Ponad 7000 publikacji medycznych!
Statystyki za 2021 rok:
odsłony: 8 805 378
Artykuły w Czytelni Medycznej o SARS-CoV-2/Covid-19

Poniżej zamieściliśmy fragment artykułu. Informacja nt. dostępu do pełnej treści artykułu
© Borgis - Postępy Nauk Medycznych 2/2012, s. 103-108
*Anna Filipowicz-Sosnowska
Wczesne zapalenie stawów – aktualny stan wiedzy
Early arthritis – current state of knowledge**
Professor Eleonora Reicher Institute of Rheumatology, Warsaw
Consultant: prof. Anna Filipowicz-Sosnowska, MD, PhD
Streszczenie
Wczesne zapalenie stawów jest często niezróżnicowanym zapaleniem o różnym początku (jedno-, kilku- i wielostawowym) w którym czas trwania choroby nie przekracza 3 miesięcy. U wielu chorych czynnik reumatoidalny (RF-IgM) jest ujemny oraz brak jest innych objawów umożliwiających spełnienie kryteriów klasyfikacyjnych. Większość chorych z wczesnym niezróżnicowanym zapaleniem stawów rozwija w różnie długim okresie czasu reumatoidalne zapalenie stawów (RZS). W doniesieniu przedstawiono znaczenie występowania, miana i typu przeciwciał anty-cytrulinowych w diagnostyce i prognozowaniu we wczesnym zapaleniu stawów, rolę zakażenia Porphyromonas gingivalis jako potencjalnego czynnika etiopatogenetycznego w RZS, trudności w ocenie klinicznej wczesnego zapalenia błony maziowej i niską przydatność konwencjonalnej radiografii we wczesnym wykrywaniu zmian destrukcyjnych w stawach. Przedstawiono różnice w odniesieniu do czułości i specyficzności starych (ACR 1987) i nowych (ACR/EULAR 2010) kryteriów klasyfikacyjnych RZS.
Summary
Early arthritis is often undifferentiated with various oncet (mono, oligo or polyarticular) and the duration of the symptoms less than 3 months. Most of the patients have negative rheumatoid factor (RF-IgM) and also there is no present other clinical symptoms satisfied for fulfiling classification criteria. Majority of patients with undifferentiated arthritis, in the various period of time, progress to rheumatoid arthritis (RA). In this review focuses on the importance of occurrence anti-citrullinated peptides (ACPA), they level and nature in making the diagnosis and prognosis of early arthritis, the role of Porphyromonas gingivalis infection as potential etiological factor of inflammation in RA, diffculty in clinical assessment of synovitis and inability of conventional radiography to detect early destructive changes in the joints. The differences in the sensitivity and specyficity the old (ACR 1987) and new (ACR/EULAR 2010 ) classification criteria for RA was discussed.



What is early arthritis?
Early arthritis is a group of rheumatic and nonrheumatic disorders characterized by unclassified arthritis beginning with mono-, oligo-, or polyarthritis, lasting up to 3 months. Rheumatoid factor (RF-IgM) is negative in many patients, and the patients have so other symptoms corresponding to the classification criteria for other diseases. The course of the disease is impossible to predict, as well as the time needed to diagnose the disease in individual patients. There are no laboratory tests that clearly differentiate early rheumatoid arthritis from other types of early arthritis, such as arthritis in infectious (viral or bacterial), reactive arthritis, arthritis accompanying cancer and systemic connective tissue diseases (1, 2).
Early arthritis represents an essential diagnostic, prognostic and therapeutic issue, all the more that the majority of patients with early unclassified arthritis develop RA at different time points (3).
There are many reasons why it is difficult to diagnose RA at an early stage of its development. Early unclassified arthritis needs to be differentiated from a number of inflammatory joint diseases, such as: systemic lupus erythematosus and other systemic connective tissue diseases, reactive arthritis, psoriatic arthritis, osteoarthritis (mainly hand osteoarthritis), as well as arthritis associated with infections and cancer.
Other factors that make early RA diagnosis difficult can be as follows: low discriminative power of the conventional ACR 1987 classification criteria for early forms of the disease, inability to detect moderate synovitis in a physical examination, absence of diagnostically reliable laboratory tests, late detecting joint erosions in conventional radiography, and difficulty in obtaining early rheumatological consultation (tab. 1).
Table 1. Difficulties in establishing an early diagnosis of rheumatoid arthritis.
– Differential diagnosis with other types of polyarthritis.
– Moderate synovitis is not detected in a physical examination.
– There are no reliable diagnostic laboratory tests.
– Conventional radiography does not detect early erosive lesions.
– Difficulties in obtaining early rheumatological consultation.
– The 1987 ACR classification criteria offer poor discriminative ability for early RA.
According to the European League Against Rheumatism recommendations for the diagnosis of early arthritis, patients presenting with arthritis of more than one joint should be referred to and seen by a rheumatologist, ideally within six weeks after the onset of symptoms. Another step in the diagnostic procedure should be also to try to determine the patients at risk of developing persistent erosive arthritis in order to introduce an optimum therapeutic strategy as early as possible (4).
Antibodies as an early rheumatoid arthritis biomarker
RA is associated with two antibody systems: rheumatoid factor (RF) and ACPA-antibody to citrullinated peptide (5). Rheumatoid factor is an antibody to the Fc portion of immunoglobulin G (IgG) and has been the core factor used in the diagnostics and prognosis of RA. High rheumatoid factor levels are associated with severe erosive disease, rheumatoid nodules, vasculitis and extra-articular symptoms. The role of rheumatoid factor in pathogenesis and maintenance of RA is yet to be clearly understood. Rheumatoid factor was found not only in patients with RA, but also in patients with other diseases and in some healthy individuals, especially in the elderly, which reduces the factor’s specificity and diagnostic reliability.
Anti-citrullinated protein antibodies (ACPA), i.e.: vimentin, filaggrin, collagen type II, fibrinogen and α-enolase, represent another powerful biomarker in RA diagnostics and prognosis.
The presence of citrulline generated posttranslationally by peptidilarginine diminaze (PAD2) is essential in citrullinated peptides (6). Anti-citrulline antibodies are detected in patients with RA and have been for many years used in RA diagnostics. Anti-citrulline antibodies include in particular: anti-keratin antibodies (AKA), anti-filaggrin antibodies (AFA) and antiperinuclear factor (APF). AKA, AFA and APF have a number of variables but they react with native filaggrin, and are therefore referred to as anti-filaggrin antibodies (AFA) (9, 10). They represent relatively high specificity for RA (> 90%), but have low sensitivity (> 30%) and do not meet the diagnostic test criteria. Anti-RA33 and anti-Sa antibodies were also thought to be useful in early RA diagnostics (11, 12). Anti-RA33 antibodies are antibodies against a specific heterogeneous nuclear ribonucleoprotein complex (A2-RNP). Anti-Sa antibodies were confirmed to be directed to vimentin found in human spleen and placenta extract. Anti-filaggrin antibodies like, anti-RA33 and anti-Sa antibodies show high specificity, but low sensitivity in RA diagnostics.
The ELISA method with the use of synthetic filaggrin-derived citrullinated peptides marked a significant progress in RA diagnostics. Anti-CCP1 (1st generation) test was based on incorporating cyclic peptide into a filaggrin molecule, representing 69% sensitivity and 81% specificity in RA diagnostics. In order to achieve higher sensitivity, citrullinated peptides were used instead of filaggrin to develop an anti-CCP2 (2nd generation) test representing 82% sensitivity and 95% specificity (13, 14).
Two new tests that detect citrullinated peptides autoantibodies have been introduced recently: anti-CCP3 (3rd generation) test and anti-MCV test for modified citrullinated vimentin. Anti-CCP3 test is based on a modified cyclic peptide used in anti-CCP1 and anti-CCP2 tests. Mutated citrullinated vimentin is used in the anti-MCV test (15-17). Anti-CCP3 test has comparable sensitivity and specificity to the anti-CCP2 test, which is similar to the anti-MCV test, which offers a clinically significant benefit – identification of anti-CCP2 negative patients.
Anti-CCP2 and anti-MCV positive test combination shows 69% sensitivity and 89% specificity in the diagnostics of early rheumatoid arthritis; anti-MCV and RF-IgM positive test combination shows 71% sensitivity and 88% specificity. The highest sensitivity and specificity was shown for anti-CCP2+RF-IgM test combination (74% and 96%, respectively), which was used in the development of the new classification criteria for RA (tab. 2) (15).
Table 2. Sensitivity and specificity of anti-CCP, anti-MCV and RF-IgM tests in patients with early rheumatoid arthritis.*
Test Sensitivity (%) Specificity (%)
Anti-CCP169 71
Anti-CCP282 95
Anti-CCP382 92
Anti-MCV84 92
RF-IgM68 84
Anti-CCP2 + anti-MCV68 89
Anti-MCV + RF-IgM71 88
Anti-CCP2 + RF-IgM74 96
*Van der Linden MPM et al. Arthritis Rheum 2009; 60: 2232-41 (the summary of results modified by the author).
Anti-citrulline autoantibodies in the diagnostics and prognostics of early rheumatoid arthritis
The diagnostic parameters of anti-CCP2 test for early RA were confirmed in a number of studies. Anti-CCP2 test was found to offer 82% sensitivity and 95% specificity in the diagnostics of early RA lasting up to 3 years (19). In steady long-term RA, the test sensitivity equalled 77%. Goldbach-Mansky R et al. (20) have demonstrated 41% sensitivity and 91% specificity of the anti-CCP2 test in a group of 238 patients with very early arthritis lasting up to 3 months, while the rheumatoid factor (RF-IgM) was demonstrated to offer 66% sensitivity and 87% specificity. The differences in the assessment of anti-CCP2 test sensitivity may depend on the selection of study subjects (very early RA vs. early RA vs. advanced RA, etc.). It is commonly claimed that the anti-CCP2 test has the highest specificity for RA (97%). Rheumatoid factor (RF-IgM) shows a slightly higher sensitivity than the anti-CCP2 test (68.4%), but has a lower specificity (84%). Anti-CCP2 test is positive in 40% RA patients who remain negative for the rheumatoid-factor, which reflects the test’s additional diagnostic value. The high predictive value of anti-CCP2 and rheumatoid factor for RA development and progress was demonstrated in a number of studies (22). The presence of anti-CCP2 antibodies and the rheumatoid factor may be the predictive factor of RA, as shown on a group of blood donors and patients with unclassified arthritis (23).
Anti-CCP2 antibodies and the rheumatoid factor (RF-IgM) are the best predictors of persistent RA in patients with very early synovitis.
Based on two years of observation of a group of patients with early synovitis, Visser H et al. used a logistic regression model to develop prediction criteria for the course of early arthritis to differentiate patients with self-limiting, non-erosive, progressive and progressive erosive type of the disease. Anti-CCP2 antibodies, the rheumatoid factor and early joint erosions were once again proved to be powerful predictors of erosive RA.
Kastbom A et al. demonstrated that anti-CCP2 positive patients typically exhibit high inflammatory activity and are more likely to develop joint erosions at an early stage of the disease as compared to anti-CCP2 negative patients.

Powyżej zamieściliśmy fragment artykułu, do którego możesz uzyskać pełny dostęp.
Mam kod dostępu
  • Aby uzyskać płatny dostęp do pełnej treści powyższego artykułu albo wszystkich artykułów (w zależności od wybranej opcji), należy wprowadzić kod.
  • Wprowadzając kod, akceptują Państwo treść Regulaminu oraz potwierdzają zapoznanie się z nim.
  • Aby kupić kod proszę skorzystać z jednej z poniższych opcji.

Opcja #1

24

Wybieram
  • dostęp do tego artykułu
  • dostęp na 7 dni

uzyskany kod musi być wprowadzony na stronie artykułu, do którego został wykupiony

Opcja #2

59

Wybieram
  • dostęp do tego i pozostałych ponad 7000 artykułów
  • dostęp na 30 dni
  • najpopularniejsza opcja

Opcja #3

119

Wybieram
  • dostęp do tego i pozostałych ponad 7000 artykułów
  • dostęp na 90 dni
  • oszczędzasz 28 zł
Piśmiennictwo
1. Machold KP, Stamm TA, Eberl GJM et al.: Very recent onset arthritis-clinical, laboratory and radiological findings during the first year of disease. J Rheumatol 2002; 29: 2278-2287.
2. Van Aken J, van Bilsen JH, Allaast CF et al.: The Leiden Early Arthritis Clinic. Clin Exp Rheumatol 2003; 21 (5 suppl 31): S 100-5.
3. Van der Helm-van Mil AH, Breedveld FG, Huzinga TW: Aspects of early arthritis. Definition of disease states in early arthritis: remission versus minimal disease activity. Arthritis Res Ther 2006; 8: 216-21.
4. Combe B, Landewe R, Lukas C et al.: EULAR recommendation for the management of early arthritis: raport of a task force of the European Standing Committee for International Clinical Studies including therapeutics (ESCISIT). Ann Rheum Dis 2007; 66: 34-45.
5. Ven Boekel MA, Vossenaar ER, van der Hoogen FH et al.: Autoantibody systems in rheumatoid arthritis: specificity, sensivity and diagnostic value. Arthritis Res 2002; 4: 87-93.
6. Marcelletti JF, Nakamura RM: Assessment of serological markers associated with rheumatoid arthritis: diagnostic autoantibodies and conventional disease activity markers. Clin Appl Immunol Rev 2003; 4: 109-23.
7. Paimela L, Gripenberg M, Kuski P et al.: Antikeratin antibodies: diagnostic and prognostic markers for early rheumatoid arthritis. Ann Rheum Dis 1992; 51: 743-746.
8. Sebbag M, Simon M, Vincent C et al.: The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis – specific autoantibodies. J Clin Invest 1995; 95: 2672-2679.
9. Vittecog O, Incaurgarat B, Jonen-Beades F et al.: Autoantibodies recognizing citrullinated rat filggrin in an ELISA using citrullinated and non-citrillinated recombinant proteins as antigens are highy diagnostic for rheumatoid arthritis. Clin Exp Immunol 2004; 135: 173-180.
10. Girbal-Neuhauser E, Durieux JJ, Arnaud M et al.: The epitopes targeted by the rheumatoid arthritis – associated antifilaggrin antoantibodies are posttranslationally generated on various sites of (pro)filaggrin by demination of arginine residues. J Immunol 1999; 162: 585-594.
11. Cordonnier C, Meyer O, Palazzo E et al.: Diagnostic value of anti RA33 antibody, antiperinuclear factor antibody in early RA comparison with rheumatoid factor. Br J Rheum 1996; 35: 620-626.
12. Hayem G, Chazerin P, Combe B et al.: Anti-Sa antibody in an accurate diagnostic and prognostic marker in adult rheumatoid arthritis. J Rheumatol 1999; 26, 7: 13-16.
13. Nielen MM, Van der Horst AR, Van Schaardenburg D et al.: Antibodies to citrullinated human fibrinogen (ACF) have diagnostic and prognostic value in early arthritis. Ann Rheum Dis 2005; 64: 1199-1204.
14. Grootenboer-Mignot S, Nicaise-Roland P, Delaunay C et al.: Second generation anti-cyclic citrullinated peptide (anti-CCP2) antibodies can replace other anti-filaggrin antibodies and improve rheumatoid arthritis diagnosis. Scand J Rheumatol 2004; 33: 218-220.
15. Van der Linden MPM, van der Wonde D, Joan-Facsinay A et al.: Value of anti-modified citrullinated vimentin and third-generation anti-cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritis. Arthritis & Rheum 2009; 60, 8: 2232-2241.
16. Bang H, Egerer K, Gauliard A et al.: Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis & Rheum 2007; 56: 2503-2511.
17. Mathsson L, Mullazehi M, Wiek MC et al.: Antibodies against citrullinated vimentin in rheumatoid arthritis: higher sensitivity and extended prognostic value concerning future radiographic progression as compared with antibodies against cyclic citrullinated peptides. Arthritis & Rheum 2008; 58: 36-45.
18. Innola L, Kokkonen H, Eriksson C et al.: Antibodies against mutated citrullinated vimentin are a better predictor of disease activity at 24 month in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides. J Rheumatol 2008; 35: 1002-1008.
19. Dubneguoi S, Solan-Gervais E, Lefranc D et al.: Evaluation of anti-citrullinated filaggrin antibodies as hallmarks for the diagnosis of rheumatic diseases. Ann Rheum Dis 2004; 63: 415-419.
20. Goldbach-Mansky R, Lee J, McCoy A et al.: Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset. Arthritis Res 2000; 2: 236-243.
21. Valbracht I, Rieberg J, Oppermann M et al.: Diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis. Ann Rheum Dis 2004; 63: 1079-1084.
22. Klareskog L, Alfredsson L, Rantapaa-Dohlquist S et al.: What precides development of rheumatoid arthritis. Ann Rheum Dis 2004; 63 (Suppl. II): 28-31.
23. Van Aken J, van Dongen H, le Cessie S et al.: Comparison of long term outcome of patients with rheumatoid arthritis presenting with undifferentiated arthritis or with rheumatoid arthritis: an observational cohort study. Ann Rheum Dis 2006; 65: 20-25.
24. 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: 357-365.
25. Kastbom A, Strandberg G, Lindroos A et al.: Anti-CCP antibody test predict the disease course during three years in early rheumatoid arthritis (the TIRA project). Ann Rheum Dis 2004; 63: 1085-1089.
26. Syversen SW, Gaarder PJ, Goll GL et al.: High anticyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann Rheum Dis 2008; 67: 212-217.
27. Suir Q, Widhe M, Hermansson M et al.: Antibodies to several citrullinated antigens are enriched in the joints of rheumatoid arthritis patients. Arthritis & Rheum 2010; 62, 1: 44-52.
28. Guzian MC, Carrier N, Cossette P et al.: Outcomes in recent onset in inflammatory polyarthritis differ according to initial titers persistence over time and specificity of the autoantibodies. Arthritis Care Res 2010; 62, 11: 1624-1632.
29. Kallberg H, Padynkow L, Plenge RM et al.: Gene=gene and gene-environment interaction involving HLA-DRB1, PTPN22 and smoking in two subsets of rheumatoid arthritis. Ann J Hum Genet 2007; 80: 867-875.
30. Mikuls TR, Payne JB, Reinhardt RA et al.: Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid arthritis and periodontitis. Int Immunopharmacol 2009; 9: 38-42.
31. De Pablo P, Dietrich T, McAlindon TE: Association of periodontal disease and tooth loss with rheumatoid arthritis in the USA population. J Rheumatol 2008; 35: 70-76.
32. De Pablo P, Chapple IL, Buckley CD et al.: Periodontitis in systemic rheumatic diseases. Nat Rev Rheumatol 2009; 5: 218-224.
33. Wegner N, Wait R, Sroka A et al.: Peptidyloarginine deminase from Pophyromonas gingivalis citrullinates human fibrinogen and α-enolase. Implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum 2010; 62, 9: 2662-2672.
34. Van Gaalen FA, van Aken J, Huizinga TW et al.: Association between HLA class II genes and autoantibodies to cyclic citrullinated peptides (CCPs) influences the severity of rheumatoid arthritis. Arthritis Rheum 2004; 50: 2113-2121.
35. Keen HI, Emery P: How should we manage early rheumatoid arthritis? From imaging to intervention. Curr Opin Rheumatol 2005; 17: 280-285.
36. Hoving JL, Buchbinder R, Hall S et al.: A comparison of magnetic resonance imaging, sonography, and radiography of the hand in patients with early rheumatoid arthritis. Rheumatol 2004; 33: 154-161.
37. Klarkund M, Ostergaard M, Jensen KE et al.: Magnetic resonance imaging, radiography and scintigraphy of the finger joints: one year follow up of patients with early arthritis. The TIRA group. Ann Rheum Dis 2000; 59: 521-528.
38. Arnett FC, Edworthy SM, Bloch DA et al.: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315-324.
39. Aletaha D, Neogi T, Silman A et al.: 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism colaborative initiative. Ann Rheum Dis 2010; 69, 9: 1580-1588.
40. Cohen S, Emery P: The American College of Rheumatology/European League Against Rheumatism Criteria fort he classification of rheumatoid arthritis: a game changer. Ann Rheum Dis 2010; 69, 9: 1675-1676.
41. Van Schaardenburg D, Dijkmans BAC: A welcome address for the new criteria. Ann Rheum Dis 2010; 69: 1577-1579.
42. Stanisławska-Biernat E, Sierakowska M, Sierakowski S: Nowe kryteria klasyfikacyjne reumatoidalnego zapalenia stawów. Reumatologia 2010; 48, 6: 361-365.
43. Van der Linden MPM, Knevel R, Huizinga WJ et al.: Classification of rheumatoid arthritis. Comparison of the 1987 American College of Rheumatology Criteria and the 2010 American College of Rheumatology/European League Against Rheumatism Criteria. Arthritis & Rheum 2011; 63: 37-42.
otrzymano: 2011-12-08
zaakceptowano do druku: 2012-01-04

Adres do korespondencji:
*Anna Filipowicz-Sosnowska
Instytut Reumatologii im. prof. Eleonory Reicher w Warszawie
ul. Spartańska 1, 02-637 Warszawa
tel.: +48 (22) 844-77-97

Postępy Nauk Medycznych 2/2012
Strona internetowa czasopisma Postępy Nauk Medycznych