Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (721 page)

   Antibodies to a host of azurophilic granule proteins can cause a pANCA staining pattern; these include antibodies directed against lactoferrin, elastase, cathepsin G, bactericidal permeability inhibitor, catalase, lysozyme, β-glucuronidase, and others. A positive pANCA IFA staining pattern may also be detected in a wide variety of inflammatory illnesses and has a low specificity for vasculitis.

   Individuals with ANA frequently have “false-positive” results on ANCA testing by IFA.

   Certain medications may induce forms of vasculitis associated with ANCA. The strongest links between medications and ANCA-associated vasculitis are with drugs employed in the treatment of hyperthyroidism: propylthiouracil, methimazole, and carbimazole. Hydralazine and minocycline are less commonly associated with the induction of ANCA-associated vasculitis. Other implicated drugs include penicillamine, allopurinol, procainamide, thiamazole, clozapine, phenytoin, rifampicin, cefotaxime, isoniazid, and indomethacin.

   Using IFA and ELISA testing in a sequential fashion substantially increases the positive predictive value of an ANCA assay.

   Elevations in the titers of ANCA do
not
predict disease flares in a timely manner. If a patient was ANCA positive during a period of active disease, a persistently ANCA-negative status is consistent with, but not absolutely a proof of, remission.

   ANCA testing should not be used to screen nonselected patient groups where the prevalence of vasculitis is low. These tests are most valuable when selectively ordered in clinical situations where some forms of ANCA-associated vasculitis are seriously considered.

   A negative ANCA result should not be used to exclude disease.

ANTINUCLEAR ANTIBODY (ANA)

   Definition

   ANAs refer to a diverse group of antibodies that target nuclear and cytoplasmic antigens. ANAs have been detected in the serum of patients with many rheumatic and nonrheumatic diseases as well as in patients with no definable clinical syndrome. The strong association of ANA with SLE is well established, and this finding satisfies the 1 of 11 criteria available for diagnosis.

   These autoantibodies may be useful as an aid in the diagnosis of systemic rheumatic diseases such as SLE, mixed connective tissue disease (MCTD), undifferentiated connective tissue disease, Sjögren syndrome, scleroderma (systemic sclerosis), polymyositis, and others. The diagnosis of a systemic rheumatic disease is based primarily on the presence of compatible clinical signs and symptoms. The results of tests for autoantibodies, including ANA and specific autoantibodies, are ancillary.

   
Normal range:
negative.

   Use