Alpha-gal syndrome (AGS), a tick-borne allergy, is increasing as its vectors migrate throughout the US and the world. There were an estimated 450,000 cases in the US. AGS reactions to mammalian foods and medical products include delayed anaphylaxis, urticaria, gastrointestinal and cardiac symptoms often difficult to connect to the source. Despite its seriousness, provider knowledge is limited. This rapid review investigated published works on AGS from 2020 to 24; it also sought to determine the breadth of AGs publications across different fields and specialties. We identified 355 studies of AGS diagnosis and management from 2020 to 2024 via Cochrane Central, Medline via the PubMed interface, and Embase (additional grey literature via Web of Science and Google Scholar). Studies were assessed for quality and risk of bias using JBI critical appraisal tools. Two hundred and nineteen studies met the criteria. One hundred and sixty-eight (77%) were full studies; 51 (23%) were conference presentations. Studies remained largely confined to allergy and immunology literature, despite their implications for other organ systems. Although patients present with symptoms to emergency departments and dermatology clinics there is a paucity of literature in those fields and others; several studies document practitioners' lack of knowledge. Inclusion of content within medical school curricula is needed to establish foundational knowledge on the topic. With the increase in patients presenting with AGS, and with the reach of AGS across multiple fields, physicians and other health care providers need to be able to diagnose and then manage AGS with their patients. This rapid review has documented the problem of silos in disseminating information about AGS widely through the medical field. The remedy for a lack of practitioner knowledge is education.
Nguyen SMT, Rupprecht CP, Haque A, Pattanaik D, Yusin J, et al.
International journal of molecular sciences •
Anaphylaxis is a severe, acute, life-threatening multisystem allergic reaction resulting from the release of a plethora of mediators from mast cells culminating in serious respiratory, cardiovascular and mucocutaneous manifestations that can be fatal. Medications, foods, latex, exercise, hormones (progesterone), and clonal mast cell disorders may be responsible. More recently, novel syndromes such as delayed reactions to red meat and hereditary alpha tryptasemia have been described. Anaphylaxis manifests as sudden onset urticaria, pruritus, flushing, erythema, angioedema (lips, tongue, airways, periphery), myocardial dysfunction (hypovolemia, distributive or mixed shock and arrhythmias), rhinitis, wheezing and stridor. Vomiting, diarrhea, scrotal edema, uterine cramps, vaginal bleeding, urinary incontinence, dizziness, seizures, confusion, and syncope may occur. The traditional (or classical) pathway is mediated via T cells, Th2 cytokines (such as IL-4 and 5), B cell production of IgE and subsequent crosslinking of the high affinity IgE receptor (FcεRI) on mast cells and basophils by IgE-antigen complexes, culminating in mast cell and basophil degranulation. Degranulation results in the release of preformed mediators (histamine, heparin, tryptase, chymase, carboxypeptidase, cathepsin G and tumor necrosis factor alpha (TNF-α), and of de novo synthesized ones such as lipid mediators (cysteinyl leukotrienes), platelet activating factor (PAF), cytokines and growth factors such as vascular endothelial growth factor (VEGF). Of these, histamine, tryptase, cathepsin G, TNF-α, LTC, PAF and VEGF can increase vascular permeability. Recent data suggest that mast cell-derived histamine and PAF can activate nitric oxide production from endothelium and set into motion a signaling cascade that leads to dilatation of blood vessels and dysfunction of the endothelial barrier. The latter, characterized by the opening of adherens junctions, leads to increased capillary permeability and fluid extravasation. These changes contribute to airway edema, hypovolemia, and distributive shock, with potentially fatal consequences. In this review, besides mechanisms (endotypes) underlying IgE-mediated anaphylaxis, we also provide a brief overview of IgG-, complement-, contact system-, cytokine- and mast cell-mediated reactions that can result in phenotypes resembling IgE-mediated anaphylaxis. Such classifications can lead the way to precision medicine approaches to the management of this complex disease.