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.

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.

Differences in pediatric versus adult clinical trial characteristics for atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a growing burden in all ages. The aim of this study was to compare trial characteristics between pediatric and adult AD trials. METHODS: Data were collected from ClinicalTrials.gov on AD therapeutic trials completed between 2003 and 2019. The trials were classified as pediatrics (mean or median age <18 years of the experimental group participants) or adults. The trials with and without results on ClinicalTrials.gov were searched on PubMed for further data collection. RESULTS: Of 210 trials, 50 (24%) were pediatric trials [mean age: 8.2 ± 4.3 years (SD)] and 160 (76%) were adult trials [mean age 35.2 ± 5.7 years (SD)]. Pediatric and adult trials were equally likely to be randomized controlled trials; however, pediatric trials were more likely to be open-label trials (P < .001) and have no comparator (P < .001). Adult trials were more likely to be industry-funded (95% vs. 80%, P = .001). Any evaluation of drug safety was more likely present in adult trials (83% vs. 60%, P = .001). In trials examining AD severity as an outcome, the Eczema Area and Severity Index (EASI) predominated in adult trials (51% vs. 29%, P < .05) and Scoring Atopic Dermatitis (SCORAD) in pediatric trials (25% vs. 10%, P < .05). CONCLUSION: The results highlight differences in trial design between pediatric and adult AD trials and show a lack of standardization in trial design.

US Prescription trends of antihistamines for atopic dermatitis, 2011-2016.

Antihistamine use for primary treatment of atopic dermatitis (AD) is not recommended, but current guidelines state that sedating antihistamines are favored over non-sedating antihistamines for relief of burdensome pruritus. We analyzed the National Ambulatory Medical Care Survey data to compare use of antihistamines between dermatologists and non-dermatologists. Overall, dermatologists are more likely to prescribe sedating than non-sedating antihistamines when compared to non-dermatologists (P < .001, δabs  = 0.45). Patients under 21 years old (P = .03, δabs  = 0.10) and Black patients (P < .001, δabs  = 0.19) were also more likely to receive sedating antihistamines than non-sedating antihistamines. These findings highlight the differential prescribing practices for atopic dermatitis among physicians.

Readability of online patient education materials for juvenile dermatomyositis.

In this study, we sought to analyze the readability of online patient education materials (PEMs) related to juvenile dermatomyositis (JDM). We analyzed the top 100 Google results and using six different readability scores, found 53 PEMs which had an average grade reading level of 17.4 (graduate level). PEMs by health care providers were written at higher grade levels than those by non-health care providers. Our findings demonstrate a clear need for online JDM PEMs that are written at an appropriate reading level and can be comprehended by patients and families of all levels of health literacy.

Biologics for Allergic Dermatologic Diseases.

PURPOSE OF REVIEW: Atopic dermatitis (AD), chronic spontaneous urticaria (CSU), and allergic contact dermatitis (ACD) represent three important allergic dermatoses with many unmet therapeutic needs. The development of biologic agents has opened the door to both new treatment options and improved understanding of the underlying pathophysiology, both shared and unique for these entities. With several FDA-approved medications available and many more in development, the biologic revolution has begun for allergic dermatoses. RECENT FINDINGS: This is a narrative review on the current state of pathomechanisms and appropriately targeted biologic agents for these three common allergic skin conditions. The importance of Th2 inflammation and the effect of inflammatory cytokines on the skin barrier may help explain the impressive efficacy of biologic agents, while maintaining relative safety. While some of the biologic agents show efficacy across multiple allergic dermatoses, more often it seems these more targeted pathways show accordingly precise efficacy. However, in each disease, multiple agents hold promise, and may be differentiated by safety and adverse effect profile rather than simply by efficacy. New understanding of the pathogenesis of the allergic dermatoses has ushered in a new era of biologic therapies. Competing mechanisms and molecules will continue to be developed and vetted in trials with hopes of continuously refined precision therapies with optimized safety and efficacy profiles.

Pearls in Mitigating Application Pain of Topical Nonsteroidal Agents.

BACKGROUND: Topical steroid-sparing agents (SSA), such as tacrolimus, pimecrolimus, and crisaborole, represent an important therapeutic option in the treatment of inflammatory dermatoses such as atopic dermatitis. While these agents lack the common side effects associated with topical corticosteroids, they all share application site pain as an important adverse effect. SUMMARY: Based on the available evidence and our experience, we suggest the following 7 practical strategies for decreasing the pain associated with SSA use. (1) Use a topical corticosteroid for a few days to reduce inflammation before starting the SSA treatment. (2) Use SSAs strategically. (3) Apply moisturizer before applying SSAs. (4) Store moisturizers in the refrigerator. (5) Ask the patient to apply the SSA on a small test area before broader application. (6) Apply the SSA on dry rather than on damp skin. (7) Consider using aspirin when appropriate for the patient.

Atopic Dermatitis and the Role of the Skin Microbiome in Choosing Prevention, Treatment, and Maintenance Options.

BACKGROUND: Atopic dermatitis (AD) is a common skin condition characterized by disturbed barrier function, skin inflammation, and cutaneous dysbiosis. Clinically, it manifests as chronic-recurrent xerosis, pruritus, and erythematous lesions. Its pathophysiology is complex, making the selection of appropriate treatment options a task. AIM: To share insights gained from a literature review and discussions with experts in dermatology on key factors related to the prevention, treatment, and management of AD in relation to the skin microbiome. METHODS: Results from an expert panel were summarized and discussed to provide updated recommendations for the treatment and maintenance of AD. RESULTS: Evidence supports a strategy for managing inflammatory skin diseases with a selenium-rich post-biotic thermal water and biomass containing moisturizer. The moisturizer helps to restore homeostasis of the skin, re-populate a diverse microbiome, encourage the growth of commensal bacteria, and improve barrier function and symptoms of AD. CONCLUSIONS: Normalization of skin microbiome diversity using a topical moisturizer containing post-biotic aqua and biomass may offer a valuable option for the treatment and maintenance of inflammatory skin diseases. Clinicians should discuss the benefits of this treatment in the context of a full AD management program that covers prevention, active treatment, and maintenance. J Drugs Dermatol. 2020;19(10):935-940. doi:10.36849/JDD.2020.5393.

Impact of Atopic Dermatitis Lesion Location on Quality of Life in Adult Patients in a Real-world Study.

BACKGROUND: Atopic dermatitis (AD) has a negative impact on patients’ quality of life (QoL). OBJECTIVE: To report the impact of specific AD lesion locations on QoL in adult patients with AD using real-world data. METHODS: The Adelphi US Disease Specific Programme was conducted between January–April 2018. Physicians documented patient demographics/characteristics, AD lesion locations, and body surface area; patients completed questionnaires reporting the impact of lesion locations on QoL. RESULTS: AD severity was moderate in 51.6% of patients and severe in 6.0%. Lesions were commonly identified in more than one location. All AD lesion locations impacted QoL. Visible areas were most bothersome, including head/neck (68%), hands/fingers (58%), front (30%), upper extremities (22%), and lower extremities (16%), with statistically significant associations for a number of Dermatology Life Quality Index (DLQI) items. Itch, soreness, pain, and stinging are also associated with a number of body areas but in particular with those that are most visible/accessible. Lesions on the head/neck and hands/fingers (58%) demonstrated an increased impact on the anxiety and depression dimension of the EuroQol 5-Dimension tool. CONCLUSIONS: In patients with AD, quality of life was most affected in patients with lesions in visible areas, including head/neck, hands/fingers, and upper extremities, with statistically significant associations for a number of DLQI domains. Physicians should be aware of the burden of AD lesions on QoL and consider having conversations with patients to better understand the impact of these lesions. Prior presentation: 28th Annual European Academy of Dermatology and Venereology Congress; 9–13 October 2019, Madrid, Spain. Poster number P0233.J Drugs Dermatol. 2020;19(10): 943-948. doi:10.36849/JDD.2020.5422.

Long-term off-label dupilumab in pediatric atopic dermatitis: A case series.

BACKGROUND/OBJECTIVES: Clinical trials of dupilumab have shown efficacy in treating moderate-to-severe atopic dermatitis (AD) in adult patients. While a phase 2 trial of dupilumab has shown efficacy and safety in children, the medication awaits Food and Drug Administration (FDA) approval, and off-label use is limited by dosing currently available to adults. We present this case series to describe the efficacy and safety profile of off-label dupilumab use in six pediatric patients treated by one provider in a private practice. METHODS: We conducted a retrospective chart review of all patients under the age of 18 receiving dupilumab for AD. Two dosing regimens were used as follows: adult dose for patients ≥ 40 kg and half dose for those < 40 kg. We recorded the investigator's global assessment (IGA) and body surface area (BSA) prior to dupilumab initiation and following treatment. All patients were warned of potential side effects including injection site reaction, conjunctivitis, increased risk of infection, and lack of information about use in children. RESULTS: Six pediatric patients were identified with an average age of 10.8 years (range: 7-15). All patients had a decrease in IGA of at least 2 points using biweekly 300 or 150 milligram (mg) doses for an average treatment duration of 8.5 months (range: 6-11). Three patients (50%) had an IGA of 1 after treatment. No side effects were reported. CONCLUSIONS: Dupilumab appears to be an effective treatment for AD in pediatric patients. Optimal dose and delivery have yet to be determined.

Head-and-neck dermatitis: Diagnostic difficulties and management pearls.

Head-and-neck dermatitis is a variant of atopic dermatitis (AD) often seen in children and is challenging to diagnose, as it frequently overlaps with other eczematous dermatoses. Successful head-and-neck dermatitis (HND) treatment requires identification of common triggers and clinical mimickers, such as airborne dermatitis, periorificial dermatitis, and steroid-induced rosacea. Head-and-neck involvement negatively impacts quality of life and is often harder to treat than other body parts, as long-term topical corticosteroid use carries higher risks for skin atrophy on the face. Heating and flushing associated with HND further exacerbate the itch-and-scratch-cycle and disrupt sleep. We aim to address diagnostic gaps, identify clinical mimickers, and share clinical pearls in managing HND, including cooling pillows, thermal water sprays, rice starch paper facial masks, and tips to minimize food and saliva-induced facial irritation.

Comparison of psoriasis and atopic dermatitis guidelines-an argument for aggressive atopic dermatitis management.

The development of effective systemic treatments has revolutionized the treatment of inflammatory skin diseases. The availability of safe new treatments and the understanding of psoriasis as a systemic disease with comorbidities and effects on quality of life have driven the current aggressive treatment paradigm of psoriasis. Historically the morbidity of atopic dermatitis (AD) has been dismissed, given the perception of AD as "just" a rash. Differences in the guidelines for psoriasis and AD management may suggest variations in the current conceptualization of disease severity and effects on quality of life. Published guidelines from the American Academy of Dermatology for the management of psoriasis and AD were reviewed. We recorded the similarities and differences in disease assessment and therapy. The threshold to use biologic agents for moderate to severe psoriasis highlights the aggressive nature of modern psoriasis treatment. AD guidelines include an assessment of quality of life but do not designate a disease severity threshold for systemic treatment. AD and psoriasis have a tremendous effect on quality of life. The AD guidelines have a less aggressive approach to disease management than the psoriasis guidelines. We should think critically about rapid advancement to systemic agents in AD management, especially now that more and better agents are being developed.