D1.230 - Efficacy and Safety of Hymenoptera Venom Immunotherapy in a Patient with Systemic Mastocytosis

Background: Systemic mastocytosis (SM) is a major risk factor for severe systemic reactions to Hymenoptera venom (HV). Patients with SM have an increased prevalence of HV allergy and frequently present severe anaphylaxis, often without cutaneous manifestations. Severe reactions associated with persistently elevated baseline serum tryptase warrant investigation for SM, as this diagnosis has important prognostic and therapeutic implications, including consideration of prolonged or lifelong venom immunotherapy (VIT).

Case Presentation: A male patient living in a rural area, employed in quality control and engaged in beekeeping as a hobby, was referred in 2015 for evaluation of anaphylaxis after two honeybee stings. Approximately 25 minutes post-sting, he developed abdominal cramps, nausea, vomiting, headache, hand paresthesia, dyspnea, and presyncope, without cutaneous symptoms. Previous stings had been tolerated. Physical examination revealed light-brown macules on the upper chest with a positive Darier’s sign.

Skin prick tests to honeybee venom were negative, whereas intradermal testing was positive (0.1 µg/mL). Tests to vespid venoms were negative. Total IgE was 9.74 kU/L, and specific IgE to honeybee venom was 1.24 kU/L. Baseline serum tryptase was elevated (28.6 µg/L; repeat 34.9 µg/L).

Bone marrow biopsy demonstrated multifocal mast cell aggregates (>15 mast cells per cluster), with >60% atypical spindle-shaped mast cells and aberrant CD2 and CD25 expression. Cutaneous biopsy was consistent with urticaria pigmentosa. SM was diagnosed according to WHO criteria (one major and three minor criteria).

Honeybee VIT was initiated using a conventional protocol with antihistamine premedication. Despite the known increased risk of systemic reactions during VIT in patients with SM, treatment was remarkably well tolerated, with no adverse events during up-dosing or maintenance. Over approximately 10 years of follow-up, the patient experienced multiple accidental re-stings without any systemic reactions, demonstrating sustained clinical protection. Given the coexistence of SM and ongoing high occupational exposure, lifelong VIT was recommended.

Conclusion: This case underscores the importance of measuring baseline serum tryptase and actively investigating SM in patients with severe HV-induced anaphylaxis, particularly in the absence of skin symptoms. Importantly, it provides further real-world evidence that VIT can be both safe and highly effective in patients with SM when performed in specialized centers, supporting prolonged or lifelong treatment in high-risk individuals.