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Introduction: Immune checkpoint inhibitors (ICI) are increasingly being used to treat numerous cancer types. Together with improved recognition of toxicities, this has led to more frequent identification of rare immune-related adverse events (irAE), for which specific treatment strategies are needed. Neutropenia is a rare hematological irAE that has a potential for a high mortality rate because of its associated risk of sepsis. Prompt recognition and timely treatment of this life-threatening irAE are therefore critical to the outcome of patients with immune-related neutropenia. Methods: This multicenter international retrospective study was conducted at 17 melanoma centers to evaluate the clinical characteristics, diagnostics, treatment, and outcomes of melanoma patients with grade 4 neutropenia (

Kein CA

\(\ bf Background\) The diagnostic significance of the atopy patch test for the management of dermatitis possibly triggered by aeroallergens is still controversial. However, sufficiently large studies with routinely tested standardized aeroallergen patch test preparations in dermatitis patients are lacking. \(\ bf Objective\) To evaluate the reaction frequency and the reaction profiles of 10 until mid-2015 commercially available, standardized aeroallergen patch test preparations of the ‘Stallerpatch’ test series (Stallergenes, Antony Cedex, France) in a large multicentre patient cohort. \(\ bf Methods\) A retrospective data analysis of patients with suspected aeroallergen-dependent eczematous skin lesions was performed, who were patch tested in 15 Information Network of Departments of Dermatology-associated clinics between 2000 and 2015. Patients were stratified according to their atopic dermatitis (AD) status. \(\ bf Results\) The study group included 3676 patients (median age 41 years, 34.8% males, 54.5% AD). The most common aeroallergens causing positive patch test reactions were Dermatophagoides pteronyssinus (19.6%), Dermatophagoides farinae (16.9%), birch (6.2%), timothy grass (6.0%), cat dander (5.4%), mugwort (4.9%) and dog dander (4.6%). Reactions to other pollen allergen preparations, that is 5 grasses (3.2%), cocksfoot (2.1%) and plantain (1.6%), were less common. Positive patch test reactions to aeroallergens were consistently more frequent in patients with AD. These patients showed proportionally less dubious, follicular, irritant and weak positive reactions. Independent of AD status, a patient history of past or present allergic rhinitis was associated with an increased chance of a positive aeroallergen patch test reaction to pollen allergens. \(\ bf Conclusion\) The aeroallergen patch test is a useful add-on tool in clinical routine, especially in patients with AD and/or respiratory allergy. A patch test series comprising Dermatophagoides pteronyssinus, Dermatophagoides farinae, birch, timothy grass, cat dander and mugwort seems to be suitable. Controlled studies with specific provocation and elimination procedures are required to further evaluate the diagnostic significance of the proposed screening series.

Background Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction. Methods Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil. Results The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one. Conclusions Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians.

Arbeitsplatzbezogene Atembeschwerden eines Hufschmiedes können auf chemisch-irritative oder allergisierende Effekte zurückgeführt werden. In der Diagnostik spielen neben einer subtilen allgemeinen und Berufs-Anamnese eine longitudinale und tätigkeitsparallele Lungenfunktionsanalytik und eine gezielte Allergiediagnostik eine entscheidende Rolle, in deren Verlauf sich - wie in der folgenden Kasuistik - auch die Diagnose einer seltenen Differentialdiagnose - einer EAA - stellen kann.

Die Nanotechnologie gilt als Schlüsseltechnologie des 21. Jahrhunderts. Mit Nanomaterialien wurden jedoch nicht nur technologisch hoch interessante, vielfältig einsetzbare nanoskalige Produkte geschaffen, sondern auch eine neue Kategorie von potentiell toxischen Substanzen für Beschäftigte, Endverbraucher und Umwelt. Vor dem Hintergrund individueller Faktoren, potentieller Wirkprinzipien und adverser Gesundheitseffekte durch Nanomaterialien erfolgte die Konzeption eines vielschichtigen Diagnostik-Programms, welches einer Gruppe von Beschäftigten in der Nanotechnologie angeboten wurde.

The rapid development of nanotechnology - the key technology of the 21th century - demands a consideration of risks and assessment of health effects during exposures to nanomaterials. Due to their high surface to volume ratio, nanoscaled materials exhibit exceptional physical and chemical properties when compared to larger particles of the same composition. Therefore toxicological informations of the bulk material should be carefully applied to nano particles. One of the most relevant uptake pathways is the inhalation of nanoscaled particles. Effects on the respiratory tract like inflammation, oxidative stress and pulmonary fibrosis, adverse effects on the cardiovascular and central nervous system are considered. In addition, nanotubes with their structure similar to asbestos-fibres may have a carcinogenic potential. Taking into consideration the various possible working mechanism of nanomaterials, an extensive diagnostic program was designed and offered to a collective of employees in chemical nanotechnology.

Prognostic significance of CD28 autoantibodies in patients with malignant melanoma under therapy with ipilimumab For an effective response, the two opponents CD28 and CTLA-4 on T cells are crucial. While the CD28 receptor as a costimulatory receptor has the role as a catalyst during the immune response, CTLA-4 has blocking effects and downregulates the immune response after activation. In previous studies, autoantibodies against CD28 were detected in patients with atopic diathesis and in patients with autoimmune diseases. Immunomodulatory therapies with e.g. interferon appear to induce the occurrence of autoantibodies against CD28. Studies including patients with malignant melanoma showed a correlation between the occurrence of CD28 autoantibodies and interferon treatment. It is thinkable that CD28 autoantibodies may act immunostimulating by activating T cells as superagonists. On the other hand is also thinkable that these antibodies lead to immunosuppression by preferential activation of regulatory T cells or by blocking the CD-28 receptor directly. The occurrence and the relevance of CD28 autoantibodies in patients with malignant melanoma under therapy with ipilimumab have not yet been examined. Ipilimumab is approved for the treatment of patients with metastatic melanoma. The substance modulates the immune system by blocking the CTLA-4 receptor and this indirectly leads to a persistent immune stimulation. The aim of the present study was to investigate the incidence and prevalence of CD28 autoantibodies in melanoma patients treated with ipilimumab and their possible effects on progression-free and overall survival. Seventeen of 19 patients included in this study died during the observation period. Eighteen patients developed a progressive disease during or after treatment with Ipilimumab. In nine patients (47.4 %) CD28 autoantibodies were detected in serum samples conected under therapy. Eight patients (44.1 %) developed a seroconversion during the therapy with Ipilimumab. In one patient (5.3 %) CD28-autoantibodies were detected prior to therapy with ipilimumab. The titer of CD28 autoantibodies showed a correlation between therapy with Ipilimumab and the occurrence of CD28 autoantibodies, as therapy with ipilimumab appears to induce the production of CD28 autoantibodies. The median progression-free survival of stage IV patients was 85 days for patients with CD28 autoantibodies and 69 days for patients with no CD28 autoantibodies. On average, the stage IV patients without CD28 autoantibodies showed no progression for 114 days, while patients with CD28 antibodies had no progression of disease for 67 days. The differences were not statistically significant. The median overall survival of stage IV patients was 183 days for patients without CD28 antibodies, compared to 216 days for patients with CD28 abs. The median overall survival of patients with stage IV disease was 231 days for patients with CD28-autoantibodies compared to 183 days for patients without CD28-autoantibodies. The differences were not statistically significant. The present study could show that the presence of CD28 autoantibodies on its own represents no prognostic factor. In the meantime, other experimental investigations that were not part of this study, identified not yet a characterised serum component, that was able to trump the inhibitory effect of CD28 abs on T cells in vitro. Für eine funktionierende Immunantwort sind die beiden Gegenspieler CD28 und CTLA-4 von entscheidender Bedeutung. Während dem CD28-Rezeptor als costimulatorischem Rezeptor die Rolle eines Katalysators während der Immunantwort zukommt, hat CTLA-4 blockierende Wirkungen und regelt die Immunantwort nach Aktivierung wieder herab. Autoantikörper gegen CD28 konnten zuvor bei Patienten mit atopischer Diathese und bei Patienten mit Autoimmunerkrankungen nachgewiesen werden. Immunmodulierende Therapien, z.B. mit Interferonen scheinen das Auftreten von Autoantikörpern, u.a. gegenüber CD28, zu induzieren. Untersuchungen an Patienten mit malignem Melanom konnten einen Zusammenhang zwischen dem Auftreten von CD28-Autoantikörpern und einer Interferonbehandlung nachweisen. Es ist möglich, dass CD28-Autoantikörper immunstimulierend wirken, indem sie als Superagonisten T-Zellen direkt ohne weitere Signale aktivieren. Andererseits ist ebenfalls denkbar, dass diese Antikörper immunsuppressiv wirken, indem sie z. B. präferentiell die Aktivierung regulatorischer T-Zellen fördern oder aber den CD-28-Rezeptor direkt blockieren. Das Vorkommen und die Bedeutung von CD28-Autoantikörpern bei Patienten mit malignem Melanom unter einer Therapie mit Ipilimumab sind bislang noch nicht untersucht worden. Ipilimumab ist zur Behandlung von Patienten mit metastasiertem Melanom zugelassen. Die Substanz greift in das Immungeschehen ein, indem sie den CTLA-4-Rezeptor auf T-Zellen blockiert und damit indirekt eine fortbestehende Immunstimulation erlaubt. Ziel der vorliegenden Arbeit war es, die Inzidenz und die Prävalenz von CD28-Autoantikörpern bei Melanompatienten unter Therapie mit Ipilimumab und deren mögliche Auswirkungen auf das progressionsfreie und das Gesamtüberleben zu untersuchen. Von 19 in dieser Studie eingeschlossenen Patienten verstarben 17 während des Beobachtungszeitraumes. Bei 18 Patienten konnte eine Krankheitsprogression während oder nach der Ipilimumabbehandlung nachgewiesen werden. Bei neun Patienten (47,4 %) konnten CD28-Autoantikörper im Serum nachgewiesen werden. Acht Patienten (44,1 %) wiesen im Verlauf der Ipilimumabtherapie eine Serokonversion auf. Ein Patient (5,3 %) war bereits vor Therapiebeginn CD28-positiv. Die Titerverläufe der CD28-Autoantikörper zeigten einen Zusammenhang zwischen der Ipilimumabtherapie und dem Auftreten der CD28-Autoantikörper. Die Ipilimumabtherapie scheint die Produktion der CD28-Autoantikörper zu induzieren. Der Median des progressionsfreien Überlebens im Stadium IV der Tumorerkrankung betrug für Patienten mit CD28-Autoantikörpern 69 Tage, für Patienten ohne nachweisbare CD28-Autoantikörper 85 Tage. Im Mittel waren Patienten im Stadium IV ohne CD28-Autoantikörper 114 Tage progressionsfrei, während es bei den Patienten mit positivem Antikörpernachweis 67 Tage waren. Die Unterschiede waren statistisch nicht signifikant. Der Median des Gesamtüberlebens der Patienten im Stadium IV betrug 183 Tage für Patienten ohne Antikörpernachweis im Serum, im Vergleich zu 216 Tagen bei Patienten mit Antikörpernachweis. Das mittlere Gesamtüberleben der Patienten im Stadium IV betrug 183 Tage für CD28-negative Patienten verglichen mit 231 Tagen für CD28-positive Patienten. Die Unterschiede waren statistisch ebenfalls nicht signifikant. Die vorliegende Arbeit zeigt, dass das Vorhandensein von CD28-Autoantikörpern alleine genommen keinen prognostischen Faktor darstellt. Zwischenzeitlich konnten andere experimentelle Untersuchungen, die nicht Gegenstand dieser Arbeit waren, zeigen, dass im Serum von Melanompatienten mit und ohne CD28-Autoantikörper eine weitere Komponente vorhanden sein kann, die in vitro den inhibitorischen Effekt der CD28-Autoantikörper auf T-Zellen antagonisiert.