Background: The cause for anaphylaxis cannot be identified after extensive evaluation in a large proportion of patients, who are classified as having ‘idiopathic anaphylaxis’ (IA). As food consumption patterns, genetic background, and environmental factors can lead to differences in allergen sensitization patterns in different regions, we sought to identify the aetiology of IA in cohort of Sri Lankan patients. Methods: Of the patients referred to our clinic following anaphylaxis, 65 were recruited as a cause could not be identified. The events that led to the episode of anaphylaxis, the triggers, the severity of symptoms and treatment received were recorded and skin prick test, ISAC ImmunoCAP test and serum tryptase was carried out. Results: Of the 65 patients, 42/65 (64.6%) were females and 49/65 (75.38%) were adults. 46/65 (70.8%) had grade II anaphylaxis and 34/65 (52.3%) were found to have specific IgE to alpha-gal, with symptoms occurring 0.5 to 6 hours since ingestion of food. Of those who had specific IgE to alpha-gal, 12 (35.3%) had consumed red meat and 10 (29.4%) milk products (3 had consumed fermented buffalo milk), before the episode of anaphylaxis. Difficulty in breathing, swelling of lips and syncope was significantly higher in those who were not sensitized to alpha-gal, while diarrhoea and abdominal pain were more common in those sensitized to alpha-gal, although this was not significant. Conclusion: A large proportion of patients presenting with IA were found to be sensitized to alpha-gal, which was the likely cause of their anaphylaxis.

Vascular leak is a hallmark of severe dengue, and high leukotriene levels have been observed in dengue mouse models, suggesting a role in disease pathogenesis. We sought to explore their role in acute dengue, by assessing levels of urinary leukotriene (LTE4) and histamine in patients with varying severity of acute dengue. Urinary LTE4, histamine and creatinine were measured by a quantitative ELISA, in mid-morning urine samples collected from healthy individuals (n= 19) and patients with dengue fever (DF= 72) and dengue haemorrhagic fever (DHF= 48). The kinetics of LTE4 and histamine and diurnal variations were assessed in a subset of patients. Urinary LTE4 levels were significantly higher (p=0.004) in patients who proceed to develop DHF when compared to patients with DF during early illness (≤ 4 days) and during the critical phase (p=0.02). However, LTE4 was not a good predictive marker of DHF as ROCs gave an AUC value of 0.67 (95% CI 0.57 to 0.76), which was nevertheless significant (p=0.002). Urinary LTE4 levels did not associate with the degree of viraemia, infecting virus serotype and was not different in those with primary vs secondary dengue. LTE4, histamine and the viral loads showed a marked diurnal variation in both patients with DF and DHF. Our data suggest that LTE4 could play a role in disease pathogenesis and since there are safe and effective cysteinyl leukotriene receptor blockers, it would be important to assess their efficacy in reducing dengue disease severity.