D3.313 - Recurrent Anaphylaxis with Elevated Baseline Tryptase Revealing Hereditary Alpha-Tryptasemia with Mast Cell Activation

Background:Recurrent anaphylaxis without an identifiable trigger is a diagnostic challenge requiring exclusion of clonal and non-clonal mast cell disorders. Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait characterized by increased TPSAB1 copy number, elevated baseline serum tryptase, and a broad clinical spectrum that may mimic systemic mastocytosis. This case aims to highlight HαT as an important differential diagnosis in patients with recurrent anaphylaxis and its implications for diagnosis and management.

Case presentation:We report a 56-year-old male with three anaphylactic episodes over two years, characterized by sudden severe epigastric pain followed by generalized pruritus, erythema, and syncope or presyncope. Episodes occurred in distinct contexts, including occupational exposure in a greenhouse and perioperative settings, without consistent exposure to new foods or medications. The patient also reported long-standing gastrointestinal symptoms, including recurrent abdominal pain and epigastralgia. 

Baseline serum tryptase levels were persistently elevated (14.0-16.5 µg/L). During a peri-operative reaction, serum tryptase increased acutely from 16.5 to 23.1 µg/L, fulfilling international criteria for mast cell activation. Bone marrow biopsy, flow cytometry, and molecular analysis showed normal mast cell morphology, absence of aberrant CD2/CD25 expression, and no KIT D816V mutation, excluding systemic mastocytosis.

Tolerance to several anesthetic agents, including fentanyl, propofol, rocuronium, and cefazolin, was confirmed, while other opioids, such as morphine and tramadol, were identified as likely triggers. Genetic testing revealed increased TPSAB1 copy number (3α/2β), confirming hereditary alpha-tryptasemia. The patient showed marked clinical improvement under anti-mediator therapy with H1-antihistamines, leukotriene receptor antagonists, and oral cromolyn sodium. Subsequent surgical procedures using standardized premedication protocols were uneventful.

Conclusion:This case highlights hereditary alpha-tryptasemia as an important diagnosis in patients with recurrent anaphylaxis and elevated baseline serum tryptase. It illustrates the broad clinical spectrum of HαT, including clinically relevant mast cell activation, and underscores the need for targeted anti-mediator therapy and tailored peri-procedural prevention.