INTRODUCTION/LITERATURE REVIEW RA chronic rheumatic disease (1). - PowerPoint PPT Presentation

DR AYUNGA A.O , DR G.O.OYOO,PROF. AMAYO DR A.AMAYO

INTRODUCTION/LITERATURE REVIEW  RA ‐ chronic rheumatic disease (1). ‐ Early diagnosis ‐ empirical and difficult(2) ‐ joint damage first 2 yrs.  ACR criteria(3) ‐ not suitable for early diagnosis  Anti ‐ ccp ‐ Anti ‐ cyclic citrullinated peptide antibodies is a new serological marker that is highly specific for RA. ‐ sensitive and specific and picks RA early ‐ prognostic information on disease progression ‐ detected by ELISA

Rheumatoid Factor  Of IgM variety with low affinity.  Can be detected in 80% of the pts with RA.  Specificity of 50 ‐ 90%.  Antibodies are found in several other diseases.  Found in 10 ‐ 30% healthy controls  may take many years to become positive.  Therefore has low sensitivity for early RA(5).  5 Visser H,le Cassie S,Vos K et al. How to diagnose RA early:a prediction model for persistent(erosive) arthritis.Arthritis Rheum 1988;31:315 ‐ 24

STUDY JUSTIFICATION  Early diagnosis of RA is important .  Anti ‐ ccp is useful for early diagnosis.  No study has been done in our setup to determine the prevalence of Anti ‐ ccp.  Anti ‐ CCP has been advocated to be part of the ACR diagnostic criteria in some setups.

RESEARCH QUESTIONS  What is the prevalence of Anti ‐ CCP antibodies in pts with inflammatory arthritis at Kenyatta National Hospital?  What are their associated clinical characteristics?

OBJECTIVES BROAD OBJECTIVE :  To determine the prevalence and utility of Anti ‐ CCP antibodies in diagnosis of RA in pts with inflammatory arthritis at KNH. SPECIFIC OBJECTIVES  To determine ‐ prevalence of anti ‐ CCP antibodies. ‐ prevalence of RF antibodies. ‐ percentage of pts satisfy the ACR criteria.  To correlate the clinical characteristics in ACR criteria with RF and Anti ‐ ccp.

SELECTION CRITERIA This was a cross sectional study.133 pts were consecutively sampled and recruited into the study. Inclusion criteria •Patients referred with arthritis to the MOPCs •Patients who gave signed informed consent •Age was 18yrs and above. Exclusion criteria •Patients with acute febrile illnesses(proven viral/bacterial). •Patients known to have other autoimmune diseases such as SLE/Sjogrens syndrome. •Patients known to have gout, septic arthritis and osteoarthritis.

CASE DEFINITIONS  Arthritis :pt with inflammation of the joint,swelling,pain,stiffness and tenderness  Inflammatory arthritis :pt with arthritis that is worse in the morning and improves with activity with an elevated ESR.  Rheumatoid arthritis :pt with signs and symptoms that satisfy the ACR criteria.At least four elements of the criteria to be fulfilled.  Unspecified arthritis :pt with signs and symptoms of arthritis not satisfying the ACR criteria

VARIABLES  Elevated ESR  >15mm/hr and >20mm/hr for men and women under 50 years of age respectively  >20mm/hr and >30mm/hr for men and women older than 50years of age respectively  Anti ‐ ccp  Positive:>5.1iu Negative:<5.0 iu  RF  Positive above 50iu and negative below 50iu .

Clinical and Laboratory procedures  socio ‐ demographic characteristics, referral diagnosis and consent were obtained.  History and P/E were carried out.  5mls of blood was drawn for ESR,RF and Anti ‐ ccp measurements.  Data was recorded and analysed by SPSS ver 15.0  Associations examined using the chi ‐ square test for categorical data and Student t ‐ test for continues variables.  Associations were significant if the p=0.05

RESULTS

FLOW CHART ‐ fig 1 134 patients with arthritis in MOPC Consent, History and Physical Examination GALS 133 Eligible and 1 declined consented consent ESR 38 patients with Non ‐ Inflammatory Arthritis 95 Patients with Inflammatory Arthritis ACR 31 UA Patients 64 RA Patients Anti –CCP RF Anti –CCP RF Anti ‐ CCP +ve Anti ‐ CCP RF +ve RF ‐ ve Anti ‐ CCP +ve Anti ‐ CCP –ve RF +ve RF ‐ ve 40 Patients ‐ ve 32 Patients 32 Patients 5 Patients 26 Patients 3 Patients 28 Patients 24 Patients

Age distribution ‐ figure 2

ACR classification ‐ figure 3

Age of RA and UA patients ‐ Table 1 Variable RA UA P value Age 44.7 years 41.2 years 0.356

Fig 4 ‐ Prevalence of RA and UA by sex P=0.759

Clinical characteristics.. Duration of illness  Duration of illness range:2wks ‐ 260wks  Mean duration of illness was 62.8 weeks ± 54.8SD  The mean dura tion of illness was higher by about 10 wks among the RA pts than the UA pts. (p=0.433)

Clinical characteristics… Family history of RA  Family h/o RA was present in 25.3% of all pts. Family h/o RA in RA pts 25.8% Family h/o RA in UA pts 25%

Number of joints involved(p=0.011) Average no of joints 9.6 Joints involved in RA 10.2 Joints involved in UA 8.4

Figure 5 ‐ Number of joints involved vs Anti ‐ ccp  20     JOINTS INVOLVED 15   10 5      Negative Positiv e Prevalence of Anti-CCP

ANTI ‐ CCP AND RF ‐ PREVALENCE  The overall prevalence of anti ‐ CCP (47.4%) was higher than that of rheumatoid factor (36.8%), P=0.05. Figure 6: Prevalence of RF and Anti ‐ CCP

Anti ‐ ccp in RA and UA patients  The mean Anti ‐ ccp was 78.0 iu and 22.0 iu in RA and UA pts respectively  62.5% of RA pts (64) were Anti ‐ ccp positive compared to 16.1% of the UA pts (31).  Therefore, diagnosis of RA was significantly associated to anti ‐ CCP positivity(P=0 000) (Figure 7)

Figure 7:Prevalence of Anti ‐ ccp in RA/UA

Figure 8:Anti ‐ ccp vs RA and UA  When the levels of Anti ‐ ccp were plotted for patients in both groups, it was noted that the patients in the RA group had higher Anti ‐ ccp titres compared with those in the UA group.  200.00  150.00  P C  C - 100.00 I T N A 50.00  0.00 Not satisfied Satisfied ACR

Figure 9 ‐ prevalence of RF in both RA and UA P=0.000

SUBSET OF PATIENTS WITH UA AND POSITIVE ANTI ‐ CCP Variable UA subset Whole group of (n=5) UA (n=31) RF 3 (60%) 3 (9.7%) Anti ‐ ccp (mean iu) 127.6 22.0 No. of joints 10.4 8.4 Family history 2 (40%) 8 (25.8%) Age in yrs (mean) 45.4 41.2

Discussion ‐ demographic characteristics..  M:F=1:10.  Owino(54) 1:6.5, Oyoo(55) 1:5.  The other studies did not attend to pts with UA hence the difference.  Mean age of RA pts of 44.7 years  Oyoo(55) ‐ 44.5 and Bagg et al(57) ‐ 43. 57Bagg L.R.,Hansen D.P.,Lewis C.,et al.RA in Kenya.I.Clinical observations.Ann of Rheum Dis.1979;38:23 ‐ 25.  58Wiles N.Estimating the icidence of RA.Arth and Rheum.1999;42:1339 ‐ 1346

ACR criteria  64 pts(67.4%) satisfied the ACR criteria  Harrison BJ et al(67%) ( 61) found similar results with in an early arthritis clinic  Higher prevalence of Anti ‐ ccp than RF  Anti ‐ ccp  Nielen and coworkers( 67 ) found Anti ‐ ccp 41% and RF to be 28% in a similar study.  Anti ‐ ccp detected more positive subjects compared to RF . 1. 67Vittecoq O, Incaurgarat B, Jouen ‐ Beades F, et al . Autoantibodies recognizing citrullinated rat filaggrin in an ELISA using citrullinated and non ‐ citrullinated recombinant proteins as antigens are highly diagnostic for rheumatoid arthritis. Clin Exp Immunol 2004;135:173 ‐ 180

ANTI ‐ CCP  Forty(88.9%) of the pts who tested positive for Anti ‐ ccp were classified as RA in our study.  D.M Lee et al(62) found almost a similar figure of 83% in these subset of pts.  Hence anti ‐ ccp is significantly correlated with the ACR criteria in classifying pts into RA and UA.  62Annals of Rheumatic diseases 2003;62:870 ‐ 874

RF  RF+ in 50% of the pts classified as RA .  Earlier studies(63) ‐ 70 ‐ 80%.  Owino et al(54) ‐ 78.9%.  Pts in our study had a shorter duration of disease(62.8 wks) than the studies that were done earlier(64.97 months)(54).  63Smolen JS (1996) Autoantibodies in rheumatoid arthritis. In: van Venrooij WJ, Maini RN, (eds) Manual of biological markers of disease, Section C1.1/1–C1.1/18. Kluwer, Dordrecht .

RF NEGATIVE WITH POSITIVE ANTI ‐ CCP  60 pts RF negative,20% had positive Anti ‐ ccp .  Results elsewhere 20 ‐ 43%(65,66).  D.M Lee et al(62) found 34% .  These values suggest important diagnostic utility where previously serology had been unhelpful.  From this prevalence of Anti ‐ ccp in seronegative individuals, using Anti ‐ ccp would appear to select seronegative RA pts and so has important implications for pt management.  65Arthritis Rheum 2000;43:155 ‐ 63.

THE UA PATIENTS WITH POSITIVE ANTI ‐ CCP  5 pts UA ‐ Anti ‐ ccp positive  These pts had higher titres for Anti ‐ ccp (127.64 iu than the average(59.8iu).  Their mean joint count and the age never differed significantly from the total study population.  Hence pts with UA whose diagnosis of RA is in doubt,Anti ‐ ccp is of much help in confirming the diagnosis.

STUDY LIMITATIONS  The results might not be representative as only the MOPC was used as the study site.