Salih Ozgocmen

The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection

Objective: To validate and refine two sets of candidate criteria for the classification/diagnosis of axial spondyloarthritis (SpA). Methods: All Assessment of SpondyloArthritis international Society (ASAS) members were invited to include consecutively new patients with chronic (⩾3 months) back pain of unknown origin that began before 45 years of age. The candidate criteria were first tested in the entire cohort of 649 patients from 25 centres, and then refined in a random selection of 40% of cases and thereafter validated in the remaining 60%. Results: Upon diagnostic work-up, axial SpA was diagnosed in 60.2% of the cohort. Of these, 70% did not fulfil modified New York criteria and, therefore, were classified as having “non-radiographic” axial SpA. Refinement of the candidate criteria resulted in new ASAS classification criteria that are defined as: the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature (“imaging arm”) or the presence of HLA-B27 plus at least two SpA features (“clinical arm”). The sensitivity and specificity of the entire set of the new criteria were 82.9% and 84.4%, and for the imaging arm alone 66.2% and 97.3%, respectively. The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI (sensitivity 85.1%, specificity 65.1%) and slightly better than that of the modified Amor criteria (sensitivity 82.9, specificity 77.5%). Conclusion: The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain. Trial registration number: NCT00328068.

2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis

To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6–8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.

Vitamin D deficiency and reduced bone mineral density in multiple sclerosis: effect of ambulatory status and functional capacity

Multiple sclerosis (MS) is a chronic disease and a major cause of disability in young adults. The aims of this study were to assess bone mass in patients with MS in comparison to healthy age- and sex-matched controls, and to evaluate factors influencing bone mineral density (BMD), and the relationship of the pain threshold at peripheral and axial sites with BMD in MS. Thirty-one patients with MS and 30 matched healthy controls participated in the study. The Kurtzke expanded disability status scale (EDSS) and the functional independence measure (FIM) were used to scale disability, mobility, and functional status. Serum 25(OH) vitamin D levels were measured. BMD was measured using dual X-ray absorptiometry (DXA). MS patients had significantly lower BMD at the lumbar spine (L2-L4) and femur trochanter compared to the matched controls. BMD of the lumbar spine was nearly 1 SD lower in MS patients compared with the healthy reference population (Z scores). MS patients had significantly lower vitamin D levels (17.3 ng/ml vs 43.1 ng/ml; P < 0.001) compared to controls, and 19 patients (61%) had a serum level of vitamin D that was less than 20 ng/ml. EDSS scores in the patients were inversely correlated with proximal femur BMD but not with spinal BMD. There was a negative correlation with the cumulative steroid dose and BMD only for femur trochanter BMD. Total myalgia scores for paravertebral muscles correlated significantly with spinal BMD. In conclusion, BMD is significantly lower in MS patients than in healthy controls, vitamin D deficiency is prevalent in MS, and ambulatory status is a determinative factor for osteoporosis in MS. Patients should be encouraged to have adequate sunlight exposure and to increase their mobility. Specific strengthening exercises for hip and back muscles in MS patients would have a substantial impact on bone density, osteoporosis, fracture risk, and mobility.

Current concepts in the pathophysiology of fibromyalgia: the potential role of oxidative stress and nitric oxide

Fibromyalgia (FM) is a common chronic pain syndrome with an unknown etiology. Recent years added new information to our understanding of FM pathophysiology. Researches on genetics, biogenic amines, neurotransmitters, hypothalamic-pituitary-adrenal axis hormones, oxidative stress, and mechanisms of pain modulation, central sensitization, and autonomic functions in FM revealed various abnormalities indicating that multiple factors and mechanisms are involved in the pathogenesis of FM. Oxidative stress and nitric oxide may play an important role in FM pathophysiology, however it is still not clear whether oxidative stress abnormalities documented in FM are the cause or the effect. This should encourage further researches evaluating the potential role of oxidative stress and nitric oxide in the pathophysiology of FM and the efficacy of antioxidant treatments (omega-3 and -6 fatty acids, vitamins and others) in double blind and placebo controlled trials. These future researches will enhance our understanding of the complex pathophysiology of this disorder.

Assessment of enthesitis in ankylosing spondylitis by power Doppler ultrasonography

ObjectiveTo evaluate the relationship between power Doppler ultrasonography (PDUS) assessment and clinical variables including enthesitis index, pain threshold and disease activity parameters, and to document grey-scale US findings of the 13 entheses examined.Design and patientsA total of 390 entheses were examined in thirty patients with AS, and clinical variables of the Maastricht Ankylosing Spondylitis Enthesitis Index (MASES), anthropometric measurements, disease activity and functional parameters were documented. A total MASES score by palpation (t-PS) and algometric pressure pain threshold (t-PPT) was obtained. Grey scale and PDUS examination of 13 entheses were performed. Grey-scale changes such as altered tendon echogenity, calcification, cortical reactive changes and bursitis were noted, and flow on PDUS was graded semi-quantitatively.ResultsCumulative power Doppler (t-PDS) score significantly correlated with t-PS and t-PPT. Ultimate correlations were found between power Doppler scores and pain, disease activity and disability parameters. Changes in grey scale combined with PDUS were more prevalent in lower-extremity entheses. The intraobserver agreement of flow signal grading was excellent (kappa=0.82). Clinical and sonographic results were concordant for three regions, but were discordant for four regions where tenderness was accepted as the sole clinical manifestation of enthesis.ConclusionPain or tenderness is associated with increased vascularity of entheses. Power Doppler US examination of the entheses may be useful and complementary to the clinical evaluation, and further research is needed to assess its role in diagnosis and follow-up of disease course.

Role of diffusion-weighted MRI in the detection of early active sacroiliitis.

OBJECTIVE This study proposed to evaluate the value of diffusion-weighted MRI (DWI) to detect active inflammatory changes in the sacroiliac joints of patients with early axial spondyloarthritis (also spelled spondylarthritis). SUBJECTS AND METHODS Forty-two patients with chronic low back pain underwent clinical and MRI evaluation for axial spondyloarthritis or early ankylosing spondylitis. STIR, contrast-enhanced T1-weighted, fat-saturated T2-weighted, and diffusion-weighted (b values: 100, 600, 1,000 s/mm(2)) images were obtained. The presence of subchondral bone marrow edema, subchondral fatty marrow infiltration, or contrast enhancement in the sacroiliac joints or adjacent enthesitis sites was considered a marker for active inflammatory changes. All MRI sequences were evaluated for the presence of acute inflammatory changes and inter- and intrarater reliability of the sequences. Mean apparent diffusion coefficient (ADC) values of diffusion-weighted images were calculated from normal and involved iliac and sacral bones of sacroiliac joints. RESULTS ADC values measured from the lesions at b values of 1,000 and 600 s/mm(2) in patients with sacroiliitis (n = 13) were significantly higher than values measured from iliac and sacral bones in patients with low back pain of mechanical origin (n = 29). DWI showed sensitivity for detecting acute lesions in early sacroiliitis similar to that of T1-weighted gadolinium images (area under the curve, 0.843-0.971). Intra- and interrater reliability of DWI was acceptable. CONCLUSION DWI is a sensitive, fast sequence and does not require a contrast agent, which makes it a good and cost-effective alternative for imaging sacroiliac joints. DWI also offers the possibility of quantifying diffusion coefficients of the lesions, which helps to discriminate between normal and involved subchondral bone.

Serum nitric oxide, catalase, superoxide dismutase, and malondialdehyde status in patients with ankylosing spondylitis

In this study, serum antioxidant and oxygen derived free radical status of patients with ankylosing spondylitis (AS) was investigated and compared with that of age- and sex-matched healthy controls. The relationship of these parameters to disease activity indices was also examined. Thirty patients with AS not currently under disease-modifying antirheumatic drug (DMARD) treatment (e.g., sulfasalazine or methotrexate) (15 active and 15 inactive) and 16 age- and sex-matched healthy controls were included in the study. Catalase (EC 1.11.1.6), total (Cu-Zn and Mn) superoxide dismutase (SOD) (EC 1.15.1.1) activities, and malondialdehyde (MDA), nitrite (NO2-), and nitrate (NO3-) levels as indices of nitric oxide (NO) production were evaluated using appropriate methods. There was no statistically significant difference found in SOD activity or NO and MDA levels between active and inactive patients. Inactive patients showed no significant difference in all the measured oxidant/antioxidant parameters when compared to healthy controls. Active patients had significantly higher levels of MDA and catalase enzyme activity (P=0.002 and P=0.007, respectively). There was no significant correlation between oxidant/antioxidant parameters and disease activity, C-reactive protein, erythrocyte sedimentation rate, or Bath Ankylosing Spondylitis Disease Activity Index (CRP, ESR, or BASDAI) in either group, except catalase enzyme activity, which had a significant correlation with CRP and ESR levels in active patients (r=0.69 and P=0.004, r=0.52 and P=0.04, respectively). Our results indicate that oxidative stress and lipid peroxidation are accelerated in untreated patients with active AS. Serum catalase activity may be closely related to disease activity. In this regard, we underscore the likely benefit of some therapeutic interventions including high-potential antioxidants that will potentiate the antioxidant defense mechanism and reduce peroxidation in the management of AS.

Familial Mediterranean fever responds well to infliximab: single case experience

The most common arthritic involvement in familial Mediterranean fever (FMF) is acute recurrent monoarthritis; however, sometimes spondyloarthropathy-like findings or typical ankylosing spondylitis may also ensue. Reported here is our favorable experience with infliximab in an FMF patient who had been resistant to colchicine and disease-modifying antirheumatic drugs (sulfasalazine and methotrexate) treatments. A 72-week follow-up of the patient yielded complete remission of the febrile abdominal episodes, and spondylitis responded well. The patient’s bilateral aseptic necrosis of the femoral head deteriorated and caused hip pain, discomfort, and disability. Overall, we believe that tumor necrosis factor (TNF) alpha has an important role in the disease pathogenesis and also that anti-TNF may represent a promising robust treatment alternative in FMF.

Prevalence of comorbidities and evaluation of their screening in spondyloarthritis: results of the international cross-sectional ASAS-COMOSPA study

Background Increased risk of some comorbidities has been reported in spondyloarthritis (SpA). Recommendations for detection/management of some of these comorbidities have been proposed, and it is known that a gap exists between these and their implementation in practice. Objective To evaluate (1) the prevalence of comorbidities and risk factors in different countries worldwide, (2) the gap between available recommendations and daily practice for management of these comorbidities and (3) the prevalence of previously unknown risk factors detected as a result of the present initiative. Methods Cross-sectional international study with 22 participating countries (from four continents), including 3984 patients with SpA according to the rheumatologist. Statistical analysis The prevalence of comorbidities (cardiovascular, infection, cancer, osteoporosis and gastrointestinal) and risk factors; percentage of patients optimally monitored for comorbidities according to available recommendations and percentage of patients for whom a risk factor was detected due to this study. Results The most frequent comorbidities were osteoporosis (13%) and gastroduodenal ulcer (11%). The most frequent risk factors were hypertension (34%), smoking (29%) and hypercholesterolaemia (27%). Substantial intercountry variability was observed for screening of comorbidities (eg, for LDL cholesterol measurement: from 8% (Taiwan) to 98% (Germany)). Systematic evaluation (eg, blood pressure (BP), cholesterol) during this study unveiled previously unknown risk factors (eg, elevated BP (14%)), emphasising the suboptimal monitoring of comorbidities. Conclusions A high prevalence of comorbidities in SpA has been shown. Rigorous application of systematic evaluation of comorbidities may permit earlier detection, which may ultimately result in an improved outcome of patients with SpA.

Clinical evaluation and power Doppler sonography in rheumatoid arthritis: evidence for ongoing synovial inflammation in clinical remission.

Objective: This study proposed to assess the relationship between power Doppler ultrasound examination and spectral Doppler analysis of hand joints with clinical and laboratory parameters in rheumatoid arthritis. Methods: Patients receiving disease-modifying antirheumatic drugs or biologics (infliximab) underwent joint examination and were assessed by a Health Assessment Questionnaire, Duruozs Hand Index, and Hand Function Test. All were categorized for disease activity using the American College of Rheumatology and disease activity score 28-joint (DAS28) criteria. Ten metacarpophalangeal joints and 4 wrist joints (ulnar-carpal and radiocarpal joints) in each patient were examined by power Doppler and spectral Doppler. Flow signal in the synovium was semiquantitatively graded. A cumulative flow signal score (CFS) and mean resistive index (RI) was calculated in each patient. Results: Patients with active disease had significantly higher CFS compared with patients with inactive disease, but the mean RI was similar. Health Assessment Questionnaire, Duruozs Hand Index, Larsen, and DAS28 scores correlated significantly with CFS, but the erythrocyte sedimentation rate and C-reactive protein scores did not. Mean RI did not correlate with clinical or laboratory parameters. A majority of patients who were in clinical remission according to American College of Rheumatology or DAS28 criteria had ongoing synovial inflammation on power Doppler ultrasound (58% and 62%, respectively). Conclusion: Power Doppler examination of rheumatoid hand joints is a practical method to estimate synovial inflammation. A modification of current remission criteria by combining imaging techniques with clinical and laboratory examination may be conceivable. These results underscore the necessity of more sophisticated research, assessing the agreement between long-term Doppler changes and clinical parameters.