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Testing for antinuclear antibody (ANA) and extractable nuclear antigen (ENA) should be avoided in the investigation of widespread pain or fatigue alone. Instead, testing should be performed only in patients suspected to have a diagnosis of a connective tissue disease (e.g., lupus, rheumatoid arthritis). ANA positivity can be as high as 20% in patients with nonrheumatic conditions and healthy individuals. For this reason, proper pretest probability is important, and false-positive results may lead to further unnecessary testing. Repeat testing is also not recommended unless the clinical picture changes significantly.