Expression and Function of the Mannose Receptor CD206 on Epidermal Dendritic Cells in Inflammatory Skin Diseases

The capability to take up mannosylated protein antigens is important for the biologic function of dendritic cells, as many glycoproteins derived from bacteria and fungi, e.g., Malassezia furfur, are mannosylated. The expression of the mannose receptor CD206 has been regarded a differentiation hallmark of immature dendritic cells, whereas monocytes and mature dendritic cells as well as epidermal Langerhans cells do not express CD206. This study describes some epidermal dendritic cells that may express CD206 under inflammatory skin conditions: Immunohistochemical and flow cytometric analysis with the CD206-specific D547 antibody confirmed that Langerhans cells from normal human skin do not express CD206. Epidermal cell suspensions from atopic dermatitis and psoriasis revealed two distinct subsets of epidermal dendritic cells: a CD1a+++/CD206– cell population (i.e., Langerhans cells) and a CD1a+/CD206++ cell population, corresponding to the previously described inflammatory dendritic epidermal cells. CD206-mediated endocytosis, assessed by dextran-fluorescein isothiocyanate uptake, was demonstrated in inflammatory dendritic epidermal cells but not in Langerhans cells. CD206-independent uptake of the fluorescent dye Lucifer yellow, a pinocytosis marker, was demonstrated in both Langerhans cells and inflammatory dendritic epidermal cells. Electron microscopic examination, known to distinguish Langerhans cells from inflammatory dendritic epidermal cells by their Birbeck granules, revealed Langerhans cells with Birbeck granules and inflammatory dendritic epidermal cells without Birbeck granules. Inflammatory dendritic epidermal cells exhibited numerous coated pits and vesicles, the latter fusing with large endosome-like structures, thus suggesting a high endocytotic activity. Immunogold staining with D547 monoclonal antibody confirmed that inflammatory dendritic epidermal cells were positive for CD206. In conclusion, inflammatory dendritic epidermal cells but not Langerhans cells are expressing CD206 in situ and use it for receptor-mediated endocytosis

Acute Ischemic Stroke in Late Pregnancy Treated with Intravenous Thrombolysis and Endovascular Therapy

Pregnancy has usually been an exclusion criterion in clinical trials with thrombolysis and endovascular therapy in acute ischemic stroke. For that reason, these therapies are not recommended causing lack of evidence and vice versa. In this case report, we describe a pregnant woman in week 33 + 3 presenting with acute ischemic stroke, which was successfully treated with systemic thrombolysis and endovascular therapy, resulting in a good clinical outcome for both mother and child. The altered fibrinolytic system and the risk factors related to pregnancy constitute a challenge for clinicians when choosing the most suitable treatment modality for treating acute ischemic stroke in pregnancy. It is still uncertain whether thrombolysis in combination with endovascular therapy or endovascular therapy alone is the most appropriate treatment option. However, there is slowly growing evidence that thrombolysis and thrombectomy in pregnancy are feasible and safe with a good clinical outcome for both the mother and the child

Efficacy and safety of medications for antihistamine-refractory chronic spontaneous urticaria: a systematic review and network meta-analysis

Purpose Most medications for antihistamine-refractory chronic spontaneous urticaria (CSU) have not been compared head-to-head. This systematic review and network meta-analysis evaluates their relative efficacy and safety. Methods Electronic databases were searched until 05 May 2022 for randomized controlled trials investigating systemic medications for antihistamine-refractory CSU. The change in the urticaria activity score over seven days (UAS7) and occurrence of adverse events were compared between treatments using random-effects network meta-analysis models. Results In all, 32 studies with 3641 patients receiving 31 different systemic medical interventions were included. Among currently available drugs, omalizumab 300 mg injected every 4 weeks and cyclosporine 3–5 mg/kg daily per os were most effective in reducing the UAS7 with a reduction of −10.45 (95% confidence interval [CI]: −12.35, −8.55) and of −10.40 (95% CI: −19.4, −1.4) compared to placebo. Similar efficacies were shown by the nonapproved agents ligelizumab 72 mg injected every 4 weeks (−11.67, 95% CI: −16.80, −7.15) and fenebrutinib 400 mg daily per os (−9.50, 95% CI: −17.56, −1.44). The odds ratio for the occurrence of an adverse event with placebo as comparator was 1.09 for omalizumab (95% CI: 0.83, 1.42), 2.16 for cyclosporine (95% CI: 0.77, 6.07: GRADE; moderate certainty), 0.89 for ligelizumab (95% CI: 0.47, 1.69), and 2.14 for fenebrutinib (95% CI: 0.62, 7.38) in the mentioned dosages. Conclusion Omalizumab 300 mg injected every 4 weeks and cyclosporine 3–5 mg/kg daily per os are the most effective currently available drugs for antihistamine-refractory CSU. Cyclosporine shows a relatively less favorable safety profile

Anaphylaxis in Elderly Patients—Data From the European Anaphylaxis Registry

Background: Elicitors and symptoms of anaphylaxis are age dependent. However, little is known about typical features of anaphylaxis in patients aged 65 years or more.Methods: The data from the Network for Online Registration of Anaphylaxis (NORA) considering patients aged ≥65 (elderly) in comparison to data from adults (18–64 years) regarding elicitors, symptoms, comorbidities, and treatment measures were analyzed.Results: We identified 1,123 elderly anaphylactic patients. Insect venoms were the most frequent elicitor in this group (p < 0.001), followed by drugs like analgesics and antibiotics. Food allergens elicited less frequently anaphylaxis (p < 0.001). Skin symptoms occurred less frequently in elderly patients (77%, p < 0.001). The clinical symptoms were more severe in the elderly (51% experiencing grade III/IV reactions), in particular when skin symptoms (p < 0.001) were absent. Most strikingly, a loss of consciousness (33%, p < 0.001) and preexisting cardiovascular comorbidity (59%, p < 0.001) were more prevalent in the elderly. Finally, adrenaline was used in 30% of the elderly (vs. 26% in the comparator group, p < 0.001) and hospitalization was more often required (60 vs. 50%, p < 0.001).Discussion and Conclusion: Anaphylaxis in the elderly is often caused by insect venoms and drugs. These patients suffer more often from cardiovascular symptoms, receive more frequently adrenaline and require more often hospitalization. The data indicate that anaphylaxis in the elderly tends to be more frequently life threatening and patients require intensified medical intervention. The data support the need to recognize anaphylaxis in this patient group, which is prone to be at a higher risk for a fatal outcome

Anaphylaxis in Elderly Patients-Data From the European Anaphylaxis Registry

Background: Elicitors and symptoms of anaphylaxis are age dependent. However, little is known about typical features of anaphylaxis in patients aged 65 years or more. Methods: The data from the Network for Online Registration of Anaphylaxis (NORA) considering patients aged ≥65 (elderly) in comparison to data from adults (18–64 years) regarding elicitors, symptoms, comorbidities, and treatment measures were analyzed. Results: We identified 1,123 elderly anaphylactic patients. Insect venoms were the most frequent elicitor in this group (p < 0.001), followed by drugs like analgesics and antibiotics. Food allergens elicited less frequently anaphylaxis (p < 0.001). Skin symptoms occurred less frequently in elderly patients (77%, p < 0.001). The clinical symptoms were more severe in the elderly (51% experiencing grade III/IV reactions), in particular when skin symptoms (p < 0.001) were absent. Most strikingly, a loss of consciousness (33%, p < 0.001) and preexisting cardiovascular comorbidity (59%, p < 0.001) were more prevalent in the elderly. Finally, adrenaline was used in 30% of the elderly (vs. 26% in the comparator group, p < 0.001) and hospitalization was more often required (60 vs. 50%, p < 0.001). Discussion and Conclusion: Anaphylaxis in the elderly is often caused by insect venoms and drugs. These patients suffer more often from cardiovascular symptoms, receive more frequently adrenaline and require more often hospitalization. The data indicate that anaphylaxis in the elderly tends to be more frequently life threatening and patients require intensified medical intervention. The data support the need to recognize anaphylaxis in this patient group, which is prone to be at a higher risk for a fatal outcome

Contact allergy to the Dexcom G6 glucose monitoring system-Role of 2,2 '-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate in the new adhesive

Background: Skin reactions to the glucose monitoring systems Dexcom G5 and G6 have been rare. In 2019, the components of the adhesive were exchanged for better skin fixation. Since then, more and more patients experienced severe skin reactions. A few months ago, 2,2'-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate (MBPA) was identified as a new component in the adhesive of the G6 model. Furthermore, it was suspected that isobornyl acrylate (IBOA) was also a component of the exchanged adhesive. Objectives: Our objective was to investigate if MBPA plays a major role in the increasing skin problems of patients without a history of IBOA-sensitization. Furthermore, our aim was to examine whether IBOA is contained in the newer model adhesive and may also contribute to allergic contact dermatitis (ACD). Patients and Methods: Five patients with a newly occurred ACD caused by the glucose monitoring system Dexcom G6 were investigated. Patch testing including MBPA in three different concentrations, as well as IBOA, were performed. Gas chromatography-mass spectrometry of the newer system Dexcom G6 was carried out. Results: All patients were shown to be sensitized to MBPA, while MBPA 0,5% showed the strongest reaction. On the other hand, IBOA was tested negative. Conclusion: In our study group, MBPA was observed to be the triggering allergen of the recently changed adhesive

Contact sensitization to iron: A potentially underestimated metal allergen and elicitor of complications in patients with metal implants

Background Little is known about sensitization to iron (Fe) in private, occupational, and medical settings, particulary implantology. Objectives To investigate sensitization to metals, particularly to Fe, both in pre-implant individuals with presumed metal allergy and in patients with suspected metal implant allergy. To further characterize Fe-sensitized individuals. Methods Analysis of patch-test reactions to an Fe (II) sulfate-containing metal series in 183 consecutive patients (41 pre-implant, 142 metal implant bearers). Test readings were on day (D)2, D3, and D6. Evaluation of questionnaire-aided history of metal reactivity patterns and demographics of Fe reactors. Results Metal reactivity in pre-implant/implant/total group was: to nickel 39%/30%/32%;to cobalt 17%/15%/15%;and to chromium 7%/13%/11%. Co-sensitizations cobalt/nickel (19/58) and cobalt/chromium (11/21) were significant at P < .001;co-sensitizations Fe/nickel (4/10) and chromium/knee arthroplasty (11/73) at P = .03. Ten of 183 (5.5%) reacted to Fe (2 of 41 pre-implant patients, 8 of 142 implant bearers), with 10 reacting only on D6. Fe reactivity was highest in complicated knee arthroplasty (7/73). Further peculiarities of Fe reactors included frequent isolated Fe reactivity (6/10), occupational metal exposure (7/10), previous (par)enteral Fe substitution (6/10). Conclusions The 5.5% prevalence of Fe reactions suggests a potentially underestimated role of this metal allergen in general and in implant bearers. The latter also shows a distinct metal sensitization pattern

Improving Service Provision – The Health Care Services' Perspective

How to improve service provision in the health care sector is a question of high economic and social relevance, as the health service industry represents a major part of developed nations’ economy and health care is a service virtually everyone is touched by in their life. The topic embraces different perspectives or levers, including the (re)organization of service provision, a stronger focus on the patient in the service delivery process, and the crucial role of employees in health service provision. We invited a group of well-renown scholars from different academic fields to share with us personal observations, empirical evidence, and interpretations of how to improve service provision in health care in the form of individual commentaries that cover the different perspectives. The resulting special research article includes motivations on why changes in the health care sector make service management research (smr) more relevant, it depicts implications (of smr) for health care organizations, and it outlines suggestions for future research. This article is designed to offer avenues for further service research on different perspectives for the improvement and professionalization of health care – a discipline in which joint efforts of service and health care Researchers can have great societal impact