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Background The aim was to evaluate the safety and efficacy of a trifocal intraocular lens (IOL) for the correction of presbyopia and to assess patient satisfaction. Methods Records from three centres were reviewed to select presbyopic patients having undergone bilateral refractive lens exchange and implantation of the AT LISA tri 839MP multifocal IOL. Postoperatively, monocular and binocular distance, intermediate and near visual acuities, corrected and uncorrected, and subjective refraction were measured. Patients also completed a quality of life questionnaire. Safety evaluation included IOL stability and postoperative complications. Results 72 eyes (36 patients) were analysed. No clinically significant difference between pre- and postoperative corrected distance visual acuity (CDVA) was found for monocular or binocular measurements. Mean postoperative monocular CDVA was 0.02 ± 0.04 logMAR. Mean refractive values all improved statistically significantly compared with preoperative baseline (p ≤ 0.0064). Overall, 82.4% of eyes had spherical equivalent within ± 0.5 D and 97.1% within ± 1.0 D of emmetropia with a mean accuracy of -0.10 ± 0.41 D. Spectacle independence for distance, intermediate and near visual acuity was 87.5%, 84.4% and 78.1% respectively, and 78.1% of patients were satisfied with their postoperative, spectacle-free vision. Eight eyes received Nd:YAG laser treatment. No other IOL-related safety issues were reported. Conclusion AT LISA tri 839MP multifocal IOL bilaterally implanted in presbyopic patients provided excellent distance, intermediate and near visual outcomes with very accurate correction of refraction. These results were associated with a high level of spectacle independence and patient satisfaction. Trial registration Trial registered on https://clinicaltrials.gov/ under the identification NCT03790592 (31/12/2018).

Background The pathophysiology of the underlying paroxysmal permeability disturbances in angioedema (AE) is not well understood. Methods To identify clinical and laboratory parameters specific for a certain AE subtype, 40 AE patients were prospectively enrolled: 15 hereditary (HAE), 13 ACE-inhibitor induced (ACE-AE), and 12 mast cell-mediated without wheals in chronic spontaneous urticaria (CSU-AE). Ten healthy subjects served as controls. Serum levels of markers indicating activation of the ficolin-lectin pathway, of endothelial cells, or those indicating impairment of vascular integrity or inflammation were assessed by enzyme-linked immunosorbent assay. Results New routine clinical diagnostic criteria could not be identified, not even for distinguishing bradykinin-mediated (BK-) AE (ie, HAE and ACE-AE) from mast cell-/histamine-mediated CSU-AE. However, FAP-α and tPA were significantly increased in all AE compared to controls. In HAE, FAP- α, tPA, uPAR, pentraxin-3, Tie-2, sE-selectin, and VE-cadherin were significantly increased compared to controls. In HAE compared to CSU-AE and ACE-AE, sE-Selectin, Tie-2, and VE-Cadherin were significantly increased, whereas for Ang-2 the difference was significant compared to CSU-AE only. Tie-2 correlated strongly negatively with C4, C1-INH activity, and C1-INH function. Conclusions This study is the first to compare HAE, ACE-AE, and CSU-AE. Although significance is limited by small sample size, Tie-2 was identified as a new promising biomarker candidate for HAE. FAP- α and tPA might serve as a marker for AE in general, whereas sE-selectin and Ang-2 were increased in BK-AE only. Our results add information to the role of endothelial dysfunction and serine proteases in different AE subtypes.

Das 2011 gegründete Allergiezentrum der Medizinischen Hochschule Hannover (MHH-AZ) wurde erstmals im Januar 2016 als Comprehensive Allergy Center (CAC) zertifiziert und 3 Jahre später im Januar 2019 re-zertifiziert. Im Geltungsbereich des Zertifikats sind die Klinik für Dermatologie, Aller­gologie und Venerologie, die Abteilung experimentelle Allergologie und Immundermatologie, die Klinik für Gastroenterologie, Hepatologie und Endokrinologie, die Klinik für Pädiatrische Pneumologie, Allergologie und Neonatologie, die Klinik für Hals-, Nasen-, Ohrenheilkunde und das Fraunhofer Institut für Toxikologie und experimentelle Medizin. Weitere aktive Mitglieder sind das Institut für Epidemiologie, Sozialmedizin, Gesundheitssystemforschung, die Klinik für Augenheilkunde, die Klinik für Immunologie und Rheumatologie, die Klinik für Pneumologie und als externer Kooperationspartner die Kinderklinik Auf der Bult. Es werden die Strukturen des MHH-AZ CACs und die allergologischen Schwerpunkte vorgestellt.

Background Mas-related G protein-coupled receptor X2 (MRGPRX2) is regarded as a mast cell-specific receptor mediating non-IgE-dependent activation. We aimed to investigate whether human basophils and eosinophils express functional MRGPRX2. Methods Flow cytometry, immunocytochemistry, immunofluorescence, Western blot, and RT-PCR were performed in highly purified peripheral blood basophils and eosinophils of atopic and nonatopic donors. To assess functional activity, fluorescent avidin-based degranulation assay, calcium mobilization, cytokine production in supernatants, assessment of viability/apoptosis, and tricolor granulocyte activation test were used. Results MRGPRX2 was significantly expressed by basophils and eosinophils but not neutrophils. Functional capacity was shown by anti-MRGPRX2 mAb-induced calcium influx and concentration-dependent induction of degranulation. Sequential stimulation in the calcium mobilization assay gave no evidence for desensitization or receptor internalization. Anti-MRGPRX2 mAb significantly promoted survival. Inhibition of apoptosis could be due to released IL-3, IL-5, and GM-CSF found in supernatants. Short-term incubation with IL-3 dose-dependently upregulated MRGPRX2 expression in both, stimulation for 24 hours with anti-IgE, C5a, fMLP, and IL-3 in basophils and by IL-3, IL-5, and IL-33 in eosinophils. Among known mast cell MRGPRX2 agonists ciprofloxacin but not PMX-53 was functional on basophils and eosinophils. In basophils of allergic subjects, tricolor granulocyte activation test using grass pollen demonstrated MRGPRX2 upregulation associated with degranulation and CD63 expression. Conclusion Unraveling the regulation and signaling mechanisms of MRGPRX2 on basophils and eosinophils might enable the development of new therapeutic strategies to prevent or inhibit allergic and nonallergic hypersensitivity. Moreover, addressing MRGPRX2 might have potential for diagnostic purposes in (drug) hypersensitivity.

Background Pruritus is a major symptom of atopic dermatitis (AD) and is transmitted by a subpopulation of non-myelinated C-type free nerve endings in the epidermis and upper dermis. Stimulation of these nerve terminals is affected by histamine, neurotrophins and physical factors. Eosinophils of patients with AD are a source of neurotrophins, including brain-derived neurotrophic factor (BDNF), levels of which correlate with disease severity. Objective The purpose of this study was to determine the anatomical localization of eosinophils in the skin of patients with AD with regard to peripheral nerves and to investigate whether eosinophils induce sprouting and neurite outgrowth in murine sensory neurons. Methods Cryosections of skin derived from AD and control (NA) patients were subjected to immunofluorescence analysis with markers for eosinophils, BDNF and neuronal cells. Stimulated eosinophil supernatants were used for the treatment of cultured peripheral mouse dorsal root ganglia (DRG) neurons followed by morphometric analysis. Results Dermal axon density and the proximity of eosinophils to nerve fibres were significantly higher in AD patients vs NA. Both neuronal projections and eosinophils expressed BDNF. Furthermore, activated eosinophil supernatants induced BDNF-dependent mouse DRG neuron branching. Conclusions and clinical relevance Our results indicate that BDNF-positive eosinophils are also localized in close proximity with nerve fibres in AD, suggesting a functional relationship between BDNF-expressing eosinophils and neuronal projections. These observations suggest that eosinophils may have considerable impact on pruritus by supporting sensory nerve branching.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GALEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast-cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic urticaria, i.e. chronic spontaneous urticaria and chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This article is protected by copyright. All rights reserved.

Eosinophils are potent pro-inflammatory cells. Not only in allergic diseases but also in other diseases there is a need for treatment strategies to induce resolution of eosinophil-mediated inflammation. During the last years beneficial non-antibiotic activities of tetracyclines (TCNs) have been shown in different diseases in which eosinophils play a role, for example, asthma and bullous pemphigoid. The working mechanism of these effects remains to be clarified. Aim of the present study was to investigate the effects of TCNs on eosinophils. Flow cytometry analysis of apoptosis, mitochondrial membrane potential, activation of caspases, intracellular H2O2and calcium, surface expression of eosinophil activation markers was performed in highly purified peripheral blood eosinophils of non-atopic donors. Tetracycline hydrochloride, minocycline and doxycycline significantly induced eosinophil apoptosis. All TCNs were able to significantly overcome the strong survival enhancing effects of pro-eosinophilic cytokines and staphylococcus aureus enterotoxins. Tetracycline hydrochloride induced eosinophil apoptosis was accompanied by intracellular production of hydrogen peroxide, loss of mitochondrial membrane potential and activation of caspases. Moreover, tetracycline hydrochloride significantly down regulated eosinophil surface expression of CD9 and CD45, and of the activation markers CD11b and CD69, but not of CD54, CD63, or CD95. Our data, propably for the first time, point to a potent anti-inflammatory role of TCNs on eosinophils.

Syphilis, caused by the bacteria Treponema pallidum subspecies pallidum, is an infectious disease transmitted through direct, most frequently sexual, contact with infected mucosal lesions. In the last two decades the numbers of cases reported to the Robert Koch Institute (RKI) increased from around 2000 cases in 2000 to 7889 cases in 20191 . Syphilis is much more common in men than in women. In 2018, only 6.1% of the reported cases in Germany and 14% in the USA were female patients1,2 .

Testicular torsion is a surgical emergency. Early diagnosis and surgical treatment are vital in order to preserve the affected gonad. Current surgical teaching emphasizes sudden, severe, persistent, unilateral scrotal pain as a cardinal symptom of testicular torsion. We present the case of unilateral testicular torsion in a 14-year-old patient who presented with the absence of severe pain. Despite a delayed presentation to the emergency department, the gonad could be salvaged successfully. Literature on the topic of testicular torsion presenting with minimal pain is limited. Nevertheless, pediatric surgeons might be faced with cases similar to the one we describe. Underestimating this phenomenon might lead to a delay of treatment. In such cases, ultrasound can be a beneficial addition in the diagnosis and accelerate definitive operative treatment. The presented case clearly demonstrates that, although we do not include testicular torsion without severe pain in our surgical teaching algorithms, we might encounter it in our clinical practice.

This guideline is an update from August 2020 the S2k-guideline "Atopic dermatitis" published in 2015. The reason for updating this chapter of the guideline were the current developments in the field of systemic therapy of atopic dermatitis. The agreed recommendations for systemic treatment in atopic dermatitis of the present guideline are based on current scientific data. Due to the approval of dupilumab for the treatment of moderate to severe atopic dermatitis, which cannot be treated sufficiently with topical drugs alone, this part of the guideline has now been adapted and newly consented. The indication for systemic therapy and the therapeutic response to topical and systemic treatment should be recorded and documented in a suitable form in clinic and practice. A standardized documentation of the indication for system therapy in atopic dermatitis can be recommended and is also part of the updated chapter of this guideline.

Die vorliegende Leitlinie ist eine Aktualisierung vom August 2020 zu Systemtherapeutika der 2015 publizierten AWMF-S2k-Leitlinie Neurodermitis. Anlass fur die Aktualisierung dieses Kapitels der Leitlinie waren die aktuellen Entwicklungen zur Systemtherapie der Neurodermitis. In der vorliegenden Leitlinie sind die wissenschaftliche Datenlage und die konsentierten Empfehlungen zur Systemtherapie bei Neurodermitis aufgefuhrt. Aufgrund der Neuzulassung von Dupilumab fur die Behandlung mittelschwer bis schwer ausgepragter Neurodermitis, die mit topischen Medikamenten alleine nicht ausreichend behandelbar ist, wurde dieser Teil der Leitlinie jetzt angepasst und neu konsentiert. Die Indikation zur Systemtherapie und das therapeutische Ansprechen auf die topische und systemische Behandlung sollen in Klinik und Praxis in geeigneter Form erfasst und dokumentiert werden. Eine standardisierte Dokumentation der Indikation zur Systemtherapie bei Neurodermitis kann empfohlen werden und ist ebenfalls Bestandteil des hier vorliegenden aktualisierten Kapitels der Leitlinie.

We measured indirect calorimetry and activity parameters, VO2 and VCO2 to extract respiratory exchange ratio (RER) and energy expenditure in both sexes of 30 inbred mouse strains of 6 genetic families at 9–13 weeks during one photophase and the subsequent scotophase. We observed a continuous distribution of all traits. While males had higher body weights than females, we observed no sex difference for food and water intake. All strains drank and fed more during the night even if they displayed no day–night difference in activity traits. Several strains showed absent or weak day–night variation in one or more activity traits and these included FVB and 129X1, males of 129S1, SWR, NZW, and SM, and females of SJL. In general females showed higher rearing and ambulatory activity with 6 and 9 strains, respectively, showing a sex difference. Fine motor movements, like grooming, showed less sex differences. RER underlied a strong day–night difference and no sex effect. Only FVB females and males of the RIIIS and SM strain had no day–night variation. Energy expenditure underlies a large day–night variation which was absent in SWR and in FVB females and RIIIS males. In general, female bodies had a tendency to higher energy expenditure values, which became a significant difference in C3H, MAMy, SM, DBA1, and BUB. Our data illustrate the diversity of these traits in male and female inbred mice and provide a resource in the selection of strains for future studies.

Angioodeme konnen durch die Mediatoren Bradykinin oder durch Histamin ausgelost werden. Dabei sind geschlechtsspezifische Unterschiede sowie mogliche Biomarker zur Verlaufskontrolle/Therapieuberwachung weitgehend unbekannt. Inwieweit unterscheiden sich, bezogen auf das Geschlecht, Gendefekte, Prodromi, Triggerfaktoren, klinische Parameter wie Attackenzahl, -frequenz, -lokalisation, Laborwerte, Hormone und Therapieansprechen bei den verschiedenen Angioodemtypen. Es erfolgten eine Literaturrecherche in PubMed mit den Stichworten „angioedema“ und „sex“ oder „gender“ sowie gezieltes Screening von Ubersichtsarbeiten, Leitlinien und Zulassungsstudien mit Angioodem-relevanten Medikamenten. Bei histaminvermittelten Angioodemen sind kaum geschlechtsspezifische Unterschiede zu erkennen. Bei bradykininvermittelten hereditaren Angioodemen, insbesondere mit FXII-Mutation, aber auch bei ACE(„angiotensin-converting enzyme“)-Inhibitor-bedingten Angioodemen sind Frauen haufiger und starker betroffen und hormonelle Einflusse dokumentiert. Auch die Lokalisation der bradykininvermittelten Angioodeme ist genderspezifisch unterschiedlich. Der Anteil der Frauen in Zulassungsstudien bei HAE(hereditares Angioodem)-Therapien betragt etwa zwei Drittel. Grundsatzlich scheint eine Differenzierung zwischen ostrogenabhangigen, ostrogensensitiven und -insensitiven Angioodemen sinnvoll. Die Charakterisierung dieser Untergruppen fuhrt zu einem besseren Verstandnis des Pathomechanismus der Hormoneffekte auf die Angioodeme. Dies konnte zur Entwicklung von dringend benotigten Biomarkern fur eine schnellere und gezieltere Diagnostik sowie fur die Vorhersage von Attacken fuhren, um mittels individualisierter genderspezifischer Therapie Gesundheit und Lebensqualitat der Angioodempatienten signifikant zu verbessern.

Diese evidenz- und konsensbasierte Leitlinie wurde entsprechend den Methoden der Cochrane und der Grading of Recommendations Assessment, Development and Evaluation (GRADE)-Arbeitsgruppen entwickelt. Die Leitlinien-Konferenz fand am 1. Dezember 2016 statt. Sie ist eine gemeinsame Initiative der European Academy of Allergology and Clinical Immunology (EAACI), dem von der EU gegrundeten Global Allergy and Asthma European Network (GA2LEN), dem European Dermatology Forum (EDF) und der World Allergy Organization (WAO) mit 48 teilnehmenden Delegierten aus 42 nationalen und internationalen Gesellschaften. Die Leitlinie ist von der European Union of Medical Specialists (UEMS) akzeptiert worden. Urtikaria ist eine haufige, mastzellabhangige Erkrankung, die mit Quaddeln, Angioodemen oder beidem einhergeht. Die Lebenszeitpravalenz der akuten Urtikaria liegt bei circa 20 %. Chronische spontane Urtikaria (CSU) und andere chronische Formen der Urtikaria sind belastend, beeintrachtigen die Lebensqualitat und haben einen negativen Einfluss auf die Leistungsfahigkeit in Beruf und Schule. Diese Leitlinie umfasst die Definition und Klassifikation der Urtikaria unter Berucksichtigung der jungsten Fortschritte in der Identifikation von Ursachen, Auslosefaktoren und Pathomechanismen. Daruber hinaus skizziert sie evidenzbasierte, diagnostische und therapeutische Ansatze fur die verschiedenen Subtypen der Urtikaria.

This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Background The diagnostic approach to drug hypersensitivity includes a detailed medical history, clinical examination, and skin testing and/or oral challenge with a culprit or alternative drug, depending on the type of reaction and the suspected drugs. Although skin testing is considered to be rather safe, cutaneous and systemic, including fatal, reactions have been described. Objectives To report 3 cases with generalized delayed reactions after skin testing with clindamycin, and to review the existing literature. Methods Thorough clinical examination, blood tests and prick, intradermal and patch tests were performed in 3 patients. Results All patients experienced generalized maculopapular exanthema after intradermal and patch testing with clindamycin and amoxicillin in the first patient, and clindamycin alone in the second and third patient. None of the patients showed immediate reactions to skin tests, while positive intradermal reactions after 24 h to amoxicillin and clindamycin were observed in the first patient, and positive intradermal reactions after 24 h to clindamycin were observed in the second and third patients. Conclusions Skin testing with clindamycin in the diagnosis of drug hypersensitivity carries some risk of adverse reactions. A stepwise and individual diagnostic work-up, considering potential risk factors, and testing in a specialized centre with emergency equipment available is highly recommended.

Bullous pemphigoid (BP) is characterized by substantial skin and blood eosinophilia as well as intensive pruritus. Since the pruritogenic cytokine interleukin (IL)-31 is increased in inflammatory skin diseases the aim of this study was to determine whether IL-31 plays a role in BP. Using immunofluorescence, IL-31 expression was analysed in eosinophils derived from blister fluids and skin from patients with BP and IL-31 levels in blister fluids, serum and culture supernatants were determined by enzyme-linked immunoassay (ELISA). High levels of IL-31 expression were observed in BP blister fluids, but they were only marginally elevated in BP serum compared with healthy controls. Eosinophils from either BP blister fluids or skin biopsies showed strong expression of IL-31. Furthermore, peripheral blood eosinophils from patients with BP, but not healthy controls, released high levels of IL-31, reflecting those in blister fluids. In conclusion, eosinophils are a major source of IL-31 in BP and this cytokine may contribute to itch in patients with BP.

Placeboeffekte spielen bei der Therapie allergischer Erkrankungen eine wesentliche Rolle. In dieser Arbeit wurden die doppelblind-placebokontrollierten Studien zur allergenspezifischen Immuntherapie (ASIT) mit Inhalationsallergenen (Birke, Graser, Milben), die in den im Juli 2016 aktualisierten Tabellen zur deutschen S2k-Leitlinie zur ASIT IgE-vermittelter Erkrankungen aufgelistet werden, gezielt hinsichtlich ihrer beschriebenen Placeboeffekte analysiert. Als Placebo wurde meist Verum ohne Allergen eingesetzt, bei subkutaner Applikation teilweise Histamin zugefugt. Detaillierte Aussagen zum reinen Placeboeffekt sind in keiner der untersuchten 33 Studien zu finden. Lediglich in einer Studie wurde der Symptom-Medikations-Score (SMS) in einer adaquaten Baseline-Periode untersucht. Ein unbehandelter Arm war in keiner Studie zu finden. Indirekte Hinweise zeigen bei retrospektiven, subjektiven Parametern deutliche Placeboeffekte bei bis zu 77 % der Probanden. Bekannte Einflussfaktoren auf den Placeboeffekt wie Alter, Geschlecht, Applikationsart/Zusammensetzung des Placebos, individuelle und kulturelle Unterschiede, Symptomschwere zu Beginn und Wahrscheinlichkeit, das Verum zu erhalten, wurden nicht adressiert und konnten anhand der verfugbaren Daten nicht bewertet werden. Zusammenfassend wurde der Placeboeffekt in ASIT-Studien bisher nicht ausreichend untersucht. Trotz des erheblichen Zeit- und Kostenaufwands sollten zukunftige ASIT-Studien den SMS in einer adaquaten Baseline-Periode vor Studienbeginn erheben und moglichst einen unbehandelten Vergleichsarm integrieren. Ein besseres Verstandnis der Placeboeffekte in Studien zur allergenspezifischen Immuntherapie wird zu einem optimierten Studiendesign und einer verbesserten Einschatzung des Therapieeffekts fuhren.

This update on chronic urticaria (CU) focuses on the prevalence and pathogenesis of chronic spontaneous urticaria (CSU), the expanding spectrum of patient-reported outcome measures (PROMs) for assessing CU disease activity, impact, and control, as well as future treatment options for CU. This update is needed, as several recently reported findings have led to significant advances in these areas. Some of these key discoveries were first presented at past meetings of the Collegium Internationale Allergologicum (CIA). New evidence shows that the prevalence of CSU is geographically heterogeneous, high in all age groups, and increasing. Several recent reports have helped to better characterize two endotypes of CSU: type I autoimmune (or autoallergic) CSU, driven by IgE to autoallergens, and type IIb autoimmune CSU, which is due to mast cell (MC)-targeted autoantibodies. The aim of treatment in CU is complete disease control with absence of signs and symptoms as well as normalization of quality of life (QoL). This is best monitored by the use of an expanding set of PROMs, to which the Angioedema Control Test, the Cholinergic Urticaria Quality of Life Questionnaire, and the Cholinergic Urticaria Activity Score have recently been added. Current treatment approaches for CU under development include drugs that inhibit the effects of signals that drive MC activation and accumulation, drugs that inhibit intracellular pathways of MC activation and degranulation, and drugs that silence MCs by binding to inhibitory receptors. The understanding, knowledge, and management of CU are rapidly increasing. The aim of this review is to provide physicians who treat CU patients with an update on where we stand and where we will go. Many questions and unmet needs remain to be addressed, such as the development of routine diagnostic tests for type I and type IIb autoimmune CSU, the global dissemination and consistent use of PROMs to assess disease activity, impact, and control, and the development of more effective and well-tolerated long-term treatments for all forms of CU.

Allergische Reaktionen nach Insektenstichen mit z. T. bedrohlichen Symptomen sind sowohl im Erwachsenen- als auch im Kindesalter sehr relevant. Bei Erwachsenen sind nach aktueller Datenlage Insektenstiche sogar die haufigsten Ausloser schwerer Anaphylaxien, im Kindesalter sind sie nach den Nahrungsmitteln die zweithaufigste Ursache. Mit der spezifischen Immuntherapie ist bei der Hymenopterengiftallergie eine sehr wirksame und gut standardisierte Therapieform verfugbar. Zahlreiche Patienten konnen mit oft nur geringen Nebenwirkungen erfolgreich behandelt werden. Meist treten bei Therapieeinleitung lediglich Schwellungen im Bereich der Injektionen auf; systemische Reaktionen sind insbesondere im Kindesalter selten. Da allgemeine Masnahmen (Verordnung eines Notfallsets, vermeidendes Verhalten) das Auftreten von todlichen Reaktionen nicht verhindern konnen, sollte bei bestehender Indikation eine spezifische Immuntherapie eingeleitet werden. Zur Diagnostik gehoren die Bestimmung spezifischer IgE-Antikorper gegenuber Wespen- oder Bienengift (Gesamtgift bzw. rekombinante Majorallergene) bzw. ein Hauttest, zudem die Anamnese einer systemischen Reaktion (im Kindesalter in der Regel uber das Hautorgan hinaus aufgetretene Symptome). Zur Routinediagnostik gehort ebenfalls die Bestimmung der basalen Mastzelltryptase im Serum bzw. die korperliche Untersuchung hinsichtlich einer kutanen Mastozytose zur allgemeinen Risikoeinschatzung bei einer moglicherweise vorliegenden Mastzellerkrankung.

Several studies have shown that neurotrophins including brain-derived neurotrophic factor (BDNF) play a role in chronic inflammatory skin diseases such as atopic dermatitis (AD). BDNF is increased in the serum samples of adults with AD. Interestingly, eosinophils of these patients can release and produce BDNF. We analyzed BDNF serum levels with ELISA and their correlation with SCORAD score, eosinophil cationic protein (ECP), total IgE, IL-4, IL-13 and IL-31 in children with AD (n = 56) compared to nonatopic healthy children (n = 25). In addition, we analyzed FLG loss-of-function mutations in 17 children with AD and their connection to BDNF. BDNF serum levels were significantly higher in children with AD. Further, BDNF correlated with disease activity, serum ECP, and total IgE serum levels in AD. There was no difference in BDNF levels of filaggrin-positive or filaggrin-negative children with AD, and there was no correlation of BDNF with IL-31 and Th2 cytokines including IL-4 and IL-13. Together, our data add new insights into the pathophysiology of AD, suggesting that serum BDNF which correlates with disease severity contributes to the regulation of inflammation in an eosinophil-, but not Th2-dependent manner.

Bei dem Krankheitsbild der Neurodermitis handelt es sich um eine chronische oder chronisch-rezidivierende nicht kontagiose, entzundliche Hauterkrankung mit in der Regel starkem Juckreiz. Daruber hinaus besteht ein Risiko fur komplizierte Verlaufe mit bakteriellen oder viralen Superinfektionen. Sowohl die genetische Pradisposition als auch zahlreiche Auslosefaktoren spielen fur die Erst manifestation und das Auftreten der Erkrankungsschube eine wichtige Rolle, sodass auch das Therapiekonzept vielfaltig ist. Bei zahlreichen fur die Neurodermitis zur Verfugung stehenden Behandlungsoptionen gilt es, in Abstimmung mit den Patienten beziehungsweise Eltern erkrankter Kinder fallorientiert einen optimalen Behandlungsplan aufzustellen, der im Verlauf gegebenenfalls erneut angepasst werden muss. Die vorliegende Kurzfassung der S2k-Leitlinie gibt einen Uberblick uber alle bisher zur Verfugung stehenden, evidenzbasierten Diagnoseverfahren und Therapiemoglichkeiten sowie uber die entsprechenden Empfehlungen, die durch die an dieser Leitlinie beteiligten Fachgesellschaften und Verbande ausgesprochen werden. Diese Empfehlungen wurden auf der Grundlage der bislang zu dem jeweiligen Verfahren vorliegenden klinisch-wissenschaftlichen Datenlage, die in der ausfuhrlichen Fassung dieser Leitlinie (unter www.awmf.org und jddg.org) beschrieben ist, konsentiert.

To evaluate clinical outcomes after the implantation of a diffractive trifocal intraocular lens (IOL).Nine European ophthalmology centers.Prospective noncomparative interventional multicenter study.The trifocal diffractive AT LISA tri 839MP IOL was implanted in eyes with bilateral cataract. Monocular and binocular visual performance was assessed as was the level of perceived photic phenomena, patient satisfaction, and spectacle dependence 1 month and 3 months postoperatively.The IOL was implanted in 208 eyes of 104 patients. The mean binocular uncorrected distance visual acuity improved from 0.44 logMAR ± 0.30 (SD) to 0.02 ± 0.10 logMAR and 0.03 ± 0.09 logMAR at 1 month and 3 months, respectively (P.01). The mean binocular uncorrected intermediate visual acuity (80 cm) improved from 0.51 ± 0.30 logMAR to 0.09 ± 0.13 logMAR and 0.10 ± 0.15 logMAR at 1 month and 3 months, respectively (P.01). The mean binocular uncorrected near visual acuity improved from 0.67 ± 0.31 logMAR to 0.16 ± 0.14 logMAR and 0.15 ± 0.14 logMAR, respectively (P.01). Among the more frequently perceived photic phenomena were halos; however, approximately 75% of patients were not bothered by them. More than 90% of patients were satisfied with the outcome. Spectacle independence at all distances was higher than 90%.This IOL provided excellent visual outcomes and high refractive predictability at all distances, including intermediate, leading to high levels of patient satisfaction and spectacle independence.No author has a financial or proprietary interest in any material or method mentioned.

BACKGROUND Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease with an increased incidence particularly among the elderly. Several studies have recently reported an association between BP and neurological disorders. OBJECTIVE To evaluate the association between BP and neurological disorders in a single centre in Germany. METHODS We retrospectively assessed 183 patients with BP (diagnosed between 2011 and 2015) and 348 age- and sex-matched controls for neurological disorders. The latter were confirmed either by a neurologist or psychiatrist. RESULTS Overall, there was a highly statistically significant association between BP and neurological disorders (P < 0.0001). These included dementia (P < 0.0001), Parkinson`s disease (P = 0.0434), stroke (P = 0.0015) and other neurological disorders but not Alzheimer's diseases, which was more common among patients in the control group. CONCLUSION Our cohort of bullous pemphigoid and neurological disorders demonstrates a significant association between bullous pemphigoid and neurological disorders, including dementia, Parkinson's disease and stroke. These observations support the need for future studies in order to elucidate the immunological mechanisms responsible for these comorbidities.

Background Atopic dermatitis (AD) is a common inflammatory skin disease in both adults and children. Whilst topical calcineurin inhibitors (TCIs), tacrolimus ointment and pimecrolimus cream, have proven efficacy for the treatment of AD, it is important to involve experts to obtain their opinion on its optimal treatment. Objective Using a modified Delphi approach, this project aimed to generate consensus amongst experts on the use of TCIs in the treatment of AD, with a focus on the differentiation between tacrolimus and pimecrolimus. Methods Six expert dermatologists from different European countries participated in this project based on their experience with AD and its treatment, which was evaluated by literature analysis and expert opinion. Consensus amongst the experts was generated using a modified Delphi approach, consisting of three distinct phases, during which a web meeting (June 2017), two online rounds of blinded Delphi voting (July-September 2017) and a face-to-face meeting (November 2017) were conducted. The consensus statements concerned two main topics: (i) Background of AD; and (ii) TCIs in AD. Hot topics in the treatment of AD not supported by meta-analysis, clinical trials or large observational studies were also discussed based on clinical experience. Results In total, 25 consensus statements were defined and validated: eight statements on the general background of AD and 17 statements on the use of TCIs in AD, including their mechanism of action and therapeutic indications in AD, efficacy in adult and paediatric AD patients, pharmacokinetics, incidence of adverse events and safety concerns. Hot topics on the use of TCIs for the treatment of AD included cream vs. ointment, dosages, TCIs contact allergy, burning sensation management, superinfection and vaccination concerns. Conclusion Topical calcineurin inhibitors are a suitable therapy for AD, and selection of the specific TCI should be based on factors which differentiate tacrolimus from pimecrolimus.

Background Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary disease with an estimated 5-year survival of approximately 20%. Pirfenidone is a novel orally available antifibrotic agent that reduces disease progression and improves survival of patients with IPF. The most common adverse effects of pirfenidone include gastrointestinal symptoms, hepatic dysfunction or skin photosensitivity and rash. A 64-year-old male patient presented in our clinic with a strong generalized exfoliative erythema and intense itching accompanied by fatigue and mild fever after a mild sun exposure for 5 days during holidays in Turkey. The patient had been diagnosed with IPF 2 months ago and 1 month later he started a therapy with pirfenidone with good tolerability. Objective In this report, we noted a severe phototoxic reaction under treatment with pirfenidone which underlies the potential phototoxic effect of this drug besides the already reported photosensitivity. Methods Routine laboratory tests and a skin biopsy were performed. Results Laboratory tests indicated increased markers of inflammation. The skin biopsy showed a perivascular lymphocytic inflammatory infiltrate, ballooning of keratinocytes with increased apoptosis. These findings were most consistent with a severe phototoxic reaction to pirfenidone which had been directly discontinued. The patient was started on oral methylprednisolone 100 mg/day which was gradually tapered off along with topical corticosteroids (mometasone furoate 0.1% cream) and oral antihistamines. This treatment led to a slow but complete resolution of the skin lesions within 20 days. Conclusion To our knowledge, this is the first reported case of a severe phototoxic reaction during treatment with pirfenidone. Our aim by presenting this case is to increase the awareness of clinicians for severe phototoxic effects of oral pirfenidone.

Streszczenie Niniejsze wytyczne są wynikiem systematycznego przeglądu piśmiennictwa dokonanego w oparciu o metodologie GRADE ( Grading Recommendations Assessment, Development and Evaluation ) oraz dyskusji przeprowadzonych w trakcie konferencji dotyczącej pokrzywki, ktora odbyla sie 28 i 29 listopada 2012 roku w Berlinie. Konferencja ta byla wspolną inicjatywą kilku organizacji ( Dermatology Section of the European Academy of Allergy and Clinical Immunology [EAACI], EU-funded network of excellence, Global Allergy and Asthma European Network [GA 2 LEN], European Dermatology Forum [EDF], World Allergy Organization [WAO]) i wzieli w niej udzial delegaci z 21 towarzystw zarowno krajowych, jak i miedzynarodowych. Pokrzywka jest czesto rozpoznawaną jednostką chorobową rozwijającą sie przy dominującym udziale komorek tucznych, ktora klinicznie objawia sie wystepowaniem bąbli pokrzywkowych, obrzeku naczynioruchowego lub wspolistnieniem obu typow objawow skornych. Ryzyko wystąpienia klinicznych objawow pokrzywki ostrej w ciągu zycia w populacji ogolnej szacuje sie na okolo 20%. Przewlekla pokrzywka spontaniczna oraz inne odmiany pokrzywki przewleklej nie tylko obnizają jakośc zycia pacjenta, ale wplywają takze na poziom funkcjonowania w pracy czy szkole i z tego powodu nalezy je zaliczyc do grupy ciezkich chorob alergicznych. Niniejsze wytyczne zawierają definicje oraz klasyfikacje pokrzywek, uwzgledniając postep, ktory sie ostatnio dokonal w zakresie identyfikacji przyczyn, czynnikow wyzwalających oraz patomechanizmow zaangazowanych w rozwoj objawow klinicznych choroby. Dodatkowo przedstawiają oparte na wiarygodnych dowodach naukowo-badawczych zasady postepowania diagnostycznego i terapeutycznego w roznych podtypach pokrzywek. Niniejsze wytyczne zostaly uznane zaakceptowane przez Europejską Unie Lekarzy Specjalistow ( European Union of Medical Specialists ; UEMS).

The diagnostic approach to drug hypersensitivity includes a detailed medical history, clinical examination, and skin testing and/or oral challenge with a culprit or alternative drug, depending on the type of reaction and the suspected drugs. Although skin testing is considered to be rather safe, cutaneous and systemic, including fatal, reactions have been described.To report 3 cases with generalized delayed reactions after skin testing with clindamycin, and to review the existing literature.Thorough clinical examination, blood tests and prick, intradermal and patch tests were performed in 3 patients.All patients experienced generalized maculopapular exanthema after intradermal and patch testing with clindamycin and amoxicillin in the first patient, and clindamycin alone in the second and third patient. None of the patients showed immediate reactions to skin tests, while positive intradermal reactions after 24 h to amoxicillin and clindamycin were observed in the first patient, and positive intradermal reactions after 24 h to clindamycin were observed in the second and third patients.Skin testing with clindamycin in the diagnosis of drug hypersensitivity carries some risk of adverse reactions. A stepwise and individual diagnostic work-up, considering potential risk factors, and testing in a specialized centre with emergency equipment available is highly recommended.

Die spezifische Immuntherapie ist bei einer Hymenopterengiftallergie eine sehr wirksame und sehr gut vertragliche Therapieoption. Zahlreiche Patienten konnen mit oft nur geringen Nebenwirkungen erfolgreich behandelt werden. Meist treten bei Therapieeinleitung lediglich Schwellungen im Bereich der Injektionen auf, systemische Reaktionen sind selten. Fur die Kontrolle des Therapieansprechens sind bisher keine zuverlassigen Laborparameter bekannt. Eine Identifikation von Therapieversagern kann durch die Durchfuhrung einer Stichprovokation mit einem lebenden Insekt uberpruft werden, bei fehlendem Schutz erfolgen eine Erhohung der Behandlungsdosis und im Verlauf eine erneute Stichprovokation. Dies ist fur die Mehrzahl der Patienten ein bewahrtes Therapiekonzept. In einzelnen Fallen jedoch kann es u. a. aufgrund von individuellen Risikofaktoren zum Auftreten von schweren Anaphylaxien bereits wahrend der Einleitungsphase kommen. In der Vergangenheit fuhrte dies nicht selten zum Therapieabbruch. Durch Verfugbarkeit des fur andere Indikationen zugelassenen Omalizumab steht hier eine zusatzliche Therapieoption zur Verfugung, die seit 2005 auch in unserer Universitats-Hautklinik erfolgreich eingesetzt wird. In dem vorliegenden Beitrag soll neben den eigenen Erfahrungen auch auf aktuelle Daten eingegangen werden, um fur die Zukunft ein mogliches Vorgehen bei Durchfuhrung einer spezifischen Immuntherapie der Hymenopterengiftallergie bei besonderen Risikopatienten zu diskutieren.

ZusammenfassungHintergrund Organtransplantierte Patienten entwickeln vermehrt nicht-melanozytare Hauttumoren. Aufgrund des multiplen Auftretens und aggressiven Wachstumsverhaltens stellt die chirurgische Therapie oftmals eine Herausforderung dar. Die Umstellung der immunsuppressiven Therapie auf einen mTOR-Inhibitor kann eine antitumorale Wirkung haben. Patienten und Methodik In einer monozentrischen retrospektiven Erhebung wurden im Zeitraum von 2008 bis 2010 organtransplantierte Patienten erfasst, die sich aufgrund von nicht-melanozytaren Hauttumoren vorgestellt hatten. Erfahrungen mit Patienten, die aufgrund von nicht-melanozytaren Hauttumoren auf eine Therapie mit einem mTOR-Inhibitor umgestellt wurden, werden detailliert dargestellt und aktuelle Studiendaten dazu zusammengefasst. Ergebnisse Insgesamt wurden 60 organtransplantierte Patienten mit nicht-melanozytaren Hauttumoren erfasst. Aufgrund der Entwicklung von vielen nicht-melanozytaren Hauttumoren innerhalb weniger Jahre wurde die systemische immunsuppressive Therapie bei 7 Patienten auf Everolimus und bei 5 Patienten auf Sirolimus umgestellt. Acht Patienten konnten hinsichtlich der Anzahl neu entstehender nicht-melanozytarer Hauttumoren nach Umstellung ausgewertet werden, 4 Patienten mussten die neue immunsuppressive Therapie aufgrund verschiedener Nebenwirkungen wieder absetzen. In den 12 Monaten vor Umstellung der Immunsuppression entwickelten die 8 Patienten histologisch gesichert 16 Plattenepithelkarzinome, 3 Basalzellkarzinome und 22 Morbus Bowen. In den 12 Monaten nach Umstellung auf einen mTOR-Inhibitor war die Zahl der Plattenepithelkarzinome (n = 2) und der Morbus Bowen (n = 3), nicht jedoch die der Basalzellkarzinome (n = 2) signifikant reduziert. Auch 5 kurzlich publizierte prospektiv-randomisierte Studien konnten ein vermindertes Auftreten nicht-melanozytarer Hauttumoren nach Umstellung der immunsuppressiven Therapie auf einen mTOR-Inhibitor bei organtransplantierten Patienten zeigen. Schlussfolgerung Eine Umstellung der immunsuppressiven Therapie auf einen mTOR-Inhibitor sollte bei organtransplantierten Patienten mit nicht-melanozytaren Hauttumoren diskutiert werden.

SummaryBackground Organ transplant recipients are prone to the development of non-melanoma skin cancer. Organ transplant recipients often develop multiple non-melanoma skin cancers and the tumors show an aggressive growth pattern, therefore surgical therapy can be difficult. Switch of the immunosuppressive regimen to mTOR-inhibitors such as everolimus or sirolimus can have an antitumor effect. Patients and Methods In a monocentric retrospective study we evaluated organ transplant recipients who presented with non-melanoma skin cancer in the years 2008–2010. Experience with patients who were switched to an mTOR-inhibitor due to non-melanoma skin cancer are reported in detail, and recent clinical studies are reviewed. Results 60 organ transplant recipients with non-melanoma skin cancer were evaluated. Due to the development of multiple non-melanoma skin cancer within a few years, the immunosuppressive regimen was switched to everolimus in 7 patients and to sirolimus in 5 patients. Eight patients were evaluable for the effect of mTOR-inhibitors on the development of non-melanoma skin cancer; 4 patients had to discontinue the medication with mTOR-inhibitors early due to various side effects. In the year before the switch to mTOR-inhibitors, 8 patients developed 16 squamous cell carcinomas, 3 Basal cell carcinomas and 22 cases of Bowen's disease. All tumors were histologically confirmed. In the year after switch of immunosuppression, the rate of squamous cell carcinomas (n = 2) and Bowen's disease (n = 3), but not of basal cell carcinomas (n = 2) was significantly reduced. Moreover, 5 prospective randomized trials recently have demonstrated a reduced number of non-melanoma skin cancers in organ transplant recipients after switch of the immunosuppressive regimen to mTOR-inhibitors. Conclusion Switch of the immunosuppressive regimen to mTOR-inhibitors should be considered for organ transplant recipients suffering from multiple non-melanoma skin cancers.