse events (TEAEs) and treatment related TEAEs were low in incidence, mild in severity, and transient. 33 (18%) of 180 patients given B244 OD 5.0, 29 (16%) of 180 patients given B244 OD 20.0, and 17 (9%) of 186 patients given placebo reported treatment-emergent adverse events; headache was the most frequent (3%, 2%, and 1%, respectively). Interpretation: B244 was well tolerated and demonstrated improved efficacy compared to vehicle in all primary, secondary, and exploratory endpoints and should be further developed as a novel, natural, fast-acting topical spray treatment option for AD and associated pruritus. Funding: AOBiome Therapeutics.

Values and Preferences of Patients and Caregivers Regarding Treatment of Atopic Dermatitis (Eczema): A Systematic Review.

Importance: Patient values and preferences can inform atopic dermatitis (AD) care. Systematic summaries of evidence addressing patient values and preferences have not previously been available. Objective: To inform American Academy of Allergy, Asthma & Immunology (AAAAI)/American College of Allergy, Asthma and Immunology (ACAAI) Joint Task Force on Practice Parameters AD guideline development, patient and caregiver values and preferences in the management of AD were systematically synthesized. Evidence Review: Paired reviewers independently screened MEDLINE, Embase, PsycINFO, and CINAHL databases from inception until March 20, 2022, for studies of patients with AD or their caregivers, eliciting values and preferences about treatment, rated risk of bias, and extracted data. Thematic and inductive content analysis to qualitatively synthesize the findings was used. Patients, caregivers, and clinical experts provided triangulation. The GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative Research) informed rating of the quality of evidence. Findings: A total of 7780 studies were identified, of which 62 proved eligible (n = 19 442; median age across studies [range], 15 years [3-44]; 59% female participants). High certainty evidence showed that patients and caregivers preferred to start with nonmedical treatments and to step up therapy with increasing AD severity. Moderate certainty evidence showed that adverse effects from treatment were a substantial concern. Low certainty evidence showed that patients and caregivers preferred odorless treatments that are not visible and have a minimal effect on daily life. Patients valued treatments capable of relieving itching and burning skin and preferred to apply topical corticosteroids sparingly. Patients valued a strong patient-clinician relationship. Some studies presented varied perspectives and 18 were at high risk for industry sponsorship bias. Conclusions and Relevance: In the first systematic review to address patient values and preferences in management of AD to our knowledge, 6 key themes that may inform optimal clinical care, practice guidelines, and future research have been identified.

Identifying prevalence and inpatient outcomes of anemia and hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a multifactorial inflammatory disorder. Previous studies have ascertained an association between anemia and HS; however, they were limited by low sample size and lack of demographic information. The objective of this study is to address the concerns of prior research and identify specific subgroups and subtypes of anemia present in HS patients and evaluate how these subgroups impact hospital outcomes. We analyzed HS hospitalizations using the National Inpatient Sample from the years 2016 to 2019. HS was associated with the nutritional anemia, aplastic anemia, and acute posthemorrhagic anemia subgroups. Within these subgroups, HS was specifically associated with iron deficiency anemia, anemia of chronic disease, and other anemia subtypes. HS patients also displayed a lower risk of having aplastic anemia, also described as anemia from bone marrow failure. Our findings build upon previous studies evaluating HS and anemia and provide a clearer understanding of the association as well as how it impacts inpatient outcomes.

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.

Magnitude and Time Course of Response to Abrocitinib for Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Emerging treatments for moderate-to-severe atopic dermatitis (AD) may provide greater and faster improvement in AD signs and symptoms than current therapies. OBJECTIVE: To examine JADE COMPARE (NCT03720470) data using stringent efficacy end points. METHODS: Adults with moderate-to-severe AD were randomly assigned 2:2:2:1 to receive oral abrocitinib 200 or 100 mg once daily, subcutaneous dupilumab 300 mg every 2 weeks (600-mg loading dose), or placebo, with medicated topical therapy for 16 weeks. Stringent response thresholds were applied for Eczema Area and Severity Index (EASI), Investigator's Global Assessment, Dermatology Life Quality Index, Peak Pruritus Numerical Rating Scale, and Night Time Itch Scale severity. RESULTS: At week 16, 48.9%, 38.0%, and 38.8% of the abrocitinib 200-mg, 100-mg, and dupilumab groups, respectively, achieved greater than or equal to 90% improvement from baseline in EASI versus 11.3% placebo; 14.9%, 12.6%, and 6.5% achieved Investigator's Global Assessment 0 (clear) versus 4.8% placebo; 29.7%, 21.6%, and 24.0% achieved Dermatology Life Quality Index 0/1 (no/minimal impact on quality of life) versus 10.6% placebo; and 57.1%, 44.5%, and 46.1% achieved Night Time Itch Scale severity 0/1 (no/minimal night-time itch) versus 31.9% placebo. Kaplan-Meier median time to greater than or equal to 90% improvement from baseline in EASI was 59, 113, and 114 days in the abrocitinib 200-mg, 100-mg, and dupilumab groups, respectively, and was not evaluable for placebo; median time to Peak Pruritus Numerical Rating Scale 0/1 (no/very minimal itch) was 86 and 116 days for abrocitinib 200-mg and dupilumab groups, respectively, and was not evaluable for abrocitinib 100-mg and placebo groups. CONCLUSIONS: A greater proportion of patients treated with abrocitinib than placebo had almost complete control of AD signs and symptoms.

Complementary and Alternative Therapies for Onychomycosis: A Systematic Review of the Clinical Evidence.

Introduction: Onychomycosis is notoriously difficult to treat. While oral antifungals are the most efficacious treatment for onychomycosis, they are contraindicated in certain patient populations, and patients may desire lower risk and accessible alternatives to systemic agents. In this study, we examine the clinical evidence supporting the use of complementary and alternative therapies in the treatment of onychomycosis. Methods: PubMed, Embase, and Cochrane Library were searched for clinical trials, observational studies, and case reports/case series, examining the efficacy of a complementary or alternative therapy for the treatment of onychomycosis. Results: We identified 17 articles studying a complementary and alternative therapy for onychomycosis, including tea tree oil (n = 5), Ageratina pichinchensis (n = 3), Arthrospira maxima (n = 2), natural coniferous resin lacquer (n = 2), Vicks VapoRub® (n = 2), propolis extract (n = 2), and ozonized sunflower oil (n = 1). Conclusion: Given the rise of antifungal resistance, complementary and alternative therapies should continue to be studied as adjunctive or alternative therapy for onychomycosis. While preliminary evidence exists for several complementary and alternative therapies in the treatment of onychomycosis, large-scale, randomized, placebo-controlled trials are needed prior to endorsing their use to patients.