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Isolated Gastrointestinal Alpha-gal Meat Allergy Is a Cause for Gastrointestinal Distress Without Anaphylaxis

2021; Elsevier BV; Volume: 160; Issue: 6 Linguagem: Inglês

10.1053/j.gastro.2021.01.218

1528-0012

Michael P. Croglio, Scott P. Commins, Sarah McGill,

Contact Dermatitis and Allergies

Alpha-gal allergy is characterized by a reaction to beef, pork, and other mammalian meat and derived products, typically hours after ingestion, and is diagnosed by the presence of elevated serum alpha-gal IgE antibodies.1Commins S.P. et al.J Allergy Clin Immunol. 2014; 134: 108-115Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar, 2Platts-Mills T.A.E. et al.J Allergy Clin Immunol. 2020; 145: 1061-1071Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar, 3Commins S.P. et al.J Allergy Clin Immunol. 2009; 123: 426-433Abstract Full Text Full Text PDF PubMed Scopus (534) Google Scholar The allergy appears to develop after the bite of a hard tick and has been described in the United States (particularly the southeastern United States; Supplementary Figure 1), Europe, Africa, Australia, Central and South America, and Asia.4Commins S.P. et al.J Allergy Clin Immunol. 2011; 127: 1286-1293Abstract Full Text Full Text PDF PubMed Scopus (455) Google Scholar, 5Hamsten C. et al.Allergy. 2013; 68: 549-552Crossref PubMed Scopus (172) Google Scholar, 6van Nunen S. Intern Med J. 2007; 37: A128-A135Google Scholar Symptoms can include pruritus, rash, diarrhea, abdominal cramping, shock, and anaphylaxis, the latter of which is defined by the involvement of 2 or more systems (skin, gastrointestinal [GI], cardiac, pulmonary). GI symptoms are caused by IgE-mediated degranulation of mast cells and histamine receptors in the GI tract. Management of the allergy includes counseling on the avoidance of mammalian meat and sometimes dairy and other mammalian-derived products.7Commins S.P. Expert Rev Clin Immunol. 2020; 16: 1-11Crossref Scopus (64) Google Scholar In case of exposure, short- and long-acting oral antihistamines such as diphenhydramine and fexofenadine may be used to ameliorate both GI and allergic symptoms. Allergy and oncology journals have primarily published research on alpha-gal allergy, and it has not been described previously in the GI literature. We describe patients with the allergy who presented with isolated GI symptoms. We studied patients from 2 GI clinics in the southeastern United States who were found to have elevated serum alpha-gal IgE and GI complaints without accompanying rash, hypotension, or difficulty breathing in this retrospective cohort study. After observation by both clinic physicians that patients could have GI symptoms from the allergy, patients with functional-type symptoms were frequently screened for alpha-gal. As part of their clinical practice, patients who were alpha-gal positive were counseled to strictly avoid mammalian meat, offered a consultation with an allergist, and followed clinically. After excluding 2 patients for confounding factors (ileal Crohn's disease and daily cannabis use), we describe the remaining patients. The University of North Carolina Institutional Review Board approved the study. Clinical endpoints were compliance with meat elimination diet and improvement in GI symptoms. We defined resolution as no symptoms on an alpha-gal–free diet, significant improvement as only occasional or mild symptoms for which patients did not seek further care, and some improvement as subjective improvement but persistent symptoms that required medical follow-up. We judged meat elimination as "strict" if patients strictly avoided mammalian meat, apart from attempts to self-challenge. Abdominal pain (87.5%), nausea (75%), and diarrhea (68.75%), mainly episodic (68.8%) vs chronic (31.25%), were the most common symptoms among patients (Table 1). Nine patients (56.2%) met the criteria for diarrhea-predominant irritable bowel syndrome. Some patients reported awakening at night with GI distress given the typical delayed reaction. We observed variability in the response to mammalian meat in that some patients did not report a response to every exposure. No patient related GI symptoms to mammalian meat ingestion before diagnosis, and 75% recalled a tick bite. The median time from symptom onset to diagnosis was 21 months.Table 1Patient CharacteristicsPatient IdentificationAge Decade at DiagnosisSexMonths from Symptom Onset to Diagnosis; Prior GI DiagnosesSymptomsAlpha-gal IgE Level IU/L)Recalled Tick BitesMeat EliminationImprovementA50F2Diarrhea, abdominal bloating, mucus in stools, fecal urgency1.27YesStrictResolutionB60F2Abdominal pain, nausea, heartburn0.76NoStrictResolutionC80M7Abdominal pain, diarrhea, nausea63.6YesStrictResolutionD40M144; irritable bowel syndromeaPatients had chronic symptoms of waxing and waning abdominal pain and diarrhea but reported moderate-to-severe exacerbations.Abdominal pain, diarrhea, nausea, noncardiac chest pain0.27YesStrictSomeE60F36Abdominal pain, diarrhea, nausea>100NoStrictSignificantF60F120Abdominal pain, constipation, nausea, vomiting5.24YesPartialSignificantG80F60; irritable bowel syndromeaPatients had chronic symptoms of waxing and waning abdominal pain and diarrhea but reported moderate-to-severe exacerbations.Abdominal pain, diarrhea, nausea0.4YesStrictSomeH40F2; recurrent Clostridioides difficile infectionbThe patient underwent colonoscopy-based fecal microbiota transplantation in 2018 for recurrent Clostridioides difficile infection that had always responded to antibiotics. Two months after the procedure, she reported awakening from sleep with severe abdominal pain and diarrhea that was C. difficile negative after eating a hamburger the day before.Abdominal pain, diarrhea, nausea0.65YesPartialSignificantI70F36Abdominal pain0.11YesStrictSignificantJ60F10Abdominal pain, diarrhea0.53YesStrictResolutionK60M12Abdominal pain, nausea, vomiting0.81YesPartialSomeL80F39Nausea, vomiting0.37YesStrictSignificantM40F60Abdominal pain, diarrhea, nausea, heartburn0.26NoStrictSignificantN60F10Abdominal pain, diarrhea, nausea0.3YesStrictSignificantO50F18Abdominal pain, diarrhea, nausea, vomiting1.46NoStrictSomeP40M2Abdominal pain, diarrhea0.57YesStrictSignificanta Patients had chronic symptoms of waxing and waning abdominal pain and diarrhea but reported moderate-to-severe exacerbations.b The patient underwent colonoscopy-based fecal microbiota transplantation in 2018 for recurrent Clostridioides difficile infection that had always responded to antibiotics. Two months after the procedure, she reported awakening from sleep with severe abdominal pain and diarrhea that was C. difficile negative after eating a hamburger the day before. Open table in a new tab All patients reported symptom improvement during a median follow-up of 14 months (range, 2 months to 3 years). Four patients' symptoms resolved, all of whom followed strict avoidance diets. Eight patients (50%) reported significant improvement and 4 patients some improvement. Six patients had moderate or severe GI distress after self-challenging with beef or pork during the follow-up period and continued on an avoidance diet (patients E, H, L, N, O, and P). Only 1 patient developed anaphylaxis at follow-up (patient E) after an attempt to self-challenge. Two patients resumed eating meat regularly during the follow-up period. Patient F had intermittent attempts to challenge after diagnosis and resumed eating meat 1 year after diagnosis, at which time she ceased to have GI symptoms. Patient K resumed eating pork but not beef soon after diagnosis and eventually returned to eating beef. Of 16 patients, 13 (81%) followed a strict elimination diet on follow-up and 3 followed partial meat elimination. In addition, 10 patients reported eliminating dairy, 4 patients continued dairy consumption, and 2 patients did not report. Eight patients received formal diet counseling at the University of North Carolina allergy clinic. The median alpha-gal IgE was 0.61 IU/mL, much lower than the median of 51.3 IU/mL in a cohort of 24 alpha-gal–allergic patients with a history of anaphylaxis, angioedema, or urticaria.3Commins S.P. et al.J Allergy Clin Immunol. 2009; 123: 426-433Abstract Full Text Full Text PDF PubMed Scopus (534) Google Scholar In our study, patients with alpha-gal meat allergy developed GI symptoms—most commonly episodic abdominal pain, nausea, and diarrhea—without more traditional manifestations of food allergy such as hives, angioedema, or anaphylaxis. Adhering to a mammalian meat-free diet led to significant symptom improvement or resolution in three-fourths of patients. Within the allergy literature, reports of isolated GI alpha-gal allergy exist. Among 114 patients diagnosed with the allergy in South Africa and challenged with beef sausage under observation, 81 reacted, and among those, almost half were limited to GI symptoms—25% with vomiting and/or diarrhea and 21% with severe and persistent abdominal cramping alone.8Mabelane T. et al.Pediatr Allergy Immunol. 2018; 29: 841-849Crossref PubMed Scopus (74) Google Scholar After an observed challenge of pork sausage among 12 patients with the allergy in the United States, 2 patients developed isolated GI distress.1Commins S.P. et al.J Allergy Clin Immunol. 2014; 134: 108-115Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar This is a small observational study and has many limitations. We did not perform a formal oral challenge test, and both improvement in symptoms and reactions to meat consumption after diagnosis were based on subjective reports. There may be overlap of GI symptoms with other causes of GI distress such as lactose. Future prospective studies would ideally involve validated patient-reported symptom measures over time. Prospective studies also could better ascertain the time frame from diet change to symptom improvement and the degree of elimination, including that of dairy, gelatin, and flavorings that contain animal-derived products, that are associated with symptom resolution. We observed a lower median alpha-gal titer compared with other cohorts with anaphylaxis, and our patient with the highest titer did develop anaphylaxis on follow-up. However, more work is needed to define whether titer predicts severity of response. In conclusion, our findings suggest that screening with alpha-gal IgE may be a reasonable strategy in patients who live in areas with known cases of alpha-gal allergy and present with new-onset GI symptoms, particularly episodic abdominal pain, diarrhea, and nausea, even in the absence of rash or anaphylaxis. The authors are grateful to Melissa Rich, MD, MPH, and Aileen Naro, RN, who contributed patients to the study. Michael P. Croglio, MD (Data curation: Lead; Investigation: Lead; Writing – original draft: Equal). Scott P. Commins, MD, PhD (Conceptualization: Supporting; Writing – original draft: Supporting; Writing – review & editing: Equal). Sarah K. McGill, MD, MS (Conceptualization: Lead; Data curation: Supporting; Formal analysis: Lead; Investigation: Lead; Writing – original draft: Equal; Writing – review & editing: Equal).