Incomplete lupus, undifferentiated connective tissue disease, and mixed connective tissue disease

A significant number of patients who present for rheumatologic evaluation with concerns about having systemic lupus erythematosus (SLE) do not satisfy the classification criteria for this disease. Widespread use of antinuclear antibody (ANA) testing has in part contributed to this phenomenon. Although ANA positivity alone is not necessarily a pathologic condition and is present in a large segment of healthy individuals, concomitant expression of other clinical or immunologic findings heightens concerns. These manifestations might include skin or joint abnormalities as well as autoantibodies that are more specific for SLE or other diseases. Some of these patients may be classifiable with another disorder, whereas others may have overlap syndromes with features of two distinct conditions. Still, many do not fit any classifiable condition and have undifferentiated connective tissue disease (UCTD) or subsets of this designation, such as latent or incomplete lupus erythematosus (ILE). Despite the many years that have elapsed since terms like UCTD and ILE have been used, significant uncertainty in diagnosis and prognosis remains. This chapter will consider both the unclassifiable syndromes of UCTD and ILE as well as mixed connective tissue disease, for which classification criteria exist.