In AE-ACEI this prolonged drug latency raises the question of whether there is an additional factor/second hit event in the late presenters which i) either effects other enzymes that metabolise bradykinin, such as neprilysin, or aminopeptidase P, ii) may represent another factor that leads to increased flux through the bradykinin pathway, potentially even at the tissue-level, or iii) represents the onset of a chronic urticaria/angioedema variant independent of AE-ACEI. This evidence concerns the gene MME and angioedema.