Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: results from 13 European registries.

OBJECTIVES: In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. METHODS: Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors. RESULTS: In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (<2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), ≥10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP of >10 vs ≤10 mg/l: 1.52 (1.22-1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98-0.99). CONCLUSION: Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level.

Does obesity affect treatment response to secukinumab and survival in ankylosing spondylitis? Real-life data from the TURKBIO Registry.

OBJECTIVES: The aim of this study was to evaluate the impact of obesity on the treatment response to secukinumab and drug survival rate in patients with ankylosing spondylitis (AS). METHODS: We performed an observational cohort study that included AS patients based on the biological drug database in Turkey (TURKBIO) Registry between 2018 and 2021. The patients were divided into three groups: normal [body mass index (BMI) < 25 kg/m2], overweight (BMI: 25-30 kg/m2), and obese (BMI ≥ 30 kg/m2). Disease activity was evaluated at baseline, 3, 6, and 12 months. Drug retention rates at 12 months were also investigated. RESULTS: There were 166 AS patients using secukinumab (56.6% male, mean age: 44.9 ± 11.6 years). The median follow-up time was 17.2 (3-33.2) months. Forty-eight (28.9%) patients were obese. The mean age was higher in the obese group than in others (P = .003). There was no statistically significant difference in Bath Ankylosing Spondylitis Disease Activity Index 50, Assessment of SpondyloArthritis international Society 20 (ASAS20), ASAS40, Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity, and ASDAS clinically important improvement responses between the three groups at 3, 6, and 12 months, although they were numerically lower in obese patients. Drug retention rates at 12 months were similar in all groups (P > .05). CONCLUSIONS: This study suggested that obesity did not affect secukinumab treatment response and drug retention in AS patients.

How has the COVID-19 pandemic affected our rheumatology patients using biological/targeted DMARDs?

INTRODUCTION: We aimed to investigate the effects of the coronavirus disease 2019 (COVID-19) pandemic on the course and treatment of patients with inflammatory rheumatic musculoskeletal disease (iRMD) using biologic or targeted synthetic disease modifying and rheumatic drugs (b/tsDMARDs). METHODOLOGY: The study was carried out in two stages: in the first stage we investigated the delay of b/tsDMARD treatment in the first 3 months of the pandemic; in the second stage, we investigated all patients who decided to continue treatment after interruption in the 12-month period. RESULTS: A total of 521 patients were included in the study. The iRMD diagnosis was listed as spondyloarthritis (SpA) (54.3%), rheumatoid arthritis (RA) (25.7%), psoriatic arthritis (PsA) (8.4%), vasculitis (6.1%), and others (5.4%). Concurrent use of hydroxychloroquine (hazard ratio [HR] = 1.49), iv bDMARD use (HR = 1.34), and a history of discontinuation of drug in the first 3 months of the pandemic (HR = 1.19) were determined as factors that reduced 12-month drug retention rates. The use of glucocorticoid (HR = 3.81) and having a diagnosis of interstitial lung disease/chronic obstructive lung disease (HR = 4.96) were found to increase the risk of being infected by SARS coronavirus 2 (SARS-CoV-2). CONCLUSIONS: It was shown that approximately 1/5 of iRMD patients using b/tsDMARDs delayed their treatment due to the fear of COVID-19 in the first three months of the pandemic process. However, with good communication with the patients, b/tsDMARD treatment was restarted and the 12-month drug retention status was quite high.

Assessment of diaphragmatic function by ultrasonography in patients with systemic sclerosis and its relation to clinical parameters : A case-control study.

BACKGROUND: Diaphragmatic function can be affected in many diseases and disorders. Although systemic sclerosis (SSc) is a serious connective tissue disease that affects not only the skin but also the pulmonary and musculoskeletal systems, there is insufficient information about diaphragm function. AIMS: To compare the diaphragmatic parameters by ultrasonography (USG) in patients with SSc and healthy individuals and examine the relationship between these parameters and clinical features in patients with SSc. METHODS: This study included 13 patients with SSc and 15 healthy individuals. Muscle thickness (in deep inspiration Tins and at the end of calm expiration Texp), changes in thickness (∆T), and thickening fraction at deep breathing were evaluated by USG. Skin thickness, pulmonary function tests, respiratory muscle strength, and the perception of dyspnea were measured as clinical features. RESULTS: The results of Texp, Tins, and ∆T were similar in both groups (p > 0.05), albeit patients in the SSc group had less thickening fraction compared to the control group (79.9 ± 36.7 cm and 103.8 ± 20.6 cm, respectively, p < 0.05). The Tins, ∆T, and thickening fraction of the diaphragm were associated with skin thickness, pulmonary function test parameters, and respiratory muscle strength (p < 0.05). Besides, there was significant correlation between muscle thickening fraction and perception of dyspnea (p < 0.05). CONCLUSION: These results confirm that diaphragm thickness and contractility can be affected in patients with SSc. Therefore, ultrasonographic evaluation of the diaphragm can play a complementary role to pulmonary function test and respiratory muscle strength measurement in the diagnosis and follow-up of patients with SSc.

Evaluation of choroidal vascularity index in systemic sclerosis patients.

OBJECTIVE: To investigate the comparison of choroidal vascularity index (CVI) between patients with systemic sclerosis and healthy individuals. METHODS: This study was designed prospective non-randomized cross-sectional study. Eighty-six eyes (43 patients) with limited cutaneous systemic sclerosis (lcSSc), 60 eyes (30 patients) with diffuse cutaneous systemic sclerosis (dcSSc) and 60 eyes (30 subjects) of age-and sex-matched healthy individuals were recruited. Subfoveal choroidal thickness, CVI and modified Rodnan skin score (mRSS) were evaluated. Enhanced depth imaging- optical coherence tomography scans were binarized using Niblack's autolocal threshold and CVI was determined as the luminal choroidal area/total choroidal area ratio. RESULTS: The mean CCT values were 268.00±68.59 µm, 286.90±70.88 µm, 321.73±94.13 µm in lcSSc group, dcSSc group and control group, respectively. The mean CVI was 61.84±2.84% in lcSSc group, 54.62±5.84% in dcSSc group and 62.41±4.13% in control group (p=0.001). The mean CVI of the SSc patients was 58.91±5.58 and there was significant difference between control group (p<0.001). The mean mRSS was 3.84±2.50 in lcSSc group and 14.07±6.81 in dcSSc group (p<0.001). There was a statistically significant negative correlation between mRSS and CVI (r=-0.448, p<0.001) CONCLUSION: Choroidal vascularity index provides valuable information to monitor the disease progression and lower CVI values seem to be related to the disease severity in patients with systemic sclerosis.

Comparison of pulmonary function, respiratory symptoms, functional level, and health-related quality of life in patients with systemic sclerosis according to smoking status.

BACKGROUND: Patients with systemic sclerosis (SSc) are at high risk for pulmonary and vascular complications. Smoking is an important risk factor for respiratory symptoms and vascular complications of many diseases in the general population. However, studies on the role of smoking in SSc are insufficient. AIMS: This study aimed to compare pulmonary function, respiratory symptoms, functional level, and health-related quality of life (HRQoL) in patients with SSc according to smoking status and to assess the correlation between cigarette consumption and these parameters in patients with SSc. METHODS: Seventy-two patients with SSc (smoker group; n = 35 or nonsmoker group; n = 37) were included. The pulmonary function test was measured with a spirometer. Respiratory symptoms were questioned and the perceived severity of dyspnea and fatigue was evaluated. The functional levels were determined by questioning the patients' average daily walking distance, exercise habits, and daily sedentary time. HRQoL was assessed by Scleroderma Health Assessment Questionnaire. RESULTS: The rate of respiratory symptoms including dyspnea, cough, and sputum were higher in the smoker group (p < .001, p = .041, and p < .001, respectively). Also, the perceived severity of dyspnea and fatigue was higher in the smoker group (p < .05). The mean daily walking distance, exercise habits, and overall HRQoL were lower (p = .004, p = .002, and p = .034, respectively) and the sedentary time and vascular complications were higher (p < .001 and p = .038, respectively) in the smoker group. However, there was no significant difference between the two groups in terms of the pulmonary function test (p > .05). There was a weak to moderate correlation between cigarette consumption and respiratory symptoms, dyspnea and fatigue severity, functional level, and HRQoL in the smoker group (0.001 ≤ p ≤ .024). CONCLUSIONS: Smoking may increase respiratory symptoms and vascular complications and decrease the functional level and HRQoL in patients with SSc. To maintain functional independence in patients with SSc, awareness of the harms of smoking should be increased and smoking cessation should be encouraged, along with physiotherapy and rehabilitation programs including exercise and physical activity recommendations.

Rituximab on lung, skin, and joint involvement in patients with systemic sclerosis: A case series study and review of the literature.

OBJECTIVES: To evaluate the effectiveness of rituximab (RTX) in systemic sclerosis (SSc) patients. METHODS: Data were collected from patient charts before and after RTX administration for 1 year of follow-up time. An updated review of the literature was also done. RESULTS: Of 8 patients enrolled (mean age: 62.4 years; mean disease duration: 16.7 years), 2 patients with pulmonary arterial hypertension (PAH) died after the first RTX cycle. The follow-up data of the remaining 6 patients were evaluated. There was a significant improvement in arthritis of Disease Activity Score of 28 joints - C-reactive protein and Clinical Disease Activity Index compared with baseline. The median change in modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and carbon monoxide diffusing capacity between baseline and 12 months were similar. Lung involvement was detected in 5/6 of survivor patients, FVC was improved in 2/5, worsened in 1/5, and remained stable in 2/5 at the end of 1 year. Among the 5 diffuse cutaneous SSc patients, none of the patients' mRSS deteriorated by more than 5 points, while one patient's mRSS improved by greater than 5 points. CONCLUSION: This study suggests that RTX is effective for arthritis in patients with SSc. Also, the effectiveness of RTX in skin and lung involvement of SSc was predominantly toward stable disease or improvement. Despite the long disease duration, the presence of patients who showed improvement in skin and lung involvement after RTX treatment suggests the need to investigate predictors of RTX response.

A real-life analysis of patients with rheumatologic diseases on biological treatments: Data from TURKBIO Registry.

OBJECTIVE: TURKBIO registry, established in 2011, is the first nationwide biological database in Turkey. This study aimed to provide an overview of TURKBIO data collected by June 2018. METHODS: The registry included adult patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis (nr-AxSpA), and psoriatic arthritis (PsA). Demographic and clinical features, disease activity markers, and other follow-up parameters, current and previous treat- ments, and adverse events were registered electronically at each visit using open-source software. The registration of patient-reported outcome measures was carried out electronically by the patients using touch screens. RESULTS: TURKBIO registry included a total of 41,145 treatment series with biologicals. There were 2,588 patients with axSpA (2,459 AS and 129 nr-axSpA), 2,036 with RA, and 428 with PsA. The total number of patients, including those with other diagnoses, was 5,718. In the follow-up period, the number of patients and also visits steadily increased by years. The yearly mean number of visits per patient was found to be 2.3. Significant improvements in disease activity and health assessment parameters were observed following the biological treatments. Biologics were often given in combination with a con- ventional synthetic disease-modifying antirheumatic drug in patients with RA. Infections were the most commonly seen adverse events, followed by allergic reactions. Tuberculosis was observed in 12 patients, malignancy in 18, and treatment-related mortality in 31. CONCLUSION: TURKBIO provided a valuable real-life experience with the use of biologics in rheumatic diseases in Turkey.

Global hypomethylation pattern in systemic sclerosis: An application for absolute quantification of epigenetic DNA modification products by 2D-UPLC-MS/MS.

BACKGROUND: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by progressive fibrosis of the skin and internal organs. Besides genetics risk factors, understanding the epigenetic modifications in SSc has been gaining acceleration in recent years. Epigenetic modifications are reversible and defined as druggable targets. In this context, it is highly important to present a systemic perspective to epigenetic modifications of SSc in terms of both pathogenesis and clinical utility. MATERIAL AND METHODS: DNA samples from the whole blood specimens of the 41 SSc patients and 27 healthy controls (HCs) were obtained. Absolute quantification of 5-mC, 5-hmdC, 5-cadC, 5-fdC, and 5-hmdU as the DNA methylation and demethylation products were performed using 2D-UPLC-MS/MS. Demographic data and clinical scores were recorded in detail. RESULTS: 5-hmdU was significantly higher in SSc patients while 5-hmdC was lower compared to the HCs (p < 0.01, p = 0.012 respectively). 5-cadC and 5-fdC had upward trend in SSc (p = 0.064; p = 0.066). These results support that SSc patients tend to have a global hypomethylation pattern. Clinical analyzes revealed that lung, gastrointestinal, joint, and vascular involvement of SSc is also associated with increased demethylation or decreased methylation profile. CONCLUSION: We performed absolute quantification of epigenetic DNA modification products in SSc for the first time. We demonstrated an upward trend in global hypomethylation in SSc. Furthermore, as a result of detailed clinical analyzes, the relationship between lung, GIS, and vascular involvement with epigenetic changes was shown. We believe that absolute quantification of DNA methylation and demethylation products with novel technologies can provide a deep understanding of disease pathogenesis and has the potential to mark an era for developing new therapeutic strategies.

Protective effects of alpha-lipoic acid on bleomycin-induced skin fibrosis through the repression of NADPH Oxidase 4 and TGF-ß1/Smad3 signaling pathways.

The aim of this study was to determine the protective effects of alpha-lipoic acid (ALA), which is known as a powerful antioxidant, and the possible related molecular mechanisms that mediate its favorable action on skin fibrosis in the bleomycin (BLM)-induced scleroderma (SSc) model in mice. The experimental design was established with four groups of eight mice: Control, ALA (100 mg/kg), BLM (5 µg/kg), and BLM + ALA group. BLM was administered via subcutaneous (sc) once a day while ALA was injected intraperitoneally (ip) twice a week for 21 days. Histopathological and biochemical analyses showed that ALA significantly reduced BLM-induced dermal thickness, inflammation score, and mRNA expression of tumor necrosis factor-alpha (TNF-α) in the skin. Besides, the mRNA expressions of the subunits of NADPH oxidase, which are Nox4 and p22phox, were found to be significantly induced in the BLM group. However, ALA significantly reduced their mRNA expression, which were in parallel to its decreasing effect on serum total oxidant status (TOS) level. Moreover, it was found that ALA downregulated the mRNA expressions of alpha-smooth muscle actin (α-SMA), collagen type I and fibronectin in the skin tissue of the BLM group. Additionally, it was shown that ALA reduced significantly the TGF-ß1 and p-Smad3 protein expressions in the BLM + ALA group. On the other hand, ALA did not exhibit any significant effect on the p38 mitogen-activated kinase (MAPK) activation induced by BLM. All these findings point out that ALA may be a promising treatment for the attenuation of skin fibrosis in SSc patients.

The prevalence of Sjögren's syndrome and sicca symptoms in patients with systemic sclerosis and alpha-smooth muscle actin expression in biopsy specimens from minor salivary glands

Background/aim: This study aimed to investigate the prevalence of sicca symptoms and secondary Sjögren's syndrome (SjS) in patients with systemic sclerosis (SSc). Also this study aimed to evaluate the expression of α-smooth muscle actin (α­SMA) in minor salivary gland (MSG) specimens, a possible marker of fibrosis responsible for myofibroblastic transformation. Materials and methods: Patients with SSc who were followed in Rheumatology outpatient clinic at a university hospital evaluated. The questionnaire of sicca symptoms and classification of SjS were evaluated according to the American­European Consensus Group (AECG) criteria. Histopathologic evaluations were done in MSG specimens investigating the presence of focal lymphocytic sialadenitis and glandular fibrosis, also assessing the expression of α­SMA. Results: This cross-sectional study included 102 patients with SSc [91 females (89%), mean age 52.5 ± 12 years]. In this cohort 76 (75%) patients had sicca symptoms and 36 (35.3%) patients fulfilled the AECG criteria for SjS; all with limited form. Having SjS found to be associated with older age and the presence of positive anti-SS-A antibodies. On histopathologic examinations, glandular fibrosis was observed in 67 (80%) and lymphocytic sialadenitis was detected in 38 (45%) patients; but only 7 samples were positive for α­SMA. Conclusion: This study suggested sicca symptoms were found to be very common among patients with SSc. Also secondary SjS was detected in nearly one-third of patients with SSc; especially in limited subtype. Anti SS-A positivity and older age were detected as predictors for SjS. Histopathologic evaluations showed significant glandular fibrosis but rare α-SMA staining in patients with SSc.

Association of Leptin Levels and Disease Activity in Patients with Early Rheumatoid Arthritis.

OBJECTIVE: Previous studies have reported a link between metabolic parameters and disease activity in rheumatoid arthritis (RA), although the evidence is limited in early RA. We aimed to investigate the relationship between disease activity and adipocytokine levels in subjects with early RA. METHODS: Forty-seven patients with early RA (symptom duration ≤12 months) were enrolled. Disease activity was determined by DAS28-CRP. Patients were treated with DMARDs according to the EULAR recommendations. Subjects were tested before and five months after treatment. RESULTS: Early RA patients with high disease activity (DAS28-CRP > 4.9) had greater BMI (31.2 ± 6.8 kg/m2 vs. 26.7 ± 4.1 kg/m2; p = 0.006) and higher leptin levels (14.62 ± 15.60 ng/mL vs. 7.82 ± 8.00 ng/mL; p = 0.048). Levels of other adipocytokines were not significantly different. Leptin levels were similar in subjects with mild/moderate disease activity and controls. DAS28-CRP was correlated with leptin (r = 0.303, p = 0.039). Leptin levels decreased significantly after treatment (from 10.86 ± 12.34 ng/mL to 9.22 ± 9.29 ng/mL; p = 0.047) along with insulin levels (from 13.68 ± 21.90 mU/L to 7.09 ± 4.72 mU/L; p = 0.010) and HOMA-IR (from 4.39 ± 9.53 to 1.70 ± 1.38; p = 0.012). HDL cholesterol levels increased (from 41 ± 10 mg/dL48 ± 10 mg/dL; p <0.001). CONCLUSION: Leptin levels were associated with disease activity in patients with early RA and these levels decreased after treatment with DMARDs. Further research is needed to elicit leptin's role to regulate disease activity in early RA.

Evaluation of limited hand mobility in systemic sclerosis patients by using "prayer sign" and "tabletop sign".

OBJECTIVES: To determine limited joint mobility (LJM) of the hand in patients with systemic sclerosis (SSc). METHODS: LJM was evaluated with "prayer sign" and "tabletop sign" tests. LJM staging was done by Rosenbloom classification method. LJM (+) and LJM (-) patients were compared in terms of demographic findings (gender, age and duration of disease), laboratory results (ESR, CRP, anti-nuclear antibody (ANA), anti-topoisomerase I and anti-centromere), and modified Rodnan skin score (mRss) results. RESULTS: In our study, a total of 217 patients, including 113 patients with a diagnosis of SSc, and 104 as a healthy control group with similar age and gender distribution to these patients, were included. A total of 113 (F=98, M=15) patients (limited cutaneous SSc (lcSSc=71), diffuse cutaneous SSc (dcSSc=42)) were included in this study and LJM positivity was found in 66.4% (lcSSc=38, dcSSc=37). A statistically significant difference was observed in between lcSSc and dcSSc patients according to the presence of LJM (p<0.001). There was a moderate positivity relationship between LJM and mRss (lcSSc r=0.449, p<0.001; dcSSc r=0.565, p<0.001). CONCLUSIONS: In our study, it was found that LJM staging correlated with mRss and dcSSc patients had more severe LJM findings than lcSSc. We conclude that "prayer sign" and "tabletop sign" tests used in hand evaluation in SSc patients have similar clinical results with mRss and can be simple bedside tests in daily practice. Key Points • This is the first study examining limited joint mobility (LJM) with "prayer sign" and "tabletop sign" tests in systemic sclerosis (SSc) patients. • "Prayer sign" and "tabletop sign" tests can be easily performed in daily practice. • We found Rosenbloom LJM staging correlated with modified Rodnan skin score. LJM of the hand can be a good prognostic indicator for early stage SSc patients.

TNF-α Inhibitors for the Management of Intractable Corneal Melt: Report of Three Cases and Review of the Literature.

OBJECTIVE: To report three consecutive cases with noninfectious corneal melting, whose disease progression could only be halted with tumor necrosis-α (TNF-α) inhibitor infusion, with a review of the relevant literature. MATERIALS AND METHODS: Patients with toxic epidermal necrolysis, severe alkaline burn, and Sjögren syndrome had experienced severe corneal melting following penetrating keratoplasty, Boston type 1 keratoprosthesis implantation or spontaneously, respectively. Topical autologous serum eye-drops, medroxyprogesterone, and acetylcysteine formulations; frequent nonpreserved lubrication; systemic tetracyclines and vitamin-C supplements; topical and systemic steroids and steroid-sparing agents; surgical approaches including amniotic membrane transplantation, tectonic graft surgery; and tarsorraphy failed to alter the disease courses. RESULTS: Upon consultation with the rheumatology clinic, TNF-α inhibitor infliximab (Remicade; Centocor Ortho Biotech Inc, Horsham, PA) 5 mg/kg infusion was planned for each patient. After 0-, 2-, and 6-week doses, monthly infusion at the same dose was maintained for 12 months because of severe and intractable course of their diseases. Each case showed dramatic improvements in corneal melts; and sterile vitritis in the eye with Boston keratoprosthesis responded, as well. CONCLUSIONS: Inhibiting TNF-α-mediated expression of matrix metalloproteinases responsible for collagen breakdown should be considered in refractory cases, as a means of globe salvage.

Relationship of Wnt pathway activity and organ involvement in scleroderma types.

OBJECTIVE: Scleroderma (SSc) is a chronic inflammatory autoimmune disease characterized by fibrosis in the skin and internal organs. In SSc, the heart, lung, kidney, gastrointestinal (GIS) system, muscle, and peri-articular structures are damaged. There is no study of the relationship between SSc type, stage, pathogenesis, organ involvement, and Wnt signaling. In this study, we aimed to show the relationship of the Wnt gene family and antagonists in SSc subtypes and different organ involvement. METHODS: Eighty-five SSc patients and 77 controls were included in this study. The gene expressions and protein levels of the Wnt family and antagonists were analyzed from blood samples. The relationship between these parameters and disease stage, type, and organ involvement were evaluated. RESULTS: Wnt-1, Wnt-10b, Wnt-2, and Wnt-6 gene expressions are increased and Axin-2, DKK-1, and Kremen protein expressions are decreased in SSc. Wnt-3a and Wnt-10a gene expressions are increased in generalized SSc compared to limited SSc. Wnt-1, Wnt-2 gene expressions are increased significantly in pulmonary arterial hypertension (PAH)(+) SSc compared to PAH(-) SSc. There was a positive correlation between the modified Rodnan skin score and Wnt-2 in SSc. There was a significant positive correlation between GIS involvement score and Wnt-1, Wnt-2, Wnt-4, Wnt-8a, Wnt-9b in SSc. CONCLUSION: Wnt-1 and Wnt-2 were found higher in scleroderma and organ involvement. They may play a role in the pathogenesis of the disease.

Whole blood viscosity in systemic sclerosis: a potential biomarker of pulmonary hypertension?

OBJECTIVE: Our goal was to determine if whole blood viscosity (WBV) can be used to predict the risk of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc). METHODS: Patients with SSc were analyzed. Out of 107 patients, 26 patients, found to have confirmed diagnosis of PAH, were classified as those with (n = 26, PAH group) and without PAH (n = 81, non-PAH group). We calculated estimated WBV at both high (HSR) and low shear rates (LSR) from hematocrit and total serum protein levels. RESULTS: Total protein levels were significantly higher and the anti-centromere antibody (ACA) was more frequent in the PAH group. Furthermore, anti-topoisomerase antibody (anti-scl-70) was significantly less frequent in the PAH group. The WBV values were significantly higher at HSR (16.68 ± 0.38 vs. 16.24 ± 0.58; p < 0.001) and at LSR (51.81 ± 7.21 vs. 42.97 ± 11.76; p < 0.001) in PAH group. The multivariate analysis revealed that the WBV at both shear rates independently designated the presence of PAH in SSc patients. The ROC curve showed that the sensitivity and specificity of LSR and HSR were 92.3% and 61.7% (AUC 0.759, p < 0.001), and 88.5% and 65.4% (AUC 0.770, p < 0.001) with a cutoff value of 43.56 and 16.32 for WBV, respectively. CONCLUSION: Higher WBV levels in SSc patients were an independent indicator for PAH development in this cohort. WBV-LSR and WBV-HSR values might help exclude the PAH possibility in patients diagnosed with SSc and remain as an independently associated biomarker for follow-up of these patients for future risk of PAH development. Findings remain to be confirmed by other cohorts.Key Points• The most important cause of morbidity and mortality in systemic sclerosis patients is considered to be pulmonary arterial hypertension.• When the symptoms of PAH are not recognized earlier in the course of the SSc, the prognosis might be worse.• Higher whole blood viscosity levels in scleroderma patients with PAH was an independent indicator for PAH development.

Treatment response and drug retention rates in 24 195 biologic-naïve patients with axial spondyloarthritis initiating TNFi treatment: routine care data from 12 registries in the EuroSpA collaboration.

OBJECTIVE: To study drug retention and response rates in patients with axial spondyloarthritis (axSpA) initiating a first tumour necrosis factor inhibitor (TNFi). METHODS: Data from 12 European registries, prospectively collected in routine care, were pooled. TNFi retention rates (Kaplan-Meier statistics), Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive disease (<1.3), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) <40 mm and Assessment of SpondyloArthritis International Society responses (ASAS 20/40) were assessed at 6, 12 and 24 months. RESULTS: A first TNFi was initiated in 24 195 axSpA patients. Heterogeneity of baseline characteristics between registries was observed. Twelve-month retention was 80% (95% CI 79% to 80%), ranging from 71% to 94% across registries. At 6 months, ASDAS Inactive disease/BASDAI<40 rates were 33%/72% (LUNDEX-adjusted: 27%/59%), ASAS 20/40 response rates 64%/49% (LUNDEX-adjusted 52%/40%). In patients initiating first TNFi after 2009, 6097 patients was registered to fulfil ASAS criteria for axSpA, 2935 was registered to fulfil modified New York Criteria for Ankylosing Spondylitis and 1178 patients was registered as having non-radiographic axSpA. In nr-axSpA patients, we observed lower 12-month retention rates (73% (70%-76%)) and lower 6-month LUNDEX adjusted response rates (ASDAS Inactive disease/BASDAI40 20%/50%, ASAS 20/40 45%/33%). For patients initiating first TNFi after 2014, 12-month retention rate, but not 6-month response rate, was numerically higher compared with patients initiating TNFi in 2009-2014. CONCLUSION: A large European database of patients with axSpA initiating a first TNFi treatment in routine care, demonstrated that 27% of patients achieved ASDAS inactive disease after 6 months, while 59% achieved BASDAI <40. Four of five patients continued treatment after 1 year.

Ochronosis Involvement and Extensity With 18F-FDG PET/CT.

Ochronosis (alkaptonuria) is an autosomal recessive inherited metabolic disease that causes pigmentation by accumulation of homogenous acid in the connective tissue. The most important causes of morbidity are ochronotic arthropathy and cardiovascular involvement seen in fourth and sixth decades, respectively. In this case report, we report the prevalence of F-FDG PET/BT findings in a 48-year-old man with ochronosis who underwent F-FDG PET/BT imaging for the evaluation of mediastinal lymphadenopathy.

Infliximab-associated focal segmental glomerulosclerosis in a patient with ankylosing spondylitis.

The introduction of tumor necrosis factor-alpha (TNF-α)-targeting drugs has given new opportunities in the treatment of various inflammatory rheumatic diseases and has been the most important development in the treatment of spondyloarthritis (SpA). However, the increasing use and longer follow-up periods of treatment also pose risks of developing various adverse effects ranging from common ones including infections to uncommon renal complications. This report describes a case of infliximab-induced focal segmental glomerulosclerosis (FSGS) in a 40-year-old female patient with ankylosing spondylitis (AS) who presented with asymptomatic proteinuria and microscopic hematuria. To the best of our knowledge, this is the second reported case of FSGS attributed to infliximab (IFX). A review of the English literature was conducted for cases of possible IFX-associated renal disorders in patients with SpA and SpA spectrum diseases. In this respect, the reported renal pathologies were IgA nephropathy, crescentic glomerulonephritis, acute renal artery occlusion, acute tubulointerstitial nephritis (ATIN), FSGS, and membranous glomerulopathy. Furthermore, partial or complete resolution was reported after cessation of therapy. In conclusion, although renal complications of TNF inhibitors (TNFi) are uncommon, spot urine evaluation may be recommended in the follow-up of patients treated with TNFi.

Association between Skin Thickness Measurements with Corneal Biomechanical Properties and Dry Eye Tests in Systemic Sclerosis.

Purpose: To analyse the association between skin score with corneal biomechanics and dry eye tests in systemic sclerosis (SSc). Methods: 112 cases (limited SSc (lcSSc), n=50; diffuse SSc  (dcSSc), n=32; controls, n=30) were included in the study. Corneal hysteresis (CH), corneal resistance factor (CRF), Schirmer 1, 2 tests, OSDI score and modified Rodnan skin score (mRSS) were evaluated. Results: There was correlation between the mRSS and CH (p = 0.004, r = -0.402; p < 0.001, r = -0.786, respectively) as well as correlation with the CRF (p < 0.001, r = 0.709; p < 0.001, r = 0.848, respectively) and OSDI (p < 0.001, r = 0.74; p < 0.001, r = 0.89, respectively) score in lcSSc and dcSSc. Also, the Schirmer 1 (p < 0.001, r = -0.802) and 2 (p < 0.001, r = -0.587) test values showed correlation with the mRSS in dcSSc. Conclusion: Skin score had clinically significant importance for predicting corneal biomechanical properties and dry eye tests in both lcSSc and dcSSc.