Kyung-Bin Joo

Angiotensin-converting enzyme gene polymorphism and vascular manifestations in Korean patients with SLE.

Systemic lupus erythematosus (SLE) is an inflammatory multisystem disease of unknown etiology with immunologic aberrations.Many studies have shown that genetic and environmental factors are implicated in the development of SLE. Angiotensin-converting enzyme (ACE) affects various immune phenomena through the renin–angiotensin and kallikrein–kininogen systems by creating angiotensin II and inactivating bradykinin. We investigated the correlation between insertion= deletion polymorphism of the ACE gene and the clinical manifestations of SLE, especially vascular involvement and lupus nephritis. Two-hundred and eleven Korean patients fulfilling the ACR criteria and 114 healthy subjects were enrolled. The ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood. The nephritis patients were classified by the WHO classification. In addition, the activity and chronicity index were used to assess the severity of renal involvement.We evaluated vascular involvement by the presence or absence of hypertension, Raynauds phenomenon, livedo reticularis, antineutrophil cytoplasmic antibody and the SLICC/ACR Damage Index. The gene frequency of ACE gene polymorphism was as follows: II 39 vs 34%, ID 41 vs 50%, DD 20 vs 16% in SLE patients and controls, respectively. There was no difference in genotype frequency between both groups. There were no significant differences between the distribution of ACE gene genotypes and lupus nephritis and its related parameters, including WHO classification, activity index, chronicity index, renal dysfunction and amount of 24 h urinary protein. The ACE genotypes and alleles did not affect the presence of vascular manifestations evaluated, but the frequency of DD genotype was significantly low in SLE patients with Raynauds phenomenon compared to those without Raynauds phenomenon (P=0.002 for ACE ID vs DD and II, OR 2.7, 95% CI 1.43–5.09; P=0.023 for ACE DD vs ID and II, OR 0.33, 95% CI 0.12–0.89). Also skewing from DD to II genotype was noted in patients with anti-Sm antibody compared to those without anti-Sm antibody (P=0.025 for ACE DD vs ID and II, OR 0.21, 95% CI 0.05–0.93). The onset age of serositis was older in patients with the ID genotype than the others (ID=34.5§ 10.8, II ‡ DD=25.6§ 10.2, P=0.002). Also the onset age of malar rash was older in patients with II genotype than the others (II=26.7§ 8.4, ID ‡ DD=21.3§ 9.0; P=0.021). The patients with I allele showed a significantly higher frequency of serositis (P=0.022). Taken together, the I/D polymorphisms of ACE gene did not affect susceptibility of SLE, lupus nephritis and the vascular manifestations, including Raynauds phenomenon, in Korean SLE patients, although the DD genotype was negatively associated with Raynauds phenomenon among SLE patients. However, it would be valuable to evaluate the role of other genes potentially related to vascular events, such as endothelin, nitric oxide or angiotensin II receptor as well as ACE gene.

Prevalence of ossification of the posterior longitudinal ligament of the cervical spine

OBJECTIVES To determine the prevalence of ossification of the posterior longitudinal ligament (OPLL) in cervical spines in Koreans. METHODS We reviewed the reports of the radiologic examination of cervical spines from January 2002 to September 2005 in Hanyang University Hospital, Seoul, Korea. OPLL was indicated by the presence of heterotopic ossification in the posterior longitudinal ligament on lateral cervical radiograph. RESULTS Among 11,774 adults aged 16 years or more, 71 cases of OPLL were found (0.60%). The male to female ratio was 42:29 (1.45:1). The highest prevalence was in patients aged 50-59 years. In terms of the types of OPLL, the continuous type was noted in 32.0% of the patients, the segmental type in 31.0%, the mixed type in 31.0%, and the localized type in 5.6%. C4, C5, and C3 were most commonly involved, in that order of frequency. Diffuse idiopathic skeletal hyperostosis, which is another common hyperostotic disorder, was also found in eight male patients. CONCLUSIONS The prevalence of cervical OPLL in Koreans was 0.60%, which was lower than that of Japanese and some previous western reports.

Radiologic Changes of Cervical Spine in Ankylosing Spondylitis

Abstract Ankylosing spondylitis (AS) is characterised by its effects on the axial skeleton. The cervical spine is also vulnerable to the disease process. Our aim was to determine the frequency of radiologic changes to the cervical spine and their correlation with clinical variables. We also used the Bath Ankylosing Spondylitis Radiology Index (BASRI) system, which is one of the reliable scoring systems of radiography, to score the global radiologic changes to the cervical and lumbar spine and the hip joints in our AS cohort. There were 181 patients with anteroposterior and lateral full-flexion views on radiography of the cervical spine here included in the study. A radiologist examined the radiologic changes to all anatomical compartments of the cervical spine in detail and graded them according to the BASRI system. We used the clinical and demographic data of our AS cohort to determine their relation to the radiographic changes. Eighty-eight patients (48.6%) showed radiological changes to the cervical spine; to the discovertebral joint 35.9%; the apophyseal joint 26.0%; atlantoaxial articulation 22.1% (atlantoaxial subluxation 13.8%); the costovertebral joint 18.2%; and to the posterior ligamentous attachment 11.6%. Using the BASRI system, 73 patients (40.3%) showed radiologic changes to the cervical spine and were graded as score 1 (1.7%), 2 (22.7%), 3 (6.6%) or 4 (9.4%). Among those graded as normal by the BASRI system, 17 showed some changes to the cervical spine, such as atlantoaxial joint subluxation or narrowing, and severe osteoporosis with no other radiographic changes. Current age, disease duration, inflammatory back pain and cervical symptoms were associated with the radiographic changes to the cervical spine. The BASRI-cervical spine score correlated with the BASRI-lumbar spine and hip joint score, sacroiliitis, disease duration, and duration of inflammatory back pain and cervical symptoms. Our data suggest that radiographic changes to the cervical spine are frequent in AS, and can be predicted in the patients with old age, long duration of disease and inflammatory back pain, and cervical symptoms. Also, the BASRI scoring system showed similar results as a detailed assessment of the cervical spine in our study.

Camptodactyly, Arthropathy, Coxa vara, Pericarditis (CACP)Syndrome: A Case Report

The camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) is characterized by congenital or early-onset camptodactyly, childhood-onset noninflammatory arthropathy associated with synovial hyperplasia. Some patients have pro-gressive coxa vara deformity and/or noninflammatory pericardial effusion. CACP is inherited as an autosomal recessive mode and the disease gene is assigned to a 1.9-cM interval on human chromosome 1q25-31. We describe a 10-yr-old boy who has typical features of CACP without familial association.

FRI0235 Comparison on Radiographic Progression for 5 Years Between Juvenile Onset Ankylosing Spondylitis and Adult Onset Ankylosing Spondylitis: Observation Study of Korean Spondyloarthropathy Registry (OSKAR) Data

Background The most unique feature in ankylosing spondylitis (AS) is subchondral eburnation and syndesmophytes, possibly leading to ankylosis and spinal fusion. So far a few comparisons of spinal bone formation between adult onset AS (AoAS) and Juvenile onset AS (JoAS) have been done. However, prospective studies of this comparison have not been accomplished. Objectives The aim of this study was to evaluate difference of radiographic progression over 5 years between JoAS and AoAS. Methods A total of 533 patients (115 patients with JoAS, 418 patients with AoAS) from the Observation Study of Korean spondyloArthropathy Registry (OSKAR) cohort were enrolled. We used a two-step approach to compare the radiographic progression between the JoAS and the AoAS. First, all OSKAR data were analyzed in relation to the onset of disease on cross-sectional survey. Second, we analyzed the radiographic spinal progression between groups over 5 years. The modified Stoke AS Spinal Score (mSASSS) were examined by two experienced radiologists to validate the results. The collection of the clinical parameters was conducted to investigate the associations between clinical factors and the radiographic progression. Univariable and multivariable regression analyses were done after adjusting for potential confounding factors, such as age, gender, disease duration, history of peripheral arthritis, baseline CRP level, baseline mSASSS, and NSAID intakes). Results The agreement between the two readers regarding mSASSS was very good: ICC coefficient 0.75 (95% CI 0.61-0.82) and 0.71 (95% CI 0.58-0.82) at each time. On cross-sectional survey, in spite of adjusting for multiple comparisons by Bonferroni correction, the patients with JoAS had fewer mSASSS unit than those with AoAS (14.12±1.30 vs 18.58±0.85, p=0.005). In analysis over 5 years, the mean progression of mSASSS in patients with JoAS was 0.21±1.29 units, while that of mSASSS in patients with AoAS was 4.00±0.59 units (p=0.012). Conclusions The patients with JoAS had slower radiographic spinal damage progression over 5 years than those with AoAS. Disclosure of Interest None declared

SAT0251 Is There Clinical Association Between Radiologic Progression of Spine and Radiologic Changes of Foot in Ankylosing Spondylitis

Background Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the axial skeleton, the enthesis and peripheral joints. The most prominent and common enthesitis occur in the lower extremities, especially the foot at the insertion of Achilles tendon. Peripheral arthritis is uncommon in AS, but it usually occurs in the lower extremities presenting asymmetric oligoarthritis, too. Some suggested that when peripheral arthritis develop early in the disease course it can be a predictor of more aggressive disease and enthesitis may be associated with high disease activity. Objectives The aim of this study was to investigate the association between radiologic changes of foot and radiologic progression of spine. Methods We enrolled two-hundred patients with AS who had both feet and whole spine x-ray in similar periods at one tertiary center of rheumatology from 2005 to 2014. We collected demographic findings including sex, age and disease durations. The foot x-ray was reviewed about presence of radiologic changes such as joint space narrowing (JSN) and erosion in ten metatarsophalangeal (MTP) joints and Achilles tendinopathy such as calcaneal spur, retrocalcaneal bursitis and soft tissue thickening by orthopedic surgeon. The radiologic damage of spine was scored by modified Stokes Ankylosing Spondylitis Spinal Score (mSASSS) by two radiologists. And the annual progression rate was calculated by difference of mSASSS divided by x-ray intervals. Results There were 149 males (73.8%) and 51 females (25.2%). Their mean age and disease duration were 38.5±12.8 years old and 45.9±59.4 months. The 26.5% of patients showed the radiologic changes of MTP joints, and 25.5% of patients had Achilles tendinopathy. There was significant difference between mSASSS in AS patients with radiologic changes of foot (8.2±6.9) and without (10.6±10.9) changes (P=0.036). The mSASSS was significantly increased in patients with Achilles tendinopathy (13.2±14.1) compared to without Achilles tendinopathy (8.8±8.0) (P=0.007). However, there was no significant difference of annual progression rate of mSASSS according to presence of radiologic damages at MTP joints and Achilles tendinopathy, respectively. The risk of radiologic changes of foot in patients without Achilles tendinopathy was more increased than patients with Achilles tendinopathy [OR=2.268 (1.146-4.487), P=0.026]. Conclusions The mSASSS was increased in patients with Achilles tendinopathy, and without radiologic damage of MTP joints, respectively. However, each findings did not associate with annual progression rate of mSASSS. Therefore, the radiologic changes of foot did not show the associations with radiologic progression of spine in this study. Disclosure of Interest None declared

SAT0368 Tumor Necrosis Factor Inhibitor Has NO Influence on Radiographic Damage in Ankylosing Spondylitis: Observation Study of Korean Spondyloarthropathy Registry (OSKAR) Data

Objectives To evaluate the influence of tumor necrosis factor (TNF) blocker on the radiographic damage in ankylosing spondylitis (AS) Methods A total of 598 TNF blocker naïve AS patients from the Observation Study of Korean spondyloArthropathy Registry (OSKAR) data were recruited for this study. The subjects were stratified in relation to the using state of TNF blocker. We evaluated collected clinical and radiographic parameters at two different time points. Then we compared radiographic progression between groups. To use the mSASSS, cervical and lumbar spinal radiographs were examined. Patients with a rate of AS progression that was >2 mSASSS unit were considered progressors. Univariable and multivariable regression analyses were done after adjusting for potential confounding factors, such as age, gender, disease duration, history of eye involvement, history of peripheral arthritis, juvenile onset AS, baseline CRP level, baseline mSASSS, and NSAID intakes). Results The mean age (SD) of the AS patients was 38.1 (9.2) years, and the mean disease duration (SD) was 9.8 (7.2) years at baseline. In this data, 88.5% of the patients were male, and 96.9% were HLA–B27 positive. 39.8% of the patients had history of peripheral arthritis. Of these patients, 45.3% (271 patients) had received TNF blockers. The mean mSASSS unit (SEM) at baseline was not significantly different between groups (TNF blocker naïve 16.40±0.88 vs TNF blocker user 19.16±1.12, P=0.054). Radiographic follow-up duration from the first mSASSS assessment were comparable (5.48±0.08 vs 5.57±0.08, P=0.447). However, Patients treated with TNF blockers had a higher CRP level (2.52±0.19 vs 1.59±0.10, p<0.01) and longer disease duration (11.70±0.45 vs 8.40±0.37, p<0.01) at baseline. On simple analysis, the TNF blocker naïve patients had less radiographic progression than those with TNF blocker (2.21±0.54 vs 4.48±0.80, p=0.020). After adjustment for multiple comparisons by the Bonferroni correction, gender, history of peripheral arthritis, disease duration, baseline mSASSS, and NSAID intake had statistically significance in our registry. However, the radiographic progression between groups was no significant difference (OR 0.87, [95% CI 0.42-1.81], P=0.71). Furthermore, we stratified groups according to the proportion of disease duration exposed to TNF inhibitor (0%, <25%, 25-50%, ≥50). On simple analysis, there was a significant difference in the rate of progression in patients who continued the medication for ≥50% of their disease duration as compared to the naive patients (7.53±1.41 vs 2.21±0.54, p=0.028). However, there was no difference of radiographic progression between groups (7.61±1.99 vs 2.83±0.79, p=0.18). Conclusions Treatment with TNF inhibitors has no influence on radiographic progression in AS. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3446

FRI0131 Analysis of Magnetic Resonance Imaging Scoring System for Facet Joint in Ankylosing Spondylitis

Objectives The aim of this study is to identify radiographic damages at affected facet joint of the spine and also to compare radiographic inflammatory activity between facet joints and spinal disco-vertebral units (DVUs) in ankylosing spondylitis (AS). Methods The whole spine magnetic resonance imaging (MRI) from total 46 AS patients (male =38, 82.6%) were reviewed. Three different methods including the Ankylosing Spondylitis spine MRI-activity (ASspiMRI-a), the Berlin modification of the ASspiMRI-a, and the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system for spinal inflammation were evaluated. Facet joint scoring system identified bone marrow edema, erosion, and ankylosis at the same level of each 23 DVU, which were scored between 0 to 3 points for both sides at each lesion. Total facet joint score means sum of scores of edema, erosion, and ankylosis at each level. Results Total 131 facet joint lesions, consisting of 98 for bone edema, 18 of bone erosion, and 15 of bony ankylosis, were identified. Most frequent facet joint lesions were detected at levels of C7-T1 (8.4%), T1-T2 (9.9%), L2-L3 (9.2%), and L3-L4 (9.9%) among total 131 facet joint lesions, whereas spinal inflammatory lesions were frequently identified at mid-thoracic spine level especially at T3 to T8. Total facet joint scores were closely correlated with ASspiMRI-a, Berlin, and SPARCC scores (r =0.372, p=0.011; r =0.414, p=0.004; r =0.400, p=0.006, respectively). However, the number of affected spinal joint at each DVU was not associated with that of facet joint lesions, indicating little possibility for concurrence of spinal DUVs and facet joint lesions. Conclusions This study implicates that inflammatory disease activity at facet joint was associated with that at DUVs of spine in AS. Discordance between DUVs and facet joint for concurrence of inflammation was observed. Close attention for facet joint involvement in AS should be needed. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3418

SAT0252 HLA-B27 Homozygosity has No Influence on Radiographic Damage in Ankylosing Spondylitis: Observation Study of Korean Spondyloarthropathy Registry (OSKAR) Data

Background There is no consensus as to whether HLA-B27 homozygosity influences the clinical features of ankylosing spondylitis (AS). We already reported that HLA-B27 homozygosity has no influence on clinical and functional disability in AS. However, we did not assess spinal bony progression at that time, further radiographic study was needed to evaluate the influence of HLA-B27 on bony ankylosis. Objectives To evaluate the influence of homozygosity for HLA-B27 on the radiographic damage in AS Methods A total of 368 AS patients with positive HLA-B27 status from the Observation Study of Korean spondyloArthropathy Registry (OSKAR) cohort were recruited for this study. HLA-B27 positive patients out of all AS patients were assessed for whether they had homozygosity or heterozygosity for HLA-B27. First, all data were stratified in relation to the carrier state of positive HLA-B27 for cross-sectional survey. Then we compared the radiographic damage score between groups. Second, we evaluated collected clinical and radiographic parameters at two different time points. Then we compared radiographic progression between groups. To use the mSASSS, cervical and lumbar spinal radiographs were examined by two experienced bone and joint radiologists (S. Lee, K.B. Joo). Results The agreement between the two readers regarding mSASSS was very good: ICC coefficient 0.70 (95% CI 0.60–0.81). The mean age (SD) of the AS patients was 37.0 (9.2) years, and the mean disease duration (SD) was 15.6 (9.1) years. Of these patients, 34.5% (127 patients) had HLA-B27 homozygosity. The mean mSASSS unit (SEM) was not significantly different between groups (homozygosity 28.57±4.12 vs heterozygosity 23.34±3.44, P = 0.344) on cross-sectional survey. When it comes to radiographic progression between groups over 5 years, there was no significant difference in spite of adjusting for confounding variable (homozygosity 4.98±0.98 vs heterozygosity 4.21±0.82, P = 0.562). Conclusions The carrier state of positive HLA-B27 plays no role in determining the radiographic progression in AS. Disclosure of Interest None Declared