Bruton's tyrosine kinase (BTK), a member of the Tec kinase family, is critically involved in a range of immunological pathways. The clinical application of BTK inhibitors for B‐cell malignancies has proven successful, and there is strong rationale for the potential benefits of BTK inhibitors in some autoimmune and allergic conditions, including immune‐mediated dermatological diseases. However, the established risk‐to‐benefit profile of “first‐generation” BTK inhibitors cannot be extrapolated to these emerging, non‐oncological, indications. “Next‐generation” BTK inhibitors such as remibrutinib and fenebrutinib entered clinical development for chronic spontaneous urticaria (CSU); rilzabrutinib and tirabrutinib are being studied as potential treatments for pemphigus. Promising data from early‐phase clinical trials in CSU suggest potential for these agents to achieve strong pathway inhibition, which may translate into measurable clinical benefits, as well as other effects such as the disruption of autoantibody production. BTK inhibitors may help to overcome some of the shortcomings of monoclonal antibody treatments for immune‐mediated dermatological conditions such as CSU, pemphigus, and systemic lupus erythematosus. In addition, the use of BTK inhibitors may improve understanding of the pathophysiological roles of mast cells, basophils, and B cells in such conditions.

Background: Atopic dermatitis (AD), a relapsing, inflammatory skin disease, is associated with pruritus that can negatively affect patients' quality of life. Understanding the burden of AD is critical for informing and tailoring treatment and disease management to improve patient outcomes. This study characterized global treatment patterns and the clinical, psychosocial and economic burden of moderate‐to‐severe AD.Methods: MEASURE‐AD was a cross‐sectional 28‐country study in patients with physician‐confirmed moderate‐to‐severe AD who were either receiving or eligible for systemic therapy for AD. Patients ≥12 years were enrolled between December 2019 and December 2020 while attending routine office or clinic visit. Primary outcomes included Worst Pruritus Numeric Rating Scale (WP‐NRS; range: 0–10) and Dermatology Life Quality Index (DLQI; range: 0–30) and Children's DLQI (CDLQI; range: 0–30). Secondary outcomes included physician‐ and patient‐reported clinical, psychosocial and economic burden.Results: Of the 1591 patients enrolled, 1558 (1434 adults and 124 adolescents) fulfilled all patient selection criteria and were included in this analysis. Almost all patients (98.4%) in the total population were using AD medications and more than half (56%) were receiving systemic medication (15% systemic monotherapy). The most used systemic therapies were dupilumab (56.3%), systemic glucocorticoids (18.1%) and methotrexate (16.2%). Mean WP‐NRS was 5.3 in the total population, and most patients (≥55%) reported moderate‐to‐severe pruritus (WP‐NRS ≥4). Mean DLQI was 10.8 and mean CDLQI was 9.6. Secondary endpoints demonstrated substantial clinical, psychosocial, and economic burden of disease. Subgroup analysis demonstrated that patients receiving systemic therapy had lower disease burden than those not taking systemic medications.Conclusions: While systemic therapy lowers overall disease burden, patients with moderate‐to‐severe AD continue to have substantial multidimensional disease burden and uncontrolled disease. Overall, there is a need for effective disease management, including effective treatments that improve patients' psychosocial outcomes and reduce the economic burden of AD.

Acne is the most frequent adverse event associated with upadacitinib treatment in patients with moderate-to-severe atopic dermatitis. To characterize the adverse event of acne associated with upadacitinib. This was a post hoc integrated analysis of 3 phase 3 randomized, double-blind, placebo-controlled trials of upadacitinib, alone (NCT03569293 and NCT03607422) or in combination with topical corticosteroids (NCT03568318). Data included were from the 16-week placebo-controlled period. Over 16 weeks, 84 of 857 (9.8%), 131 of 864 (15.2%), and 19 of 862 (2.2%) patients randomized to receive upadacitinib 15 mg, upadacitinib 30 mg, and placebo, respectively, experienced acne. All cases of acne, except 1, were mild/moderate in severity; 2 patients discontinued treatment due to moderate acne. Acne occurred at higher rates among younger, female, and non-White patients. Acne required no intervention in 40.5% and 46.6% of patients receiving upadacitinib 15 and 30 mg, respectively; most remaining cases were managed with topical antibiotics, benzoyl peroxide, and/or retinoids. Acne also had no impact on patient-reported outcomes. This study was relatively short in duration and had a small patient population. Acne associated with upadacitinib for atopic dermatitis treatment is usually mild/moderate in severity and managed with topical therapies or no intervention.

Introduction: Psoriasis (PsO) is a chronic skin condition driven by immune mediators like TNFα, INFγ, IL-17, and IL-23. Psoriatic arthritis (PsA) can develop in PsO patients. Although psoriatic lesions may apparently resolve with therapy, subclinical cutaneous inflammation may persist. The role of tissue-resident memory T-cells (T_RM), and regulatory T cells (Tregs) that also contribute to chronic inflammation are being explored in this context. This systematic review explores T_RM and Tregs in psoriatic disease (PsD) and its progression.Methods: A systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was performed using Pubmed® and Web of Science™ databases on June 3^rd 2023, using patient/population, intervention, comparison, and outcomes (PICO) criteria limited to the English language.Results: A total of 62 reports were identified and included. In PsO, chronic inflammation is driven by cytokines including IL-17 and IL-23, and cellular mediators such as CD8⁺ and CD4⁺ T cells. T_RM contributes to local inflammation, while Tregs may be dysfunctional in psoriatic skin lesions. Secukinumab and guselkumab, which target IL-17A and the IL-23p19 subunit, respectively, have different effects on CD8⁺ T_RM and Tregs during PsO treatment. Inhibition of IL-23 may provide better long-term results due to its impact on the Treg to CD8⁺ T_RM ratio. IL-23 may contribute to inflammation persisting even after treatment. In PsA, subclinical enthesitis is perceived as an early occurence, and Th17 cells are involved in this pathogenic process. Recent EULAR guidelines highlight the importance of early diagnosis and treatment to intercept PsA. In PsA, CD8⁺ T_RM cells are present in synovial fluid and Tregs are reduced in peripheral blood. The progression from PsO to PsA is marked by a shift in immune profiles, with specific T-cells subsets playing key roles in perpetuating inflammation. Early intervention targeting T_RM cells may hold promising, but clinical studies are limited. Ongoing studies such as IVEPSA and PAMPA aim to improve our knowledge regarding PsA interception in high-risk PsO patients, emphasizing the need for further research in this area.Conclusion: Early intervention is crucial for PsO patients at high risk of PsA; T cells, particularly type 17 helper T cells, and CD8⁺ cells are key in the progression from PsO-to-PsA. Early targeting of T_RM in PsD shows promise but more research is needed.