Official Journal of the American Rheumatism Association Section of the Arthritis Foundation

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1 ~~ arthritis arid rheumatism Official Journal of the American Rheumatism Association Section of the Arthritis Foundation EVALUATION OF DIAGNOSTIC CRITERIA FOR ANKYLOSING SPONDYLITIS A Proposal for Modification of the New York Criteria SJEF VAN DER LINDEN. HA A. VALKENBURG, and ARNOLD CATS The New York and the Rome diagnostic criteria for ankylosing spondylitis (AS) and the clinical history screening test for AS were evaluated in relatives of AS patients and in population control subjects. The New York criterion of pain in the (dorso) lumbar spine lacks specificity, and the chest expansion criterion is too insensitive. The Rome criterion of low back pain for more than 3 months is very useful. Our study showed the clinical history screening test for AS to be moderately sensitive, but it might be better in clinical practice. As a modification of the New York criteria, substitution of the Rome pain criterion for the New York pain criterion is proposed. In rheumatology perhaps more than in any other specialty, practitioners make use of diagnostic criteria. Recently, criteria for Reiter s syndrome (1) and scleroderma (2) were proposed, and the criteria for, systemic lupus erythematosus were revised (3). There is clearly a need for criteria in diseases where signs or symptoms are not pathognomic. Diagnostic criteria can serve 2 purposes: 1) the creation of a uniform patient population, thus permitting comparisons between groups of patients treated in different From the Department of Rheumatology, University of Leiden, The Netherlands and the Department of Epidemiology. Erasmus University, Rotterdam, The Netherlands. Supported in part by The Netherlands Prevention Fund. Sjef van der Linden, MD: Department of Rheumatology, University of Leiden (present address: University of Berne, Inselspital, Switzerland); Hans A. Valkenburg, MD: Professor of Epidemiology, Erasmus University; Arnold Cats, MD: Professor of Medicine and Chairman. Department of Rheumatology, University of Leiden. Address reprint requests to Sjef van der Linden, MD, Department of Rheumatology, Inselspital, 3010 Berne, Switzerland. Submitted for publication June 6, 1983: accepted in revised form October 1 I centers or given different treatments, and 2) the promotion of early diagnosis. It is possible that both purposes cannot be reached by a single set of criteria. Diagnostic criteria for ankylosing spondylitis (AS) were specified at the Rome conference in 1963 (Table 1) (4) and were later evaluated in Blackfoot and Pima Indians (5). This led to modifications, resulting in the New York criteria formulated in 1966 (Table 2) (6). Moll and Wright evaluated these criteria in relatives, with or without spondylitis, of probands who had psoriatic arthritis (7). These authors found back pain to be too sensitive and too nonspecific, and limitation of chest expansion specific, but too insensitive. At present, the New York criteria are widely used in studies on the prevalence of AS (8-13). In 1977 Calin et a1 (14) reported on clinical history as a screening test for AS. Five items proved to characterize the inflammatory nature of the back pain in AS very well (Table 3). Those authors found a sensitivity of 95% in 42 AS patients and a specificity of 85% in 82 controls, when at least 4 of the 5 items were positive. Our family and population study, performed to assess HLA-B27 positive individuals risk of developing AS (13, enabled us to evaluate the sensitivity and specificity of the New York and Rome criteria and of clinical history used as a screening test for AS. Correlation was sought between the various clinical criteria and the presence or absence of sacroiliitis and of HLA-B27. PATIENTS AND METHODS All first-degree relatives, aged 15 years or older, of 20 HLA-B27 positive AS probands were asked to participate in the family study. The probands were randomly chosen Arthritis and Rheumatism, Vol. 27, No. 4 (April 1984)

2 362 VAN DER LINDEN ET AL Table 1. Rome clinical criteria for ankylosing spondylitis (4) I. Low back pain and stiffness for more than 3 months which is not relieved by rest. 2. Pain and stiffness in the thoracic region. 3. Limited motion in the lumbar spine. 4. Limited chest expansion. 5. History or evidence of intis or its sequelae. Ankylosing spondylitis if bilateral sacroiliitis is present associated with any I of the above clinical criteria. Table 3. The clinical history as a screening test for ankylosing spondylitis (14) Five factors differentiate the back pain produced by spondylitis from the ubiquitous back pain due to other causes. These 5 factors are: 1. Onset of back discomfort before the age of 40 years. 2. Insidious onset. 3. Persistence for at least 3 months. 4. Associated with morning stiffness. 5. Improvement with exercise. from a group of 183 HLA-B27 positive AS patients. All of these individuals fulfilled the New York criteria for definite AS. All 20 probands were heterozygous for HLA-B27, though this was not a selection criterion. Eighteen of the probands had no associated disease. One proband had developed small psoriatic lesions at the age of 7 and had onset of AS at age 23. Another had suffered from AS since the age of 21 and had developed regional enteritis 4 years later. (According to the New York criteria, these associated diseases do not necessitate exclusion, but they should be designated individually.) Of the total of 116 relatives aged 15 years or older, 102 (88%) could participate. The mean age in the response group was 39.5 years. All were typed for the HLA-A, B, and C locus determinants; 61 relatives were HLA-B27 positive, and this antigen was absent in the other 41 relatives. We also included in the study the first-degree relatives of HLA-B27 negative AS probands. Altogether, 22 HLA-B27 negative probands were available, but 8 families could not participate. Therefore, 14 probands are included, giving a response rate of 64%. One of these 14 probands was found to have AS and psoriasis, and 2 had AS and regional enteritis. Eleven probands had no associated disease. Thirteen probands fulfilled both the Rome and New York criteria for AS. At the time of investigation 1 proband fulfilled only the Rome criteria. The 14 AS probands had 82 living firstdegree relatives. An anteroposterior radiograph of the pelvis was performed on each first-degree relative after informed consent. All radiographs were read twice by 5 investigators. The readings were done blindly and the results of the first reading were not available at the time of rereading. The radiographs of the first-degree relatives of the 2 different Table 2. New York clinical criteria for ankylosing spondylitis (6) 1. Limitation of motion of the lumbar spine in all 3 planes (anterior flexion, lateral flexion, and extension). 2. A history of pain or the presence of pain at the dorsolumbar junction or in the lumbar spine. 3. Limitation of chest expansion to 1 inch (2.5 cm) or less, measured at the level of the fourth intercostal space. Definite ankylosing spondylitis if 1) grade 3-4 bilateral sacroiliitis associated with at least 1 clinical criterion; or 2) grade 3-4 unilateral or grade 2 bilateral sacroiliitis associated with clinical criterion 1 or with both clinical criteria 2 and 3. Probable ankylosing spondylitis if grade 3-4 bilateral sacroiliitis exists without any signs or symptoms satisfying the clinical criteria. proband sets were randomized arid mixed with 20 control films of patients with a clinical diagnosis of osteoarthritis of the hip joint. The interpretation of the radiographs was done without knowledge of the clinical findings or the HLA typing results. Scoring was done according to the Atlas of Standard Radiographs in Arthritis (16) and following the recommendations of the New York Conference for Population Studies (6). The scores ranged from 0-4 per reading: grade (1 = normal; grade 1 = suspicious changes: grade 2 = minimum abnormality (small localized areas with erosion or sclerosis, without alteration in the joint width); grade 3 = unequivocal abnormality (moderate or advanced sacroiliitis with erosions, evidence of sclerosis, widening, narrowing, or partial ankylosis; grade 4 = severe abnormality (total ankylosis). The scores of all 10 readings were added, divided by 10, and rounded off to the nearest whole figure. Sacroiliitis according, to the New York criteria (6) was seen in 15 (25%) of 61 HLA-B27 positive first-degree relatives, 8 (53%) of whom fulfilled the New York criteria for AS. Sacroiliitis was never seen in the HLA-B27 negative relatives of the HLA-B27 positive probands, but was found in 6 (8%) of the first-degree relatives of HLA-B27 negative probands (Table 4). One HLA-B27 positive relative with sacroiliitis also had ulcerative colitis. Clinically she had severe AS. The HLA-identical male AS proband showed no bowel disease. Psoriasis was found in 1 of the 15 HLA-B27 positive firstdegree relatives with sacroiliitis. The proband was free from skin disease. The 6 HLA-B27 negative first-degree relatives Table 4. Sacroiliitis in first-degree relatives of HIAA-B27 positive and HLA-B27 negative probands with ankylosing spondylitis Probands HLA-B27 positive (n = 20) First-degree relatives HLA-B27 positive (n = 61) First-degree relatives HLA-B27 negative (n = 41) Total (n = 102) Probands HLA-B27 negative (n = 14) First-degree relatives HLA-B27 positive (n = 0) First-degree relatives HLA-B27 negative (n = 74) Total (n = 74) Number (%) with sacroiliitis

3 AS CRITERIA 363 Table 5. Sensitivity of New York and Rome criteria in probands with ankylosing spondylitis* HLA-B27 HLA-B27 positive negative probands probands (n = 20) (n = 14) P New York criteria a) Limitation of motion lumbar spine b) Pain (dorso) lumbar spine 100 too c) Chest expansion 52.5 cm d) Combined criterion (b + c) I5 21 Rome criteria a) Low back pain 23 months b) Thoracic pain and stiffness c) Limited motion lumbar spine 100 I00 d) Iritis 45 7 * Numbers represent 96 sensitivity. = not significant. Pis c0.05 with sacroiliitis, related to 6 different probands, showed neither psoriasis nor inflammatory bowel disease. A medical history of each first-degree relative was taken, with special attention to back and joint problems. Each had a physical examination, principally of the spinal column and peripheral joints. The chest expansion was measured at a level of the fourth intercostal space (6). This measurement was done after instruction and was repeated once. The higher of the 2 values was noted. Measurement of anterior spinal flexion was done using the modified technique of Schober (7); marks were made in ink 5 cm below and 10 cm above the lumbosacral junction. After maximal anterior flexion the new distance between the 2 marks was measured. A discrepancy of less than 5 cm was considered abnormal. When evaluating the New York criteria. Moll and Wright found no overall difference between the application of subjective and objective methods of measuring spinal mobility (7). Therefore, for reasons of simplicity, extension and lateral flexion were measured on a purely subjective basis, with abnormal defined as loss of movement of 30% or more, taking into consideration age, sex, and medical history of the respondent. The New York and Rome criteria and the clinical history screening test items, which translate well into the Dutch language, were applied to the 102 participating relatives of the 20 HLA-B27 positive probands with AS. This was done immediately after the physical examination, with the examiner having no knowledge of the radiologic or HLA typing results. In 1 HLA-B27 positive relative without sacroiliitis, the criteria points were not recorded. The criteria and the screening test items were also evaluated in 34 probands-20 HLA-B27 positive and 14 HLA-B27 negative-and in a control group of 42 respondents without sacroiliitis. These control subjects participated in an open population study as age- and sex-matched controls of respondents with radiologic sacroiliitis diagnosed by epidemiologists or rheumatologists. The mean age of the control group was 54.4 years; all were 45 years or older. Four (9.5%) of the 42 population controls were HLA-B27 positive. The risk of HLA-B27 positive individuals devel- oping AS is described in detail elsewhere (15.17). The HLA- B27 phenotype frequency in the Dutch population is 7.8% (18). Statistical analysis. The chi-square test was used for calculating significance. Yates correction was applied if the total number was less than 100 or if any cell contained a value under 10. RESULTS Diagnostic criteria in probands. Fulfillment of the New York criteria was a prerequisite for inclusion of the probands in the study. The relative frequencies for each of the Rome and New York criteria are given in Table 5. The mean age of the HLA-B27 negative probands was 8.4 years higher than that of their HLA-B27 positive counterparts; the difference was significant at the P < 0.05 level. This is probably related to the later age at which AS is usually diagnosed in HLA-B27 negative patients. The mean (2SD) age at diagnosis of 18 male HLA-B27 negative AS patients was 36.4 k 13.6 years; in 135 male HLA-B27 positive patients it was 29.3 ~fr. 9.1 (P< 0.05, Student s t-test). The mean interval between first complaints related to AS and age at diagnosis was 7.2 years in the male HLA-B27 negative group and 4.4 years in the male HLA-B27 positive group. All patients at some time had pain around the dorsolumbar junction or in the lumbar spine. Almost all of the AS patients had movement limitation of the lumbar spine in all 3 planes (or, more accurate geometrically perhaps, in 2 planes: anterior flexion and extension in the sagittal plane and lateral flexion to both sides in the frontal plane). The sensitivity of the chest expansion criterion was low. The sensitivity of the combined criterionpain at the dorsolumbarjunction or in the lumbar spine plus limitation of chest expansion to 52.5 cm-was the same as for the chest expansion criterion alone, the latter being the limiting factor. The sensitivity of the Rome criteria was high, with the exception of iritis. In contrast to our earlier findings (19) but in accordance with the literature (20), a history of acute uveitis was found more often in HLA-B27 positive patients, the difference being significant at the P < 0.05 level. All probands were positive for at least 4 items of the clinical history screening test. Diagnostic criteria in relatives and population controls. The findings in the relatives of the 20 HLA- B27 positive probands and the population controls are shown in Table 6. Limitation of the lumbar spine in 3

4 364 VAN DER LINDEN ET AL Table 6. Percent positive findings according to the New York and Rome criteria in relatives of 20 HLA-B27 positive ankylosing spondylitis patients and in population controls* First-degree relatives Population controls SI+, s1-, SI-. SI-, SI-, HLA-B27+ HLA-B27t HI.A-B27- HLA-B27+ HLA-B27- (n = 15) (n = 45) (n = 41) (n -- 4) (n = 38) New York criteria a) Limitation of motion lumbar spine b) Pain (dorso) lumbar spine c) Chest expansion 52.5 cm d) Combined criterion (b + c) Rome criteria a) Low back pain 23 months b) Thoracic pain and stiffness c) limited motion lumbar spine d) Iritis * SI = sacroiliitis. + = present or positive; - = absent or negative. The differences in mean age in the groups of relatives were not significant. Sensitivity = % positive in patients with SI; specificity = 100% - % false-positive (false-positive = % positive in patients without S1). planes was seen significantly more often in relatives with sacroiliitis compared with HLA-B27 positive relatives without sacroiliitis (P < 0.01) or HLA-B27 negative relatives (P < 0.001). Pain at the dorsolumbar junction or in the lumbar spine was seen often in all groups, all differences being nonsignificant. This criterion was found to lack specificity (calculated as 100% - 36 false-positive), in accordance with the findings of Moll and Wright (7). The specificity of the chest expansion criterion was loo%, but the sensitivity was very low. The sensitivity and specificity patterns of the combined criterion (dorsolumbar pain and chest expansion) were identical with those of the chest expansion criterion. The Rome criterion of low back pain for more than 3 months, not reduced by rest was seen more often in relatives with sacroiliitis than in the HLA-B27 positive relatives without sacroiliitis (P < 0.01) or HLA-B27 negative relatives (P < 0.01). Painhtiffness in the thoracic region was significantly more common (P < 0.001) in relatives with sacroiliitis compared with HLA-B27 negative relatives without sacroiliitis. The difference between HLA-B27 positive relatives with and those without sacroiliitis was not statistically significant; in both groups, thoracic painhtiffness was seen more often than in the HLA-B27 negative relatives without sacroiliitis. Limited movement of the lumbar spine was seen more often in relatives with sacroiliitis than in HLA-B27 positive relatives without sacroiliitis (P < 0.02) or HLA-B27 negative relatives (P < 0.001). There were no significant differences between the 45 HLA-B27 positive and the 41 HLA-B27 negative relatives without sacroiliitis with one exception: thoracic paidstiffness was seen more often (P < 0.01) in the former group. To obtain a larger number of cases for evaluation of the various criteria, subgroups were combined into larger groups for analysis. We combined the 41 HLA-B27 negative relatives without sacroiliitis and the 42 population controls to form 1 control group, and we added to the 15 HLA-B27 positive relatives with sacroiliitis the 6 HLA-B27 negative patients with sacroiliitis (Table 7). The latter were first-degree relatives of the HLA-B27 negative AS probands. Findings of the clinical history screening test were positive in 38% of the sacroiliitis group and always negative in the controls. On investigation, arthritis of peripheral joints was seen in 3 relatives with sacroiliitis; in 1, swelling of both knees was found, another showed arthritis of the left wrist, and the third had arthritis of both wrist joints and of 1 metacarpophalangeal joint. All 3 were HLA-B27 positive. Arthritis of peripheral joints was not found in 45 HLA-B27 positive relatives without sacroiliitis and was always absent in the population controls and in the HLA-B27 negative relatives of HLA-B27 positive AS probands. DISCUSSION According to the New York criteria, sacroiliitis is a condition sine qua non for the diagnosis of AS (6). The sacroiliac joints seem to be normal in <1% of patients with classic AS (21). Patients with sacroiliitis

5 AS CRITERIA 365 Table 7. Results of application of the New York and Rome criteria for ankylosing spondylitis and the clinical history screening test in all (n = 21) relatives with sacroiliitis (SI) (sensitivity) and in 83 controls (specificity). The predictive value of the positive criterion (PV*) and the predictive value of the negative criterion (PV) are also indicated* Sensitivity Specificity No. % No.?6 New York criteria a) Limitation of motion 8/21 (38) 80/83 (96) lumbar spine b) Pain (dorso) lumbar spine 13/21 (62) 36/83 (43) c) Chest expansion 52.5 cm 2/21 (10) 83/83 (100) d) Combined criterion (b + c) 2/21 (10) 83/83 (100) PV + No. % 8/11 (73) 13/60 (22) 212 (100) 2/2 (100) PV - No. % ft (86) <O.OOl 36/44 (82) 83/102 (81) (81) 0.04$ Rome criteria a) Low back pain 23 months 8/21 (38) 78/83 (94) 8/13 (62) 78/91 (86) <0.001 b) Thoracic pain and stiffness 8/21 (38) 73/83 (88) 8/18 (44) 73/86 (85) CO.02 c) Limited motion lumbar spine 11/21 (52) 74/83 (89) 11/20 (55) 74/84 (88) <0.01 d) Iritis 2/21 (10) 82/83 (99) 2/3 (67) 82/101 (81) Clinical history screening test At least 4 items positive 8/21 (38) 83/83 (100) 8/8 (100) 83/96 (86) <0.001 * PV+ = true-positive resultsitotal number with criterion; PV- = true-negative results/total number without criterion. t By chi-square, using actual numbers. N.? = not significant. 4 P value was unilaterally tested. With th?cral testing. the difference is not significant (P > 0.05). should therefore be studied when evaluating the.;cn~.itivity of the other criteria. However, sacroiliitis i\ ti01 restricted to AS, but may also be found in psm.i:i:i; arthritis, Reiter s syndrome, and even in rheuiy\::!c;id arthritis. Other conditions sometimes leading to I die) graphic abnormalities of sacroiliac joints thi4.l m y mimic sacroiliitis include brucellosis, tuberc:i!o>:!,r, hyperparathyroidism, Paget s disease, or metas; it malignant diseases. Therefore, these causes 01!:i<!Li. logic involvement of the sacroiliac joint shwld ;jc excluded as much as possible before testing (#! :;S criteria. The occurrence of sacroiliitis in relaiiw?; {it AS patients fulfills this requirement of excludirig o! h.1. causes, but sacroiliitis alone is not sufficieni. f5i ;L definite diagnosis of AS (Table 2). Among the 102 relatives of 20 HLA-B2 : p~-.itive AS probands, we found 15 cases of sacroillitis: Y (53%) of which fulfilled the New York criteria for AS. The diagnosis was already known in 4 of these subjects and they had been treated elsewhere; the other 4 had mild features. In a radiologic survey like this, the individuals with previously undetected disease can be expected to have relatively few features of the disease. Criteria which occur significantly more often in our subjects with sacroiliitis compared with controls will therefore be more sensitive in clinical practice since, in general, painful limitations will compel people to consult a physician. The specificity was tested in population con- trols and in those relatives of HLA-B27 positive AS probands who lacked sacroiliitis and the risk factor HLA-B27. This enabled us to evaluate the occurrence of features of AS in HLA-B27 positive relatives in the absence of sacroiliitis. We found an increased frequency of thoracic pain and stiffness complaints in HLA-B27 positive relatives without sacroiliitis. This suggests an association between these complaints and HLA-B27, even in the absence of sacroiliitis. However, complaints of pain and stiffness in the thoracic region are also related to age. The criterion was positive in only I (2%) of the 4 1 HLA-B27 negative first-degree relatives without sacroiliitis (a group with a mean age of 39.2 years), but was positive more often in thc population controls (mean age 54.4). Nine (21%) of these 42 controls fulfilled this criterion, 7 of them being HLA-B27 negative. The difference was significant at the P < 0.05 level. It seems reasonable to assume that these complaints might be related to degenerative changes in the older age group. However, HLA-B27 seems to predispose for thoracic pain and stiffness at a younger age, irrespective of the presence of sacroiliitis. Analogous findings have been reported in seronegative peripheral arthritis, where an increased prevalence of HLA-B27 was found in patients with or without sacroiliitis (22). The New York criterion of limitation of motion of the lumbar spine in all 3 planes is moderately sensitive, but highly specific. The usefulness of this criterion in the early stages of AS is, however, doubt-

6 366 VAN DER LINDEN ET AL Table 8. Modified New York criteria for ankylosing spondylitis A. Diagnosis I. Clinical criteria a) Low back pain and stiffness for more than 3 months which improves with exercise, but is not relieved by rest. b) Limitation of motion of the lumbar spine in both the sagittal and frontal planes. c) Limitation of chest expansion relative to normal values corrected for age and sex (23.24). 2. Kadiologic criterion Sacroiliitis grade 22 bilaterally or sacroiliitis grade 3-4 unilaterally. B. Grading 1. Definite ankylosing spondylitis if the radiologic criterion is associated with at least 1 clinical criterion. 2. Probable ankylosing spondylitis if a) Three clinical criteria are present. b) The radiologic criterion is present without any signs or symptoms satisfying the clinical criteria. (Other causes of sacroiliitis should be considered.) ful. It seems better suited to describe groups of definite AS patients. We prefer this criterion above the Rome criterion of limited motion in the lumbar spine because it is more clearly defined, thereby limiting interobserver variability. The New York criterion of history or presence of pain at the dorsolumbar junction or in the lumbar spine has no discriminating value at all. It should therefore be abandoned and replaced by a slightly modified Rome criterion: low back pain and stiffness for more than 3 months and improving with exercise. This criterion describes the inflammatory back pain of AS very well and is more realistic than the original version, with the qualification not relieved by rest. In our study, all those who fulfilled the original version also replied positively to the modified formulation and therefore already fulfilled 2 of the 5 items of the clinical history screening test for AS. Reduction of chest expansion to 2.5 cm or less is a highly specific, but too insensitive, criterion. Taking 5.0 cm as the cutoff point improves the sensitivity. Nine (60%) of the 15 HLA-B27 positive relatives with sacroiliitis had a reduction of chest expansion to 5.0 cm or less, but the specificity diminished with the use of this cutoff. We found a specificity of 67% in the 83 controls. Here, age has an effect. Moll and Wright demonstrated physiologically progressive reduction of chest expansion with age, and in females chest expansion is lower than in males (23,24). Therefore, in interpreting chest expansion, normograms corrected for age and sex should be used. Chest expansion should be measured at the level of the fourth intercostal space (6). Not only this level, but also the breathing instructions, should be standardized in order to minimize interobserver variations. We measured the chest expansion twice. Usually the maximal value was obtained at the second attempt. Possibly, this explains the differences between findings of the study done in Leeds (24) and those of our study. In the former, 60 (57%) of 106 AS patients had a chest expansion of 2.5 cm or less, whereas we found this in 6 (16%) of 37 patients. The mean duration of disease may contribute to differences in chest expansion. If AS had been present less than 5 years, 19% of more than 150 patients were reported to have a chest expansion of less than 2.5 cm, but if the disease duration was at least 20 years, 62% of the patients fulfilled this criterion (25). Treatment also influences chest expansion: with breathing exercises an increase was reported in 40% of AS patients; usually the increase was less than 2.5 cm (26). Moll and Wright have discussed in detail the age- and sex-related reduction of both chest expansion and spinal mobility, and the overlapping values of these AS criteria between patients and controls (23, 24). The combined criterion (reduction of chest expansion to 52.5 cm plus history or presence of pain at the dorsolumbar junction or in the lumbar spine) has no additional value compared with chest expansion cm alone, because the latter is the limiting factor in the sensitivity. We found no significant difference in the occurrence of iritis in relatives with and those without sacroiliitis. This was seen in 2 (13%) of the 15 HLA- B27 positive relatives with sacroiliitis and in 2 (4%) of 45 HLA-B27 positive relatives without sacroiliitis. Acute anterior uveitis is more precisely defined as iritis; therefore, we believe this expression should be preferred. Acute anterior uveitis is more closely related to HLA-B27 than to sacroiliitis (20). In this study, we have already suggested the same for thoracic pain and stiffness complaints. In our opinion, the existing New York criteria can be improved by replacing the New York pain criterion with the Rome pain criterion in a slightly modified form. The aim of this paper was not to introduce new elements (e.g., HLA-B27 typing results) into the existing criteria, but to evaluate and, if necessary, revise these criteria relying on clinical and radiographic features only. Therefore we have omitted discussion about HLA typing as one of the diagnostic criteria. The proposed modifications of the New York criteria for AS are summarized in Table 8. What effect will this modification of the New

7 AS CRITERIA 367 Ydrk criteria have in clinical practice? Ten of the 21 relatives with sacroiliitis fulfilled the New York criteria for definite AS. These 10 all had AS according to the modified criteria as well. However, the number of relatives with sacroiliitis who fulfilled the modified New York criteria increased slightly: 2 relatives with sacroiliitis who originally fulfilled the Rome criteria for AS, but not the New York criteria, had definite AS according to the modified criteria. Possibly the revised criteria are more sensitive than the original ones. The 3 revised clinical criteria together were always negative in the relatives without sacroiliitis and in the population controls. However, these modified criteria should be tested in other groups of patients. Such studies should also include early stages of AS, because we suspect that the official New York criteria are less useful in such cases. The proposed modification seems to be more promising for the definition of these early cases. The clinical history screening test was only moderately sensitive (38%) in relatives with sacroiliitis (Table 7), but patients with relatively few symptoms are possibly overrepresented in our study. Therefore in clinical practice, where patients present with back pain, the sensitivity of the test might be better. The usefulness of the test in early cases of AS should, however, be further evaluated. For the detection of early cases a highly sensitive test is indicated, and loss of specificity might be acceptable. Surely if this test gives positive results, radiologic investigation of the sacroiliac joints is indicated, and appropriate treatment should be given. In this study, arthritis of peripheral joints was only found at examination in HLA-B27 positive, sacroiliitis positive relatives of HLA-B27 positive AS probands. A history of knee swelling has been found to suggest early AS in young subjects with persistent low back pain (27). However, in our opinion, it might be difficult to differentiate inflammatory causes of knee swelling from mechanical causes, if the swelling has occurred at some time in the past. To clarify this point, a prospective study seems desirable and should include analysis of synovial fluid. ACKNOWLEDGMENTS The authors wish to acknowledge Dr. Herma Hazevoet, Herman Colenbrander, Dirk Jan de Rooy, and Huub Haanen for reading the radiographs and are grateful for the assistance of Hermine van der Linden, Bram van Laar, Leo Muller, and Dr. Leo van Romunde. Hanny Hins and Madeleine Kummer typed the manuscript. Tissue typing was performed by the Blood Bank of the Leiden University Hospital (Prof. J.J. van Rood). The help of Prof. L. Nijenhuis and Dr. J. Hermans in preparing the manuscript is gratefully acknowledged REFERENCES Willkens RF, Arnett FC, Bitter T, Calin A, Fisher L, Ford DK, Good AE, Masi AT: Reiter s syndrome: evaluation of preliminary criteria for definite disease. Arthritis Rheum 24: , 1981 Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee: Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23: , 1980 Tan EM, Cohen AS, Fries JF, Masi Ar, McShane DJ, Rothfield NF, Schaller JG, Tala1 N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25: , 1982 Kellgren JH, Jeffrey MR, Ball J: The Epidemiology of Chronic Rheumatism. Vol. I. Oxford, Blackwell Scientific Publications, 1963, pp Gofton JP, Lawrence JS, Bennett PH, Burch TA: Sacroiliitis in eight populations. Ann Rheum Dis , 1966 Bennett PH, Burch TA: Population Studies of the Rheumatic Diseases. Amsterdam, Excerpta Medica Foundation, 1968, pp Moll JMH. Wright V: New York clinical criteria for ankylosing spondylitis. Ann Kheum Dis 32: , 1973 Calin A, Fries JF: Striking prevalence of ankylosing spondylitis in healthy W27 positive males and females: a controlled study. N Engl J Med , I975 Cohen I,M. Mittal KK, Schmid FR, Rogers LF, Cohen KL: Increased risk for spondylitis stigmata in apparently healthy HL-A W27 men. Ann Intern Med 84:l-7, 1976 Truog P, Steiger U. Contu L, Galfre G, l rucco M, Bernoco D, Bernoco M, Birgen I, Ceppellini R: Ankylosing spondylitis (AS): a population and family study using HL-A serology and MLR, Histocompatibility Testing. Edited by F Kissmeyer-Nielsen. Copenhagen, Munksgaard, 1975, pp Christiansen FI, Owen ET, Dawkins RL, Hanrahan P: Symptoms and signs among relatives of patients with HLA-B27 ankylosing spondylitis: correlation between back pain, spinal movement, sacroiliitis and HLA antigens. J Kheumatol (suppl 3) 4: 11-17, 1977 Christiansen FT, Hawkins BR, Dawkins RL, Owen ET, Potter RM: The prevalence of AS among B27 positive normal individuals: a reassessment. J Rheumatol 6: , 1979 Dawkins RL, Owen ET, Cheah PS, Christiansen FT, Calin AA, Gofton J: Prevalence of ankylosing spondyli-

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