Recurrent Anaphylaxis Linked to Defensin Sensitization
Key Takeaways
- A case report about one 34-year-old man described 3 grade IV anaphylactic episodes after different meals in October 2022, one year later, and August 2025, with the diagnostic narrative ultimately converging on a defensin-related trigger hypothesis.
- Component-resolved ALEX2 testing showed no increased specific IgE to plant or animal food allergens, but hypersensitivity to inhalant defensins Amb a 4 and Art v 3 was reported, alongside positive native skin prick tests to celery, sunflower seeds, and mango.
- Persistently elevated basal tryptase and KIT D816V raised concern for a clonal mast cell disorder, DAO results and a prolonged histamine wheal left a histamine-related contribution unresolved, MCAS was not confirmed because no acute-phase tryptase was collected, and no further anaphylaxis was reported after the documented management plan.
The reaction history began with fruit mousse in October 2022, followed one year later by herring in cream sauce with a wheat roll, and then an August 2025 barbecue exposure after multiple foods, with potatoes with herbs reported as the last food eaten before symptoms. In the latest event, symptoms began within 20–30 minutes and included burning of the face and tongue, dyspnea, tachycardia, facial swelling, conjunctival hyperemia, vomiting, and loss of consciousness; physical exercise was identified as a cofactor in that episode. The first reaction was treated with intramuscular adrenaline plus intravenous antihistamines, glucocorticosteroids, and fluids, the second with self-administered adrenaline, and the third with adrenaline administered by the patient’s wife, followed each time by roughly 5 hours of emergency department observation without inpatient transfer. No acute-phase tryptase sample was obtained during any of the reactions.
The patient was assessed at the University Hospital in Kraków 3 years after the first reaction and 1 month after the most recent one. Molecular allergy testing with ALEX2 showed no increased specific IgE to plant or animal food allergens, but hypersensitivity to inhalant defensins Amb a 4 and Art v 3 was reported; no detectable specific IgE was found to the evaluated nsLTPs, PR-10 proteins, or profilins, and the article noted a positivity threshold of 0.35 kUA/L while values from 0.1 to 0.35 kUA/L could still be clinically relevant in context. Native skin prick testing showed wheals of 5 × 5 mm for celery, 3 × 3 mm for sunflower seeds, and 5 × 6 mm for mango, while targeted meal-component testing was positive for herring in cream sauce and negative for the wheat roll; prick-to-prick testing with raw and cooked herring was negative, supporting celery as the likely eliciting factor in that episode. In the authors’ interpretation, the combined testing findings supported a defensin allergy diagnosis.
Mast cell-related findings were also present, with basal serum tryptase values of 20.20, 20.60, and 18.80 µg/L against a reference value below 11.4 µg/L, and KIT D816V detected at 0.05% variant allele frequency. The report framed those results as fulfilling 2 minor criteria for systemic mastocytosis and prompting hematologic evaluation including bone marrow biopsy, with TPSAB1 copy number analysis planned, but it did not establish systemic mastocytosis; MCAS also could not be confirmed because acute-phase tryptase was unavailable during reactions. In the same overlapping workup, DAO values were 8.92 U/mL and 5.34 U/mL in the indeterminate range, the histamine-induced wheal remained positive after 50 minutes, and the Histamine 50 approach was described as having uncertain utility. The documented plan included bilastine 2 × 40 mg daily, a low-histamine diet, elimination of celery, mango, peanuts, sunflower seeds, and chestnuts, anaphylaxis education for the patient and family, and 2 adrenaline auto-injectors, after which no further anaphylaxis had been reported.
Clinician Questions
What allergy testing supported a defensin-related trigger in recurrent severe anaphylaxis after different meals?
In this case, ALEX2 showed no increased specific IgE to plant or animal food allergens, but hypersensitivity to inhalant defensins Amb a 4 and Art v 3 was reported, and native skin prick testing was positive for celery, sunflower seeds, and mango.
How was the herring in cream sauce anaphylaxis episode linked to celery rather than herring or wheat?
For the herring in cream sauce episode, native testing was positive for herring in cream sauce and negative for the wheat roll, while prick-to-prick testing with raw and cooked herring was negative; because the sauce contained trace celery, the workup supported celery as the likely eliciting factor in that reaction.
Why was mast cell activation syndrome not confirmed in this recurrent anaphylaxis case despite elevated basal tryptase and KIT D816V positivity?
Basal serum tryptase remained elevated at 20.20, 20.60, and 18.80 µg/L and KIT D816V was detected at 0.05% variant allele frequency, but no acute-phase tryptase sample was collected during any reaction, so the transient rise needed to confirm mast cell activation syndrome was unavailable and the diagnosis was not confirmed.
What management and follow-up were reported after the recurrent anaphylaxis workup?
The reported plan included bilastine 2 × 40 mg daily, a low-histamine diet, elimination of celery, mango, peanuts, sunflower seeds, and chestnuts, anaphylaxis education for the patient and family, and prescription of 2 adrenaline auto-injectors; no further anaphylaxis had been reported after the plan was started.
Recommended Reading
- For more on mast cell disease after recurrent anaphylaxis: Living With Systemic Mastocytosis: Bridging Clinical Decisions and Patient Realities
- For more on KIT D816V in mast cell disorders: Navigating Today and Shaping Tomorrow in ISM: Personalized Strategies With Current and Emerging KIT Inhibitors