S3 Guideline Atopic dermatitis: Part 1 - General aspects, topical and non-drug therapies, special patient groups.

This S3 guideline was created based on the European S3 guideline, with special consideration of the medical conditions in the German-speaking region and incorporating additions from the previous German-language version. The interdisciplinary guideline commission consisted of representatives from the German Dermatological Society, the Professional Association of German Dermatologists, the Austrian Society of Dermatology and Venereology, the Swiss Society of Dermatology and Venereology, the German Society for Allergology and Clinical Immunology, the German Society for Pediatric and Adolescent Medicine, the Professional Association of Pediatricians and Adolescent Medicine, the Society for Pediatric Allergology and Environmental Medicine, the German Society for Pediatric Rehabilitation and Prevention, the German Society for Psychosomatic Medicine and Medical Psychotherapy, the German Network for Health Services Research, the German Eczema Association and the German Allergy and Asthma Association. This first part of the guideline focuses on the definition and diagnostic aspects of atopic dermatitis (AD), addressing topical therapy as well as non-pharmacological treatment approaches such as UV therapy, psychoeducational therapy, dietary interventions for AD, allergen immunotherapy for AD, and complementary medicine. This part of the guideline also covers specific aspects of AD in children and adolescents, during pregnancy and lactation, and in the context of family planning. Additionally, it addresses occupational aspects of AD and highlights the perspective of the patients. The second part of the guideline, published separately, addresses the systemic therapy of AD.

S3 guideline Atopic dermatitis: Part 2 - Systemic treatment.

The present S3 guideline was created based on the European English-language S3 guideline, with special consideration given to the medical conditions in the German-speaking region, and with additions from the previous German-language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off-label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non-drug therapy approaches, and addresses aspects related to special patient groups.

Update "Systemic treatment of atopic dermatitis" of the S2k-guideline on atopic dermatitis.

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.

Design of experiments as a valuable tool for biopharmaceutical analysis with (imaged) capillary isoelectric focusing.

Capillary isoelectric focusing is indispensable for characterizing charge heterogeneity and isoelectric points of biopharmaceuticals. However, there are many influencing parameters and therefore method development is challenging. This study was performed to obtain an in-depth understanding of the imaged CIEF methodology by applying a design of experiments approach. To describe the parameter's effects as objectively as possible, a polynomial regression model was derived for the most important responses. For this purpose, the reference monoclonal antibody suggested by the National Institute of Standards and Technology (NISTmAb) was used as test molecule. The total concentration and the mixing ratio of two types of carrier ampholytes and the added amounts of urea and l-arginine were selected as factors. The effects of these factors on 13 different responses such as resolution or pI values were investigated. In order to reduce the total number of experiments, a d-optimal design with 20 different parameter combinations and six replicates each was chosen. The most significant effects of the four factors were shown for the parameters related to separation efficiency and peak position. In addition, the extent of the factor's effect could be assessed. Depending on the selected factor combination, the pI value can differ up to approximately 0.15 pI units and the resolution value between main peak and adjacent basic peak can range from approximately 1.6 to 2.5, for example.

Determination of protein charge variants with (imaged) capillary isoelectric focusing and capillary zone electrophoresis.

Biopharmaceuticals are increasingly present in pharmaceutical therapy. These highly complex molecules are still challenging for development and quality control. Charge heterogeneity is next to size heterogeneity, glycan analysis, or peptide mapping one main aspect of their thorough characterization. This review focuses on the charge-based analysis of biopharmaceuticals through CE. An overview is given about the three separation techniques cIEF, imaged cIEF and CZE for the analyses of charge variants, emphasizing assays and their precision. Especially the developments in the experimental conditions have been given a high priority: sample preparation, capillary properties, anolytes and catholytes, carrier ampholytes, sacrificing agents, solubility enhancement, isoelectric point marker, mobilization techniques, and detection modes have been discussed. CIEF shows a particularly high heterogeneity in its methods. Therefore, a design space is suggested that states the most important adjustable parameters and their range. This enables an adequate design of experiments for individual sample separations, in order to accelerate and simplify method developments.

The next generation of capillary electrophoresis instruments: Performance of CE-SDS protein analysis.

Over the last decade, capillary electrophoresis gained tremendous importance, because it became an indispensible tool for the quality control of biologics, e.g. therapeutic antibodies. Consequently, there has been a continuous development within the CE market. Microchip techniques have been established in the last years. Further trends are complete solutions for specific applications by the usage of reagent kits. Step by step instructions and facilitated handling of the instruments are becoming more common. This work focuses on the sized-based protein analysis with CE-SDS. The instruments CE 7100 by Agilent Technologies, LabChip® GXII Touch HT by PerkinElmer, Maurice S. by Protein Simple and PrinCE NextI870 by Prince Technologies have been evaluated, mainly analyzing protein mixtures of different molecular weights in long series. Published data of the PA 800 plus by SCIEX are also included in the tabled results. Precision, reliability, flexibility, and speed have been identified as the most important performance parameters, others such as resolution, sensitivity, linearity, ease of use and sustainability have also been considered. All tested instruments have shown an excellent performance. Depending on application and necessities, each user can find the most appropriate one.

S2k guideline on diagnosis and treatment of atopic dermatitis--short version.

Atopic dermatitis (AD) represents a pruritic, non-contagious, chronic or chronically relapsing, inflammatory skin disease. The course of the disease may be complicated by bacterial or viral superinfections. The first manifestation of the disease and further flare-ups are due to genetic predisposition and also to a variety of further trigger factors. The therapy regimen should be adapted to disease symptoms that are actually present and consider individual features of the disease as reported by the patients or their parents. This short version of the German guideline on AD provides an overview of evidence-based diagnostic and treatment options. All recommendations made here are the result of a consensus of the scientific medical societies, working groups and support groups based on scientific data published to date. Abstracts and details of the studies cited are provided in the long version of this guideline (see: www.awmf.org).

Milk ladder as a therapeutic option for cow's milk allergy: Proposal for a step-by-step plan for cow's milk introduction in cow's milk allergy.

In regard to cow's milk allergy, the current option of avoiding can be expanded by (re-)introducing milk using a milk ladder. So-called "food ladders" are internationally well known and utilized for both non-IgE-mediated and IgE-mediated cow's milk allergy. Stepping up the stairs from highly processed baked goods with milk via cooked milk products to pasteurized fresh milk reflects the status of acquired tolerance of each level. The allergenicity of milk depends on processing and amount. By implementing the milk ladder, it can enhance the clinical process of tolerance development, lead to meeting nutrient requirements quickly, and involve parents actively in the therapeutical process. The milk ladder, for the first time being published and adapted for Germany, describes a structured framework that might be adapted individually regarding the time period on a certain level or other variations such as preparation/amount of milk products. From a safety perspective, healthcare professionals should pay great attention to patient selection and education prior to implementing the milk ladder. Detailed advice as well as recipes and a graphical presentation can be found in the supplemental material.

Comparative charge-based separation study with various capillary electrophoresis (CE) modes and cation exchange chromatography (CEX) for the analysis of monoclonal antibodies.

Charge heterogeneity is an important critical quality attribute for the analysis of monoclonal antibodies (mAbs). For this, (imaged) capillary isoelectric focusing ((i)cIEF), ion exchange chromatography (IEC) and, recently, capillary zone electrophoresis (CZE) are the predominantly used techniques. In order to investigate which one is most suitable to answer a specific analytical question, here, the four aforementioned separation techniques were systematically evaluated using NISTmAb and Infliximab as test molecules. The performance parameters (precision, separation efficiency, linearity and sensitivity) were determined under comparable conditions. Moreover, important aspects for daily routine such as speed and ease of use were considered. Each technique has its own pros and cons. The (i)cIEF methodology is distinguished by its excellent separation efficiency. In addition, the native fluorescence mode in icIEF is a good tool to analyze small sample amounts (LOQ: 2.8 mg/l for Infliximab). Nevertheless, high performance liquid chromatography (HPLC) still has superior precision. CZE, and also micellar electrokinetic chromatography (MEKC), have emerged as further interesting alternatives. For all techniques, variations connected to the sample preparation strongly influence precision. Looking at the relative standard deviation (RSD) values of the relative peak areas, all techniques provide acceptable performance (RSD: 0.6-1.6%).

Interlaced Size Exclusion Chromatography for faster protein analysis.

In this research note, interlaced Size Exclusion Chromatography (SEC) is used to shorten the duration of protein analysis. The applied method has a threefold higher sample throughput than comparable ones using conventional SEC. Further important advantages are the identical area's precision and the preservation of protein stability. Two different applications are presented where a short time interval of analysis is very important. One application is the determination of aggregates of monoclonal antibodies (mAbs). A high number of antibody samples have to be analyzed during the development process. The antibody sample was measured in a series of 60 injections within only 5.5 h instead of 16 h. The second application is the two-dimensional (2 D) separation of protein mixtures. The number of samples typically increases from the first to the second dimension. Thus, interlaced SEC is a reasonable option for the second dimension. This work confirms the functionality of interlaced SEC and widens the applicable range. Interlaced SEC can become a convenient option for method acceleration in the future.

S2k guideline on diagnosis and treatment of atopic dermatitis - short version.

Atopic dermatitis (AD) represents a pruritic, non-contagious, chronic or chronically relapsing, inflammatory skin disease. The course of the disease may be complicated by bacterial or viral superinfections. The first manifestation of the disease and further flare-ups are due to genetic predisposition and also to a variety of further trigger factors. The therapy regimen should be adapted to disease symptoms that are actually present and consider individual features of the disease as reported by the patients or their parents. This short version of the German guideline on AD provides an overview of evidence-based diagnostic and treatment options. All recommendations made here are the result of a consensus of the scientific medical societies, working groups and support groups based on scientific data published to date. Abstracts and details of the studies cited are provided in the long version of this guideline (see: www.awmf.org).