Mayo Clinic

Understanding Alpha-Gal Syndrome: A Systematic Review and Meta-Analysis of Clinical Manifestations and Outcomes.

Alpha-gal syndrome (AGS) is an IgE-mediated hypersensitivity to galactose-α-1,3-galactose, triggered by tick bites. It typically presents with delayed onset allergic or gastrointestinal symptoms after red meat consumption. This study aims to evaluate the prevalence of clinical symptoms and outcomes in AGS patients. A systematic search of PubMed, Embase, and Cochrane Central was conducted to identify studies with at least five AGS patients that utilized alpha-gal IgE for diagnosis and reported symptomatology. A random-effects model calculated pooled prevalence and 95% confidence intervals (CIs) for clinical characteristics of AGS. Of the 739 studies screened, 15 met the inclusion criteria, comprising 1162 AGS patients (57% female). Urticaria was identified as the most prevalent symptom (63.8%, CI: 34.5-88.3, I = 98.8%). At least one gastrointestinal symptom was reported in 69.2% of patients (CI: 49.3-85.9, I = 97.5%), including abdominal pain (58.3%, CI: 36.0-78.9, I = 96.0%), diarrhea (41.7%, CI: 22.3-62.5, I = 93.4%), nausea (39.1%, CI: 29.2-49.6, I = 79.1%), and vomiting (31.1%, CI: 21.9-41.2, I = 70.4%). Tick bite history was recalled by 78.7% (CI: 46.4-98.1; I = 99.1%), and 91.8% (CI: 84.6-96.8; I = 70.3%) had symptom onset ≥ 1 h post red meat intake. Symptomatic improvement was observed in 86.5% (CI: 73.9-95.4, I = 80.9%) of patients, with complete resolution in 42.7% (CI: 26.4-59.8, I = 73.8%). AGS typically presents with delayed onset allergic and GI symptoms after red meat intake, often with tick bite history. Majority of patients report symptomatic improvement on follow-up.

Clinical Presentation and Outcomes of Alpha-Gal Syndrome.

Alpha-gal syndrome (AGS) is an IgE-mediated allergic reaction to galactose-α-1,3-galactose, primarily linked with Lone Star tick bites in the United States. It presents with symptoms ranging from urticaria and gastrointestinal (GI) manifestations to delayed anaphylaxis following red meat consumption. We aimed to study AGS patients' clinical manifestations, diagnosis, and outcomes. A retrospective chart review of patients who underwent serological testing for suspected AGS between 2014 and 2023 at Mayo Clinic was performed. Patients with positive serology were age and sex matched with those who tested negative. Clinical characteristics of seropositive cohort with and without GI symptoms were compared, and outcomes assessed. Of 1260 patients who underwent testing, 124 tested positive for AGS. They were matched with 380 seronegative control subjects. AGS patients reported a higher frequency of tick bites (odds ratio [OR], 26.0; 95% confidence interval [CI], 9.8-68.3), reported a higher prevalence of urticaria (56% vs 37%; P = .0008), and were less likely to have asthma (OR, 0.4; 95% CI, 0.3-0.7). They had a lower prevalence of heartburn (6% vs 12%; P = .03) and bloating (6% vs 13%; P = .03). A total of 47% had GI symptoms, and a higher proportion were female than those without GI symptoms (69% vs 35%; P = .002). During a mean follow-up of 27 months, 22 of 40 patients reported symptom resolution after avoiding red meat, and 7 were able to transition to regular diet. A diagnosis of AGS should be strongly considered in patients with a history of tick bites and clinical presentation of allergic or GI manifestations. Dietary intervention is effective in most but not all patients.

Neurosurgical Management of Patients with Alpha-Gal Syndrome.

Alpha-gal syndrome (AGS) is an immunoglobulin E-mediated hypersensitivity to galatcose-alpha-1,3-galactose (alpha-gal), a carbohydrate compound present in nonprimate mammalian products. Initial exposure to alpha-gal most often occurs through a tick bite, most commonly the lone star tick in the United States. Repeated exposure to alpha-gal may elicit severe allergic reactions, including anaphylaxis. The allergy restricts dietary intake and may significantly impact perioperative risk, as many medications, anesthetics, and intraoperative surgical products utilize bovine or porcine-derived agents, including those containing magnesium stearate, glycerol, and gelatin. Here, we review the perineurosurgical care of two individuals with AGS and highlight pertinent clinical practices and perioperative management of these patients.

Incorrect laboratory test selection is common in the evaluation of alpha-gal syndrome and Fabry disease.

Anaphylaxis: Epidemiology and Differential Diagnosis.

Anaphylaxis-related emergency department (ED) visits and hospitalizations are increasing. Triggers for anaphylaxis include food, medications, and stinging insects. Idiopathic anaphylaxis accounts for 30% to 60% of cases of anaphylaxis in adults and up to 10% of cases in children with novel allergens such as galactose-α-1,3 galactose reclassifying these cases. Recent practice guidelines have recommended against the routine use of systemic corticosteroids and antihistamines for the prevention of biphasic reactions and recommend an extended observation, up to 6 hours, for those with risk factors for biphasic anaphylaxis and those with lack of access to epinephrine and to emergency medical services.

Global Trends in Anaphylaxis Epidemiology and Clinical Implications.

The true global scale of anaphylaxis remains elusive, because many episodes occur in the community without presentation to health care facilities, and most regions have not yet developed reliable systems with which to monitor severe allergic events. The most robust data sets currently available are based largely on hospital admissions, which are limited by inherent issues of misdiagnosis, misclassification, and generalizability. Despite this, there is convincing evidence of a global increase in rates of all-cause anaphylaxis, driven largely by medication- and food-related anaphylaxis. There is no evidence of parallel increases in global all-cause anaphylaxis mortality, with surprisingly similar estimates for case-fatality rates at approximately 0.5% to 1% of fatal outcomes for hospitalizations due to anaphylaxis across several regions. Studying regional patterns of anaphylaxis to certain triggers have provided valuable insights into susceptibility and sensitizing events: for example, the link between the mAb cetuximab and allergy to mammalian meat. Likewise, data from published fatality registers can identify potentially modifiable risk factors that can be used to inform clinical practice, such as prevention of delayed epinephrine administration, correct posturing during anaphylaxis, special attention to populations at risk (such as the elderly on multiple medications), and use of venom immunotherapy in individuals at risk of insect-related anaphylaxis.

Anaesthetic management of patients with pre-existing allergic conditions: a narrative review.

This narrative review seeks to distinguish the clinical patterns of pre-existing allergic conditions from other confounding non-allergic clinical entities, and to identify the potential related risks and facilitate their perioperative management. Follow-up investigation should be performed after a perioperative immediate hypersensitivity to establish a diagnosis and provide advice for subsequent anaesthetics, the main risk factor for perioperative immunoglobulin E (IgE)-mediated anaphylaxis being a previous uninvestigated perioperative immediate hypersensitivity reaction. The concept of cross-reactivity between drugs used in the perioperative setting and food is often quoted, but usually not supported by evidence. There is no reason to avoid propofol in egg, soy, or peanut allergy. The allergenic determinants have been characterised for fish, shellfish, and povidone iodine, but remain unknown for iodinated contrast agents. Iodinated drugs may be used in seafood allergy. Evidence supporting the risk for protamine allergy in fish allergy and in neutral protamine Hagedorn insulin use is lacking. Conversely, cross-reactivity to gelatin-based colloid may occur in α-gal syndrome. Atopy and allergic asthma along with other non-allergic conditions, such as NSAID-exacerbated respiratory disease, chronic urticaria, mastocytosis, and hereditary or acquired angioedema, are not risk factors for IgE-mediated drug allergy, but there is a perioperative risk associated with the potential for exacerbation of the various conditions.

The changing face of anaphylaxis in adults and adolescents.

Our institution has published serial studies of adults and adolescents with anaphylactic events. The first series was published in 1993 and the last was published in 2006. It was our perception that the nature of anaphylactic episodes had changed over the 2 decades since the last review. To determine whether the etiologies and presentations of anaphylaxis have changed during the past decade in our population. Patient charts were identified based on International Classification of Diseases, Ninth Revision codes for anaphylactic shock. Charts identified were analyzed for clinical symptoms reported, comorbidities, etiology, investigative testing, and subsequent treatment. These cases were categorized as definitive, probable, or idiopathic based on history and results from testing, similar to our prior reports. We identified 281 possible cases, of which 218 met criteria for anaphylaxis. Of these cases, median age was 42 years (range 9-78) and 64% were female. In the review of cases, 85 (39%) were determined to have a definitive etiology, 57 were determined to have a probable etiology (26%), and 76 (35%) were idiopathic. Interestingly, of those with a definitive cause, the most common etiology identified was galactose-α-1,3-galactose, accounting for 28 cases (33%). Foods were the second leading cause, accounting for 24 cases (28%). In this follow-up report on anaphylaxis etiology from a single center, the most common etiology was galactose-α-1,3-galactose. This differs greatly from prior reports from our center. Interestingly, the percentage of cases attributed to idiopathic anaphylaxis decreased from 59% in our previous report to 35% in the present report, which could largely be explained by the number of galactose-α-1,3-galactose cases.