Contributions of the study
This study adds to the current knowledge about HAE prodromes and their importance as attack-predicting harbingers. It presents a new robust, sensitive and specific instrument that employs the attributes of prodromes, its expressions, typology, consistency and power to predict the occurrence of attacks. Early detection of impending attack is expected to assist in clinical decision-making regrading the timing of an early response (”prodrome-triggered intervention”) expected to shorten or avert the attacks. The study findings can be applied to similar conditions with relapsing-remitting patterns, whose attacks are also antedated by prodromes. 25-28 A similar approach was recently employed in the treatment of acute Familial Mediterranean Fever (FMF) attacks by Babaoglu et al. 29 This strategy can improve the patients’ self-management skills and contribute to improved quality of life. The newly developed PRO instrument can be used to alert patients to approaching attacks and allow fast deployment of therapeutic strategies to preempt the attack. It can be used by HAE patients worldwide as an internet-based application after cross-cultural translation and validation, to monitor prodromes and attacks over time, transmit real-time data, obtain treatment directions and communicate with the medical staff. 30 We propose to include prodrome reports in disease registries data and management guidelines of diagnosis and treatment of HAE.31-33