Allergologie select最新文献

The development of targeted therapies for atopic diseases, urticaria, and angioedema with biologics is progressing rapidly: New "targets" of clinical-therapeutic relevance have been identified, the corresponding targeted antibodies developed, tested in clinical trials, and approved for therapy. These include the anti-IgE antibody omalizumab (also effective and approved for the treatment of urticaria), the anti-IL-4/13 receptor-specific antibody dupilumab, the two anti-IL-13 antibodies lebrikizumab and tralokinumab, the anti-TSLP antibody tezepelumab, the two anti-IL-5 antibodies mepolizumab and reslizumab, and the anti-IL5 receptor-specific antibody benralizumab for the treatment of atopic diseases. For the treatment of hereditary angioedema, C1 inhibitor and the antibody lanadelumab (directed against kallikrein) have also long been approved as biologics in addition to low-molecular substances. Other therapeutic antibodies are in various stages of development. Furthermore, the range of indications for some very effective biologics has been successfully expanded to include additional diseases. In this context, the first results on biologic therapy of food allergy and eosinophilic esophagitis are interesting. Biologics that address different target structures are also increasingly being administered in combination, either simultaneously or sequentially, in order to achieve optimal efficacy. A developing area is the use of biologics in children and the observation of immunological and non-immunological side effects. In some cases, new unexpected side effects and hypersensitivity reactions have emerged, which in turn raise pathomechanistic questions, such as conjunctivitis with dupilumab therapy, which only appears to occur in the treatment of atopic dermatitis but not in the treatment of other atopic diseases. In dermatology, paradoxical reactions have been described under therapy with some biologics. And immune reactions of type alpha to epsilon to biologics (hypersensitivity reactions) continue to be a clinically relevant problem, whereby the selection of an alternative therapeutic agent is a challenge and the diagnostics that support this have not yet been sufficiently incorporated into routine work.

Background: In hereditary angioedema (HAE), numerous factors are known to trigger an attack. The possible influence of diet or recreational sports has been given little consideration in studies. The aim of our work was to investigate the influence of nutrition and physical activity in patients with HAE at the Leipzig ACARE Center.

Materials and methods: Patients with HAE were given a self-designed questionnaire inquiring for family history, disease progression, and encountered burden due to HAE, current therapy, and disease control (angioedema control test (AECT)) as well as the influence of diet and/or recreational sports on HAE attacks.

Results: Inclusion of 30 patients (23 female, 77%) with a mean age of 49.5 ± 16.9 years and mean body mass index of 25.1 ± 6.4 kg/m². 60% received prophylactic treatment, and 37% received exclusively on-demand therapy. The mean AECT score was 10.9 ± 5.1 and patients reported 15.5 ± 26.9 days of absence due to HAE attacks in the last 12 months. 33% reported an association with food intake, in particular worsening of abdominal symptoms (n = 7), swelling of the extremities (n = 3), face, larynx, or genital area (n = 1 each). 70% reported regular exercise, most commonly cycling (n = 11), running or walking (n = 10), or strength training (n = 10). 62% reported a worsening of HAE due to recreational exercise.

Conclusion: Dietary factors and physical activity frequently led to an aggravation of HAE in our cohort and should be taken into consideration when counseling patients with regard to trigger avoidance.

Background and objectives: Patients with rare diseases like hereditary angioedema (HAE) are usually referred to an angioedema center to ensure guideline-compliant and experience-based therapy. Even though there are established guidelines and several approved therapeutics, there are still open questions and situations in the daily care of HAE patients, where an exchange between centers is needed.

Materials and methods: A survey was conducted among physicians from German angioedema centers regarding challenges and issues in everyday HAE treatment. The main focus was on the topic of long-term prophylaxis (LTP). For rarer subcategories of angioedema, the centers conducted a literature review to discuss open questions.

Results: The responses of 12 physicians from 8 angioedema centers were analyzed in the survey. The attack frequency was the most important criterion for deciding to initiate LTP in HAE patients (100%). Two centers no longer generally recommend the initiation of pre-interventional prophylaxis in HAE patients under LTP. The therapeutic concepts of acquired angioedema due to C1 inhibitor deficiency and HAE in children were two associated specialized areas that were discussed in more detail.

Conclusion: The current guideline serves as the foundation for daily practice in treating HAE at specialized centers. Thus, for rare conditions like HAE, an exchange among the treating centers is essential to adequately address specific issues and rare subgroups.

Modern management of hereditary angioedema (HAE) due to reduced C1 inhibitor (C1-INH) function or concentration (HAE-C1-INH) focuses on individualized therapeutic strategies to address the specific needs of children and adolescents as well as the severity of the disease. Psychosocial factors such as the burden of disease and therapy on quality of life and participation play an important role. New medications have already significantly improved the prognosis and health related quality of life in HAE patients, but not all of these therapies have yet been approved for children. Further treatment options that inhibit bradykinin effects are currently being investigated. They target factor XIIa, prekallikrein, plasma kallikrein, or the bradykinin B2 receptor. Modern research focuses on oral options or long-acting parenteral therapy approaches to further optimize care and, in particular, the needs of children. There are also initial developments in the field of gene therapy, which could represent a causal treatment option for HAE in the future. This article focuses on the presentation and treatment of HAE type I (reduced C1-INH concentration) and HAE type II (impaired C1-INH function) in children and adolescents. Acquired AE and HAE with normal C1-INH are rare in the pediatric age group and are not discussed in detail here.

Hymenoptera stings can cause severe anaphylactic reactions in patients with an underlying Hymenoptera venom allergy (HVA). In such cases, venom immunotherapy (VIT) is a highly effective measure to prevent future anaphylaxis. The management of patients with a clear allergological indication for VIT and contraindications to VIT (e.g., autoimmune diseases) remains a clinical challenge. We report the case of a 54-year-old male gardener who experienced life-threatening anaphylaxis after being stung by wasps in the head and neck region. After confirmation of a Vespula venom allergy (VVA) by intradermal test and VV-specific serum IgE antibodies, VIT was started using a rush protocol. One month after reaching the maintenance dose, the patient experienced a worsening of his pre-existing Crohn's disease and ankylosing spondylitis. VIT was stopped, and the autoimmune diseases were treated with systemic steroids and sulfasalazine. As the patient wished to remain in his profession, and in view of the previous severe anaphylaxis, we restarted VIT after the autoimmune diseases had resolved, using a slower up-dosing protocol. This approach was tolerated without side effects, and the patient tolerated a sting challenge and several field stings without anaphylactic symptoms.

More than 10 years ago, the British Society for Allergy and Clinical Immunology (BSACI) published guidelines for the management of egg allergy [1]. For the first time, these included a stepwise plan for the reintroduction of egg for egg-allergic children who could already tolerate well-cooked egg, such as cakes and cookies. Since then, various egg ladders have been developed [2, 3, 4, 5, 6, 7, 8, 9]. In the past 3 years, several studies have been published suggesting that a gradual introduction of highly processed to less processed egg containing foods contribute to the acceleration of tolerance development [2, 3, 4, 5]. However, depending on the study and egg ladder, the egg products vary in their level of processing (wheat matrix, degree, and location of heating (e.g., oven, pan, pot), egg quantity, and egg protein). In the UK, the introduction of the egg ladder is recommended at the age of 12 months or if the last reaction occurred 6 months before. The benefits of introducing egg at home include an early increase in the variety of foods, reduction of food fears, improved nutrient intake, and the avoidance of hospitalization fears in children [10]. Children with mild reactions in the past can start with small amounts of baked goods at home. Food challenges in an inpatient setting to exclude or reconfirm the allergy should be conducted if the patients have previously had severe allergic reactions, i.e., anaphylaxis, or if the smallest amounts triggered an allergic reaction or if existing asthma is poorly controlled [10, 11]. The present work includes, in addition to the evaluation of study results, a presentation of the recent studies regarding egg ladders. From these, a new egg ladder as therapeutic option for the German-speaking region has been developed. As already done for the milk ladder a detailed step-by-step plan, selection criteria, a recipe collection, and also ideas for commercial prepackaged food items can be found in the appendices [11].

Primary atopic disorders (PAD) are monogenic disorders caused by pathogenic gene variants encoding proteins that are key for the maintenance of a healthy skin barrier and a well-functioning immune system. Physicians face the challenge to find single, extremely rare PAD patients/families among the millions of individuals with common allergic diseases. We describe case scenarios with signature PAD. We review the literature and deduct specific clinical red flags for PAD detection. They include a positive family history and/or signs of pathological susceptibility to infections, immunodysregulation, or syndromic disease. Results of conventional laboratory and most immunological lab studies are not sufficient to make a definitive diagnosis of PAD. In the past, multistep narrowing of differential diagnoses by various immunological and other laboratory tests led to testing of single genes or gene panel analyses, which was a time-consuming and often unsuccessful approach. The implementation of whole-genomic analyses in the routine diagnostics has led to a paradigm shift. Upfront genome-wide analysis by whole genome sequencing (WGS) will shorten the time to diagnosis, save patients from unnecessary investigations, and reduce morbidity and mortality. We propose a rational, clinical landmark-based approach for deciding which cases pass the filter for carrying out early WGS. WGS result interpretation requires a great deal of caution regarding the causal relationship of variants in PAD phenotypes and absence of proof by adequate functional tests. In case of negative WGS results, a re-iteration attitude with re-analyses of the data (using the latest data base annotation)) may eventually lead to PAD diagnosis. PAD, like many other rare genetic diseases, will only be successfully managed, if physicians from different clinical specialties and geneticists interact regularly in multidisciplinary conferences.

Mastocytosis or an elevated basal serum tryptase (bST) level are known risk factors for patients with insect venom allergy. We report on 3 patients with a history of severe anaphylactic insect sting reactions who underwent a detailed workup for insect venom allergy before starting venom immunotherapy. In addition to insect venom sensitization, an elevated concentration of bST (15.5, 20.8, and 23.2 µg/L) was found in all cases. There was no evidence of mastocytosis in the skin (MIS). Further testing revealed hereditary α-hypertryptasemia (HαT) in 2 patients and a D816V mutation by liquid biopsy in 1 patient, which is a minor diagnostic criterion for indolent systemic mastocytosis. Even without iliac crest puncture, causes of elevated bST can be narrowed down with minimally invasive diagnostic measures. As this has practical implications, patients with elevated bST should always undergo further work-up to determine the cause of this abnormal finding.

Hypersensitivity pneumonitis (HP) is a rare, mostly occupational allergic disease of the lungs. There are many inhalable antigens that can cause HP. Most are organic dusts, rarely chemicals. A clinical case of HP is presented in a cable production worker with exposure to plasticizers who was initially diagnosed with idiopathic pulmonary fibrosis. The presence of specific IgG antibodies (sIgG) to phthalic anhydride in the patient's serum, together with reduced carbon monoxide diffusion capacity, hypoxemia at rest and on exertion, and the findings on computed tomography and histology, seemed to confirm the diagnosis of chronic HP due to phthalates, particularly as exposure to phthalate compounds at work was reported by the Technical Inspection Service. A review of the literature revealed that there is evidence of plasticizer alveolitis. While in four previous case reports phthalic anhydride was suspected as the cause of occupational HP because of work-related symptoms, we were able to detect sIgG to phthalic anhydride for the first time. This case illustrates that phthalates, which have rarely been described as triggers of HP, should be considered in cases of suspected occupational HP.

Introduction: When deferasirox is used in iron chelation therapy, maculopapular rash occurs in 10% of patients, but there is no accepted and implemented protocol for the management of these drug reactions in adults.

Case report: A 23-year-old woman diagnosed with thalassemia major is presented. She had taken 1,500 mg oral deferasirox for 1 week. Five hours after the last dose, a pruritic maculopapular rash developed on the body, face, and hands. The rash spread to the whole body within 3 days. The absolute necessity for the patient to take the drug was clarified by the hematology department. The patient's history was evaluated. A delayed-type hypersensitivity reaction due to deferasirox was considered.

Management: The slow desensitization protocol described in the literature and applied on a case-by-case basis in pediatric patients was modified to shorten the duration by determining appropriate doses for the current preparation. The desensitization process was started with 1/100,000 of the total dose and the therapeutic dose was reached with a 2- to 2.5-fold increase in dose. No pre-medication was applied. During the procedure, at a low dose of 0.1 mg, local flushing and erythema was observed around the auricle on the face. The reaction did not progress.

Conclusion: Slow desensitization protocol for oral deferasirox was successfully applied in an adult patient.