Abstract
Overlap syndromes are inflammatory rheumatic conditions in which patients have clinical manifestations suggestive of multiple distinct immune diseases. The diseases most commonly involved in overlap syndromes include rheumatoid arthritis, lupus, scleroderma, and myositis. The most well-characterized overlap syndrome, mixed connective tissue disease (MCTD), is defined by anti-RNP autoimmunity along with features of at least two of these four conditions, and very often includes sufficient lupus manifestations to fulfill the SLICC lupus classification criteria. Overlap syndromes are generally less common than the conditions they encompass; the prevalence of MCTD, for example, is approximately one-twentieth that of SLE. Some autoantigen systems are particularly linked with overlap syndromes, such as RNP in MCTD. Overlap syndromes provide unique opportunities to understand links between autoimmunity and end organ immune targeting. While insights can be extrapolated from studies of disease processes present in overlap, few treatment trials have focused specifically on overlap syndromes themselves.