Clinical and Serological Features of Patients Referred through a Rheumatology Triage System because of Positive Antinuclear Antibodies

<div><p>Background</p><p>The referral of patients with positive anti-nuclear antibody (ANA) tests has been criticized as an inappropriate use of medical resources. The utility of a positive ANA test in a central triage (CT) system was studied by determining the autoantibody profiles and clinical diagnoses of patients referred to rheumatologists through a CT system because of a positive ANA test.</p><p>Methods</p><p>Patients that met three criteria were included: (1) referred to Rheumatology CT over a three year interval; (2) reason for referral was a “positive ANA”; (3) were evaluated by a certified rheumatologist. The CT clinical database was used to obtain demographic and clinical information and a serological database was used to retrieve specific ANA and/or extractable nuclear antigen (ENA) test results. Clinical information was extracted from the consulting rheumatologist's report.</p><p>Results</p><p>15,357 patients were referred through the CT system; 643 (4.1%) of these because of a positive ANA and of these 263 (40.9%) were evaluated by a certified rheumatologist. In 63/263 (24%) of ANA positive patients, the specialist provided a diagnosis of an ANA associated rheumatic disease (AARD) while 69 (26.2%) had no evidence of any disease; 102 (38.8%) had other rheumatologic diagnoses and 29 (11%) had conditions that did not meet AARD classification criteria. Of ANA positive archived sera, 15.1% were anti-DFS70 positive and 91.2% of these did not have an AARD.</p><p>Conclusions</p><p>This is the first study to evaluate the serological and clinical features of patients referred through a CT system because of a positive ANA. The spectrum of autoantibody specificities was wide with anti-Ro52/TRIM21 being the most common autoantibody detected. Approximately 15% of referrals had only antibodies to DFS70, the vast majority of which did not have clinical evidence for an AARD. These findings provide insight into the utility of autoantibody testing in a CT system.</p></div

Consultant's Opinion of 263 Patients in the ARC.

<p>*Other includes gout, tendonitis, bursitis, patellofemoral syndrome, palindromic rheumatism, spondyloarthropathy, psoriatic arthritis, unspecified polyarthropathy.</p

Autoantibody Specificities of the 116 patients in the ARC with a positive anti-ENA^*.

<p>Note: 116/263 patients referred with a positive ANA had a detectable ENA autoantibody. Some patients had more than 1 autoantibody, hence % totals will not  = 100.</p><p>*results available for 76 samples.</p><p>**Clinical diagnoses associated with specific autoantibodies see Table S1 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093812#pone.0093812.s001" target="_blank">File S1</a>.</p

Likelihood ratios differentiate AARD from non-AARD in ANA positive patients (n = 208, 55 excluded due to missing results; dsDNA based on 76 samples).

<p>NOTE: Anti-DFS70 positivity was indicative for non-AARD. ‘DFS70 mono’ represents patients that have anti-DFS70, but no other detectable autoantibody.</p

Supervised cluster analysis with patients sorted according to the presence or absence of ANA associated rheumatic disease (AARD) was performed with antibodies to extractable nuclear antigens (ENA), chromatin, ribosomal P and to DFS70.

<p>ENA, Ro52/TRIM21, SS-A/Ro60 and SS-B/La cluster most closely with AARD whereas DFS70 antibodies and Jo-1 demonstrate high distance clustering.</p

Derivation of the ARC via the diagnostic profile of 15,537 patients referred to rheumatology central triage over a three year audit period.

<p>Derivation of the ARC via the diagnostic profile of 15,537 patients referred to rheumatology central triage over a three year audit period.</p