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Published in: Arthritis Research & Therapy 1/2019

Open Access 01-12-2019 | Magnetic Resonance Imaging | Research article

A search to the target tissue in which RA-specific inflammation starts: a detailed MRI study to improve identification of RA-specific features in the phase of clinically suspect arthralgia

Authors: Xanthe M. E. Matthijssen, Fenne Wouters, Debbie M. Boeters, Aleid C. Boer, Yousra J. Dakkak, Ellis Niemantsverdriet, Annette H. M. van der Helm-van Mil

Published in: Arthritis Research & Therapy | Issue 1/2019

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Abstract

Objective

Based on a unique cohort of clinically suspect arthralgia (CSA) patients, we analysed which combinations of MRI features at onset were predictive for rheumatoid arthritis (RA) development. This was done to increase our comprehension of locations of RA onset and improve the predictive accuracy of MRI in CSA.

Methods

In the discovery cohort, 225 CSA patients were followed on clinical arthritis development. Contrast-enhanced 1.5 T MRIs were made of unilateral metacarpophalangeal (MCP) (2–5), wrist, and metatarsophalangeal (1–5) joints at baseline and scored for synovitis, tenosynovitis, and bone marrow edema. Severity, number, and combinations of locations (joint/tendon/bone) with subclinical inflammation were determined, with symptom-free controls of similar age category as reference. Cox regression was used for predictor selection. Predictive values were determined at 1 year follow-up. Results were validated in 209 CSA patients.

Results

In both cohorts, 15% developed arthritis < 1 year. The multivariable Cox model selected presence of MCP-extensor peritendinitis (HR 4.38 (2.07–9.25)) and the number of locations with subclinical inflammation (1–2 locations HR 2.54 (1.11–5.82); ≥ 3 locations HR 3.75 (1.49–9.48)) as predictors. Severity and combinations of inflammatory lesions were not selected. Based on these variables, five risk categories were defined: no subclinical inflammation, 1–2 locations, or ≥ 3 locations, with or without MCP-extensor peritendinitis. Positive predictive values (PPVs) ranged 5% (lowest category; NPV 95%) to 67% (highest category). Similar findings were obtained in the validation cohort; PPVs ranged 4% (lowest category; NPV 96%) to 63% (highest category).

Conclusion

Tenosynovitis, particularly MCP-extensor peritendinitis, is among the first tissues affected by RA. Incorporating this feature and number of locations with subclinical inflammation improved prediction making with PPVs up to 63–67%.
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Literature
4.
go back to reference ISRCTN registry: ISRCTN46017566 https://doi.org/10.1186/ISRCTN46017566. Accessed 06-06-2019. ISRCTN registry: ISRCTN46017566 https://​doi.​org/​10.​1186/​ISRCTN46017566.​ Accessed 06-06-2019.
5.
go back to reference Burgers LE, Allaart CF, Huizinga TWJ, van der Helm-van Mil AHM. Brief report: clinical trials aiming to prevent rheumatoid arthritis cannot detect prevention without adequate risk stratification: a trial of methotrexate versus placebo in undifferentiated arthritis as an example. Arthritis Rheumatol. 2017;69(5):926–31.CrossRef Burgers LE, Allaart CF, Huizinga TWJ, van der Helm-van Mil AHM. Brief report: clinical trials aiming to prevent rheumatoid arthritis cannot detect prevention without adequate risk stratification: a trial of methotrexate versus placebo in undifferentiated arthritis as an example. Arthritis Rheumatol. 2017;69(5):926–31.CrossRef
6.
go back to reference Nam JL, Hunt L, Hensor EM, Emery P. Enriching case selection for imminent RA: the use of anti-CCP antibodies in individuals with new non-specific musculoskeletal symptoms - a cohort study. Ann Rheum Dis. 2016;75(8):1452–6.CrossRef Nam JL, Hunt L, Hensor EM, Emery P. Enriching case selection for imminent RA: the use of anti-CCP antibodies in individuals with new non-specific musculoskeletal symptoms - a cohort study. Ann Rheum Dis. 2016;75(8):1452–6.CrossRef
7.
go back to reference van Steenbergen HW, van der Helm-van Mil AH. Clinical expertise and its accuracy in differentiating arthralgia patients at risk for rheumatoid arthritis from other patients presenting with joint symptoms. Rheumatology (Oxford). 2016;55(6):1140–1.CrossRef van Steenbergen HW, van der Helm-van Mil AH. Clinical expertise and its accuracy in differentiating arthralgia patients at risk for rheumatoid arthritis from other patients presenting with joint symptoms. Rheumatology (Oxford). 2016;55(6):1140–1.CrossRef
8.
go back to reference van Steenbergen HW, Mangnus L, Reijnierse M, Huizinga TW, van der Helm-van Mil AH. Clinical factors, anticitrullinated peptide antibodies and MRI-detected subclinical inflammation in relation to progression from clinically suspect arthralgia to arthritis. Ann Rheum Dis. 2016;75(10):1824–30.CrossRef van Steenbergen HW, Mangnus L, Reijnierse M, Huizinga TW, van der Helm-van Mil AH. Clinical factors, anticitrullinated peptide antibodies and MRI-detected subclinical inflammation in relation to progression from clinically suspect arthralgia to arthritis. Ann Rheum Dis. 2016;75(10):1824–30.CrossRef
9.
go back to reference Rakieh C, Nam JL, Hunt L, Hensor EM, Das S, Bissell LA, et al. Predicting the development of clinical arthritis in anti-CCP positive individuals with non-specific musculoskeletal symptoms: a prospective observational cohort study. Ann Rheum Dis. 2015;74(9):1659–66.CrossRef Rakieh C, Nam JL, Hunt L, Hensor EM, Das S, Bissell LA, et al. Predicting the development of clinical arthritis in anti-CCP positive individuals with non-specific musculoskeletal symptoms: a prospective observational cohort study. Ann Rheum Dis. 2015;74(9):1659–66.CrossRef
10.
go back to reference van de Stadt LA, Witte BI, Bos WH, van Schaardenburg D. A prediction rule for the development of arthritis in seropositive arthralgia patients. Ann Rheum Dis. 2013;72(12):1920–6.CrossRef van de Stadt LA, Witte BI, Bos WH, van Schaardenburg D. A prediction rule for the development of arthritis in seropositive arthralgia patients. Ann Rheum Dis. 2013;72(12):1920–6.CrossRef
11.
go back to reference Zufferey P, Rebell C, Benaim C, Ziswiler HR, Dumusc A, So A. Ultrasound can be useful to predict an evolution towards rheumatoid arthritis in patients with inflammatory polyarthralgia without anticitrullinated antibodies. Joint Bone Spine. 2017;84(3):299–303.CrossRef Zufferey P, Rebell C, Benaim C, Ziswiler HR, Dumusc A, So A. Ultrasound can be useful to predict an evolution towards rheumatoid arthritis in patients with inflammatory polyarthralgia without anticitrullinated antibodies. Joint Bone Spine. 2017;84(3):299–303.CrossRef
12.
go back to reference Wakefield RJ, O'Connor PJ, Conaghan PG, McGonagle D, Hensor EM, Gibbon WW, et al. Finger tendon disease in untreated early rheumatoid arthritis: a comparison of ultrasound and magnetic resonance imaging. Arthritis Rheum. 2007;57(7):1158–64.CrossRef Wakefield RJ, O'Connor PJ, Conaghan PG, McGonagle D, Hensor EM, Gibbon WW, et al. Finger tendon disease in untreated early rheumatoid arthritis: a comparison of ultrasound and magnetic resonance imaging. Arthritis Rheum. 2007;57(7):1158–64.CrossRef
13.
go back to reference Mangnus L, van Steenbergen HW, Reijnierse M, van der Helm-van Mil AH. Magnetic resonance imaging-detected features of inflammation and erosions in symptom-free persons from the general population. Arthritis Rheumatol. 2016;68(11):2593–602.CrossRef Mangnus L, van Steenbergen HW, Reijnierse M, van der Helm-van Mil AH. Magnetic resonance imaging-detected features of inflammation and erosions in symptom-free persons from the general population. Arthritis Rheumatol. 2016;68(11):2593–602.CrossRef
14.
go back to reference Zubler V, Agten CA, Pfirrmann CW, Weiss BG, Dietrich TJ. Frequency of arthritis-like MRI findings in the forefeet of healthy volunteers versus patients with symptomatic rheumatoid arthritis or psoriatic arthritis. AJR Am J Roentgenol. 2017;208(2):W45–w53.CrossRef Zubler V, Agten CA, Pfirrmann CW, Weiss BG, Dietrich TJ. Frequency of arthritis-like MRI findings in the forefeet of healthy volunteers versus patients with symptomatic rheumatoid arthritis or psoriatic arthritis. AJR Am J Roentgenol. 2017;208(2):W45–w53.CrossRef
15.
go back to reference Boer AC, Burgers LE, Mangnus L, Ten Brinck RM, Nieuwenhuis WP, van Steenbergen HW, et al. Using a reference when defining an abnormal MRI reduces false-positive MRI results-a longitudinal study in two cohorts at risk for rheumatoid arthritis. Rheumatology (Oxford). 2017;56(10):1700–6.CrossRef Boer AC, Burgers LE, Mangnus L, Ten Brinck RM, Nieuwenhuis WP, van Steenbergen HW, et al. Using a reference when defining an abnormal MRI reduces false-positive MRI results-a longitudinal study in two cohorts at risk for rheumatoid arthritis. Rheumatology (Oxford). 2017;56(10):1700–6.CrossRef
16.
go back to reference van Steenbergen HW, van Nies JA, Huizinga TW, Bloem JL, Reijnierse M, van der Helm-van Mil AH. Characterising arthralgia in the preclinical phase of rheumatoid arthritis using MRI. Ann Rheum Dis. 2015;74(6):1225–32.CrossRef van Steenbergen HW, van Nies JA, Huizinga TW, Bloem JL, Reijnierse M, van der Helm-van Mil AH. Characterising arthralgia in the preclinical phase of rheumatoid arthritis using MRI. Ann Rheum Dis. 2015;74(6):1225–32.CrossRef
18.
go back to reference van Nies JA, Brouwer E, van Gaalen FA, Allaart CF, Huizinga TW, Posthumus MD, et al. Improved early identification of arthritis: evaluating the efficacy of early arthritis recognition clinics. Ann Rheum Dis. 2013;72(8):1295–301.CrossRef van Nies JA, Brouwer E, van Gaalen FA, Allaart CF, Huizinga TW, Posthumus MD, et al. Improved early identification of arthritis: evaluating the efficacy of early arthritis recognition clinics. Ann Rheum Dis. 2013;72(8):1295–301.CrossRef
19.
go back to reference Haavardsholm EA, Ostergaard M, Ejbjerg BJ, Kvan NP, Kvien TK. Introduction of a novel magnetic resonance imaging tenosynovitis score for rheumatoid arthritis: reliability in a multireader longitudinal study. Ann Rheum Dis. 2007;66(9):1216–20.CrossRef Haavardsholm EA, Ostergaard M, Ejbjerg BJ, Kvan NP, Kvien TK. Introduction of a novel magnetic resonance imaging tenosynovitis score for rheumatoid arthritis: reliability in a multireader longitudinal study. Ann Rheum Dis. 2007;66(9):1216–20.CrossRef
20.
go back to reference Ostergaard M, Edmonds J, McQueen F, Peterfy C, Lassere M, Ejbjerg B, et al. An introduction to the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. Ann Rheum Dis. 2005;64(Suppl 1):i3–7.CrossRef Ostergaard M, Edmonds J, McQueen F, Peterfy C, Lassere M, Ejbjerg B, et al. An introduction to the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. Ann Rheum Dis. 2005;64(Suppl 1):i3–7.CrossRef
21.
go back to reference van Steenbergen HW, van Nies JA, Huizinga TW, Reijnierse M, van der Helm-van Mil AH. Subclinical inflammation on MRI of hand and foot of anticitrullinated peptide antibody-negative arthralgia patients at risk for rheumatoid arthritis. Arthritis Res Ther. 2014;16(2):R92.CrossRef van Steenbergen HW, van Nies JA, Huizinga TW, Reijnierse M, van der Helm-van Mil AH. Subclinical inflammation on MRI of hand and foot of anticitrullinated peptide antibody-negative arthralgia patients at risk for rheumatoid arthritis. Arthritis Res Ther. 2014;16(2):R92.CrossRef
22.
go back to reference Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69(9):1580–8.CrossRef Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69(9):1580–8.CrossRef
23.
go back to reference Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31(3):315–24.CrossRef Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31(3):315–24.CrossRef
24.
go back to reference van der Helm-van Mil AH, Zink A. What is rheumatoid arthritis? Considering consequences of changed classification criteria. Ann Rheum Dis. 2017;76(2):315–7.CrossRef van der Helm-van Mil AH, Zink A. What is rheumatoid arthritis? Considering consequences of changed classification criteria. Ann Rheum Dis. 2017;76(2):315–7.CrossRef
25.
go back to reference Boeters DM, Gaujoux-Viala C, Constantin A, van der Helm-van Mil AHM. The 2010 ACR/EULAR criteria are not sufficiently accurate in the early identification of autoantibody-negative rheumatoid arthritis: results from the Leiden-EAC and ESPOIR cohorts. Semin Arthritis Rheum. 2017;47(2):170–4.CrossRef Boeters DM, Gaujoux-Viala C, Constantin A, van der Helm-van Mil AHM. The 2010 ACR/EULAR criteria are not sufficiently accurate in the early identification of autoantibody-negative rheumatoid arthritis: results from the Leiden-EAC and ESPOIR cohorts. Semin Arthritis Rheum. 2017;47(2):170–4.CrossRef
26.
go back to reference Efron B., Hastie T. JI, Tibschirani R. Least angle regression. Ann Stat 2004;32(2):407–499. Efron B., Hastie T. JI, Tibschirani R. Least angle regression. Ann Stat 2004;32(2):407–499.
27.
go back to reference Burgers LE, Siljehult F, Ten Brinck RM, van Steenbergen HW, Landewe RBM, Rantapaa-Dahlqvist S, et al. Validation of the EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis. Rheumatol (Oxford). 2017;56(12):2123–8.CrossRef Burgers LE, Siljehult F, Ten Brinck RM, van Steenbergen HW, Landewe RBM, Rantapaa-Dahlqvist S, et al. Validation of the EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis. Rheumatol (Oxford). 2017;56(12):2123–8.CrossRef
28.
go back to reference van Steenbergen HW, Aletaha D, Beaart-van de Voorde LJ, Brouwer E, Codreanu C, Combe B, et al. EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis. Ann Rheum Dis. 2017;76(3):491–6.CrossRef van Steenbergen HW, Aletaha D, Beaart-van de Voorde LJ, Brouwer E, Codreanu C, Combe B, et al. EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis. Ann Rheum Dis. 2017;76(3):491–6.CrossRef
30.
go back to reference Stomp W, Krabben A, van der Heijde D, Huizinga TW, Bloem JL, van der Helm-van Mil AH, et al. Aiming for a shorter rheumatoid arthritis MRI protocol: can contrast-enhanced MRI replace T2 for the detection of bone marrow oedema? Eur Radiol. 2014;24(10):2614–22.CrossRef Stomp W, Krabben A, van der Heijde D, Huizinga TW, Bloem JL, van der Helm-van Mil AH, et al. Aiming for a shorter rheumatoid arthritis MRI protocol: can contrast-enhanced MRI replace T2 for the detection of bone marrow oedema? Eur Radiol. 2014;24(10):2614–22.CrossRef
31.
go back to reference Ohrndorf S, Boer AC, Boeters DM, Ten Brinck RM, Burmester GR, Kortekaas MC, et al. Do musculoskeletal ultrasound and magnetic resonance imaging identify synovitis and tenosynovitis at the same joints and tendons? A comparative study in early inflammatory arthritis and clinically suspect arthralgia. Arthritis Res Ther. 2019;21(1):59.CrossRef Ohrndorf S, Boer AC, Boeters DM, Ten Brinck RM, Burmester GR, Kortekaas MC, et al. Do musculoskeletal ultrasound and magnetic resonance imaging identify synovitis and tenosynovitis at the same joints and tendons? A comparative study in early inflammatory arthritis and clinically suspect arthralgia. Arthritis Res Ther. 2019;21(1):59.CrossRef
Metadata
Title
A search to the target tissue in which RA-specific inflammation starts: a detailed MRI study to improve identification of RA-specific features in the phase of clinically suspect arthralgia
Authors
Xanthe M. E. Matthijssen
Fenne Wouters
Debbie M. Boeters
Aleid C. Boer
Yousra J. Dakkak
Ellis Niemantsverdriet
Annette H. M. van der Helm-van Mil
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2019
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-019-2002-z

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