Successful introduction of peanut in sensitized infants with reported reactions at home.

BACKGROUND AND OBJECTIVE: Previous studies have shown efficacy of early introduction of peanut to prevent peanut allergy. It is currently unknown which diagnostic pathway is optimal after parental-reported reactions to peanut at home after early introduction. METHODS: The PeanutNL cohort study included high-risk infants that were referred for early introduction of peanut. A subgroup of 186 infants with reactions to peanut at home underwent peanut skin prick tests and a supervised open oral food challenge (OFC) at a median age of 8 months. After a negative OFC, peanut was introduced at home. RESULTS: Sensitization to peanut was detected in 69% of 186 infants, of which 80% had > 4mm wheals in skin prick tests. An OFC with a cumulative dose of 4.4 gr peanut protein was performed in 163 infants with Sampson severity score grade I-III reactions at home; 120 challenges were negative. Peanut was subsequently introduced at home in infants with a negative challenge outcome. After 6 months, 96% were still eating peanut and 81% ate single portions of 3.0 gr peanut protein. One patient was considered to be peanut allergic after reintroduction of peanut at home. CONCLUSION: These data show that 65% of infants with reported reactions to peanut at home have negative OFCs. In those children, peanut could be introduced safely and 96% were able to consume peanut regularly without reactions. Challenging infants under 12 months of age prevents the misdiagnosis of peanut allergy, and enables safe continued exposure to peanut and the induction of long-term tolerance.

Serum proteomics reveals hemophagocytic lymphohistiocytosis-like phenotype in a subset of patients with multisystem inflammatory syndrome in children.

Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children.

Introduction of Heated Cow's Milk Protein in Challenge-Proven Cow's Milk Allergic Children: The iAGE Study.

The introduction of baked milk products in cow's milk (CM) allergic children has previously been shown to accelerate induction tolerance in a selected group of children. However, there is no standardized baked milk product on the market. Recently, a new standardized, heated and glycated cow's milk protein (HP) product was developed. The aim of this study was to measure safety and tolerability of a new, well characterized heated CM protein (HP) product in cow's milk allergic (CMA) children between the age of 3 and 36 months. The children were recruited from seven clinics throughout The Netherlands. The HP product was introduced in six incremental doses under clinical supervision. Symptoms were registered after introduction of the HP product. Several questionnaires were filled out by parents of the children. Skin prick tests were performed with CM and HP product, sIgE to CM and α-lactalbumin (Bos d4), ß-lactoglobulin (Bos d5), serum albumin (Bos d 6), lactoferrin (Bos d7) and casein (Bos d8). Whereas 72% percent (18 out of 25) of the children tolerated the HP product, seven children experienced adverse events. Risk factors for intolerance to the HP product were higher skin prick test (SPT) histamine equivalent index (HEP) results with CM and the HP product, higher specific IgE levels against Bos d4 and Bos d8 levels and Bos d5 levels. In conclusion, the HP product was tolerated by 72% of the CM allergic children. Outcomes of SPT with CM and the HP product, as well as values of sIgE against caseins, α-lactalbumin, and ß-lactoglobulin may predict the tolerability of the HP product. Larger studies are needed to confirm these conclusions.

Concentration and avidity of anti-Haemophilus influenzae type b (Hib) antibodies in serum samples obtained from patients for whom Hib vaccination failed.

Haemophilus influenzae type b (Hib) conjugate vaccines are extremely effective in protecting infants and children from invasive Hib infections; however, vaccine failures do occur. The anti-Hib antibody production was studied both quantitatively and qualitatively in 12 patients who experienced Hib failure, all of whom had normal serum immunoglobulin concentrations and all of whom were without clinical risk factors for invasive Hib disease. Both anti-Hib antibody concentration and immunoglobulin-G2 anti-Hib antibody avidity were significantly lower in patients who experienced Hib failure, at onset of disease and after reconvalescence, when compared with controls. This finding suggests that the patients who developed invasive Hib disease--despite having received 3-4 Hib conjugate vaccinations--were inadequately primed by these vaccinations.