Off the top of my head the two possibilities are 1) something food related, or 2) something predatory.
In the fall I lost my brown, over the course of its decline it would look like it was irritated, then it would get better, then irritated again and got better, but eventually starting receding and stopped feeding and that was it - once they stop eating I don't think there's any turnaround. I never really knew why it suddenly stopped doing well after 5 years.
Recently the same thing started up with my green, which I've had for 4 years. This time I noticed something strange, the side that was irritated was actually wounded (I have pictures of what it looked like but I can't find the thread atm - I'll post back when I find it). I surmised that something in the tank was picking on it. I had a cowry in the tank .. I would never see it since it's nocturnal mostly, but I decided to remove it to the sump once I found it (took some doing, but I did find it). And then I decided to start feeding it daily once the flesh didn't look torn. It has been at least a month now and it is finally starting to show signs of recovery. It seems that even if the flesh isn't still torn, it must take an enormous amount of energy to heal internally because it really shrank down at first (down to 50% of its former size, despite the daily feedings). It is only now starting to show signs of growing once again.
So there's my story to support my theory of predation. It can be the strangest things .. I wouldn't have guessed a small cowry could take down a carpet but who knows. Then again, who knows, maybe it's something else still too. I guess the lesson learned is that even if you've had them for a while, something can happen and you can lose them all of a sudden.
The other thing I've heard about (mainly on here in the amemone forum on RC) is people who think it was feeding them a bad silverside or something. Guess we need to be careful about the foods we offer too then.