P. Atagunduz

Agreement Between Quantiferon-TB Gold Test and Tuberculin Skin Test in the Identification of Latent Tuberculosis Infection in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

Objective. To compare the Quantiferon-TB Gold test (QTF-G) with the tuberculin skin test (TST) for the detection of latent tuberculosis infection (LTBI) among patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), with reevaluation of the patients treated with tumor necrosis factor-α (TNF-α) antagonists in the followup. Methods. The study involved 140 consecutive patients, 82 with RA and 58 with AS. Thirty patients were evaluated with QTF-G for detection of LTBI before and after 6 months of TNF-α antagonist treatment. QTF-G was also performed on 49 healthy controls. QTF-G results were recorded as positive, negative, or indeterminate. A positive TST was defined as ≥ 5 mm for RA and AS. Results. The percentages of positive QTF-G were comparable in RA and AS (37% vs 32%). The rate of positive QTF-G in healthy controls (29%) was also similar to RA and AS. In contrast to QTF-G results, a high rate of TST positivity was observed in AS compared to RA (82% vs 55%; p = 0.02). The total agreement between QTF-G and TST was observed to be 61% (κ = 0.29) in the whole group, 70% (κ = 0.42) in RA, and 49% (κ = 0.14) in AS. After 6 months of treatment with TNF-α antagonists, a high rate of QTF-G change was observed in patients with indeterminate results (23% vs 3%; p = 0.03). Conclusion. The comparable prevalence of LTBI among the study groups according to QTF-G supports the view that QTF-G is less susceptible to external factors than TST. Sequential testing for QTF-G in patients with indeterminate or negative results may also be helpful in discriminating LTBI better.

Determinants of Early Radiographic Progression in Ankylosing Spondylitis

Objective. To investigate the demographic and clinical characteristics associated with early, extensive radiographic changes in ankylosing spondylitis (AS). Methods. Radiographic severity was assessed cross-sectionally in 235 patients with AS using the Bath AS Radiological Index spine score (BASRI-s). Patients with extensive radiographic changes on the lumbar portion of BASRI-s were defined as the early axial ankylosis (EAA) Group. ANCOVA and logistic regression analyses were used to identify factors affecting EAA. Results. Most study patients were men (139/235, 59.0%). Mean disease duration was 12.4 ± 9.3 years. Fifteen percent of women and 34.8% of men with AS were in the EAA group. HLA-B27-positive men with AS had significantly higher BASRI-lumbar scores, while HLA-B27 had no effect on radiographic progression of axial disease in women with AS. Peripheral joint involvement was associated with slow radiographic progression. Hip involvement had no effect on axial progression but uveitis was more frequent in the male EAA group. The odds for an HLA-B27-positive male patient with AS who did not have peripheral arthritis of having a BASRI-lumbar score of 3 or higher were 3.4 (77% chance to have axially progressive disease). Presence of uveitis increased these odds to 93%. Only 15% of female patients with AS had EAA, and the absence of peripheral arthritis was the only clinical measure associated with EAA in this group. Conclusion. EAA was more frequent in men with AS than in women. Absence of peripheral arthritis, HLA-B27 positivity, and uveitis were associated with multiple syndesmophytes or fusion of multiple vertebrae of the lumbar vertebrae.

Validation of ultrasound imaging for Achilles entheseal fibrocartilage in bovines and description of changes in humans with spondyloarthritis

Background Entheseal fibrocartilage (EF) derangement is hypothesised to be pivotal to the pathogenesis of spondyloarthritis. Ultrasound is useful for visualisation of the enthesis but its role in EF visualisation is uncertain. This work aimed to demonstrate face and content validity of ultrasound for EF visualisation both by bovine histological evaluation and EF imaging in spondyloarthritis. Methods Achilles enthesis of 18 bovine hindfeet was visualised using a MyLab 70 ultrasound machine. The presence of tissue with EF characteristics was documented and histological confirmation was performed on five randomly selected sections using Masson trichrome staining. Ultrasound of the Achilles tendon (AT) was performed in 19 patients with spondyloarthritis and 21 healthy controls (HC). Results The bovine EF could be visualised in all cases and seen as a thin, uncompressible, well-defined, anechoic layer between the hyperechoic bone and the hyperechoic fibrils of the enthesis both in longitudinal and transverse scans. This region corresponded to EF on histological examination. The same pattern of low signal corresponding to EF location was seen in 17/19 patients and all HC. Discontinuities of the anechoic layer around the erosions and enthesophytes were observed in the spondyloarthritis group. The thickness of the anechoic layer was not significantly different in spondyloarthritis and HC (0.5±0.1 vs 0.5±0.2 mm, p=0.9) whereas the thickness of the EF was greater in men (0.6±0.2 vs 0.5±0.1 mm; p=0.009) compared with women. Conclusion Ultrasound can visualise EF of the AT insertion, which can be abnormal in cases of spondyloarthritis. This has implications for a better understanding of enthesopathy.

Conventional DMARD therapy (methotrexate-sulphasalazine) may decrease the requirement of biologics in routine practice of ankylosing spondylitis patients: a real-life experience.

The effect of disease‐modifying antirheumatic drugs (DMARDs) in ankylosing spondylitis (AS) is still controversial. We aimed to evaluate the efficacy of sulphasalazine (SSZ) mono‐ or combination therapy with methotrexate (MTX) in AS patients naive to anti‐tumor necrosis factor alpha (TNFα) agents.

Assessment of the New 2012 EULAR/ACR Clinical Classification Criteria for Polymyalgia Rheumatica: A Prospective Multicenter Study

Objective. To assess the performance of the new 2012 provisional European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) polymyalgia rheumatica (PMR) clinical classification criteria in discriminating PMR from other mimicking conditions compared with the previous 5 diagnostic criteria in a multicenter prospective study. Methods. Patients older than 50 years, presenting with new-onset bilateral shoulder pain with elevated acute-phase reactants (APR), were assessed for the fulfillment of the new and old classification/diagnostic criteria sets for PMR. At the end of the 1-year followup, 133 patients were diagnosed with PMR (expert opinion) and 142 with non-PMR conditions [69 rheumatoid arthritis (RA)]. Discriminating capacity, sensitivity, and specificity of the criteria sets were estimated. Results. Discriminating capacity of the new clinical criteria for PMR from non-PMR conditions and RA as estimated by area under the curve (AUC) were good with AUC of 0.736 and 0.781, respectively. The new criteria had a sensitivity of 89.5% and a specificity of 57.7% when tested against all non-PMR cases. When tested against all RA, seropositive RA, seronegative RA, and non-RA control patients, specificity changed to 66.7%, 100%, 20.7%, and 49.3%, respectively. Except for the Bird criteria, the 4 previous criteria had lower sensitivity and higher specificity (ranging from 83%–93%) compared with the new clinical criteria in discriminating PMR from all other controls. Conclusion. The new 2012 EULAR/ACR clinical classification criteria for PMR is highly sensitive; however, its ability to discriminate PMR from other inflammatory/noninflammatory shoulder conditions, especially from seronegative RA, is not adequate. Imaging and other modifications such as cutoff values for APR might increase the specificity of the criteria.

The 2013 ACC/AHA 10-year atherosclerotic cardiovascular disease risk index is better than SCORE and QRisk II in rheumatoid arthritis: is it enough?

OBJECTIVE To determine the ability of the new American College of Cardiology and American Heart Association (ACC/AHA) 10-year atherosclerotic cardiovascular disease (ASCVD) risk algorithm in detecting high cardiovascular (CV) risk, RA patients identified by carotid ultrasonography (US) were compared with Systematic Coronary Risk Evaluation (SCORE) and QRisk II algorithms. METHODS SCORE, QRisk II, 2013 ACC/AHA 10-year ASCVD risk and EULAR recommended modified versions were calculated in 216 RA patients. In sonographic evaluation, carotid intima-media thickness >0.90 mm and/or carotid plaques were used as the gold standard test for subclinical atherosclerosis and high CV risk (US+). RESULTS Eleven (5.1%), 15 (6.9%) and 44 (20.4%) patients were defined as having high CV risk according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. Fifty-two (24.1%) patients were US + and of those, 8 (15.4%), 7 (13.5%) and 23 (44.2%) patients were classified as high CV risk according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. The ACC/AHA 10-year ASCVD risk index better identified US + patients than SCORE and QRisk II (P < 0.0001). With EULAR modification, reclassification from moderate to high risk occurred only in two, five and seven patients according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. CONCLUSION The 2013 ACC/AHA 10-year ASCVD risk estimator was better than the SCORE and QRisk II indices in RA, but still failed to identify 55% of high risk patients. Furthermore adjustment of threshold and EULAR modification did not work well.

Subclinical Atherosclerosis in Systemic Sclerosis: Not Less Frequent Than Rheumatoid Arthritis and Not Detected With Cardiovascular Risk Indices.

To determine the frequency of subclinical atherosclerosis in patients with systemic sclerosis (SSc; scleroderma) compared to healthy subjects (HS) and rheumatoid arthritis (RA) patients and to determine the ability of cardiovascular (CV) risk indices in detecting SSc patients with subclinical atherosclerosis.

A rare case of spontaneous, bilateral Achilles tendon rupture in systemic lupus erythematosus and a review of the literature.

Sir – A 30-year-old woman, diagnosed with SLE at the age of 13 with class II lupus nephritis, presented with acute pain on both heels. She was treated with cyclophosphamide (Cyc) and methyl-prednisolone (MP) for 6 months initially, and cyclosporine-A, azathioprine and chloroquine was prescribed thereafter. A mild increase in the dose of steroids was necessary for acute pericarditis at the age of 21. After a renal flare despite intensive therapy, rebiopsy confirmed class IV lupus nephritis. After 6 months of IV Cyc and steroid treatment, she was lost to follow-up. She was under 2 mg/day of MP when she presented with her second flare of class IV lupus nephritis after 7 years. Monthly IV Cyc was started and p.o. MP (1 mg/kg) was tapered down to 32 mg/day within 3 months. She later developed iatrogenic Cushing’s syndrome and cataract. On her last visit, she described intensive right heel pain of acute spontaneous onset with the duration of 3 weeks. Although pain on walking eventually ceased, loss of plantar flexion remained. Three weeks later spontaneous left heel pain was added, she was unable to walk and had loss of plantar flexion on both feet. There was a palpable gap in both Achilles tendons near their insertion to the calcaneus. Her clinical and laboratory findings ruled out a lupus flare. Ultrasonographic evaluation of the left Achilles tendon is shown in Figure 1. The patient underwent open surgery for tendon repair on both sides.

Association of , and Polymorphisms with Radiographic Severity of Ankylosing Spondylitis

Background: Radiographic severity of ankylosing spondylitis (AS) shows such great variance that some patients never develop syndesmophytes throughout the entire disease span, whereas some develop bamboo spine relatively early. Objective: To study the association between ERAP1, IL23R and PTGER4 single nucleotide polymorphisms (SNPs) and radiographic severity in AS patients. Methods: rs27044 and rs30187 (ERAP1), rs11209032 (IL23R) and rs10440635 (PTGER4) SNPs were genotyped in 235 AS patients fulfilling the modified New York criteria. Patients were classified as mild- and severe-AS according to modified Stoke AS spinal score (mSASSS). Mild-AS is defined as having mSASSS of “0” following at least 10 years of disease duration. Severe-AS is defined as having mSASSS of >20 (patients with mild vertebral changes (i.e. squaring or erosions) were omitted for clear stratification) regardless of disease duration. Results: The genotype distributions and allele frequencies of ERAP1 rs27044 and rs30187, IL23R rs11209032 and PTGER4 rs10440635 SNPs were similar in mild- (n=171, mSASSS=0, 55.6% HLA-B27 positive) and severe-AS patients (n=64, mSASSS=48.5±17.8, 73.4% HLA-B27 positive). After adjustment for clinical differences between groups (gender, disease duration, HLA-B27 and smoking status) by logistic regression analysis, none of the alleles in the investigated SNPs were found to be associated with radiographic severity of AS. Conclusion: In radiographically well-categorized AS patients, ERAP1 rs27044 and rs30187, IL23R rs11209032 and PTGER4 rs10440635 SNPs are not found to be associated with radiographic severity of AS.

Limited reliability of radiographic assessment of spinal progression in ankylosing spondylitis

Objectives Conventional radiography is key to assessing AS-related spinal involvement and has become increasingly important given that spinal fusion may continue under biologic therapy. We aimed to compare the reliability of radiographic scoring of the spine by using different approaches to understand how different readers agree on overall scores and on individual findings. Method Six investigators scored 68 plain radiographs of the cervical and lumbar spine of 34 patients with a 2-year interval, for erosions, sclerosis, squaring, syndesmophytes and ankyloses using the Spondyloarthritis Radiography (SPAR) module. The intraclass correlation coefficients were calculated compared with two gold standards. The reproducibility of each finding in 1632 vertebral corners and new syndesmophytes in each corner was calculated by kappa analysis and positive agreement rates. Results The intraclass correlation coefficients mostly revealed good to excellent agreement with the gold standards (0.69-0.95). The kappa analysis showed worse agreement, being relatively higher for syndesmophytes (0.163-0.559) and ankylosis (0.48-0.95). Positive agreement rates showed that erosions were never detected at the same vertebral corner by two readers (positive agreement rate: 0%). The mean (range) positive agreement rates were 10.1% (0-27.7%) for sclerosis and 19.2% (0-59.7%) for squaring, and were higher for syndesmophytes [38.8% (21.4-62.5%)] and ankylosis [77.3% (64-95.3%)]. Conclusion Our results show that there is a poor agreement on the presence of grade 1 lesions included in the Modified Stoke Ankylosing Spondylitis Spine Score-mostly for erosions and sclerosis-which may increase the measurement error. The currently used definitions of reliability have a risk of overestimating reproducibility.