[[ As far as I know, we’re never told in canon. 

Given nothing is mentioned about him being sick pre-massacre, we can only assume it’s something that happened during his time in Akatsuki, and rapidly began shortening his life.  There’s a super good theory about what he has, but in the end it’s just a theory. (a game theory….)

Here’s the page I have on it. 

At the best I’d assume it’s the stress that went into working for Akatsuki. He pushed his body too hard. His guilt might have made his body weaker, too. 

I believe in the Jinraiden volume, it’s mentioned that Itachi went to a special village to get his medications. I should read that and see what else about his illness is mentioned. ]]