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Background: Mas‐related G protein‐coupled receptor X2 (MRGPRX2) is regarded as a mast cell‐specific receptor mediating non–IgE‐dependent activation. We aimed to investigate whether human basophils and eosinophils express functional MRGPRX2. Methods: Flow cytometry, immunocytochemistry, immunofluorescence, Western blot, and RT‐PCR were performed in highly purified peripheral blood basophils and eosinophils of atopic and nonatopic donors. To assess functional activity, fluorescent avidin‐based degranulation assay, calcium mobilization, cytokine production in supernatants, assessment of viability/apoptosis, and tricolor granulocyte activation test were used. Results: MRGPRX2 was significantly expressed by basophils and eosinophils but not neutrophils. Functional capacity was shown by anti‐MRGPRX2 mAb‐induced calcium influx and concentration‐dependent induction of degranulation. Sequential stimulation in the calcium mobilization assay gave no evidence for desensitization or receptor internalization. Anti‐MRGPRX2 mAb significantly promoted survival. Inhibition of apoptosis could be due to released IL‐3, IL‐5, and GM‐CSF found in supernatants. Short‐term incubation with IL‐3 dose‐dependently upregulated MRGPRX2 expression in both, stimulation for 24 hours with anti‐IgE, C5a, fMLP, and IL‐3 in basophils and by IL‐3, IL‐5, and IL‐33 in eosinophils. Among known mast cell MRGPRX2 agonists ciprofloxacin but not PMX‐53 was functional on basophils and eosinophils. In basophils of allergic subjects, tricolor granulocyte activation test using grass pollen demonstrated MRGPRX2 upregulation associated with degranulation and CD63 expression. Conclusion: Unraveling the regulation and signaling mechanisms of MRGPRX2 on basophils and eosinophils might enable the development of new therapeutic strategies to prevent or inhibit allergic and nonallergic hypersensitivity. Moreover, addressing MRGPRX2 might have potential for diagnostic purposes in (drug) hypersensitivity. [ABSTRACT FROM AUTHOR]

Urticaria, defined by the presence of wheals and/or angioedema, is a common condition in children, prompting parents to consult physicians. For its successful management, paediatric-specific features must be taken into account, regarding the identification of eliciting triggers and pharmacological therapy. This review systematically discusses the current best-available evidence on spontaneous acute and chronic urticaria as well as physical and other urticaria types in children. Potential underlying causes, namely infections, food and drug hypersensitivity, autoreactivity and autoimmune or other conditions, and eliciting stimuli are considered, with practical recommendations for specific diagnostic approaches. Second-generation antihistamines are the mainstay of pharmacological treatment aimed at relief of symptoms, which require dose adjustment for paediatric use. Other therapeutic interventions are also discussed. In addition, unmet needs are highlighted, aiming to promote research into the paediatric population, ultimately aiming at the effective management of childhood urticaria. [ABSTRACT FROM AUTHOR]

Urticaria is a group of diseases that share a distinct skin reaction pattern. Triggering of urticaria by infections has been discussed for many years but the exact role and pathogenesis of mast cell activation by infectious processes is unclear. In spontaneous acute urticaria there is no doubt for a causal relationship to infections and all chronic urticaria must have started as acute. Whereas in physical or distinct urticaria subtypes the evidence for infections is sparse, remission of annoying spontaneous chronic urticaria has been reported after successful treatment of persistent infections. Current summarizing available studies that evaluated the course of the chronic urticaria after proven Helicobacter eradication demonstrate a statistically significant benefit compared to untreated patients or Helicobacter-negative controls without urticaria (p < 0.001). Since infections can be easily treated some diagnostic procedures should be included in the routine work-up, especially the search for Helicobacter pylori. This review will update the reader regarding the role of infections in different urticaria subtypes. [ABSTRACT FROM AUTHOR]

Background: Chronic urticaria and concurrent angioedema are frustrating problems for both physicians and patients. Methods: 100 patients with chronic urticaria (mean duration 33.3±48.2 months) attending the urticaria consulting hour of our Department of Dermatology within 1 year were carefully analyzed for pathogenesis to avoid extensive unnecessary diagnostic approach in the future. Results: In 43 cases a potential infectious trigger could be identified, 35 were of idiopathic origin, and 15 demonstrated pseudoallergic reactions to acetylsalicylic acid or food additives, 5 had antibodies to thyroid gland, and 2 had malignant diseases. Of patients with foci, 26 had Helicobacter pylori–associated gastritis, 9 chronic tonsillitis or sinusitis, 4 infections with Epstein–Barr virus or cytomegalovirus, 2 dental focal infections and 2 suffered from Yersinia infection. High prevalence of H. pylori gastritis was found since 47% of patients showed elevated H. pylori–specific IgA and/or IgG antibodies. 27 patients underwent endoscopy and in all but 1 (96%) antral H. pylori infection was found. In contrast, a prevalence rate of 37% among asymptomatic adults has been published. Disappearance (67%) or improvement of urticaria (24%) occurred in most antimicrobially treated patients after 3–12 weeks. In contrast, only 50% of untreated H. pylori–seropositive patients with chronic urticaria showed spontaneous remission or improvement within 12 weeks. Prevalence of H. pylori infection may even be underestimated since only 27/100 patients underwent endoscopy. It is suggested that H. pylori infection may be present at least in all seropositive subjects (47%). Moreover, we found H. pylori infection in 2 seronegative subjects demonstrating gastric complaints. Conclusions: Thus, measurement of H. pylori–specific antibodies and/or gastroscopy should be included in the diagnostic management of chronic urticaria to identify patients who may profit from eradication treatment with disappearance of long–standing and annoying urticaria symptomatology. [ABSTRACT FROM AUTHOR]

Since more than a century ago, there has been awareness of the connection between viral infections and the onset and exacerbation of urticaria. Our knowledge about the role of viral infection and vaccination in acute and chronic urticaria improved as a result of the COVID-19 pandemic but it has also highlighted knowledge gaps. Viral infections, especially respiratory tract infections like COVID-19, can trigger the onset of acute urticaria (AU) and the exacerbation of chronic urticaria (CU). Less frequently, vaccination against viruses including SARS-CoV-2 can also lead to new onset urticaria as well as worsening of CU in minority. Here, with a particular focus on COVID-19, we review what is known about the role of viral infections and vaccinations as triggers and causes of acute and chronic urticaria. We also discuss possible mechanistic pathways and outline the unmet needs in our knowledge. Although the underlying mechanisms are not clearly understood, it is believed that viral signals, medications, and stress can activate skin mast cells (MCs). Further studies are needed to fully understand the relevance of viral infections and vaccinations in acute and chronic urticaria and to better clarify causal pathways. [ABSTRACT FROM AUTHOR]

Introduction: Allergic diseases represent a broad spectrum of high-prevalence, chronic conditions that remain underdiagnosed and undertreated. The aims of this interdisciplinary, questionnaire-based, non-interventional study were to identify and analyze potential barriers to clinical allergological care in Germany. Methods: All hospitals listed in the German hospital register involved in the treatment of allergological patients (n = 899) were invited to participate. The study yielded a response rate of 52.1% (n = 468). Results: Overall, 88.5% of clinics agreed that allergological care in Germany needs improvement, especially in terms of reimbursement for diagnostics and therapy. More than 80% of participating clinics reported that the decreased availability of test substances and the time-intensity of allergological testing represent relevant barriers. For dermatology and pulmonology, the former is the strongest barrier, while for pediatric and ENT clinics, time-intensity is regarded as the strongest barrier. The availability of good therapy and appropriate guidelines present no barriers to allergological care. Regarding the use of digital healthcare concepts, a very large majority of clinics (n = 352; 91.4%) do not offer video consultations or the use of health applications in patient care. Conclusion: In conclusion, we have identified several structural barriers to allergological care in Germany. Reimbursement and the use of digital healthcare concepts in German clinics providing allergological care need improvement. Based on the results of this study, there is an urgent need for researchers and policymakers to further investigate and support allergology departments in their clinical work and in their implementation of digital healthcare concepts. [ABSTRACT FROM AUTHOR]

Compares eosinophil (EOS) survival and apoptosis in nonatopic volunteers and in patients with inhalant allergy or acute exacerbation of atopic dermatitis. Cytokines that support EOS survival and delay apoptosis; Use of the ELISA technique.

Background: Systemic allergic reactions to vaccines are very rare. In this study we assessed the management and outcome of suspected SARS‐CoV‐2 vaccine hypersensitivity. Methods: Totally, 334 individuals underwent an allergy work up regarding SARS‐CoV‐2 vaccination (group A: 115 individuals suspected to be at increased risk for vaccine‐related reactions before vaccination and group B: 219 patients with reactions after COVID vaccination). The large majority of the SPT/IDT with the vaccines were negative; however, we identified in 14.1% (n = 47) a possible sensitization to the SARS‐CoV‐2 vaccine and/or its ingredients defined as one positive skin test. Of the 219 individuals (group B) who experienced symptoms suspicious for a hypersensitivity reaction after vaccination, 214 were reported after the first vaccination with a mRNA vaccine (157 mRNA (Comirnaty®, 38 Spikevax®) and 18 with a vector vaccine (Vaxzevria®), 5 cases were after the second vaccination. Results: The symptom profile in group B was as follows: skin symptoms occurred in 115 cases (n = 59 angioedema, n = 50 generalized urticaria and n = 23 erythema/flush. Seventy individuals had cardiovascular, 53 respiratory and 17 gastrointestinal symptoms. Of the overall 334 individuals, 78 patients tolerated (re)‐vaccination (out of skin test positive/negative 7/19 from group A and 17/35 from group B). Conclusion: Proven IgE‐mediated hypersensitivity to SARS‐CoV‐2 vaccines is extremely rare and not increased in comparison with reported hypersensitivity to other vaccines. The value of skin tests is unclear and nonspecific reactions, in particular when intradermal testing is applied, should be considered. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of the underlying paroxysmal permeability disturbances in angioedema (AE) is not well understood. Methods: To identify clinical and laboratory parameters specific for a certain AE subtype, 40 AE patients were prospectively enrolled: 15 hereditary (HAE), 13 ACE‐inhibitor induced (ACE‐AE), and 12 mast cell‐mediated without wheals in chronic spontaneous urticaria (CSU‐AE). Ten healthy subjects served as controls. Serum levels of markers indicating activation of the ficolin‐lectin pathway, of endothelial cells, or those indicating impairment of vascular integrity or inflammation were assessed by enzyme‐linked immunosorbent assay. Results: New routine clinical diagnostic criteria could not be identified, not even for distinguishing bradykinin‐mediated (BK‐) AE (ie, HAE and ACE‐AE) from mast cell‐/histamine‐mediated CSU‐AE. However, FAP‐α and tPA were significantly increased in all AE compared to controls. In HAE, FAP‐ α, tPA, uPAR, pentraxin‐3, Tie‐2, sE‐selectin, and VE‐cadherin were significantly increased compared to controls. In HAE compared to CSU‐AE and ACE‐AE, sE‐Selectin, Tie‐2, and VE‐Cadherin were significantly increased, whereas for Ang‐2 the difference was significant compared to CSU‐AE only. Tie‐2 correlated strongly negatively with C4, C1‐INH activity, and C1‐INH function. Conclusions: This study is the first to compare HAE, ACE‐AE, and CSU‐AE. Although significance is limited by small sample size, Tie‐2 was identified as a new promising biomarker candidate for HAE. FAP‐ α and tPA might serve as a marker for AE in general, whereas sE‐selectin and Ang‐2 were increased in BK‐AE only. Our results add information to the role of endothelial dysfunction and serine proteases in different AE subtypes. [ABSTRACT FROM AUTHOR]

Background: Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction. Methods: Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil. Results: The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one. Conclusions: Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians. [ABSTRACT FROM AUTHOR]

Summary: Background: The diagnostic approach to drug hypersensitivity includes a detailed medical history, clinical examination, and skin testing and/or oral challenge with a culprit or alternative drug, depending on the type of reaction and the suspected drugs. Although skin testing is considered to be rather safe, cutaneous and systemic, including fatal, reactions have been described. Objectives: To report 3 cases with generalized delayed reactions after skin testing with clindamycin, and to review the existing literature. Methods: Thorough clinical examination, blood tests and prick, intradermal and patch tests were performed in 3 patients. Results: All patients experienced generalized maculopapular exanthema after intradermal and patch testing with clindamycin and amoxicillin in the first patient, and clindamycin alone in the second and third patient. None of the patients showed immediate reactions to skin tests, while positive intradermal reactions after 24 h to amoxicillin and clindamycin were observed in the first patient, and positive intradermal reactions after 24 h to clindamycin were observed in the second and third patients. Conclusions: Skin testing with clindamycin in the diagnosis of drug hypersensitivity carries some risk of adverse reactions. A stepwise and individual diagnostic work‐up, considering potential risk factors, and testing in a specialized centre with emergency equipment available is highly recommended. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Increased levels of serum IL-31 in chronic spontaneous urticaria. Experimental Dermatology 2010; 19: 464–466. IL-31 represents a novel cytokine involved in pruritic skin diseases including atopic dermatitis (AD). We, therefore, aimed at investigating IL-31 levels in chronic spontaneous urticaria (CU). We included 46 patients with CU, 26 non-atopic skin healthy subjects as negative and 28 patients with AD as positive controls. IL-31 serum levels were analysed using commercial ELISA kit. IL-31 serum levels were higher in patients with CU compared to healthy controls ( P < 0.001), but lower compared to patients with AD ( P < 0.001). There was no difference in IL-31 serum levels in autologous serum skin test positive or negative CU patients and patients with infectious trigger factors including helicobacter pylori infection. IL-31 serum levels may play a role in the pathophysiology of CU. This is supported by the finding that not all patients with CU respond to antihistamine treatment but to the treatment with immunosuppressive drugs. [ABSTRACT FROM AUTHOR]

Background/purpose: Using a new eosinophil isolation kit, we were not able to confirm our previous findings of a delayed apoptosis of eosinophils in atopic dermatitis. Thus, we investigated whether this new isolation kit modulates the functional activity of eosinophils. Methods: Peripheral blood eosinophils were isolated with the new isolation kit as well as conventionally with anti-CD16-conjugated MicroBeads. We analysed viability, apoptosis, CD69 and CD95 expression, streptavidin binding and superoxide anion release. Results: Purity of eosinophils was higher using the new isolation kit ( P < 0.05). However, these eosinophils had a decreased survival ( P < 0.05–0.01), presented morphological features of apoptosis, showed an increased percentage of apoptotic nuclei ( P < 0.01), an increased release of superoxide anions ( P < 0.05), a higher expression of CD69 and CD95 ( P < 0.05) and an increased binding to streptavidin compared to eosinophils isolated with anti-CD16 conjugated MicroBeads. Conclusion: The new eosinophil isolation kit should not be used for the investigation of eosinophils as it potently affects their functional activity. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 38-year-old woman with three episodes of inflammatory reactions. The first inflammatory reaction occurred after an operation made on her left forearm, the second episode happened seven days after suturing because of a lower leg fracture, and the third occurred six days after suturing because of healing problems with inflammation around the stitches. It discusses how acid blue 158 in Seralon blue thread causes contact dermatitis to the patient.

Focuses on the delayed-type hypersensitivity to protamine as a complication of insulin therapy. Reactions to insulin therapy; Suggestion that serological investigation of insulin-specific IgE is not very helpful for the diagnosis and management of patients with insulin allergy.