Umut Kalyoncu

Mean platelet volume (MPV) as an inflammatory marker in ankylosing spondylitis and rheumatoid arthritis

AIMS The aim of this retrospective study was to investigate the correlation between MPV and the clinical disease activity indices of rheumatoid arthritis and ankylosing spondylitis. METHODS The study consisted of 32 active RA patients (males/females: 7/25, mean age: 49+/-13) and 30 active AS patients (males/females: 15/15, mean age: 36+/-12) along with 26 osteoarthritis (OA) patients (males/females: 4/22, mean age: 52+/-8) and 29 age-matched healthy subjects (males/females: 5/24, mean age: 41+/-7) as control groups for RA and AS, respectively. RESULTS MPV was significantly lower in both AS patients and RA patients with active disease as compared to controls (RA vs OA p<0.001, AS vs healthy subjects p<0.001). After treatment MPV values significantly increased in AS and RA (p<0.001 for all). However, MPV values remained somewhat lower in RA patients than OA patients (p=0.019). There was a negative correlation between MPV values and BASDAI scores in AS patients after two months of treatment (r=-0.507; p=0.004). CONCLUSION Our results suggest that assessment of MPV may provide additional information about inflammation in AS and RA.

A patient-derived and patient-reported outcome measure for assessing psoriatic arthritis: elaboration and preliminary validation of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, a 13-country EULAR initiative

Introduction The objective was to develop a questionnaire that can be used to calculate a score reflecting the impact of psoriatic arthritis (PsA) from the patients’ perspective: the PsA Impact of Disease (PsAID) questionnaire. Methods Twelve patient research partners identified important domains (areas of health); 139 patients prioritised them according to importance. Numeric rating scale (NRS) questions were developed, one for each domain. To combine the domains into a single score, relative weights were determined based on the relative importance given by 474 patients with PsA. An international cross-sectional and longitudinal validation study was performed in 13 countries to examine correlations of the PsAID score with other PsA or generic disease measures. Test–retest reliability and responsiveness (3 months after a treatment change) were examined in two subsets of patients. Results Two PsAID questionnaires were developed with both physical and psychological domains: one for clinical practice (12 domains of health) and one for clinical trials (nine domains). Pain, fatigue and skin problems had the highest relative importance. The PsAID scores correlated well with patient global assessment (N=474, Spearman r=0.82–0.84), reliability was high in stable patients (N=88, intraclass correlation coefficient=0.94–0.95), and sensitivity to change was also acceptable (N=71, standardised response mean=0.90–0.91). Conclusions A questionnaire to assess the impact of PsA on patients’ lives has been developed and validated. Two versions of the questionnaire are available, one for clinical practice (PsAID-12) and one for clinical trials (PsAID-9). The PsAID questionnaires should allow better assessment of the patients perspective in PsA. Further validation is needed.

Detection of Subclinical Cardiac Involvement in Systemic Sclerosis by Echocardiographic Strain Imaging

Background: Cardiac involvement is one of the major problems in systemic sclerosis (SSc). Subclinical cardiac involvement has a higher frequency than thought previously. In this study we investigated whether subclinical cardiac involvement can be detected by using echocardiographic strain imaging in SSc patients without pulmonary hypertension. Methods: Echocardiographic examinations were performed to 27 SSc patients and 26 healthy controls. Left ventricular strain parameters were obtained from apical views and average strain value was calculated from these measurements. Results: There were no significant differences between patients and controls regarding two‐dimensional (2D), conventional Doppler and tissue Doppler velocity measurements. Strain was reduced in 6 of 12 segments of the left ventricle (LV) and in 1 of 2 segments of the right ventricle (RV). Strain rate (SR) was reduced in 2 of 12 segments of the LV and 1 of 2 segments of the RV in SSc patients as compared to controls (P < 0.05 for all). These involvements did not match any particular coronary artery distribution. More important differences were detected by average strain and SR values of the LV between patients and controls (19.78 ± 3.00% vs 23.41 ± 2.73%, P < 0.001; 2.01 ± 0.41 vs 2.23 ± 0.27/sec, P = 0.026, respectively). Furthermore, carbon monoxide diffusion capacity (DLCO) in scleroderma patients significantly correlated with LV average strain (r = 0.59; P = 0.001). Conclusion: Evaluation of ventricular function by using echocardiographic strain imaging appears to be useful to detect subclinical cardiac involvement in SSc patients with normal standard echocardiographic and tissue Doppler velocity findings.

Pneumocystis carinii pneumonia in a rheumatoid arthritis patient treated with adalimumab

Patients with rheumatoid arthritis (RA) have an increased risk of infection as a result of alterations in immune regulation, debility, and comorbid illnesses. TNF-α is of central importance in the pathophysiological responses to infection and inflammation, and plays a crucial role in host defence. Pneumocystis carinii is an opportunistic pathogen that commonly affects individuals with inadequate T-cell mediated immune response. Patients with acquired immune deficiency, as well as those receiving immunosuppressive drugs for various conditions have an increased risk of P. carinii pneumonia (PCP). We report the development of PCP in a woman with RA shortly after the initiation of anti-TNF-α treatment with adalimumab.

Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: a multicentre study

OBJECTIVE The primary aim of this study was to investigate the prevalence of amyloidosis and its related factors in a large number of FMF patients. METHODS Fifteen centres from the different geographical regions of Turkey were included in the study. Detailed demographic and medical data based on a structured questionnaire and medical records were collected. The diagnosis of amyloidosis was based on histological proof of congophilic fibrillar deposits in tissue biopsy specimens. RESULTS There were 2246 FMF patients. The male/female ratio was 0.87 (1049/1197). The mean age of the patients was 34.5 years (S.D. 11.9). Peritonitis was the most frequent clinical finding and it was present in 94.6% of patients. Genetic testing was available in 1719 patients (76.5%). The most frequently observed genotype was homozygous M694V mutation, which was present in 413 (24%) patients. Amyloidosis was present in 193 patients (8.6%). Male sex, arthritis, delay in diagnosis, M694V genotype, patients with end-stage renal disease (ESRD) and family history of amyloidosis and ESRD were significantly more prevalent in patients with amyloidosis compared with the amyloidosis-negative subjects. Patients with homozygous M694V mutations had a 6-fold higher risk of amyloidosis compared with the other genotypes (95% CI 4.29, 8.7, P < 0.001). CONCLUSION In this nationwide study we found that 8.6% of our FMF patients had amyloidosis and homozygosity for M694V was the most common mutation in these patients. The latter finding confirms the association of homozygous M694V mutation with amyloidosis in Turkish FMF patients.

A Case Series of Adenosine Deaminase 2-deficient Patients Emphasizing Treatment and Genotype-phenotype Correlations.

To the Editor: Deficiency of adenosine deaminase 2 (DADA2) causes a vasculopathy with autoinflammatory features associated with mutations in CECR1 1. The phenotype of DADA2 varies from only cutaneous lesions to full-blown systemic disease with central nervous system (CNS) involvement and aneurysms in visceral arteries that may overlap with the spectrum of polyarteritis nodosa (PAN)1,2,3. The Chapel Hill Consensus Conference (CHCC) 2012 defines PAN as a necrotizing vasculitis of medium or small arteries without glomerulonephritis or vasculitis in arterioles, venules, or capillaries and not associated with antineutrophil cytoplasmic antibodies4. Now, with the discovery of DADA2, we know that monogenic disorders may cause a PAN-like vasculopathy. Thus, DADA2 should be classified under the group of “vasculitis with a probable cause” in CHCC 20124. We herein present the characteristics of 6 DADA2 patients and their response to various therapies. Three of our patients had been initially screened at the U.S. National Institutes of Health (NIH) because they had suggestive features for the CECR1 mutations. Subsequently, we screened 17 patients with suggestive features and identified 3 new cases. We have evaluated the course of these patients for a followup of median 8.5 years. All patients were Turkish and were followed in the departments of Rheumatology and Pediatric Rheumatology at Hacettepe University, Ankara, Turkey. Three (patients 2, 3, and 5) had been included in a previous paper2. Peripheral blood samples for DNA extraction were obtained. Sanger sequencing was performed to sequence 10 exons of CECR1 in NIH (n = 3) and Hacettepe University (n = 3). Primer sequences are available in the Appendix. PCR products were directly sequenced using ABI Prism 3130 Automated Sequencer (Applied Biosystems). We defined 6 DADA2 patients from 5 families. The characteristics and treatment of patients … Address correspondence to Dr. S. Ozen, Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey. E-mail: sezaozen{at}hacettepe.edu.tr

Familial Mediterranean fever and central nervous system involvement: a case series.

We conducted this study to determine familial Mediterranean fever (FMF)-associated central nervous system involvement including demyelinating lesions, stroke, and posterior reversible leukoencephalopathy syndrome (PRES). Patients with MEFV mutations were systematically reviewed through the Medical Biology Unit database. All samples sent for mutation analysis were screened for 10 common MEFV mutations. Patients with FMF and neurologic disorders according to the clinical records were invited for reevaluation. Lumbar puncture, electroencephalography, and evoked potentials were used to determine the type of neurologic involvement in selected cases. Electrocardiography, transthoracic and/or transesophageal echocardiography, and magnetic resonance imaging and/or angiography were performed to clarify the etiology of cerebrovascular disease. Of 8864 patients in the genetic testing database, 18 with neurologic signs were assessed. The mean age of patients was 31.0 ± 11.8 years, mean age at first FMF symptom was 12.6 ± 5.6 years, and mean age at neurologic involvement was 25.8 ± 12.2 years. Fifty-five percent of patients were women. A homozygote MEFV mutation was detected in 16 of 18 patients (88.8%), and a homozygote M694V mutation was found in 72.2% of patients. We found 7 FMF patients with demyelinating lesions, 7 with cerebrovascular disease, and 4 with PRES. The mean interval between first FMF sign and neurologic involvement was 13.7 ± 8.9 years in the demyelinating group, and 23.4 ± 10.3 years in the group with cerebrovascular disease. Mean stroke age was 28.5 ± 16.4 years. All patients in the PRES group had hypertension. Three different neurologic conditions in FMF patients were noticeable. Demyelinating lesions and cerebrovascular disease were the most common clinical presentations. Approximately 70% of patients had the homozygote M694V mutation. Neurologic involvement is rare but serious in FMF. Abbreviations: BAEP = brainstem auditory evoked potentials, CNS= central nervous system, CSF = cerebrospinal fluid, EEG = electroencephalography, ESR = erythrocyte sedimentation rate, FMF= familial Mediterranean fever, HSP = Henoch-Schönlein purpura, IL = interleukin, MEFV = the FMF gene, MRI = magnetic resonance imaging, PAN= polyarteritis nodosa, PRES = posterior reversible leukoencephalopathy syndrome, SEP = somatosensorial evoked potential, VEP= visual evoked potential.

Specific adsorption of the autoantibodies from rheumatoid arthritis patient plasma using histidine-containing affinity beads

Rheumatoid arthritis is characterized by chronic polyarthritis and destruction of multiple joints. In this study, poly(hydroxyethyl methacrylate-N-methacryloyl-(L-histidine)-methylester) (PHEMAH) beads were used in the removal of pathogenic antibodies from rheumatoid arthritis patient plasma in a packed bed column. PHEMAH beads, in the size range of 80–120 μm, were produced by suspension polymerization. The beads were contacted with blood in an in vitro system. Loss of blood cells and clotting times were followed. PHEMAH beads were characterized by scanning electron microscopy. We found that PHEMAH beads had a spherical shape and porous structure. Loss of cells in the blood contacting with PHEMAH beads was negligible. IgM-antibody adsorption capacity decreased significantly with the increase of the plasma flow-rate. With increasing IgM-antibody concentration, the amount of IgM-antibody adsorbed per unit mass increased and then reached saturation. Maximum IgM-antibody adsorption amount was 69.2 mg/g. IgM-antibody molecules could be repeatedly adsorbed and desorbed without noticeable loss in the IgM-antibody adsorption amount.

Left and Right Ventricular Function Is Impaired in Behcet's Disease

Objectives: Subclinical cardiac involvement may occur in patients with Behçets disease (BD). The purpose of our study was to assess the noninvasive parameters of biventricular function derived from Doppler tissue imaging (DTI) of the tricuspid and mitral annular motion in BD. Methods: Twenty‐one patients with BD and 20 control subjects were enrolled in this study. All subjects were selected to exclude those with cardiovascular risk factors. Standard echocardiography and pulsed DTI were obtained in every patient. Results: Peak systolic (13.71 ± 2.09 vs 20.01 ± 1.57, P < 0.001), peak early diastolic (11.26 ± 2.52 vs 15.35 ± 2.06, P < 0.001) tricuspid annular velocities were significantly lower in patients than controls. Peak systolic (8.68 ± 1.4 vs 12.25 ± 1.7, P < 0.001), peak early diastolic (7.89 ± 1.07 vs 9.94 ± 1.12, P < 0.001), and peak end diastolic (8.30 ± 1.32 vs 9.23 ± 0.91, P = 0.013) lateral mitral annular velocities were significantly lower in patients than controls. Conclusions: We demonstrated that myocardial velocities, were affected in patients with BD. Therefore, we conclude that right and left ventricular function is impaired in patients with BD.

Updating the Psoriatic Arthritis (PsA) Core Domain Set: A Report from the PsA Workshop at OMERACT 2016

Objective. To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS). Methods. At OMERACT 2016, research conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants. Results. We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted 24 focus groups with 130 patients from 7 countries representing 5 continents to identify patient domains. We achieved consensus through 2 rounds of separate surveys with 50 patients and 75 physicians, and a nominal group technique meeting with 12 patients and 12 physicians. We conducted a workshop and breakout groups at OMERACT 2016 in which findings were presented and discussed. The updated PsA Core Domain Set endorsed with 90% agreement by OMERACT 2016 participants included musculoskeletal disease activity, skin disease activity, fatigue, pain, patient’s global assessment, physical function, health-related quality of life, and systemic inflammation, which were recommended for all RCT and LOS. These were important, but not required in all RCT and LOS: economic cost, emotional well-being, participation, and structural damage. Independence, sleep, stiffness, and treatment burden were on the research agenda. Conclusion. The updated PsA Core Domain Set was endorsed at OMERACT 2016. Next steps for the PsA working group include evaluation of PsA outcome measures and development of a PsA Core Outcome Measurement Set.