Alpha-gal syndrome presenting in the emergency department: a case report
Khutaija Noor1
, Justin Orren2, Kyle Kennedy2
Contributions: (I) Conception and design: K Noor; (II) Administrative support: J Orren; (III) Provision of study materials or patients: J Orren, K Kennedy; (IV) Collection and assembly of data: K Noor; (V) Data analysis and interpretation: K Noor; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
Background: Alpha-gal syndrome (AGS), also known as “red meat allergy”, is a unique immune response to a carbohydrate molecule called galactose-alpha-1,3-galactose (alpha-gal), which is commonly found in red meat, such as beef, pork, and lamb, as well as in certain dairy products. This condition was first identified in 2009 and has since been the subject of extensive research to understand its underlying mechanisms, clinical presentation, and management strategies. The development of AGS is typically initiated by a tick bite, which can trigger the production of immunoglobulin E (IgE) antibodies against the alpha-gal carbohydrate. These antibodies can react with the alpha-gal molecules present in red meat, leading to an allergic response that can range from mild to severe, including symptoms such as hives, angioedema, nausea, vomiting, diarrhea, and in rare cases, anaphylaxis. The exact mechanisms behind the development of this syndrome are not fully understood, AGS is believed to involve a complex interplay between genetic, environmental, and immunological factors.
Case Description: This is a case report of a 66-year-old male patient seen in the Emergency Department who presented with symptoms of vomiting, diarrhea, chest pain, difficulty breathing, fever, chills, and hypertension. Specific allergy testing was crucial for the diagnosis of the AGS, emphasizing the need for education on avoiding meat and dairy products containing the alpha-gal allergen-specific to IgE sensitization. This case report addresses the importance of reviewing medication ingredients for the presence of mammalian-derived products during treatment.
Conclusions: This case report highlights the importance of recognizing and managing AGS promptly to prevent severe allergic reactions especially in response to medications containing mammalian proteins. It underscores the necessity for specific allergy testing and comprehensive patient education on allergen avoidance.
Keywords: Alpha-gal syndrome (AGS); galactose-alpha-1,3-galactose (alpha-gal); tick-bite; meat allergy; case report
Received: 11 June 2024; Accepted: 17 March 2025; Published online: 21 May 2025.
doi: 10.21037/jeccm-24-80
Highlight box
Key findings
• This case underscores the critical need for early and accurate diagnosis of alpha-gal syndrome (AGS) to prevent severe allergic reactions.
• Role of galactose-alpha-1,3-galactose (alpha-gal)-specific immunoglobulin E (IgE) antibodies testing to confirm AGS.
• Comprehensive patient education on avoiding mammalian-derived allergens significantly reduces the risk of recurrent hypersensitivity reactions.
• An individualized allergen and medication avoidance checklist was instrumental in ensuring adherence to dietary and pharmaceutical restrictions, serving as a practical tool for long-term management.
• Healthcare providers, particularly in tick-endemic regions, must recognize AGS symptoms and ensure timely diagnosis and intervention to prevent complications and improve patient outcomes.
What is known and what is new?
• AGS is a tick-borne allergic condition caused by IgE sensitization to alpha-gal, a carbohydrate found in mammalian products. It presents as delayed hypersensitivity reactions, since its identification in 2009, research has expanded on its immunological mechanisms, diagnostic criteria, and management.
• This case report of a 66-year-old patient with severe AGS symptoms highlights the importance of timely diagnosis through alpha-gal-specific IgE testing. It presents structured management strategies, emphasizing allergen avoidance, patient education, and a tailored checklist.
• The increasing prevalence of AGS necessitates greater awareness to prevent delayed diagnosis and severe hypersensitivity reactions.
• Enhance awareness and training on AGS symptoms, risk factors, and diagnostic and management protocols.
• Comprehensive educational resources on allergen avoidance and emergency preparedness.
• Implement clearer labeling of mammalian-derived ingredients in food and medications.
• Expand studies on AGS pathophysiology, regional prevalence, and long-term management strategies while establishing surveillance systems to track incidence and intervention effectiveness.
Introduction
Alpha-gal syndrome (AGS) is an immunoglobulin E (IgE)-mediated hypersensitivity condition diagnosed in patients who are allergic to galactose-alpha-1,3-galactose (alpha-gal) after certain types of tick bites. Amblyomma americanum, commonly known as the lone star tick, is the most common tick associated with this illness in the United States. The condition is also referred to as red meat allergy or tick-bite meat allergy. Patients typically have a history of intolerance to mammalian meat, monoclonal antibodies, prosthetic heart valves, drugs, or vaccines that contain alpha-gal products. Early symptoms are often mistaken for idiopathic anaphylaxis, as the extended interval between ingestion and the appearance of symptoms makes it difficult to identify the trigger (1).
The symptoms vary from mild to life-threatening events in certain individuals. Patients can present with a myriad of symptoms including hives, pruritic rash, nausea and vomiting, heartburn, diarrhea, cough, dyspnea, hypotension, oropharyngeal edema, angioedema, dizziness, and abdominal pain. The symptoms can present from 2–6 hours after eating or exposure to the allergen alpha-gal.
Methodology
Research design: This case report follows established guidelines for developing health research reporting, adhering to a structured four phases consensus process.
Participants: A 66-year-old male in the emergency department at Freeman Hospital.
Phase 1: written informed consent was obtained from the patient to publish this case report.
Phase 2: a face-to-face interview was conducted in the hospital facility and the patient signed a medical records release form to retrieve clinical history and laboratory data.
Phase 3: a literature review was performed on PubMed to explore alpha-gal syndrome, and the Centers for Disease Control and Prevention (CDC) database was utilized to gather information on the geographic epidemiology of the condition. Additionally, a PubMed search was conducted to identify relevant case reports on alpha-gal syndrome to support the article submission.
Phase 4: the case report was written, reviewed, and edited by the authors via post-meeting conducted.
We present this case in accordance with the CARE reporting checklist (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-80/rc).
Case presentation
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report. A copy of the signed consent form is available for review by the editorial office of this journal.
A 66-year-old male presented to the Freeman Health System Emergency Department with episodes of vomiting, diarrhea, chest pain, difficulty breathing, fever, chills, and hypertension. His symptoms prompted a one-day visit to the Emergency Department for evaluation and management. The patient reported having eaten at a buffet six days prior, where he had consumed sausage with potatoes.
Upon arrival at the Emergency Department, the patient described persistent chest pain, rated 6/10, and described as a constant pressure sensation. He also experienced difficulty breathing, which was alleviated by movement and relieved when lying on his chest. Additionally, he reported a frontal headache described as a pressure sensation, scoring 9/10 on the pain scale. Notably, six days earlier, the patient experienced an allergic reaction triggered by sausage consumption, characterized by vomiting of chewed food, a single episode of diarrhea, and transient lip cyanosis. For the current symptoms, the patient had been advised to use epinephrine if future symptoms such as swollen throat, urticaria, or difficulty breathing occurred, but the patient did not administer it. To manage his current discomfort, he took Advil.
The alpha-gal panel was conducted in July 2023 at the diagnostic center (Table 1). A comprehensive diagnostic panel workup revealed elevated pork IgE, beef IgE, and galactose-α-1,3-galactose (alpha-gal) levels. The patient was advised to follow a diet without mammalian meat, dairy products, or mammalian protein-containing drugs. The patient was prescribed an epinephrine autoinjector by his primary care provider due to the risk of future anaphylaxis.
Table 1
| Allergy | Type | Severity | Reaction | Status | Date |
|---|---|---|---|---|---|
| Acetaminophen (from Lorcet 10/650) | Allergy | Mild | Rash | Verified | October, 2023 |
| Hydrocodone (from Lorcet 10/650) | Allergy | Mild | Rash | Verified | October, 2023 |
| Penicillin | Allergy | Mild | Rash | Verified | October, 2023 |
| Propoxyphene (from Darvocet-N) | Allergy | Mild | Rash | Verified | October, 2023 |
| Tramadol (from Ultram) | Allergy | Mild | Rash | Verified | October, 2023 |
| Alpha-Gal | Allergy | Mild | Rash | Verified | October, 2023 |
| Latex | Allergy | – | Rash, itching | Verified | October, 2023 |
Clinical significance of the alpha-gal panel
This in vitro allergen-specific IgE panel is used to quantitatively measure an individual’s IgE response to alpha-gal, an allergen component, and three types of meat (beef, pork, and lamb) that commonly trigger alpha-gal-associated meat allergy (Table 2). This IgE panel may be used in conjunction with other clinical information to aid in the diagnosis of AGS, a severe allergic reaction to mammalian meat triggered by prior bites from the Lone Star tick (Amblyomma americanum).
Table 2
| Test | Result | Flag range | Reference unit |
|---|---|---|---|
| Pork (F26) IgE | 0.25 | H | <0.10 KU/L |
| Beef (F27) IgE | 0.20 | H | <0.10 KU/L |
| Lamb (F86) IgE | <0.10 | N | <0.10 KU/L |
| Galactose alpha 1,3 galactose IgE | 0.32 | H | <0.10 KU/L |
H, high; IgE, immunoglobulin E; N, normal.
The alpha-gal IgE test helps evaluate the etiology of meat allergies in patients with delayed onset of symptoms (2 to 6 hours after consuming meat). IgE antibodies to alpha-gal are the likely mediators of anaphylactic reactions in individuals who develop hypersensitivities to beef, pork, and/or lamb as adults (2).
On physical examination, the patient was oriented to person, place, and time. He appeared well-developed, well-nourished and well-hydrated. The patient’s pharynx was normal, breath sounds were clear, and heart sounds were regular with a normal rate and rhythm. Pulses were equal bilaterally. His abdomen was soft, non-tender, and exhibited normal bowel sounds. There was no edema in the lower extremities, and the skin was warm and dry. The patient remained hemodynamically stable, with oxygen saturation of 97% at admission and 100% at discharge. Blood pressure ranged from 160/87 to 117/76 mmHg, and heart rate ranged from the 70 to 90 s. The patient did not report any emergent medical or surgical concerns during his Emergency Department visit.
Due to his history of AGS, medications used to treat his symptoms had to be carefully selected to avoid any potential mammalian-derived proteins. Medication options were discussed with the pharmacist, and per their recommendations, the patient received intravenous diphenhydramine, metoclopramide, and normal saline. Notably, while the intravenous formulation of metoclopramide was free of mammalian proteins, the oral formulation did contain them, as confirmed by the pharmacist. The patient responded well to the treatment, and his symptoms were alleviated.
The following is the list of lab values obtained in the Emergency Department. Lab studies revealed no significant abnormalities, although lab testing did show elevated creatinine kinase. Other lab values, including white blood cell (WBC), red blood cell (RBC), platelets, electrolytes, cardiac enzymes, renal workup, and blood glucose were unremarkable (Table 3). Chest X-ray showed no acute cardiopulmonary abnormalities. The electrocardiogram (ECG) demonstrated normal sinus rhythm with normal rate, intervals, and no ST segment or T wave abnormalities.
Table 3
| Lab test | Values |
|---|---|
| WBC, ×103/μL | 5.0 |
| RBC, ×106/μL | 5.25 |
| Hgb, g/dL | 16.0 |
| Hct, % | 47.7 |
| MCV, fL | 90.9 |
| MCH, pg | 30.5 |
| MCHC, g/dL | 33.5 |
| RDW, % | 12.9 |
| Platelet count, ×103/μL | 301 |
| MPV, fL | 9.3 |
| Neutrophils, % | 38.0 |
| Lymphocyte, % | 48.3 |
| Monocyte, % | 9.9 |
| Eosinophil, % | 2.8 |
| Basophil, % | 0.8 |
| Absolute neutrophils, ×103/μL | 1.9 |
| Absolute lymphocytes, ×103/μL | 2.4 |
| Absolute monocytes, ×103/μL | 0.5 |
| Absolute eosinophils, ×103/μL | 0.1 |
| Absolute basophils, ×103/μL | 0.0 |
| Sodium, mmol/L | 139 |
| Potassium, mmol/L | 4.3 |
| Chloride, mmol/L | 104 |
| Carbon dioxide, mmol/L | 24 |
| Plasma anion gap, mmol/L | 11 |
| BUN, mg/dL | 12 |
| Creatinine, mg/dL | 1.0 |
| GFR calculation, mL/min/1.73 m2 | 79 |
| Creatinine ratio | 12 |
| Glucose, mg/dL | 106 |
| Calculated osmolality, mOsm/kg | 278 |
| Plasma calcium, mg/dL | 9.7 |
| Creatinine kinase, U/L | 605 (H) |
| CK-MB (CK-2), ng/mlL | 1.86 |
| Troponin I, ng/mL | <0.012 (L) |
BUN, blood urea nitrogen; CK-MB, creatine kinase-myocardial band; GFR, glomerular filtration rate; Hgb, hemoglobin; Hct, hematocrit; H, High; L, Low; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MPV, mean platelet volume; RBC, red blood cell; RDW, red cell distribution width; WBC, white blood cell.
The patient’s medical history includes AGS, diagnosed 15 months ago following a bite from the lone star tick (Amblyomma americanum). An alpha-gal panel confirmed IgE sensitization to alpha-gal. Despite being referred to an allergist, the patient declined the referral, stating he had self-educated about the condition. He also has a history of hypertension, managed with amlodipine 5 mg daily, and pre-diabetes, controlled through lifestyle modifications. Additionally, he has osteoarthritis, and previously underwent bilateral knee replacement surgery. He denies tobacco use, alcohol consumption, or illicit drug use.
Discussion
AGS is an allergic condition triggered by exposure to mammalian-derived products, has been increasing in prevalence, particularly in regions with high populations of lone star ticks, such as the southeastern United States. In recent years, other tick species in Europe, Australia, Asia, and parts of the northern and western United States have also been implicated in the development of AGS. The pathophysiology of AGS is believed to involve an immune response to the carbohydrate alpha-gal, which is present in mammalian meats, dairy products, and various animal-derived substances. The condition leads to the production of specific IgE antibodies that can trigger severe allergic reactions—including anaphylaxis—upon subsequent exposure.
Challenges in diagnosing and managing AGS in emergency settings
This case provides a clear example of how AGS can be present in the emergency department. He was diagnosed with AGS after a tick bite during a hiking trip in Missouri 15 months ago. This temporal relationship between tick exposure and subsequent onset of symptoms, including vomiting, diarrhea, chest pain, dyspnea, fever, chills, and hypertension, is a common pattern seen in AGS patients. The patient’s known history of AGS prompted the emergency team to exercise caution when choosing medications in the emergency setting, as the wrong medication could potentially worsen his condition.
Before administering any drugs, the patient’s medical team conducted a thorough review of potential drug allergies and interactions with substances containing alpha-gal antigens. This is crucial for AGS patients, as exposure to alpha-gal-containing substances—such as medications, vaccines, food, and certain diagnostic agents—can trigger life-threatening reactions. In this case, the patient was advised to continue avoiding red meat, dairy products, and alcohol—common triggers for AGS symptoms. While clinical caution is commonly exercised regarding mammal-derived excipients like magnesium stearate and lactose in medications for AGS patients, solid evidence directly linking these excipients to adverse reactions remains limited.
While alcohol, nonsteroid anti-inflammatory drugs (NSAIDs), and exercise are not primary triggers of AGS, they are recognized as co-factors that may amplify allergic reactions when combined with exposure to alpha-gal antigens (3). In this case, alcohol avoidance was recommended as a precautionary measure due to the patient’s history of severe symptoms. However, routine avoidance of alcohol is not necessary for all patients with AGS and should be tailored to individual co-factor sensitivity. Healthcare providers should assess each patient’s history to provide personalized recommendations on lifestyle modifications and co-factor management.
The patient’s history highlights the challenges of managing alpha-gal syndrome (AGS), particularly the difficulty of completely avoiding alpha-gal antigens. The absence of clear labeling on food and medications containing mammalian-derived ingredients further complicates avoidance efforts. As a result, patients with AGS must be vigilant and often rely on healthcare providers to guide them in making safe choices.
In this specific case, diphenhydramine, an antihistamine commonly used in emergency settings to treat allergic reactions, was administered to manage the patient’s symptoms. While diphenhydramine provides relief for associated symptoms such as itching and other allergic symptoms, it does not directly address the underlying pathophysiology of AGS. Although its sedative effects may offer short-term relief, diphenhydramine is not considered a first-line treatment for AGS-related symptoms such as headache or anaphylaxis (4).
Metoclopramide, another commonly used medication in the emergency setting, was also administered to address the patient’s nausea and vomiting. Metoclopramide works by increasing gastric motility and blocking dopamine receptors, which can help alleviate nausea and improve the absorption of other pain medications. However, it does not specifically target the root cause of the headache pain or the underlying allergic response associated with AGS.
For treating AGS symptoms in emergency settings, particularly headaches or severe allergic reactions, alternative medications are typically recommended. triptans, NSAIDs, and dopamine receptor antagonists are commonly prescribed to directly target the mechanisms of headache pain (5). In addition, corticosteroids may be considered to manage more severe allergic reactions, such as anaphylaxis, in patients with AGS.
Medications commonly used to treat chest pain, such as nitroglycerin and morphine, may not be suitable for patients with AGS due to the potential presence of mammalian proteins (3). For example, morphine, a standard analgesic for chest pain, may contain trace amounts of mammalian-derived substances, posing a risk of hypersensitivity reactions in individuals with AGS. As such, alternative medications were carefully considered to avoid triggering an allergic response.
Diagnostic considerations
The diagnosis of AGS in this case is complicated by modest alpha-gal-specific IgE levels and the absence of tryptase measurement during the acute presentation. Although the patient’s history of a lone star tick bite and allergic symptoms following mammalian meat consumption are suggestive of AGS, low IgE levels are infrequently associated with severe anaphylactic reactions. Furthermore, the endemic prevalence of alpha-gal IgE antibodies in the southeastern United States raises the possibility of overdiagnosis.
The elevated creatine kinase (CK) level introduces alternative considerations, including muscle injury, inflammatory myopathy, viral myositis, or rhabdomyolysis, any of which could explain symptoms such as chest pain and dyspnea. The absence of elevated tryptase, a key marker of systemic allergic reactions, further complicates the attribution of these symptoms to AGS.
This case emphasizes the need for a thorough differential diagnosis, particularly in regions where alpha-gal IgE antibodies are common. While AGS is plausible, alternative etiologies should be thoroughly considered to avoid premature conclusions based on incomplete evidence.
Prevention and management strategies for AGS
As AGS continues to rise in incidence (6), the challenge of managing it in emergency settings will only grow. Preventive strategies, such as wearing protective clothing, using tick repellents, and taking precautions to avoid tick bites, are essential for reducing the risk of AGS. However, the persistent difficulty in avoiding alpha-gal antigens, especially in non-food products and medications, highlights the need for improved product labeling and standardized guidelines to help both healthcare providers and patients prevent exposure.
Effective management of AGS requires a coordinated approach involving physician, allergist, nutritionist, pharmacist, and patient. Close communication among these professionals ensures that patients receive individualized treatment plan that minimizes the risk of exposure to alpha-gal antigens and reduces the likelihood of severe allergic reactions. The nutritionist plays a critical role by providing a dietary sheet detailing foods to avoid and suggesting suitable substitutes to ensure patients maintain a balanced and safe diet (3). This multidisciplinary approach is essential for improving patient outcomes and preventing future complications associated with AGS.
Limitations
While this case report offers valuable insights into the clinical presentation and management of AGS, several limitations should be acknowledged. Firstly, this study is based on a single case, which limits its generalizability to broader populations or different clinical contexts. In addition, the healthcare team highlighted the value of conducting drug challenges and ensured that patients were adequately informed and equipped with an emergency action plan to address any allergic reactions. The findings and management strategies described here may not be universally applicable to all patients with AGS due to individual variations in symptoms, allergen sensitivities, and treatment responses.
Secondly, the retrospective nature of the study and reliance on medical records and patient recall introduce potential biases and incomplete data. Inconsistencies in symptom reporting and medical history documentation could affect the accuracy and completeness of the information presented.
Thirdly, the availability and accuracy of specific allergy testing methods and allergen avoidance strategies may vary across different healthcare settings and regions. These disparities may impact the reproducibility of the diagnostic approach, and the effectiveness of management recommendations proposed in this report.
Despite these limitations, this case report underscores the importance of early recognition, comprehensive assessment, and tailored management of AGS to optimize patient outcomes and minimize the risk of severe allergic reactions. Further research involving larger cohorts and standardized protocols is warranted to enhance our understanding and management of this complex hypersensitivity syndrome.
Future research
Further studies are required to evaluate the safety of mammal-derived excipients in AGS patients, which support the development of provide evidence-based guidance for healthcare providers.
Conclusions
AGS is a delayed hypersensitivity reaction that can present with a range of symptoms, including urticaria, gastrointestinal symptoms, angioedema, anaphylaxis, and drug-induced hypersensitivity. In this case, the patient had a history of tick bite, and confirmed allergies to red meat, dairy products, and alcohol which can trigger hypersensitivity reactions.
This case report aims to educate healthcare providers about the need to avoid medications that contain mammalian-derived proteins. It is crucial to consult with pharmacists to ensure that any medications that are to be given either in the acute setting, such as the Emergency Department or in an outpatient setting, are approved to be free from mammalian protein components to prevent any allergic reactions. The patient was treated for presenting symptoms in the Emergency Department without complication.
Acknowledgments
We gratefully acknowledge the patient for providing consent to publish this case report. We also extend our sincere thanks to the healthcare team at Freeman Hospital for their dedicated care. We appreciate the valuable contributions of all participants involved in the consensus process for case reporting guidelines. Additionally, we acknowledge the use of medical literature sources that supported the development of this report.
Footnote
Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-80/rc
Peer Review File: Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-80/prf
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-80/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
References
- Božan M, Vukičević Lazarević V, Marković I, et al. Alpha-gal syndrome-Food or drug allergy: A case report. Clin Case Rep 2023;11:e7830. [Crossref] [PubMed]
- Quest Diagnostics. Alpha-gal panel. Available online: https://testdirectory.questdiagnostics.com/test/test-detail/10555/alpha-gal-panel?q=10555&cc=MASTER
- Commins SP. Diagnosis & management of alpha-gal syndrome: lessons from 2,500 patients. Expert Rev Clin Immunol 2020;16:667-77. [Crossref] [PubMed]
- Pinder RM, Brogden RN, Sawyer PR, et al. Metoclopramide: a review of its pharmacological properties and clinical use. Drugs 1976;12:81-131. [Crossref] [PubMed]
- Gelfand AA, Goadsby PJ. A Neurologist's Guide to Acute Migraine Therapy in the Emergency Room. Neurohospitalist 2012;2:51-9. [Crossref] [PubMed]
- Thompson JM, Carpenter A, Kersh GJ, et al. Geographic Distribution of Suspected Alpha-gal Syndrome Cases - United States, January 2017-December 2022. MMWR Morb Mortal Wkly Rep 2023;72:815-20. [Crossref] [PubMed]
Cite this article as: Noor K, Orren J, Kennedy K. Alpha-gal syndrome presenting in the emergency department: a case report. J Emerg Crit Care Med 2025;9:23.
