001679 - Alpha-gal sensitization as a cause of allergy to heparins and collagen

Sensitization to galactose-α-1,3-galactose (alpha-gal) is an IgE-mediated allergy to an oligosaccharide present in non-primate mammalian tissues. Although classically associated with allergic reactions to mammalian meat ingestion and cetuximab, alpha-gal may also be present in other products containing mammalian-derived components, such as gelatins, collagen, and low-molecular-weight heparins derived from porcine intestinal mucosa.

We describe the case of a patient with several episodes of anaphylaxis triggered by different foods and drugs, all attributable to alpha-gal sensitization.

A 62-year-old male on chronic anticoagulant therapy developed an episode of anaphylaxis 20 minutes after ingestion of hydrolyzed collagen, characterized by generalized urticaria, facial angioedema, vomiting, diarrhea, uvular edema, and elevated tryptase levels. He reported a history of cutaneous and gastrointestinal symptoms after ingestion of beef and pork, as well as episodes of abdominal pain and diarrhea occurring hours after bemiparin administration. He also reported multiple tick bites throughout his life.

The allergological work-up included skin testing: prick tests with foods and meats; prick and intradermal tests with heparins and fondaparinux; prick tests with hydrolyzed collagen and cetuximab; measurement of total and specific IgE, and baseline serum tryptase. A controlled subcutaneous challenge with an alternative low-molecular-weight heparin was performed.

Positive skin prick tests were observed with cetuximab and hydrolyzed collagen. Intradermal tests were positive with sodium heparin, enoxaparin, bemiparin, and dalteparin, and negative with fondaparinux and tinzaparin. Baseline tryptase was 8.10 ng/mL. Total IgE was 327 kUA/L; specific IgE to beef 32.2 kUA/L, pork 16.9 kUA/L, lamb 12.5 kUA/L, and alpha-gal 81.9 kUA/L. Administration of tinzaparin at a dose of 3,500 IU was well tolerated, confirming it as a safe alternative.

Alpha-gal sensitization may trigger hypersensitivity reactions to drugs containing this oligosaccharide, such as low-molecular-weight heparins. Identification of these hidden sources enables accurate diagnosis, prevention of severe reactions, and selection of safe therapeutic alternatives.