Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Lebrikizumab, a high-affinity IgG4 monoclonal antibody targeting interleukin-13, prevents the formation of the interleukin-4Rα-interleukin-13Rα1 heterodimer receptor signaling complex. METHODS: We conducted two identically designed, 52-week, randomized, double-blind, placebo-controlled, phase 3 trials; both trials included a 16-week induction period and a 36-week maintenance period. Eligible patients with moderate-to-severe atopic dermatitis (adults [≥18 years of age] and adolescents [12 to <18 years of age, weighing ≥40 kg]) were randomly assigned in a 2:1 ratio to receive either lebrikizumab at a dose of 250 mg (loading dose of 500 mg at baseline and week 2) or placebo, administered subcutaneously every 2 weeks. Outcomes for the induction period were assessed up to 16 weeks and are included in this report. The primary outcome was an Investigator's Global Assessment (IGA) score of 0 or 1 (indicating clear or almost clear skin; range, 0 to 4 [severe disease]) with a reduction (indicating improvement) of at least 2 points from baseline at week 16. Secondary outcomes included a 75% improvement in the Eczema Area and Severity Index score (EASI-75 response) and assessments of itch and of itch interference with sleep. Safety was also assessed. RESULTS: In trial 1, the primary outcome was met in 43.1% of 283 patients in the lebrikizumab group and in 12.7% of 141 patients in the placebo group (P<0.001); an EASI-75 response occurred in 58.8% and 16.2%, respectively (P<0.001). In trial 2, the primary outcome was met in 33.2% of 281 patients in the lebrikizumab group and in 10.8% of 146 patients in the placebo group (P<0.001); an EASI-75 response occurred in 52.1% and 18.1%, respectively (P<0.001). Measures of itch and itch interference with sleep indicated improvement with lebrikizumab therapy. The incidence of conjunctivitis was higher among patients who received lebrikizumab than among those who received placebo. Most adverse events during the induction period were mild or moderate in severity and did not lead to trial discontinuation. CONCLUSIONS: In the induction period of two phase 3 trials, 16 weeks of treatment with lebrikizumab was effective in adolescents and adults with moderate-to-severe atopic dermatitis. (Funded by Dermira; ADvocate1 and ADvocate2 ClinicalTrials.gov numbers, NCT04146363 and NCT04178967, respectively.).

Efficacy and safety of rademikibart (CBP-201), a next-generation mAb targeting IL-4Rα, in adults with moderate to severe atopic dermatitis: A phase 2 randomized trial (CBP-201-WW001).

BACKGROUND: Rademikibart (CBP-201) is a next-generation IL-4 receptor alpha-targeting antibody. OBJECTIVE: We sought to evaluate rademikibart in adults with moderate to severe atopic dermatitis. METHODS: A total of 226 patients were randomized, double-blind, to subcutaneous rademikibart (300 mg every 2 weeks [Q2W], 150 mg Q2W, 300 mg every 4 weeks [Q4W]; plus 600-mg loading dose) or placebo. Randomization began in July 2020. The trial was completed in October 2021. RESULTS: The WW001 phase 2 trial achieved its primary end point: significant percent reduction from baseline in least-squares mean Eczema Area Severity Index (EASI) to week 16 with rademikibart 300 mg Q2W (-63.0%; P = .0007), 150 mg Q2W (-57.6%; P = .0067), 300 mg Q4W (-63.5%; P = .0004) versus placebo (-39.7%). EASI scores decreased significantly with 300 mg Q2W and Q4W at the earliest assessment (week 2), with no evidence of plateauing by week 16. Significant improvements were also observed in secondary end points, including pruritus. Across the primary and secondary end points, efficacy tended to be comparable with 300 mg Q2W and Q4W dosing. Rademikibart and placebo had similar, low incidence of treatment-emergent adverse events (TEAEs) (48% vs 54%), serious TEAEs (1.8% vs 3.6%), TEAEs leading to treatment discontinuation (1.2% vs 1.8%), conjunctivitis of unspecified cause (2.9% vs 0%), herpes (0.6% vs 1.8%), and injection-site reactions (1.8% vs 1.8%). Although no discontinuations were attributed to coronavirus disease 2019, pandemic-related restrictions likely had an impact on trial conduct. CONCLUSIONS: Rademikibart was efficacious and well tolerated at Q2W and Q4W intervals. Q4W dosing is a more convenient frequency than approved for current therapies.

Bacterial colonisation of the airway in neonates and risk of asthma and allergy until age 18†years.

BACKGROUND: We previously showed an association between neonatal bacterial airway colonisation and increased risk of persistent wheeze/asthma until age 5 years. Here, we study the association with persistent wheeze/asthma and allergy-related traits until age 18 years. METHODS: We investigated the association between airway colonisation with Streptococcus pneumoniae, Moraxella catarrhalis and/or Haemophilus influenzae in 1-month-old neonates from the COPSAC2000 mother-child cohort and the development of persistent wheeze/asthma and allergy-related traits longitudinally until age 18 years using generalised estimating equations. Replication was sought in the similarly designed COPSAC2010 cohort of 700 children. RESULTS: Neonatal airway colonisation was present in 66 (21%) out of 319 children and was associated with a 4-fold increased risk of persistent wheeze/asthma (adjusted OR 4.01 (95% CI 1.76-9.12); p<0.001) until age 7 years, but not from age 7 to 18 years. Replication in the COPSAC2010 cohort showed similar results using 16S data. Colonisation was associated with an increased number of exacerbations (adjusted incidence rate ratio 3.20 (95% CI 1.38-7.44); p<0.01) until age 7 years, but not from age 7 to 18 years. Colonisation was associated with increased levels of blood eosinophils (adjusted geometric mean ratio 1.24 (95% CI 1.06-1.44); p<0.01) and tumour necrosis factor (TNF)-α (adjusted geometric mean ratio 1.09 (95% CI 1.02-1.16); p=0.01) until age 12 years. There were no associations with lung function, bronchial reactivity, fractional exhaled nitric oxide, allergic sensitisation, total IgE or atopic dermatitis up to age 18 years. CONCLUSIONS: Neonatal airway colonisation was associated with early-onset persistent wheeze/asthma, exacerbations, elevated blood eosinophils and elevated TNF-α in blood, most prominent in early childhood, thereafter diminishing and no longer evident by age 18 years.

The involvement of keratinocytes in pruritus of chronic inflammatory dermatosis.

Frequent itching and incessant scratching are commonly observed in various chronic inflammatory skin conditions, including atopic dermatitis and psoriasis. The persistent and prolonged nature of pruritus can worsen one's quality of life. Keratinocytes (KCs), the predominant cells of the epidermis, have been confirmed to interact with sensory neurons and immune cells and be involved in chronic skin inflammatory diseases associated with pruritus. Initially, KCs and sensory neurons form a unique synapse-like connection within the epidermis, serving as the structural foundation for their interaction. Additionally, several receptors, including toll-like receptors and protease-activated receptor 2, expressed on KCs, become activated in an inflammatory milieu. On the one hand, activated KCs are sources of pro-inflammatory cytokines and neurotrophic factors, such as adenosine triphosphate, thymic stromal lymphopoietin, and nerve growth factor, which directly or indirectly participate in stimulating sensory neurons, thereby contributing to the itch sensations. On the other hand, KCs also function as primary transducers alongside intraepidermal nerve endings, directly initiating pruritic responses. This review summarizes the current literature and highlights the critical role of KCs in the development and persistence of chronic itch in inflammatory skin disorders.

Efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis and comorbid allergies.

BACKGROUND: Abrocitinib efficacy by comorbidity status in patients with moderate-to-severe atopic dermatitis (AD) has not been previously assessed. This post hoc analysis evaluated the efficacy and safety of abrocitinib in patients with AD and allergic comorbidities. METHODS: Data were pooled from patients who received abrocitinib 200 mg, 100 mg, or placebo in phase 2b (NCT02780167) and phase 3 (NCT03349060, NCT03575871) monotherapy trials. Patients with and without allergic comorbidities (allergic asthma, rhinitis, conjunctivitis, or food allergy) were evaluated for Investigator's Global Assessment (IGA) response (clear [0] or almost clear [1]), ≥75% improvement in the Eczema Area and Severity Index (EASI-75), ≥4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4), and Dermatology Life Quality Index (DLQI) response (<2 with baseline score ≥2). Other outcomes were Patient-Oriented Eczema Measure (POEM), SCORing Atopic Dermatitis (SCORAD), Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD), and treatment-emergent adverse events (TEAEs). RESULTS: Of 942 patients, 498 (53%) reported at least one allergic comorbidity (asthma only, 33%; conjunctivitis only or rhinitis only or both, 17%; food allergies only, 15%; >1 allergic comorbidity, 34%). Regardless of comorbidity status, from Week 2 to Week 12, higher percentages of patients treated with either abrocitinib dose achieved IGA 0/1, EASI-75, PP-NRS4, or DLQI 0/1 versus placebo-treated patients. Changes from baseline in POEM, SCORAD, and PSAAD were greater with abrocitinib than with placebo in patients with and without allergic comorbidities. Most TEAEs were mild or moderate. CONCLUSIONS: Efficacy and safety data support abrocitinib use to manage AD in patients with or without allergic comorbidities.

Association between allergic conditions and COVID-19 susceptibility and outcomes.

BACKGROUND: The relationship between underlying type 2 inflammation and immune response to COVID-19 is unclear. OBJECTIVE: To assess the relationships between allergic conditions and COVID-19 susceptibility and outcomes. METHODS: In the Optum database, adult patients with and without major allergic conditions (asthma, atopic dermatitis [AD], allergic rhinitis, food allergy, anaphylaxis, or eosinophilic esophagitis) and patients with and without severe asthma/AD were identified. Adjusted incidence rate ratios for COVID-19 were compared among patients with vs without allergic conditions or severe asthma/AD vs non-severe asthma/AD during April 1, 2020, to December 31, 2020. Among patients with COVID-19, adjusted hazard ratios (aHRs) of 30-day COVID-19-related hospitalization/all-cause mortality were estimated for the same comparisons during April 1, 2020, to March 31, 2022. RESULTS: Patients with (N = 1,273,231; asthma, 47.2%; AD, 1.5%; allergic rhinitis, 58.6%; food allergy, 5.1%; anaphylaxis, 4.1%; eosinophilic esophagitis, 0.9%) and without allergic conditions (N = 2,278,571) were identified. Allergic conditions (adjusted incidence rate ratios [95% CI], 1.22 [1.21-1.24]) and asthma severity (1.12 [1.09-1.15]) were associated with increased incidence of COVID-19. Among patients with COVID-19 (patients with [N = 261,076] and without allergic conditions [N = 1,098,135] were matched on age, sex, region, index month), having an allergic condition had minimal impact on 30-day COVID-19-related hospitalization/all-cause mortality (aHR [95% CI] 0.96 [0.95-0.98]) but was associated with a lower risk of mortality (0.80 [0.78-0.83]). Asthma was associated with a higher risk of COVID-19-related hospitalization/all-cause mortality vs non-asthma allergic conditions (aHR [95% CI], 1.27 [1.25-1.30]), mostly driven by higher hospitalization. CONCLUSION: Allergic conditions were associated with an increased risk of receiving COVID-19 diagnosis but reduced mortality after infection.

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.

Venous thromboembolism risk is lower in patients with atopic dermatitis than other immune-mediated inflammatory diseases: A retrospective, observational, comparative cohort study using US claims data.

BACKGROUND: Certain immune-mediated inflammatory diseases (IMIDs) may increase patients' risk for venous thromboembolisms (VTEs), yet how atopic dermatitis (AD) influences VTE risk remains unclear. OBJECTIVE: Describe VTE incidence in patients with AD compared with other IMIDs and unaffected, AD-matched controls. METHODS: This retrospective, observational, comparative cohort study used Optum Clinformatics United States claims data (2010-2019) of adults with AD, rheumatoid arthritis (RA), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS). Unaffected control patients were matched 1:1 with patients with AD. RESULTS: Of 2,061,222 patients with IMIDs, 1,098,633 had AD. Patients with AD had a higher VTE incidence (95% CI) than did unaffected, AD-matched controls (0.73 [0.72-0.74] versus 0.59 [0.58-0.60] cases/100 person-years). When controlling for baseline VTE risk factors, however, AD was not associated with increased VTE risk (HR 0.96 [0.90-1.02]). VTE risk was lower in patients with AD versus RA, UC, CD, AS, or PsA; VTE risk was similar to patients with PsO. LIMITATIONS: Disease activity and severity were not accounted for. CONCLUSION: AD did not increase VTE risk when accounting for underlying risk factors. AD was associated with lower VTE risk compared with several rheumatologic and gastrointestinal IMIDs.

Topical therapy and skin care for transplant-associated atopic dermatitis in children and adolescents.

BACKGROUND: New-onset allergic diseases, such as food allergy or atopic dermatitis, can develop after allogeneic transplantation. There are limited reports of new-onset atopic dermatitis after allogeneic hematopoietic stem cell transplantation in children and adolescents, and its treatment is yet to be established. The pathogenesis may differ from typical atopic dermatitis in terms of alloimmunity including graft-versus-host disease. METHODS: We present five children and adolescents with new-onset atopic dermatitis after allogeneic hematopoietic stem cell transplantation. The characteristics and clinical profiles of skin treatment after hematopoietic stem cell transplantation are summarized. RESULTS: Graft-versus-host disease prophylaxis included systemic tacrolimus for all patients. After hematopoietic stem cell transplantation, all patients achieved complete donor chimerism of the bone marrow and had acute graft-versus-host disease of the skin. After engraftment, all patients had skin lesions that met the international consensus diagnostic criteria for atopic dermatitis. None of the patients met the diagnostic criteria for chronic graft-versus-host disease. Topical therapy and skin care based on atopic dermatitis guidelines improved skin condition and atopic dermatitis severity scores in all patients. In addition, type 2 inflammatory markers improved accordingly. CONCLUSION: Topical therapy and skin care may be effective for transplant-related atopic dermatitis after hematopoietic stem cell transplantation. When extensive dermatitis is observed after hematopoietic stem cell transplantation, this treatment may avoid excessive immunosuppressive therapy if it meets the diagnostic criteria for atopic dermatitis.

Perforating lichen nitidus in the setting of atopic dermatitis.

Perforating lichen nitidus is a rare subtype of lichen nitidus, with approximately 11 cases reported worldwide. Lesions typically present in young male patients at sites prone to mechanical irritation, including the hands, feet, forearms, elbows, and knees. Classic histopathologic features of perforating lichen nitidus show a lymphohistiocytic infiltrate within the papillary dermis between hyperplastic rete ridges with transepidermal elimination of dermal contents. Very few cases are reported in the literature of lichen nitidus and its association with atopic dermatitis. This is the first case describing perforating lichen nitidus in a patient with a history of atopic dermatitis being treated with dupilumab injections. Lesions of perforating lichen nitidus worsened with successful treatment of atopic dermatitis. These findings suggest a unique pathophysiology of perforating lichen nitidus lesions.

Global influence of dupilumab on Quality of Life in a severe asthma patient with T2 multimorbidities: a case report on atopic dermatitis, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis.

INTRODUCTION: Interleukin (IL)-4 and IL-13 are considered key drivers of type 2 inflammatory diseases. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for IL-4 and IL-13, thus inhibiting signaling of both cytokines. CASE STUDY: We report a case of a patient with uncontrolled severe asthma and other T2 inflammatory diseases (atopic dermatitis, chronic rhinosinusitis with nasal polyposis and eosinophilic esophagitis) treated with dupilumab. RESULTS: After one year of treatment, dupilumab improved asthma control together with lung function parameters and airway inflammation. Additionally, a positive impact on quality of life (QoL), evaluated by validated questionnaires, across all the diseases was observed. CONCLUSION: In this case report, a positive and objectively measurable of global improvement on QoL across all four T2 comorbidities was observed after treatment with dupilumab, demonstrating the important role of IL-4 and IL-13 and the existence of a unifying pathological mechanism in T2 diseases.

Risk of Type 1 Diabetes Mellitus in Patients with Atopic Dermatitis: A Nationwide Population-Based Cohort Study.

INTRODUCTION: Atopic dermatitis (AD) is a disease frequently occurring in children. The immune response is characterized by T-helper (Th)-2-dependent inflammation. Type 1 diabetes mellitus (T1DM) is an autoimmune disease that destroys pancreatic islet beta cells. In contrast, it is mainly mediated by a Th-1-dependent response. An inverted association has been hypothesized between T1DM and AD since Th1 and Th2 responses are mutually inhibitory. METHODS: Data was retrieved from a nationwide healthcare database in Taiwan. A logistic regression model was used to evaluate the association of T1DM in patients with AD within a year. A Cox proportional hazards analysis was used to evaluate the subsequent risk of developing T1DM 1 year after AD diagnosis. RESULTS: We identified 396,461 patients with AD and 1,585,844 age- and sex-matched controls. During the first year of follow-up, after adjusting variates, the association between T1DM and AD showed no statistical differences (odds ratio: 1.40; 95% confidence interval [CI]: 0.83-2.38, p = 0.207). After excluding those T1DM cases within 1 year of AD diagnosis and those with a follow-up duration of less than 1 year, AD did not significantly increase the risk of T1DM (hazard ratio [HR]: 1.02; 95% CI, 0.83-1.25, p = 0.843). CONCLUSIONS: Our study revealed that there was no significant association between AD and T1DM in the first year after AD diagnosis, and there was no increased risk of T1DM in AD patients in the average 5-year follow-up in our study.

Abrocitinib Provides Rapid and Sustained Improvement in Skin Pain and Is Associated with Improved Quality of Life Outcomes in Adult and Adolescent Patients with Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Skin pain in atopic dermatitis (AD) increases with disease severity and is associated with substantial quality of life (QoL) burden. OBJECTIVES: The aim of the study was to evaluate abrocitinib efficacy on skin pain and QoL in adults and adolescents with moderate-to-severe AD. METHODS: This post hoc analysis included data with abrocitinib administered as monotherapy (pooled phase 2b [NCT02780167] and phase 3 JADE MONO-1 [NCT03349060] and JADE MONO-2 [NCT03575871]) or in combination with topical therapy (phase 3 JADE COMPARE [NCT03720470] and JADE TEEN [NCT03796676]). Patients received oral, once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 or 16 weeks (JADE COMPARE). Skin pain was rated using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) skin pain Numerical Rating Scale (NRS) item ("How painful was your skin over the past 24 h?") on a scale from 0 (not painful) to 10 (extremely painful). Itch (Peak Pruritus NRS) and QoL (Dermatology Life Quality Index or Children's Dermatology Life Quality Index) were assessed. Least squares mean (LSM) change from baseline was analyzed using mixed-effects repeated measures modeling. RESULTS: A total of 1,822 patients (monotherapy pool, n = 942; JADE COMPARE, n = 595; and JADE TEEN, n = 285) were analyzed. LSM change from baseline in PSAAD skin pain score was significantly greater with abrocitinib versus placebo from week 2 through week 12 or 16 across all 3 study populations and occurred in a dose-dependent manner. A greater proportion of patients achieved a ≥4-point improvement from baseline in PSAAD skin pain score with abrocitinib (200 mg and 100 mg) versus placebo in the monotherapy pool (56% and 38% vs. 12%; week 12), JADE COMPARE (72% and 52% vs. 26%; week 16), and JADE TEEN (51% and 60% vs. 31%; week 12). Additionally, a greater proportion of patients achieved a stringent threshold of skin pain improvement (PSAAD skin pain score <2) with abrocitinib versus placebo. Adults and adolescents who achieved a ≥4-point improvement in skin pain reported greater QoL improvement than those who did not achieve a ≥4-point improvement. A positive correlation (≥0.3) was observed between skin pain and QoL and separately between skin pain and itch across the 3 study populations. CONCLUSION: Abrocitinib as monotherapy or in combination with topical therapy improved skin pain and was associated with improved QoL in both adults and adolescents with moderate-to-severe AD across all evaluated studies.

Associations of Atopic Dermatitis with Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND: Atopic dermatitis (AD) shares similarities with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) regarding pathogenesis involving neuroinflammation and genetics. Nevertheless, evidence on the associations of AD with ADHD and/or ASD is inconclusive. This study aimed to systematically examine the existing evidence on the associations between AD, ADHD, and ASD. METHODS: The Meta-Analysis of Observational Studies in Epidemiology guideline was followed. We searched MEDLINE, Embase, Cochrane Library, and Web of Science databases from their respective inceptions to March 4, 2022. Observational studies providing adjusted estimates and/or prevalences for ADHD and ASD in patients with AD were enrolled. A random-effects model meta-analysis was conducted to calculate pooled odds ratios (ORs) and confidence intervals (CIs). Subgroup analyses according to AD severity, age, geographic location, and study design were performed. RESULTS: Overall, a total of 24 studies with 71,373,639 subjects were enrolled. Our meta-analysis demonstrated significant associations of AD with ADHD (pooled OR: 1.28; 95% CI: 1.18-1.40) and ASD (pooled OR: 1.87; 95% CI: 1.30-2.68). Subgroup analyses revealed that the associations for ADHD were the most prominent in studies evaluating severe AD patients as well as in studies focusing on school-age children and adolescents. Among patients with AD, the pooled prevalence of ADHD was 6.6%, and the respective prevalence of ASD was 1.6%. CONCLUSION: The evidence to date suggests significant associations of AD with ADHD and ASD. Psychiatric consultation and an interdisciplinary approach would benefit patients with AD presented with behavioral symptoms suggestive of ADHD or ASD.

Comprehensive Ophthalmological Evaluation in Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD), a chronic type 2 inflammatory skin disease, is frequently associated with ocular surface diseases (OSD) which may appear or worsen under anti-type 2-targeted treatments. However, the exact prevalence of OSD and the ophthalmology referral criteria remain ill-defined in AD patients before initiating such biotherapies. We aimed to characterize the prevalence, the nature and the factors related to OSD development in AD that may justify an ophthalmological management. METHODS: A total of 98 consecutive AD inpatients without biological treatment were retrospectively included. These were systematically evaluated by an ophthalmologist during their dermatological care. Clinical and laboratory data were analysed to characterize OSD and their risk factors. RESULTS: OSD were found in 83/98 AD patients (85%); mainly dry eye syndrome (64%, 63/98), allergic conjunctivitis (42%, 41/98), posterior (33%, 32/98), and anterior blepharitis (27%, 26/98). In AD patients without ocular symptoms, OSDs were also frequently found (63%, 12/19) and were mostly mild. Risk factors for OSD were history of allergic rhinitis, allergic sensitization, head and neck AD, ocular symptoms (foreign body sensation in the eye, burning, itching, photophobia), and total IgE level >3,000 kU/L. CONCLUSION: The prevalence of OSD was high, even in asymptomatic patients. The risk factors identified may indicate the need for ophthalmological examination for therapeutic management, especially when biological agents targeting type 2 inflammation are considered.

Does Molluscum Contagiosum Need to be Managed Differently in Atopic Children?

The association between molluscum contagiosum and concomitant atopic dermatitis and its impact on clinical features and treatment outcomes remains unclear. This retrospective study, conducted in the paediatric dermatology clinic of a tertiary medical centre, aimed to compare molluscum patients with and without atopic dermatitis. A total of 615 children with molluscum were included, 13.17% of whom had atopic dermatitis. While the latter group exhibited higher lesion count and itchiness (p=0.026 and p=0.044, respectively), no significant differences were observed in average lesion diameter, ulceration, purulence, and erythema (p=0.239, p=0.730, p=0.682, and p=0.296, respectively). Both groups showed comparable responses to molluscum-specific and supportive treatments, with no distinct difference in outcomes or recurrence of visits. It was concluded that atopic dermatitis does not exacerbate molluscum morbidity, inflammation markers, treatment outcomes or recurrence rates.

Short-term Heat Application Reduces Itch Intensity in Atopic Dermatitis: Insights from Mechanical Induction and Real-life Episodes.

Heat application is known to activate transient receptor potential (TRP) channels, which play a crucial role in sensory perception, including itch. In this study, the effect of a 5-s, 49°C heat application on itch intensity in atopic dermatitis (AD) patients was evaluated. The study comprised 2 parts: a controlled trial investigating the impact of brief heat treatment on mechanically induced itch, and a real-life study of AD patients experiencing itch attacks. A significant and immediate reduction in itch sensations following heat application was shown, with effects enduring over time. This response, however, showed notable individual variability, underscoring the potential of personalized approaches in AD treatment. Repeated applications of heat showed no habituation effect, suggesting its viability as a non-pharmacological, patient-tailored option for managing itch in AD. Further research in larger cohorts is warranted to refine treatment protocols and deepen understanding of the mechanisms involved.

A Qualitative Tool to Guide in the Interpretation of the Numerical Rating Scale for Pruritus Intensity in Patients with Atopic Dermatitis.

Atopic dermatitis is a cutaneous inflammatory disease characterized by intense pruritus, which is often underestimated despite its direct impact on patients' health-related quality of life and the high burden it poses. The authors' goal was to design a qualitative tool to guide patients and healthcare professionals in their assessment and interpretation of pruritus intensity using a numerical rating scale. The draft of this tool, henceforth "guideline", was developed based on a systematic literature review and focus groups comprising patients and a scientific committee. This draft was validated with an independent group of patients and the final version was designed following their feedback. According to the results of the systematic review, pruritus impacts 6 health-related quality of life domains: sleep quality; emotional status; overall health-related quality of life; physical function; social/sexual activity; productivity, particularly affecting sleep quality and the emotional domain. Patients considered that physical function was the most strongly affected domain, followed by sleep quality and emotional well-being, establishing that a minimum pruritus intensity of 4 and 7 points impacts moderately and severely, respectively, on the different domains of patients' health- related quality of life. The guideline may help patients and healthcare professionals to interpret and assess pruritus intensity using a numerical rating scale and to understand the impact of pruritus on patients' health-related quality of life.

The Circadian Rhythm of Itching among 241 Adults with Atopic Dermatitis: A Cross-sectional Study.

The pattern of itching in patients with atopic dermatitis has not been systematically studied. Therefore, this study aimed to assess the pattern of itching in adults with atopic dermatitis using questionnaires to assess for a circadian rhythm of itching in participating patients at a single institution (n = 241). A self-report questionnaire was used to assess circadian rhythm and intensity of itching in patients. In addition, the patients' disease severity (Eczema Area and Severity Index [EASI]) and quality of life (Dermatology Life Quality Index [DLQI]) were assessed. Itching occurred most frequently (74.69%) and with the greatest severity (62.66%) between 20:00 and 00:00, and the least number of patients (25.31%) experienced itching between 04:00 and 08:00. The DLQI and EASI scores both correlated with the average and maximum itch intensity (r = 0.582, r = 0.533, respectively; r = 0.539, r = 0.517, respectively; p < 0.001). The DLQI and EASI scores were associated with average itch intensity (B = 0.179, B = 0.204, respectively; 95% CI: 0.112 to 0.246, 95% CI: 0.096 to 0.313, respectively; p < 0.001), and the EASI score was associated with males and family history (B = 0.285, B = 0.287, respectively; 95% CI: 0.094 to 0.476, 95% CI: 0.096 to 0.478, respectively; p = 0.003). Adult patients with atopic dermatitis exhibited a circadian rhythm of itching; these study results could positively impact treatment approaches.

Causal relationships between atopic dermatitis and psychiatric disorders: a bidirectional two-sample Mendelian randomization study.

BACKGROUND: Observational studies have suggested the potential associations between atopic dermatitis (AD) and psychiatric disorders. However, the causal relationship between them remains uncertain. This study aimed to evaluate the potential bidirectional causal relationship between AD and psychiatric disorders, including autism spectrum disorder (ASD), major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), anorexia nervosa (AN), Tourette syndrome (TS), schizophrenia, and anxiety. METHODS: Bidirectional two-sample Mendelian randomization (MR) was employed to elucidate the causality between AD and psychiatric disorders, using summary statistics from the most comprehensive genome-wide association studies conducted on AD (Ncases = 60,653, Ncontrols = 804,329). Psychiatric disorders were derived from the Psychiatric Genomics Consortium and were independent of AD data sources. The MR analysis entailed the implementation of multiple methods, including the inverse variance weighted method, MR-Egger regression method, weighted median method, simple mode method, and weighted mode method. RESULTS: Bidirectional two-sample MR analysis uncovered significant causal associations between AD and severe psychiatric disorders. Specifically, liability to AD was associated with increased risk of ADHD (OR = 1.116; 95% CI: [1.009, 1.234]; P = 0.033) and ASD (OR = 1.131; 95% CI: [1.023, 1.251]; P = 0.016). Additionally, evidence suggested that liability to ADHD (OR = 1.112; 95% CI: [1.094, 1.130]; P = 9.20e-40), liability to AN (OR = 1.1; 95% CI: [1.068, 1.134]; P = 4.45e-10) and liability to BD (OR = 1.067; 95% CI: [1.009, 1.128]; P = 0.023) were associated with an increased risk of AD. Only the causal association between AD and ASD was independent of the reverse effect bias. These causal associations were robust and not affected by biases of heterogeneity and horizontal pleiotropy. CONCLUSIONS: Our study emphasizes the significant causal association between AD and an increased risk of ASD, and also identifying BD and AN as risk factors for AD.