D3.322 - Successful management with Omalizumab and high-dose venom immunotherapy in a patient with Kounis Syndrome and Clonal Mast Cell Activation Syndrome

Background: Hymenoptera venom allergy can present with severe systemic reactions, including Kounis Syndrome. Management is challenging when patients remain unprotected despite conventional venom immunotherapy (VIT), especially with underlying clonal mast cell disorders.

Methods: We present the case of a 48-year-old male with no previous cardiac history who suffered a grade IV anaphylactic reaction after a bee sting, presenting with loss of consciousness and chest pain. Emergency electrocardiography showed ST-segment elevation in the inferior leads, with normal coronary arteries on catheterization, confirming type I Kounis syndrome. An allergological work-up included skin tests, serum specific IgE to Apis mellifera, basal serum tryptase, REMA score calculation, and bone marrow studies.

Results: Skin tests and serum specific IgE to Apis mellifera were positive. Basal serum tryptase levels were within normal range (7.4–9.8µg/L). However, the REMA score was 4. Bone marrow analysis revealed 0.002% clonal mast cells (CD2+/CD25+), leading to a diagnosis of clonal mast cell activation syndrome (cMCAS). The patient started VIT with Apis mellifera (100µg). After one year, a controlled re-sting test was positive, causing a severe systemic reaction with neurological involvement suggestive of cerebral vasospasm, indicating VIT failure. Treatment was intensified by increasing the VIT dose to 200 µg and adding omalizumab (300mg every 4 weeks). Following this intensification, specific IgG4 levels to Apis mellifera rose significantly from 0.04 mgA/l to 11.60 mgA/l.  In September 2025, a new controlled re-sting test performed in the intensive care unit was negative, demonstrating complete clinical protection.

Conclusions: This case highlights the importance of screening for clonal mast cell disorders in patients with severe Hymenoptera venom anaphylaxis, even when basal tryptase levels are normal. Adjuvant therapy with omalizumab combined with high-dose VIT proved to be a successful strategy for achieving protection in a high-risk patient with previous Kounis syndrome and refractory cMCAS.