Publications by authors named "Julia Pickert"

9 Publications

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Long-term impact of hymenoptera venom immunotherapy on clinical course, immune parameters, and psychosocial aspects.

Allergol Select 2021 26;5:57-66. Epub 2021 Jan 26.

Department of Dermatology and Allergology, Allergy Center Hessen, University Medical Center Marburg, Marburg, Germany.

Background: Venom immunotherapy (VIT) is highly efficient in subjects suffering from IgE-mediated allergy to hymenoptera venom (HV), and VIT results in substantial improvement of quality of life (QoL). However, VIT-induced tolerance may be lost over time after cessation of treatment, putting patients at risk of re-sting anaphylaxis.

Materials And Methods: To study the effect of VIT on maintenance of HV tolerance we evaluated the natural history of 54 patients who were treated with VIT up to 29 years ago, with a special focus on re-stings and their subsequent course. Furthermore, we analyzed HV-specific IgE, IgG, and IgG4 antibody titers. Finally, we assessed the long-term impact of VIT on various psychosocial aspects like dealing with hymenoptera exposures, daily life activities, self-assurance, and personal environment.

Results: 29 (53.7%) subjects experienced at least one re-sting after stopping VIT, with 23 (79%) showing no systemic reaction (SR). Eleven of these (37.9%) took emergency drugs as a safety measurement. Six individuals (21%) showed loss of tolerance experiencing an anaphylactic reaction. No difference in HV-specific IgE, IgG4, or IgG antibody concentrations was noticed among the different patients. Subjects who tolerated a re-sting without applying emergency drugs felt least affected in their social-behavioral leisure activities when hymenoptera were around or by anxiety for new stings.

Conclusion: VIT leads to long-term tolerance in the majority of HV-allergic patients, however, ~ 1/5 may lose protection over time, arguing for continued follow-up on VIT-treated subjects and keeping them equipped with an emergency kit. Notably, VIT also results in a lasting, strong impact on self-assurance and sense of well-being in individuals who tolerated a re-sting without employing emergency drugs, which emphasizes the need to use them only in case of systemic symptoms after stopping successful VIT.
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http://dx.doi.org/10.5414/ALX02175EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841418PMC
January 2021

Biologics for atopic diseases: Indication, side effect management, and new developments.

Allergol Select 2021 5;5:1-25. Epub 2021 Jan 5.

Department of Dermatology and Allergy, Charité Universitätsmedizin, Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Comprehensive Allergy Center, Berlin, Germany.

With the advent of biologicals, more and more therapeutics are available that specifically address specific switch points in the pathomechanism of immunologically dominated diseases. Thus, the focus of diagnostics and therapy (precision medicine) is more on the individual disease characteristics of the individual patient. Regarding the different phenotypes of atopic diseases, severe asthma was the first entity for which biologicals were approved, followed by urticaria, and finally atopic dermatitis and chronic rhinosinusitis with nasal polyps. Experience in the treatment of severe bronchial asthma has shown that the intensity of the response to biological therapy depends on the quality of clinical and immunological phenotyping of the patients. This also applies to different diseases of the atopic form, as patients can suffer from several atopic diseases at the same time, each with different characteristics. Biologics are already emerging that may represent a suitable therapy for allergic bronchial asthma, which often occurs together with severe neurodermatitis, and chronic rhinosinusitis with nasal polyps. In practice, however, the question of possible combinations of biologicals for the therapy of complex clinical pictures of individual patients is increasingly arising. In doing so, the side effect profile must be taken into account, including hypersensitivity reactions, whose diagnostic and logistical management must aim at a safe and efficient therapy of the underlying disease. Increased attention must also be paid to biological therapy in pregnancy and planned (predictable) vaccinations as well as existing infections, such as SARS-CoV-2 infection. Before starting a biological therapy, the immune status should be checked with regard to chronic viral and bacterial infections and, if necessary, the vaccination status should be refreshed or missing vaccinations should be made up for before starting therapy. Currently, reliable data on the effect of biologicals on the immunological situation of SARS-CoV-2 infection and COVID-19 are not available. Therefore, research and development of suitable diagnostic methods for detection of immunologically caused side effects as well as detection of potential therapy responders and non-responders is of great importance.
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http://dx.doi.org/10.5414/ALX02197EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787364PMC
January 2021

Healthcare provision for insect venom allergy patients during the COVID-19 pandemic.

Allergo J Int 2020 8;29(8):257-261. Epub 2020 Dec 8.

Department and Outpatient Clinic for Dermatology and Allergology, University Hospital Munich, Munich, Germany.

The population prevalence of insect venom allergy ranges between 3-5%, and it can lead to potentially life-threatening allergic reactions. Patients who have experienced a systemic allergic reaction following an insect sting should be referred to an allergy specialist for diagnosis and treatment. Due to the widespread reduction in outpatient and inpatient care capacities in recent months as a result of the COVID-19 pandemic, the various allergy specialized centers in Germany, Austria, and Switzerland have taken different measures to ensure that patients with insect venom allergy will continue to receive optimal allergy care. A recent data analysis from the various centers revealed that there has been a major reduction in newly initiated insect venom immunotherapy (a 48.5% decline from March-June 2019 compared to March-June 2020: data from various centers in Germany, Austria, and Switzerland). The present article proposes defined organizational measures (e.g., telephone and video appointments, rearranging waiting areas and implementing hygiene measures and social distancing rules at stable patient numbers) and medical measures (collaboration with practice-based physicians with regard to primary diagnostics, rapid COVID-19 testing, continuing already-initiated insect venom immunotherapy in the outpatient setting by making use of the maximal permitted injection intervals, prompt initiation of insect venom immunotherapy during the summer season, and, where necessary, using outpatient regimens particularly out of season) for the care of insect venom allergy patients during the COVID-19 pandemic.
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http://dx.doi.org/10.1007/s40629-020-00157-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722411PMC
December 2020

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.

Allergy 2021 03 29;76(3):816-830. Epub 2020 Dec 29.

Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology and Venereology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Introduction: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown.

Aim: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19.

Materials And Methods: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences.

Results: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19.

Conclusions: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.
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http://dx.doi.org/10.1111/all.14687DOI Listing
March 2021

Therapeutic Targeting of Th17/Tc17 Cells Leads to Clinical Improvement of Lichen Planus.

Front Immunol 2019 31;10:1808. Epub 2019 Jul 31.

Department of Dermatology and Allergology, Philipps-Universität Marburg, Marburg, Germany.

Lichen planus (LP) is a common, chronic relapsing inflammatory disorder of the skin and mucous membranes which often poses a major therapeutic challenge due to its refractory course. Novel pathogenesis-based therapies are urgently needed. As several studies have shown that IL-17 may contribute to LP pathogenesis, we investigated whether therapeutic targeting of IL-17 T cells leads to clinical improvement of mucosal and cutaneous LP lesions. A total of five patients with lichen planus were treated in a compassionate use trial with either secukinumab (anti-IL-17; 3 patients with acute and chronic recalcitrant muco-cutaneous LP), ustekinumab (anti-IL-12/IL-23; 1 patient with recalcitrant oral LP) or guselkumab (anti-IL-23; 1 patient with recalcitrant oral LP). The clinical course of the patients was assessed by the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) reflecting both extent and severity of disease and functional sequelae of oral involvement for at least 12 weeks. The inflammatory infiltrate in lesional and post-lesional skin was analyzed by immunohistochemistry before and after treatment. Furthermore, the cytokine profile of peripheral blood T cells from the treated patients was assessed by flow cytometry and/or ELISpot assay. Treatment with secukinumab induced rapid and prolonged clinical amelioration of muco-cutaneous LP. Clinical improvement was accompanied by a strong reduction of the Th1 and Th17/Tc17 cellular mucosal and cutaneous infiltrate. Moreover, long-term treatment of one patient with recalcitrant oral LP with ustekinumab led to healing of the ulcerative oral lesions and a reduction of peripheral blood and lesional IL-17 T cells. Finally, treatment with guselkumab led to a marked clinical improvement in a patient with recalcitrant erosive oral LP. These findings show for the first time that therapeutic targeting of Th17/Tc17 cells leads to a pronounced clinical amelioration of mucosal and cutaneous LP and strongly suggests that IL-17-producing T cells are central to disease pathogenesis. Thus, therapeutic targeting of Th17/Tc17 cells opens new therapeutic avenues in the treatment of recalcitrant LP.
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http://dx.doi.org/10.3389/fimmu.2019.01808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685396PMC
September 2020

Thymoma-Associated Paraneoplastic Autoimmune Multiorgan Syndrome-From Pemphigus to Lichenoid Dermatitis.

Front Immunol 2019 21;10:1413. Epub 2019 Jun 21.

Department of Dermatology and Allergology, Philipps-University, Marburg, Germany.

Paraneoplastic autoimmune multi-organ syndrome (PAMS) is a rare clinical condition characterized by variable and heterogeneous clinical phenotypes in the presence of neoplasias which largely depend on the activation of humoral and cellular immune responses. Clinically, these patients present with a spectrum of antibody-driven pemphigus-like lesions to graft-vs.-host-disease-like exanthemas with a lichenoid inflammatory infiltrate in the skin. PAMS is occasionally associated with thymoma, in which altered immune surveillance eventually leads to multiorgan autoimmunity which often includes variable cutaneous symptoms. This disorder is associated with a profound disturbance of peripheral immune tolerance against human autoantigens. We here present a patient with relapsing thymoma who developed PAMS with several cutaneous and extracutaneous autoimmune disorders. Peripheral blood mononuclear cells (PBMC), sera, and lesional skin biopsies were obtained at different clinical disease stages. Peripheral T cell subsets were characterized phenotypically and the cytokine profile of the peripheral blood T cellular response against distinct epidermal and dermal autoantigens of the skin was analyzed by ELISpot assay. Serological screening was performed by ELISA and immunoblot analysis. Skin biopsies were subjected to immunohistochemical analysis of distinct T cell subsets. Thymoma tissue was analyzed for the presence of T regulatory cells and compared with adult thymus and indolent thymoma. In the present case, thymoma was the cause of the observed multi-organ autoimmune syndromes as its recurrence and surgical removal was associated with the relapse and regression of the cutaneous symptoms, respectively. Initially, the patient presented with two autoimmune disorders with Th2/Th1 imbalance, myasthenia gravis (MG) and pemphigus foliaceus (PF), which regressed upon immunosuppressive treatment. Months later, the patient developed a lichenoid exanthema with a Th1-dominated skin infiltrate. Further clinical evaluation revealed the recurrence of the thymoma and the lichenoid exanthema gradually regressed upon thymectomy. Our contention that T cell recognition against distinct cutaneous autoantigens, such as desmoglein 1 (Dsg1), shifted from a Th2 to a Th1-dominated immune response could not be fully substantiated as the patient was on a stringent immunosuppressive treatment regimen. We could only observe a decrease of the initially present serum IgG autoantibodies against Dsg1. Phenotypic analysis of the associated thymoma showed a lower number of T regulatory cells compared to adult thymus and indolent thymoma, suggesting that impaired thymus-derived immune surveillance had a direct impact on the outcome of the observed cutaneous autoimmune disorders.
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http://dx.doi.org/10.3389/fimmu.2019.01413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598597PMC
October 2020

Birch pollen allergen-specific immunotherapy with glutaraldehyde-modified allergoid induces IL-10 secretion and protective antibody responses.

Allergy 2019 08 11;74(8):1575-1579. Epub 2019 Apr 11.

Clinical & Experimental Allergology, Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.

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http://dx.doi.org/10.1111/all.13774DOI Listing
August 2019

Teaching differential diagnosis in primary care using an inverted classroom approach: student satisfaction and gain in skills and knowledge.

BMC Med Educ 2015 Apr 1;15:63. Epub 2015 Apr 1.

Marburg Interactive Skills Lab (MARIS), Faculty of Medicine, University of Marburg, Marburg, Germany.

Background: Differential diagnosis is a crucial skill for primary care physicians. General practice plays an increasing important role in undergraduate medical education. Via general practice, students may be presented with an overview of the whole spectrum of differential diagnosis in regard to common symptoms encountered in primary care. This project evaluated the impact of a blended learning program (using the inverted classroom approach) on student satisfaction and development of skills and knowledge.

Methods: An elective seminar in differential diagnosis in primary care, which utilized an inverted classroom design, was offered to students. Evaluation followed a mixed methods design: participants completed a pre- and post-test, a questionnaire, and a focus group discussion. Interviews were transcribed verbatim and answers were grouped according to different themes. Test results were analysed using the Wilcoxon matched-pairs signed-ranks test.

Results: Participants (n = 17) rated the course concept very positively. Especially the inverted classroom approach was appreciated by all students, as it allowed for more time during the seminar to concentrate on interactive and practice based learning. Students (n = 16) showed a post-test significant overall gain in skills and knowledge of 33%.

Conclusions: This study showed a positive effect of the inverted classroom approach on students' satisfaction and skills and knowledge. Further research is necessary in order to explore the potentials of this approach, especially the impact on development of clinical skills.
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http://dx.doi.org/10.1186/s12909-015-0346-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404043PMC
April 2015