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BACKGROUND. Pemphigus, a rare autoimmune bullous disease mediated by antidesmoglein autoantibodies, can be controlled with systemic medication like rituximab and high-dose systemic corticosteroids combined with immunosuppressants. However, some patients continue to experience chronically recurrent blisters in a specific area and require long-term maintenance systemic therapy. METHODS. Skin with chronic blisters was obtained from patients with pemphigus. Immunologic properties of the skin were analyzed by immunofluorescence staining, bulk and single-cell RNA and TCR sequencing, and a highly multiplex imaging technique known as CO-Detection by indEXing (CODEX). Functional analyses were performed by flow cytometry and bulk RNA-Seq using peripheral blood from healthy donors. Intralesional corticosteroid was injected into patient skin, and changes in chronically recurrent blisters were observed. RESULTS. We demonstrated the presence of skin tertiary lymphoid structures (TLSs) with desmoglein-specific B cells in chronic blisters from patients with pemphigus. In the skin TLSs, [CD4.sup.+] T cells predominantly produced CXCL13. These clonally expanded [CXCL13.sup.+][CD4.sup.+] T cells exhibited features of activated Th1-like cells and downregulated genes associated with T cell receptor-mediated signaling. Tregs are in direct contact with [CXCL13.sup.+][CD4.sup.+] memory T cells and increased CXCL13 production of [CD4.sup.+] T cells through IL-2 consumption and TGF-p stimulation. Finally, intralesional corticosteroid injection improved chronic blisters and reduced skin TLSs in patients with pemphigus. CONCLUSION. Through this study we conclude that skin TLSs are associated with the persistence of chronically recurrent blisters in patients with pemphigus, and the microenvironmental network involving [CXCL13.sup.+][CD4.sup.+] T cells and Tregs within these structures plays an important role in CXCL13 production. TRIAL REGISTRATION. ClinicalTrials.gov NCT04509570. FUNDING. This work was supported by National Research Foundation of South Korea (NRF-2021R1C1C1007179) and Korea Drug Development Fund, which is funded by Ministry of Science and ICT; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare (grant RS-2022-00165917)., Introduction Pemphigus is a rare and life-threatening autoimmune disease that manifests as blisters and erosions on skin and/or mucosa. It is mediated by autoreactive B cells targeting desmoglein 1 (DSG1) [...]

BackgroundSeveral European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management.ObjectiveWe now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations.MethodsA preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus.ResultsThe 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion.LimitationsEach recommendation represents the majority opinion and therefore may not reflect all possible treatment options available.ConclusionsWe present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.

Perovskite solar cells have made significant progress in the past decade, demonstrating promising potential for next‐generation solar technology. However, the strain‐induced intrinsic instability of mixed‐halide perovskites poses a significant obstacle to their widespread commercialization. Relaxation of the perovskite lattice strain is a crucial approach for enhancing photovoltaic performance and broadening their application potential. In this study, the authors conduct an analysis of strain progression in perovskite thin films, examining its impact on the physical properties of perovskites and the performance of perovskite solar cells. Furthermore, they explore its influence on device stability from the perspectives of phase transitions, chemical decomposition, and mechanical fragility. Additionally, they provide a summary of key advancements in strain‐relaxation strategies and offer design principles and synthetic approaches to address the issue of lattice strain in perovskites. This paper is intended to lay the groundwork for the theoretical development of effective strain‐relaxation methods, moving beyond sole reliance on empirical optimization. [ABSTRACT FROM AUTHOR]

Rituximab is a monoclonal antibody that targets CD20 antigen in B cells. For pemphigus, rituximab has been highly effective in steroid‐sparing therapy for moderate to severe cases. Originator rituximab has demonstrated favorable treatment effects in patients with pemphigus, but its high cost remains a challenge. Biosimilar rituximab is expected to offer a potential solution. However, it is required for the comparative study of efficacy and safety between biosimilar and originator because all biosimilars may not be identical to the originator. In this study, we compared the treatment effects and safety of biosimilar (Truxima) and originator (MabThera) rituximab in patients with pemphigus. A final cohort of 52 patients in the MabThera group and 72 patients in the Truxima group was enrolled. Except for the intravenous immunoglobulin administration rate, there were no differences in baseline characteristics between the two groups, and for the purpose of comparing efficacy, investigations into time to complete remission, total steroid intake to complete remission, and total steroid intake for 6 months following rituximab treatment revealed no significant differences between the two groups. Truxima can be considered a relatively affordable alternative treatment option for pemphigus, offering cost‐effectiveness to patients who are indicated for the treatment with MabThera. [ABSTRACT FROM AUTHOR]

Rituximab has been the mainstay treatment for autoimmune bullous diseases (AIBDs). Among the side effects of rituximab, rituximab‐induced thrombocytopenia (RIT) is a rare but critical complication. However, there have been no reports or identification of risk factors for RIT in patients with AIBD. In our retrospective study, we compared rituximab‐treated AIBD in patients with and without thrombocytopenia to explore the risk factors. In addition, we compared two different rituximab protocols (rheumatoid arthritis [RA] and lymphoma) in terms of the incidence and severity of thrombocytopenia. A total of 222 patients were enrolled, and 46 patients (20.7%) developed RIT. Multivariate logistic regression analysis identified age and chronic kidney disease (CKD) as significant factors for RIT. We also found that patients treated with the lymphoma protocol demonstrated a significantly higher mean post‐rituximab platelet count compared with those on the RA protocol. This was the first analysis, to our knowledge, of risk factors for RIT in patients with AIBD. Individuals aged 70 or older and those with multiple comorbidities, particularly CKD, should be closely monitored for thrombocytopenia. For patients with CKD, it may be safer to use the lymphoma protocol for rituximab administration as it results in a lesser reduction in post‐rituximab platelet count. [ABSTRACT FROM AUTHOR]

Refractory pruritus is the most distressing, disease‐related symptom in patients with dystrophic epidermolysis bullosa (DEB), inducing an itch‐scratch‐blister cycle. Chronic inflammation is a hallmark of DEB, thus upregulation of inflammatory cytokines and Janus kinase (JAK) signaling may play a role in DEB‐related pruritus. We retrospectively reviewed the medical records of DEB patients with refractory pruritus who were treated with either baricitinib, a JAK1/2 inhibitor, or upadacitinib, a selective JAK1 inhibitor. Patients received baricitinib (4 mg) or upadacitinib (15 mg) once a day for 2–32 weeks. A total of 12 DEB patients (six recessive DEB and six dominant DEB) were included in this study. The mean±SD baseline pruritus visual analog scale (VAS) score was 7.5 ± 1.7. Upadacitinib or baricitinib treatment resulted in a rapid and sustained decrease in itch. Four out of 12 patients (33.3%) and seven out of 10 patients (70%) showed a decrease of at least 3 points in the pruritus VAS score from baseline at weeks 2 and 4, respectively. The mean percentage changes from baseline in pruritus VAS scores at weeks 2 and 4 were −42.9% and −52.7%, respectively. Subgroup analysis showed greater reductions in the pruritus VAS score in the baricitinib group (n = 5) compared to the upadacitinib group (n = 7), and in patients with epidermolysis bullosa pruriginosa (n = 3) compared to other subtypes of DEB (n = 9); however, these differences did not reach statistical significance. Three out of 10 (33.3%) patients showed at least a 2‐point reduction in pain intensity from baseline at week 4. Eight out of 12 patients (66.7%) also showed a reduction in the number of new blisters, which correlated with a reduction in the pruritus score. No patient discontinued treatment because of serious adverse events. Our results suggest that JAK1 or JAK1/2 inhibitors could be a promising treatment option for DEB‐related pruritus. Long‐term safety should be assessed in future studies. [ABSTRACT FROM AUTHOR]

Patients with refractory bullous pemphigoid (BP) achieve remission after rituximab treatment but require high‐dose systemic corticosteroids until the remission. The aim of this retrospective study was to examine the clinical efficacy of omalizumab as an adjuvant treatment to rituximab in patients with refractory BP. Patients with BP receiving treatment with either rituximab monotherapy or rituximab plus omalizumab were considered for the study. The total dose of corticosteroids received for 60 days after administration of rituximab, mortality and relapse rates, and median time to relapse were also investigated. Of 49 patients included in the study, 25 received rituximab monotherapy and 17 received the combination therapy with rituximab and omalizumab. The rituximab plus omalizumab group showed shorter time to disease control with minimal treatment (15 days vs. 67.5 days, p < 0.001) and lower corticosteroid dose for 60 days after administration of rituximab (698.4 mg vs. 1087.4 mg of methylprednisolone, p < 0.001) compared to the rituximab monotherapy group. The results of this study suggest that combination therapy with rituximab and omalizumab can achieve disease control status faster than the rituximab monotherapy, reducing the total dose of corticosteroids. [ABSTRACT FROM AUTHOR]