Similar pathophysiological mechanisms within autoimmune diseases have stimulated searches for common genetic roots. Polyautoimmunity is defined as the presence of more than one autoimmune disease in a single patient. When three or more autoimmune diseases coexist, this condition is called multiple autoimmune syndrome (MAS). We analyzed the presence of polyautoimmunity in 1,083 patients belonging to four autoimmune disease cohorts. Polyautoimmunity was observed in 373 patients (34.4%). Autoimmune thyroid disease (AITD) and Sj？gren's syndrome (SS) were the most frequent diseases encountered. Factors significantly associated with polyautoimmunity were female gender and familial autoimmunity. Through a systematic literature review, an updated search was done for all MAS cases (January 2006–September 2011). There were 142 articles retrieved corresponding to 226 cases. Next, we performed a clustering analysis in which AITD followed by systemic lupus erythematosus and SS were the most hierarchical diseases encountered. Our results indicate that coexistence of autoimmune diseases is not uncommon and follows a grouping pattern. Polyautoimmunity is the term proposed for this association of disorders, which encompasses the concept of a common origin for these diseases. 1. Introduction Autoimmune diseases (ADs) have particular clinical characteristics and phenotypes depending on their nature (i.e., organ specific or systemic diseases). However, there is strong evidence that ADs share several clinical signs and symptoms, physiopathological mechanisms, and environmental and genetic factors, and this fact indicates that they have a common origin [1], which has been called the autoimmune tautology. The clinical evidence of the autoimmune tautology highlights the cooccurrence of distinct ADs within an individual (i.e., polyautoimmunity) [1]. In an earlier paper, we described the foremost systematic literature review grouping all published cases of multiple autoimmune syndromes (MAS), defined by the presence of three or more well-defined ADs in a single patient, up until 2006. Initially, MAS was first mentioned by Pirofsky and Vaughn [2] and deeply described by Humbert and Dupond [3]. They provided a taxonomy for the cooccurrent phenotypes [4, 5]. MAS together with polyglandular autoimmune syndromes (PAS) II through IV, which are all MAS, represent the best example of polyautoimmunity [4]. Three basic, large clusters were found. Each of them had a predominant disease that was named the “chaperones” of autoimmunity, namely, autoimmune thyroid disease (AITD), Sj？gren’s
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