The lifetime prevalence of urticaria, a severe allergic disease, is almost 20%. It not only limits the quality of life of those affected, but also their general performance at work and in their daily activities. This publication is the first section of the Urticaria Guideline. It covers the classification and diagnosis of urticaria, taking into account the major advances in research into its causes, triggering factors and pathomechanisms. It also addresses strategies for the efficient diagnosis of the different subtypes of urticaria. This is crucial for individual, patient-oriented treatment, which is covered in the second part of the guideline, published separately. This German-language guideline was developed according to the criteria of the AWMF on the basis of the international English-language S3 guideline with special consideration of health system characteristics in the German-speaking countries. This first part of the guideline describes the classification of urticaria, distinguishing spontaneously occurring wheals (hives) and angioedema from forms of urticaria with inducible symptoms. Urticaria is defined as sudden onset of wheals, angioedema, or both, but is to be distinguished from conditions in which wheals occur as a short-term symptom, such as anaphylaxis. The diagnosis is based on (a limited number of) laboratory tests, but especially on medical history. In addition, validated instruments are available to measure the severity, activity and course of the disease.

Peanut allergy is a lifelong, increasingly prevalent, and potentially life-threatening disease burdening families and communities. Dietary, particularly polyunsaturated fatty acids (PUFAs), intakes can exert positive effects on immune and inflammatory responses, and the red blood cell (RBC) membrane lipidome contains stabilized metabolic and nutritional information connected with such responses. The fatty-acid-based membrane lipidome profile has been exploratorily evaluated in a small cohort of patients (eight males and one female, age range 4.1-21.7 years old, body mass index BMI < 25) with angioedema and/or anaphylaxis after peanut ingestion. This analysis was performed according to an ISO 17025 certified robotic protocol, isolating mature RBCs, extracting membrane lipids, and transforming them to fatty acid methyl esters for gas chromatography recognition and quantification. Comparison with a group of age- and BMI-matched healthy individuals and with benchmark interval values of a healthy population evidenced significant differences, such as higher levels of ω-6 (arachidonic acid), lower values of ω-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), together with an increased ω-6/ω-3 ratio in allergic patients. A significant inverse correlation was also found between specific immunoglobulin E (IgE) levels and ω-6 di-homo-gamma-linolenic acid (DGLA) and total PUFAs. Results of this preliminary study encourage screenings in larger cohorts, also in view of precision nutrition and nutraceuticals strategies, and stimulate interest to expand basic and applied research for unveiling molecular mechanisms that are still missing and individuating treatments in chronic allergic disorders.

Aim of this study is to clarify the impact of cofactors on allergic reactions in patients sensitized to LTP and ω-5-gliadin. We retrospectively examined the charts of our outpatients from January 2015 to July 2019 and identified 157 patients seen for urticaria/angioedema or anaphylaxis after a meal, in presence or absence of cofactors and sensitized to LTPs (Pru p 3 and/or Tri a 14) and/or ω-5-gliadin (Tri a 19). we compared LTPs-positive patients and those sensitized to Tri a 19 in order to assess the difference in cofactors involved and in frequency of clinical presentation. Our data show that exercise is the most frequent cofactor in FDEIAn and the involvement of exercise, alcohol and multiple cofactors was more frequently found in males than in females. We found that exercise, pollen counts peaks and multiple cofactors were more often related to anaphylaxis than mild reactions. Finally, we performed a comparison between patients LTPs+ and Tri a 19+ that showed in the latter group a lower frequency of allergic comorbidities, a higher median age at the onset of symptoms and frequency of alcohol exposure. Our data show that the search for possible cofactors involved in food allergy is essential not only for diagnostic purposes, but also for risk assessment strategies.

Background. Allergic patients may develop reactions following COVID-19 vaccination more frequently than non-allergic individuals. The aim of our study was to assess the risk of reactions in high-risk allergic patients vaccinated for COVID-19 at the University Health Agency Giuliano-Isontina (ASUGI) of Trieste (northeastern Italy). Methods. Patients were considered at high risk for allergic reactions in case of: prior anaphylactic reaction to any drug/vaccine; multiple drug allergy; intolerance to polyethylene glycol (PEG) or polysorbate 80 (PS80) containing drugs; and mast cell disorders. High-risk allergic patients were immunized in hospital by a dedicated allergy team supported by resuscitation staff. Patients were interviewed over the phone one month after vaccination to complete a structured questionnaire investigating signs and symptoms developed after immunization. Results. From March 2021 to February 2022, 269 patients with a history of severe allergic reactions were assessed, of whom 208 (77.3%) eventually received COVID-19 vaccination, 50 (18.6%) refused to be immunized, 10 (3.7%) were deferred for medical reasons and one was declared exempted due to testing positive for PS80. Mild reactions (urticaria, angioedema, rhinitis, erythema) to COVID-19 vaccines were reported by 30.3% of patients, 8.7% within 4 h and 21.6% > 4 h after immunization. No anaphylactic events were observed. Although they were 80 times (3.8%) more prevalent than in COVID-19 vaccinees from the general population (0.047%), vaccine allergic reactions in high-risk patients were mainly mild and late, more likely affecting women (OR = 3.05; 95% CI 1.22-7.65). Conclusions. High-risk allergic patients with urticaria and angioedema may experience mild flare-ups of mast cell activation-like symptoms following COVID-19 vaccination, supporting antihistamine premedication before vaccination and to be continued for one week afterwards.

Objectives Anaphylaxis is an acute, life-threatening immediate allergic reaction caused by the sudden systemic release of mediators from mast cells. This study aims to assess the current practice of emergency management of children and adults diagnosed with anaphylaxis at the Royal Hospital, Muscat, Oman, in line with the National Institute for Health and Clinical Excellence (NICE) guidelines. Methods This is an observational retrospective study of all anaphylaxis cases seen at the emergency department (ED) from January 2013 to January 2018 and compared with the management of anaphylaxis in the ED as per the NICE guidelines. Inclusion criteria were all patients, children (age 16 and below), and adults diagnosed with anaphylaxis based on the World Allergy Organization (WAO) criteria. Exclusion criteria are all cases labeled as anaphylaxis that did not match the WAO criteria for anaphylaxis. Results Of 100 patients with a preliminary diagnosis of anaphylaxis, 49 patients (49%) were true-anaphylaxis cases based on the WAO definition 16 were children (age 16 years and below), and 33 were adults (age 16 years and above). The other 51 patients (51%) with misdiagnosed anaphylaxis were later diagnosed with spontaneous urticaria, septic shock, vocal cord dysfunction, severe asthma, and anxiety attack. All 49 patients with true-anaphylaxis appropriately received adrenaline intramuscularly at the ED. All 16 children were admitted, seen by an allergist, and received an adrenaline auto-injector when indicated. Only 5 of the 33 adults were admitted and seen by an allergist, and 4 of those required an adrenaline auto-injector upon discharge. The remaining 28 adults were discharged from the ED, and only 3 of these were referred to the allergist. None received an adrenaline auto-injector upon discharge from the ED, and no mention in the ED notes on patient education regarding allergen avoidance. Conclusion Third of the patients who presented to ED were children (<16 years), and two third were adults. Insect venom was the main reason for anaphylaxis in both age groups. There was an underutilization of adrenaline auto-injector prescriptions for adult patients. This could be very well improved by disseminating policies and guidelines to adult physicians.

Many patients report symptoms after wheat ingestion experiencing a wide spectrum of clinical manifestations. Three possible diagnoses have been recognized: celiac disease (CD), wheat allergy (WA), and non-celiac (gluten) wheat sensitivity (NCGS/NCWS). CD is a chronic immune-mediated disease of the small bowel caused by exposure to dietary gluten in genetically predisposed individuals, with a prevalence of approximately 1%. It is characterized by mucosal inflammation and atrophy following exposure to gluten and improvement after gluten withdrawal. Food allergies are immunological responses to a food antigen. WA is the expression of an immunologically mediated process that can be immunoglobulin E (IgE) or non-IgE mediated; its many symptoms include urticaria/angioedema, asthma, rhinitis, and anaphylaxis. NCGS/NCWS is characterized by gastrointestinal and/or extra-intestinal symptoms after ingestion of gluten-containing food in subjects not affected by CD or WA. The aim of this review is to help physicians and nutritionists diagnose the cause of symptoms reported after wheat ingestion, thus avoiding patient frustration, inappropriate testing, and incorrect or missed diagnoses. An algorithm for the diagnostic approach in these patients is provided, to help to diagnose CD, WA, NCGS/NCWS or to identify possible functional disorders as the wheat-sensitive irritable bowel syndrome. A personalized approach, regular follow-up, and the help of a skilled healthcare professional are mandatory for patients with symptoms following wheat ingestion is provided. A gluten-free-diet is often recommended for patients with self-reported gluten/wheat-dependent symptoms; for patients with symptoms similar to those of functional diseases while there is evidence that a low-FODMAP diet could be the first option.

Hereditary angioedema (HAE) is a rare disease caused by mutations in the SERPING1 gene. This results in deficient or dysfunctional C1 esterase inhibitor (C1-INH) and affects multiple proteases involved in the complement, contact-system, coagulation, and fibrinolytic pathways. Current options for the treatment and prevention of HAE attacks include treating all affected pathways via direct C1-INH replacement therapy; or specifically targeting components of the contact activation system, in particular by blocking the bradykinin B2 receptor (B2R) or inhibiting plasma kallikrein, to prevent bradykinin generation. Intravenously administered plasma-derived C1-INH (pdC1-INH) and recombinant human C1-INH have demonstrated efficacy and safety for treatment of HAE attacks, although time to onset of symptom relief varied among trials, specific agents, and dosing regimens. Data from retrospective and observational analyses support that short-term prophylaxis with intravenous C1-INH products can help prevent HAE attacks in patients undergoing medical or dental procedures. Long-term prophylaxis with intravenous or subcutaneous pdC1-INH significantly decreased the HAE attack rate vs. placebo, although breakthrough attacks were observed. Pathway-specific therapies for the management of HAE include the B2R antagonist icatibant and plasma kallikrein inhibitors ecallantide, lanadelumab, and berotralstat. Icatibant, administered for treatment of angioedema attacks, reduced B2R-mediated vascular permeability and, compared with placebo, reduced the time to initial symptom improvement. Plasma kallikrein inhibitors, such as ecallantide, block the binding site of kallikrein to prevent cleavage of high molecular weight kininogen and subsequent bradykinin generation. Ecallantide was shown to be efficacious for HAE attacks and is licensed for this indication in the United States, but the labeling recommends that only health care providers administer treatment because of the risk of anaphylaxis. In addition to C1-INH replacement therapy, the plasma kallikrein inhibitors lanadelumab and berotralstat are recommended as first-line options for long-term prophylaxis and have demonstrated marked reductions in HAE attack rates. Investigational therapies, including the activated factor XII inhibitor garadacimab and an antisense oligonucleotide targeting plasma prekallikrein messenger RNA (donidalorsen), have shown promise as long-term prophylaxis. Given the requirement of lifelong management for HAE, further research is needed to determine how best to individualize optimal treatments for each patient.

Non-allergic angioedema has a worrying morbidity. Clinical examination is central, as C1-esterase inhibitor deficiency will not be documented in the acute phase. In the case of anaphylaxis that does not respond to adrenaline, an early diagnosis can optimise referral of the patient to a reference healthcare establishment for a specific therapeutic protocol (icatibant, C1 inhibitor) recently updated by recommendations.

Acute urticaria is a common condition that presents with wheals and/or angioedema. However, these symptoms are also frequent in anaphylaxis, a life-threatening reaction that should be immediately diagnosed and treated. In both, mast cells play a central role in the physiopathology. Causes and triggers of acute urticaria and anaphylaxis are similar in general, but some peculiarities can be observed. The diagnostic approach may differ, accordingly to the condition, suspicious causes, age groups and regions. Adrenaline is the first-line treatment for anaphylaxis, but not for acute urticaria, where H1-antihistamines are the first choice. In this paper, we review the main aspects, similarities and differences regarding definitions, mechanisms, causes, diagnosis and treatment of acute urticaria and anaphylaxis.

Emergency clinicians are tasked with managing a variety of patients with acute deformities. One of the most acute situations management of the patient who presents with an airway emergency. Patients present with various pathologies may result in anatomically challenging intubation scenarios. Deferral of intubation is often not an option in the emergency department. In some cases, challenging anatomic issues can be predicted before beginning laryngoscopy, but in many situations, prediction models fall short. It is critically important for emergency clinicians to anticipate anatomic issues in all airways and to have premeditated strategies for managing them.

We describe here the third reported case of anaphylaxis after ingestion of some leavers of Moringa oleifera, causing a widespread angioedema, a respiratory distress, and an elevation of serum tryptase. M. oleifera leaves were confirmed as the causative allergen by prick testing with fresh leavers.

Angioedema is defined as " subcutaneous tissues and/or submucosal tissues circumscribed non-pitting edema affecting lips, face, neck, and extremities oral cavity, larynx, and gut." It becomes life-threatening when it involves the larynx, while intestinal angioedema is painful and mimics acute abdomen.[1][2] Angioedema was first described in 1882 by Quincke, then by Osler in 1888 (hereditary angioedema), and finally in 1963 by Donaldson et al (the role of C1 inhibitor).[3] Classification of angioedema Acquired: Allergic (histaminergic angioedema) associated with anaphylaxis. Non-allergic (non-histaminergic angioedema), presenting isolated or in combination with urticaria. Drug-induced, e.g., angiotensin-converting enzyme inhibitors and non-steroidal anti-inflammatory drugs. Complement-mediated secondary to acquired deficiency of C1-inhibitor. Idiopathic which is subdivided into histaminergic and non-histaminergic. Hereditary forms C1-Inhibitor deficiency divided into type 1 (lack of C1-inhibitor molecule) and typed 2 (dysfunctional C1-inhibitor molecule) with normal C1 inhibitor.

Allergic diseases are common medical conditions that now show an increasing trend globally and contributes to poor quality of life of the affected individual. Allergies can be fatal in a few instances such as anaphylaxis, severe asthma, and hereditary angioedema if the symptoms are not recognized and treated correctly. (1, 2) The first Allergy Conference in Qatar aimed to highlight the burden of allergic diseases in Qatar and globally with a special focus on educating both the physicians and the community. The preparation for this conference over the past three years threw up a few challenges, mainly owing to the coronavirus disease 2019 (COVID-19) pandemic that affected all forms of face-to-face interactions and social gatherings. Therefore, our conference was held virtually on February 05, 2022, which was more than two years from the first planned date. The conference was sponsored by the Hamad Medical Corporation in partnership with the Qatar Allergy and Immunology Society. In our scientific program, the scientific committees selected topics related to 3 major areas in allergy practice (systemic, respiratory, and skin allergy disorders). Abstract submissions were encouraged in areas related to audits, case reports, service development, and clinical and basic research in the field of allergy. Additional topics were included related to the current COVID-19 pandemic and COVID-19 vaccinations. We received 34 abstracts and accepted 28 for poster abstracts. Among them, 6 received approval for oral presentations; and 6 (21.4%) had the term COVID-19 or SARS-CoV-2 in their title, which supported the burden related to COVID-19 in our community and association between this new pandemic and our allergy practice and disorders.

Background: The diagnosis of typical cold urticaria (ColdU) relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). Till date, it is largely unclear how often patients with ColdU receive adrenaline treatment and are provided with an adrenaline autoinjector (AAI). Methods: An international, cross-sectional study, COLD-CE (i.e., comprehensive evaluation of ColdU and other cold-induced reactions), was carried out at 32 UCAREs. Detailed histories were taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold-induced (i.e., by cold water, air, or surfaces) involvement of the skin and/or visible mucosal tissue and at least one of the symptoms (cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms). Results: Of the 551 ColdU patients, 75% (n = 412) had a positive CST. Of them, concomitant chronic spontaneous urticaria was diagnosed in 10%. Of 372 patients with stand-alone ColdU, 69% were women and 91% adults. Their median age was 36 (IQR 26 - 48) years. Patients were also categorized into residents of countries with a tropical (n = 33), temperate (n = 264), or cold (n = 75) climate (Table 1: R13C1, R17C1, R21C1). AAI was more often prescribed to residents of temperate than tropical countries (30% vs. 12%, p = .038; Table 1: R31C1), although the frequency of ColdA did not significantly differ between these countries (44% vs. 42%, p = 1.000; R29C2). Residents of tropical countries had a higher frequency of ColdA induced by cold air than residents of temperate (36% vs. 12%, p = .001; R29C4) or cold (36% vs. 12%, p = .007; R25C4) countries. Cardiovascular manifestations induced by cold air were diagnosed in 33% (n = 11) of residents of tropical countries, but only 18% (n = 2) and 36% (n = 4) of them had received adrenaline and AAI, respectively (R13 - 15C7). Furthermore, hypotension and/or loss of consciousness induced by cold air occurred in 18% (n = 6) of patients, but only 17% (n = 1) received adrenaline (R13 - 14C10). ColdA was induced by complete cold water immersion in 9% (n = 3) of patients, and none of them received adrenaline treatment nor AAI (R13 - 15C3). Conclusion: Our findings suggest that ColdA is undertreated and call for changes in ColdU management.

Concerns have been raised about allergic reactions to messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccines. A history of allergic reactions, including anaphylaxis to drugs, has been frequently reported in individuals with anaphylaxis to mRNA vaccines. To estimate the rate of immediate allergic reactions in patients with a history of drug allergy or other allergic disorders. We included adult patients who had received at least 1 dose of an mRNA COVID-19 vaccine at the Special Hospital for Pulmonary Diseases between March 1, 2021, and October 1, 2021, and who reported a history of drug allergy or other allergic diseases (asthma, allergic rhinitis, atopic dermatitis, food or insect venom allergy, mastocytosis, idiopathic anaphylaxis, acute or chronic urticaria, and/or angioedema). Immediate allergic reactions, including anaphylaxis, occurring within 4 hours of vaccination were recorded. Six immediate allergic reactions were noted in the cohort of 1679 patients (0.36%). One patient experienced anaphylaxis (0.06%), which resolved after epinephrine administration, and the other reactions were mild and easily treatable. Most patients with a history of allergies can safely receive an mRNA COVID-19 vaccine, providing adequate observation periods and preparedness to recognize and treat anaphylaxis.

The α-Gal syndrome (AGS) is a pathognomonic immunoglobulin E (IgE)-mediated delayed anaphylaxis in foods containing the oligosaccharide galactose-α-1,3-galactose (α-Gal) such as mammalian meat or dairy products. Clinical presentation of AGS can also comprise immediate hypersensitivity due to anticancer therapy, gelatin-containing vaccines or mammalian serum-based antivenom. The IgE initial sensitization is caused by hard-bodied tick bites and symptomatic individuals typically develop delayed pruritus, urticaria, angioedema, anaphylaxis, malaise or gut-related symptoms. Due to inapparent presentation, delayed reactions and a wide variety of patients´ clinical history, the AGS diagnosis and treatment remain challenging. This review covers not only current diagnostic methods used for AGS such as the skin prick test (SPT), the oral food challenge (OFC), anti-α-Gal IgE levels measurement and the basophil activation test (BAT), but also potentially relevant next-generation diagnostic tools like the mast cell activation test (MAT), the histamine-release (HR) assay, omics technologies and model-based reasoning (MBR). Moreover, it focuses on the therapeutical medical and non-medical methods available and current research methods that are being applied in order to elucidate the molecular, physiological and immune mechanisms underlying this allergic disorder. Lastly, future treatment and preventive tools are also discussed, being of utmost importance for the identification of tick salivary molecules, with or without α-Gal modifications, that trigger IgE sensitivity as they could be the key for further vaccine development. Bearing in mind climate change, the tick-host paradigm will shift towards an increasing number of AGS cases in new regions worldwide, which will pose new challenges for clinicians in the future.

The immune system plays a crucial role in maintaining health and protecting the human body against microbial invasions. However, this same system can lead to exaggerated immune and inflammatory responses that result in adverse outcomes known as hypersensitivity reactions. There are four traditional classifications for hypersensitivity reactions, and these include Type I, Type II, Type III, and Type IV reactions: Type I hypersensitivity is also known as an immediate reaction and involves immunoglobulin E (IgE) mediated release of antibodies against the soluble antigen. This results in mast cell degranulation and release of histamine and other inflammatory mediators. Type II hypersensitivity is also known as cytotoxic reactions and engages IgG and IgM antibodies, leading to the complement system activation and cell damage or lysis. Type III hypersensitivity is also known as immune complex reactions and involves IgG, IgM, and sometimes IgA antibodies. The build-up of these immune complexes results in complement system activation, which leads to polymorphonuclear leukocytes (PMNs) chemotaxis and eventually causing tissue damage. Type IV hypersensitivity is also known as delayed-type and involves of T-cell-mediated reactions. T-cells or macrophages are activated as a result of cytokine release, leading to tissue damage. There has been a more recent classification introduced by Sell et al. that accounts for multiple components of the immune system and categorizes the reactions into seven parts. However, the focus of this article will be on the classic Type I hypersensitivity reactions. Type I hypersensitivities include atopic diseases, which are an exaggerated IgE mediated immune responses (i.e., allergic: asthma, rhinitis, conjunctivitis, and dermatitis), and allergic diseases, which are immune responses to foreign allergens (i.e., anaphylaxis, urticaria, angioedema, food, and drug allergies). The allergens that result in a type I hypersensitivity may be harmless (i.e., pollen, mites, or foods, drugs, etc.) or more hazardous such as insect venoms. The reaction may be manifested in different areas of the body and may result in instances such as: Nasal allergic rhinitis or hay fever . Ocular allergic conjunctivitis, potentially due to seasonal allergens such as pollen or mold spores . Dermatological hives, atopic eczema, or erythema. Soft tissue angioedema. Pulmonary reactions, such as allergic asthma or hypoxia. Systemic reaction, which is a life-threatening medical emergency, and also known as anaphylaxis. There are certain risk factors that increase the risk of allergic diseases. These factors include geographical distribution, environmental risks such as pollution or socioeconomic status, genetic predisposition, or the “hygiene hypothesis”. The “hygiene hypothesis” suggests that our modern society practices of good hygiene and the lack of early exposure to many microbes or antigens may result in failures of the immune system functionality. As such, the hypothesis suggests that early exposure to a diverse range of microorganisms and antigens may actually lead to overall decreased rates of allergies, asthma, and other immune disorders.