Hi Lynne, and thanks for getting back to me.
I can understand why you and your vets are mystified. There is nothing that immediately stands out in my mind as to what could be causing this problem.
Pitting edema is normally secondary to some type of inflammatory process, and as it sounds as if his most recent episode involved a fever, it would appear to be the case for your horse as well.
What comes to mind, and perhaps worthy of some investigation, would be some type of low-lying sepsis, or a bacterial infection in the bloodstream, which can be linked to fever of unknown origin. Diagnosis involves a series of blood samples taken in special tubes, that are then plated out for bacterial culture. It can often be difficult to isolate an organism, but is rewarding when finally achieved. Samples are best taken when there is a fever present and there are no antibiotics present in the bloodstream, so if you decide to pursue this possibility, I would probably wait until the onset of another episode, and then take multiple samples on consecutive days. Once an organism is isolated, an antibiotic sensitivity test can be performed so an appropriate antibiotic can be administered.
I hope this has helped, and please let me know if you have any further questions.
Thanks, XXXXX XXXXX the best!