Conventional X-Ray in Early Arthritis

Rheum Dis Clin N Am 31 (2005) 681–698

Conventional X-Ray in Early Arthritis

Annelies Boonen, MD, PhDT,Desiree van der Heijde, MD, PhD

Division of Rheumatology, Department of Internal Medicine, University Hospital Maastricht Care and

Public Health Research Institute, University Maastricht, Maastricht, The Netherlands

The importance of early identification of patients with inflammatory arthritis

and in particular identifying patients at risk of an unfavorable long-term outcome

is recognized. Patients who develop a persistent or erosive arthritis are considered

to have an unfavorable long-term outcome. Rheumatoid arthritis (RA), oligoar-

thritis, polyarticular psoriatic arthritis (PsA), and the other spondyloarthropathies

(SpAs) all are inflammatory conditions that place patients at risk of developing

persistent or erosive disease. The role of conventional radiology of peripheral

joints is well established for RA and has been studied increasingly for PsA, but

less so for the other SpAs. This situation is due at least in part to primarily axial

involvement in these conditions. In RA, radiographic damage can be assessed by

several scoring systems. These methods have proved to be reliable and sensitive

to changes that are clinically relevant. In addition, data from numerous clinical

trials and cohort studies have shown that radiographic damage progresses linearly

over time, reflects cumulative disease activity, is linked to functional outcome,

and can be suppressed by disease controlling antirheumatic therapies (DCARTs).

In the preclassification stage of early inflammatory arthritis (EIA), the role of

conventional radiology has not been explored fully with respect to the diagnostic

or prognostic value or with respect to progression of damage. EIA differs from

the classic diagnostic entities in many aspects. The spectrum of patients included

is heterogeneous from a diagnostic and from a prognostic point of view. Patients

can present with monarticular, oligoarticular, or polyarticular disease, and any

0889-857X/05/$ – see front matter D 2005 Elsevier Inc. All rights reserved.

doi:10.1016/j.rdc.2005.07.004 rheumatic.theclinics.com

T Corresponding author. Division of Rheumatology, Department of Internal Medicine, University

Hospital Maastricht and Care and Public Health Research Institute (CAPHRI), University Maastricht,

P. Debyelaan 25, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.

E-mail address: [email protected] (A. Boonen).

boonen & van der heijde682

joint site can be involved. Many patients have self-limiting arthritis, which is

unlikely to become erosive, whereas a few patients develop severe destructive

disease. This latter group of patients likely has no radiographic abnormalities at

the first evaluation. When treated early, patients with erosive disease show less

progression than observed in advanced disease and may show repair when treated

with drugs able to induce repair. The data available on assessing radiographic

damage in RA or PsA cannot simply be transferred to patients with EIA with

respect to diagnosis, prognosis, or evaluation of progression. This article reviews

the literature on conventional radiographic assessments of peripheral joints in

cohorts of patients with EIA. Also, specific issues on conventional radiology in

EIA compared with early RA and early PsA are discussed. Finally, the role of

conventional radiography in EIA is considered.

Overview of cohorts reporting radiographic assessment in patients with

early inflammatory arthritis

Conventional radiographs have been included as outcome measures in several

EIA cohorts. Publications that limited the analyses of radiographic data to

patients who fulfilled at inclusion criteria for RA [1,2] or PsA [3] are excluded

in this overview because they represent early RA or early PsA. Table 1 presents

the design of the six cohort studies with emphasis on the patient inclusion cri-

teria, method to assess and report radiographic outcome, and results of the ra-

diographic outcome.

Cohorts differed with respect to the maximum disease duration at inclusion

and the definition of the diagnoses at the final follow-up. Radiographs of hands

and feet were included in all cohorts, but methods to assess damage in hands and

feet were not uniform. Further, the following specific characteristics of some

studies should be considered when interpreting the results. In the Norfolk Ar-

thritis Register (NOAR), radiographs were not systematically performed at

inclusion [4,5]. In the Austria Early Arthritis (EA) Action, radiographic data are

limited to patients fulfilling criteria of RA at 1-year follow-up [6]. In the

Amsterdam EA Cohort, the patients with PsA at baseline were excluded, and

radiologic data were presented only for the patients with undifferentiated ar-

thritis (UA) or RA at inclusion [7]. In addition to the radiographs of hands and

feet, symptomatic large joints were imaged in the Austrian EA Action [6] and the

sacroiliac joints were imaged in the Brittany EA Cohort [8,9], but findings of

these films were not yet reported.

Baseline radiographic findings of hands and feet in early inflammatory arthritis

and baseline damage as predictor of final diagnosis

In the Brittany EA Cohort, 15% of patients had erosions in their hands or feet

at baseline (n = 149), 32.5% in the group that was classified at the 2 years as RA

early arthritis: conventional x-ray 683

(37%) compared with 5.5% of patients classified at 2 years as non-RA (P b .02)

[8,9]. Baseline Sharp scores in the hands (n = 285) were 5.9 and 2.5 in the RA

and non-RA groups (P b .001) and in the feet (n = 149) were 2.3 and 1.2 in the RA

and non-RA groups. The authors studied the radiographic item of the American

College of Rheumatology (ACR) 1987 criteria for RA (item 7). This item con-

siders erosions or decalcification in the joints of fingers or wrists. Sensitivity and

specificity of this radiographic criterion in patients with EIA, to predict the

expert’s diagnosis of RA at 2 years, was reported first when using the radiographs

of hands only. The results were compared with sensitivity and specificity after

including the radiographs of the feet and when applying the full Sharp score

instead of erosions and decalcification only. First, it was concluded that decal-

cification had a low reliability. The addition of assessing erosions of the feet

improved sensitivity (from 17% to 33%), while maintaining specificity (95%).

Quantification of erosions and including joint space narrowing by applying

the Sharp score modified by Plant did not improve test characteristics [10].

The positive and negative predictive values of erosions in hands and feet in

this population were 75% (positive predictive value) and 29% (negative predic-

tive value).

In the Leiden EA Cohort, 15% of all patients were erosive at baseline [11].

In the predictive model for unfavorable outcome, the authors used a prognostic

classification instead of the classic classifications and distinguished persistent

synovitis (16%) and erosive disease (24%) as the unfavorable outcomes as

opposed to self-limiting disease (60%) after 1 year. They showed that erosions at

baseline predicted persistent synovitis (relative risk 2.75) and progressive erosive

disease (relative risk infinite) after 2 years. Other predictors of erosive disease

(compared with nonerosive persistence) were morning stiffness lasting longer

than 1 hour, arthritis in more than three joint groups, bilateral compression pain in

the metatarsophalangeal joints, presence of rheumatoid factor (RF), and presence

of anticitrulline peptide.

In the Amsterdam EA Cohort, patients with RA meeting the 1987 ACR

criteria were distinguished at inclusion from patients with undifferentiated

oligoarthritis or undifferentiated polyarthritis (UPA) [7]. After 1-year follow-up,

the latter group was classified as mild or progressive UPA, based on either a

Sharp score greater than or equal to 10 points, increase of radiographic damage

4 or more Sharp points, or a Health Assessment Questionnaire (HAQ) score

greater than or equal to 1. Total Sharp scores, but not frequency of erosive dis-

ease, were reported. In patients with the final diagnosis of mild UA, the median

Sharp score at baseline was 2 (range 0–55) compared with 8 (range 0–58) and

5 (range 0–136) in patients classified at follow-up as progressive UPA or RA.

Of the National Institutes of Health Early Synovitis (ES) Cohort, 8% was

erosive at baseline, with 18% of patients classified as having RA and 5% of

patients classified as having non-RA (P b.01) erosions at follow-up. In a sub-

group of 66 patients, serum matrix metalloproteinase-1 (MMP-1) and C-reactive

protein (CRP) differed between erosive and nonerosive patients (P b.01).

Proteinases did not discriminate RA from non-RA [12,13].

Table

1

Overview

ofstudiesreportingoutcomeofconventional

radiographsin

patientswithearlyinflam

matory

arthritis

Cohort(startyear),

firstauthor,year

[Ref.]

Inclusion,exclusion,

andclinical

outcomea

Radiographic

characteristics

Radiographic

outcomereported

Patientsin

whom

radiographyreported

Radiographic

outcome

Comments

NIH

ESCohort

(1994),Goldbach-

Mansky,

2000

[12];Goldbach-

Mansky,

2000[13]

Inclusion:synovitis

�1joint,�

6wk,

b12mo.

Exclusion:septic

arthritis,crystal

arthritis,defined

system

icdisease.

Clinicaloutcome:

RA

diagnosisat

1y

accordingto

ACR

1987criteria.

Handsandfeet

at

baselineandat

12mo.

Erosion:definiteloss

ofcortical

liningin

�2joints.

Radiologistsblinded

forpatient

characteristics.

Definiteerosion

atbaseline.

Cross-sectional

associationbetween

serum

MMPsand

TIM

Psanderosive

disease.

238patients.

At1y:

45%

RA;9%

ReA

;

6%

PsA

orother

SpA;5%

other;

35%

UA.96%

of

patientsin

RA

group

at1yhad

RA

at

inclusion[12].

66/238patientshad

synovialtissuesamples

andserum

assessments

ofMMPandTMP

proteinases

[13].

Baseline:

18%

inRAgroupat

follow-upand5%

in

thenon-RA

group

wereerosive

(Pb0.01).

At1y:

36%

inRA

group.

Associationerosions

MMP:

MMP-1

inserum

associated

with

erosions(yes/no)

butNOT

with

the

distinctionRA

and

non-RA

[13].

Resultsofpaired

film

swereonly

reported

inpatients

withearlyRA

and

notincluded

in

thisreview.

BrittanyEA

Cohort,

(1995–1997GPre-

ferral)Devauchelle-

Pensec,2001[8];

Devauchelle-

Pensec2004[9]

Inclusion:b1y

synovitis;�

16-y-old;

�1sw

ollen

joint;no

previousdiagnosis

other

arthritis.

Evaluationstopped:if

clinical

diagnosis

ofdefined

jointdisease

andfulfilspublished

Handsat

baselineand

biannually

thereafter.

Pelvic

radiographat

baseline.

Erosions,decalcification,

orboth

inhands(item

7

ofACRcriteria

RA)and/orfeet.

Sharpscore

ofhands

Reliabilityofscoring

erosionsand/ordecal-

cificationin

thehands

(item

7ofACRcri-

teriaRA)and/orfeet

(n=130film

s).

Agreem

entbetween

blinded

observer

and

unblinded

office

258/270patientsfor

assessmentincluding

handradiography

only

[8]and149/270

patientin

studyon

feet

andhand

radiography[9].

Atlastvisit(meanfollow-

upof30mo)36%

Baseline:

Erosions:hands:

17%

ofRA

and4%

ofnon-RA

(Pb0.001);feet:

18%

ofRA

and2%

non-RA

(Pb0.02).

Decalcification:

hands:5.5%

ofRA


(continued

onnextpage)

criteria

ofjoint

disease.

Clinicaloutcome:

expertpanel

classifi-

cationofRA

ornon-

RA,based

onclinical,

laboratory

andradio-

logic

featuresafter

final

visit

(meanfol-

low-up30mo).Sen-

sitivityandspecificity

ofACR

1987criteria

forexpertdiagnosis

(91%

and75%).

andPlantmodification

ofSharpforthe

feet:erosion,narrowing

andtotalscore.

1observer

blindfor

patientcharacteristics.

Intraobserver

(6mo)

andinterobserver

variabilityonsubset

of130film

s.

based

rheumatologist

onerosionsand

decalcificationin

hands(item

7ACR

criteria).

Comparativesensitiv-

ityandspecificityfor

RA

atfollow-up;ero-

sions,

and/ordecalci-

ficationin

handsand/

orfeet;Sharpscore

of

handsand/orhands

andfeet

combined

(bestcut-offbased

onreceiver

operatorcurves).

ofpatientshad

expert

diagnosisofRA.

and8.5%

ofnon-

RA;feet:3.5%

of

RA

and4%

of

non-RA.

Sharpscore:hands:

5.9

inRA

and2.5

innon-RA

(Pb0.001);feet:

2.3

inRA

and1.2

innon-RA

(Pb0.004).

Reliability:

Intraobserver

variation;erosions:

hands:0.88;

feet:0.87.

Decalcification:

hands:0.65;

feet:0.52

Interobserver

variationSharp:

hands:0.98;feet:

0.90;agreem

entfor

item

7hands

rheumatologist/

observer:0.29.

Sensitivity

and

specificityforclini-

caldiagnosisRA:

Erosions:hands:

17%

and96%;


Table

1(continued)

Cohort(startyear),

firstauthor,year

[Ref.]


andclinical

outcomea

Radiographic

characteristics

Radiographic

outcomereported

Patientsin

whom

radiographyreported

Radiographic

outcome

Comments

BrittanyEA

Cohort,

(1995–1997GPre-

ferral)Devauchelle-

Pensec,2001[8];

Devauchelle-

Pensec2004[9]

NOAR(1990–1994

GPreferral),

Bukhari,2001[5];

Bukhari,2002[4]

Inclusion:�

6yor;

�2sw

ollen

joint;

�4wk;new

referrals

(mostb3y).

Excluded:other

than

UPA,RA,postviral

arthritis,PsA

.

Clinicaloutcome:

diagnosisRA

accordingto

ACR1987criteria.

Handsandfeet:

(1)Within

24moif

3ACRcriteria

atfirst

follow-upvisitorif

classificationRA

could

bemadein

case

erosionwould

bedetected.

(2)Allpatientsat

y5

(meantimeinterval

48mo).

Larsenmethod:

Erosive:

score

�2

inindividual

joint

2or3readersblindfor

sequence.Consensus

ifdiscrepancy.

Intraobserver

and

interobserver

agree-

ment90%

and81%.

Erosivein

functionof

symptom

duration[5].

Predictors

ofprogres-

sionin

those

with

pairedfilm

s[4].

416/759patients

contributedfilm

sfor

analysesoffirst

occurrence

of

erosions[5].

439

patients

contrib-

utedto

studyof

pairedfilm

s.By5y

75%

had

RA

[4].

feet:18%

and

98%;handsand

feet:33%

and95%.

Sharperosion

score:handsand

feet:(cutoff3.5)

28%

and90%.

Studyfirst

erosion[5]:

Of337patients

withafirstfilm

within

24mo

(suspectedRA),

36%

erosive.

In

those

noterosiveor

suspectedofRA

after24mo,23%,

28%

and47%

becam

eerosivein

the2nd,3rd,and

4th

year[5].

Studypaired

films

[4]:

33%

erosiveat

firstfilm

(median

symptom

duration

24mo)and49%

at

secondfilm

;

Filmswerenot

system

atically

taken

atbaseline.


(continued

onnextpage)

Leiden

EA

Clinic

(1993GPreferral

andregular

rheumatology

clinic),Visser,

2002[11]

Inclusion:�1

swol-

lenjoint;�2ysymp-

toms;firstcontact

witharheumatologist.

Follow-upstops:

after

1y:iftransientsyno-

vitisOR

inremission

incase

thediagnosis

was

crystal

synovitis

ortraumaorreactive

arthritis,sarcoid

arthritisorUA.

Clinicaloutcome:

self-lim

ited

arthritis

(orremission),persis-

Handsandfeet

at

inclusion,6moand

yearlyafterw

ards.

Chestradiograph.

SHSmethod:erosive:

erosionscore

�1

1reader

blinded

for

patientcharacteristics

(notstated

if

chronologic).

Erosivearthritis

compared

topersis-

tentnonerosiveor

self-lim

ited

arthritis.

Erosion(s)as

predic-

torofpersistentand

erosivedisease.

524/566patientsin

thefollow

upat

2y

Atfollow-up:

30%

RA,26%

UA,

11%

crystal-induced

arthritis,6%

OA,

5%

sarcoid,15%

other

(including

PsA

);60%

self-

limiting,16%

persis-

tentnonerosive.

and24%

persistent

erosive.

increase

ofLarsen

from

meanof2to

7over

ameanof

48mo;Larsenfirst

film

associated

withbaselineCRP

(highesttertile)

and

RF;Larsenlast

film

mainly

predictedby

Larsenbaseline

andto

lesser

extent

CRPandRF.

Baseline:

Erosive:

15%.

At2y:

Erosive:

24%.

(ofthose

83%

RA,

6%

UA,5%

PsA

,

1.6%

SpA.

Erosionsaspredictor

ofoutcome:

Predicts(1)persistent

synovitis

[OR

2.75]

and(2).erosive

disease

[OR

infinite].


Table

1(continued)

Cohort(startyear),

firstauthor,year

[Ref.]


andclinical

outcomea

Radiographic

characteristics

Radiographic

outcomereported

Patientsin

whom

radiographyreported

Radiographic

outcome

Comments

Leiden

EA

Clinic

(1993GPreferral

andregular

rheumatology

clinic),Visser,

2002[11]

Austrian

EA

Action

(1995),Machold,

2002[6]

tentsynovitisor

erosiveafter(1

or)

2y;remission:6mo

symptom-freeandno

DMARD.

Other

classifications:

ACR1987

criteria

RA.

Inclusion:�

12wk;

swellingin

�1joint

withouttrauma;

pain

in�

1jointwith

morningstiffness

N60min.

Atleast1lab:RF+,

ESRN20,CRPN5,

leucocytesNupper

limitnorm

al.

Clinicaloutcome:

1958ACRcriteriaRA.

Handsandfeet

at

entryandyearly

afterw

ards.

Other

involved

joints

ifapplicable.

Larsenmethod:

Erosive:

score

�2in

atleastonejoint;

Totalscore.

2rheumatologistsand2

radiologistsin

one

session.Blindfor

chronology.

Test-retest:0.86.

Erosiveat

baseline

and1y.

Softtissuesw

elling

atbaseline.

Score:mean(SD).

108/219had

atleast

1-y

follow-up.66of

those

had

final

diagnosisRA

aty1.

At1y:

61%

RA,13%

UA,

2%

PsA

.

Radiographic

outcomereported

inthose

withfinal

diagnosisRA

(n=66).

OfRApatients:

Erosive:baseline:

12%;1y:28%;

Softtissuesw

elling:

baseline:

21%.

Larsen

score:

baseline:

3.5

(6.6);

1y:6.3

(10.9).

Predictors

of

becomingerosive:

RF[O

R:9.7(1.05–

89.93)].

Noradiographic

data

onpatientswhohad

nofinal

diagnosis

RA.


Amsterdam

EA

Clinic

(1995–1998),

Jansen,2000[7]

Inclusion:N18y;

�2joints;b3y.

Exclusion:previous

DMARD;diagnosis

ofReA

,PsA

,crystal

arthritis,

OA,sarcoi-

dosis,bacterial

arthri-

tis,defined

system

ic

disease.

Handsandfeet

at

baselineand1y.

SHSmethod:Total

Sharpscore.

1observer

blindfor

patientcharacteristics

andchronology.

Predictors

for

progressiveUPA

at1y.

Predictors

for

radiographic

dam

age/

progressionin

the

entire

groupat

1y.

323patientseligible,

316could

be

contacted

and

280participated.

Atbaseline:

72%

RA;27%

UA

(58%

polyarthritis

and24%

oligoarthritis).

Baselinemedian

Sharp:

MildUPA:2.0

Progressive

UPA:0.9

RA:1.1

1-y

meanSharp:

MildUPA:2.0

Progressive

Patientsexcluded

if

notclassified

after1y

into

progressiveand

notprogressive.

The

progressiveUPA

werenotseparately

analysedforRA

or

non-RA,butit

Clinicaloutcome:

1987ACRcriteriafor

RA

forthose

already

fulfillingthse

criteria

atentry;ifat

baseline

UPA,the1-y

follow-

up

considered

arthri-

tis[1]progressive;

if

radiographic

progres-

sion�

4points,radio-

graphic

score

�10or

HAQ�

1or[2]mild;

ifnotprogressive.

Aty1:

58%

(n=45)mild

UPA

and42%

progressive(n=32)

ofwhich10fulfilled

ACRcriteria

forRA.

UPA:12.5

RA:9.5.

1-y

meanSharp

progression:

MildUPA:0

ProgressiveUPA:

3.0

(itwas

mentioned

there

was

nodifference

betweenRA

and

non-RA)

RA:4.5.

Predictors

progressiveUPA:

Age[O

R:1.5],

arthritishands

[OR:4.2](uncertain

ifradiographic

score

atbaseline

was

included

in

analysis).

was

mentioned

that

progressiveUPA

diagnosedas

RAwere

notdifferentfrom

other

progressive

UPA

patientswith

regardto

radiographic

progression.

Abbreviations:

NIH

,National

InstitutesofHealth;OA,osteoarthritis;TIM

Ps,tissueinhibitors

ofmetalloproteinases.

aDescriptionoutcomeat

follow-up.



Progression and predictors of radiographic damage over time

NOAR suggests that the proportion of patients with EIA who become erosive

is linear. In patients classified as having RA or suspected to have RA in the first

24 months after inclusion, 36% were erosive at entry into the cohort. In patients

not erosive on the first film, 23%, 38%, and 47% were erosive 2, 3, and 4 years

after symptom onset [5]. In patients with paired films within the first 5 years,

33% were erosive at the first film, and 49% were erosive after a mean interval of

48 months [4]. During that period, the Larsen score progressed from 2 to 7 points.

In the Leiden EA Cohort, the proportion of patients with erosive disease

increased from 15% at inclusion to 24% after 2 years [11].

Within the Austrian EA Action, more substantial progression was seen, but the

analyses were limited to patients classified as having RA at the 1-year follow-up

(61% of all EIA) [6]. At baseline, 12% were erosive, increasing to 28% at follow-

up. Of patients with RA at 1 year, 68% had RA at the baseline. RF at baseline

predicted development of erosions during the first year.

In the Amsterdam EA Cohort, 42% of patients with UPA were classified as

progressive at 1 year [7]. Mean progression in Sharp score was zero points in the

mild UPA group, 3 in the progressive UPA group, and 3.5 in the initial RA group.

In patients with progressive UPA, 31% fulfilled ACR 1987 criteria for RA at

follow-up, but radiographic progression was not different in these patients com-

pared with the non-RA patients in this group. Progressive UPA could be pre-

dicted by age (odds ratio [OR] 1.05) and presence of arthritis in the hands (OR

4.2). It is not clear if baseline Sharp scores were included in the multivariate

regression. DCARTs were given in 86% of patients with a final diagnosis of

progressive UPA and in 100% of patients with the initial diagnosis of RA.

Relationship between radiographic damage and functioning

The relationship between radiographic damage and functional outcome was

not examined in any of the studies. In the Amsterdam EA Cohort, mean HAQ

score improved approximately 0.2 in patients with mild UPA, showed no change

in patients with progressive UPA, and improved by approximately 0.3 points in

patients with the initial diagnosis of RA [7].

Issues in conventional radiology in early inflammatory arthritis and

comparison with early rheumatoid arthritis and psoriatic arthritis

Diagnosis: joints, features, and scoring method

EIA is a descriptive and not a diagnostic concept. Conventional radiographs at

the first presentation of a patient with EIA can help to make a classic diagnosis

because the radiographs allow application of the established knowledge of


that diagnosis to these patients. Up to now, all radiographic studies in EIA con-

centrated on the role of erosions or joint space narrowing in hands or feet and

on the contribution to predict RA in an early stage. Erosions and joint space

narrowing are not a unique feature of RA, however. In the French EA Cohort,

erosions in hands and feet had a high (95%) specificity for the expert’s diagnosis

of RA, but the diagnostic considerations in patients with erosions but without RA

were not discussed [8,9]. In the Leiden EA cohort, most (83.5%) patients with

erosive disease after 2 years fulfilled the ACR 1987 classification for RA, but

5.5% had PsA, 1.6% had SpAs, and 6.3% had UA [11]. In the Amsterdam EA

Cohort, radiographic progression in patients with progressive UPAwas similar in

patients classified as having RA compared with non-RA [7].

To improve classification (diagnosis) and to establish prognosis, it is important

to consider features other than erosions and joint space narrowing, and sites other

than those traditionally evaluated in RA should be assessed. In the French study,

it was shown that decalcification (part of item 7, the radiographic criterion of the

1987 criteria for RA) as a separate feature had low reliability and was not

explored further with regard to test characteristics [8]. The relevance of features

such as periostitis and bone apposition and of imaging additional joints (eg, the

distal interphalangeal joints or large joints) needs to be clarified, however.

Rahman and colleagues [14] compared radiographic damage of 39 RA and

42 PsA patients who were matched for gender and age (within 10 years) and

had a mean disease duration of 6.1 and 6.9 years, respectively. Conventional

films of hands and feet were assessed for abnormalities by the Steinbrocker score

modified for PsA (including distal interphalangeal joints of the hands and

interphalangeal joints of the feet). In addition, several additional abnormal

features were recorded. In the hands periostitis was observed in 2.6% of RA

patients compared with 9.5% of PsA patients, and bony proliferation was

observed in 2.6% of RA patients compared with 4.8% of PsA patients. Dactylitis

was not seen in RA, but was seen in 7.1% of patients with PsA. None of these

differences were significant, and for the feet the differences were even less

pronounced. This was a study in patients with established disease. Three studies

reported radiographic abnormalities in early PsA, but did not report on features

other than erosions and narrowing and did not compare the additive value of

including distal interphalangeal joints in the scores [3,15,16].

The diagnostic (or prognostic) value of including large joint radiographs in the

initial assessment of a patient with EIA has not been studied. For RA, it is

established that patients who are nonerosive in the hands and feet do not have

erosions in large joints [17]. In the St. Vincent’s Early PsA Cohort, the rele-

vance of imaging of the sacroiliac joints was studied. At a median of 24 months

(range 11–56), sacroiliitis was seen in 17% of patients (unilateral in 60%) [3].

Magnitude of structural damage and progression over time

Limited data are available to estimate the magnitude of progression of joint

damage in patients with EIA. Considering the studies analyzing unselected EIA


patients (ie, not limited to patients with the follow-up diagnosis of RA), 8% [13]

to 15% [11,18] of patients had erosions in hands or feet at baseline. The

progression of patients with erosive disease was reported only in the Leiden EA

Cohort, which increased from 15% to 24% after 2 years [11]. Although in the

analyses of NOAR, the clinician’s suspicion of the ACR diagnosis of RA in-

fluenced the decision to obtain radiographic assessment, the results suggest a

fairly linear increase in the number of patients becoming erosive over time (23%

at 2 years, 28% at 3 years, and 47% at 4 years) [5]. Progression in radiographic

scores was not reported for unselected patients with EIA. In the NOAR, the

Larsen progression (range 0–190) was 5 points over a mean of 48 months (2.5 per

year; 1.5% of the maximal score) [4]. In the Austrian EA Action, the progression

in mean Larsen (range 0–160) over 1 year was 2.8 points (1.75% of the maximal

score) [6]. In the Amsterdam study, mean progression of the Sharp score (range

0–448) was 3 over 1 year (0.67% of maximal score) in patients with progressive

UPA compared with 4.5 in patients with RA (1% of maximal score) [7]. Of

patients with UPA at baseline, 42% were progressive over the 1-year period. The

magnitude of radiographic progression was similar in all patients with pro-

gressive UPA, independent of whether they fulfilled at the final visits 1987 ACR

classification criteria for RA. The films of the NOAR, the Austrian EA Action,

and the Amsterdam cohort were scored by readers blind for chronology. None of

the studies reported on the presence of negative scores. The box plots of the

radiographic change in Sharp score in the Amsterdam publication indicate a large

proportion of negative scores.

Comparison between studies, and even more so between EIA, early RA, and

early PsA, needs to be done with caution. Of patients in early RA cohorts, 5%

[19] to 77% [20] had erosions at inclusion, and 80% of patients had erosions after

5 years [19]. The occurrence of erosions over time was linear, at least in the first

years of the disease. Yearly progression in the Larsen score of hands and feet in

three EIA cohorts was estimated to be 3.8 units per year (2.5% of possible

damage) compared with 6 points per year in three studies that applied the Sharp

score of hands and feet (1.3% of possible damage) [21]. In early RA, there is

evidence that the radiographic damage and progression of damage has become

less severe in recent years. Sokka and colleagues [22] compared radiographic

outcome in three consecutive Finnish EA Cohorts (�1 or 2 years). Cohort A

included patients between 1983 and 1985, Cohort B included patients between

1988 and 1989, and Cohort C included patients between 1995 and 1996. Al-

though the increase in patients with at least one erosion over 5 years was only

slightly lower in the later cohorts, the decline in patients with important

radiographic damage defined as Larsen score greater than 10 was significant. The

proportions of patients with a Larsen score greater than 10 were 8.7%, 0%, and

2.6% at baseline and 54.5% (+45.8%), 32.6% (+32.6%), and 14% (+11.4)

after 5 years in Cohorts A, B, and C. The median 5-year progression in Larsen

score (0–100) in hands and feet was 12 (2.4 per year; 2.4% of maximal score),

6 (1.2 per year; 1.2% of maximal score), and 4 (0.8 per year; 0.8% of maximal

score) over 5 years in Cohorts A, B, and C.


The more important influence on the cumulative radiographic damage

compared with the proportion of patients having erosions illustrates that both

outcomes have additional value, at least in early RA. For RA, a simplified

scoring method (Simple Erosion and Narrowing Scale: SENS) was developed,

including the same joints as in the Sharp van der Heijde Score (SHS) and

counting the number of eroded joints and the number of narrowed joints

(0–86). In early RA, this method showed similar sensitivity to change as

the SHS [23]. Because the data in EIA suggest the increase in number of

erosive patients was linear over time, this method might prove interesting in

EIA. When evaluating progression, the time period wherein changes can be

reliably detected is relevant. Bruynesteyn and colleagues [24] showed it was

possible to detect changes reliably (higher than the smallest detectable change)

by the SHS for RA after 3 months of follow-up, especially when scored in

chronologic order. The likelihood of progression was higher in patients with

established RA compared with early RA, influencing the sample sizes required

for studies.

Data on progression of structural damage in early PsA are limited. In

NOAR (early PsA with isolated axial disease excluded), 22% were erosive at

baseline, and median Larsen score was 2.5 [15]. Punzi and colleagues [16]

compared patients with young onset (�60 years old) and elderly (N 60 years

old) onset early (�1 year) PsA. After 2 years, the mean number of erosions

in the hands had increased from 2.4 to 4.4 in the younger group and from

2.2 to 2.7 in the older group of patients. In the feet, the number of ero-

sions increased from 2.7 to 4.7 and from 1.1 to 2.1 in the younger and older

groups. In the early PsA cohort of the St. Vincent ES clinic, 26% were

erosive at baseline, and 47% were erosive after a median follow-up of

24 months (Sharp PsA method) [3]. The number of joints with erosions was

highest in the hands at baseline, but in the feet at follow-up. In the latter

group, the increase measured by the Sharp PsA method was 1.6 for erosions

(0.8 per year; 0.3% of maximal damage) and 1.8 for narrowing (0.9 per year;

0.4% of maximal damage). An observation was made during a drug in-

tervention trial with respect to the sensitivity to change of features considered

specific for PsA (periostitis and tuft resorption) with respect to the influence

of including the distal interphalangeal joints on the sensitivity to change of

the Sharp score for PsA [25]. Although important differences were seen in

the total Sharp PsA score between the treatment groups, inclusion or exclusion

of the distal interphalangeal joints did not change the results of the trial.

Scoring of the additional features did not provide additional information

when considering change. In the Ratingen PsA score, the proliferation score

(quantifying bony proliferation in 40 joints of hands and feet) and the dis-

ability score (quantifying destruction in the same 40 joints) proved to have a

good intraobserver and interobserver variability and to be sensitive to change

over a mean interval of 3 years [26]. The correlation in progression of both

subscores was weak, suggesting both subscores provide additional information

on progression.

Box 1. Conclusions drawn for X-ray studies in six early arthritiscohorts

Diagnosis� Radiographs of the feet in addition to radiographs of the handsimprove the sensitivity in predicting RA compared with clinicaldiagnosis alone.

� Periarticular decalcification is unreliable as a radiographic feature.� Periostitis and tuft resorption do not differentiate adequatelybetween RA and PsA. These features are not sensitive tochange in PsA, at least in advanced disease. Bone proliferationin advanced PsA can be assessed reliably and is sensitive tochange. It is not known whether this feature is present in earlydisease, and whether it can discriminate reliably between RAand PsA.

� Including distal interphalangeal joints in scores of erosions andnarrowing does not improve sensitivity to change in patientswith advanced PsA. It is not known whether changes in thesejoints differentiate between PsA and other inflammatory jointdisease in patients with EIA.

� Patients with isolated abnormalities in large joints are un-likely to have RA. The contribution of abnormalities in thelarge joints for other diagnostic or prognostic classificationis unknown.

� A substantial proportion of patients with early PsA haveradiographic sacroiliitis. In patients without psoriasis and ES,it is unknown if this would contribute to classify patientswithin the group of SpAs.

Damage and progression of damage� A substantial proportion of patients with EIA have erosivechanges in their hands and feet and have radiographic damagethat is quantifiable by classic scoring methods.

� The amount of damage and increase in damage is low, butseems to be comparable to results of more recent studies inearly RA.

� In early RA, scoring methods can detect changes within3 months if films are read in chronologic order.

� Repair in EIA has not yet been studied.� In early RA, studying the proportion of patients whose diseasebecomes erosive and the increase in damage over time givesadditional information.


� The relationship between disease activity, bone metabolism,and joint damage in EIA has not been resolved.

Reporting radiographic outcome in clinical trials� The large number of zero values, low damage scores, andexpected lower progression in patients who are treated earlyhave consequences for sample sizes of patients in clinical trials.


Prognosis for functional outcome

Independent of the diagnostic value, radiographs can play a prognostic role

when evaluating patients with EIA. In early RA, the predictive value of ra-

diographic damage at baseline for future disability (defined as worse physical

function [HAQ] [21], work disability [27,28], direct medical costs [29], joint

surgery [30], and mortality [31]) has been well established in several longitudinal

studies. In PsA, one study revealed the radiographic damage predicted mortality

[32]. In EIA, Visser and colleagues [11] showed that erosions predicted persis-

tent synovitis and progressive erosive disease. None of the EIA cohorts studied

the independent prognostic value of radiographic abnormalities on functional

outcome. The major bottleneck to answering this question is that long-term ob-

servations are necessary to prove this relationship reliably. In early RA, it was

known that cumulative damage reflects the cumulative disease activity [33].

Increasingly, it is recognized in RA that independent pathophysiologic effects

on bone metabolism have an additional role in the development of structural

damage [34,35]. Nevertheless, disease activity can be used as a substitute to

predict damage and functional outcome. For PsA, the role of clinical inflam-

mation and bone metabolism to predict damage has not been addressed yet. The

relationship between clinical disease activity and bone metabolism on the one

hand and structural damage and functioning on the other hand might differ

between diseases and needs to be studied in longer follow-up studies of patients

with EIA. There are some indications to support the hypothesis that pathways

other than disease activity alone contribute to structural damage in EA. In NOAR,

the Larsen score at the last evaluation was only weakly explained by baseline

CRP (OR of middle tertile CRP 1.5 [95% confidence interval 1–2.3] and OR of

highest tertile CRP 1.1 [95% confidence interval 1.7–3.2]) [4]. In the Austrian

EA Action, there was no difference in the baseline inflammatory variables

between patients who developed erosive compared with nonerosive RA [6]. In

the Amsterdam cohort, baseline disease activity scale (DAS) 28 was higher in

patients with progressive UPA after 1 year compared with patients with mild

UPA in univariate, but not in multivariate, analyses [7]. It is important to exa-

mine the relative contribution of clinical inflammation and other pathways (eg,

bone metabolism) to occurrence of structural damage in EIA. This contribution

would have consequences for treatment choices because there is evidence that


some DCARTs have independent effects on disease activity and bone metabo-

lism [36].

Reporting radiographic outcome in clinical trials

The large number of zero values, low damage scores, and expected lower

progression in patients who are treated early have consequences for radiographic

outcome in clinical trials. Landewe and van der Heijde [37] made some

recommendations with regard to radiographic outcome in EIA clinical trials.

Radiographic change in radiographs of hands and feet as a primary outcome is

less relevant compared with the clinical outcomes. It was discussed that it could

be worthwhile to stratify patients according to their likelihood to develop erosive

change, but more data are needed to predict such outcomes reliably. Such strata

need to be powered sufficiently to be able to measure differences.

Summary and recommendations

EIA is a clinical description preceding the classification of disease (RA, PsA,

UA) or determination of the prognosis-related classification of the disease (per-

sistent synovitis, erosive). The role of conventional radiography in the assessment

of patients with EIA is to enhance such classifications. This would allow

rheumatologists to apply existing knowledge about the specific conditions to the

preclassification period of the disease.

Studies on conventional radiology in EIA so far have concentrated on early

prediction of RA. Because most patients with EIA have self-limiting disease or

progress to classic RA, the ability to predict RA is certainly relevant. However,

many patients with EIA develop PsA or remain classified as having persistent

UA, of which a substantial proportion are, or will become, erosive. Formal data

on the prevalence of UA and outcome of these patients are lacking. It is still

unknown if these patients represent a spectrum of patients with RA or a sepa-

rate disease entity. Similarly, it cannot be determined whether the relationship

between disease activity, radiographic damage, and functional outcome is unique

for RA or universal for all inflammatory arthritides. Conclusions following the

X-ray studies of six cohorts of patients who have ES (Box 1) suggest it is

important to identify erosive disease in an early phase of joint inflammation.

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Conventional X-Ray in Early Arthritis

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