Clinically suspect arthralgia: a current view of the preclinical phase of rheumatoid arthritis
Authors:
M. Filková
Authors place of work:
Revmatologický ústav, Revmatologická klinika, 1. lékařská fakulta, Univerzita Karlova, Praha
Published in the journal:
Čes. Revmatol., 26, 2018, No. 4, p. 162-170.
Category:
Review Article
Summary
Rheumatoid arthritis (RA) is being considered a multistep process. Certain genetic background along with environmental risk factors result to the break of immune tolerance and trigger autoimmune processes associated with production of autoantibodies. These are followed by first symptoms without any apparent arthritis and then first manifestation of clinically detectable arthritis - either undifferentiated or fulfilling criteria for definite RA. Despite joints being the typical site of manifestation of RA, the pathogenesis of the disease starts off far away of any joint structures. It is suggested that the first immunopathogetic processes start in the lungs or other mucous barriers such as periodont. This theory is supported by normal synovial tissue obtained from the joints of otherwise healthy carriers of anti-citrullinated protein antibodies (ACPA). ACPA can be detected months or even years before the first manifestation of RA. Combination of ACPA and rheumatoid factors are associated with 10x higher risk of developing RA in comparison with individuals lacking these autoantibodies.
Knowledge of the pathogenesis of RA brings the threshold for diagnosis, treatment or measures aiming for prevention of the development of RA to earlier stages even before the first manifestation of arthritis – the preclinical stage of RA (pre-RA). The EULAR definition characterizing individuals considered at risk of progression to RA (clinically suspect arthralgia, CSA) unifies the clinical characteristics of these individuals and future patients. At present, this definition is used for research purposes and clinical trials. This new perspective of looking at the pre-RA is appreciated in ongoing clinical trials aiming for delay or even prevention from manifestation of RA using different treatment approach.
Key words:
rheumatoid arthritis, arthralgia, ACPA
Zdroje
1. Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, et al. Rheumatoid arthritis. Nat Rev Dis Primers 2018; 4: 18001.
2. 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.
3. Smolen JS, Landewe R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017; 76(6): 960–77.
4. Raza K, Klareskog L, Holers VM. Predicting and preventing the development of rheumatoid arthritis. Rheumatology (Oxford) 2016; 55(1): 1–3.
5. Catrina AI, Svensson CI, Malmstrom V, Schett G, Klareskog L. Mechanisms leading from systemic autoimmunity to joint-specific disease in rheumatoid arthritis. Nat Rev Rheumatol 2017; 13(2): 79–86.
6. Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 1987; 30(11): 1205–13.
7. Viatte S, Plant D, Han B, Fu B, Yarwood A, Thomson W, et al. Association of HLA-DRB1 haplotypes with rheumatoid arthritis severity, mortality, and treatment response. JAMA 2015; 313(16): 1645–56.
8. Barra L, Scinocca M, Saunders S, Bhayana R, Rohekar S, Racape M, et al. Anti-citrullinated protein antibodies in unaffected first-degree relatives of rheumatoid arthritis patients. Arthritis Rheum 2013; 65(6): 1439–47.
9. Klareskog L, Malmstrom V, Lundberg K, Padyukov L, Alfredsson L. Smoking, citrullination and genetic variability in the immunopathogenesis of rheumatoid arthritis. Semin Immunol 2011; 23(2): 92–8.
10. Sokolove J, Bromberg R, Deane KD, Lahey LJ, Derber LA, Chandra PE, et al. Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS One 2012; 7(5): e35296
11. Wigerblad G, Bas DB, Fernades-Cerqueira C, Krishnamurthy A, Nandakumar KS, Rogoz K, et al. Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism. Ann Rheum Dis 2016; 75(4): 730–8.
12. Kuhn KA, Kulik L, Tomooka B, Braschler KJ, Arend WP, Robinson WH, et al. Antibodies against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis. J Clin Invest 2006; 116(4): 961–73.
13. Firestein GS, McInnes IB. Immunopathogenesis of Rheumatoid Arthritis. Immunity 2017; 46(2): 183–96.
14. Gerlag DM, Norris JM, Tak PP. Towards prevention of autoantibody-positive rheumatoid arthritis: from lifestyle modification to preventive treatment. Rheumatology (Oxford) 2016; 55(4): 607–14.
15. Stack RJ, van Tuyl LH, Sloots M, van de Stadt LA, Hoogland W, Maat B, et al. Symptom complexes in patients with seropositive arthralgia and in patients newly diagnosed with rheumatoid arthritis: a qualitative exploration of symptom development. Rheumatology (Oxford) 2014; 53(9): 1646–53.
16. Ten Brinck RM, van Steenbergen HW, Mangnus L, Burgers LE, Reijnierse M, Huizinga TW, et al. Functional limitations in the phase of clinically suspect arthralgia are as serious as in early clinical arthritis; a longitudinal study. RMD Open 2017; 3(1): e000419.
17. Burgers LE, van Steenbergen HW, Ten Brinck RM, Huizinga TW, van der Helm-van Mil AH. Differences in the symptomatic phase preceding ACPA-positive and ACPA-negative RA: a longitudinal study in arthralgia during progression to clinical arthritis. Ann Rheum Dis 2017; 76(10): 1751–4.
18. 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.
19. Krabben A, Stomp W, van der Heijde DM, van Nies JA, Bloem JL, Huizinga TW, et al. MRI of hand and foot joints of patients with anticitrullinated peptide antibody positive arthralgia without clinical arthritis. Ann Rheum Dis 2013; 72(9): 1540–4.
20. Kleyer A, Krieter M, Oliveira I, Faustini F, Simon D, Kaemmerer N, et al. High prevalence of tenosynovial inflammation before onset of rheumatoid arthritis and its link to progression to RA-A combined MRI/CT study. Semin Arthritis and Rheum 2016; 46(2): 143–50.
21. 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.
22. 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.
23. van de Stadt LA, Bos WH, Meursinge Reynders M, Wieringa H, Turkstra F, van der Laken CJ, et al. The value of ultrasonography in predicting arthritis in auto-antibody positive arthralgia patients: a prospective cohort study. Arthritis Res Ther 2010; 12(3): R98.
24. van de Sande MG, de Hair MJ, van der Leij C, Klarenbeek PL, Bos WH, Smith MD, et al. Different stages of rheumatoid arthritis: features of the synovium in the preclinical phase. Ann Rheum Dis 2011; 70(5): 772–7.
25. de Hair MJ, Lehmann KA, van de Sande MG, Maijer KI, Gerlag DM, Tak PP. The clinical picture of rheumatoid arthritis according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria: is this still the same disease? Arthritis Rheum 2012; 64(2): 389–93.
26. Demoruelle MK, Weisman MH, Simonian PL, Lynch DA, Sachs PB, Pedraza IF, et al. Brief report: airways abnormalities and rheumatoid arthritis-related autoantibodies in subjects without arthritis: early injury or initiating site of autoimmunity? Arthritis Rheum 2012; 64(6): 1756–61.
27. van Baarsen LG, de Hair MJ, Ramwadhdoebe TH, Zijlstra IJ, Maas M, Gerlag DM, et al. The cellular composition of lymph nodes in the earliest phase of inflammatory arthritis. Ann Rheum Dis 2013; 72(8): 1420–24.
28. Ten Brinck RM, van Steenbergen HW, van Delft MAM, Verheul MK, Toes REM, Trouw LA, et al. The risk of individual autoantibodies, autoantibody combinations and levels for arthritis development in clinically suspect arthralgia. Rheumatology (Oxford) 2017; 56(12): 2145–53.
29. 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.
30. Sparks JA, Iversen MD, Yu Z, Triedman NA, Prado MG, Miller Kroouze R, et al. Disclosure of Personalized Rheumatoid Arthritis Risk Using Genetics, Biomarkers, and Lifestyle Factors to Motivate Health Behaviour Improvements: A Randomized Controlled Trial. Arthritis Care Res (Hoboken) 2018; 70(6): 823–33.
31. Cope AP. Emerging therapies for pre-RA. Best Pract Res Clin Rheumatol 2017; 31(1): 99–111.
32. Scott IC, Seegobin SD, Steer S, Tan R, Forabosco P, Hinks A, et al. Predicting the risk of rheumatoid arthritis and its age of onset through modelling genetic risk variants with smoking. PLoS Genet 2013; 9(9): e1003808
33. an Dongen H, van Aken J, Lard LR, Visser K, Ronday HK, Hulsmans HM, et al. Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2007; 56(5): 1424–32.
34. Emery P, Durez P, Dougados M, Legerton CW, Becker JC, Vratsanos G, et al. Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial). Ann Rheum Dis 2010; 69(3): 510–6.
35. Verstappen SM, McCoy MJ, Roberts C, Dale NE, Hassell AB, Symmons DP, et al. Beneficial effects of a 3-week course of intramuscular glucocorticoid injections in patients with very early inflammatory polyarthritis: results of the STIVEA trial. Ann Rheum Dis 2010; 69(3): 503–9.
36. Machold KP, Landewe R, Smolen JS, Stamm TA, van der Heijde DM, Verpoort KN, et al. The Stop Arthritis Very Early (SAVE) trial, an international multicentre, randomised, double-blind, placebo-controlled trial on glucocorticoids in very early arthritis. Ann Rheum Dis 2010; 69(3): 495–502.
37. Bos WH, Dijkmans BA, Boers M, van de Stadt RJ, van Schaardenburg D. Effect of dexamethasone on autoantibody levels and arthritis development in patients with arthralgia: a randomised trial. Ann Rheum Dis 2010; 69(3): 571–4.
38. Gerlag DM, Safy M, Maijer KI, Tang MW, Tas SW, Starmans-Kool MJF, et al. Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study. Ann Rheum Dis. 2018 Dec 1. [Epub ahead of print]
39. ISRCTN registry. ISRCTN46017566 Arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept. BioMed Central http://dx.doi.org/10.1186/ISRCTN46017566 (2015)
40. US National Library of Medicine. ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/NCT02778906 (2016)
41. Nederlands Trial Register. Trialregister.nl http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4853 (2014)
42. Nederlands Trial Register. Trialregister.nl http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5265 (2015)
43. US National Library of Medicine. ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/NCT02603146 (2017)
Štítky
Dermatology & STDs Paediatric rheumatology RheumatologyČlánok vyšiel v časopise
Czech Rheumatology
2018 Číslo 4
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