Not only is there no downside, if you do separate your rare plain italics (say _italic_) from your custom one (*cloze*), you can always come back later at this problem knowing that the information you want to present is preserved.
And I have thought of a possible approach that doesn’t involve altering the Markdown parser. You can run a simple conversion before Markdown runs, turning _italic_ *cloze* into _italic_ <em class=cloze>cloze</em> or to a custom HTML tag. Then when Markdown runs, it will convert the remaining italics blocks for you.
Of course I didn’t know how to do this either, but it seems likely to be simpler and more robust than meddling with the parser. It might be worth pursuing.