α-Gal Syndrome vs Chronic Urticaria | Allergy and Clinical Immunology | JAMA Dermatology | JAMA Network
[Skip to Navigation]
Sign In
Table 1.  Characteristics of Study Population
Characteristics of Study Population
Table 2.  Characteristics for Patients With Detectable Serum Levels of IgE Antibodies Against α-Gal and Available Dietary History
Characteristics for Patients With Detectable Serum Levels of IgE Antibodies Against α-Gal and Available Dietary History
1.
Commins  SP, Satinover  SM, Hosen  J,  et al.  Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose.  J Allergy Clin Immunol. 2009;123(2):426-433. doi:10.1016/j.jaci.2008.10.052PubMedGoogle ScholarCrossref
2.
Wilson  JM, Schuyler  AJ, Schroeder  N, Platts-Mills  TAE.  Galactose-α-1,3-galactose: atypical food allergen or model IgE hypersensitivity?  Curr Allergy Asthma Rep. 2017;17(1):8. doi:10.1007/s11882-017-0672-7PubMedGoogle ScholarCrossref
3.
Commins  SP, James  HR, Kelly  LA,  et al.  The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose.  J Allergy Clin Immunol. 2011;127(5):1286-1293.e6. doi:10.1016/j.jaci.2011.02.019PubMedGoogle ScholarCrossref
4.
Kennedy  JL, Stallings  AP, Platts-Mills  TAE,  et al.  Galactose-α-1,3-galactose and delayed anaphylaxis, angioedema, and urticaria in children.  Pediatrics. 2013;131(5):e1545-e1552. doi:10.1542/peds.2012-2585PubMedGoogle ScholarCrossref
5.
Ghahramani  GK, Temprano  J.  Tick bite-related meat allergy as a cause of chronic urticaria, angioedema, and anaphylaxis in endemic areas.  Int J Dermatol. 2015;54(2):e64-e65. doi:10.1111/ijd.12672PubMedGoogle ScholarCrossref
6.
Maurer  M, Church  MK, Metz  M, Starkhammar  M, Hamsten  C, van Hage  M.  Galactose-alpha-1,3-galactose allergy is not a hitherto unrecognized cause of chronic spontaneous urticaria.  Int Arch Allergy Immunol. 2015;167(4):250-252. doi:10.1159/000440653PubMedGoogle ScholarCrossref
Research Letter
January 2019

α-Gal Syndrome vs Chronic Urticaria

Author Affiliations
  • 1Department of Dermatology, University of Virginia, Charlottesville
  • 2Department of Medicine, University of Virginia, Charottesville
  • 3Department of Microbiology, University of Virginia, Charottesville
  • 4Division of Rheumatology, Allergy & Immunology, The University of North Carolina at Chapel Hill, Chapel Hill
JAMA Dermatol. 2019;155(1):115-116. doi:10.1001/jamadermatol.2018.3970

Galactose-α-1,3-galactose (α-gal) is an oligosaccharide expressed on glycoproteins and glycolipids of nonprimate mammals and is the causal epitope of an IgE-mediated allergy to mammalian meat.1,2 First reported in 2009, the α-gal syndrome is an increasingly appreciated problem across the southeastern United States and other parts of the world.2 It is clear that tick bites, specifically relating to Amblyomma americanum (lone star tick), are causal in many, if not most, cases of α-gal sensitization in the United States.3 Following sensitization, many individuals will experience allergic symptoms on ingestion of meat or other products (eg, dairy) derived from nonprimate mammals. In contrast to typical IgE-mediated reactions, which occur within minutes of exposure, the α-gal allergy typically has a delayed onset of 2 to 6 hours.2 The severity of the reaction varies from general urticaria to anaphylaxis, and individuals may not react to every exposure. Because of these atypical features, proper diagnosis can prove challenging. An epidemiological investigation of a pediatric population reported that α-gal may be misdiagnosed as recurrent urticaria or idiopathic anaphylaxis.4 While a recent report postulated that α-gal syndrome might represent a novel cause of chronic urticaria, further research failed to find such an association.5,6 Nevertheless, in areas where α-gal sensitization is prevalent, the potential for misdiagnosing cases of α-gal syndrome as chronic urticaria still exists. Here, we report cases labeled as chronic urticaria or chronic idiopathic urticaria within a cohort of patients in central Virginia being evaluated for α-gal syndrome.

Methods

Approval from the institutional review board at University of Virginia and patient informed consent were obtained. Medical records were available from 401 patients seen in the University of Virginia Allergy Clinic who were initially enrolled in a study designed to assess a population with IgE antibodies specific to α-gal and to compare their features with those of nonsensitized participants. Data regarding medical history were subsequently extracted. Patients with a history or a previous diagnosis of chronic urticaria or chronic idiopathic urticaria were identified. In this study and the parent study, α-gal syndrome was defined by a clinical history of delayed reactions to mammalian meat (≥2 hours) and detection of IgE antibodies to α-gal of 0.35 IU/mL or more using ImmunoCAP IgE assays (ThermoFisher Scientific) as previously described.1

Results

Of the 401 participants, 29 (17 female, 12 male; age range at enrollment, 10-78 years) met the final inclusion criteria. Of this group, 20 patients (69%) had detectable serum levels of IgE antibodies against α-gal (Table 1). The geometric mean level of IgE antibodies to α-gal was 8.1 IU/mL (95% CI, 3.7-18.0) and the total IgE level was 259 IU/mL (95% CI, 145-463). Dietary information was available for 15 of 20 patients with detectable levels of IgE antibodies against α-gal; 9 experienced a complete remission of their symptoms after avoidance of mammalian meat or mammalian-derived products. Another 5 patients demonstrated partial improvement (Table 2).

Discussion

The delayed reactions to mammalian products experienced by patients with the α-gal syndrome can easily be misdiagnosed as chronic urticaria. Moreover, these 2 entities can also coexist; it is uncertain whether the 5 participants with only partial improvement of their symptoms had incomplete compliance with an avoidance diet or had coexisting chronic urticaria. Nevertheless, testing for IgE antibodies to α-gal involves a simple blood test and, on dietary modification, those with symptoms attributable to the syndrome should experience relief. Because chronic urticaria is a condition that severely affects a patient’s quality of life, it is crucial to recognize potential mimickers or confounders. Though larger studies are needed, we postulate a benefit for screening patients undergoing evaluation for chronic urticaria who have a suggestive dietary history and live in regions where the α-gal syndrome is common.

Back to top
Article Information

Accepted for Publication: September 6, 2018.

Corresponding Author: Jeffrey M. Wilson, MD, PhD, Asthma and Allergic Diseases Center, University of Virginia, PO Box 801355, Charlottesville, VA 22908-1355 (jmw2gc@virginia.edu).

Published Online: November 21, 2018. doi:10.1001/jamadermatol.2018.3970

Author Contributions: Ms Pollack and Dr Wilson had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Pollack, Zlotoff, Borish, Commins, Wilson.

Acquisition, analysis, or interpretation of data: Pollack, Borish, Commins, Platts-Mills, Wilson.

Drafting of the manuscript: Pollack, Wilson.

Critical revision of the manuscript for important intellectual content: Zlotoff, Borish, Commins, Platts-Mills, Wilson.

Statistical analysis: Pollack, Wilson.

Obtained funding: Borish, Commins, Platts-Mills.

Administrative, technical, or material support: Borish, Platts-Mills.

Study supervision: Zlotoff, Borish, Commins, Wilson.

Conflict of Interest Disclosures: Relationships relevant to this article: Dr Platts-Mills has a patent on the IgE assay for α-gal and has received unrestricted assay support from the manufacturer, Phadia Laboratory Systems/ThermoFisher Scientific. All other authors have no relevant financial interests to report. All other relationships: Dr Borish is on the speakers’ bureau for Merck and the advisory board for Genentech and receives grant support from Genentech. Dr Commins receives an honorarium from UpToDate, is on the speakers’ bureau for Genentech, and receives grant support from the National Institutes of Health. Dr Platts-Mills is on the scientific advisory committee for Indoor Biotechnologies and receives grant support from Phadia Laboratory Systems/ThermoFisher Scientific and the National Institute of Allergy and Infectious Diseases. All other authors have no relevant financial interests to report.

Funding/Support: Funding for the design and conduction of this study was provided by National Institutes of Health grants R01 AI-20565 (Dr Platts-Mills) and K08 AI-085190 (Dr Commins).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Commins  SP, Satinover  SM, Hosen  J,  et al.  Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose.  J Allergy Clin Immunol. 2009;123(2):426-433. doi:10.1016/j.jaci.2008.10.052PubMedGoogle ScholarCrossref
2.
Wilson  JM, Schuyler  AJ, Schroeder  N, Platts-Mills  TAE.  Galactose-α-1,3-galactose: atypical food allergen or model IgE hypersensitivity?  Curr Allergy Asthma Rep. 2017;17(1):8. doi:10.1007/s11882-017-0672-7PubMedGoogle ScholarCrossref
3.
Commins  SP, James  HR, Kelly  LA,  et al.  The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose.  J Allergy Clin Immunol. 2011;127(5):1286-1293.e6. doi:10.1016/j.jaci.2011.02.019PubMedGoogle ScholarCrossref
4.
Kennedy  JL, Stallings  AP, Platts-Mills  TAE,  et al.  Galactose-α-1,3-galactose and delayed anaphylaxis, angioedema, and urticaria in children.  Pediatrics. 2013;131(5):e1545-e1552. doi:10.1542/peds.2012-2585PubMedGoogle ScholarCrossref
5.
Ghahramani  GK, Temprano  J.  Tick bite-related meat allergy as a cause of chronic urticaria, angioedema, and anaphylaxis in endemic areas.  Int J Dermatol. 2015;54(2):e64-e65. doi:10.1111/ijd.12672PubMedGoogle ScholarCrossref
6.
Maurer  M, Church  MK, Metz  M, Starkhammar  M, Hamsten  C, van Hage  M.  Galactose-alpha-1,3-galactose allergy is not a hitherto unrecognized cause of chronic spontaneous urticaria.  Int Arch Allergy Immunol. 2015;167(4):250-252. doi:10.1159/000440653PubMedGoogle ScholarCrossref
×