Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study.

BACKGROUND: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed. OBJECTIVE: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies. METHODS: The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63+ basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed allergic status in a blinded fashion to develop a generalizable statistical model for comparison to extract and marker allergen-specific IgE. RESULTS: A mixed effect model integrating BAT results for 10 and 100 ng/mL of peanut and individual tree nut extracts was optimal. The area under the ROC curve (AUROC) was 0.98 for peanut, 0.97 for cashew, 0.92 for hazelnut, 0.95 for pistachio, and 0.97 for walnut. The BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut (AUROC 0.95, 0.94, 0.92) in a sub-analysis in sensitized patients undergoing OFC. CONCLUSIONS: Basophil activation test can predict allergic clinical status to peanut and tree nuts in multi-nut-sensitized children and may reduce the need for high-risk OFCs in patients.

Prospective evaluation of testing with baked milk to predict safe ingestion of baked milk in unheated milk-allergic children.

BACKGROUND: Cow's milk allergy is one of the most common food allergies affecting young children. A subset of milk-allergic individuals can eat baked milk without allergic symptoms which is beneficial in terms of prognostication and liberalization of the diet. A retrospective study suggested that skin prick testing (SPT) with a baked milk (muffin) slurry may provide a sensitive means of predicting the outcome of a medically supervised baked milk oral food challenge. We evaluated the predictive value of SPT with baked milk to identify unheated milk-allergic children who are able to safely eat baked milk. METHODS: Children aged 2-16 years with a prior history of reaction to milk and a milk extract SPT of 8-14 mm were recruited. Investigator-blinded SPT to muffin slurry and powdered milk in triplicate and specific IgE (sIgE) to casein and milk were performed. Graded oral challenge to egg-free baked milk muffins (total 2.6 gm milk protein) was performed in the hospital. Reliability of tests was analyzed for intraclass correlation. Statistical significance for clinical characteristics of population and muffin testing versus baked milk reactivity was calculated with Fisher exact test for dichotomous and t-test for continuous variables. Wilcoxon rank sum test was used to compare immunological characteristics between individuals who tolerated or reacted to baked milk. Fitted predicted probability curves and ROC curves were generated. RESULTS: Thirty-eight children were consented and 30 met study criteria. The muffin SPT and casein sIgE were significantly different in those who passed versus failed baked milk challenge. Negative (<3 mm) baked milk tests were found in 8/30 children (27 %) and were associated with non-reactivity to baked milk (p = 0.01) with a sensitivity of 1 (0.70-1.00). All children with negative SPT for baked milk passed the oral challenge. Specificity was 0.41 (0.19-0.67). The optimal decision point for the muffin SPT was 4 mm and the casein sIgE was 6 kU/L. The powdered milk test was not helpful. CONCLUSIONS: Skin prick testing with a baked milk (muffin) slurry may have a role in clinical practice to identify baked milk tolerance in milk-allergic patients.