- D1.533 - Systemic mastocytosis despite normal baseline tryptase: a diagnostic pitfall in recurrent life-threatening anaphylaxis

Background:

Systemic mastocytosis (SM) is usually suspected in patients with recurrent anaphylaxis and elevated baseline serum tryptase>20 µg/L. However, normal baseline tryptase does not exclude clonal mast cell disease and may delay diagnosis.

Case: A 48-year-old man presented with syncope, hypotension (blood pressure 88 mmHg), tachycardia, and transient oxygen desaturation initially occurring during physical exercise. The patient was initially evaluated for suspected cardiac syncope and  a comprehensive cardiologic investigations was performed, including coronary angiography, cardiac MRI, exercise testing, telemetry monitoring, pulmonary angiography , all without pathological findings. Acute serum tryptase during reaction was markedly elevated (45 µg/L). Based on the temporal association with physical activity, food-dependent exercise-induced anaphylaxis was suspected.

However, subsequent episodes occurred without exercise and with similar clinical presentation, including hypotension and elevation of acute serum tryptas (33 µg/L). Baseline tryptase was repeatedly normal (9.1–9.3 µg/L). Allergy work-up, including omega-5 gliadin testing and multiplex component diagnostics, did not identify a causative allergen. Given recurrent anaphylaxis with documented mast cell activation and no clear trigger, the patient was referred to hematology for further evaluation. A molecular testing was pursued despite normal baseline tryptase. Quantitative PCR confirmed a KIT D816V mutation in peripheral blood (allele burden 0.1%), establishing clonal mast cell disease, with subsequent bone evaluation revealing osteopenia not requiring treatment at present. The patient is treated with maximal dose antihistamines, carries an adrenaline auto-injector and undergoes annual follow-up.

Conclusion:

Systemic mastocytosis may initially mimic exercise-induced anaphylaxis and can present with normal baseline tryptase. In patients with recurrent anaphylaxis with significant acute tryptase elevation, an underlying clonal mast cell disorder may be considered, particularly when cardiological and allergologic evaluations are inconclusive.