Psoriatic arthritis definition and classification criteriaPhilip HelliwellSenior Lecturer in RheumatologyUniversity of Leeds

Psoriatic arthritis Wright VAnnals of Rheumatic Diseases1961;20:123-132

Too sensitive?Too specific?

Moll and Wright 1973

All of the following:1. Inflammatory arthritis (axial or peripheral joints)2. Psoriasis3. Negative for rheumatoid factor (RF)

Table 2. Bennett (1979) original

Clinically apparent psoriasis (skin or nails) in association with pain and soft tissue swelling and/or limitation of motion in at least one joint, observed by a physician for six weeks or longer

Plus 6 of the following:

Pain and soft tissue swelling and/or limitation of motion in one or more other joints observed by a physician

Presence of an inflammatory arthritis in distal interphalangeal joint that is not a Heberdens node

Presence of a sausage digit

Asymmetric distribution of arthritis in hands and feet

Absence of subcutaneous nodules

A negative test for rheumatoid factor (RF)

An inflammatory synovial fluid with a normal or increased C3 or C4 level and an absence of infection or MSU, calcium pyrophosphate crystals

A synovial biopsy showing synovial lining hypertrophy with a predominantly mononuclear cell infiltrate and absence of granuloma formation or tumour

Peripheral radiographs showing erosive arthritis of small joints with a relative lack of osteoporosis, specifically excluding erosive osteoarthritis

Axial radiographs showing one or more of: sacroiliitis, syndesmophytes, paravertebral ossification

Bennett proposed a rather more complex definition, that includes synovial biopsy and synovial fluid analysis. If you cant read it then clearly it is too complex. Clearly impractical.

All data

Criteria positive disorderHospital numberANA related diseaseANA +/-Study numberDiagnosisANA titreAgeSex

00

NOgne4610NOpositive4Undifferentiated spondyloarthropathy16029male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!01

YESfeg7474NOnegative5Gout39male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!11

NOgab5577NOnegative6Regional soft tissue disorder65female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOdym5392NOpositive7Regional soft tissue disorder4042female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOakx7934NOnegative16Osteoarthritis52female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOdgf5117NOnegative17Psoriatic arthritis51female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEScct1832YESpositive25SLE128063female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOmkc6420NOpositive30Ankylosing spondylitis64038female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESbyv6492NOnegative32Polymyalgia rheumatica72male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOkzz8156NOpositive33Osteoarthritis8047female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOcra2312YESpositive34Undifferentiated CTD16069female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEScty6759NOnegative44Fibromyalgia51female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESlfp9125NOnegative45Fibromyalgia41female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESegn7065NOpositive46Psoriatic arthritis4043male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESlka9742NOpositive50Rheumatoid arthritis4080female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESmkw3291NOpositive53Gout4053male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEScfn8422NOpositive54Gout4065male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESfgs2093NOnegative60Osteoporosis46female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESgma4095NOnegative61Ankylosing spondylitis49male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOcbf9604NOpositive62Chronic pain disorder16059female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESbzg8014NOpositive63Rheumatoid arthritis4034female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOfyj4109NOpositive65Undifferentiated CTD16057male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOdut4188NOpositive66Regional soft tissue disorder8071male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESday2814NOnegative68Reactive arthritis37male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOevu5994NOnegative69Regional soft tissue disorder25female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOfgp7919NOpositive70Osteoarthritis8050male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOdbg4873NOpositive71Osteoarthritis4049female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOgav9856N0negative72Psoriatic arthritis25female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOmht8239NOpositive73Osteoarthritis4065female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESceb8103NOnegative74Osteoporosis82female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NObzt7352NOpositive75Reactive arthritis4053female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOell2028NOpositive76Regional soft tissue disorder4019female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESmbb8064NOpositive78Rheumatoid arthritis16055male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NObfv0896NOpositive81Osteoarthritis16071female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOcbj8078NOnegative85Chronic pain disorder53female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESghk1461YESpositive86Scleroderma8053female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESlbf2994YESpositive89SLE256029female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESctl9540NOnegative90Gout43male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOcay2799NOpositive92Osteoarthritis8085male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NObyu8031NOpositive93Regional soft tissue disorder16063female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEScbb0273YESpositive94Sjogren's syndrome256046female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESccg7105NOpositive95Rheumatoid arthritis16063female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESfax1593NOnegative97Gout47male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESczr5654NOnegative99Polymyalgia rheumatica64female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOemz513NOpositive100Other8029female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOgba4570NOnegative101Other35female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEShdw0126NOpositive104Gout8081male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOdnb1338NOnegative105Osteoarthritis53female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOcbz6883NOpositive106Other8060female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESgup7089NOpositive108Rheumatoid arthritis4028female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESejb5142NOpositive111Polymyalgia rheumatica16082female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESddp7357YESpositive112SLE256044female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOeek0707NOpositive115Other16047female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEScd8253NOnegative118Psoriatic arthritis27male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESmmz9813NOnegative119Reactive arthritis52female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESleu7699YESpositive121SLE16069female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOmaj8076NOnegative123Chronic pain disorder32female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEScmt9079NOnegative124Gout52male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOaee5600NOnegative127Other54female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOdew7015NOpositive128Osteoarthritis8079female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOedq0378NOnegative130Osteoarthritis66female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEScyh4382NOpositive131Rheumatoid arthritis8048female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOdsy6804NOnegative132Osteoarthritis36female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOlrj7279NOpositive133Undifferentiated spondyloarthropathy80female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOmne2577NOnegative134Chronic pain disorderfemale00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESYESpositive135SLE2560female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESenv6811NOnegative136Gout40male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESmne3069YESpositive138SLE16042female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEScsb0999YESpositive139SLE32038female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEScfz7764NOnegative140Polymyalgia rheumatica77female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOcbf1964NOnegative141Regional soft tissue disorder48male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESdcy7122NOnegative142Ankylosing spondylitis54male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOceq2114NOnegative144Other42male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEScrv2138NOnegative145Undifferentiated spondyloarthropathy36male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEScat4263YESpositive146Scleroderma256072female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESguq1949NOnegative147Polymyalgia rheumatica67female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOmqp6651NOpositive148Other8050male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESgbn4265NOpositive150Rheumatoid arthritis8079male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESlnx7209NOpositive152Rheumatoid arthritis8069male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESljt8523NOpositive153Reactive arthritis64063female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESlkt1884NOnegative154Polymyalgia rheumatica75female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESakr5351NOpositive155Polymyalgia rheumatica4085male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESerh1052NOpositive156Other256076female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOcwy4539NOnegative157Osteoarthritis72female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESbzc5536N0positive158Rheumatoid arthritis64055female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOmpx4763NOnegative161Osteoarthritis57female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOdud2391NOpositive166Regional soft tissue disorder8080female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESNOpositive169Rheumatoid arthritis8074male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEScmt3534NOpositive171Rheumatoid arthritis4039female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESadk1488NOnegative173Fibromyalgia54female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESdsn2472YESpositive175SLE16050female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YESbzc5307NOnegative177Rheumatoid arthritis71male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOdct4495NOnegative180Osteoarthritis91male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NObzj2939NOpositive182Osteoarthritis8066male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOcut9500NOpositive184Osteoarthritis4048male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOcfy5499NOnegative185Osteoarthritis81female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

YEScax3668NOpositive186Rheumatoid arthritis4067female00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

NOmdk3502NOnegative187Undifferentiated spondyloarthropathy37male00000000000000#ERROR!000#ERROR!0000000000#ERROR!#ERROR!

53129854.9684210526

criteria +veANA disease16.6205798037

&A

Page &P

All data ROC

10

11

11

0.9166666667

0.6666666667

0.5833333333

0.5

0.4166666667

0

ANA titre

Perfect

1 - specificity

sensitivity

LR CI

SensitivitySpecificityABLR+upper limitlower limitCDLR-upper limitlower limit

10.5124422.98389801721.34052838840.0000144000

10.662790697712292.96551724144.70056626911.87090065440.0000157000

0.91666666670.848837209311136.064102564110.72904520283.42745689041730.0981735160.64252900750.0150001621

0.66666666670.96511627918319.111111111142.09377546498.6766882724830.34538152610.76956436030.1550076962

0.58333333330.96511627917316.722222222239.9470824987.0000785685830.43172690760.8442641820.2207699044

0.50.9883720936143114.136405898116.1999143526850.50588235290.89120245080.2871591688

0.41666666670.9883720935135.8333333333107.530517697211.94105455157850.59019607840.95259994720.3656638991

All data analysis

ANA titreNumber of patients with ANA related diseaseNumber of patients with non-ANA related diseaseNumber of patients with ANA related diseaseNumber of patients with non-ANA related diseaseFalse positive rateTrue positive rateLikelihood ratio +Likelihood ratio -Y error bars+_Lower 95% CI lineUpper 95% CI line

Cutoff levels10.735400.264610.735411

0042012861110.735400.26460.50.73540.23881

4001515401244400.512.000.0010.735400.26460.33720930230.73540.15116279070.9979

8011617801229800.337209302312.970.000.99790.61520.08123333330.30146666670.15116279070.61520.0830.9166666667

1603101316011131600.15116279070.91666666676.060.100.90080.34890.23413333330.31776666670.09860.58333333330.03488372090.9008

320101320833200.03488372090.666666666719.110.350.84830.27670.26496666670.30663333330.06310.50.0116279070.7891

640123640736400.03488372090.583333333316.720.430.78910.21090.28910.28910.06310.416666666700.5

128010112806112800.0116279070.543.000.510.72330.15170.30663333330.26496666670.03488372090.276700

256051625605125600.0116279070.416666666735.830.590.0116279070.1517

12860000

2X2 tablesx error bars

0.958100.042

012860.4140.6210.1210.086

Classification rules ranked by Youdens index [(sens + spec) 1]

Vasey0.984

Gladman0.963

McGonagle0.959

Moll and Wright0.934

Bennett0.687

ESSG0.542

Table 4. Vasey & Espinoza (1984)

Criteria 1 plus either Criteria 2 or 3

Criteria 1: Psoriatic skin or nail involvement

Criteria 2: Peripheral pattern

Pain and soft tissue swelling with or without limitation of motion of the DIP joint for over 4 weeks

Pain and soft-tissue swelling with or without limitation of motion of the peripheral joints involved in an asymmetric pattern for over 4 weeks; this includes a sausage digit

Symmetric peripheral arthritis for over 4 weeks, in the absence of rheumatoid factor or subcutaneous nodules

Pencil-in-cup deformity, whittling of terminal phalanges, fluffy periostitis and bony ankylosis

Criteria III: Central pattern

Spinal pain and stiffness with the restriction of motion present for over 4 weeks

Grade 2 symmetric sacroiliitis according to the New York criteria

Grade 3 or 4 unilateral sacroiliitis

Vasey and Espinoza considered Bennetts criteria too complex but wanted to retain xray features of psoriatic arthritis and sacroiliitis. This doesnt require absence of RF as long as the pattern of peripheral arthritis isnt symmetrical.

Percentage of different subgroups from 1973 to 1994

Psoriatic arthritis key individual featuresPsoriasisSymmetryRheumatoid factor

PsoriasisMay be hiddenMay be comingMay have goneMay be in familyMay be misdiagnosed

Symmetry in early and late psoriatic and rheumatoid arthritis

Joint frequency by disease

Psoriatic arthritis - the significance of rheumatoid factorMoll and Wright excluded (usually)Gladman (and others) included ( up to 15%)Not unreasonable to allow RF as may just reflect a chronic inflammatory stateNeed to:Reliably exclude the seronegative rheumatoid arthritisReliably include the seropositive psoriatic arthritis

Rheumatoid factorCould we make this test more specific?Rheumatoid factor isotypesOr use other tests?Anti-perinuclear factorAnti-CCP antibodies

Summary of CART analysis

Variables enteredSplitters selected by CARTSensSpecAll dataCurrent psoriasis0.980.99All data excluding psoriasisRF, dactylitis0.970.78All except psoriasis and RFDactylitis, nodules, symmetry, chest wall pain, juxta-articular new bone, 4 mcp joints, sacroiliitis, PVO, ankylosis, entheseal new bone, chest wall pain, clinical spondylitis0.890.73

Psoriatic arthritis one disease or more?Large joint mono/oligoarthritisEntheseal disease (including spinal disease)SAPHO/CRMODiP and mutilansSymmetrical polyarthritis + Ps = RA?

Psoriatic arthritis does it exist?Cats believed psoriasis merely modifies inflammatory responseImmunogenetic data not all that convincingInflammatory response has an array of common pathways

NOAR

Inception cohort inflammatory arthritis in the communityOne year outcomes5% psoriasis + IAPattern of arthritis and outcome same at 12 monthsMore males, less RF

Harrison BJ. Et al. J Rheumatology. 24(9):1744-9, 1997 Sep.

Psoriatic arthritis why bother?Same NSAIDsSame DMARDsSame biologics

BUTNosologyGood and bad prognostic diseaseTreatment outcomeTreatment indications

Impairment, disability and quality of life in RA and PsA

Disability and quality of life in RA and psoriatic arthritis according to severity of arthritis

Validation of classification criteria for psoriatic arthritis

700 patients with psoriatic arthritis700 controls with inflammatory arthritis and inflammatory OAStandardised proformaClinical and historic dataRadiographic dataGenetic dataQuality controlA prospective multi-centre international case control study

Analysis by:Conditional logistic regressionLatent class analysisClassification and regression treesInternational studyAll major playersConsensus criteriaBased on sound methodologyValidation of classification criteria for psoriatic arthritis RESULTS AVAILABLE IN 2003 2004

What will CASPAR do?Enable us all to use the same criteriaDistinguish between seronegative rheumatoid arthritis and psoriatic arthritis Facilitate studies of natural historyTreatmentimmunogenetics

Psoriatic arthritisIs a distinctive disorderNew criteria need to encapsulate this while not being exclusiveA distinctive (and preferably pathogenic) biologic marker would help

In York I introduced the idea of discriminating between psoriatic arthritis and other disorders using plain xrays. Today Im going to describe the larger classification project that includes clinical and laboratory features as well as plain xrays.Basically, the idea is that we need a validated case-definition of psoriatic arthritis and at the moment we dont have one.