Belgian Case Series Identifies Non-Cow Mammalian Milk Allergy as a Rare, Severe, Selective, and Late-Onset Condition

Background: Cow's milk allergy (CMA) is the most common food allergy in children, typically resolving by adolescence. In contrast, the clinical spectrum of allergies to non-cow mammalian milk and their patterns of IgE cross-reactivity are less well documented. Nutritional differences between various mammalian milks may also impact dietary management in milk-allergic patients. Objectives: To characterize clinical features, onset age, and IgE cross-reactivity patterns of non-cow mammalian milk allergies in adult patients seen at a tertiary allergy center, and to compare these findings with published cases. Methods: A retrospective analysis of patients included in the "Extended Laboratory Investigation for Rare Causes of Anaphylaxis study" with mammalian milk allergy was performed using clinical history, skin testing, and serum-specific IgE measurements. Cross-reactivity patterns were assessed in selected cases using immunoblotting, specific IgE inhibition, and basophil activation testing, and compared with published reports of non-cow mammalian milk allergy. Results: In our case series of 22 patients with mammalian milk allergy and 10 healthy control subjects, 3 patients were identified with isolated adult-onset non-cow mammalian milk allergy (n = 1 buffalo milk; n = 2 mare milk), confirmed via immunoblotting and basophil activation testing. Streptavidin-based specific IgE measurement for buffalo cheese was positive in the buffalo milk allergic patient. The literature review identified 82 cases of non-cow mammalian milk allergy. These cases typically showed late onset (mean age 8.6 years; range 1-70 years), severe reactions (CoFAR (Consortium for Food Allergy Research) grade 3 or 4 in 66%, and one fatality), and selective sensitization (affecting sheep and/or goat, camel, mare, buffalo, donkey, or combinations thereof in 56, 10, 5, 5, 4, and 2 cases, respectively). Conclusions: Non-cow mammalian milk allergies are rare but generally present later in life with selective IgE cross-reactivity, differing from the broader cross-reactivity observed in CMA. This selectivity may allow for safe dietary alternatives. These findings underscore the need for improved diagnostics and personalized dietary management in this patient population.