ORIGINAL INVESTIGATION Diagnostic Accuracy for Lupus and Other Systemic Autoimmune Diseases in the Community Setting Sonali Narain, MD, MPH; Hanno B. Richards, MD; Minoru Satoh, MD, PhD; Marlene Sarmiento, BSN; Richard Davidson, MD, MPH; Jonathan Shuster, PhD; Eric Sobel, MD, PhD; Paulette Hahn, MD; Westley H. Reeves, MD Background: Most individuals with autoimmune and were seropositive for antinuclear antibodies but did not other immune disorders undergo initial evaluation in the have autoimmune disease. The degree of agreement for community setting. Since misdiagnosis of systemic au- referring rheumatologists (␬=0.55) was better than that toimmune diseases can have serious consequences, we for nonrheumatologists (␬=0.32). Stepwise logistic re- evaluated community physicians’ accuracy in diagnos- gression indicated that rheumatologists were 4 times more ing autoimmune diseases and the consequences of mis- likely to make an accurate diagnosis of SLE than were diagnosis. nonrheumatologists (PϽ.003). Thirty-nine patients who were seropositive for antinuclear antibodies but had no Methods: We studied the patients referred to our Au- autoimmune disease had been treated with corticoste- toimmune Disease Center for 13 months (n=476). We roids at dosages as high as 60 mg/d. estimated the degree of agreement with the final diag- nosis (␬ statistic) and the accuracy indexes (sensitivity, Conclusions: Many patients with a positive anti- specificity, and predictive values) of the referring phy- nuclear antibody test are incorrectly given a diagnosis of sicians’ diagnoses. SLE and sometimes treated with toxic medications. The data support the importance of continuing medical edu- Results: We found a 49% agreement between the refer- cation for community physicians in screening for auto- ring and final diagnoses (␬=0.36). Of 263 patients re- immune diseases and identifying patients who may ben- ferred with a presumptive diagnosis of systemic lupus ery- efit from early referral to a specialist. thematosus (SLE), 125 received a diagnosis of other conditions (␬=0.34). Of those referred with SLE, 76 (29%) Arch Intern Med. 2004;164:2435-2441 HE DIAGNOSES OF SYSTEMIC reduce health care costs, the need to train lupus erythematosus (SLE), primary care physicians in rheumatologi- progressive systemic scle- cal diagnosis has been increasingly recog- rosis, and Sjögren syn- nized.9 drome are aided by well- The objective of this study was to evalu- Testablished clinical criteria.1-5 Since many ate the accuracy of community physi- patients with these potentially serious dis- cians in diagnosing autoimmune disor- eases undergo evaluation and treatment ders. We also examined the factors initially by community physicians, it is im- associated with a misdiagnosis of these portant that they be recognized so that af- conditions and the question of how fre- fected individuals can be referred to spe- quently an inaccurate diagnosis led to in- Author Affiliations: Division of cialists in a timely manner. Misdiagnosis appropriate therapy. Rheumatology & Clinical can have a serious negative impact on Immunology and Center for health as well as economic and emo- METHODS Autoimmune Disease tional consequences. The risks of overdi- (Drs Narain, Richards, Satoh, agnosis include inappropriate treatment Sobel, Hahn, and Reeves and with potentially dangerous medications, PATIENT RECRUITMENT Ms Sarmiento), Program in unnecessary referrals6,7 and laboratory AND DEMOGRAPHICS Epidemiology & Public Health tests,8 and difficulty obtaining health or life (Drs Narain and Davidson), and Four hundred seventy-six patients referred Departments of Biostatistics insurance. Conversely, underdiagnosis can between September 1, 2001, and September (Dr Shuster) and Medicine lead to a delay in appropriate therapy, cul- 30, 2002, to the University of Florida Auto- (Dr Davidson), University of minating in irreversible complications such immune Disease Center (ADC), Gainesville, Florida, Gainesville. as renal failure or pulmonary fibrosis. Be- consented to participate in this institutional Financial Disclosure: None. cause an accurate and timely diagnosis can review board–approved study. The referring (REPRINTED) ARCH INTERN MED/ VOL 164, DEC 13/27, 2004 WWW.ARCHINTERNMED.COM 2435 ©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 physician was asked to complete a prescreening question- tion of patients with a final diagnosis of that condition divided naire indicating the reasons for referral and a working diag- by the total number of patients undergoing analysis. nosis. Sensitivity, specificity, and positive and negative predic- Date of birth, ethnicity, education, referring diagnosis, and tive values were calculated as indicators of the ability of the re- final diagnosis were obtained from medical records and data ferring physician to diagnose autoimmune disorders. Sensitiv- collected at the ADC. Median annual household income was ity was defined as the probability that the referring physician used as an indicator of socioeconomic status. Block group in- correctly diagnosed an autoimmune disease. Specificity was the formation was obtained using the home ZIP code and matched probability that the referring physician was able to exclude the with income data provided in the Inforum software (Thom- presence of a particular autoimmune disease in the popula- son Medstat, Franklin, Tenn). The referring physician’s spe- tion found not to have that disease by the subspecialists at the cialty and year of graduation from specialty training were ob- ADC. Positive predictive value was the probability that the re- tained from the American Medical Association Web site ferring diagnosis was confirmed. (available at: http://www.ama-assn.org/aps/amahg.htm; last ac- Stepwise forward logistic regression for patients with a re- cessed August 31, 2002). Referring physicians were classified ferring diagnosis of SLE was conducted, with age, years of edu- as rheumatologists or nonrheumatologists. cation, type of insurance, median annual household income, physician’s specialty, and physician’s year of graduation as in DIAGNOSTIC CLASSIFICATION dependent variables. A diagnosis of SLE by the referring phy- sician was scored as 1 (SLE final at ADC) or 0 (not SLE final Subjects were interviewed and examined by 1 of 4 autoim- diagnosis). Similarly, 12 or fewer years of patients’ education mune disease subspecialists (H.B.R., E.S., P.H., or W.H.R.). Di- was scored as 0, and greater than 12 years was scored as 1; me- agnostic criteria were reviewed after the evaluation by 2 sub- dian annual household income of $40000 or less was scored specialists (H.B.R. and W.H.R.). Systemic autoimmune diseases as 0 and greater than $40000 as 1. Type of insurance was scored were classified using validated criteria for SLE,1,10 progressive as 1 for privately insured and 0 for those on Medicare/ systemic sclerosis,2 Sjögren syndrome,3 rheumatoid arthritis,4 Medicaid; referring physician was scored as 1 if referred by a and polymyositis/dermatomyositis.5 rheumatologist and 0 if referred by a nonrheumatologist. Based Diagnoses were categorized as follows: (1) SLE, (2) pro- on the results of the regression procedure, we calculated the gressive systemic sclerosis, (3) Sjögren syndrome, (4) poly- odds ratio (OR) estimates of correct diagnosis and 95% confi- myositis/dermatomyositis, (5) positive for antinuclear anti- dence intervals (CI). A P value of less than .05 was accepted as bodies (hereafter referred to as positive ANA; ANA titer Ն1:40 significant. using Hep-2 substrate [The Binding Site Limited, Birming- ham, England] in the absence of autoimmune disease), (6) fi- RESULTS bromyalgia, and (7) other, including undifferentiated connec- tive tissue disease (Ն2 clinical manifestations suggestive of connective tissue disease and the presence of Ն1 non–organ- Demographic characteristics of the cohort are shown in specific autoantibody),11 Raynaud phenomenon, Wegener granu- the following tabulation. lomatosis, antiphospholipid antibody syndrome, interstitial lung disease, or sarcoidosis. Characteristic No. (%) of Patients Female 435 (91) Referring physician AUTOANTIBODY TESTING Rheumatologists 75 (16) Nonrheumatologists 336 (71) All patients underwent extensive autoantibody testing on their Unknown 65 (13) first visit. Antinuclear antibodies were detected by means of in- Ethnicity direct immunofluorescence using Hep-2 cell substrate. Anti– White 338 (71) double-stranded (ds) DNA antibodies were detected using the African American 92 (19) Crithidia luciliae kinetoplast-staining assay (DiaSorin, Stillwa- Hispanic 19 (4) ter, Minn). Antiphospholipid antibodies were detected using Others 27 (6) a commercial IgG and IgM anticardiolipin antibody enzyme- Total 476 (100) linked immunosorbent assay (The Binding Site Limited) and/or Mean±SD age of the cohort was 44.5±14.0, and the lupus anticoagulant activity. Anti-Sm antibodies were de- ethnicity of 1 patient was unknown. Most patients were tected by means of enzyme-linked immunosorbent assay referred with the diagnosis of SLE (56%) (Table 1). Other (Varelisa; Pharmacia Diagnostics, Uppsala, Sweden), and their referring diagnoses included progressive systemic scle- presence was confirmed by means of immunoprecipitation.12 Anti–ribosomal P autoantibodies were detected by means of im- rosis (8%), Sjögren syndrome (4%), polymyositis/ munoprecipitation of the P0, P1, and P2 proteins.12 dermatomyositis (3%), fibromyalgia (1%), positive ANA