Hymenoptera venom allergy:Challenges in diagnosis and treatment

This thesis gives an overview of some of the main challenges and controversies in the understanding, diagnosis, and treatment of insect allergy and provides a practical guidance for clinical decision-making. A special focus is given to patients with concurrent indolent systemic mastocytosis (ISM) because these patients are at particular risk for severe anaphylactic sting reactions. The first part of the thesis addresses the diagnostic challenges in patients at risk for allergic reactions to insect stings. In chapter 2, the diagnostic sensitivity of yellow jacket venom extract is improved by spiking the extract with recombinant allergen Ves v 5. Chapter 3 demonstrates a lower diagnostic sensitivity of specific IgE to yellow jacket venom in patients with ISM and proposes an adjusted reference value for these patients. Chapter 4 shows that methylimidazole acetic acid in urine is a better predictor for the need of a bone marrow biopsy in older overweight ISM-suspected subjects than serum tryptase. The second part of the thesis addresses challenges in the treatment of patients at risk for allergic reactions to insect stings. Chapter 5 gives a first indication that venom immunotherapy (VIT) initiation at the maintenance dose might prove to be a safe, time efficient and cost-effective option for selected patients in the future. Chapter 6 demonstrates that successful VIT relates to duration of therapy, type of venom, and venom dose. Adult-onset cutaneous mastocytosis and/or a basal serum tryptase >20 μg/L, allergic reactions during VIT, and ACE-inhibitor medication at the time of the sting challenge increase the risk of VIT failure