Thymic Stromal Lymphopoietin Interferes with the Apoptosis of Human Skin Mast Cells by a Dual Strategy Involving STAT5/Mcl-1 and JNK/Bcl-xL

Mast cells (MCs) play critical roles in allergic and inflammatory reactions and contribute to multiple pathologies in the skin, in which they show increased numbers, which frequently correlates with severity. It remains ill-defined how MC accumulation is established by the cutaneous microenvironment, in part because research on human MCs rarely employs MCs matured in the tissue, and extrapolations from other MC subsets have limitations, considering the high level of MC heterogeneity. Thymic stromal lymphopoietin (TSLP)-released by epithelial cells, like keratinocytes, following disturbed homeostasis and inflammation-has attracted much attention, but its impact on skin MCs remains undefined, despite the vast expression of the TSLP receptor by these cells. Using several methods, each detecting a distinct component of the apoptotic process (membrane alterations, DNA degradation, and caspase-3 activity), our study pinpoints TSLP as a novel survival factor of dermal MCs. TSLP confers apoptosis resistance via concomitant activation of the TSLP/ signal transducer and activator of transcription (STAT)-5 / myeloid cell leukemia (Mcl)-1 route and a newly uncovered TSLP/ c-Jun-N-terminal kinase (JNK)/ B-cell lymphoma (Bcl)-xL axis, as evidenced by RNA interference and pharmacological inhibition. Our findings highlight the potential contribution of TSLP to the MC supportive niche of the skin and, vice versa, highlight MCs as crucial responders to TSLP in the context of TSLP-driven disorders

Pemphigus Foliaceus—Repeated Treatment With Rituximab 7 Years After Initial Response: A Case Report

Pemphigus foliaceus is an autoimmune skin disease mediated by autoantibodies directed against desmoglein-1 located in the upper epidermal layer. Rituximab, a monoclonal anit-CD20 antibody depleting b-cells, offers an effective treatment possibility for therapy-resistant pemphigus foliaceus. Here, we present the case of 55-year-old man who did not respond sufficiently to conventional treatment with prednisolone, azathioprine, and cyclophosphamide, but underwent almost complete remission after rituximab treatment. The patient relapsed 7 years later, and a repeated course of rituximab infusions led to a partial remission

Severe Refractory Paraneoplastic Mucous Membrane Pemphigoid Successfully Treated With Rituximab

Mucous membrane pemphigoid (MMP) is a rare autoimmune bullous disease of the mucous membranes, which can cause irreversible scarring and is discussed to be associated with cancer, if laminin-332-autoantibodies are present. MMP with severe ocular and laryngeal involvement is difficult to treat and can be treatment-refractory to conventional immunosuppressant therapy. A 67-year-old man with a history of prostate cancer presented to our clinic with sore throat, intraoral bullae, odynophagia, dysphonia, exertional dyspnea, and erosions of the glans penis. Clinical examination confirmed a laryngo-pharyngitis with involvement of the epiglottis and bilateral symblepharon. Diagnostics comprising multiple biopsies, direct and indirect immunofluorescence, serology analysis, and immunoblotting confirmed the diagnosis of a paraneoplastic MMP by showing a subepithelial split in histology and the presence of anti-laminin-332-antibodies. Despite combined systemic treatment with prednisolone and either dapsone or azathioprine, a progress of the disease occurred leading to severe ocular and laryngeal complications. Two month after rituximab treatment, complete disease control was achieved. This case report shows a severe ocular and life threatening laryngeal involvement of therapy-refractory paraneoplastic MMP highlighting the importance of interdisciplinary management and difficulty of diagnosing MMP despite repeated diagnostic testing

Proximity-Based Emergency Response Communities for Patients With Allergies Who Are at Risk of Anaphylaxis: Clustering Analysis and Scenario-Based Survey Study

BACKGROUND: Anaphylaxis is a potentially fatal allergic reaction. However, many patients at risk of anaphylaxis who should permanently carry a life-saving epinephrine auto injector (EAI) do not carry one at the moment of allergen exposure. The proximity-based emergency response communities (ERC) strategy suggests speeding EAI delivery by alerting patient-peers carrying EAI to respond and give their EAI to a nearby patient in need. OBJECTIVES: This study had two objectives: (1) to analyze 10,000 anaphylactic events from the European Anaphylaxis Registry (EAR) by elicitor and location in order to determine typical anaphylactic scenarios and (2) to identify patients' behavioral and spatial factors influencing their response to ERC emergency requests through a scenario-based survey. METHODS: Data were collected and analyzed in two phases: (1) clustering 10,000 EAR records by elicitor and incident location and (2) conducting a two-center scenario-based survey of adults and parents of minors with severe allergy who were prescribed EAI, in Israel and Germany. Each group received a four-part survey that examined the effect of two behavioral constructs-shared identity and diffusion of responsibility-and two spatial factors-emergency time and emergency location-in addition to sociodemographic data. We performed descriptive, linear correlation, analysis of variance, and t tests to identify patients' decision factors in responding to ERC alerts. RESULTS: A total of 53.1% of EAR cases were triggered by food at patients' home, and 46.9% of them were triggered by venom at parks. Further, 126 Israeli and 121 German participants completed the survey and met the inclusion criteria. Of the Israeli participants, 80% were parents of minor patients with a risk of anaphylaxis due to food allergy; their mean age was 32 years, and 67% were women. In addition, 20% were adult patients with a mean age of 21 years, and 48% were female. Among the German patients, 121 were adults, with an average age of 47 years, and 63% were women. In addition, 21% were allergic to food, 75% were allergic to venom, and 2% had drug allergies. The overall willingness to respond to ERC events was high. Shared identity and the willingness to respond were positively correlated (r=0.51, P<.001) in the parent group. Parents had a stronger sense of shared identity than adult patients (t243= -9.077, P<.001). The bystander effect decreased the willingness of all patients, except the parent group, to respond (F1,269=28.27, P<.001). An interaction between location and time of emergency (F1,473=77.304, P<.001) revealed lower levels of willingness to respond in strange locations during nighttime. CONCLUSIONS: An ERC allergy app has the potential to improve outcomes in case of anaphylactic events, but this is dependent on patient-peers' willingness to respond. Through a two-stage process, our study identified the behavioral and spatial factors that could influence the willingness to respond, providing a basis for future research of proximity-based mental health communities

Current developments in the treatment of peanut allergy

Peanut allergy is a potentially life-threatening disease because it leads to severe allergic reactions, especially in children but also in adults. So far, allergen avoidance is the most effective therapy for treating peanut allergy. In this article, current developments of peanut allergy specific immunotherapy are critically discussed based on the existing literature. These include sublingual, epicutaneous and oral peanut immunotherapy. Nonspecific treatment approaches with new-targeted antibodies such as anti-IgE (omalizumab) or anti-IL-4/IL-13 receptor antibodies (dupilumab) can also be used to treat peanut allergy with regard to the mode of action of these antibodies. Multiple studies are already available for omalizumab and are currently performed with dupilumab. Whether and which therapies for the treatment of peanut allergy will be available on the market in the future is not only relevant in terms of clinical effectiveness in the sense of a long-term stable increase in the threshold level, but also in terms of the tolerability in everyday life of affected patients