Biphasic, Refractory, and Persistent Anaphylaxis in Children

A Delphi consensus report refined anaphylaxis phenotypes as biphasic, refractory, and persistent anaphylaxis (BA, RA, and PA). To date, no study in either pediatric or adult populations has comprehensively evaluated the full spectrum of anaphylaxis phenotypes as outlined in this consensus. The primary aim of this study was to identify these phenotypes and compare them with conventional anaphylaxis in children.

Patients aged ≤ 18 years who were diagnosed with or followed up for anaphylaxis at our department over the past 15 years were retrospectively screened for this study. All anaphylaxis cases were categorized as conventional anaphylaxis (Group 1) or as BA, RA, and PA phenotypes (Group 2). A comparative analysis was conducted between Group 1 and Group 2 with respect to demographics, triggers, clinical features, severity, management, and outcomes.

A total of 393 patients and 529 anaphylaxis episodes were included. Twenty-six (6.6%) of all anaphylaxis cases were classified as BA (3.5%), RA (1.5%), or PA (1.5%). For BA, the median time to recurrence of symptoms and signs was 4 h (1-24 h), whereas the median duration of PA manifestations was 4 h (4-6 h). These phenotypes (Group 2) were more common in older children and were associated with increased cardiovascular manifestations, greater severity, and higher use of systemic corticosteroid (p < 0.001). They did not differ significantly from Group 1 with respect to gender, comorbidities, family history of atopy, timing or location of the anaphylaxis, or number of episodes. Drugs, followed by venoms, were more frequent triggers in Group 2, whereas food was significantly more common in Group 1 (p < 0.05). IM adrenaline was administered in 69.2% of Group 2 and 52.3% of Group 1, with no significant difference (p > 0.05). Comparisons among BA, RA, and PA could not be performed due to the limited sample size within each phenotype.

BA, RA, and PA are rare anaphylaxis phenotypes, more frequently drug or venom induced, seen at older ages, with ongoing gaps in proper IM adrenaline use.