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O6 Subclinical atherosclerosis and endothelial dysfunction in patients with early rheumatoid arthritis as evidenced by measurement of carotid intima-media thickness and flow mediated vasodilatation and their response to therapy with disease-modifying anti-rheumatic drugs*
S2
Indian Journal of Rheumatology 2011 November; Vol. 6, No. 3 (Suppl)
Methods: RA patients naïve to MTX/DMARDs and glucocorticoids were treated with a gradually escalating dose of MTX till a maximum of 25 mg/week or best-tolerated dose was reached at week 8. Expression and function of MDR-1 was carried out by flowcytometry at baseline and after 4 months of therapy. MDR-1 expression was measured by relative fluorescence intensities and percentage of positive cells and function by rhodamine efflux assay. Reduction in disease activity score 28 (DAS-28) of value ≥ 1.2 was defined as responder and of value < 1.2 as non-responder. Results: Among 52 patients (mean age 41.6 years, mean duration of RA 43.1 months) enrolled in the study, 11 were grouped as non-responders. Compared to baseline, the expression (P < 0.001) and function (P < 0.001) of the MDR-1 reduced significantly at 4th month in the responder group, whereas in the non-responders it either increased or remained unchanged. Compared to non-responders there was a significant decrease in expression (P < 0.02) and function (P < 0.005) of MDR-1 in responders at 4th month. Conclusion: Resistance to MTX may be due to persistent expression and function of MDR-1.
O6 Subclinical atherosclerosis and endothelial dysfunction in patients with early rheumatoid arthritis as evidenced by measurement of carotid intima-media thickness and flow mediated vasodilatation and their response to therapy with disease-modifying anti-rheumatic drugs* Maitrayee Chatterjee Adhikari, Aharna Guin, Pradyot Sinhamahapatra, Alakendu Ghosh Department of Rheumatology, Institute of Post-Graduate Medical Education and Research, SSKM Hospital, Kolkata Introduction: Patients with rheumatoid arthritis (RA) have an increased morbidity and mortality due to cardiovascular diseases (CVD). Atherosclerotic process in RA is thought to be accelerated by systemic chronic inflammation in addition to traditional CV risk factors. The present study examined the frequency of endothelial dysfunction and subclinical atherosclerosis in early RA patients by carotid intima-media thickness (cIMT) and endothelial-dependent flow-mediated vasodilatation (ED-FMD) as compared with healthy controls and followed them over 12 months while they were on disease-modifying anti-rheumatic drugs (DMARDs). Materials and patients: The study included 35 early RA patients (29 females, 6 males) who had disease duration of < 12 months and 35 healthy controls (28 females, 7 males). The consecutive patients were selected from among the patients visiting the ‘early arthritis clinic’ of Rheumatology Department at IPGME&R, SSKM Hospital, Kolkata. After one year, five patients were lost to follow-up. Methods: cIMT and ED-FMD were measured by high-resolution ultrasonography at baseline in patients and controls, and re-assessed after 12 months in patients, and the changes in the respective parameters were calculated. Data were analysed by paired and unpaired t-tests. Results: RA patients had an average disease duration of 0.46 ± 0.28 years. Mean cIMT and FMD% had significant differences in RA patients when compared with those in controls (P = 0.007 and P = 0.004, respectively). Both the parameters significantly improved after one year of treatment with DMARDs (P = 0.002 and P = 0.046, respectively). Conclusion: Early RA patients have altered cIMT and FMD% signifying both structural and functional abnormalities, but early control of the disease with DMARDs may reduce atherosclerotic progression.
O7 To determine the prevalence and clinically significant cut-off titre of anti-cyclic citrullinated peptide antibody in the diagnosis of early rheumatoid arthritis in Indian population Parasar Ghosh, Jana Debarshi, Dhar Sanjay, Ghosh Alakendu Department of Rheumatology and Clinical Immunology, Institute of Post-Graduate Medical Education and Research, Kolkata Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory symmetric polyarthritis affecting about 1% of the Indian population. The anti-cyclic citrullinated peptide (anti-CCP) antibody has come up as a useful marker for diagnosing RA early. The sensitivity and specificity of second-generation anti-CCP antibody is 64–89% and 88–99%, respectively. The objective was to find out the prevalence and the cut-off level of the second-generation anti-CCP antibody in our population which will distinguish RA patients from healthy controls best. Subjects and methods: We collected serum of 150 patients with early RA (disease duration < 2 years), of 100 patients with undifferentiated arthritis and of 250 healthy controls. The second-generation anti-CCP was measured by the enzyme-linked immunosorbent assay (ELISA) method. The cut-off of titre was determined by the receptor operator characteristics (ROC) curve analysis. Results: The anti-CCP antibody level was useful in differentiating patients with early RA from healthy controls and not from undifferentiated arthritis. The different cut-off levels of antiCCP antibody levels differentiating early RA patients from healthy controls were as follows: Anti-CCP level (IU/mL) 5.06 7.7 10.1 15
Sensitivity (%)
Specificity (%)
Positivity in RA patients (%)
Positivity in controls (%)
66 60 56 50
63.6 82.4 89.4 94
66 60 56 50
37.5 19.6 11.6 6.4
*Nominated for DRA young investigator awards.
Oral Presentations Area under curve: 0.703 (95% confidence interval, 0.643–0.764, P < 0.001). At the cut-off value of 10 IU/mL, the anti-CCP positivity was 11.6% in healthy controls and 56% in early RA patients. Conclusion: The cut-off level of anti-CCP antibody differentiating patients with early RA from that of healthy controls was 10 IU/mL, and its prevalence in healthy population was 11.6%.
O8 Change in pain pressure threshold reflects disease activity but does not correlate to inflammatory parameter in rheumatoid arthritis MS Arun, S Chandrashekara, KP Suresh ChanRe Rheumatology and Immunology Centre, Bangalore, India Introduction: Measuring pain in chronic painful disease is challenging. Currently, pain visual analogue scale (VAS) and tender joint counts are used to measure the pain, though the latter is more a measure of active joints rather than that of the pain measure. The VAS reflects the perception of pain and may not reflect the true change in the pain or its absolute component, since in VAS the scoring method adopted is to rank the pain experienced by the patient over a specified period comparing to his experience; this makes the scale relative and patient-specific. This feature of the scale makes it little vulnerable to variation when being used to compare in a group of patients. We hypothesised pain pressure threshold (PPT) being a measure, in terms of application of pressure we expected it to be a useful tool to measure the pain. We studied the change of PPT at different locations and points and its correlation to corset measures and disease activity score (DAS). Material methods: Twenty freshly diagnosed, female RA patients were recruited for the study after careful exclusion of fibromyalgia. The patients were assessed for Tender joint count (TJC), Swollen joint count (SJC), VAS pain scale and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in their three consecutive follow-ups of 6-week intervals. PPT was measured using digital algometer at three fibromyalgia tender point sites and three pairs of joint areas (MCPs, wrists and active joints). Average PPT-arithmetic mean of all areas was computed. Data were analysed using correlation coefficient and Deming regression. Results: Average PPT Visit 1
DAS ESR DAS CRP ESR CRP
Visit 2
Visit 3
r value
P value
r value
P value
r value
P value
−0.766 −0.755 −0.036 −0.192
0.000 0.005 0.881 0.550
−0.583 −0.592 −0.049 −0.229
0.007 0.042 0.838 0.475
−0.644 −0.820 −0.183 −0.611
0.002 0.002 0.441 0.035
Conclusions: PPT does change over a period of time and correlates significantly with DAS ESR and DAS CRP, TJC, SJC and VAS pain scale. It is not correlated with changes in inflammatory parameters ESR and CRP independently.
Connective Tissue Disorders O9 Clinical profile of primary Sjogrens syndrome with renal tubular acidosis P Sandhya1, Nihal Thomas2, Simon Rajaratnam2, Debashish Danda1 Department of Clinical Immunology and Rheumatology, 2Department of Endocrinology, Christian Medical College, Vellore, Tamilnadu, India
1
Introduction: Primary Sjogrens syndrome (pSS) is an under-recognised systemic autoimmune disease with protean manifestations. Although renal tubular acidosis (RTA) is a known complication, osteomalacia is reported only as isolated cases. We describe clinical, radiological and autoantibody profiles of our cohort of pSS with RTA. Methods: Electronic records were screened for patients with suspected pSS with RTA seen as inpatients or outpatients at the Christian Medical College, Vellore between 2003 and 2011. Demography, clinical and autoantibody profiles, minor salivary gland histology, electrolytes, blood gas profiles and imaging features were retrieved from case records. Apart from those fulfilling American-European Consensus (AEC) criteria for pSS, patients with three criteria, inclusive of positive SSA/SSB antibody or biopsy or both, were also included in this cohort. RTA was diagnosed by the presence of hyperchloraemic metabolic acidosis with urinary pH > 6.5. Results: Demography: Of the 25 females, 19 patients fulfilled AEC criteria and 6 patients fulfilled only three criteria (5 positive for both SSA and SSB antibody and 1 positive for histology). Incomplete RTA was found in 6 patients. Median age: 32 (18–60) years, median duration of symptoms at diagnosis: 36 (0.5–168) months. Commonest clinical presentation: Hypokalaemic paralysis −16 (64%). Serology: SSA—100%, SSB—85.71%, ANA—88% and RF—64.71%. Mean vitamin D value: 27.5 ± 15.8 ng/mL. Obstetrical outcome: Spontaneous abortion and intrauterine death/stillbirth, 3 each; primary infertility, 2; and neonatal lupus and neonatal death, 1 each. Renal complications: Chronic kidney disease, 2; nephrocalcinosis, 5; renal stone, 1 and proteinuria, 19 (76%). Renal biopsy: n = 7; mesangial proliferative nephritis and chronic interstitial nephritis, 3 each and arterial sclerosis, 1. Skeletal: Pseudofractures n = 7 (28%), healing in 2 cases after 1 year of potassium and bicarbonate supplementation and antimalarial treatment. Others: Vasculitis, 4; monoclonal gammopathy of uncertain significance, 3; lymphoma, 2; autoimmune hepatitis, autoimmune haemolytic anaemia and first-degree heart block, 1 each. Conclusion: Median delay in diagnosis of pSS is 36 months. Hypokalaemic paralysis (64%) and positive SSA/SSB antibody (100%) were the commonest clinical and laboratory features,
Indian Journal of Rheumatology 2011 November; Vol. 6, No. 3 (Suppl)
Methods: RA patients naïve to MTX/DMARDs and glucocorticoids were treated with a gradually escalating dose of MTX till a maximum of 25 mg/week or best-tolerated dose was reached at week 8. Expression and function of MDR-1 was carried out by flowcytometry at baseline and after 4 months of therapy. MDR-1 expression was measured by relative fluorescence intensities and percentage of positive cells and function by rhodamine efflux assay. Reduction in disease activity score 28 (DAS-28) of value ≥ 1.2 was defined as responder and of value < 1.2 as non-responder. Results: Among 52 patients (mean age 41.6 years, mean duration of RA 43.1 months) enrolled in the study, 11 were grouped as non-responders. Compared to baseline, the expression (P < 0.001) and function (P < 0.001) of the MDR-1 reduced significantly at 4th month in the responder group, whereas in the non-responders it either increased or remained unchanged. Compared to non-responders there was a significant decrease in expression (P < 0.02) and function (P < 0.005) of MDR-1 in responders at 4th month. Conclusion: Resistance to MTX may be due to persistent expression and function of MDR-1.
O6 Subclinical atherosclerosis and endothelial dysfunction in patients with early rheumatoid arthritis as evidenced by measurement of carotid intima-media thickness and flow mediated vasodilatation and their response to therapy with disease-modifying anti-rheumatic drugs* Maitrayee Chatterjee Adhikari, Aharna Guin, Pradyot Sinhamahapatra, Alakendu Ghosh Department of Rheumatology, Institute of Post-Graduate Medical Education and Research, SSKM Hospital, Kolkata Introduction: Patients with rheumatoid arthritis (RA) have an increased morbidity and mortality due to cardiovascular diseases (CVD). Atherosclerotic process in RA is thought to be accelerated by systemic chronic inflammation in addition to traditional CV risk factors. The present study examined the frequency of endothelial dysfunction and subclinical atherosclerosis in early RA patients by carotid intima-media thickness (cIMT) and endothelial-dependent flow-mediated vasodilatation (ED-FMD) as compared with healthy controls and followed them over 12 months while they were on disease-modifying anti-rheumatic drugs (DMARDs). Materials and patients: The study included 35 early RA patients (29 females, 6 males) who had disease duration of < 12 months and 35 healthy controls (28 females, 7 males). The consecutive patients were selected from among the patients visiting the ‘early arthritis clinic’ of Rheumatology Department at IPGME&R, SSKM Hospital, Kolkata. After one year, five patients were lost to follow-up. Methods: cIMT and ED-FMD were measured by high-resolution ultrasonography at baseline in patients and controls, and re-assessed after 12 months in patients, and the changes in the respective parameters were calculated. Data were analysed by paired and unpaired t-tests. Results: RA patients had an average disease duration of 0.46 ± 0.28 years. Mean cIMT and FMD% had significant differences in RA patients when compared with those in controls (P = 0.007 and P = 0.004, respectively). Both the parameters significantly improved after one year of treatment with DMARDs (P = 0.002 and P = 0.046, respectively). Conclusion: Early RA patients have altered cIMT and FMD% signifying both structural and functional abnormalities, but early control of the disease with DMARDs may reduce atherosclerotic progression.
O7 To determine the prevalence and clinically significant cut-off titre of anti-cyclic citrullinated peptide antibody in the diagnosis of early rheumatoid arthritis in Indian population Parasar Ghosh, Jana Debarshi, Dhar Sanjay, Ghosh Alakendu Department of Rheumatology and Clinical Immunology, Institute of Post-Graduate Medical Education and Research, Kolkata Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory symmetric polyarthritis affecting about 1% of the Indian population. The anti-cyclic citrullinated peptide (anti-CCP) antibody has come up as a useful marker for diagnosing RA early. The sensitivity and specificity of second-generation anti-CCP antibody is 64–89% and 88–99%, respectively. The objective was to find out the prevalence and the cut-off level of the second-generation anti-CCP antibody in our population which will distinguish RA patients from healthy controls best. Subjects and methods: We collected serum of 150 patients with early RA (disease duration < 2 years), of 100 patients with undifferentiated arthritis and of 250 healthy controls. The second-generation anti-CCP was measured by the enzyme-linked immunosorbent assay (ELISA) method. The cut-off of titre was determined by the receptor operator characteristics (ROC) curve analysis. Results: The anti-CCP antibody level was useful in differentiating patients with early RA from healthy controls and not from undifferentiated arthritis. The different cut-off levels of antiCCP antibody levels differentiating early RA patients from healthy controls were as follows: Anti-CCP level (IU/mL) 5.06 7.7 10.1 15
Sensitivity (%)
Specificity (%)
Positivity in RA patients (%)
Positivity in controls (%)
66 60 56 50
63.6 82.4 89.4 94
66 60 56 50
37.5 19.6 11.6 6.4
*Nominated for DRA young investigator awards.
Oral Presentations Area under curve: 0.703 (95% confidence interval, 0.643–0.764, P < 0.001). At the cut-off value of 10 IU/mL, the anti-CCP positivity was 11.6% in healthy controls and 56% in early RA patients. Conclusion: The cut-off level of anti-CCP antibody differentiating patients with early RA from that of healthy controls was 10 IU/mL, and its prevalence in healthy population was 11.6%.
O8 Change in pain pressure threshold reflects disease activity but does not correlate to inflammatory parameter in rheumatoid arthritis MS Arun, S Chandrashekara, KP Suresh ChanRe Rheumatology and Immunology Centre, Bangalore, India Introduction: Measuring pain in chronic painful disease is challenging. Currently, pain visual analogue scale (VAS) and tender joint counts are used to measure the pain, though the latter is more a measure of active joints rather than that of the pain measure. The VAS reflects the perception of pain and may not reflect the true change in the pain or its absolute component, since in VAS the scoring method adopted is to rank the pain experienced by the patient over a specified period comparing to his experience; this makes the scale relative and patient-specific. This feature of the scale makes it little vulnerable to variation when being used to compare in a group of patients. We hypothesised pain pressure threshold (PPT) being a measure, in terms of application of pressure we expected it to be a useful tool to measure the pain. We studied the change of PPT at different locations and points and its correlation to corset measures and disease activity score (DAS). Material methods: Twenty freshly diagnosed, female RA patients were recruited for the study after careful exclusion of fibromyalgia. The patients were assessed for Tender joint count (TJC), Swollen joint count (SJC), VAS pain scale and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in their three consecutive follow-ups of 6-week intervals. PPT was measured using digital algometer at three fibromyalgia tender point sites and three pairs of joint areas (MCPs, wrists and active joints). Average PPT-arithmetic mean of all areas was computed. Data were analysed using correlation coefficient and Deming regression. Results: Average PPT Visit 1
DAS ESR DAS CRP ESR CRP
Visit 2
Visit 3
r value
P value
r value
P value
r value
P value
−0.766 −0.755 −0.036 −0.192
0.000 0.005 0.881 0.550
−0.583 −0.592 −0.049 −0.229
0.007 0.042 0.838 0.475
−0.644 −0.820 −0.183 −0.611
0.002 0.002 0.441 0.035
Conclusions: PPT does change over a period of time and correlates significantly with DAS ESR and DAS CRP, TJC, SJC and VAS pain scale. It is not correlated with changes in inflammatory parameters ESR and CRP independently.
Connective Tissue Disorders O9 Clinical profile of primary Sjogrens syndrome with renal tubular acidosis P Sandhya1, Nihal Thomas2, Simon Rajaratnam2, Debashish Danda1 Department of Clinical Immunology and Rheumatology, 2Department of Endocrinology, Christian Medical College, Vellore, Tamilnadu, India
1
Introduction: Primary Sjogrens syndrome (pSS) is an under-recognised systemic autoimmune disease with protean manifestations. Although renal tubular acidosis (RTA) is a known complication, osteomalacia is reported only as isolated cases. We describe clinical, radiological and autoantibody profiles of our cohort of pSS with RTA. Methods: Electronic records were screened for patients with suspected pSS with RTA seen as inpatients or outpatients at the Christian Medical College, Vellore between 2003 and 2011. Demography, clinical and autoantibody profiles, minor salivary gland histology, electrolytes, blood gas profiles and imaging features were retrieved from case records. Apart from those fulfilling American-European Consensus (AEC) criteria for pSS, patients with three criteria, inclusive of positive SSA/SSB antibody or biopsy or both, were also included in this cohort. RTA was diagnosed by the presence of hyperchloraemic metabolic acidosis with urinary pH > 6.5. Results: Demography: Of the 25 females, 19 patients fulfilled AEC criteria and 6 patients fulfilled only three criteria (5 positive for both SSA and SSB antibody and 1 positive for histology). Incomplete RTA was found in 6 patients. Median age: 32 (18–60) years, median duration of symptoms at diagnosis: 36 (0.5–168) months. Commonest clinical presentation: Hypokalaemic paralysis −16 (64%). Serology: SSA—100%, SSB—85.71%, ANA—88% and RF—64.71%. Mean vitamin D value: 27.5 ± 15.8 ng/mL. Obstetrical outcome: Spontaneous abortion and intrauterine death/stillbirth, 3 each; primary infertility, 2; and neonatal lupus and neonatal death, 1 each. Renal complications: Chronic kidney disease, 2; nephrocalcinosis, 5; renal stone, 1 and proteinuria, 19 (76%). Renal biopsy: n = 7; mesangial proliferative nephritis and chronic interstitial nephritis, 3 each and arterial sclerosis, 1. Skeletal: Pseudofractures n = 7 (28%), healing in 2 cases after 1 year of potassium and bicarbonate supplementation and antimalarial treatment. Others: Vasculitis, 4; monoclonal gammopathy of uncertain significance, 3; lymphoma, 2; autoimmune hepatitis, autoimmune haemolytic anaemia and first-degree heart block, 1 each. Conclusion: Median delay in diagnosis of pSS is 36 months. Hypokalaemic paralysis (64%) and positive SSA/SSB antibody (100%) were the commonest clinical and laboratory features,