Our French bulldog who is 7 has battled skin/allergy issues since age 1. She has been to the vet on many occasions and we have tried and had temporary success with several things including homemade food, she’s been allergy tested and is allergic to pretty much everything, prescription diets (currently on hydro protein kibble), cytopoint, Apoquel (several years), and most recently on  Zenrelia (1.5 years).  We have also done medicated baths, and she no longer goes for walks outdoors due mostly to having open sores prone to infections. She also seems to prefer to be a couch potato.   
We recently felt Zenrelia was a game changer for her, as she seemed to help more than any of her past treatments. She has had 3 flares in the past 2 years where she gets large open sores. The first two times, she was treated with Prednisolone and antibiotics and responded well. This last time (starting two months ago) she did not respond to two rounds of Prednisolone and antibiotics. She has had swelling and drainage and is uncomfortable and not eating much. She went in last week for cytology and biopsies (lip, feet, belly, arm). So far we have cytology back so we are targeting again with antibiotics, and are waiting on biopsy results. I feel she has likely developed resistance to her treatments after years of issues. I know prescription meds can also suppress her immune system. But it’s a vicious cycle. Has anyone else been in this position long term (5+ years)? I feel horrible for her and know she is uncomfortable. I am also exhausted from worry. I hate putting the cone on her to keep her from causing more damage, but sometimes it’s necessary. She’s been off the Zenrelia (per vet) a week and is itchier than ever. I’ve included pics of her worst spots now. Some shots are pre biopsy and some are post (shaved/stitches). She also has a “fur bumps” that don’t ulcerate which I see often on this forum. 

Lifelong skin issues