Some of these helper programs like Mod Organizer do very odd things (write protecting .ini files, changing DLL search paths etc.). Please do not use them to avoid potential issues. SKSE alone shouldn’t be a problem, but since it also hooks into the game similar to vorpX there’s always a chance that it breaks things with some mod.
If you use mods and experience problems, remove all of them and add them back one by one to check which mod may cause an issue.