I get this on one of my secondary clients somewhat often, but not the other. The fix for me is to manually click the button with the trinket macro which unlocks the key and lets me use ESC again.

Another side effect of this problem is that you can't activate items in the game, like open up a box or click on a portal (anything with the gear icon). Instead when you right click to open, it turns your cursor into the hand icon with a blue highlight (like the cursor you get when you disenchant something).