Juvenille idiopatic arthritis

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Concise Report

Clinical assessment and core outcome variables are poorpredictors of hip arthritis diagnosed by MRI in juvenileidiopathic arthritis

K. Nistala, J. Babar, K. Johnson, P. Campbell-Stokes, K. Foster, C. Ryder

and J. E. McDonagh1

Objectives. To compare the diagnostic performance of clinical assessment against magnetic resonance imaging (MRI)

diagnosed hip arthritis in a juvenile idiopathic arthritis (JIA) population. To determine the clinical and serological predictors of

MRI diagnosed hip arthritis.

Methods. A total of 34 JIA patients with established disease (mean disease duration 6.3 yrs) had their hip MRIs scored for

features of active hip arthritis and hip damage. Results were compared with clinical variables (disease subtype, history of hip

pain, core outcome variables (COV)) and the clinicians assessment of active hip arthritis.

Results. MRI features of active hip arthritis were found in 45 hips (70%) and hip damage in 36 hips (56%). Clinical assessment

had fair agreement with MRI scoring of active arthritis in patients with disease duration 6 months. Symptoms of hip pain and the cliniciansassessment of hip arthritis (active, inactive or unsure), active joint

count, demographic data and erythrocyte sedimentation rate(ESR) were collected from case notes. Core outcome variables(COV) are routinely recorded for every patient at every clinic visitand include the marking of the active and restricted joints on askeletal diagram. COV [8] included physicians global assessmentof overall disease activity (VAS-PGA) assessed using a 100mmvisual analogue scale, the childhood health assessment question-naire (CHAQ), as modified for use in the UK [9] and which also

Birmingham Childrens Hospital and 1Institute of Child Health, Diana, Princess of Wales Childrens Hospital, Steelhouse Lane, Birmingham B4 6NH, UK.

Submitted 30 March 2006; revised version accepted 27 October 2006.

Correspondence to: K. Nistala, Paediatric Rheumatology Department, Birmingham Childrens Hospital, Steelhouse Lane, Birmingham B4 6NH, UK.

E-mail: [email protected]

Rheumatology 2007;46:699702 doi:10.1093/rheumatology/kel401

Advance Access publication 7 December 2006

699 The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]


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included 100 mm visual analogue scales for overall patient well-being (VAS-global). All patients are examined by either aconsultant paediatric rheumatologist or an experienced paediatricrheumatologist in training, during their routine clinic visits at thehost institution.

A total of 19 hip MRIs were reported blind to clinical detailssimultaneously by two experienced paediatric radiologists (K.J.,K.F.). Any disagreement was resolved by consensus. A further 15hip MRIs were independently reported by the same radiologiststo assess inter-observer agreement. Hips were scored for signsof active synovitis with 1 point each for synovial effusion,gadolinium-enhancing synovium >2 mm, peri-articular boneoedema. Damage was scored with 1 point each for bony erosions,cartilage loss, bony remodelling and acetabular protrusion. Thescoring system was developed for this study, and is at presentunvalidated, being based on previous literature [10, 11] and thepaediatric radiologists clinical experience. MRI images wereconsidered to be abnormal if the respective activity and damagescores were >0.

All scans were performed on a Siemens (Erlanger, Germany)1.5 Tesla symphony scanner. The sequences obtained werecoronal T1, T2, short tau inversion recovery and axial protondensity of the hips and bony pelvis. All children had postgadolinium (0.01mmol/kg) DTPA fat saturated coronal T1weighted sequences.

AnalysisThe hips of each individual patient were considered to beindependent when comparing lateralizing variable such asclinicians assessment and pain with MRI scores. Non-lateralizingvariables such as disease duration and ESR were compared withthe patients combined hip scores. The association between totalMRI scores and clinical variables was tested using Pearsonscorrelation. Individual hip MRI scores were compared withclinician defined active and inactive groups using the MannWhitney test. Kappa scores were used to assess inter-observervariability and concordance between clinicians assessment andMRI results [12]: Clinicalradiological correlation was not made ifthe interval between clinical assessment, and MRI was >3 monthsas changes in disease activity may have occurred (three patients).Chi-squared test for trend was used to elucidate the effect ofdamage on the concordance between clinicians assessment and

MRI activity scores [13]. For this analysis hips classified byclinicians as unsure were excluded. P 0.05 was defined as beingstatistically significant in this study. Computer analysis wascarried out using SPSS software version 12, from SPSS Inc.,Chicago, IL, USA.

ResultsSixteen patients had repeat MRIs, which were excluded. Thirty-four MRI scans (68 hips) were analysed. Frequency of JIAsubtypes were as follows: twelve enthesitis-related arthritis, ninepolyarthritis, seven systemic onset, four extended oligoarthritisand two psoriatic arthritis. Mean patient age 14.4yrs(range4.319.7 yrs), disease duration 6.3yrs (0.813.6 yrs),ESR 23 mm/h (296) and active joint count of 2 (213), CHAQ0.84 (01.88), physicians global (VAS-PGA) 14mm (085),patient well-being (VAS-global) 30 mm (081). Eight patientswere receiving etanercept, 13 methotrexate and four oralprednisolone.

MRI examination

Hip effusions and synovial enhancement were present more oftenthan bone oedema (36, 33 and 15%, respectively). Of all hipsscanned, 30% had no MRI features of disease activity, and 15%scored 3 points. Of all hips, 44% had no evidence of damage,and 28% scored 3. None of the patients had MRI features ofacetabular protrusion. MRI activity and damage scores did notcorrelate. There was substantial inter-observer agreement forindividual aspects of the activity and damage scoring systems( 0.761.0).

Comparison of MRI findings and clinicians assessment

There was a limited relationship between clinicians assessmentand MRI activity scores (Fig. 1). MRI scores were higher inpatients thought to have clinically active hips vs inactive although

this did not achieve statistical significance (1.9 vs 1.2, P 0.066).Agreement between MRI activity and clinical assessment was fairin cases with arthritis less than 4 years from diagnosis ( score0.38, P 0.045). There was no agreement in longer standingdisease ( score 0.02, P 0.62).

We analysed the agreement between clinical assessmentand MRI activity score according the severity of damage.Concordance between clinician and MRI result was highestin undamaged hips with agreement in 11 out of 18 cases.This worsened with increasing damage score (2Trend5.18,1 df, P 0.023) and in hips with a damage score of 3, there wasagreement in only 4 of 16 cases.

If cases where the clinician was unsure are excluded, clinicalexamination has a sensitivity of 25.7% and specificity of 91% fordetecting MRI-diagnosed arthritis.

Predictors of MRI activity score

COV, history of pain, disease subtype and duration of arthritiswere compared with total MRI activity scores using multipleregression to assess their predictive value. In exploratoryunivariate analyses, only ESR had significant correlation withMRI scores (r0.44, P0.014, Fig. 2). Physicians globalassessment and hip pain were associated with MRI activityscore (P 0.37 and 0.2, respectively) and using a cutoff ofP7 that predicts hip arthritis on MRI witha sensitivity of 72% and specificity of 80%.

Inactive Unsure Active

Clinicians assessment

FIG. 1. MRI activity scores compared with clinicians assessment.MRI activity for each hip was scored as 1 point each for boneoedema, enhancing synovium, effusion, maximum score 3. Eachtriangle represents one hip. Filled triangles have evidence ofdamage on MRI (MRI damage scores >0). Horizontal linesrepresent mean MRI activity score.

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Discussion

Over the last decade, there has been an increasing move towardsearlier and more aggressive treatment of JIA with methotrexateand biological agents in the hope of preventing joint damage [14].In the context of coxitis, decisions to escalate treatment may belimited because of the difficulties in confirming arthritis by clinicalexamination. In our study, we have shown that the cliniciansassessment of active hip arthritis has only fair agreement withMRI-based diagnosis and this is limited to early disease.Clinicians misjudged coxitis on MRI when hips were moredamaged and in particular underestimated MRI features ofinflammation. We found that damage worsened with diseaseduration and this may account for the poor concordance between

doctor and MRI results in patients with long-standing disease.It is possible that clinicians are incorrectly attributing their clinicalfindings of pain and restriction to pre-existing bony damage ratherthan disease activity. In contrast, clinicians were invariably correctin labelling hips without inflammation on MRI as inactive, asevidenced by the high specificity for clinicians assessment.

Recognizing the limitations of clinical examination, we ques-tioned if other clinical or core outcome variables would betterpredict MRI changes. Our data from JIA patients with establisheddisease suggests that from COV only ESR is predictive of activehip arthritis on MRI. Taken from a clinical perspective a highlyelevated ESR is specific for hip inflammation, but a normal ESRdoes not exclude coxitis on MRI. MRI scores did not differsignificantly between disease subtypes, but patients with systemicJIA had the highest mean scores, consistent with reported results

by Argyropoulou et al. [11].The MRI features of hip disease in JIA have been reported

[10, 11] but not standardized and do not currently play a role inthe diagnostic criteria for JIA [6]. Our study piloted a scoringsystem for disease activity and damage on hip MRI that showedvery good levels of inter-observer agreement. Damage and activityscores were independent suggesting that separate disease char-acteristics were being assessed. Our study did not include a healthycontrol group. Although normative data on paediatric hip MRI isavailable [15, 16], formal validation of a scoring system willrequire control subjects to ensure that MR abnormalities are notbeing over-called.

Our study has the weakness of being a retrospective reviewalthough standardized clinical data recording systems mitigateagainst some of these flaws. The numbers scanned are small andare biased by being a cohort selected for MRI on clinical grounds

and are, therefore, at increased risk of coxitis. The results may notbe applicable to all JIA patients particularly those with lessaggressive disease. Our findings of inflammation on hip MRI inthe absence of clinical signs, are likely to reflect the high sensitivityof MRI, and are consistent with results from MRI of kneearthritis [17]. However, it is difficult to make treatmentrecommendations on MR findings alone as the long-termsignificance of these abnormalities is still unclear. Similar

difficulties are faced in the MRI of sacroilitis in ankylosingspondylitis (AS) [18]. In AS, there is evidence that juxta-articularbony inflammation can be suppressed with anti-TNF agents [19]and prospective studies are underway to see if this favourablyinfluences long-term outcome. Finally, as the use of MRI remainsconstrained by cost and the need for sedation in the paediatric agegroup, comparisons between MRI and more sensitive ultrasoundtechniques such as power Doppler would be important in thefuture.

In conclusion we have reported pilot data that show thatclinical assessment of active hip arthritis has a limited relationshipwith MRI features of inflammation, particularly when there isco-existent damage. Of core outcome variables only ESR is ofvalue in predicting MRI results. Our results highlight the

contribution of MRI when there is clinical uncertainty betweenactive and damaged hips. A prospective cohort study is nowplanned that will facilitate the formal validation of the scoringsystem for hip MRI abnormalities in JIA detailed here.

Acknowledgements

J.E.McD. is an ARC funded Clinical Senior Lecturer in Paediatricand Adolescent Rheumatology (www.arc.org.uk). P.C.S. isfunded by the New Zealand Arthritis Foundation. The authorsare indebted to the clinical staff in the paediatric rheumatologydepartment for data collection and Carole Cummins (BirminghamChildrens Hospital) and Tim Cole (Institute of Child Health,London) for statistical advice.

The authors have declared no conflicts of interest.

References

1. McDonagh JE. The hip joint in juvenile idiopathic arthritis.In: Banta JV, Scrutton D, eds. Hip disorders in childhood. London:

MacKeith Press, 2003;13045.

2. Bekkering WP, ten Cate R, Suijlekom-Smit LW et al. The relationship

between impairments in joint function and disabilities in independent

function in children with systemic juvenile idiopathic arthritis.

J Rheumatol 2001;28:1099105.

3. Packham JC, Hall MA. Long-term follow-up of 246 adults with

juvenile idiopathic arthritis: functional outcome. Rheumatology

2002;41:142835.

4. Neidel J, Boehnke M, Kuster RM. The efficacy and safety of

intraarticular corticosteroid therapy for coxitis in juvenile rheumatoid

arthritis. Arthritis Rheum 2002;46:16208.

5. Fedrizzi MS, Ronchezel MV, Hilario MO et al. Ultrasonography in

the early diagnosis of hip joint involvement in juvenile rheumatoid

arthritis. J Rheumatol 1997;24:18205.

FIG. 2. Correlation of total MRI activity score with ESR(mmHg). MRI activity was scored as 1 point each for boneoedema, enhancing synovium, effusion per hip, maximumscore6.

Rheumatology

Key message

Clinical assessment of active hip arthritishas a limited relationship with MRIfeatures of inflammation, particularlywhen there is co-existent damage.

Clinical assessment and MRI in JIA coxitis 701


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6. Petty RE, Southwood TR, Manners P et al. International League of

Associations for Rheumatology classification of juvenile idiopathic

arthritis: second revision, Edmonton, 2001. J Rheumatol 2004;31:3902.

7. Soini I, Kotaniemi A, Kautiainen H, Kauppi M. US assessment of hip

joint synovitis in rheumatic diseases. A comparison with MR imaging.

Acta Radiol 2003;44:728.

8. Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT,

Martini A. Preliminary definition of improvement in juvenile arthritis.

Arthritis Rheum 1997;40:12029.9. Nugent J, Ruperto N, Grainger J et al. The British version of the

childhood Health Assessment Questionnaire (CHAQ) and the Child

Health Questionnaire (CHQ). Clin Exp Rheumatol 2001;19:S1637.

10. Murray JG, Ridley NT, Mitchell N, Rooney M. Juvenile chronic

arthritis of the hip: value of contrast-enhanced MR imaging. Clin

Radiol 1996;51:99102.

11. Argyropoulou MI, Fanis SL, Xenakis T, Efremidis SC,

Siamopoulou A. The role of MRI in the evaluation of hip joint

disease in clinical subtypes of juvenile idiopathic arthritis. Br J Radiol

2002;75:22933.

12. Landis JR, Koch GG. An application of hierarchical kappa-type

statistics in the assessment of majority agreement among multiple

observers. Biometrics 1977;33:36374.

13. Fleiss JL. Statistical methods for rates and proportions. New York:

Wiley, 1981;144.

14. Ramanan AV, Whitworth P, Baildam EM. Use of methotrexate in

juvenile idiopathic arthritis. Arch Dis Child 2003;88:197200.

15. Kramer J, Laub G, Czerny C, Recht MP. MR and MR arthrography.

In: Davies AM, Johnson K, Whitehouse RW, eds. Imaging hip and

bony pelvis. Berlin: Springer-Verlag, 2006;3148.

16. Herwig I. Arthritis: hip. In: Davies AM, Johnson K, Whitehouse RW,

eds. Imaging hip and bony pelvis. Berlin: Springer-Verlag,2006;28398.

17. Gardner-Medwin J, Ryder CAJ, Bradshaw K, Johnson K. Magnetic

resonance imaging identifies subclinical features predicting extension

of arthritis in children with monoarthritis. Clin Exp Rheumatol

2004;22:525.

18. Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and

classification in early ankylosing spondylitis: do we need new criteria?

Arthritis Rheum 2005;52:10008.

19. Sieper J, Baraliakos X, Listing J et al. Persistent reduction of spinal

inflammation as assessed by magnetic resonance imaging in patients

with ankylosing spondylitis after 2 yrs of treatment with the

anti-tumour necrosis factor agent infliximab. Rheumatology

2005;44:152530.

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Juvenille idiopatic arthritis