While meat is a vital source of protein in Western diets, developing a meat allergy is generally uncommon. Specifically for mammalian meats, the proteins are quite similar across species, which reduces the chance of triggering a specific IgE antibody response. When reactions to meats do occur, they are often due to cross-reactivity with substances like serum albumin (SA) or actin, rather than a unique sensitivity to meat proteins themselves. A notable example of this cross-reactivity is seen in the pork-Cat Syndrome.
This unusual condition involves patients who develop IgE antibodies against cat serum albumin. These antibodies then react with porcine albumin, found in pork. This cross-reaction can lead to significant allergic reactions, even life-threatening anaphylaxis, upon consuming pork. Interestingly, pork-cat syndrome has been primarily reported in Europe. However, our recent evaluation of patients with suspected meat allergies has uncovered eight cases of pork-cat syndrome in the United States. This article presents the first report of these US cases, detailing the IgE specificity and clinical responses to dietary changes in two representative patients, strongly suggesting this diagnosis. It’s important to note that confirmatory food challenges were not conducted in these eight patients.
Research suggests that the primary trigger for pork-cat syndrome is sensitization to cat serum albumin, which then leads to the cross-reactive IgE response. A study on young patients in Luxembourg showed that IgE reactivity to cat serum albumin encompassed all reactivity to pork, but not vice versa. Those patients were selected because they were highly allergic to cats. In contrast, the eight patients in our report were evaluated for suspected meat allergy.
Patient E364 (Table I) experienced abdominal cramps, nausea, itching, and hives within 20 minutes of eating pork tenderloin, potatoes, and green beans. His symptoms worsened to include lightheadedness, requiring emergency treatment for anaphylaxis. Given the rapid onset after eating, alpha-gal allergy was less likely. Tests revealed positive IgE responses to cat, dog, and pork, but not beef or lamb. Further tests for serum albumins and gelatin (Table I) showed positive results for cat and dog SA (Re220 and Re221, respectively), but negative for bovine SA (Re204). These results indicated that pork triggered his anaphylactic reaction due to cross-reacting IgE, consistent with pork-cat syndrome. He was advised to avoid pork and has remained reaction-free for two years.
Table I.
Eight US Cases of Pork-Cat Syndrome: Patient Characteristics and IgE Profiles
| Subject | E364 | E533 | E572 | T559 | E584 | T625 | E710 | E724 |
|---|---|---|---|---|---|---|---|---|
| Sex | M | F | F | F | F | M | F | F |
| Age (yr) | 52 | 34 | 21 | 14 | 44 | 11 | 13 | 41 |
| Symptoms with Meat | ANA | OA/URT | OA/GI | URT | ANA | OA | ANA | OA/GI |
| Avoidance Diet Results | No episodes at 2 yrs | No episodes at 1.5 yrs | No episodes at 15 mo | No episodes at 9 mo | No episodes at 13 mo | Fewer episodes | No episodes at 1 yr | Fewer episodes |
| Symptoms with Cat or Dog exposure | No | R | R, C, U | A | No | Yes | R, C | R |
| Animal Exposure | Cat | Cat, Dog | Dog, Horse | No | Cat, Dog, Guinea Pig | Dog | Cat, Dog | Cat |
| SPT Dog Dander | + | + | − | − | − | + | ND | ND |
| SPT Cat Dander | + | − | + | + | + | + | ND | ND |
| SPT Pork | + | + | + | + | + | + | ND | ND |
| Total IgE (IU/ml) | 83.4 | 252 | 328 | 791 | 42.3 | 1860 | 2619 | 133 |
| Specific IgE (IU/ml) to: | ||||||||
| Cat Albumin | 2.28 | 98.8 | 12.3 | 9.96 | 4.18 | 2.33 | 130 | 26.8 |
| Dog Albumin | 2.59 | 65.0 | 15.2 | 6.53 | 4.87 | 1.71 | 110 | 10.8 |
| Bovine Albumin | 6.79 | 1.92 | 4.76 | 3.56 | 6.31 | |||
| Cat Dander | 3.74 | 33.8 | 5.71 | 121 | 3.87 | 23.6 | 155 | 17.7 |
| Fel d 1 | 1.58 | 1.94 | 2.16 | 103 | ND | 90.1 | 0.81 | |
| Alpha-Gal | 1.41 | |||||||
| Pork | 0.65 | 13.2 | 7.10 | 7.96 | 0.53 | 42.8 | 43.8 | 3.40 |
| Beef | 2.22 | 1.10 | 4.45 | 0.91 | 2.62 |
ND: Not Done
*ANA: anaphylaxis; OA: oropharyngeal itching; URT: urticaria; GI: gastrointestinal symptoms
† A: asthma; C: conjunctivitis; R: rhinitis; U: urticaria
‡ Defined as consistent exposure at home, work or regular activity (e.g., horseback riding); NB – subject T559 had to limit animal exposure due to symptoms
SPT positive (+) defined as >4mm wheal with flare present; (−) = negative
$Each subject reported fewer symptoms or no episodes when following an avoidance diet
The second case, patient T559, a 14-year-old female, experienced recurrent abdominal pain 30–45 minutes after meals, occurring 3–5 times monthly for 14 months. The pain resolved in 45–60 minutes without treatment, with no nausea, vomiting, diarrhea, or bowel changes noted. Initially, no food association was recognized. Sometimes, the abdominal pain was accompanied by hives. Testing revealed sIgE to cat and dog albumin and pork (Table I, case 4), but no alpha-gal sIgE. She was advised to eliminate pork from her diet but could continue eating beef. After nine months, she reported no further abdominal pain or hives.
As shown in Table I, pork-cat syndrome, like other food allergies, presents with varied symptoms, and the severity isn’t always predicted by IgE levels to cat serum albumin. To assess binding specificity, tests were performed on sera from three patients with sufficient samples (Table II). IgE responses to cat SA and pork decreased significantly after pre-incubation with cat albumin. However, pork albumin and human albumin did not significantly inhibit the cat SA response (Table II; porcine SA and human SA share 82% and 76% protein homology with cat SA, respectively). The IgE specificity in our patients aligns with previous findings, supporting cat SA as the primary sensitizer.
Table II.
Serum Absorption in Pork-Cat Syndrome Subjects Using Different Mammalian Albumins
| Subject | Specific IgE (IU/ml) | Sepharose Beads Used for Absorption |
|—|—|—|—|—|—|
| | | Control | Cat | Pork | Dog | Human |
| E533 | Cat Albumin | 24.9 | 0.69 | 20.6 | 6.65 | 31.9 |
| | Pork Meat | 6.37 | 0.36 | 0.39 | 6.65 | |
| | Pork Albumin | 6.09 | | 6.09 | | |
| E710 | Cat Albumin | 51.3 | 1.58 | 30.2 | 6.05 | 47.3 |
| | Pork Meat | 12.8 | 1.38 | 1.43 | 1.24 | 12.7 |
| | Pork Albumin | 9.8 | 0.51 | 0.43 | 0.45 | 9.32 |
| E724 | Cat Albumin | 13.1 | 0.53 | 8.76 | 5.04 | 12.1 |
| | Pork Meat | 1.65 | 1.51 | | | |
| | Pork Albumin | 1.56 | | 1.34 | | |
*Each serum was diluted 1:2 or 1:4, and then 200 microliters was absorbed for 4 hours with 40 microliters of either Sepharose beads coated with the relevant albumin or uncoated blank beads. Sera were then assayed for specific IgE to cat albumin (Re220), pork meat (f26), and pork albumin (e222) using ImmunoCAP as described.
†Pre-incubation with alpha-gal or bovine gelatin did not affect the response to cat serum albumin.
Key Aspects of Pork-Cat Syndrome
Several important features of pork-cat syndrome warrant discussion. Firstly, pork sensitivity typically develops later in life, with most patients being older children, teenagers, or adults. It appears that sensitization to cat serum albumin builds up over time. Therefore, a new food allergy onset in an older child or adult should raise suspicion for pork-cat syndrome.
Secondly, reactions are not consistent with every pork consumption. Both the European cases and our US cases show that fresh meat or cured pork like barbecue are more likely to cause reactions, while well-cooked pork is less problematic.
Thirdly, reactions to pork are rapid, usually starting soon after ingestion. This timing is crucial in distinguishing pork-cat syndrome from delayed anaphylaxis caused by alpha-gal allergy. While both are IgE-mediated mammalian meat allergies and may show similar skin test and immunoassay results, pork-cat syndrome symptoms are faster, sometimes starting with oral itching during the meal, typically followed by gastrointestinal symptoms like abdominal cramping within 30–45 minutes.
Fourthly, the long-term course of pork-cat syndrome is not well understood, but IgE to cat serum albumin may decrease over time. Continued cat exposure might be necessary to maintain sensitization, potentially explaining why some patients can eventually tolerate pork again. Data suggests that about 30% of sensitized individuals actually experience allergic symptoms related to pork consumption.
Interestingly, while alpha-gal allergy patients react to both beef and pork, cross-reactivity to bovine albumin in pork-cat syndrome is variable. Some pork-cat syndrome patients tolerate beef, while others do not. We haven’t routinely advised beef avoidance unless patients report beef-related symptoms. In our study, only one patient (E710) reported beef reactions and was advised to avoid both pork and beef.
Diagnosing Pork-Cat Syndrome
If a patient’s history suggests a possible link between mammalian meat and allergic episodes, we recommend testing for IgE to pork, beef, cat serum albumin, and alpha-gal. This simple panel can help identify patients whose symptoms are likely due to pork-cat syndrome and guide further investigations. In conclusion, this report highlights the first identified US cases of pork-cat syndrome, where sensitivity to cat serum albumin, cross-reacting with pork albumin, causes rapid reactions after pork consumption.
Acknowledgments
These studies were supported by NIH grants: AI-20565, U19-AI-070364, R21-AI-087985, and K08-AI-1085190. Dr. Platts-Mills has a patent related to IgE antibody testing and consults for Viracor/IBT.
Abbreviations
alpha-gal: galactose-α-1,3-galactose
SA: serum albumin
Footnotes
No conflicts of interest reported by other authors.
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