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A point of view about undifferentiated connective tissue disease and undifferentiated arthritis

A point of view about undifferentiated connective tissue disease and undifferentiated arthritis

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Undifferentiated Arthritis - Undifferentiated connective tissue disease (a point of view) Presentation Transcript

  • 1. Undifferentiated Arthritis Ahmed Fathi Blasi MSc Rheumatology, P.M & Rehab.
  • 2. Definition Undifferentiated Connective Tissue Disease people who have symptoms and certain lab test results that look like a systemic autoimmune disorder or connective tissue disease. But they don't have enough of such characteristics to meet the diagnosis for a well-defined connective tissue disease.
  • 3. Definition Early Arthritis patients that cannot be classified according to EULAR/ACR criteria and in whom the arthritis is not septic or reactive in origin have per exclusion an Undifferentiated Arthritis (UA).
  • 4. EARLY R.A Early ArthritisUA Other Diagnosis
  • 5. PAST
  • 6. 1987
  • 7. The criteria were formulated by experts based on characteristics of patients with long-standing RA (mean disease duration of 8 years) Harrison BJ, Symmons DP, Barrett EM, Silman AJ. Th e performance of the 1987 ARA classifi cation criteria for rheumatoid arthritis in a population based cohort of patients with early infl ammatory polyarthritis. American Rheumatism Association. J Rheumatol 1998;25(12): 2324–2330.
  • 8. PRE-DISEASE PROCESSES A number of abnormalities have been observed in pre-disease samples that can be distinguished in the onset of autoantibodies, the onset of an inflammatory response, and the onset of lipid abnormalities.
  • 9. MID-1970 S ACPA In studies from Finland from the 1970s, it was already identified that autoantibodies are present before disease onset. Aho K, Heliovaara M, Maatela J, et al. Rheumatoid factors antedating clinical rheumatoid arthritis. J Rheumatol 1991;18: 1282–1284. Aho K, von Essen R, Kurki P, et al. Antikeratin antibody and antiperinuclear factor as markers for subclinical rheumatoid disease process. J Rheumatol 1993;20:1278–1281.
  • 10. A T H E RO S C L E RO T I C EVENTS Recent-onset RA is associated with dyslipidemia. Patients who later developed rheumatoid arthritis had a considerably more atherogenic lipid profile at least 10 years before onset of symptoms. Georgiadis AN, Papavasiliou EC, Lourida ES, et al. Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: eff ect of early treatment—a prospective, controlled study. Arthritis Res Th er 2006;8(3):R82.
  • 11. In the early phases of RA, only 13% of the patients have erosive disease. Additionally, erosions often initially present in the small joints of the feet and appear in the small joints of the hands at a later point in the disease course. Van der Heijde DM, van Leeuwen MA, van Riel PL. Radiographic progression on radiographs of hands and feet during the fi rst 3 years of rheumatoid arthritis measured according to Sharp’s method (van der Heijde modifi cation). J Rheumatol 1995;22(9): 1792–1796. Symmons DP, Silman AJ. Th e Norfolk Arthritis Register (NOAR). Clin Exp Rheumatol 2003;21(5 Suppl 31):S94–S99.
  • 12.  Rheumatoid nodules are very rare in the early phases of RA
  • 13.  Rheumatoid factor is present in only 50% of the patients with early RA. Quinn MA, Green MJ, Marzo-Ortega H, et al. Prognostic factors in a large cohort of patients with early undiff erentiated infl ammatory arthritis after application of a structured management protocol. Arthritis Rheum 2003;48(11):3039–3045.
  • 14. Patients fulfill the criteria for at least 6 weeks, a disease duration of less than 6 weeks is by definition impossible in case of early RA.
  • 15. This indicates that at present a set of criteria is needed that applies to early Undifferentiated Arthritis and that differentiate the UA patients that will progress to RA from those that will have a more benign disease course.
  • 16. The syndrome RA can now be identified in ACPA-positive & ACPA-negative disease. Van Gaalen FA, Linn-Rasker SP, van Venrooij WJ, et al. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undiff erentiated arthritis: A prospective cohort study. Arthritis Rheum 2004;50(3):709–715.
  • 17. This applies to UA as well with a different disease course in these two syndromes with a much higher chance to develop RA in the ACPA-positive UA patients. Van Gaalen FA, Linn-Rasker SP, van Venrooij WJ, et al. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undiff erentiated arthritis: A prospective cohort study. Arthritis Rheum 2004;50(3):709–715.
  • 18. The Natural Disease Course of Patients with Early Arthritis and UA Rheumatoid Arthritis Differentiated Persistent undifferentiated Arthritis EARLY ARTHRITIS 30-50% 26% arthritis Other diagnoses Undifferentiated Arthritis Remission 16% 35-54% 26-55% • Reported percentages differ among early arthritis cohorts, which explains why the total may add to more than 100%.
  • 19. • The duration of symptoms are of importance for the outcome of the patient group. In other words UA from recent onset (several weeks) has a different natural course than an arthritis that after 1 year of follow-up is still undifferentiated arthritis). unclassified (persistent
  • 20. • The reported rates of spontaneous remission in patients with UA are importantly different from those in RA. • Where as remission was achieved in 40% to 55% of the patients with recent-onset undifferentiated arthritis. Harrison BJ, Symmons DP, Brennan P, et al. Natural remission in inflammatory polyarthritis: Issues of definition and prediction. Br J Rheumatol 1996;35(11):1096–1100. Linn-Rasker SP, Allaart CF, Kloppenburg M, et al. Sustained remission in a cohort of patients with RA: Association with absence of IgMrheumatoid factor and absence of anti-CCP antibodies. Int J Adv Rheumatol 2004:2(4):4–6. Van der Helm-van Mil AH, Dieude P, Schonkeren JJ, et al. No association between tumour necrosis factor receptor type 2 gene polymorphism and rheumatoid arthritis severity: A comparison of the extremes of phenotypes. Rheumatology (Oxford) 2004;43(10): 1232– 1234.
  • 21. • The remission rate in RA is less than 10% to 15%. • Apparently, the chance to achieve a natural remission becomes smaller when the disease process is more mature. • This supports the notion that chronicity might be more easily reversed in the UA phase. Harrison BJ, Symmons DP, Brennan P, et al. Natural remission in inflammatory polyarthritis: Issues of definition and prediction. Br J Rheumatol 1996;35(11):1096–1100. Linn-Rasker SP, Allaart CF, Kloppenburg M, et al. Sustained remission in a cohort of patients with RA: Association with absence of IgM-rheumatoid factor and absence of anti-CCP antibodies. Int J Adv Rheumatol 2004:2(4):4–6. Van der Helm-van Mil AH, Dieude P, Schonkeren JJ, et al. No association between tumour necrosis factor receptor type 2 gene polymorphism and rheumatoid arthritis severity: A comparison of the extremes of phenotypes. Rheumatology (Oxford) 2004;43(10): 1232–1234.
  • 22. Important Points • UA has a variable disease course. • Disease-modifying antirheumatic drug (DMARD) therapy is potentially toxic. • only the UA patients that have a high probability of developing RA are preferentially treated with DMARDs.
  • 23. Predicting Progression from Undifferentiated Arthritis to Rheumatoid Arthritis
  • 24. The construction of a prediction rule • Initial attempts to define such prognostic criteria have been made. • This model predicts disease persistency development of erosions. Visser H, le Cessie S, Vos K, et al. How to diagnose rheumatoid arthritis early: A prediction model for persistent (erosive) arthritis. Arthritis Rheum 2002;46(2):357–365 and
  • 25. The construction of a prediction rule • Form Used to Calculate Prediction Score in Points for Individual Patients with Undifferentiated Arthritis Van der Helm-van Mil AH, le Cessie S, van Dongen H, et al. A rule to predict disease outcome in patients with recent-onset undifferentiated arthritis to guide individual treatment decisions. Arthritis Rheum 2007;56(2):433–440.
  • 26. Age in years Gender Multiply by 0.02 If female 1 point
  • 27. Distribution of involved joints If small joints in hands/feet 0.5 point If symmetric 0.5 point If upper extremities 1 point If upper and lower extremities 1.5 points
  • 28. Length of VAS morning stiffness (range 0–100 mm) If 26–90 mm 1 point If > 90 mm 2 points
  • 29. Number of tender joints If 4–10 0.5 point If ≥ 11 1 point Number of swollen joints If 4–10 0.5 point If ≥ 11 1 point
  • 30. C-reactive protein level (mg/L) If 5–50 0.5 point If ≥ 51 1.5 points Positive rheumatoid factor If yes 1 point Positive anti-CCP antibodies (ACPA) If yes 2 points
  • 31. Total Score • Age • gender
  • 32. Total Score • Distribution of involved joints. • Morning stiffness severity • Number of tender and swollen joints.
  • 33. Total Score • C-reactive proteins • Rheumatoid factor • Anti-CCP antibodies
  • 34. Question
  • 35. Presentation Patterns of ACPA positive Versus ACPA negative Disease Question of whether anti-CCP positive and negative RA are different disease entities with distinct clinical characteristics ?
  • 36. Presentation Patterns of ACPA positive Versus ACPA negative Disease • After 4 years of follow-up, patients with ACPA had more swollen joints and more severe radiologic destruction. • In conclusion, the phenotype of RA patients with or without ACPA is similar with respect to clinical presentation but differs with respect to disease course. Van der Helm-van Mil AH, Verpoort KN, Breedveld FC, et al. Antibodies to citrullinated proteins and diff erences in clinical progression of rheumatoid arthritis. Arthritis Res Th er 2005;7(5): R949–R958.
  • 37. So What ?
  • 38. Outcomes of Treatment in Undifferentiated Arthritis Van Gaalen F, Ioan-Facsinay A, Huizinga TW, et al. Th e devil in the details: Th e emerging role of anticitrulline autoimmunity in rheumatoid arthritis. J Immunol 2005;175(9):5575–5580. Van Dongen H, van Aken J, Lard LR, et al. Effi cacy of methotrexate treatment in patients with probable rheumatoid arthritis: A doubleblind, randomized, placebo-controlled trial. Arthritis Rheum 2007; 56(5):1424–1432.
  • 39. Outcomes of Treatment in Undifferentiated Arthritis • In a double-blind clinical trial, patients were randomized for treatment Methotrexate Placebo 18 month Progression towards RA Level of joint destruction Van Gaalen F, Ioan-Facsinay A, Huizinga TW, et al. Th e devil in the details: Th e emerging role of anticitrulline autoimmunity in rheumatoid arthritis. J Immunol 2005;175(9):5575–5580. Van Dongen H, van Aken J, Lard LR, et al. Effi cacy of methotrexate treatment in patients with probable rheumatoid arthritis: A doubleblind, randomized, placebo-controlled trial. Arthritis Rheum 2007; 56(5):1424–1432.
  • 40. Outcomes of Treatment in Undifferentiated Arthritis • A significantly lower number of MTX-treated UA patients had progressed to RA compared to the placebo-treated patients. Van Gaalen F, Ioan-Facsinay A, Huizinga TW, et al. Th e devil in the details: Th e emerging role of anticitrulline autoimmunity in rheumatoid arthritis. J Immunol 2005;175(9):5575–5580. Van Dongen H, van Aken J, Lard LR, et al. Effi cacy of methotrexate treatment in patients with probable rheumatoid arthritis: A doubleblind, randomized, placebo-controlled trial. Arthritis Rheum 2007; 56(5):1424–1432.
  • 41. Outcomes of Treatment in Undifferentiated Arthritis • In addition, the UA patients that were treated with methotrexate had a significantly lower level of radiologic joint destruction, indicating a less severe disease course. Van Gaalen F, Ioan-Facsinay A, Huizinga TW, et al. Th e devil in the details: Th e emerging role of anticitrulline autoimmunity in rheumatoid arthritis. J Immunol 2005;175(9):5575–5580. Van Dongen H, van Aken J, Lard LR, et al. Effi cacy of methotrexate treatment in patients with probable rheumatoid arthritis: A doubleblind, randomized, placebo-controlled trial. Arthritis Rheum 2007; 56(5):1424–1432.
  • 42. Outcomes of Treatment in Undifferentiated Arthritis • After the cessation of methotrexate at 18 months, the difference in the number of patients who developed RA remained statistically significant but the difference became smaller. Van Gaalen F, Ioan-Facsinay A, Huizinga TW, et al. Th e devil in the details: Th e emerging role of anticitrulline autoimmunity in rheumatoid arthritis. J Immunol 2005;175(9):5575–5580. Van Dongen H, van Aken J, Lard LR, et al. Effi cacy of methotrexate treatment in patients with probable rheumatoid arthritis: A doubleblind, randomized, placebo-controlled trial. Arthritis Rheum 2007; 56(5):1424–1432.
  • 43. Outcomes of Treatment in Undifferentiated Arthritis • This suggests that in some patients methotrexate had hampered the progression of the disease, but had not been able to totally stop the underlying pathophysiologic mechanisms. Van Gaalen F, Ioan-Facsinay A, Huizinga TW, et al. Th e devil in the details: Th e emerging role of anticitrulline autoimmunity in rheumatoid arthritis. J Immunol 2005;175(9):5575–5580. Van Dongen H, van Aken J, Lard LR, et al. Effi cacy of methotrexate treatment in patients with probable rheumatoid arthritis: A doubleblind, randomized, placebo-controlled trial. Arthritis Rheum 2007; 56(5):1424–1432.
  • 44. Age in years Multiply by 0.02 Gender If female 1 point Distribution of involved joints If small joints in hands/feet If symmetric If upper extremities If upper and lower extremities 0.5 point 0.5 point 1 point 1.5 points Length of VAS morning stiffness (range 0–100 mm) If 26–90 mm If > 90 mm 1 point 2 points Number of tender joints Number of swollen joints If 4–10 If ≥ 11 If 4–10 If ≥ 11 0.5 point 1 point C-reactive protein level (mg/L) If 5–50 0.5 point If ≥ 51 1.5 points Positive anti-CCP antibodies If yes 2 points 0.5 point 1 point Positive rheumatoid factor If yes 1 point
  • 45. Revision ?  Radiology  Sex  Family History  Morning Stiffness
  • 46. Early diagnosis, Early referral to a specialist, Early aggressive therapy 2- The concept of early initiation of more aggressive therapy is important because irreversible joint damage develops within the first 3 month after disease onset.
  • 47. Take Home Message Early diagnosis, early referral to a specialist and early aggressive therapy(window of opportunity, i.e. within the first 3 month of diagnosis), will delay or prevent the risk of bone erosions, joint destruction, deformity; which may improve patient’s survival and increase the number of years that patients enjoy a better quality of life.
  • 48. Thank You