Australian anaphylaxis fatality rates (most causes) have increased over the last 16 years, contrasting with UK- and US-based studies that describe overall lower and static overall anaphylaxis fatality rates (0.047-0.069/10(5) population).

A large number of patients use the Internet to find information that influences their attitudes to health care. The services of a medical informatics professional would likely benefit both patients and doctors.

Cutoffs (decision points) of the peanut skin prick test (SPT) and specific IgE level for predicting peanut allergy have been proposed. It is not known whether decision points indicating a significant risk of severe reactions on challenge differ from those indicating probable allergy. We aimed at determining the usefulness of allergy tests for predicting the risk of anaphylaxis on challenge following the ingestion of up to 12 g of peanut in peanut-sensitized children. Children attending the Allergy Clinic who had a positive peanut SPT and completed open-label in-hospital peanut challenges were included. The challenge protocol provided for challenges to be continued beyond initial mild reactions. Eighty-nine in-hospital peanut challenges were performed. Thirty-four were excluded as the challenge was not completed, leaving 55 for analysis. Children who completed the challenge and did not react (n = 28) or reacted without anaphylaxis (n = 6) represented the comparison group (n = 34). The study group comprised 21 children whose challenge resulted in anaphylaxis. The mean peanut SPT wheal size and specific IgE level were associated with the severity of reactions on challenge. Among the 21 children, who developed anaphylaxis, in only 3 cases was anaphylaxis the initial reaction. Unexpectedly, a history of anaphylaxis was not predictive of anaphylaxis on challenge. Anaphylaxis developed at cumulative doses of peanut ranging from 0.02 to 11.7 g. Provided that a fixed amount of peanut is ingested, available tests for peanut allergy may assist in predicting the risk of anaphylaxis during challenge in peanut-sensitized children.

BackgroundMutations in the gene encoding stimulator of interferon genes (STING) underlie a type I interferon (IFN) associated disease, STING-associated vasculopathy with onset in infancy (SAVI). Patients suffer cutaneous vasculopathy and interstitial lung disease, but are not known to suffer life-threatening infection.CaseWe describe a child who presented with Pneumocystis jirovecii pneumonia in early life, from which he recovered. He went on to suffer failure to thrive, developmental delay, livedo reticularis, and vesicular rash, but without cutaneous vasculitis, and with normal C-reactive protein and erythrocyte sedimentation rates. At 3 years of age, he developed life-threatening pulmonary hypertension.MethodsWhole genome sequencing (WGS) was performed using the Illumina HiSeqX10 platform and the Seave platform was used for bioinformatic analysis. mRNA expression of IFN-stimulated genes and inflammatory cytokines from peripheral blood mononuclear cells was determined by quantitative polymerase chain reaction. Luciferase assay was used to model IFNβ and NF-κB activity in vitro.ResultsWGS revealed a de novo mutation p.Arg284Ser in STING at an amino acid previously associated with SAVI. Although this mutation did not fall in the dimerization domain (DD), mRNA analysis revealed constitutive IFN-gene activation consistent with an interferonopathy, which correlated to STING activation in vitro. The patient was treated with corticosteroids and the JAK inhibitor Ruxolitinib, resulting in a rapid improvement of pulmonary hypertension, general well-being, and resolution of the IFN gene signature. However, he did go on to evolve a nasal septal erosion suggesting incomplete control of disease.ConclusionThis case provides molecular evidence to support the p.Arg284Ser variant in STING exerting pathogenicity through a gain-of-function mechanism. The lack of cutaneous vasculitis or elevated systemic inflammatory markers, and the occurrence of an opportunistic infection are notable, and raise the possibility that variants outside the STING DD may potentially manifest with an atypical SAVI phenotype. Nevertheless, there was an objective clinical improvement in response to JAK inhibition.