This dev-blog article from 2015 pretty-much admits that it's all done manually: https://web.archive.org/web/20151108110741/http://bindingofi...

> now as some of you know, item combos have to be hard coded at this point due to how nutty some of the tears are in rebirth. the most requested update you guys wanted in afterbirth was item combos, so the team has been hard at work the past few weeks mostly focusing on said combos.