Case Series Analysis of Late-Onset Atopic Dermatitis: Unraveling Clinical Variants.

Atopic Dermatitis (AD), recognized as one of the most prevalent chronic inflammatory skin disorders among children, is characterized by skin barrier dysfunction and immune system abnormalities. Historically viewed as a childhood condition, recent findings underscore a notable prevalence of AD in adults, prompting a critical examination of this demographic. Diagnosis hinges largely on subjective clinical assessments due to the absence of universally accepted biomarkers. Consequently, efforts are underway to identify dependable biomarkers to enhance diagnostic precision. This paper underscores the scarcity of AD diagnoses in adults despite its pediatric prominence, emphasizing the need for heightened awareness and tailored diagnostic approaches in adult populations. Severity scores such as SCORing Atopic Dermatitis (SCORAD) and dermatological life quality index (DLQI) play pivotal roles in evaluating disease severity and its impact on quality of life, guiding the development of personalized treatment strategies for adult AD patients. In this study, we aim to present four compelling cases of adult-onset atopic dermatitis, each offering unique insights into this increasingly recognized phenomenon. What makes these cases particularly noteworthy is the absence of any prior atopic history in two out of four patients, challenging the conventional understanding of AD as a condition predominantly linked to childhood. Moreover, the clinical presentation in all four cases was markedly atypical, underscoring the elusive nature of adult-onset AD diagnosis. In our investigation, interleukin 4 (IL-4), interleukin 13 (IL-13), and Immunoglobulin E (IgE) were utilized as diagnostic biomarkers for our patient cohort. Given the established pivotal roles of IL-4 and IL-13 in AD pathogenesis, elevated serum levels of these biomarkers, although not universally endorsed, hold potential for diagnostic utility. Furthermore, heightened levels of IgE, indicative of allergic responses and inflammation inherent to the condition, emphasize its significance as a key biomarker and therapeutic target in AD management.

Itchy and Swollen: Atopic Dermatitis With Cephalocervical Lymphadenitis in an Infant.

We present a case of a three-month-old Hispanic female seen in the clinic for atopic dermatitis (AD) along with a rare incidence of associated cephalocervical lymphadenitis. The patient had a three-month history of redness, irritation, inflammation, and pruritus of the scalp, face, torso, and lymph nodes. The history and examination originally indicated seborrheic dermatitis with AD, impetigo, and folliculitis on the differential. Due to the rarity of this presentation, it is crucial to increase clinical recognition and awareness of this combination among physicians to improve patient outcomes. Recognizing this unusual presentation can lead to more accurate diagnoses and tailored treatment plans, ultimately benefiting the patient while also advancing our understanding of similar cases.

Preclinical Models of Atopic Dermatitis Suitable for Mechanistic and Therapeutic Investigations.

Atopic dermatitis (AD) is a complex immune-mediated abnormality of the skin characterized by impaired barrier function, eczematous dermatitis, chronic pruritus and itch. The immunological response in AD is mediated by a Th2-dominated immune response in the early acute phase followed by a Th1/ Th2 mixed immune response in the chronic phase. AD is the first step of the "atopic march" that progresses into food allergy, allergic rhinitis, and asthma. Different models are indispensable for studying AD pathogenesis and for designing pre-clinical studies for therapeutic discovery. They reflect the characteristic morphological features of typical human AD with regard to epidermal thickening, hyperkeratosis, acanthosis, and spongiosis and help understand the immunopathogenesis of the disease with respect to IgE levels and cellular infiltration of eosinophils, mast cells, and lymphocytes. Although it is difficult to replicate all human AD clinical features in a model, several AD in vivo models comprising spontaneous, induced, transgenic, and humanized and in vitro models, including 2D, co-culture, and 3D, have been described previously. However, several questions remain regarding whether these models satisfactorily reflect the complexity of human AD. Therefore, this review comprehensively highlights the diversity of currently available models and provides insights into the selection of suitable models based on research questions. It also summarizes the diverse mechanisms associated with each model, which may be valuable for better study design to test new therapeutic options.

Post-hoc safety/efficacy analyses from pediatric delgocitinib atopic dermatitis trials.

BACKGROUND: Delgocitinib ointment is usually recommended for use in children at a concentration of 0.25%. However, there are no clear criteria for dosing, except that a 0.5% formulation may also be used, depending on symptom severity. Treatment of atopic dermatitis is based on combinations of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment, but there are no reports on the safety of delgocitinib ointment when used in combination with other drugs. METHODS: This is a post-hoc analysis of data from two delgocitinib ointment trials with pediatric atopic dermatitis patients. The efficacy and safety of the 0.25% and 0.5% formulations were compared. Efficacy and safety were evaluated after up to 4 and 56 weeks of treatment, respectively. The safety of delgocitinib ointment when used in combination with topical corticosteroids and/or tacrolimus ointment was investigated. RESULTS: The dose-response relationship was examined according to baseline disease severity. The proportions of subjects with mild disease who achieved cumulative investigator's global assessment of 0 (clear) or 1 (almost clear) were 46.2% (0.25% ointment), 71.4% (0.5% ointment), and 7.7% (vehicle). For subjects with moderate to severe disease, the corresponding proportions were 19.0%, 20.0%, and 0.0%, respectively. No overall differences were seen in the safety profiles of the 0.25% and 0.5% delgocitinib ointment doses, or in the safety profiles of the two doses relating to disease severity or to concomitant use of topical corticosteroids and/or tacrolimus ointment. CONCLUSIONS: These analyses indicate that after up to 4 weeks of treatment, delgocitinib 0.5% ointment may be more effective than the 0.25% dose for mild atopic dermatitis, and that after up to 56 weeks of treatment, delgocitinib is well tolerated in a pediatric trial population when used as prescribed in combination with topical corticosteroids and/or tacrolimus ointment.

A scalable approach to assess the safety of recently marketed systemic treatments for atopic dermatitis in clinical practice.

Targeted systemic immune-modulating drugs (IMDs) to treat atopic dermatitis (AD) were highly efficacious in randomized trials. Trials with limited number of subjects leave questions about their safety. We describe a data and analytics structure for the production of timely, high-quality evidence on the comparative safety of recently approved IMDs in patients with AD in clinical practice. We established a series of sequential propensity score (PS)-balanced cohorts that grow in size with each annual data refresh. Nine health outcomes of interest plus conjunctivitis as a positive tracer outcome were identified. The initial treatment comparison was dupilumab, an interleukin-4/13 inhibitor, or tralokinumab, an interleukin-13 inhibitor, versus abrocitinib/upadacitinib, both JAK inhibitors. The first analysis cycle (December 2021-February 2023) compared 269 patients initiating JAK inhibitors and 2,650 initiating IL-4/IL-13 inhibitors. Patient characteristics were well balanced after PS-matching. Outpatient infections within 180 days occurred in 18% of JAK-1 inhibitor initiators versus 12% of dupilumab/ tralokinumab initiators (RR=1.50; 0.96 to 2.33) whereas acne risks were 7% vs. 3%, respectively (RR=2.29, 0.96 to 5.46). This sequential monitoring system will produce essential knowledge on the safety of IMDs to treat AD based on its growing study size of patients observed in clinical practice.

Refractory Dupilumab-Induced Inflammatory Arthritis Treated by Upadacitinib: A 'Janus Kinase (JAK)' of All Trades.

Dupilumab, a monoclonal interleukin (IL)-4 receptor α antagonist, is used to treat moderate-to-severe atopic dermatitis. Uncommonly, inflammatory arthritis and enthesitis may occur upon initiation of dupilumab. Upadacitinib, a Janus kinase (JAK) inhibitor, is an alternative medication approved for moderate-to-severe atopic dermatitis but is also used to treat inflammatory arthritis. We report a case of dupilumab-induced inflammatory arthritis that was refractory to oral nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids and was successfully treated by upadacitinib, which also treated the atopic dermatitis. A 40-year-old female with moderate-to-severe atopic dermatitis was treated with dupilumab for 10 months, showing improvement in her skin. However, she then developed recurrent right knee effusions, polyarthritis in her hands, feet, and knees, and prolonged stiffness. She noticed swelling which developed abruptly in her right knee, then progressed to multiple joints including fingers, wrists, ankles, and persisted for four weeks prior to seeking additional medical care. She denied any recent preceding trauma. Joint pain was worsened by movement and morning stiffness lasted over two hours. Trials of ibuprofen or celecoxib and application of ice did not alleviate it. She had an elevated erythrocyte sedimentation rate of 29 mm/hr and C-reactive protein of 21.6 mg/dL. She tested negative for antinuclear antibody, rheumatoid factor, anti-cyclic citrullinated protein, human leukocyte antigen B27, Lyme enzyme-linked immunosorbent assay (ELISA), and Western blot. She was initially treated with a prednisone taper, but the symptoms returned upon reaching 10 mg daily. She continued on dupilumab for four weeks, but stopped as the joint symptoms progressed. With cessation, her atopic dermatitis also became active again. Despite stopping the dupilumab, she continued to have diffuse swelling and tenderness in her hands, feet, knees, and wrists over the next 12 weeks. Upadacitinib, within one month of initiating, led to improvement in both joints and skin. She was able to taper off the corticosteroids. At five months, she continued to not have swelling or tenderness in her joints, and her skin was well-controlled. We report the first successful use of upadacitinib for the treatment of refractory dupilumab-induced inflammatory arthritis as well as atopic dermatitis. The use of JAK inhibitors should be considered to treat this uncommon condition, given that they also treat atopic dermatitis.

The antimicrobial protein RNase 7 directly restricts herpes simplex virus infection of human keratinocytes.

Approximately 22% of moderately to severely affected atopic dermatitis (AD) patients have a history of eczema herpeticum, a disseminated rash primarily caused by herpes simplex virus type 1 (HSV-1). Reduced activity of antimicrobial peptides may contribute to the increased susceptibility of AD patients to HSV-1. We previously demonstrated that the antimicrobial protein RNase 7 limits HSV-1 infection of human keratinocytes by promoting self-DNA sensing. Here, we addressed whether RNase 7 has any effect on HSV-1 infection when infecting keratinocytes without exogenously added costimulatory DNA, and which step(s) of the infection cycle RNase 7 interferes with. We quantified viral gene expression by RT-qPCR and flow cytometry, viral genome replication by qPCR, virucidal effects by plaque titration, and plaque formation and the subcellular localization of incoming HSV-1 particles by microscopy. Recombinant RNase 7 restricted HSV-1 gene expression, genome replication, and plaque formation in human keratinocytes. It decreased HSV-1 immediate-early transcripts independently of the induction of interferon-stimulated genes. Its main effect was on intracellular infection processes and not on extracellular virions or virus binding to cells. RNase 7 reduced the amount of cell-associated capsids and the HSV-1 envelope glycoprotein D at 3 but not at 0.5 h postinfection. Our data show that RNase 7 directly restricts HSV-1 infection of human keratinocytes, possibly by promoting the degradation of incoming HSV-1 particles. This suggests that RNase 7 may limit HSV-1 spread in the skin and that mechanisms that reduce its activity in the lesional skin of AD patients may increase their susceptibility to eczema herpeticum.

Botanical oleander extract and oleandrin have superior effects on innate immune functions pertaining to dermal allergic reactions in canine cells when compared to oclacitinib.

OBJECTIVE: To perform testing for cytokines involved in dermal inflammatory reactions and to document and compare the effects of an oleander extract (OE), oleandrin, and oclacitinib on biomarkers relevant to allergic reactions. The effects of these compounds under inflamed culture conditions are of direct importance to the treatment of canine atopic dermatitis. METHODS: Testing involved primary canine dermal fibroblasts and the canine DH82 macrophage cell line; both cell types are important for initiating, regulating, and resolving dermal allergic reactions via cytokine communication. RESULTS: Under inflamed conditions, OE and oleandrin downregulated key cytokines secreted by canine dermal fibroblasts and the DH82 macrophage cell line; all of which are treatment targets in dermatitis. In the DH82 macrophage cultures, the most noteworthy reductions involved IL-6, IL-12/IL-23p40, interferon-γ, tumor necrosis factor-α, VEGF, and nerve growth factor-ß. Oclacitinib triggered reductions of some cytokines involved in allergic reactions, including TGF-ß1, IL-12/IL-23p40, and tumor necrosis factor-α; however, these reductions were less robust than the reductions triggered by OE and oleandrin and accompanied by increases in other cytokines involved in dermal inflammation, including IL-6, interferon-γ, and nerve growth factor-ß. In cultures of primary dermal fibroblasts, OE and oleandrin reduced the levels of IL-8 and monocyte chemoattractant protein-1, whereas oclacitinib had little or no effect. CONCLUSIONS: Oleander extract and oleandrin directly modulate immune responses under inflamed conditions. Moreover, OE and oleandrin appear to provide a more beneficial overall cytokine regulation than oclacitinib under inflamed culture conditions. CLINICAL RELEVANCE: These results suggest that OE and oleandrin are efficacious agents to treat canine atopic dermatitis. Future studies should evaluate the efficacy of these compounds in dogs affected by atopic dermatitis.

A Case Series of Refractory Pediatric Atopic Dermatitis Effectively Treated With Dupilumab in Combination With Abrocitinib.

Children with severe atopic dermatitis (AD), refractory to conventional systemic treatment as well as single-agent biologic and Janus kinase inhibitor (JAKi) such as abrocitinib, currently face a lack of treatment options. In response to this clinical conundrum, we present three cases of severe and refractory pediatric AD successfully managed with combined dupilumab and abrocitinib. These children had exhausted all conventional treatments and had undergone treatment with both dupilumab and abrocitinib individually, as well as dupilumab in conjunction with methotrexate. It was only when the combination of dupilumab and abrocitinib was introduced that they finally achieved noticeable and sustained improvements in disease control.

Single-Atom Catalysts with Isolated Cu1-N4 Sites for Atopic Dermatitis Cascade Catalytic Therapy via Activating PPAR Signaling.

Atopic dermatitis (AD) is one of the most common allergic skin disorders affecting over 230 million people worldwide, while safe and efficient therapeutic options for AD are currently rarely available. Reactive oxygen species (ROS) accumulation plays a key role in AD's disease progression. Therefore, a novel single-atom catalyst is designed with isolated Cu1-N4 sites anchored on carbon support (Cu1-N4 ISAC), featuring triple antioxidant enzyme-mimicking activities, for efficient AD cascade catalytic therapy (CCT). The excellent superoxide dismutase (SOD)-, glutathione peroxidase (GPx)-, and ascorbate peroxidase (APx)-like activities of Cu1-N4 ISACs enable the sequential conversion of O2•- to H2O2 and then to harmless H2O, thereby protecting keratinocytes from oxidative stress damage. Notably, two novel experimental methods are developed to directly prove the SOD-GPx and SOD-APx cascade catalytic activities for the first time. In vivo experiments show that Cu1-N4 ISACs are more potent than a recommended typical medicine (halcinonide solution). Additionally, RNA sequencing and bioinformatic analysis reveal that Cu1-N4 ISACs reduce inflammation and inhibit ROS production by activating PPAR signaling, which is aberrantly reduced in AD. Therefore, the synthesized catalytic medicine offers an alternative to alleviate AD and has the potential to serve as PPAR agonists for treating similar diseases.

Alitretinoin versus phototherapy as the first-line treatment in adults with severe chronic hand eczema: the ALPHA RCT.

Background: Hand eczema is common and a cause of morbidity and occupational disability. When education, irritant/contact allergen avoidance, moisturisation and topical corticosteroids are insufficient to control chronic hand eczema, ultraviolet therapy or systemic immune-modifying drugs are used. There is no treatment pathway generally accepted by UK dermatologists. Primary objective: Compare alitretinoin and ultraviolet therapy as first-line therapy in terms of disease activity at 12 weeks post planned start of treatment. Design: Prospective, multicentre, open-label, two-arm parallel group, adaptive randomised controlled trial with one planned interim analysis, and an economic evaluation. Setting: UK secondary care dermatology outpatient clinics. Participants: Patients with severe chronic hand eczema unresponsive to at least 4 weeks of treatment with potent topical corticosteroids. Primary end point: Natural logarithm of the Hand Eczema Severity Index + 1, 12 weeks post planned start of treatment. Randomisation: Participants randomised 1 : 1 by minimisation to alitretinoin or ultraviolet therapy for 12 to 24 weeks. Blinding: Blinded primary end-point assessor. Results: Intention-to-treat population: 441 (100.0%) participants; 220 (49.9%) alitretinoin and 221 (50.1%) ultraviolet therapy. At least one dose was received by 212 (96.4%) alitretinoin and 196 (88.7%) ultraviolet therapy participants. Primary outcome: The unadjusted median (interquartile range) relative change in hand eczema severity index at 12 weeks was 30% (10-70%) of that at baseline for alitretinoin compared with 50% (20-100%) for ultraviolet therapy. There was a statistically significant benefit of alitretinoin compared with ultraviolet therapy at 12 weeks, with an estimated fold change or relative difference (95% confidence interval) = 0.66 (0.52 to 0.82), p = 0.0003 at 12 weeks. There was no evidence of a difference at 24 or 52 weeks, with the estimated fold change (95% confidence interval) equal to 0.92 (0.798 to 1.08) and 1.27 (0.97 to 1.67), respectively. Primary analysis results were consistent for secondary end points: Fifty-nine per cent allocated to alitretinoin and 61% allocated to ultraviolet therapy achieved a clear/almost clear assessment during the trial period. Differential treatment compliance observed: 145 (65.9%) alitretinoin and 53 (24.0%) ultraviolet therapy participants confirmed compliance (≥ 80% received, no treatment breaks > 7 days during first 12 weeks). High levels of missing data were observed. Safety: One hundred and thirty-five reportable adverse events across 79 participants, 55 (25.0%) alitretinoin and 24 (10.9%) ultraviolet therapy. Four serious adverse events (two alitretinoin, two ultraviolet therapy). Four pregnancies reported (three alitretinoin, one ultraviolet therapy). No new safety signals were detected. Conclusion: As a first-line therapy, alitretinoin showed more rapid improvement and superiority to ultraviolet therapy at week 12. This difference was not observed at later time points. Alitretinoin is cost-effective at weeks 12 and 52. Ultraviolet therapy is cost-effective after 10 years, with a high degree of uncertainty. Hand eczema severity index may be a useful primary outcome measure for hand eczema trials; ALPHA results will inform future trials. Limitations: Treatment compliance was poor for ultraviolet therapy. Regular twice weekly treatment was not received by most patients. Assessment of long-term effects of randomised treatments was complicated by use of second-line treatments post treatment phase. Further work: Further analysis of substudies and pilot data will provide valuable information for future studies. A clear need for better therapeutic approaches for severe chronic hand eczema remains. Future studies will need to further address long-term benefits of treatments given. Trial registration: This trial is registered as ISRCTN80206075. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/186/01) and is published in full in Health Technology Assessment; Vol. 28, No. 59. See the NIHR Funding and Awards website for further award information.

The main question was which treatment was better at easing symptoms of severe hand eczema after 12 weeks. The two treatments compared were ones used most often by UK dermatologists. The first is a tablet called alitretinoin, which is taken once a day. The second is called ultraviolet therapy, where hands are soaked in a special liquid and placed under ultraviolet light twice a week at a hospital. We treated 220 patients with alitretinoin and 221 patients with ultraviolet therapy. Patients received treatment for 12 to 24 weeks depending on how well their hand eczema responded. Patients could have different treatments afterwards, and we collected information on their hand eczema symptoms for up to 1 year. After 12 weeks, severe hand eczema symptoms improved for both groups of patients but improved most for patients who took alitretinoin. However, 1 year after joining the trial, there was no evidence of a difference between alitretinoin and ultraviolet therapy as a first-line treatment. More patients stopped ultraviolet therapy early compared with patients who received alitretinoin. Different treatments may have been prescribed after the first treatment. Alitretinoin provides a convenient, instant relief or a 'quick fix' for patients with severe hand eczema. Alitretinoin is more convenient for lots of people, but it is important to have other options available for people who would prefer not to, or are unable to, take alitretinoin. For example, people who take alitretinoin can experience unwanted side effects, and people who are able to become pregnant must also use contraception. Long-term control of severe hand eczema is important. Individual discussions on the pros and cons of each treatment for hand eczema symptoms is needed. Providing flexible options to attend ultraviolet therapy appointments could be helpful (e.g. weekend/evenings).

Skin diseases among adults in Tasiilaq, East Greenland.

Cold climate and unique genetic and environmental factors may influence the prevalence of skin diseases in Greenland. However, there is a lack of epidemiological studies on skin diseases in the adult Greenlandic population. To address this unmet need a cross-sectional study, run by dermatologists from Denmark, the UK, and Switzerland estimated the prevalence and clinical manifestations of skin diseases among adults in East Greenland in May 2022. All adults ≥18 years in the town of Tasiilaq were invited, and 295 individuals aged 18-78 years participated (22.5% of the overall adult population in Tasiilaq). Two-hundred and three participants (69%) had visible signs of current skin disease, and among these, 242 cases of dermatoses were identified. The most common skin diseases were hand eczema (22.4%), lichen simplex (9.5%), discoid eczema (7.1%), psoriasis, atopic dermatitis and acne vulgaris (5.8% each). Scabies was the most frequent infectious skin disease (4.4%). No cases of skin cancer were identified. Atopic dermatitis and psoriasis presented with disease that was of limited extent and different from the classical presentations. Skin diseases showed a high prevalence among adults in East Greenland, and some of them were severe. This indicates a noteworthy public health problem that warrants better access to dermatologist support.

Skin Lipid Barrier: Structure, Function and Metabolism.

Lipids are important skin components that provide, together with proteins, barrier function of the skin. Keratinocyte terminal differentiation launches unique metabolic changes to lipid metabolism that result in the predominance of ceramides within lipids of the stratum corneum (SC)-the very top portion of the skin. Differentiating keratinocytes form unique ceramides that can be found only in the skin, and generate specialized extracellular structures known as lamellae. Lamellae establish tight hydrophobic layers between dying keratinocytes to protect the body from water loss and also from penetration of allergens and bacteria. Genetic and immunological factors may lead to the failure of keratinocyte terminal differentiation and significantly alter the proportion between SC components. The consequence of such changes is loss or deterioration of skin barrier function that can lead to pathological changes in the skin. This review summarizes our current understanding of the role of lipids in skin barrier function. It also draws attention to the utility of testing SC for lipid and protein biomarkers to predict future onset of allergic skin diseases.

Oral Administration of Lactococcus lactis Expressing Mite and Cockroach Major Allergens Alleviates Progression of Atopic March in a Mouse Model.

PURPOSE: Atopic march is defined as the development of atopic dermatitis in early childhood. We recently developed an atopic march mouse model through skin sensitization with aeroallergens from house dust mites and cockroaches. Using this model, this study aimed to evaluate the oral immunotherapy efficacy of Lactococcus lactis harboring specific antigens on the progression of atopic march. METHODS: Dust mite major allergen Der p 2 and cockroach Per a 2-372 were expressed in L. lactis as a fusion recombinant clone (D2P2). L. lactis-D2P2 was administered intragastrically to Aeroallergen patch-sensitized mice once a day for a total of 35 times. The immunological variables in sera, scratching behavior, airway hyperresponsiveness (AHR), and pathology of lungs and skin were evaluated. RESULTS: Our data showed that L. lactis-D2P2 significantly lowered total immunoglobulin E levels, decreased scratch bouts, and relieved AHR compared with the control mice. Histological analysis of the skin and lung tissue demonstrated the therapeutic effects of L. lactis-D2P2 to modulate immune responses via decreased eosinophil infiltration and reduced expression of key cytokines, interleukin (IL)-31 and IL-13, respectively. CONCLUSIONS: The results imply that mucosal allergen-specific immunotherapy of L. lactis-D2P2 is a more cost-effective alternative to conventional subcutaneous allergen-specific immunotherapy. This study provides a promising platform for the development of novel oral protein-based vaccines in the early prevention of allergies.

"Infantgram?" recruitment of infants to a clinical sleep study via social media.

Study Objectives: This study aimed to outline the strategy and outcomes of a study team in recruiting participants for an infant sleep study via social media during the COVID-19 pandemic, to assess the feasibility of recruitment via social media, and to quantitatively and qualitatively explore parental satisfaction and perceptions of recruitment via social media. Methods: The assessing sleep in infants with early-onset atopic dermatitis by longitudinal evaluation (SPINDLE) study recruited infants with and without atopic dermatitis for a longitudinal study assessing sleep. Infants were recruited via social media and their parents were interviewed to explore their experience of recruitment via social media. Results: In total, 57 controls and 33 cases were recruited. Of the 45 controls recruited via social media, 43 (95.6%) were recruited via Instagram and 2 (4.4%) were recruited via Twitter. Of the seven cases recruited via social media, 6 (85.7%) were recruited via Facebook (via sharing of Instagram posts by third parties on Facebook) and 1 (14.3%) was recruited via Instagram. All (100%, n = 28) mothers recruited via social media who completed the full study were satisfied with this approach to recruitment. Specific reasons why mothers reported engaging following exposure to the social media posts included the benefit of additional health checks for their baby, the benefit to scientific advancement, and the opportunity for a stimulating outing following the COVID-19 lockdowns. Conclusions: Our experience highlights parents' acceptance of recruitment via social media, the optimization of time and financial resources, and the benefit of using internet-based recruitment during a pandemic.

Matching-Adjusted Indirect Comparison of the Efficacy and Safety of Difamilast 1% and Delgocitinib 0.5% in Patients with Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic condition with an increasing incidence in Japan. Difamilast and delgocitinib are both new topical drugs for AD proven to be efficacious and safe in phases 2 and 3 clinical trials in Japan. However, there are no head-to-head trials comparing their efficacy and safety. The aim of this study was to determine the proportion of patients by severity and compare the clinical efficacy and safety of difamilast with delgocitinib among patients with moderate-to-severe AD using a matching-adjusted indirect comparison (MAIC). METHODS: Phase 3 clinical trials of difamilast and delgocitinib for treating AD were included. The trials had similar designs but differed in baseline population characteristics. Anchored MAIC was used to align the baseline characteristics and calculate clinical outcomes. The primary outcome was to determine severity stages of the proportion of patients with AD through Eczema Area and Severity Index (EASI), while the secondary outcome included comparing other clinical efficacy and safety of difamilast with delgocitinib. RESULTS: A total of 340 patients were selected (170 each received difamilast and placebo) from the difamilast trial, with 158 (106 received delgocitinib; 52 received placebo) from the delgocitinib trial for the analysis. After matching patients from the difamilast trial with those from the delgocitinib trial, the effective sample sizes (ESS) reduced to 32.7-43.3% of the original difamilast (treatment/placebo) patients. At week 4, the ESS in the difamilast group demonstrated no statistically significant differences in the distribution of AD severity stages, as per EASI scores, compared with the delgocitinib group. In addition, no significant differences were found in modified EASI (mEASI) scores, mEASI 50 and 75 scores, and safety outcomes between the two treatments. CONCLUSIONS: The anchored MAIC analysis indicates that difamilast treatment, like delgocitinib, is a useful option for the treatment of patients with moderate-to-severe AD in Japan.

Dietary glutamine supplementation improves both Th1 and Th17 responses via CARD11-mTORC1 pathway in murine model of atopic dermatitis.

Glutamine (GLN) is considered an immunomodulatory nutrient, while caspase recruitment domain 11 (CARD11) is a susceptibility locus for atopic dermatitis (AD). T-cell antigen receptor (TCR)-stimulated GLN uptake requires CARD11. However, the specific pathogenesis of AD via GLN uptake remains unclear. This study aimed to elucidate the association between dietary GLN supplementation and the CARD11 pathway in the pathogenesis of AD, focusing on T helper type 1 (Th1) and Th17 cell expression in AD. Herein, wild-type (WT) mice with house dust mite epidermal-sensitized skin exhibited increased expression of interferon-gamma (IFN-gamma) and interleukin (IL)-17, whereas CARD11 deficiency impaired Th1 and Th17 responses at the same site. CARD11 is a key mediator of Th1 and Th17 expression in AD. Additionally, we suppressed mammalian target of rapamycin complex 1 (mTORC1) signaling, downstream of CARD11, to underscore the critical role of CARD11 in mediating Th1 and Th17 expression in AD. Further, dietary supplementation of GLN to CARD11-/- mice restored Th1 and Th17 responses, whereas inflammatory expression was reduced in WT mice, and p-CARD11 expression and mTORC1 signaling activity were increased in JPM50.6 cells and CARD11-/- mice. Upon inhibiting the GLN transporter, alanine-serine-cysteine transporter carrier 2 (ASCT2), we observed that the Th1 and Th17 response in AD was reduced. Conclusively, ASCT2-mediated GLN uptake improves the expression of Th1 and Th17 cells via CARD11-mTORC1 signaling pathway in AD, suggesting the potential of glutamine supplementation for AD treatment.

[Efficacy of biologics for severe asthma on allergic comorbidities]. / Efficacité des biothérapies de l'asthme sévère sur les comorbidités allergiques.

Identification of therapeutic targets other than asthma can guide the choice of biologics in cases of severe asthma. Some of the allergic diseases (atopic dermatitis, food allergies, allergic rhinoconjunctivitis) that may be associated with asthma can be treated with biologics. In this review, we aim to assess the effectiveness of these biologic therapies on the allergic comorbidities of asthma. In the treatment of atopic dermatitis, only Dupilumab, an anti-IL4Rα, has proven its effectiveness and has received reimbursement authorization for this indication. In patients presenting with allergic rhinoconjunctivitis, Omalizumab has shown effectiveness, but has not been approved for this indication. Data from post-hoc analyses of studies on severe asthma likewise suggest the effectiveness of Dupilumab regarding allergic rhinitis. While these two biologic therapies have shown positive signals, inducing oral food tolerance, the relevant data are not robust. Biologic therapies targeting IL-5 or its receptor (Mepolizumab, Benralizumab) have seldom been evaluated in allergic comorbidities, excepting atopic dermatitis, for which their effectiveness has not been proven. Lastly, there are interesting data on the combination of biologic therapy and allergen immunotherapy in cases of allergic rhinitis and food allergies, but they need to be confirmed by randomized studies.