I am running Windows 10 on external SSD drives in Thunderbolt LaCie "Rugged" enclosures on both 2012 and 2014 iMacs with internal SSDs. I had been running Win 7 and 8 prior to this and did the normal upgrades when available. The only issue I had was with the initial upgrade to Windows 10 on the 2014 iMac which I determined was probably going to require "disconnecting" the internal SSD ... which of course I wasn't going to do. The 2012 oddly didn't have this issue.
To solve it, I temporarily moved my Windows installation to a BootCamp created partition on the internal SSD using WinClone. The Windows 10 upgrade then ran without a problem. Once everything was stable again, I again used WinClone to move the installation back to the external Thunderbolt SSD and deleted the BootCamp partition returning the space back to OS X.
Both iMac Windows on external SSDs have been operating normally ever since, and the updates and upgrades have not been a problem. On both systems, I also use the bootable Windows installation as a Virtual Machine under VMware Fusion in OS X and that too is working fine.