1. How Shall Fibromyalgia Be Diagnosed? A Comparison of Clinical, Survey and ACR Criteria Robert S Katz 1, Frederick Wolfe 2, Kaleb Michaud 2,3 1 Rush University Medical Center, Chicago, IL 2 National Data Bank for Rheumatic Diseases, Wichita, KS 3 Stanford University, Stanford, CA ABSTRACT BACKGROUND. The American College of Rheumatology (ACR) criteria for fibromyalgia are the de facto criteria for research studies, and they also play a role in certifying diagnosis in fibromyalgia-related litigation. However, it is widely recognized that ACR criteria are not generally utilized by non-rheumatologists, and that rheumatologists may diagnose fibromyalgia even in patients who do not satisfy ACR criteria. We undertook this study to determine concordance between ACR criteria and clinical criteria and to evaluate concordance between proposed survey criteria and clinical criteria. METHODS. Consecutive patients in a clinical practice setting were evaluated until approximately 100 with and 100 without fibromyalgia were identified by a rheumatologist’s clinical diagnosis. Patients underwent a separate tender point examination by a metrologist and completed the Regional Pain Scale (RPS) (0-19) and a VAS fatigue scale (0-10). Survey fibromyalgia was diagnosed in patients who had an RPS >=8 and a fatigue score >= 6 scale. Agreement between diagnostic methods was assessed by Kendall’s tau-a. RESULTS. Of the 206 study cases, the clinician’s diagnosis was fibromyalgia in 101 (49.0%). Sixty-six of the 206 patients (32.0%) satisfied ACR criteria, and 83 or 40.3% satisfied survey criteria. Clinical and survey criteria were concordant in 74.8% of cases (kappa = 0.49 (95% C.I. 0.38 to 0.61)). Clinical criteria and ACR criteria agreed in 75.2% (kappa = 0.50 (95% C.I. 0.40 to 0.61)), and survey criteria and tender point criteria were concordant in 70.4% of cases (kappa = 0.36 (95% C.I. 0.28 to 0.51)). Strongest agreement for clinical diagnosis (tau-a >0.30) (Table 2) was found for count of somatic symptoms, tender point count and regional pain score, while for survey criteria strongest agreement was noted with fatigue, HAQ-2, pain, global, somatic symptoms and regional pain scale. Although agreement was good with tender point (TP) count, agreement was considerably less good with the tender point criterion (TP >=11), and the criterion appeared to be generally ignored by clinical and survey diagnosis. Survey criteria had higher levels of agreement (p<0.05) with patient symptom variables than did clinician diagnosis. CONCLUSIONS. Clinical, survey and ACR criteria for fibromyalgia diagnosis have moderate levels of concordance (70-75%), and tap into the same pool of fibromyalgia symptoms. As there is no gold standard for fibromyalgia and because fibromyalgia is often considered to be a trait diagnosis, all methods of diagnosis appear appropriate. The survey method has the advantage that does not require physical examination. Agreement between clinical and survey criteria Results. Of the 206 study cases, the clinician’s diagnosis was fibromyalgia in 101 (49.0%). Sixty of the 206 patients (29.1%) satisfied ACR criteria, and 83 or 40.3% satisfied survey criteria. Clinical and survey criteria were concordant in 74.8% of cases (kappa = 0.49 (95% C.I. 0.36 to 0.60)). Clinical criteria and ACR criteria agreed in 75.2% (kappa = 0.50 (95% C.I. 0.35 to 0.59)), and survey criteria and ACR criteria were concordant in 72.3% of cases (kappa = 0.40 (95% C.I. 0.25 to 0.51)). The inter- relationships of the three diagnostic groups are seen graphically in Figure 1. For patients positive for fibromyalgia by at least one method, only 33% were positive by all three methods. Isolated positive cases were noted 15%, 11% and 4% of diagnoses by clinical diagnosis, survey and ACR criteria, respectively. Table 2 explores the relationship between methods of diagnosis and diagnostic and clinical variables. Within the survey and clinical columns, greater values mean stronger association with diagnosis and with fibromyalgia symptoms. Differences (column 3) indicate how much stronger (+) or weaker (-) in percent is the variable for survey diagnosis compared with clinical diagnosis. Among the diagnostic items, the tender point count (0.40) and the RPS (0.35) were most strongly associated with diagnosis among patients diagnosed clinically. Of interest, the tender point criterion (≥11 tender points) has a weaker effect (0.25). The reason for this is that the tender point count discriminates maximally at a count ≥6. However, the ACR criterion (≥11) has reduced sensitivity (Figure 2). The relationship between tender point count and clinical and survey diagnosis can be seen in more detail in Figure 3. For clinical diagnosis, where tender points would be expected to influence diagnosis, as well as in survey diagnosis, where tender points would not be expected to influence diagnosis because their values are unknown to the diagnosis process, a level of ≥6 tender points graphically separates diagnosis and non-diagnosis. These data provide evidence of the role of tender points in fibromyalgia, but suggest that the ≥11 level is not consistent with clinical or survey diagnosis. In contrast to the tender point count, the RPS had the highest tau-a level for clinical diagnosis as well as being a criterion for survey diagnosis. Figure 4 indicates the survey diagnosis level for RPS (≥8) is at the appropriate sensitivity, specificity and percent correct level. In data not shown, the survey criterion level for fatigue (≥6) was as the optimum predictive level. In addition to diagnostic elements, Table 2 shows that patients diagnosed with survey criteria compared with clinical criteria are more likely to have elevated levels of functional disability, pain, and global severity than patients diagnosed with clinical criteria. They are also more likely to have higher levels of fatigue and regional pain; however, this would be expected to occur because these variables are survey criteria diagnostic elements. By contrast, the tender point count is more likely to be higher in persons diagnosed clinically. Taken as a whole, survey criteria are more strongly associated with measures of clinical severity than are clinical criteria. Table 1. Demographic and Clinical Characteristics of Patients Meeting and Not Meeting Survey Fibromyalgia Criteria Table 2. Concordance of Survey and Clinical Fibromyalgia Criteria for Demographic and Clinical Variables According to Kendall’s Tau-a. Figure 2. ROC curve for the relationship between clinical fibromyalgia diagnosis and tender point count. The tender point count discriminates maximally at a count >=6. The ACR criterion (>=11) is relatively insensitive. Figure 1. Venn diagram demonstrating the inter- relationship of clinical, ACR and survey diagnostic criteria. For patients positive for fibromyalgia by at least one method, only 33% were positive by all three methods. Isolated positive cases were noted 17%, 12% and 2% of diagnoses by clinical survey and ACR criteria, respectively. Figure 3. Graphs of kernel density estimates of the tender point count for patients diagnosed as having fibromyalgia (+) and as not having fibromyalgia (-) by clinical and survey diagnosis methods. Because these are probabilistic estimates, tender point values 18 are seen. These data show that, regardless of diagnostic method, there is a substantial block of positive diagnoses occurring at tender point counts between 6 and 18. Negative diagnosis is strongest at levels ≤ 2-3. Figure 4. The ROC relationship between Regional Pain Scale (RPS) and the clinical diagnosis of fibromyalgia. The sensitivity, specificity and percent correct is 83.2%, 87.6% and 85.4% at the diagnostic criterion level of RPS level ≥8. Percent correct at ≥6 is 86.4%. The difference between these two levels is not significant, Somer’s D 0.01 (95% C.I. 0.03 to 0.05, p=0.59). Methods. In the practice of one of the authors (RK), consecutive patients completed a questionnaire that included the Regional Pain Scale and a visual analog fatigue scale, underwent a tender point examination by an experienced and specially trained nurse, and had their clinical diagnosis entered by the author. The regional pain scale is a self-administered count of the number of painful non- articular regions. The RPS score ranges from 0 to 19. Survey fibromyalgia was diagnosed when the RPS >= 8 and a score on a 0-10 visual analog fatigue scale was >=6. The diagnosis of fibromyalgia was made regardless of any other diagnosis. Patients were classified as having clinical fibromyalgia if the clinician diagnosed fibromyalgia and survey fibromyalgia if they satisfied the survey fibromyalgia criteria. The clinician was unaware of the survey diagnosis status or the nurse’s examination. Every patient had a full rheumatology examination performed by the first author that included a fibromyalgia tender point examination at some time during his clinical care. Diagnosis as to whether the patient had fibromyalgia for this study was made considering the long-term patient-clinician experience and included factors related to pain, tenderness, fatigue, sleep disturbance, comorbidity and psychosocial variables. At the time of the study visit, a tender point examination was performed if the clinician believed it was necessary to make the study diagnosis. Patients were classified as having ACR fibromyalgia if they had 11 or more tender points on the nurse’s examination and satisfied the ACR criteria for widespread pain as determined from the regional pain score pain site questionnaire Discussion. The finding of moderate agreement by two methods raises an issue about the ACR criteria and what the use of ACR criteria means to fibromyalgia diagnosis. It should be noted that the 1990 ACR criteria study did not find just “one” fibromyalgia. Different sets of potential criteria, including symptom criteria, performed almost as well as the official criteria. Although different criteria didn’t change the percent correctly classified appreciably, the actual patients in the positive and negative predicted categories were often different. In fact, many similar but slightly different definitions of fibromyalgia existed in the ACR study, which resulted in patients around the interface of fibromyalgia/not fibromyalgia being classified differently by different criteria. As there is really no gold Standard for diagnosis, there is also no absolutely correct diagnosis, though for research purposes the ACR criteria have filled that role. The data of this table, as well as the results of Table 1, indicate that survey diagnostic criteria identify fibromyalgia clinical associations at least as well as do the clinician’s diagnosis. The study results raise the question of whether published papers based on ACR criteria actually represent patients seen and managed by rheumatologists in clinical practice. The issue is complicated, as it is likely that most all patients with fibromyalgia met the ACR criteria at one time. We suspect that outcome studies should include patients who meet fibromyalgia at sometime during their course, but that treatment studies should require criteria positive patients for enrollment. In summary, clinical, survey and ACR criteria for fibromyalgia diagnosis have moderate levels of concordance (72-75%), and tap into the same pool of fibromyalgia symptoms. As there is no gold standard for fibromyalgia and because fibromyalgia is often considered to be a trait diagnosis, all methods of diagnosis appear appropriate. However, the level of tender points required by the ACR criteria is ignored in clinical diagnosis and by survey criteria. The survey method has the advantage that it does not require physical examination.