A natural red pigment as a hidden allergen in delayed idiopathic anaphylaxis: carmine-induced food allergy

Report: A 56-year-old female experienced 2 anaphylactic reactions after eating chicken tikka masala and after a croissant with wild berries topping. She showed immediate nausea, vomiting and diarrhea followed by urticarial rash and facial edema several hours later. Afterwards, patient had, with exception of the wild berries topping, the same food again but without complaints. Skin and immunoCAP (Thermofisher-Phadia) testing were negative with all food allergens relevant to the history, including Tri a19 and galactose-alpha-1,3-galactose. Idiopathic anaphylaxis was diagnosed and an adrenalin auto-injector was prescribed. Several months later, after performing an urea breath test for Helicobacter pylori with a Fortimel energy strawberry (Nutricia) drink, which contains as potential allergens milk, rape seed oil, sunflower seed oil, soy lecithin and carmine acid, patient experienced immediate epigastric pain followed by dyspnea, facial edema and generalized urticaria. Skin testing with Fortimel energy strawberry was clearly positive (negative in 5 controls) and negative for milk and soy milk. Specific IgE showed positivity for cochineal extract (2.77 kU/L) (retrospective serum analysis one month before: IgE 1.92 kU/L). Flow cytometric analysis of activated peripheral blood basophils (CD63CD123 HLA-DR), including a positive control (anti-IgE), a negative control (without allergen), carmine (Sigma-Aldrich) and fast green (E143), showed clear CD63 positivity after stimulation with carmine and not with fast green (see Figure). This response was absent in the control patient.