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1.
Handb Exp Pharmacol ; 268: 173-193, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34104993

RESUMO

IgE-mediated food allergies affect both children and adults and are associated with dramatic decreases in the quality of life. In the majority of cases, food allergens have to be avoided which may be difficult, particularly in patients who suffer from life-threatening symptoms following the ingestion of minimal doses of food allergens. Several novel therapeutic approaches have been studied during the recent past and are summarized in this review. Therapies with novel therapeutic monoclonal antibodies, innovative allergen-specific immunotherapies using subcutaneous, sublingual, or epicutaneous routes, and oral immunotherapies leading to increases of individual thresholds of tolerable foods upon their continuous ingestion showed promising results which may change future management strategies in moderate to severe food allergy.


Assuntos
Hipersensibilidade Alimentar , Qualidade de Vida , Alérgenos , Criança , Dessensibilização Imunológica , Alimentos , Hipersensibilidade Alimentar/terapia , Humanos
2.
Handb Exp Pharmacol ; 268: 487-500, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34219201

RESUMO

Allergic diseases are characterized by a complex complex chronic pathophysiology. Therapeutic patient education (TPE) programs are an important part of health care for allergic patients. These programs aim to increase the patient's adherence to evidence-based treatment and improve their ability to cope with the disease. TPE led by a multiprofessional team covers the complex pathogenesis of the disease, trigger factors, nursing and dietary issues, and the broad variety of treatment options available including psychological and behavioral aspects.Regarding atopic dermatitis (AD), randomized, controlled studies have demonstrated the beneficial effects of delivering structured group training to children, their caregivers, and adult patients with AD. Such intervention achieved substantial improvements in quality of life and objective clinical disease parameters. Besides AD, training programs have also been developed and evaluated for patients with anaphylaxis and asthma. This article provides an overview of the multitude of TPE concepts and their impact on subjective and objective outcomes. It focuses on AD but also sheds light on other allergic diseases such as anaphylaxis and asthma.


Assuntos
Asma , Dermatite Atópica , Adulto , Criança , Dermatite Atópica/terapia , Humanos , Educação de Pacientes como Assunto , Qualidade de Vida , Projetos de Pesquisa
3.
Handb Exp Pharmacol ; 268: 101-115, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34236520

RESUMO

Atopic eczema (AE) is a chronic inflammatory disease hallmarked by intense pruritus and eczematous lesions. It depicts one of the most common skin diseases affecting a major part of children and several percentages of adults.Both pathogenesis and pathophysiology are based on complex orchestrated interactions of skin barrier defects, immunological changes, the environment, and an abundance of other contributing factors. Frequently, AE displays the starting point for other allergic diseases such as allergic asthma and rhinoconjunctivitis. Additionally, the risk of developing food allergy is increased. Furthermore, the disease is accompanied by a susceptibility to bacterial, fungal, and viral infections. The development of new therapies received great impetus by an ample research of the pathophysiological mechanisms, leading to a new era in the treatment of severe atopic eczema due to targeted treatments, e.g. the IL-4R alpha specific monoclonal antibody dupilumab.This article provides an overview of the causative and pathophysiological characteristics, the clinical and diagnostic aspects as well as current and future therapeutical possibilities focusing allergic aspects contributing to the course of the disease.


Assuntos
Asma , Dermatite Atópica , Eczema , Hipersensibilidade , Adulto , Criança , Dermatite Atópica/tratamento farmacológico , Humanos
4.
J Dtsch Dermatol Ges ; 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34958179

RESUMO

BACKGROUND: TREATgermany, a registry for patients with moderate to severe atopic dermatitis (AD), established an additional questionnaire in spring 2020 to investigate the effects of the coronavirus pandemic on the daily life of patients with AD. MATERIAL AND METHODS: A questionnaire was used to analyze general information regarding a patient's experience of the coronavirus pandemic and, using the Inventory of Life-Changing Events, the resulting personal burden. To analyze possible associations between disease severity (EASI score, oSCORAD, IGA, PGA, POEM), quality of life (DLQI) and personal burden, t-tests, analyses of variance and correlations were evaluated, controlled for sex and age. RESULTS: 58 % (n = 233) of the included 400 registry patients reported high burden scores caused by the coronavirus pandemic, regardless of an actual infection. Men showed significantly higher burden scores than women, and younger than older respondents (both P = 0.03). There were no differences in burden scores related to the physician's assessment of disease severity. However, patients with higher quality of life impairments and higher disease severity perceived the burden of the coronavirus pandemic as less severe (DLQI P = 0.019, PGA P = 0.044). CONCLUSIONS: Our data show that registry patients considered the coronavirus pandemic as a life-changing event and perceived the burden differently. This should be taken into account in the treatment of patients with moderate to severe AD as well as in further studies.

5.
J Clin Invest ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34847081

RESUMO

Ulcerating skin lesions are manifestations of human ISG15 deficiency, a type I interferonopathy. However, chronic inflammation may not be their exclusive cause. We describe two siblings with recurrent skin ulcers that healed with scar formation upon corticosteroid treatment. Both had a homozygous nonsense mutation in the ISG15 gene, leading to unstable ISG15 protein lacking the functional domain. We characterized ISG15-/- dermal fibroblasts, HaCaT keratinocytes, and human induced pluripotent stem cell-derived vascular endothelial cells. ISG15-deficient cells exhibited the expected hyperinflammatory phenotype, but also dysregulated expression of molecules critical for connective tissue and epidermis integrity, including reduced collagens and adhesion molecules, but increased matrix metalloproteases. ISG15-/- fibroblasts exhibited elevated ROS levels and reduced ROS scavenger expression. As opposed to hyperinflammation, defective collagen and integrin synthesis was not rescued by conjugation-deficient ISG15. Cell migration was retarded in ISG15-/- fibroblasts and HaCaT keratinocytes, but normalized under ruxolitinib treatment. Desmosome density was reduced in an ISG15-/- 3D epidermis model. Additionally, there were loose architecture and reduced collagen and desmoglein expression, which could be reversed by treatment with ruxolitinib/doxycycline/TGF-ß1. These results reveal critical roles of ISG15 in maintaining cell migration and epidermis and connective tissue homeostasis, whereby the latter likely requires its conjugation to yet unidentified targets.

6.
Hautarzt ; 72(12): 1102, 2021 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-34817627
8.
Int J Mol Sci ; 22(21)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34769080

RESUMO

The chemokine CCL18 is produced in cells of the myelomonocytic lineage and represents one of the most highly expressed chemokines in lesional skin and serum of atopic dermatitis patients. We investigated the role of histamine in CCL18 production in human monocyte-derived M2 macrophages differentiated in the presence of M-CSF and activated with IL-4, IL-13 or with IL-10. Since expression and regulation of histamine H1 receptor (H1R), H2R and H4R by IL-4 and IL-13 on human M2 macrophages were described, we analyzed expression of the histamine receptors in response to IL-10 stimulation by quantitative RT-PCR. IL-10 upregulated H2R and downregulated H4R mRNA expression by trend in M2 macrophages. IL-10, but in a more pronounced manner, IL-4 and IL-13, also upregulated CCL18. Histamine increased the cytokine-induced upregulation of CCL18 mRNA expression by stimulating the H2R. This effect was stronger in IL-10-stimulated M2 macrophages where the upregulation of CCL18 was confirmed at the protein level by ELISA using selective histamine receptor agonist and antagonists. The histamine-induced CCL18 upregulation in IL-10-activated M2 macrophages was almost similar in cells obtained from atopic dermatitis patients compared to cells from healthy control persons. In summary, our data stress a new function of histamine showing upregulation of the Th2 cells attracting chemokine CCL18 in human, activated M2 macrophages. This may have an impact on the course of atopic dermatitis and for the development of new therapeutic interventions.

9.
Hautarzt ; 72(12): 1103-1112, 2021 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-34792615

RESUMO

Since the first report of allergen-specific immunotherapy (AIT) by Noon et al. 110 years ago, a multitude of clinical and in vitro studies have been performed to identify the effects of the only curative treatment for allergies. However, in atopic dermatitis (AD), one of the most prevalent skin diseases, it is rarely used, despite evidence showing that aeroallergens can contribute to disease exacerbation. This review gives an overview about the studies, meta-analyses, and current guideline recommendations regarding AIT in AD patients. There is a distinct heterogeneity in the study designs, different allergens and application forms, endpoints and patient cohorts, which hinders the comparability of studies. Several trials depict a beneficial effect of AIT in AD patients suggesting that at least a subgroup of patients can benefit from treatment. Further developments in the field of AIT may advocate broader use in AD patients.


Assuntos
Dermatite Atópica , Eczema , Hipersensibilidade , Alérgenos , Dermatite Atópica/diagnóstico , Dermatite Atópica/terapia , Dessensibilização Imunológica , Humanos
12.
J Dtsch Dermatol Ges ; 19(10): 1463-1475, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34622544

RESUMO

BACKGROUND AND OBJECTIVES: Documenting patient data in psoriasis clinical practice can improve care, but standardized and transparent documentation is rare. The current project aimed to develop a data set for the documentation of psoriasis in daily practice. MATERIAL AND METHODS: In four online Delphi rounds and one in-person meeting, 27 psoriasis experts allocated variables to a standard, an optimal and an optional data set. Most of the questions were standardized. Open questions were included to allow for the provision of reasons and to enlarge the data sets. Furthermore, in the in-person meeting we considered a) patients' attitudes and b) dermatologists' information on the current usage and acceptability in Germany. RESULTS: The consensus approach resulted in a data set with 69 variables. The standard data set includes 20, the optimal data set 31 and the optional data set 18 variables. In summary, the data set can mainly be grouped into master data, general status and medical history data, medical history of psoriasis, status of psoriasis, diagnostics and comorbidity, therapies and patient-reported outcomes. CONCLUSIONS: The consensus recommendation of a standard, an optimal and an optional data set for routine care of psoriasis intends to be a decision-making aid and an orientation for both daily practice and further development of documentation systems.


Assuntos
Psoríase , Consenso , Técnica Delfos , Documentação , Alemanha , Humanos , Psoríase/diagnóstico , Psoríase/epidemiologia , Psoríase/terapia
13.
Allergy ; 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34601735

RESUMO

BACKGROUND: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases worldwide and Staphylococcus aureus colonization and secondary infections occur in the majority of AD patients. Allergic sensitizations against microbial antigens have been discussed as possible trigger factors of AD. Recently, we reported IgE sensitization against fibronectin-binding protein 1 (FBP1), an essential virulence component in S. aureus, in a subgroup of patients suffering from AD. To expand these findings by investigating delayed-type immune reactions, the objective of this study was to detect and phenotypically characterize FBP1-specific T cells as possible trigger factors in AD. METHODS: Immunodominant T-cell epitopes were mapped by proliferation testing of patient-derived FBP1-specific T-cell lines after stimulation with single 15mer peptides, which were derived from different functional domains of the FBP1 sequence. Major histocompatibility complex class II tetramers carrying immunodominant epitopes successfully stained T helper cells in 8 out of 8 HLA-matched, IgE-sensitized AD patients. RESULTS: Cytokine profiling of multimer-sorted cells revealed that predominantly the type 2 cytokines IL-13 and IL-4 were secreted by these cells. In contrast, IL-17, the marker cytokine for response to extracellular pathogens, was scarcely detectable. CONCLUSIONS: We demonstrate that FBP1 contains immunodominant peptides that induce a specific pro-inflammatory T helper cell response with increased Th2 levels that can drive an allergic inflammation in sensitized AD patients.

15.
Allergol Select ; 5: 305-314, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34651098

RESUMO

Adverse reactions to food or food ingredients are more often perceived than objectively verifiable. However, reliable laboratory tests are often lacking. As a result, people with perceived adverse reactions to food often follow extensive elimination diets for years and unnecessarily restrict their diet, as in the case of the frequently suspected histamine intolerance. In this condition, laboratory parameters such as the determination of diamine oxidase in serum have been shown to be inconclusive. The lack of symptom reproducibility calls into question the clinical picture of adverse reactions to ingested histamine. In order to approach persons with perceived histamine intolerance and to support them in moving from blanket restrictions, which are often unnecessarily strict, to effective personalized therapeutic strategies, the present guideline of the Working Group on Food Allergy of the German Society of Allergology and Clinical Immunology (DGAKI) in cooperation with the Medical Association of German Allergists (AeDA), the Pediatric Allergology and Environmental Medicine (GPA) as well as the Swiss Society of Allergology and Immunology (SGAI) and the Austrian Society of Allergology and Immunology (ÖGAI) recommends a practicable diagnostic and therapeutic approach.

16.
Allergol Select ; 5: 274-286, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34532636

RESUMO

BACKGROUND: The TREATgermany registry collects data from children, adolescents, and adults with moderate-to-severe atopic dermatitis (AD) in Germany. For this purpose, clinical and patient-reported outcomes, the course of the disease, and applied therapies are observed. METHODS: TREATgermany recruits patients with moderate-to-severe AD according to the diagnostic criteria of the UK Working Party, an "Objective Scoring for Atopic Dermatitis" (oSCORAD) > 20 and/or currently antiinflammatory systemic treatment for AD or previous anti-inflammatory systemic treatment for AD within past 24 months before inclusion. No study related interventions will be performed. Currently, 59 dermatological practices, clinics, and university hospitals are participating in TREATgermany (as of May 2021). Based on the interim analysis of October 13, 2020, patient characteristics were described from 4,373 documented visits of adult participants (n = 1,025). RESULTS: The mean age at inclusion in TREATgermany was 42 years, 57.7% of patients were men (n = 591) and 42.3% were women (n = 434). According to oSCORAD, 85.8% of those included suffered from moderate-to-severe AD. At baseline visit, 744 patients had already received one or more systemic treatments for AD (glucocorticosteroids n = 600, ciclosporin A (CSA) n = 307, dupilumab n = 98). 597 patients received dupilumab during their participation in TREATgermany, 134 patients received CSA. CONCLUSION: With the increasing number of recruitment centers (October 2020: 38 centers; May 2021: 59 centers), TREATgermany can continue to make an important contribution to health services research for patients with moderate-to-severe AD. The registry fulfills the methodological requirements of IQWiG for the collection and processing of healthcare-related data. With the successful and expected approval of further systemic treatments, these can be compared in terms of efficacy and safety in the future. In addition, with the recruitment of children and adolescents started in 2021, this patient group can also be observed.

17.
Allergol Select ; 5: 293-304, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34532638

RESUMO

The JAK-STAT pathway is involved in the signaling of multiple cytokines driving cutaneous inflammation in atopic dermatitis (AD). Janus kinase (JAK) inhibitors target individual receptor-associated kinases, thereby preventing the mediation of inflammatory signals. Several JAK inhibitors with varying mechanism of action, potency, and safety represent potential therapeutic options for AD in both topical and systemic application. The JAK1/2 selective JAK inhibitor baricitinib was the first substance from this class of drugs approved by the EMA for the systemic oral treatment of AD. The clinical development program of the JAK1 selective inhibitors upadacitinib and abrocitinib is finalized with positive results for AD. The PAN-JAK inhibitor delgocitinib was the first substance being approved for the treatment of AD (in Japan). This review article covers the rising data on investigational and approved JAK inhibitors in the context of the treatment of AD.

18.
Allergol Select ; 5: 251-259, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34533543

RESUMO

BACKGROUND: Vaccinations against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are intended to induce an immune response to protect against infection/disease. Allergen immunotherapy (AIT) is thought to induce a (different) immune response, e.g., to induce tolerance to allergens. In this position paper we clarify how to use AIT in temporal relation to COVID-19 vaccination. Four SARS-CoV-2 vaccines are currently approved in the EU, and their possible immunological interactions with AIT are described together with practical recommendations for use. MATERIALS AND METHODS: Based on the internationally published literature, this position paper provides specific recommendations for the use of AIT in temporal relation to a SARS-CoV-2 vaccination. RESULTS: AIT is used in 1) allergic rhinitis, 2) allergic bronchial asthma, 3) insect venom allergy, 4) food allergy (peanut). CONCLUSION: For the continuation of an ongoing AIT, we recommend an interval of 1 week before and after vaccination for subcutaneous immunotherapy (SCIT). For sublingual immunotherapy (SLIT) and oral immunotherapy (OIT), we recommend taking them up to the day before vaccination and a break of 2 - 7 days after vaccination. Initiation of a new SCIT, SLIT, or OIT should be delayed until 1 week after the day of the second vaccination. For SCIT, we generally recommend an interval of ~ 1 week to COVID-19 vaccination.

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