Abstract
This cohort study assesses the use of a blood test to distinguish galactose-α-1,3-galactose (α-gal) allergy from chronic urticaria.
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).
Table 1. Characteristics of Study Population.
| Demographics | Patients, No. (%) | P Valueb | |
|---|---|---|---|
| With Detectable Levels of α-Gala (n = 20) | Without Detectable Levels of α-Gala (n = 9) | ||
| Female | 10 (50) | 7 (78) | .23 |
| Racec | |||
| White | 20 (100) | 5 (56) | .005 |
| Other | 0 | 4 (54) | .005 |
| Age at enrollment, mean (range), y | 50.5 (10-76) | 42.6 (24-78) | .24 |
| History of tick bitesc | 19 (95) | 1 (11) | <.001 |
| History of lone star tick bitec | 9 (45) | 0 (0) | .03 |
| Total serum IgE, geometric mean, IU/mL (95% CI) | 259 (145-463) | 49 (15-159) | .008 |
| α-Gal level, geometric mean, IU/mL (95% CI) | 8.1 (3.7-18.0) | Not applicable | Not applicable |
| α-Gal IgE, mean (95% CI), % | 8.5 (2.0-15) | Not applicable | Not applicable |
Abbreviation: α-gal, galactose-α-1,3-galactose.
Level of detection was defined as IgE to α-gal ≥0.35 IU/mL.
Continuous variables were compared with Mann-Whitney U test and categorical variables were compared with Fisher exact test.
Relative to each subgroup of patients with (n = 20) or without (n = 9) detectable levels of α-gal.
Table 2. Characteristics for Patients With Detectable Serum Levels of IgE Antibodies Against α-Gal and Available Dietary History.
| Patient No./Sex/Age at Enrollment, y | Diagnosis | α-Gal Level, IU/mL | Total Serum IgE, IU/mL | Improvement on Diet |
|---|---|---|---|---|
| 1/M/59 | CIU | 7.1 | 434 | Partiala |
| 2/M/47 | CU | 0.5 | 176 | No |
| 3/M/57 | CU | 6.1 | 409 | Complete |
| 4/F/38 | CIU | 40.9 | 181 | Completeb |
| 5/F/60 | CIU | 16.3 | 168 | Complete |
| 6/F/15 | CIU | 1.7 | 44 | Completec |
| 7/F/37 | CIU | 0.6 | 350 | Partialc |
| 8/F/17 | CU | 49.5 | 896 | Completed |
| 9/F/43 | CU | 1.0 | 66 | Partialc |
| 10/F/74 | CU | 31.3 | 54 | Partial |
| 11/F/59 | CU | 12.4 | 44 | Complete |
| 12/M/71 | CU | 8.4 | 307 | Complete |
| 13/M/10 | CIU | 22.2 | 172 | Complete |
| 14/F/65 | CU | 1.2 | 76 | Completec |
| 15/M/55 | CIU | 4.4 | 353 | Partial |
Abbreviations: α-gal, galactose-α-1,3-galactose; CIU, chronic idiopathic urticaria; CU, chronic urticaria.
Patient continued to be treated for CIU.
Patient was concomitantly placed on omalizumab.
Patient continued to consume dairy.
Information on dairy consumption not available through record review.
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.
References
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