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.

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
• steoarthritis.

SELECTION CRITERIA

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

ESR 133 Eligible and consented Consent, History and Physical Examination GALS 95 Patients with Inflammatory Arthritis 38 patients with Non‐Inflammatory Arthritis 134 patients with arthritis in MOPC 1 declined consent ACR 64 RA Patients 31 UA Patients

Anti –CCP Anti –CCP RF RF Anti‐CCP +ve 40 Patients Anti‐CCP ‐ve 24 Patients RF +ve 32 Patients RF ‐ve 32 Patients Anti‐CCP +ve 5 Patients Anti‐CCP –ve 26 Patients RF +ve 3 Patients RF ‐ve 28 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 duration 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

Prevalence of Anti-CCP

JOINTS INVOLVED

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.

ACR

A N T I

• C

C P

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 (n=5) Whole group of 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).

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.

CONCLUSIONS

• 1. Anti‐ccp antibodies are prevalent in pts with

inflammatory arthritis at 47.4%.

• 2. RF is prevalent at 36.8% in pts with

inflammatory arthritis 3.A greater percentage of pts who satisfied the ACR criteria were Anti‐ccp positive than RF.

• 4. A greater percentage of pts negative for RF are

positive for Anti‐ccp

• 5. Pts positive for Anti‐ccp had more joints

involved than those who were negative for Anti‐ccp.

RECOMMENDATIONS

• 1. Anti‐ccp should be done to confirm

diagnosis of RA where diagnosis of RA is doubtful..

• 2. That in pts classified as UA and have a RF

negative to have Anti‐ccp done on them to exclude RA.

• 3. That a follow up study be done to evaluate

the course of the illness in pts with both positive and negative Anti‐ccp

.

THANK YOU

APPENDIX 1: SOCIO‐DEMOGRAPHICS

Marital status Single Married Separated Widowed 27 (28.4) 59 (62.1) 4 (4.2) 5 (5.3) Level of education None Primary Secondary Tertiary 8 (8.4) 31 (32.6) 27 (28.4) 29 (30.5) Residence Urban Periurban Rural 51 (53.7) 40 (42.1) 4 (4.2)

ACR CRITERIA

 1. Morning stiffness  Morning stiffness in and around joints, lasting at

least one hour before maximal improvement.

 2.Arthritis of three or more joint areas  At least three joint areas simultaneously have had

soft tissue swelling or fluid[not bony overgrowth alone] observed by a physician.The fourteen possible areas are right or left PIP,MCP,wrist,elbow,knee,ankle and MTP joints.

 3.Arthritis of hand joints  At least one area swollen[as defined above] in a

wrist,MCP,or PIP joint.



ACR CRITERIA

4.Symmetric arthritis Simultaneous involvement of the same joint

areas[as defined above in 2] on both sides of the body[bilateral involvement of PIPs,MCPs or MTPs is acceptable without absolute symmetry].

5.Rheumatoid nodules Subcutaneous nodules,over bony

prominences,or externsor surfaces, or juxta‐ articular regions obser ed b a ph sician

ACR..

 6.Serum rheumatoid factor  Demonstration of abnormal amounts of serum RF

by any method for which the result has been positive in <5% of normal subjects.

 7.Radiographic changes  Radioraphic changes typical of RA on postero‐

anterior hand and wrist radiographs,which must include erosions or equivocal bony decalcification localized in or most marked adjacent to the involved joints[osteoarthritis alone do not qualify].For classification purposes,a patient shall be said to have RA if she /he has satisfied at least

PPV/NPV

 PPV FOR ANTI‐CCP

 PPV=TP/TN+FN =40/26+24=40/50=80%  NPV=TN/TN+FN=26/26+24=26/50=52%

 PPV FOR RF

 PPV=TP/TN+FN=32/28+32=32/60=53.3%  NPV=TN/TN+FN=28/28+32=28/60=46.7%