IGHE and osteoarthritis: We propose a model wherein IgE-mediated mast cell activation via FcεRI and Syk which results in mast cell degranulation and the release of pro-inflammatory and degradative mediators, including tryptase, leads to cartilage and joint breakdown. This results in a vicious cycle of tissue damage, inflammation, and unchecked mast cell activation, and thus causes the development and progression of osteoarthritis.