895

PRELIMINARY CRITERIA FOR THE
CLASSIFICATION OF THE ACUTE
ARTHRITIS OF PRIMARY GOUT
STANLEY L. WALLACE, HARRY ROBINSON, ALFONSE T. MASI, JOHN L. DECKER,
DANIEL J. McCARTY. and T’SAI-FAN Y o

The American Rheumatism Association sub- ies of the natural history of gout, of the evaluation of
committee on classification criteria for gout analyzed data therapy, and of the epidemiology of the disorder have
from more than 700 patients with gout, pseudogout, rheu- suffered from the lack of a standard classification. I n an
matoid arthritis, or septic arthritis. Criteria for classify- attempt to achieve a more uniform system for reporting
ing a patient as having gout were a) the presence of and comparing data, a subcommittee of the Diagnostic
characteristic urate crystals in the joint fluid, and/or b) a and Therapeutic Criteria Committee of the American
tophus proved to contain urate crystals by chemical or Rheumatism Association was charged with assembling
polarized light microscopic means, and/or c) the presence information, so that criteria for the classification of
of six of the twelve clinical, laboratory, and X-ray phe- arthritis due to primary gout could be developed.
nomena listed in Table 5.

Acute gouty arthritis has been clinically recog- DATA COLLECTION
nized since antiquity. Nevertheless comparisons of stud-
Rheumatologists in teaching clinics and in private
From the Gout Classification Criteria Subcommittee of the practice collected data on patients with the following diag-
American Rheumatism Association Committee on Diagnostic and noses: primary gout; definite or classic rheumatoid arthritis
Therapeutic Criteria. (RA) ( I ) of 2 years or less duration; definite or classic RA of
Supported in part by The Arthritis Foundation, by P H S more than 2 years duration; pseudogout; and acute septic
Research Grant AM-12049 from the NIAMDD, and by the Jonathan arthritis (other than tuberculosis). Thirty-eight rheumatolo-
Joseph Research Foundation. gists from 38 centers distributed across the United States
Stanley L. Wallace, M.D.: Associate Director of Medicine, contributed data on up to 5 patients in each category. The
Jewish Hospital of Brooklyn, and Professor of Medicine, State Uni- following fiumbers of acceptable protocols were submitted:
versity of New York, Downstate Medical Center, Brooklyn, New gout-178, RA I2 years duration-143, R A > 2 years dura-
York; Harry Robinson, Sc.D.: Professor and Chief, Section on Biosta-
tistics, University of Tennessee College of Medicine, Memphis, Ten- tion-156, pseudogout-I 10, and acute septic arthritis-I 19,
nessee: Alfonse T. Masi, M.D., Dr. P.H.: Professor of Medicine and yielding a total of 706 patients for analysis. Contributors were
Director of the Division of Connective Tissue Diseases, University of selected by the committee on the basis of interest in and
Tennessee College of Medicine, Memphis, Tennessee; John L. Decker, experience with gout and its differential diagnosis.
M.D.: Chief. Arthritis and Rheumatism Branch, National Institute of It must be noted here that no information was col-
Arthritis and Metabolic Diseases, Bethesda, Maryland; Daniel J. lected o n patients with secondary gout. All subsequent con-
McCarty, M.D.: Professor and Chairman, Department of Medicine, clusions to be drawn from the data can only be applied to
Medical College of Wisconsin, Milwaukee, Wisconsin; T’sai-Fan Yii, primary gout. In addition, no control groups consisting of
M.D.: Research Professor of Medicine, Mount Sinai School of Medl- patients with degenerative joint disease, Reiter’s syndrome,
cine, City University of New York, New York, New York.
Address reprint requests to Stanley L. Wallace, M.D.. Jewish psoriatic arthritis, etc, were used in the study. The com-
Hospital of Brooklyn, 555 Prospect Place, Brooklyn, New York parisons to b e made are between acute gout and the specified
11238. control diseases.
Submitted for publication November 8, 1976; accepted No- The data reporting form designed by the committee
vember 24. 1976. included seven pages of questions relating t o the details of

Arthritis and Rheumatism, Vol. 20, No. 3 (April 1977)

to yield a more limited number of criteria. Oligoarthritis attack 4. tests of renal function. Asymmetric swelling within a joint on x ray* considered to demonstrate the claimed diagnosis and to have 11. questions were asked about family history of gout. 13 criteria were chosen. variables of high specificity but low sensitivity (e. Hyperuricemia The problem of incomplete data was considered at 10. Further analyzed as a dichotomous variable: normouricemia/hyper. Joint fluid culture negative for organisms during attack is ideal. Analysis of over 200 variables in five study history and physical exam were analyzed according to first groups totaling over 700 patients had to be simplified in a attack. In subsequent analyses the not known entries then to select the fewest possible which. when totaled. These cri- 8. 9. All forms 7.g. Hyperuricemia was defined separately for each crimination observed. or with a paucity of information in control 3. continuous variables were created for analysis of the patients The committee recognized that not all the variables in the different diagnostic groups. present or allow acceptable sensitivity and specificity for classification. would either were not included or were assigned values. Distribution of joint involvement was noted. consideration was given to proposed criteria. Monosodium urate monohydrate microcrystals in joint presence or absence in the patients in whom appropriate infor- fluid during attack mation was available. In 1. in proportion to its 12. First metatarsophalangeal joint painful or swollen tor. If there was no arthritis of primary gout. and lute value and in relation to the upper limit of normal for that analysis of variance tests. were accepted for analysis. Unilateral first metatarsophalangeal joint attack composite list was reviewed for duplication.g. 3. More than one attack of acute arthritis from the first episode or onset. Unilateral tarsal joint attack of committee evaluation. Subcortical cysts without erosions on x ray allocate missing information randomly. Hyperuricemia utors because of internal inconsistencies. Data were coded rational fashion. Proposed Criteria for Acute Arthritis of Primary Gout fication of acute gout compared to the other disease groups. Monoarthritis attack groups (e. the information was coded individual variables that best discriminated the study groups. Continuous data were coded directly. response to colchicine) were not selected. or not known. In any system in which classification depends upon the x ray. Tophus (proven or suspected) mittee chairman (SLW). Only those forms 10. Table 2. N o method of coping with missing data 13. 205 dichotomous and 30 by the method used. evidence of renal calculi. * This criterion could logically be found on examination as well as on x ray. 2. Proposed Suroey Criteria for Acute Arthritis of Primary Gout ning of arthritis) as well as the most recent attack. Complete termination of an attack consistent data. absent. t. By such 4. incomplete data in a regard to examination. At least half the variables showed method in that laboratory. most recent attack. or either attack. ing the degree of independence of the selected variables. Maximum inflammation developed within 1 day renal stone). Only the most discriminatory of related variables was used. Unilateral first metatarsophalangeal joint attack rays. i. whether or not all details were available. with noncontinuous variable respon. patient means that each missing variable cannot be counted . selection of variables was based on the overall degree of dis- uricemia. and joint X 6. joint fluid analysis. but random allocation allows maximal data utilizatiori ~ ~ ~~ ~ on all patients.896 WALLACE ET AL onset and joint involvement during the first attack (or begin. Redness observed over joints laboratory findings including serum uric acid. The 6. However the protocol did not request this information in regard to examination. A final decision was made to 11. rheumatoid fac- 5 . of occurrence in the study groups by series of xz. Maximum inflammation developed within 1 day factors precipitating attacks. Thus the highest uric Each variable was analyzed in terms of its probability acid value was coded directly. Specificity was de- for some variables. as not known. First it was decided to identify those response to a particular question. From 53 items on the form. However the protocol did not request this information in presence of a specified number of criteria. METHODS OF ANALYSIS tions from the mean uric acid level for a healthy population. for computer processing. according to a program of random allocation of results Sensitivity was defined as the proportion of patients with as described below. Unilateral tarsal joint attack were reviewed for accuracy and completeness by the com- 8. Multi- variate analysis was used to verify that variables selected for consideration as criteria contributed significantly to the classi- Table 1. Redness observed over joints processes. and tends to allow for optimal sensitivity of the * This criterion could logically be found on examination as well as on criteria. Some were returned to the contrib- 9. 2. First metatarsophalangeal joint painful or swollen seemed best to discriminate gout from the other disorders. Tophus (proven or suspected) teria are listed in Table 1. if different 1. differences in the upper limits of normal. as well as o n clinical judgment regard- laboratory as a level above the mean plus two standard devia. In addition. More than one attack of acute arthritis addition. Asymmetric swelling within a joint on x ray* great length by the committee. absent. which could then be applied to the classification of the acute ses recorded as present. Serum uric acid levels were also some degree of statistical difference by these analyses. and analyzed both as an abso. but primary gout fulfilling proposed criteria. each committee member selected 10 variables that 5 . response to colchicine therapy. such as serum uric acid determinations fined as the proportion of control patients that did not fulfill performed in different laboratories. Most of the items from the were independent.e. and by a process 7.

septic arthritis.6%) of the gout of those with rheumatoid arthritis or with pseudogout. crystals. As might be expected. the gout group had the 119 patients with septic arthritis.3 70.2 68. had their joint fluid examined for summarized in Table 4.3 1. patient with rheumatoid arthritis. and in 4 patients with septic arthritis.4%). and in all cases was found in The sex distribution and the mean values for age typical sites. The survey cri. In part it may be because inflamed failure to find crystals in the remaining patients are not tarsal and interphalangeal joints are difficult to aspirate. not available.3 64.2 38. pseudogout showed urate crystals. being found in 84. The crystals were defined by of the crystal criterion lies in its absolute specificity. exhib- iting white to yellowish content. no needle or rod shape and by negative birefringence. No urate crystals were seen in any of the other population of gouty patients.3 Joint fluid examined for crystals (%) 50. certain.6 Mean age (years) 56. as de- lowest proportion of females (13. this information was often those circumstances. seen by academic rheumatologists with a par. and in 112 of the analysis. contain sodium urate crystals either chemically or by teria were analyzed separately in order to evaluate their sensi. in none interesting that only about half (50. Urate Crystals in Joint Fluid and Proven Tophi Primary Pseudo. in comparison to nearly 25% of the rheumatoid The presence of urate crystals in joint fluid was a patients and more than 80% of pseudogout and 70% of moderately sensitive classification criterion for acute septic arthritis patients.7 21. Proven tophus. Table 4.0 26.CRITERIA FOR PRIMARY GOUT 897 Table 3. Clinical Features of Primary Gout and Control Patients Primary Pseudo.6 82. Joint ical diagnostic techniques. and which was proved t o aspiration was not required for these criteria.8 47.6 54. The patients in whom crystals were not urate monohydrate were seen in synovial fluid in 76 found were not clinically different from the rest of the (84.4% of patients with gout in frequency of joint aspiration in the patients with acute whom joint fluid was analyzed. or in popu. all with shown in Table 3 for the 706 patients accepted for rheumatoid arthritis and pseudogout. These data are ticular interest in gout. polarized light microscopy. grossly demonstrable in body tissues by phys- lation surveys by history and review of clinic records. RA I RA > Septic Gout gout 2 Years 2 Years Arthritis (n = 178) ( n = 110) (n = 143) ( n = 156) ( n = 119) Urate crystals 76 of 90 0 of 91 0 of 30 0 of 41 0 of 84 Proven tophi 52 of 172 0 of 110 0 of 143 0 of 156 4 of 112 . tive for the variable. under tion of the crystal by uricase. RA I RA > Septic Gout gout 2 Years 2 Years Arthritis Clinical Features (n = 178) (n = 110) ( n = 143) (n = 156) (n = 119) Women (%) 13. The location of the suspected tophus was described. as if the patient were known to be nega. able size. The net effect is the same. fined as a subcutaneous or intracutaneous mass. Ques.1 6.2 11.3 Duration of disease (years) 10. The skill of the searcher and the vigor with Of the 90 patients with gout who had joint fluid which crystals were looked for are variables that were examinations.1 51. was found in 52 of 172 patients with gout. patients. which was not tested RESULTS for sodium urate crystals.6 64. characteristic microcrystals of sodium not studied. The reason for the relative in.0 - toward the necessary number. The overwhelming value disease groups (Table 4). A related list of criteria (Table 2) was developed to be A proven tophus was defined as a mass of vari- used in a single patient visit to a clinic or office. It was particularly fined. The presence or absence of proven tophus and duration of disease for each of the five groups are could be established in 172 patients with gout. The reasons for the gout was not clear.6%). or tions were asked about extinction angle and about diges. gout. A suspected tophus was de- tivity and specificity in the classification of acute arthritis of primary gout.6 52.

4 (142) 44.2 (166) 51. Percentage Distribution of Positive Responses and Number of Specijied Responses to Individual Criteria Among Diagnostic Groups Primary Pseudo. Table 5 reports the information col- abling the classification of any patient with the appro.0 (156) 1.0 1 0. nevertheless respects every individual on whom information is avail- seems to be most useful in distinguishing acute gout able is included in this analysis. although none was seen in this study.9 (49) 96. in all other criterion.0 RA > 2 years 156 13 8.8 (103) 32.3 (97) 18. and 7 1 had neither demonstrable crys- tophus had been considered as an absolute criterion.9 (108) 8. disorders). Of those Their acute episodes might have been misclassified as with primary gout. Clearly a further set of classification It seems reasonable.0 (104) * Numbers in parentheses indicate the number of individuals with each disorder on whom information was available far each criterion.7 3 2.8 (137) 9.3 12 10.3 (93) More than one attack 86.1 (124) 10.0 (20) 24.8 * Criteria are those listed in Table 5.5 (108) 1. WALLACE ET AL Table 5. including priate crystals in the joint fluid as having acute gout.0 (113) 11. However tive and 99% specific (against the totality of control proven tophi were nearly as specific as urate crystals. when present.1 (154)* 59. % Primary gout I78 170 95.1 (137) 5.0 (101) 0 (139) 0 (152) 0.9 (117) 13. rather than as septic arthritis. therefore.7 RA I 2 years I43 10 7.0 4 2. table shows the percentage of patients in each group that Proven tophus is both less sensitive and less spe.6 (156) 49.9 (178) 63.5 (130) 20.1 (174) 0.0 (173) 6. and septic arthritis.2 (141) 58.1 Pseudogou t 110 30 27.5 I 0.5 156 87. RA I RA > Septic Gout gout 2 Years 2 Years Arthritis Individual Criteria (n = 178) (n = 110) (n = 143) (n = 156) (n = 119) Maximum inflammation 1 day 85.0 (14) 100. lected in regard to the other twelve criteria. pseu- Other rheumatic diseases may occasionally coexist with dogout. had each criterion.0 (119) Suspected tophus 19.3 1 0.0 (102) 38. in all patients with acute gout.5 (122) 43. The variable suspected tophus ex- cific than joint fluid crystals. of 5 o r More 6 or More 7 o r More Disease Group Patients No.4 (145) 1.7 (122) 32.8 (119) Monoarticular arthritis 71.0 (99) 2. This acute gout.1 (155) 11.4 (118) Unilateral first MTP 47.9 (108) H yperuricemia 92.4 (77) Asymmetric swelling 41.8 (82) 12.1 (171) 1. not searched for or not found when sought.3 (83) 8. Although not an absolute cludes those patients with proven tophi.9 3 2. if proven described above.2 (167) 17.7 (152) 3. rheumatoid arthritis. This criterion is 30%sensi- only in about 30% of patients with gout. .2 (99) Subcortical cysts.8 (156) 5. proven tophus.5 (178) 71. Table 6. to consider urate criteria is necessary to distinguish acute gout from the crystals in the joint fluid as an absolute criterion en. % No. being found from the control disorders.0 (108) First MTP pain o r swelling 78.9 (108) 5.9 (130) 75.6 (110) 13.6 Total RA 299 23 7.5 (97) 11.8 0 0. Number and Percentage of Patients in Each Disease Group with Selected Numbers of Positive Criteria Positive Criteria' No.6 I32 74.3 Septic arthritis 1 I9 8 6.5 (118) 3. 126 did not have proven tophi as acute gout.7 (119) Unilateral tarsal 21.0 (90) 9. suspected tophus.7 (106) 36.3 (143) 9.5 (57) 100. fewer than 1% (4 of 521) of the control group had There were 102 individuals with primary gout in tophaceous deposits. no erosions 11. Proven tophi were less sensitive. control diseases.9 (126) 2.3 2 1.7 6 2. tals nor tophi.6 ( I 19) Redness 92.0 (102) Negative organisms on culture 95. Presumably these four positive this study in whom joint fluid urate crystals were either patients had both tophaceous gout and septic arthritis. % No.

but not subcortical cyst without reasons the presence of a proven tophus cannot be an erosion on X ray. Number and Percentage of Patients in Each Disease Group with Selected Numbers of Positive Survey Criteria Positive Criteria No. for. and over 96% against septic arthritis). the best combination of urate crystals either chemically or by polarized light specificity and sensitivity seems to be with six of the microscopy. the remaining clinical. an unacceptable lack of tual practices among rheumatologists interested in gout specificity. This survey of ac- gout also satisfied five criteria. the been substituted for monoarthritis and complete termi.3-2.8 Table 6 shows the number and percentage of these criteria. proved to contain sodium proven tophus are excluded. but 85% of the time.2 2 I . 7% No.1%. have discussed in detail possible reasons for this failure. patients with acute gout in this study.9 1 0.4 151 84.3 2 I . % ~~~~ ~ ~~ Primary gout 178 168 94.8 RA I 2 years 143 6 4. However 27.4). Nevertheless. Another patient with septic arthritis and were also analyzed.0 5 1. characteristic crystals were found in acute gout only teria reduced the sensitivity in acute gout to 74. nohydrate crystals in the joint fluid.7 1 0. present to produce acceptable sensitivity and specificity. radiologic. The total is eleven (over 99% totally.7 3 2.4 0 0. When urate crystals in the joint fluid and/or The presence of tophi. Five or more DISCUSSION criteria were found in 95. specificity of proven tophus for acute gout was very high nation of an attack has been added. . and in only single criterion. In this study proven tophi were considered. criteria. Six or more of these criteria were found in demonstrates the difficulties in restricting oneself to this 87. or joint absolute criterion that the associated acute arthritis is fluid culture negative for organisms. It must be remembered The presence of crystals. For these (proven or suspected).3% of patients with septic or rheuma. 97. acute pseudogout more criteria level from Table 5.5 1 0. When searched fied six or more criteria. of 5 or More 6 or More 7 or More Disease Group Patients No.3 Septic arthritis I19 8 6.5 8 7.7-8. and/or that every patient entered into the project had articular combinations of the various criteria from Table 5 in our inflammation of some sort. At the six-or. urate crystals in joint fluid. % No. Six of the eleven criteria would have to be patients within each disease group who had five or more. gout is to demonstrate characteristic sodium urate mo- toid arthritis.5% of patients with primary The best way t o classify a patient as having acute gout. proven tophi.7% of patients reported a group of patients with acute gouty arthritis in with pseudogout and less than 1% of those with other whom crystals were sought and not found.5 3 I . Oligoarthritis has gouty. and they control disorders had seven criteria. Gout may infrequently coex- patients with gout has been evaluated. ist with acute septic arthritis (3. ticular disorder were established in only 4 patients with The related survey criteria recorded in Table 2 septic arthritis. Schumacher et al (2) have recently improved the specificity greatly. The requirement of seven cri.8% of gout patients simultaneous proven tophaceous gout and a second ar- satisfied one or more of these methods of classification.0 RA > 2 years 156 18 11.8% of those with septic arthritis or rheumatoid time in the patient’s course in only about half of the arthritis. only 2. also has been shown by this study to be twelve criteria listed in Table 5 . six or more.CRITERIA FOR PRIMARY GOUT 899 Table I. Table 7 records the number and percentage of In the absence of either joint fluid or tophaceous patients in each disease group who had five or more of sodium urate crystals. These criteria include tophus one with pseudogout had suspected tophi. Nearly 11% of patients with pseudogout satis.2 Pseudogout 110 28 25. or active rheumatoid arthritis (6). Crystals were actually sought at any 1. when urate crystals and (4.3% of patients with pseudo. useful in categorizing patients.5). although sensitivity was low. and in 6.6% of patients with acute primary gout.6 Total RA 299 24 8.8 116 65. or seven or more positive criteria from among the twelve criteria listed in Table 5.

tophi. 197 1 review of clinic records. JAMA 197:953-956. Grahame R. 1972 useful in population surveys. 3. it identified 97. Irby R:Coexistent rheumatoid arthri- test them in the future in such an investigation.9%of patients with acute pseudogout. Phelps P: Septic arthritis. pseudogout and eleven criteria to produce a somewhat greater specificity osteoarthritis in a patient with multiple myeloma. x-ray.900 WALLACE ET AL and laboratory criteria listed in Table 1 (and in Table 5 ) REFERENCES served as reasonable classification criteria for acute gouty arthritis. 1975 The proposed survey criteria listed in Table 2.7% against pseudogout) and lower sensitivity Rheum 15:89-96. Bull Rheum 10. Arthritis (92. et al: 1958 revision of twelve were found in 87. Rheum 18:603-612. and in much Dis 9:175-176. gout. Sutor D. Bennett G A . 1972 (84. and laboratory criteria was highly ination of synovial fluid: report on nine patients. Smith J R . and it seems appropriate to 6.6% of patients with gout. Owen DS. 2. 1958 smaller percentages of the other control disease patients.8%) than the six of twelve criteria described above. 1966 . 5. JAMA ascertainable in a single patient visit or by history and 218:592-593. Ropes MW.8% of our patients with gout. et al: Acute gouty The combination of crystals. Hess RJ. Six or more criteria from this list of 1. Toone E. in diagnostic criteria for rheumatoid arthritis. Gibson T. Cobb S. Mitchener SM: Crystal deposition in However these criteria were chosen specifically t o be hyperparathyroidism. and/or six or more arthritis without urhte crystals identified on initial exam- of the clinical. tis and chronic tophaceous gout. Arthritis sensitive. Schumacher H R . required the presence of six of 4. Martin JH: Pyarthrosis complicating gout. Jiminez SA. Ann Rheum Dis 30597-604.