Essentials in Rheumatology: Disease Management * I29. Recognition and Management of the Auto-Inflammatory Diseases

Historically immunology was considered to be the science of self–non-self discrimination and inflammation against self was invariably considered in relationship to B and T cell tolerance failure. Indeed the classical autoantibody associated autoimmunity paradigm, that sometimes powerfully manifests as fulminant lupus-related thrombosis, for example, attests to the veracity of the autoimmunity concept that underpins much of rheumatology practice. However, non-infectious inflammation against self was suspected not to be exclusively within the realms of autoimmunity, but until recently a clearly defined concept of what exactly this represented did not exist. The teaching of immunology commences with the fact that the immune system is composed of an innate and an adaptive arm and that these are ultimately functionally integrated. Over a decade ago the word autoinflammation was used to describe rare monogenic disorders including familial mediterranean fever (FMF) and TNF-associated peroidic fever syndrome (TRAPS) where the inflammation was not onstensibly linked to autoimmunity. Recognizing that perturbation of immune responses could equally be dependent on aberrant innate immunity we defined autoinflammmation as the diametric opposite boundary to autoimmunity where disease is driven by intrinsic perturbation of the non-immune cells of the target tissues or the innate immune populations that patrol these sites [1]. The innate immune-dependent or autoinflammatory disorders have clinical phenotypes distinct from those of autoimmunity and at the molecular level often converge on key cytokines such as IL-1 or TNF. The purpose of this talk is to show how autoinflammation can be recognized based on clinical features, serology and genetics. It also shows how diseases that were formerly designated as autoimmune may in some cases be autoinflammatory at disease inception. Diseases that are intermediate between autoinflammation and autoimmunity will be briefly touched on. The proper clinical designate of autoinflammation is key for treatment strategies. Thus far, many of the autoinflammatory diseases have shown a remarkable response to strategies of IL-1 antagonism. Illustrative cases including those where a clear diagnosis was not initially evident will be used to show treatment strategies. Disclosures: Reference 1. McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med 2006;3:e297.