MEAT PIES: Mammalian Meat Allergy in Patients Investigated for Gastrointestinal Symptoms

ABSTRACT

Background

Alpha‐gal syndrome (AGS), an IgE‐mediated allergy to galactose‐α‐1,3‐galactose acquired via tick bites, often presents with a delayed gastrointestinal (GI) phenotype without anaphylaxis. We evaluated a local diagnostic guideline in a Far North Queensland gastroenterology outpatient clinic.

Methods

A retrospective quality assurance audit at Cairns Hospital identified serum‐specific IgE (ssIgE) requests to alpha‐gal 12 months before and 6 months after guideline implementation (12 March 2025). ImmunoCAP ssIgE ≥ 0.1 kU/L was positive.

Results

Of 19 patients tested, 5 (26%) were sensitized. All had GI‐predominant symptoms—most commonly diarrhea (58%) and abdominal pain (53%)—with no anaphylaxis or respiratory features, and negative preliminary investigations including endoscopy. All three patients completing meat avoidance trials had symptom resolution. Diagnostic yield rose from 2/16 (12.5%) to 3/3 (100%) post‐guideline, though testing was driven almost exclusively by a single clinician.

Conclusion

The GI phenotype of AGS is present and likely underrecognized in this tick‐endemic region. Targeted ssIgE testing after careful clinical assessment yields high diagnostic value, supporting consideration of AGS in unexplained GI symptoms and extending the recognized distribution of the condition.

1. Background

Alpha‐gal syndrome (AGS), also known as mammalian meat allergy, has had considerable news attention in Australia following a coronial review into an AGS‐related fatality in New South Wales [1]. AGS is an IgE‐mediated allergy to the oligosaccharide galactose‐α‐1,3‐galactose, a carbohydrate found on the cells of nonprimate mammals [2]. The first allergic reactions to meat products following tick bites were reported in Australia by Van Nunen et al. [3].

While anaphylaxis is the most recognized presentation, a gastrointestinal (GI) phenotype has been increasingly described, characterized by delayed abdominal pain, diarrhea, nausea, and vomiting occurring 2–6 h after ingestion of mammalian meat. This has been sufficiently recognized to prompt a dedicated Clinical Practice Update by the American Gastroenterological Association, outlining the investigation and management of AGS in a clinical population [4]. The outline suggests clinicians should consider AGS in the differential diagnosis of patients with unexplained GI symptoms of abdominal pain, diarrhea, nausea, and vomiting, particularly those who live or have lived in an Ixodes holocyclus –prevalent area.

AGS has been diagnosed in the Cairns and Hinterland Hospital and Health Service's (CHHHS) Clinical Immunology and Allergy clinic; it was suspected that there were GI phenotype patients unrecognized in the Gastroenterology service [5]. A clinical guideline for detection and diagnosis of AGS was thus implemented within the Gastroenterology department at Cairns Hospital. This brief report describes the outcomes of a quality assurance (QA) audit evaluating the impact of that guideline on testing practices and diagnostic yield for AGS in the gastroenterology outpatient setting.

The CHHHS is the primary provider of acute health services for an estimated 270 552 residents, covering an area of 142 900 km². The Gastroenterology clinic is one component of this service, with 4535 outpatient occasions of service (primarily clinic appointments) for the financial year 2025. It is the only public service of its kind in the region.

2. Methods

A retrospective QA audit was conducted at the Cairns Hospital Gastroenterology outpatient clinic. Requests for serum‐specific IgE (ssIgE) to galactose‐α‐1,3‐galactose were identified 12 months before and 6 months post‐implementation of a local clinical guideline for AGS testing (implementation 12 March 2025). The guideline was largely adapted from the AGA Clinical Practise Update [4]. The guideline implementation was preceded by a departmental education session.

Of note, the temporal relationship between meat ingestion and symptom onset was established in all cases before ssIgE testing; however, given the likely significant delays between reviews, a practical approach of meat avoidance with concurrent testing for ssIgE was deemed acceptable. Patient records were reviewed for symptomatology, tick bite history, established diagnoses, and response to mammalian meat avoidance. Patients under 18 years of age and those tested by other departments for unrelated indications were excluded.

The local pathology service utilizes the ImmunoCAP assay (Thermo Fisher Scientific), a result ≥ 0.1 kU/L was classified positive for sensitization, consistent with product‐specific diagnostic threshold [6].

Total gastroenterology outpatient occasions of service for the financial year 2025 were obtained from hospital administrative data (n = 4535). Data were de‐identified and analyzed descriptively. This activity was approved as a QA project exempt from full Human Research Ethics Committee review (EX/2025/QCH/120901).

3. Results

A total of 5/19 (26%) patients tested positive for alpha‐gal ssIgE sensitization during the study period. There were 16 patients tested before and 3 patients tested after guideline implementation. All had GI‐predominant symptoms, most commonly diarrhea (11/19, 58%) and abdominal pain (10/19, 53%). All patients with positive serology presented with a history of diarrhea, of which 3 had nocturnal symptoms. None had features of anaphylaxis, angioedema, or respiratory symptoms. Clinical characteristics of patients with alpha‐gal sensitization are included (Table 1). Prior to AGS testing, one patient with positive serology was treated for helicobacter pylori , without symptomatic improvement (abdominal pain and diarrhea).

TABLE 1.

Clinical characteristics, allergy cofactors, and diagnostic work‐up of patients with alpha‐gal sensitization (n = 5).

Characteristic	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
Demographics and key findings
Age range (years)	50–59	60–69	70–79	30–39	60–69
Sex	F	M	F	F	M
Tick bite history	✓	Unknown	✓	✓	✓
Alpha‐gal ssIgE (kUA/L)	0.25	0.12	0.18	13.4	0.21
Mammalian meat avoidance trial	✓	Pending	✓	✓	Pending
Symptom resolution on avoidance	✓	—	✓	✓	—
Predominant GI symptoms
Diarrhea	✓	✓	✓	✓	✓
Nocturnal symptoms	✓	—	✓	✓	—
Abdominal pain	✓	—	—	✓	—
Relevant past medical history
Irritable bowel syndrome	✓	—	—	—	—
Gastro‐esophageal reflux	—	—	✓	—	—
Pancreatic insufficiency	—	—	—	—	✓
Cholecystectomy	—	—	✓	—	—
Hypertension	—	—	✓	—	✓
Dyslipidaemia	—	—	—	✓	—
Neurological diagnosis a	✓	—	—	—	—
Allergy cofactors
NSAID use	—	—	—	—	—
Alcohol (standard drinks/week)	49	0	6	0	0
Diagnostic work‐up
Coeliac serology (tTG/DGP)	Negative	Negative	Negative	Negative	Negative/ND
H. pylori testing	Negative	Negative	Negative	Positive b	Negative
Hydrogen breath test (ppm)	Positive (51)	Negative	Negative	Negative	Positive (29)
Fecal infection screen c	Negative	Negative	Negative	Negative	Negative
Fecal calprotectin	Negative	Negative	Negative	Negative	Negative
Fecal elastase	ND	ND	Negative	Negative	Negative
Endoscopic evaluation
Colonoscopy—macroscopic	Normal	Normal	Normal	Normal	Normal
Colonoscopy—histology	Normal	ND	Normal	Normal	Normal
Gastroscopy—macroscopic	Normal	ND	Normal	Normal	Normal
Gastroscopy—histology	Normal	ND	Normal	Normal	Normal

Note: Ages reported in 10‐year bands and one neurological diagnosis withheld to preserve anonymity in a small cohort from a single regional centre. Alpha‐gal ssIgE measured by ImmunoCAP (Thermo Fisher Scientific); positive threshold ≥ 0.10 kUA/L. ✓ = present; — = absent.

Abbreviations: DGP, deamidated gliadin peptide; ND, not done; NSAID, nonsteroidal anti‐inflammatory drug; ppm, parts per million; ssIgE, serum‐specific IgE; tTG, tissue transglutaminase.

^a Specific diagnosis withheld to avoid identification.

^b Eradication therapy completed without symptomatic improvement.

^c Bacterial, viral, protozoal, and Clostridioides difficile screen.

Testing yield improved from 2/16 (12.5%) to 3/3 (100%), and the proportional rate of alpha‐gal ssIgE testing relative to total clinic encounters decreased (0.35%, 0.13%) in the pre‐ and post‐guideline periods, respectively. Three of five patients with alpha‐gal sensitization had subsequent review by the time of writing, all with resolution of symptoms post avoidance of mammalian meat, supporting the diagnosis of AGS. Guideline contribution to the reduced testing volume and increased yield is limited by a small sample size. Of note, all testing during this period was on direction from a single consultant.

4. Discussion

These findings establish the presence of alpha‐gal sensitization and the GI phenotype of AGS at our centre. Of those diagnosed with AGS, none had anaphylaxis or other systemic allergic features. All had multiple negative preliminary investigations including endoscopic evaluation. This is a novel finding in our clinic and has broader implications for the practice of gastroenterology in the region. As the northernmost tertiary gastroenterology centre on the eastern seaboard of Australia, further studies are required to establish AGS rates in the southern regions of Queensland.

Implementation of the local guideline was associated with increased testing; however, uptake was almost exclusively driven by a single clinician. A single clinician‐led study allowed for highly targeted testing for AGS, which may account for the high detection rate of sensitization to alpha‐gal (5/19, 26%). It is unclear what the community prevalence of sensitization is, which requires further evaluation.

Early results suggest high correlation of sensitization to alpha‐gal and AGS diagnosis at our centre, supporting the utility of targeted testing for ssIgE to alpha‐gal in this population. Of critical importance, as with all allergy testing, sensitization does not necessarily imply allergy (i.e., clinical hypersensitivity to alpha‐gal containing products needs to be established). The diagnosis of AGS does not consist of only a positive ssIgE titer and must be in association with clear improvement after ceasing consumption of alpha‐gal containing products, including mammalian meat (i.e., pork, lamb, beef), dairy and gelatine. A thorough history prior to alpha‐gal sensitivity testing is strongly advocated to improve the utility of the test [7].

The low rate of testing for ssIgE broadly at our facility highlights a recognized challenge in guideline implementation: awareness alone may be insufficient without ongoing reinforcement and integration into departmental workflows [8].

5. Conclusion

Alpha‐gal sensitization and the gastrointestinal phenotype of AGS are present in the Far North Queensland gastroenterology outpatient population.

Implementation of a targeted diagnostic guideline increased testing and identified clinically relevant cases, all of whom presented without classical anaphylaxis but with gastrointestinal‐predominant symptoms. Targeted testing following careful clinical assessment appears to have a high diagnostic yield at our centre.

These findings support AGS being considered in patients with otherwise unexplained gastrointestinal symptoms in tick‐endemic regions. As the northernmost tertiary gastroenterology service on Australia's eastern seaboard, these findings extend the recognized distribution of AGS and suggest that the condition may be more prevalent than currently appreciated.

Challenges of translating emerging evidence into practice underscore the need for ongoing clinician education and integration of diagnostic pathways.

Ethics Statement

This audit was assessed by the Far North Queensland Human Research Ethics Committee and formal ethics review was waived. The project complied with the National Statement on Ethical Conduct in Human Research.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The de‐identified data we analyzed are not publicly available, but requests to the corresponding author for the data will be considered on a case‐by‐case basis. All data were de‐identified and stored securely in accordance with institutional policy.