How to evaluate an unexplained positive ANA in a patient with nonspecific arthralgias?
• History and physical examination: Listen for symptoms and look for objective signs of a connective tissue disease, particularly occult Sjögren’s syndrome.
• Obtain an ANA profile: ANA titers ≥ 1:160 or the presence of disease-specific autoantibodies usually indicates that the ANA is significant.
• Consider testing for anti-DFS70 antibodies. This antibody is against a coactivator of nuclear transcription and is a recognized cause of a positive ANA in healthy individuals. Therefore, if this is the only autoantibody present, the patient is unlikely to have an autoimmune disease as the cause of the positive ANA.
• Obtain additional studies looking for evidence of immune hyperactivity and/or organ involvement:
• Complete blood count: Look for anemia of chronic disease, neutropenia, and thrombocytopenia.
• Liver enzymes: If elevated, consider autoimmune hepatitis.
• Creatinine, urinalysis: look for evidence of end-organ disease which, if present, would warrant an expedited evaluation.
• C3, C4: Look for hypocomplementemia.
• Consider measuring cell-bound complement activation products (CB-CAPS) in patients with normal complement levels. The presence of an elevated CB-CAPS is consistent with complement activation and may suggest SLE as the cause of the positive ANA.
• SPEP: Look for polyclonal gammopathy.
• RF, ESR, VDRL (false-positive), PTT (lupus anticoagulant).
If any of these are abnormal, the ANA may be indicative of an evolving autoimmune disease and the patient will need to be followed closely. Note that a history of Hashimoto’s thyroiditis can be associated with a positive ANA with negative specific autoantibodies.