The Clinical, Mechanistic, and Social Impacts of Air Pollution on Atopic Dermatitis.

Atopic dermatitis (AD) is a complex disease characterized by dry, pruritic skin and significant atopic and psychological sequelae. Although AD has always been viewed as multifactorial, early research was dominated by overlapping genetic determinist views of either innate barrier defects leading to inflammation or innate inflammation eroding skin barrier function. However, the incidence of AD in the US has increased since 1970 at a pace that far exceeds genetic drift and thus suggests a modern, environmental etiology. Another implicated factor is Staphylococcus aureus; however, a highly contagious microorganism is unlikely to be the primary etiology of a non-communicable disease. Recently, the roles of the skin and gut microbiomes have received greater attention as potentially targetable drivers of AD. Here too however, dysbiosis on a population scale would require induction by an environmental factor. In this review, we describe the evidence supporting the environmental hypothesis of AD etiology and detail the molecular mechanisms of each AD-relevant toxins. We also outline how a pollution focused paradigm demands earnest engagement with environmental injustice if the field is to meaningfully address racial and geographic disparities. Identifying specific toxins and their mechanisms can also inform in-home and national mitigation strategies.

Regulatory T-cell dysfunction and cutaneous exposure to Staphylococcus aureus underlie eczema in DOCK8 deficiency.

BACKGROUND: Dedicator of cytokinesis 8 (DOCK8)-deficient patients have severe eczema, elevated IgE, and eosinophilia, features of atopic dermatitis (AD). OBJECTIVE: We sought to understand the mechanisms of eczema in DOCK8 deficiency. METHODS: Skin biopsy samples were characterized by histology, immunofluorescence microscopy, and gene expression. Skin barrier function was measured by transepidermal water loss. Allergic skin inflammation was elicited in mice by epicutaneous sensitization with ovalbumin (OVA) or cutaneous application of Staphylococcus aureus. RESULTS: Skin lesions of DOCK8-deficient patients exhibited type 2 inflammation, and the patients' skin was colonized by Saureus, as in AD. Unlike in AD, DOCK8-deficient patients had a reduced FOXP3:CD4 ratio in their skin lesions, and their skin barrier function was intrinsically intact. Dock8-/- mice exhibited reduced numbers of cutaneous T regulatory (Treg) cells and a normal skin barrier. Dock8-/- and mice with an inducible Dock8 deletion in Treg cells exhibited increased allergic skin inflammation after epicutaneous sensitization with OVA. DOCK8 was shown to be important for Treg cell stability at sites of allergic inflammation and for the generation, survival, and suppressive activity of inducible Treg cells. Adoptive transfer of wild-type, but not DOCK8-deficient, OVA-specific, inducible Treg cells suppressed allergic inflammation in OVA-sensitized skin of Dock8-/- mice. These mice developed severe allergic skin inflammation and elevated serum IgE levels after topical exposure to Saureus. Both were attenuated after adoptive transfer of WT but not DOCK8-deficient Treg cells. CONCLUSION: Treg cell dysfunction increases susceptibility to allergic skin inflammation in DOCK8 deficiency and synergizes with cutaneous exposure to Saureus to drive eczema in DOCK8 deficiency.

Exploring the skin microbiome in atopic dermatitis pathogenesis and disease modification.

Inflammatory skin diseases such as atopic eczema (atopic dermatitis [AD]) affect children and adults globally. In AD, the skin barrier is impaired on multiple levels. Underlying factors include genetic, chemical, immunologic, and microbial components. Increased skin pH in AD is part of the altered microbial microenvironment that promotes overgrowth of the skin microbiome with Staphylococcus aureus. The secretion of virulence factors, such as toxins and proteases, by S aureus further aggravates the skin barrier deficiency and additionally disrupts the balance of an already skewed immune response. Skin commensal bacteria, however, can inhibit the growth and pathogenicity of S aureus through quorum sensing. Therefore, restoring a healthy skin microbiome could contribute to remission induction in AD. This review discusses direct and indirect approaches to targeting the skin microbiome through modulation of the skin pH; UV treatment; and use of prebiotics, probiotics, and postbiotics. Furthermore, exploratory techniques such as skin microbiome transplantation, ozone therapy, and phage therapy are discussed. Finally, we summarize the latest findings on disease and microbiome modification through targeted immunomodulatory systemic treatments and biologics. We believe that targeting the skin microbiome should be considered a crucial component of successful AD treatment in the future.

Genetically proxied IL-6 receptor inhibition is associated with increased risk of atopic dermatitis.

BACKGROUND: Dermatitis has been reported after initiation of IL-6 receptor (IL-6R) inhibitors (IL-6Ri), while genetic association studies of atopic dermatitis (AD) have implicated IL-6R pathway signaling. However, causality remains unclear. As the indications for IL-6Ri expand, so do the clinical importance of determining whether there is mechanistic evidence linking it to AD. OBJECTIVE: Our aim was to examine the association between IL-6Ri and risk of AD. METHODS: To genetically mimic IL-6Ri, we selected single-nucleotide polymorphisms within or near the IL6R gene associated with C-reactive protein at genome-wide significance among 343,524 individuals. Genetic data were obtained from 10,788 individuals with AD and 30,047 controls of European ancestry. We used inverse variance-weighted and pleiotropy-robust methods and examined genetic confounding using colocalization. Analyses were replicated by using 13,473 Finnish and 2,385 East Asian individuals with AD. The results from 3 independent analyses were pooled by meta-analysis. RESULTS: Genetically proxied IL-6Ri was associated with increased risk of AD (odds ratio [OR] = 1.78 per 4.4-mg/L reduction in C-reactive protein level [95% CI = 1.28-2.48] [P = 6.5 × 10-4]). The results were replicated using Finnish outcome data (OR = 2.07 [95% CI = 1.58-2.72] [P = 1.57 × 10-7]) and Eastern Asian data (OR = 1.68 [95% CI = 1.12-2.54] [P = .013]). Meta-analysis of 3 independent populations (OR = 1.89 [95% CI = 1.57-2.28] [P = 2.68 × 10-11]) showed no evidence of heterogeneity (P = .65). We found no statistical evidence for pleiotropy or genetic confounding. CONCLUSION: This genetic investigation provides consistent evidence (across independent multiancestry populations) that IL-6R signaling is causally implicated in AD susceptibility. Clinicians should remain vigilant for adverse effects resembling AD when using IL-6R inhibitors for immune-mediated inflammatory diseases.

Effects of pregnancy and lactation prebiotics supplementation on infant allergic disease: a randomized controlled trial.

BACKGROUND: Ingestion of prebiotics during pregnancy and lactation may have immunomodulatory benefits for the developing fetal and infant immune system and provide a potential dietary strategy to reduce the risk of allergic diseases. OBJECTIVE: The aim of this trial was to determine whether maternal supplementation with dietary prebiotics reduces the risk of allergic outcomes in infants with hereditary risk. METHODS: We undertook a double-blind, randomized controlled trial in which pregnant women were allocated to consume prebiotics (14.2g daily of galacto-oligosaccharides and fructo-oligosaccharides in ratio 9:1) or placebo (8.7g daily maltodextrin) powder from <21 weeks gestation until 6-months postnatal during lactation. Eligible women had infants with a first-degree relative with a history of medically diagnosed allergic disease. The primary outcome was infant medically diagnosed eczema by 1-year of age, and secondary outcomes included allergen sensitization, food allergy, and recurrent wheeze by 1-year of age. RESULTS: 652 women were randomized between June 2016 and November 2021 (n=329 prebiotics, n=323 placebo). There was no significant difference between groups in the percentage of infants with medically diagnosed eczema by 1-year of age (prebiotics 31.5% (103/327 infants) compared to placebo 32.6% (105/322 infants); adjusted relative risk 0.98 (95% CI 0.77, 1.23; p=0.84). Secondary outcomes and safety measures also did not significantly differ between groups. CONCLUSION: We found little evidence that maternal prebiotics supplementation during pregnancy and lactation reduces the risk of infant medically diagnosed eczema by 1-year of age in infants who are at hereditary risk of allergic disease.

Disease heterogeneity and molecular classification of inflammatory palmoplantar diseases.

BACKGROUND: Palmoplantar pustulosis (PPP) is an inflammatory disease characterized by relapsing eruptions of neutrophil-filled, sterile pustules on the palms and soles that can be clinically difficult to differentiate from non-pustular palmoplantar psoriasis (palmPP) and dyshidrotic palmoplantar eczema (DPE). OBJECTIVE: We sought to identify overlapping and unique PPP, palmPP, and DPE drivers to provide molecular insight into their pathogenesis. METHODS: We performed bulk RNA sequencing of lesional PPP (n = 33), palmPP (n = 5), and DPE (n = 28) samples, as well as 5 healthy nonacral and 10 healthy acral skin samples. RESULTS: Acral skin showed a unique immune environment, likely contributing to a unique niche for palmoplantar inflammatory diseases. Compared to healthy acral skin, PPP, palmPP, and DPE displayed a broad overlapping transcriptomic signature characterized by shared upregulation of proinflammatory cytokines (TNF, IL-36), chemokines, and T-cell-associated genes, along with unique disease features of each disease state, including enriched neutrophil processes in PPP and to a lesser extent in palmPP, and lipid antigen processing in DPE. Strikingly, unsupervised clustering and trajectory analyses demonstrated divergent inflammatory profiles within the 3 disease states. These identified putative key upstream immunologic switches, including eicosanoids, interferon responses, and neutrophil degranulation, contributing to disease heterogeneity. CONCLUSION: A molecular overlap exists between different inflammatory palmoplantar diseases that supersedes clinical and histologic assessment. This highlights the heterogeneity within each condition, suggesting limitations of current disease classification and the need to move toward a molecular classification of inflammatory acral diseases.

Management of Atopy with Dupilumab and Omalizumab in CADINS Disease.

The caspase activation and recruitment domain 11 (CARD11) gene encodes a scaffold protein required for lymphocyte antigen receptor signaling. Dominant-negative, loss-of-function (LOF) pathogenic variants in CARD11 result in CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease. Patients with CADINS suffer with severe atopic manifestations including atopic dermatitis, food allergy, and chronic spontaneous urticaria in addition to recurrent infections and autoimmunity. We assessed the response of dupilumab in five patients and omalizumab in one patient with CADINS for the treatment of severe atopic symptoms. CARD11 mutations were validated for pathogenicity using a T cell transfection assay to assess the impact on activation-induced signaling to NF-κB. Three children and three adults with dominant-negative CARD11 LOF mutations were included. All developed atopic disease in infancy or early childhood. In five patients, atopic dermatitis was severe and recalcitrant to standard topical and systemic medications; one adult suffered from chronic spontaneous urticaria. Subcutaneous dupilumab was initiated to treat atopic dermatitis and omalizumab to treat chronic spontaneous urticaria. All six patients had rapid and sustained improvement in atopic symptoms with no complications during the follow-up period. Previous medications used to treat atopy were able to be decreased or discontinued. In conclusion, treatment with dupilumab and omalizumab for severe, refractory atopic disease in patients with CADINS appears to be effective and well tolerated in patients with CADINS with severe atopy.

Management of Infant Atopic Eczema to Prevent Severe Eczema and Food Allergy.

Early intervention and active management of infant atopic eczema may play a crucial role in limiting eczema severity and preventing the onset of immediate-type food allergy. Eczema management involves education, skincare and medications targeting skin inflammation and barrier repair. Topical corticosteroids are the mainstay of anti-inflammatory therapy, with nonsteroidal options available for some infants. Proactive therapy, addressing subclinical inflammation, is useful for preventing eczema flares, especially in infants with recurrent eczema flares despite reactive therapy. In clinical practice, holistic consideration of overall infant and family health is essential. Providing advice on maternal stress management, nutritional guidance and recommendations for proper sleep and lifestyle is crucial for the well-being of children and their families, not limited to eczema treatment alone.

Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study.

OBJECTIVE: To examine the association between early-life atopic manifestations and later risk of inflammatory bowel disease (IBD), for which prospective data are scarce. STUDY DESIGN: The population-based All Babies in Southeast Sweden (ABIS) and Norwegian Mother, Father, and Child (MoBa) cohorts follow children from birth (ABIS 1997-1999; MoBa 2000-2009) to the end of 2021. Based on validated questionnaires, parents prospectively reported information on asthma, food-related allergic symptoms, atopic dermatitis, and allergic rhinitis by age 3. IBD was defined by ≥ 2 diagnostic records in the national health registries. Cox regression estimated hazard ratios adjusted (aHRs) for parental IBD, atopy, education level, smoking habits, and national origin. Cohort-specific estimates were pooled using a random-effects model. RESULTS: We compiled data on 83 311 children (ABIS, n = 9041; MoBa, n = 74 270). In over 1 174 756 person-years of follow-up, 301 participants were diagnosed with IBD. Children with atopic dermatitis at age 3 had an increased risk of IBD (pooled aHR = 1.46 [95% CI = 1.13-1.88]), Crohn's disease (pooled aHR = 1.53 [95%CI = 1.04-2.26]), and ulcerative colitis (pooled aHR = 1.78 [95%CI = 1.15-2.75]). Conversely, any atopic manifestation by age 3 was not associated with IBD (pooled aHR = 1.20 [95%CI = 0.95-1.52]), nor were analyses specifically focused on early-life food-related allergic symptoms, asthma, and allergic rhinitis. CONCLUSION: While atopic manifestations in early childhood were overall not associated with IBD, children with atopic dermatitis specifically were at increased risk of developing IBD, suggesting shared etiologic traits; these findings might be useful in identifying at-risk individuals for IBD.

Efficacy and safety of narrowband ultraviolet B versus combined ultraviolet A/narrowband ultraviolet B phototherapy in the treatment of chronic atopic dermatitis: A randomised double-blind study.

Phototherapy is a useful treatment modality for atopic dermatitis (AD). This is a prospective randomised double-blind study comparing the clinical efficacy of combined ultraviolet-A (UVA)/narrowband ultraviolet-B (NBUVB) versus NBUVB phototherapy in the treatment of chronic AD. Patients with moderate-to-severe AD were randomised to receive either UVA/NBUVB or NBUVB phototherapy twice weekly over 12 weeks. At baseline, weeks 6 and 12, Eczema Area And Severity Index (EASI), itch score and adverse effects were assessed. At baseline and week 12, disease-related quality of life was evaluated using the Dermatology Life Quality Index (DLQI). Nine patients were randomised to receive UVA/NBUVB and 10 received NBUVB. At week 12, both groups showed significant improvement in EASI and itch scores (p < 0.05). Significant improvement in DLQI was seen in the UVA/NBUVB arm (p = 0.009) with a trend towards improvement in the NBUVB arm (p = 0.11). The efficacy of both modalities were comparable, as were reported adverse effects aside from skin dryness which was higher in the NBUVB arm (40% vs. 0%, p = 0.033). Combined UVA/NBUVB and NBUVB phototherapy have comparable clinical efficacy and safety in the treatment of chronic AD. NBUVB may induce greater skin dryness.

OFFSPRING: A SPRING Follow-Up Study Assessing the Efficacy of Maternal Probiotics and Allergic Disease in the Child.

INTRODUCTION: There are a variety of factors that contribute to the development of allergic diseases in children, including environmental exposures during the maternal prenatal period. It has been proposed that probiotic supplementation during pregnancy could be used as a possible preventative measure to target childhood allergic disease. METHODS: Participants from a previously conducted prospective double-blind randomised control trial of probiotics versus placebo study (Study of PRrobiotics IN Gestation) were sent electronic questionnaires to complete about their child, who are now between 3 and 7 years of age. Demographic data and rates of allergic diseases were compared between the two groups. RESULTS: One hundred and seven women responded to the questionnaires. Between the two groups, there was no difference in the frequency of allergic diseases, with similar rates of eczema, asthma, and hospital presentations seen. CONCLUSION: In this follow-up study, infants of mothers who were exposed to probiotics during their pregnancy do not appear to have any paediatric health advantages in terms of allergic diseases.

Clinical, immunological, and genetic description of a Mexican cohort of patients with DOCK8 deficiency.

PURPOSE: We aimed to describe the clinical, immunological, and genetic features of patients with DOCK8 deficiency (DOCK8-Def) in a tertiary care center for children. METHODS: Retrospective chart review of patients' clinical, immunological, and genetic characteristics with DOCK8-Def. Genetic analysis was performed with targeted- or whole-exome sequencing; we also assessed DOCK8 protein expression and a lymphoproliferation assay and analyzed survival by the Kaplan-Meier method. RESULTS: We described 11 patients from 8 unrelated kindreds. The median age at symptoms' onset was 10 months (range 1-54 months). The median follow-up time was 53.4 months (4.8-118.8). All patients presented eczema and recurrent sinopulmonary and cutaneous infections. Besides those symptoms, the most frequent manifestations were bronchiectases (8/11), food allergies (6/11), and severe infections (6/11). Infrequent characteristics were detection of CMV in bronchial lavage, C. parvum-driven sclerosing cholangitis, Takayasu vasculitis, neurological syndromes, pulmonary tuberculosis, and lymphomatoid granulomatosis. CONCLUSION: DOCK8-Def has a broad spectrum of manifestations, including allergy, autoimmunity, inflammation, infection, and cancer. The hallmark of this inborn error of immunity is IEI-associated eczema with eosinophilia and increased IgE. Here, we report six new mutations causing human DOCK8 deficiency and symptoms previously unrecognized to occur in DOCK8-Def. Therefore, an early diagnosis of DOCK8-Def is essential to facilitate an adequate treatment such as HSCT.

Role of skin management in the prevention of atopic dermatitis and food allergy.

Food allergy is postulated to originate from cutaneous sensitization through a disrupted skin barrier, particularly in atopic dermatitis (AD). Strategies for food allergy prevention currently centre around early allergic food introduction, but there is now increasing evidence for the role of early skin barrier restoration in the form of prophylactic emollient therapy and early aggressive, proactive treatment of established AD for food allergy prevention. Research gaps that remain to be addressed include the type of emollient or anti-inflammatory medication, which confers the greatest efficacy in preventive or proactive skin treatment, respectively, the duration of therapy, and the window of opportunity for these interventions.

Maternal dietary indexes are not linked to early childhood wheezing or atopic eczema.

BACKGROUND: Several recent studies have investigated the association between maternal diet during pregnancy and wheezing or asthma in children. However, whether a specific dietary pattern during pregnancy protects children from wheezing or atopic diseases remains unclear. This study investigated the association between The Alternative Healthy Eating Index for Pregnancy (AHEI-P), the Dietary Inflammatory Index (DII), and the risk for wheezing and atopic eczema in children during the first year of life. METHODS: This study included 1330 mother-child pairs who attended the Kuopio Birth Cohort (KuBiCo) study and had dietary information during the last trimester and information on children's health in the first year of life. AHEI-P and DII indicate a healthy diet and dietary inflammation potential during pregnancy. The AHEI-P and DII were compared with reported wheezing and doctor-diagnosed atopic eczema in children during the first year of life. RESULTS: Neither AHEI-P nor DII is associated with wheezing or atopic eczema in children when analyzed by continuous variables and by tertiles. The odds ratio (95% CI) for AHEI-P and wheezing was 0.99 (0.98-1.01), for AHEI-P and atopic eczema1.01 (0.99-1.02), for DII and wheezing 1.02 (0.95-1.09), and for DII and atopic eczema 0.97 (0.91-1.04). CONCLUSION: In this cohort study, AHEI-P and DII during pregnancy were not associated with wheezing or atopic eczema in the offspring during the first year of life.

Environmental Interventions for Preventing Atopic Diseases.

PURPOSE OF REVIEW: In this review, we detail the exposome (consisting of environmental factors such as diet, microbial colonization, allergens, pollutants, and stressors), mechanistic and clinical research supporting its influence on atopic disease, and potentiation from climate change. We highlight contemporary environmental interventions and available evidence substantiating their roles in atopic disease prevention, from observational cohorts to randomized controlled trials, when available. RECENT FINDINGS: Early introduction to allergenic foods is an effective primary prevention strategy to reduce food allergy. Diverse dietary intake also appears to be a promising strategy for allergic disease prevention, but additional study is necessary. Air pollution and tobacco smoke are highly associated with allergic disease, among other medical comorbidities, paving the way for campaigns and legislation to reduce these exposures. There is no clear evidence that oral vitamin D supplementation, prebiotic or probiotic supplementation, daily emollient application, and antiviral prophylaxis are effective in preventing atopic disease, but these interventions require further study. While some environmental interventions have a well-defined role in the prevention of atopic disease, additional study of many remaining interventions is necessary to enhance our understanding of their role in disease prevention. Alignment of research findings from randomized controlled trials with public policy is essential to develop meaningful public health outcomes and prevent allergic disease on the population level.

Comparison of Old and New Systemic Treatments for Moderate to Severe Atopic Dermatitis.

PURPOSE OF REVIEW: Historically, systemic treatments for atopic dermatitis (AD) primarily consisted of immunosuppressive agents such as corticosteroids and Disease Modifying Antirheumatic Drugs (DMARDS), which provided symptomatic relief but often had long-term adverse effects. Newer treatments have shown significant efficacy with less side effects in clinical trials. This review discusses and compares conventional and newer systemic treatments for AD. RECENT FINDINGS: Newer medications for AD including dupilumab, tralokinumab, lebrikizumab, and oral JAK inhibitors have been shown to be safe and efficacious. High dose cyclosporine and dupilumab were more effective than methotrexate and azathioprine in improving clinical signs of AD. High-dose upadacitinib was shown in another meta-analysis to be most effective in the measured outcomes but had the highest frequency of adverse events. Targeted biologic treatments are increasingly favored over traditional immunosuppressive treatments of AD. Treatment can be individualized based on potency, adverse side effects, mechanism of action, and administration preference. Ongoing research continues to expand treatment options for AD.

Kaposi varicelliform eruption: an unusual presentation caused by varicella zoster virus in a healthy adult patient - a case report.

BACKGROUND: Kaposi Varicelliform Eruptions (KVE), also known as eczema herpeticum, is a rare and potentially life-threatening dermatological condition primarily attributed to herpes simplex virus (HSV) infection, with less frequent involvement of Coxsackie A16, vaccinia, Varicella Zoster, and smallpox viruses. Typically associated with pre-existing skin diseases, especially atopic dermatitis, KVE predominantly affects children but can manifest in healthy adults. Characterized by painful clusters of vesicles and sores on the skin and mucous membranes, it often masquerades as other dermatological disorders. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain relief and inflammation, though their potential role as KVE triggers remains uncertain. CASE REPORT: Here, we present a case of an 18-year-old female with KVE attributed to Varicella Zoster virus (VZV) and successfully treated with oral acyclovir within a week, underscoring the significance of early recognition and intervention. KVE can manifest with systemic symptoms like fever, fatigue, and lymphadenopathy and may involve multiple organ systems, necessitating possible antibiotic use for complications. CONCLUSION: This case underscores the importance of prompt KVE identification and consideration of antiviral therapy to enhance patient outcomes. Further research is warranted to elucidate predisposing factors for this rare condition.

Dupilumab provides sustained effectiveness on patient-reported outcomes and favorable safety in patients with moderate-to-severe atopic dermatitis: Up to 5-year results from the daily practice BioDay registry.

BACKGROUND: Long-term daily practice data on patient-reported benefits of dupilumab for atopic dermatitis (AD) remains limited. OBJECTIVE: To evaluate patient-reported outcome measures (PROMs) and the safety of dupilumab in patients with moderate-to-severe AD over a follow-up period of up to 5 years. METHODS: Data were extracted from the prospective, multicenter BioDay registry (October 2017-2022) of patients with moderate-to-severe AD treated with dupilumab in daily practice. RESULTS: In total 1223 patients, 1108 adults and 115 pediatric patients were included. After ≥1 year of treatment, mean Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numeric rating scale (NRS)-pruritus ranged between 7.8 and 8.7, 3.5 and 4.2, and 2.9 and 3.1 in adults, respectively, whilst these patient-reported outcome measures (PROMs) ranged between 8.9 and 10.9, 4.4 and 6.4, and 3.0 and 3.7 in pediatric patients, respectively. At follow-up, overall work impairment decreased from 40.1% to 16.3% to 13.3% in adults. Furthermore, class I obesity and itch-dominant patients generally had less favorable treatment response. Of all patients, 66.8% reported ≥1 adverse event, with conjunctivitis being the most common (33.7%). LIMITATIONS: The overall percentage of missing values for selected PROMs was 26% in adults and 46% in pediatric patients. CONCLUSION: In addition to favorable safety, dupilumab has demonstrated sustained effectiveness across various PROMs, underscoring the treatment benefits from patients' perspectives.

Dupilumab treatment improves signs, symptoms, quality of life, and work productivity in patients with atopic hand and foot dermatitis: Results from a phase 3, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Despite high disease burden, systemic treatment options for patients with atopic hand and/or foot dermatitis (H/F AD) are limited. OBJECTIVES: To evaluate efficacy and safety of dupilumab in H/F AD using specific instruments for assessing disease severity on hands and feet. METHODS: In this multicenter phase 3 trial, adults and adolescents with moderate-to-severe H/F AD were randomized to dupilumab monotherapy (regimen approved for generalized AD), or matched placebo. The primary endpoint was proportion of patients achieving Hand and Foot Investigator's Global Assessment score 0 or 1 at week 16. Secondary prespecified endpoints assessed the severity and extent of signs, symptom intensity (itch, pain), quality of life, and sleep. RESULTS: A total of 133 patients (adults = 106, adolescents = 27) were randomized to dupilumab (n = 67) or placebo (n = 66). At week 16, significantly more patients receiving dupilumab (n = 27) than placebo (n = 11) achieved Hand and Foot Investigator's Global Assessment score 0 or 1 (40.3% vs 16.7%; P = .003). All other prespecified endpoints were met. Safety was consistent with the known AD dupilumab profile. LIMITATIONS: Short-term, 16-week treatment period. CONCLUSION: Dupilumab monotherapy resulted in significant improvements across different domains of H/F AD with acceptable safety, supporting dupilumab as a systemic treatment approach for this often difficult to treat condition.

Tapinarof cream 1% once daily: Significant efficacy in the treatment of moderate to severe atopic dermatitis in adults and children down to 2 years of age in the pivotal phase 3 ADORING trials.

BACKGROUND: Tapinarof cream 1% once daily (QD), a topical aryl hydrocarbon receptor agonist, downregulates pro-inflammatory Th2 cytokines, upregulates skin-barrier components, and reduces oxidative stress. OBJECTIVE: To assess tapinarof efficacy and safety in adults and children down to 2 years of age with atopic dermatitis (AD). METHODS: Eight hundred and thirteen patients were randomized to tapinarof or vehicle QD in two 8-week phase 3 trials. RESULTS: The primary efficacy endpoint, Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and ≥2-grade improvement from baseline at Week 8, was met with statistical significance in both trials: 45.4% versus 13.9% and 46.4% versus 18.0% (tapinarof vs vehicle; both P < .0001). Significantly superior Eczema Area and Severity Index 75 (EASI75) responses were also observed with tapinarof versus vehicle at Week 8: 55.8% versus 22.9% and 59.1% versus 21.2% (both P < .0001). Rapid improvements in patient-reported pruritus were also significant with tapinarof versus vehicle. Common adverse events (≥5%) of folliculitis, headache, and nasopharyngitis were mostly mild or moderate, with lower discontinuations due to adverse events in the tapinarof groups than with vehicle. LIMITATIONS: Long-term efficacy was not assessed. CONCLUSION: Tapinarof demonstrated highly significant efficacy and favorable safety and tolerability in a diverse population of patients with AD down to 2 years of age.