Severe Atopic Dermatitis Research Articles

Ctrl-X, Ctrl-C and Ctrl-V in Veterinary Dermatology: Skin microbiota transplantation as a promising approach for dogs with cutaneous adverse food reactions

The probability of influencing the skin microbiome for addressing skin disorders opens a novel aisle of therapy. This study aimed to evaluate the efficacy of skin microbiota transplantation (sMt) for cutaneous adverse food reactions (caFr) in dogs. Ten client-owned dogs with caFr were included in the study. Unenriched heterologous sMt was performed using Nivea Skin Refining Clear-Up Strips (N-cUs). The bacterial microbiota of skin samples was analysed by next-generation sequencing of the 16S rRNA gene. Other relevant biomarkers were involved in VAS (visual analogue scale of pruritus score), CADESI-04 (canine atopic dermatitis extent and severity index) and epidermal corneometric analysis. Increased Faecalibacterium (0 to 1.9 %), Peptoclostridium (5.49 % to 9.11 %) and Collinsella (0.65 % to 8.91 %), and decreased Fusobacterium (19.16 % to 9.06 %), Porphyromona (8.75 % to 0.13 %), Streptococcus (1.63 % to 0.14 %) and Staphylococcus (1.09 % to 0.49 %) was evidenced before and after sMt, respectively. Treatment with sMt effectively controlled clinical signs and drastically reduced median VAS pruritus (6.5 vs. 2) and CADESI-04 scores (74.50±22.62 to 19.30±11.30) (p<0,001). In addition, skin pH and hydration values were improved (p<0,001) after sMt. The heterologous and unenriched sMt with N-cUs could be responsible for the clinical recovery observed in this study.

Analysis of the sensitization spectrum in patients with severe allergic diseases using the ImmunoCAP ISAC method

BACKGROUND: An important advance in modern allergology has been made by the introduction of allergenic molecules/components, including their detection by the ImmunoCAP ISAC method. This method is useful in patients with a complex spectrum of sensitization and severe forms of allergic diseases, where various predictors of severe course are actively searched for.
 AIM: To evaluate the informativeness of component resolved diagnostic by ISAC ImmunoCAP method in patients with severe bronchial asthma and severe atopic dermatitis.
 MATERIALS AND METHODS: A single-center retrospective study was conducted from January to August 2023. 100 patients who were candidates for biologicals for severe bronchial asthma (group 1; 63 patients), severe atopic dermatitis (group 2; 20 patients), or their combination (group 3; 17 patients) were included. Component restlved diagnostic was performed by ImmunoCAP ISAC method.
 RESULTS: Polysensitization and high occurrence of food and fungal allergens were more frequently detected in the groups of patients with severe atopic dermatitis. When analyzing the pollen sensitization spectrum in groups 2 and 3, Bet v 1 and PR-10 family cross-linked molecules (Mal d 1, Pru p 1, Ara h 8, Gly m 4, Cor a 1.04), as well as Ole e 9, Cyn d 1, Ph p 1 and Par j 2 were the most common. Epidermal allergens were common in all three groups. Lipocains (Can f 1, Can f 4, Can f 6, Ecu q 1, Mus m 1), kallikreins (Can f 5), and albumin (Fel d 2) dominated among them. The presence of sensitization to household allergens was detected only in group 2 and only to the molecule Der p 23. Among fungal allergens, the allergen Asp f 6 was predominant in the groups with severe atopic dermatitis, and the component Alt a 1 in patients with severe bronchial asthma. Among food allergens, one of the most common allergens was the molecule Gad c 1, Gal d 1, Gal d 2, Gal d 5 and Bos d 6.
 CONCLUSION: Component resolved diagnostic is an accurate assay suitable for determining the spectrum of sensitization in patients; its result can serve as a distinct biomarker for severe allergic diseases.

Clinical efficacy of modern emollients in atopic dermatitis: case reports

Atopic dermatitis is the most common chronic inflammatory skin disease, characterized by itching, chronic recurrent course, and in most cases is associated with respiratory allergies ― allergic rhinitis and asthma. The incidence of atopic dermatitis varies from 15 to 30% or more among children and from 2 to 14% among adults in different countries. The pathophysiological mechanisms of atopic dermatitis are based on a genetic predisposition to allergies, immune dysregulation, and the influence of environmental factors. Recent studies have shown that a key feature of atopic dermatitis is a barrier defects in compromised skin which leads to increased permeability and penetration of environmental factors (e.g., microbes, allergens) and finally to allergen sensitization and to the development of specific allergic inflammation in the target organ ― the skin.
 The article presents a series of clinical cases of moderate and severe atopic dermatitis, demonstrated an integrated approach to the treatment and selection of emollients, considering the phenotypic features of atopic dermatitis.

Combined metagenomic- and culture-based approaches to investigate bacterial strain–level associations with medication-controlled mild-moderate atopic dermatitis

The skin microbiome is disrupted in atopic dermatitis (AD). Existing research focuses on moderate to severe, unmedicated disease. We sought to investigate metagenomic- and culture-based bacterial strain-level differences in mild, medicated AD and the effects these have on human keratinocytes (HKs). Skin swabs from anterior forearms were collected from 20 pediatric participants (11 participants with AD sampled at lesional and nonlesional sites and 9 age- and sex-matched controls). Participants had primarily mild to moderate AD and maintained medication use. Samples were processed for microbial metagenomic sequencing and bacterial isolation. Isolates identified as Staphylococcus aureus were tested for enterotoxin production. HK cultures were treated with cell-free conditioned media from representative Staphylococcus species to measure barrier effects. Metagenomic sequencing identified significant differences in microbiome composition between AD and control groups. Differences were seen at the species and strain levels for Staphylococci, with S aureus found only in participants with AD and differences in Staphylococcus epidermidis strains between control and AD swabs. These strains showed differences in toxin gene presence, which was confirmed invitro for S aureus enterotoxins. The strain from the participant with the most severe AD produced enterotoxin B levels more than 100-fold higher than the other strains (P< .001). Strains also displayed differential effects on HK metabolism and barrier function. Strain-level differences in toxin genes from Staphylococcus strains may explain varying effects on HK, with S aureus and non-aureus strains negatively affecting viability and barrier function. These differences are likely important in AD pathogenesis.

Comprehensive real-world comparisons between baricitinib and dupilumab treatments for moderate to severe atopic dermatitis

Comprehensive real-world comparisons between baricitinib and dupilumab treatments for moderate to severe atopic dermatitis

Integrated Omics Analysis Uncovers the Culprit behind Exacerbated Atopic Dermatitis in a Diet-Induced Obesity Model.

Atopic dermatitis (AD), a chronic inflammatory skin disease, is exacerbated by obesity, yet the precise linking mechanism remains elusive. This study aimed to elucidate how obesity amplifies AD symptoms. We studied skin samples from three mouse groups: sham control, AD, and high-fat (HF) + AD. The HF + AD mice exhibited more severe AD symptoms than the AD or sham control mice. Skin lipidome analysis revealed noteworthy changes in arachidonic acid (AA) metabolism, including increased expression of pla2g4, a key enzyme in AA generation. Genes for phospholipid transport (Scarb1) and acyltransferase utilizing AA as the acyl donor (Agpat3) were upregulated in HF + AD skin. Associations were observed between AA-containing phospholipids and skin lipids containing AA and its metabolites. Furthermore, imbalanced phospholipid metabolism was identified in the HF + AD mice, marked by excessive activation of the AA and phosphatidic acid (PA)-mediated pathway. This imbalance featured increased expression of Plcb1, Plcg1, and Dgk involved in PA generation, along with a decrease in genes converting PA into diglycerol (DG) and CDP-DG (Lpin1 and cds1). This investigation revealed imbalanced phospholipid metabolism in the skin of HF + AD mice, contributing to the heightened inflammatory response observed in HF + AD, shedding light on potential mechanisms linking obesity to the exacerbation of AD symptoms.

Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: A retrospective cohort study

Dupilumab, a human monoclonal antibody targeting the interleukin 4 alpha receptor, is used for treatment of moderate to severe atopic dermatitis (AD). Previous studies have reported diagnoses of cutaneous T cell lymphoma (CTCL) after dupilumab use. Investigate the risk of CTCL after dupilumab use in patients with AD. Using the TrinetX database, incidence of cutaneous and lymphoid malignancies including CTCL was compared between a cohort of patients with AD who used dupilumab and a cohort of patients with AD who never used dupilumab. A second analysis excluding prior disease-modifying antirheumatic drug use was performed. Propensity score matching was performed to control for covariates. An increased risk of CTCL was found in the cohort of AD patients who used dupilumab (odds ratio 4.1003, 95% confidence interval 2.055-8.192). The increased risk persisted after exclusion of prior disease-modifying antirheumatic drug use. Risk was not increased for other cutaneous or lymphoid malignancies. Most (27/41) cases of CTCL were diagnosed more than 1year after dupilumab use. There is potential for misclassification in the database. Severity of AD could not be assessed. Association between dupilumab and CTCL does not prove causality. Dupilumab use is associated with an increased risk of CTCL in patients with AD in this cohort.

Atopic dermatitis: treatment and innovations in immunotherapy.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by itching and skin barrier dysfunction. Moderate to severe AD is often refractory to first-line topical treatments, and systemic immunosuppressants have been shown to be effective but have significant adverse effects. The paucity of basic treatments has contributed to the development of targeted topical and systemic immunotherapies based on the use of small molecules and biologic drugs which can directly interact with AD pathogenetic pathways. They represent a new era of therapeutic innovation. Additional new treatments are desirable since AD is a heterogeneous disease marked by different immunological phenotypes. This manuscript will review the mechanism of action, safety profile, and efficacy of promising new systemic immunological treatments for AD. Since moderate to severe AD can result in poor quality of life, the development of targeted and well-tolerated immunomodulators is a crucial purpose. The introduction of new pharmacological agents may offer new therapeutic options. However, there is the need to evaluate how "narrow-acting" agents, such as individual interleukin inhibitors, will perform under the safety and efficacy profiles compared with "broad-acting" agents, such as JAK inhibitors.

Population-based cohort study to investigate the changes in prevalence, severity profile, and treatment modalities used in Korean atopic dermatitis patients

In this retrospective study spanning from 2002 to 2019, we analyzed data from 355,277 Korean patients diagnosed with atopic dermatitis (AD) through the National Health Insurance System. Our objective was to comprehensively analyze the trends in prevalence, severity profiles, and treatment approaches for AD in Korea over this 18-year period. Initially, AD prevalence stood at 3.88% in 2002 but notably rose to 5.03% by 2019. During the same period, while AD prevalence decreased in the 0–1-year-old group (from 34.52% to 24.83%), it remained relatively stable in the 1–11-year-old group. Conversely, the 12–19-year-old and 20 years or older age groups witnessed substantial increases in AD prevalence, climbing from 2.55 to 6.02% and 1.44% to 3.53%, respectively. Moreover, the proportion of patients classified as having moderate to severe AD grew from 30.96 to 39.78%. Surprisingly, the prescription pattern, predominantly based on corticosteroid administration, exhibited minimal change despite the rising prevalence of moderate and severe AD cases. These findings underline a persistent reliance on corticosteroid-based treatments for AD, even as the condition's severity escalates among Korean adolescents and adults. Consequently, there is a pressing need to develop novel treatment guidelines emphasizing biologics that offer enhanced safety and efficacy.

Dupilumab in patients with atopic dermatitis: assessing treatment response, clinical features and potential biomarkers in real-life.

Background. The clinical and pathophysiological heterogeneity of atopic dermatitis (AD) endophenotypes is associated with wide diversity in response to therapy. The aim of this study was to evaluate the response to dupilumab in a group of AD patients and identify clinical/immunological features associated with different patterns of response. Methods. A retrospective observational study was performed, including 30 adults with AD who completed 12 months treatment with dupilumab, in a Portuguese Immunoallergology Department. Demographic, clinical, and immunological data were analyzed, including total serum IgE, sensitization to aeroallergens, peripheral eosinophilia and inflammatory biomarkers (sedimentation rate, C-reactive protein and lactate dehydrogenase-LDH). Patients who achieved EASI-75/EASI ≤ 7, SCORAD-75/SCORAD ≤ 24, NRS-pruritus ≤ 4 or DLQI≤5 at 6 months of treatment were considered responders and those that achieved all these goals at 16 weeks were considered super-responders. Results. Clinical evaluation revealed a significant reduction in median SCORAD, EASI, DLQI, NRS-pruritus and NRS-sleep over 12 months on dupilumab (p less than 0.01), in parallel with decrease in serum Th2 pathway biomarkers and LDH. All patients responded to dupilumab, and 26.7% were super-responders, supporting that dupilumab is highly effective in moderate to severe Th2-high AD. Conclusions. In this cohort, none of the evaluated biomarkers at baseline were associated with a better/earlier clinical response to dupilumab. Dupilumab treatment for 52 weeks resulted in a significant and sustained reduction in blood levels of total IgE and allergen-specific IgE to aeroallergens. The potential long-term clinical benefit of these effects, even after discontinuing dupilumab therapy in patients with AD, should be explored to a greater extent.

Parameter-based transfer learning for severity classification of atopic dermatitis using hyperspectral imaging.

Because atopic dermatitis (AD) is a chronic inflammatory skin condition that causes structural changes, there is a growing need for noninvasive research methods to evaluate this condition. Hyperspectral imaging (HSI) captures skin structure features by exploiting light wavelength variations in penetration depth. In this study, parameter-based transfer learning was deployed to classify the severity of AD using HSI. Therefore, we aimed to obtain an optimal combination of classification results from the four models after constructing different source- and target-domain datasets. We designated psoriasis, skin cancer, eczema, and AD datasets as the source datasets, and the set of images acquired via hyperspectral camera as the target dataset for wavelength-specific AD classification. We compared the severity classification performances of 96 combinations of sources, models, and targets. The highest classification performance of 83% was achieved when ResNet50 was trained on the augmented psoriasis dataset as the source, with the resulting parameters used to train the model on the target Near-infrared radiation (NIR) dataset. The second highest classification accuracy of 81% was achieved when ResNet50 was trained on the unaugmented psoriasis dataset as the source, with the resulting parameters used to train the model on the target R dataset. ResNet50 demonstrated potential as a generalized model for both the source and target data, also confirming that the psoriasis dataset is an effective training resource. The present study not only demonstrates the feasibility of the severity classification of AD based on hyperspectral images, but also showcases combinations and research scalability for domain exploration.

Patients' and Caregivers' Experiences Navigating the Burden of Atopic Dermatitis in Argentina.

Background and Objectives: Little is known about patients' and caregivers' experiences with atopic dermatitis (AD) in Argentina, so a survey was administered to learn more. Materials and Methods: A 53-item anonymous survey was administered in Spanish to adult AD patients (n = 334) and caregivers (n = 339) of pediatric AD patients in Argentina (total n = 673). Demographics, healthcare provider information, financial burden, disease severity, disease burden, level of disease-specific education, and experience with shared physician/patient decision making were collected. Linear and logistic regression models were used for statistical comparisons. Results: Survey respondents were overwhelmingly female (90.8%), as was the overall patient population (72.8%). Patients were seen mostly by healthcare specialists (66.8% dermatologists, 13.5% pediatricians, 7.7% allergists, and 7.2% general practitioners). Only 2.8% of respondents reported no symptoms, while 33.3%, 52.4%, and 11.5% reported mild, moderate, and severe AD disease, respectively. Anxiety/depression and pain/discomfort were the most impactful on respondents' quality of life. Caregivers of children with moderate to severe AD and adult patients with severe AD reported a significant financial burden, including using savings or not purchasing food or other essentials to afford medical care. Few people reported receiving disease-specific education or having their own treatment priorities taken into consideration. For adult patients, receiving disease education and being asked about treatment priorities were associated with higher treatment satisfaction and AD control. Discussion: Mental health, pain/discomfort, and financial worries are the most important burdens for adult AD patients and caregivers of children with AD in Argentina. We recommend prioritizing disease-specific education and shared decision making to improve AD care in Argentina.

Risk factors determining the development of food allergy intolerance at the first age in infants with atopic dermatitis

Objective: Very few studies have examined the risk factors for developing tolerance to food allergy in infants with atopic dermatitis (AD). To understand the risk factors for developing tolerance to food allergy in the first year in infants with atopic dermatitis and food allergy coexistence.Methods: Ninety-three infants were included in this retrospective study. Food allergy was detected using food-specific IgE, skin prick, and oral food challenge tests. The severity of the disease was evaluated using Scoring Atopic Dermatitis (SCORAD). Demographic parameters were recorded from medical records.Results: The rate of patients who tolerated food allergy in the first year was 61 (65.6%). The median age to tolerate food allergy was 12 (6-18 months). According to the SCORAD, 8 (8.6%) patients had mild, 50 (53.8%) had moderate AD, and 35 (37.6%) had severe AD. The median SCORAD value was 45.2 (35.2-54.6). There was no difference between the groups who tolerated food allergy and those who could not at the first age of life in terms of age, gender, gestational week, maternal age, and familial atopy history (p&gt;0.05 for all). Egg allergy [p=0.035; OR:6.623 (CI:0.996-44.043)], parental atopy [p=0.024. OR:2.450 (CI:0.699-23.056], and AD severity [p=0.030. OR:1.240 (CI:1.001-22.105)] emerged as statistically significant variables at potential risk factors for food allergy intolerance in the first year.Conclusion: Egg allergy, parental atopy, and severity of atopic dermatitis emerged as potential risk factors for intolerance to food allergy in the first year of life in infants with atopic dermatitis and food allergy coexistence.

Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

Background: Atopic Dermatitis (AD) is a prevalent inflammatory skin disease whose course is often complicated by the presence of concomitant anxiety and depressive disorders. Dupilumab has been demonstrated to be largely effective in AD. The aims of the present study were to (1) to verify the effectiveness of 2-year dupilumab treatment on the depressive and anxiety symptoms of patients affected by AD and (2) to identify predictors of the persistence of psychiatric symptoms despite maintenance treatment with dupilumab. Methods: A total of 331 patients with severe AD were assessed at baseline and at different times over 2 years by a large set of rating scales, including the Eczema Area and Severity Index (EASI), the Hospital Anxiety and Depression Scale (HADS), and the Dermatology Life Quality Index (DLQI). Paired sample t-tests were performed to verify the effectiveness of dupilumab on the severity of AD and mental health items. Two binary logistic regression models were then used to identify the predictors of the persistence of clinically significant depression and anxiety, defined by a score ≥ 8 on each sub-scale of the HADS. Results: After 2 years of treatment with dupilumab, the patients benefited, showing a significant improvement in both the dermatological disease and comorbid depression/anxiety (p < 0.001 for all scales). Overall, 17.5% and 13% of patients, respectively, reported residual depressive and anxiety symptoms after the 2-year treatment with dupilumab. The baseline predictors of the persistence of clinically significant depressive symptoms after the 2-year treatment with dupilumab were found to be a higher body mass index (BMI) (p = 0.012), a lower impact of dermatological disease on quality of life (p = 0.015), and more severe depressive symptoms (p < 0.01), while for anxiety, the only predictor was found to be female gender (p = 0.03). Conclusions: Using a multidisciplinary approach, at baseline, dermatologists should more closely monitor patients who are at a greater risk of maintaining residual psychiatric symptoms despite therapy, such as those with more severe depressive symptoms and those who are overweight.

Characteristics of infectious complications in moderate and severe forms of atopic dermatitis

Atopic dermatitis (AD) is a multifactorial, genetically determined disease with a chronic relapsing course and a predisposition to hyperimmunoglobulinemia E. Abnormal colonization of Staphylococcus aureus, Malassezia furfur, and Herpes Simplex plays a significant role in maintaining inflammation in AD. Objective — to determine the frequency of bacterial, mycotic and viral complications in a group of patients with moderate and severe AD. Materials and methods. From 2018 to 2023, 80 patients with AD (moderate and severe forms) aged from 1 year to 53 years (average age 14.6 years) were under our observation. Patients with a SCORAD index ≥ 25 were included in the study. To confirm the nature of the infectious complication, additional examination methods were used: microscopy, bacteriological culture, amplification methods of research, dermatoscopy, immunoenzyme analysis. Results and discussion. An analysis of the total number of relapses of AD during the year was carried out, depending on the age and gender of the patients. The largest number of relapses was observed in the age group from 6 to 10 years — 9.4 ± 0.6. The frequency of AD relapses had a certain correlation with the severity of the course of dermatosis — the SCORAD index increased to 31.2 ± 0.4 in the group of patients with the highest frequency of disease relapses (9.4 ± 0.6) per year and, as a result, increase in the frequency of infectious complications. The conducted analysis showed that each age group of AD patients had its own characteristic spectrum of bacterial, mycotic and viral complications. The most frequent infectious complications of AD observed in the examined patients were streptostaphyloderma (18.8 %), molluscum contagiosum (11.3 %), mycotic lesions (10.0 %), herpes infection (6.3 %), Coxsackie virus (3.8 %), EBV ­infection (2.5 %). Conclusions. As a result of the clinical study, it was established that infectious complications in AD have age, gender, and topographic features that can change the course and prognosis of dermatosis. Against the background of reduced immunoreactivity, the risk of disseminated, life­threatening forms of infections increases in patients with atopic dermatitis.

Interplay of cytokines in the pathophysiology of atopic dermatitis: insights from Murin models and human.

The pathogenesis of atopic dermatitis (AD) is understood to be crucially influenced by three main factors: dysregulation of the immune response, barrier dysfunction, and pruritus. In the lesional skin of AD, various innate immune cells, including Th2 cells, type 2 innate lymphoid cells (ILC2s), and basophils, produce Th2 cytokines [interleukin (IL)-4, IL-5, IL-13, IL-31]. Alarmins such as TSLP, IL-25, and IL-33 are also produced by epidermal keratinocytes, amplifying type 2 inflammation. In the chronic phase, not only Th2 cells but also Th22 and Th17 cells increase in number, leading to suppression of filaggrin expression by IL-4, IL-13, and IL-22, which further deteriorates the epidermal barrier function. Dupilumab, which targets IL-4 and IL-13, has shown efficacy in treating moderate to severe AD. Nemolizumab, targeting IL-31RA, effectively reduces pruritus in AD patients. In addition, clinical trials with fezakinumab, targeting IL-22, have demonstrated promising results, particularly in severe AD cases. Conversely, in murine models of AD, several cytokines, initially regarded as promising therapeutic targets, have not demonstrated sufficient efficacy in clinical trials. IL-33 has been identified as a potent activator of immune cells, exacerbating AD in murine models and correlating with disease severity in human patients. However, treatments targeting IL-33 have not shown sufficient efficacy in clinical trials. Similarly, thymic stromal lymphopoietin (TSLP), integral to type 2 immune responses, induces dermatitis in animal models and is elevated in human AD, yet clinical treatments like tezepelumab exhibit limited efficacy. Therapies targeting IL-1α, IL-5, and IL-17 also failed to achieve sufficient efficacy in clinical trials. It has become clear that for treating AD, IL-4, IL-13, and IL-31 are relevant therapeutic targets during the acute phase, while IL-22 emerges as a target in more severe cases. This delineation underscores the necessity of considering distinct pathophysiological aspects and therapeutic targets in AD between mouse models and humans. Consequently, this review delineates the distinct roles of cytokines in the pathogenesis of AD, juxtaposing their significance in human AD from clinical trials against insights gleaned from AD mouse models. This approach will improve our understanding of interspecies variation and facilitate a deeper insight into the pathogenesis of AD in humans.

IL-4-induced decrease in both the number and CTLA-4 expression of Treg impairs suppression of Th2 type inflammation in severe atopic dermatitis

BackgroundTreg plays a pivotal role in the suppression of Th2 cell and the maintenance of immune homeostasis. The precise molecular mechanism underlying the disruption of Treg suppression of Th2 cell and the promotion of Th2 type inflammation in allergic diseases remains elusive. ObjectiveThis study aims to investigate the molecular mechanism underlying quantitative and functional changes of Treg in AD. MethodsThe molecular mechanism was investigated using flow cytometry, mRNA sequencing, co-culture experiments, co-immunoprecipitation, chromatin immunoprecipitation, and bisulfite sequencing in vitro or in AD mice model and patients with AD. ResultsIncreased proportion of Treg was detected in mild and moderate AD. Conversely, characteristic decrease in both the number and CTLA-4 expression of Treg was relevant to serum IL-4 level in severe AD patients, which was verified under a high concentration of IL-4 treatment in vitro. The underlying mechanism is that IL-4/pSTAT6 pathway recruits DNMT1 and HDAC2 to inhibit transcriptional regulation of Foxp3 and CTLA-4 loci. High level of IL-4 impaired the suppression of Treg against Th2 cell differentiation mediated by CTLA-4, and blockade of IL-4Rα signaling in Treg restored Treg number and suppression of Th2 cell in AD model mice and patients with AD. ConclusionThe number of Treg is relevant to stratification of severity and serum IL-4 level in patients with AD. Abnormal high level of IL-4 epigenetically triggers a decrease in both the number and CTLA-4 expression of Treg. The reduced expression of CTLA-4 on Treg induced by IL-4 impairs suppression of Th2 cell differentiation.

Infantile atopic dermatitis – increasing severity predicts negative impacts on maternal and infant sleep: a mixed methods study

BackgroundWhile the impacts of atopic dermatitis (AD) on maternal and child sleep outcomes have been previously explored, less is known about the associations between infantile AD and sleep quality and quantity.ObjectiveTo describe the perceived causes of AD-associated maternal sleep disturbances and the association between AD severity and infant sleep outcomes.MethodsMothers with infants aged < 19 months old with a diagnosis of AD were recruited from social media and medical clinics in Winnipeg, Canada between October 2021 and May 2022. Infant AD severity was classified using maternal-reported data on the Patient-Oriented Scoring Atopic Dermatitis tool (PO-SCORAD). Quantitative data were collected via a series of questionnaires with a subset of mothers subsequently completing semi-structured interviews. Quantitative and qualitative data were integrated in the discussion.ResultsMothers of infants with moderate/severe AD (6/12) were more likely to report their infant suffering from a higher degree of sleeplessness (i.e., ≥ 5 on a scale of 0–10) over the past 48 h compared to mothers of infants with mild AD (0/18). This was supported by qualitative findings where mothers described how their infant’s sleep quality and quantity worsened with AD severity. Additionally, 7/32 mothers reported that their child’s AD, regardless of severity, disturbed their sleep. Maternal sleep loss was most commonly attributed to infant itching (6/7), followed by worry (4/7).ConclusionInfantile AD severity was associated with worse sleep outcomes for both mothers and infants. We propose that maternal and infantile sleep quality and quantity can be improved by reducing AD severity through adherence to topical treatments.

Re-engagement, quality of life, and burden of treatment in adults on dupilumab for severe atopic dermatitis-A mixed methods study.

Targeted biologic therapies have revolutionised the treatment of severe atopic dermatitis (AD). To assess effects of dupilumab on patient re-engagement, quality of life (QOL), and burden of treatment (BOT) in severe AD. Adults on dupilumab for AD completed questionnaires on QOL, BOT, and provided qualitative reflections, with a subset interviewed to explore experience of leaving and re-engaging with dermatology. Prior treatments, adverse events, and clinical severity scoring were evaluated. Statements and interviews were qualitatively reviewed. Of 41 patients; median age was 34years, 68% were male; and 93% (n=38) had trialled ≥1 immunomodulatory therapies before dupilumab. Median dermatology life quality index was 21 (range 9-30, SD±5.1) pre-dupilumab, and 2 (range 0-11, SD±3.4) post-dupilumab. Median eczema area and severity index was 31.4 (range 10-46.4, SD±11.8) pre-dupilumab, and 6.4 (range 0.4-13.2, SD±3.6) on dupilumab. Burden of treatment scores on dupilumab were low (median 0-3/10) across all domains. Themes identified pre-dupilumab included sleep disturbance, low self-esteem, social isolation, disempowerment, frustration with ineffective treatments, and high financial costs. Benefits included confidence reacquisition, enhanced sleep, liberation from time-consuming 'messy' topical regimes, improved relationships, and reclaimed autonomy. Side effects included red/itchy eyes (37%, n=13) and facial dermatitis (20%, n=7).Twelve patients had deeper interviews. Regarding disengagement with dermatology, themes included ineffectiveness and toxicity of older treatments, attendance futility, dermatologist fatigue, and 'fizzling out'. Regarding re-engagement with dermatology, themes included social media influence, novelty, exasperation with QOL, and life-changing improvements seen with dupilumab. The emergence of novel effective treatments for AD has significant implications for dermatology workforce and financial planning.

Efficacy Outcomes in Clinical Trials of Atopic Dermatitis Treatments: A Systematic Literature Review

Introduction: Complete skin clearance is a key atopic dermatitis (AD) treatment goal. Treatment efficacy in AD trials is evaluated using a range of clinical measures with the Investigator’s Global Assessment (IGA) as a key endpoint. Multiple and varied forms of the IGA scale are utilized across trials, including the Investigator’s Static Global Assessment and the Validated Investigator Global Assessment for ADTM. IGA scores usually range from 0 (clear) to 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe), but contain differences in detail assessed. Efficacy endpoints using IGA scales include achieving IGA=0 or 1 with ≥2-point improvement from baseline, or IGA=0. The Eczema Area and Severity Index (EASI) and achievement of ≥75% or ≥90% improvement from baseline (EASI75 and EASI90) are additional gold-standard measurements.&#x0D; Objective: To compare differences in efficacy outcomes in recent clinical trials of FDA-approved AD treatments for adults and children.&#x0D; Methods: A systematic literature search was conducted using MEDLINE, Embase, Cochrane Library, and hand search to identify AD trials published in English language between January 1, 2016 and August 16, 2023. Trials could include patients with any severity of AD who were treated with topical therapies (crisaborole, ruxolitinib), injectable systemics (dupilumab, tralokinumab), or oral systemics (upadacitinib, abrocitinib) according to approved indications. Efficacy outcomes of IGA=0 or 1 with ≥2-point improvement, IGA=0, EASI75, and EASI90 were categorized and summarized by AD severity, treatment type, and age groups in the trials.&#x0D; Results: Of 50 publications identified, 40 (80%) reported randomized controlled trials, 2 (4%) single-arm trials, and 8 (16%) open-label extension trials. By patient age groups, 11 publications were on children (&lt;12 years), 8 on adolescents (12–17 years),15 on patients ≥12 years, and 17 on adults (≥18 years). Moderate to severe AD was the most frequently studied severity (38/50 publications), of which all trials were either as systemic monotherapy or systemic therapy combined with a topical. Topical monotherapy for mild to moderate AD only was reported in 8/50 publications. For topicals, achievement of IGA=0 (clear) was not reported for any age group, and no trials reported EASI90 for children &lt;12 years. For injectable systemics, no outcome was reported for IGA=0 (clear) in children &lt;12 years. For oral systemics, no outcomes were reported for children &lt;12 years.&#x0D; Conclusions: This literature search of AD trial publications on FDA-approved treatments from 2016 onwards revealed several gaps in available outcomes data. There were no trials that assessed a topical therapy for moderate to severe AD, and complete disease clearance (IGA=0) was not demonstrated for any topicals. The findings reinforce the unmet need for a topical AD treatment that can provide high efficacy including complete clearance without restriction based on age or disease severity.&#x0D; Funding Support: Dermavant Sciences, Inc.