IL-4 receptor engagement in human neutrophils impairs their migration and extracellular trap formation

Background Type 2 immunity serves to resist parasitic helminths, venoms, and toxins, but the role and regulation of neutrophils during type 2 immune responses are controversial. Helminth models suggested a contribution of neutrophils to type 2 immunity, whereas neutrophils are associated with increased disease severity during type 2 inflammatory disorders, such as asthma. Objective We sought to evaluate the effect of the prototypic type 2 cytokines IL-4 and IL-13 on human neutrophils. Methods Human neutrophils from peripheral blood were assessed without or with IL-4 or IL-13 for (1) expression of IL-4 receptor subunits, (2) neutrophil extracellular trap (NET) formation, (3) migration toward CXCL8 in vitro and in humanized mice, and (4) CXCR1, CXCR2, and CXCR4 expression, as well as (5) in nonallergic versus allergic subjects. Results Human neutrophils expressed both types of IL-4 receptors, and their stimulation through IL-4 or IL-13 diminished their ability to form NETs and migrate toward CXCL8 in vitro. Likewise, in vivo chemotaxis in NOD-scid-Il2rg−/− mice was reduced in IL-4–stimulated human neutrophils compared with control values. These effects were accompanied by downregulation of the CXCL8-binding chemokine receptors CXCR1 and CXCR2 on human neutrophils on IL-4 or IL-13 stimulation in vitro. Ex vivo analysis of neutrophils from allergic patients or exposure of neutrophils from nonallergic subjects to allergic donor serum in vitro impaired their NET formation and migration toward CXCL8, thereby mirroring IL-4/IL-13–stimulated neutrophils. Conclusion IL-4 receptor signaling in human neutrophils affects several neutrophil effector functions, which bears important implications for immunity in type 2 inflammatory disorders

Oral, esophageal and cutaneous lichen ruber planus controlled with alitretinoin: case report and review of the literature

BACKGROUND: Therapy-resistant lichen planus (LP) can be a challenging condition for dermatologists. There are some case reports about successful treatments with alitretinoin of cutaneous and oral, but not of esophageal LP. OBJECTIVE: We present the unique case of a patient with cutaneous, oral and esophageal LP which was refractory to classical treatment options (topical clobetasol propionate and pimecrolimus, intramuscular triamcinolone acetonide); because of systemic side effects the patient did not tolerate systemic acitretin dosed up to 25 mg daily. Methods: Oral alitretinoin was used at a dose of 30 mg daily. RESULTS: Both oral and skin changes as well as dysphagia completely resolved within 4 weeks without any severe side effects and the drug was used for 6 months. No papules, intraoral striae or dysphagia recurred during the 6 months of treatment. After 4 months the patient relapsed with mucosal patches so that a second cycle was initiated for 6 months where oral LP lesions resolved after 4 weeks also (with sporadic mild headache). CONCLUSION: Further studies are needed to better understand the impact of alitretinoin in LP. Our observation suggests alitretinoin as a new, well-tolerated treatment option for esophageal LP after failed response to conventional treatments

Assessment of treatment response in cardiac sarcoidosis based on myocardial 18^{18}F-FDG uptake

OBJECTIVE Immunosuppressive therapy for cardiac sarcoidosis (CS) still largely consists of corticosteroid monotherapy. However, high relapse rates after tapering and insufficient efficacy are significant problems. The objective of this study was to investigate the efficacy and safety of non-biological and biological disease-modifying anti-rheumatic drugs (nb/bDMARDs) considering control of myocardial inflammation assessed by $^{18}$F-fluorodeoxyglucose positron emission tomography/computed tomography ($^{18}$F-FDG PET/CT) of the heart. METHODS We conducted a retrospective analysis of treatment response to nb/bDMARDs of all CS patients seen in the sarcoidosis center of the University Hospital Zurich between January 2016 and December 2020. RESULTS We identified 50 patients with CS. Forty-five patients with at least one follow-up PET/CT scan were followed up for a mean of 20.5 ± 12.8 months. Most of the patients were treated with prednisone and concomitant nb/bDMARDs. At the first follow-up PET/CT scan after approximately 6.7 ± 3 months, only adalimumab showed a significant reduction in cardiac metabolic activity. Furthermore, comparing all serial follow-up PET/CT scans (143), tumor necrosis factor inhibitor (TNFi)-based therapies showed statistically significant better suppression of myocardial $^{18}$F-FDG uptake compared to other treatment regimens. On the last follow-up, most adalimumab-treated patients were inactive (n = 15, 48%) or remitting (n = 11, 35%), and only five patients (16%) were progressive. TNFi was safe even in patients with severely reduced left ventricular ejection fraction (LVEF), and a significant improvement in LVEF under TNFi treatment was observed. CONCLUSION TNFi shows better control of myocardial inflammation compared to nbDMARDs and corticosteroid monotherapies in patients with CS. TNFi was efficient and safe even in patients with severely reduced LVEF

Efficacy of omalizumab in mastocytosis: allusive indication obtained from a prospective, double-blind, multicenter study (XOLMA Study)

BACKGROUND: Patients with mastocytosis often suffer from a variety of symptoms caused by mast cell mediators where treatments remain difficult, showing various success rates. Omalizumab, a monoclonal anti-IgE antibody, has been postulated to have a positive impact on mastocytosis-associated symptoms such as flush, vertigo, gastrointestinal problems, or anaphylaxis. OBJECTIVE: To investigate the efficacy and safety of omalizumab in systemic mastocytosis. METHODS: Patients with histologically proven mastocytosis were investigated in a multicenter prospective double-blind placebo-controlled trial to receive either omalizumab or placebo, dosed according to IgE and body weight. The primary endpoint was change in the AFIRMM activity score after 6 months of treatment. Different laboratory parameters were analyzed. RESULTS: Sixteen patients were analyzed: 7 to omalizumab and 9 to placebo (mean age 47.7 ± 13.8 vs. 45.4 ± 8.8 years; 66.6 vs. 85.7% were female; mean disease duration 10.0 ± 5.1 vs. 4.5 ± 2.9 years, respectively). After 6 months the median AFIRMM score decreased 50% from 52.0 to 26.0 in the omalizumab group versus 104.0-102.0 in the placebo group (p = 0.286); however, the difference was not significant (p = 0.941). Secondary endpoints, including the number of allergic reactions, changes in major complaints, wheal-and-flare reaction due to mechanical irritation (Darier's sign), and frequency of the use of mastocytosis-specific drugs improved in the omalizumab group, but not significantly. Adverse events like urticaria, bronchospasm, and anaphylactic shock showed no significant difference between the groups. No severe adverse events occurred. FcεRI (Fc-epsilon receptor) expression on basophils decreased after receiving omalizumab versus placebo. CONCLUSION: Omalizumab was safe and showed a tendency to improve mastocytosis-related symptoms, in particular diarrhea, dizziness, flush, and anaphylactic reactions, including the AFIRMM score and secondary endpoints; however, the difference was not significant. Due to the small study size and difference at baseline between the study groups, further studies are required to confirm our findings

Überblick symptomatische Therapien : Akuttherapie bei allergischen Erkrankungen der oberen und unteren Atemwege

Therapien einer Rhinoconjuctivitis allergica (RCA) umfassen Aufklärung, Allergenkarenz, symptomatische Therapie, spezifische Immuntherapie und Rhinochirurgie Die medikamentöse Asthma-Therapie unterteilt sich in eine Dauer (Controler) und Akut-Therapie (Reliever). Der Status asthmaticus ist ein medizinischer Notfall, der intensivmedizin versorgt werden mus

Psoriasis - effiziente Diagnose und Therapie

Psoriasis (Schuppenflechte) stellt eine der häufigsten Diagnosen des dermatologischen Alltags dar und betrifft ca. 2–3 % der kaukasischen Bevölkerung. Die Diagnose wird in der Regel anhand von klinischem Bild und Histologie gestellt. Therapien umfassen topische Steroide, häufig kombiniert mit Vitamin-D-Derivaten, entschuppender Therapie sowie Rückfettung; im Weiteren bei mittelschwerer bis schwerer Psoriasis Lichttherapie sowie Systemtherapien. Die Systemtherapien werden unterteilt in small molecules (Methotrexat, Fumarsäure-Ester, Acitretin, Ciclosporin A, Apremilast) und Biologika (TNF-Blocker Etanercept, Adalimumab, Infliximab, p40-Inhibitor Ustekinumab und IL-17-Inhibitor Secukinumab). Komorbiditäten wie Psoriasis-Arthritis, kardiovaskuläre Erkrankungen sowie Depression sind häufig mit Psoriasis assoziiert. Die Forschung der letzten Jahre brachte zahlreiche neue effektive und gut verträgliche Medikamente auf den Markt, die einen guten Behandlungserfolg der Patienten ermöglichen können