Rheumatoid Arthritis-Related Lung Disease and Its Association With Mortality.

PURPOSE: The aim of this study was to determine the association of rheumatoid arthritis-related lung disease (RA-LD) and its subtypes with all-cause mortality. MATERIALS AND METHODS: For the present analyses, patients with RA who underwent computed tomography of the chest (chest-CT) were evaluated. RA-LD was defined in 4 subtypes as follows: interstitial lung disease (RA-ILD), airway disease (RA-AD), rheumatoid pulmonary nodules (RA-PN), and RA-related pleural disease (RA-PD). The date of RA-LD diagnosis was considered the date of the first chest-CT detecting the pathology. To assess the factors associated with mortality, multivariable logistic regression analyses were performed with variables selected based on their causal associations with the outcome. RESULTS: Of 576 RA patients, 253 (43.9%) had RA-LD (38.7% male; mean age at RA-LD diagnosis, 59.9 ± 9.8 years). The most common subtype was RA-AD, which was detected in 119 (47.0%) patients followed by 107 (42.3%) with RA-ILD, 70 (27.7%) with RA-PN, and 31 (12.3%) with RA-PD. Sixty-one (24.1%) patients had 2+ subtypes. After median follow-up of 10.2 years, 97 (16.8%) died. The existence of at least 1 subtype and 2+ subtypes increased the all-cause mortality, as indicated by odds ratios of 1.60 (95% confidence interval [CI], 1.03-2.48) and 2.39 (95% CI, 1.26-4.54), respectively. Among RA-LD patients, RA-ILD and RA-PD were associated with increased mortality (odds ratios were 2.20 [95% CI, 1.18-4.08] and 1.62 [95% CI, 0.70-3.75], respectively). CONCLUSIONS: In this study, RA-AD was the most common subtype, and the presence of RA-LD increased mortality. This effect was particularly pronounced in patients with RA-ILD and RA-PD or those presenting with 2+ subtypes.

The factors predicting development of serious infections in ANCA-associated vasculitis.

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare autoimmune disease usually involving small vessels and progressing with necrotizing inflammation. Treatment requires long-term use of immunosuppressive agents to inhibit disease activity. Serious infections (SIs) are a common complication in AAV. OBJECTIVE: The aim of this study was to identify the risk factors for serious infections which required hospitalization in patients with AAV. METHODS: In this retrospective cohort study., we included 84 patients admitted to the Ankara University Faculty of Medicine in the last 10 years with a diagnosis of AAV. RESULTS: In 42 (50%) of 84 patients followed up with the diagnosis of AAV, an infection requiring hospitalization was identified. The patients' total corticosteroid dose, use of pulse steroids, induction regimen, levels of C-reactive protein (CRP) and the presence of pulmonary and renopulmonary involvement were found to be associated with the frequency of infection (p=0.015, p=0.016, p=0.010, p=0.03, p= 0.026 and p=0.029, respectively). In multivariable analysis, it was found that renopulmonary involvement (p=0.002, HR=4.95, 95% CI= 1.804-13.605), age of over 65 (p=0.049, HR=3.37, 95% CI=1.004-11.369) and high CRP levels (p=0.043, HR=1.006, 95% CI=1.000-1.011) constituted independent predictors of serious infection risk. CONCLUSION: The frequency of infection is known to be increased in ANCA-associated vasculitis. Our study showed that renopulmonary involvement, age and elevated CRP levels on admission are independent risk factors of infection.

Frequency of Helicobacter pylori in Patients With Rheumatoid Arthritis Whose Methotrexate Was Stopped Due to Gastrointestinal Intolerance.

OBJECTIVE: The aims of this study were to compare the frequency of Helicobacter pylori between patients with rheumatoid arthritis (RA) with and without methotrexate (MTX)-related gastrointestinal system (GIS) intolerance, and to demonstrate the associated factors with such intolerance. METHODS: The data of 9756 patients with RA who presented between January 2011 and December 2020 were evaluated. Methotrexate-related GIS intolerance was defined as the discontinuation of MTX owing to the dyspeptic symptoms despite supportive measures and was detected in 1742 (31.3%) patients among 5572 MTX users. A total of 390 patients with and without intolerance who had at least 1 gastroscopic evaluation were included in the final analyses. The demographic, clinical, laboratory, and pathologic characteristics of patients with and without MTX-related GIS intolerance were compared. To determine the associated factors with MTX-related GIS intolerance, logistic regression analysis was performed. RESULTS: Of 390 patients, 160 (41.0%) patients had MTX-related GIS intolerance. According to the pathology results, the presence of H. pylori , inflammation, and activity were significantly higher in patients with MTX-related GIS intolerance ( p < 0.001 for each comparison). In multivariable logistic regression analysis, the use of biologic disease-modifying antirheumatic drugs (DMARDs) or targeted synthetic DMARDs was found to be an independently associated factor for MTX-related GIS intolerance (odds ratio [OR], 3.03 for model 1; OR, 3.02 for model 2) in addition to H. pylori presence (OR, 9.13 for model 1; OR, 5.71 for model 2). CONCLUSIONS: In this study, we found that the presence of H. pylori and the use of biologic or targeted synthetic DMARDs were associated with MTX-related GIS intolerance.

Predictors of pain catastrophizing in women with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to identify predictive factors associated with pain catastrophizing in women with systemic lupus erythematosus (SLE). METHODS: A total of 104 volunteered women with a diagnosis of systemic lupus erythematosus participated in the study. Pain Catastrophizing Scale, Body Awareness Questionnaire, Tampa Scale of Kinesiophobia, and Beck Depression Inventory were used to assess patients. Correlations between pain catastrophizing (dependent variable) and independent variables (age, body mass index, disease activity, organ damage, depression, kinesiophobia, and body awareness) were analyzed with Pearson's rho correlation analysis. The multiple stepwise linear regression models with R2 were used to compare across the models and explain the total variance. The significance level of a p-value was considered significant if p≤0.05. RESULTS: There were no correlations between Pain Catastrophizing Scale and age, Beck Depression Inventory, disease activity, and organ damage (p>0.05). Pain Catastrophizing Scale was correlated with Tampa Scale of Kinesiophobia (r=0.585; p<0.001), Beck Depression Inventory (r=0.511; p<0.001), and Body Awareness Questionnaire (r=0.277; p<0.005). The regression analysis showed that the predictor factors of pain catastrophizing in women with systemic lupus erythematosus were TSK (B 0.411; p<0.001), Beck Depression Inventory (B 0.363; p<0.001), Body Awareness Questionnaire (B 0.273; p<0.001), and body mass index (B -0.169; p=0.02) (Nagelkerke R2=0.52). CONCLUSIONS: As a result, the most related factors on pain catastrophizing were kinesiophobia, depression, body awareness, and body mass index in women with systemic lupus erythematosus. We suggest assessing these parameters as predictive of pain catastrophizing throughout systemic lupus erythematosus management.

Predictors of pain catastrophizing in women with systemic lupus erythematosus

SUMMARY OBJECTIVE: The aim of this study was to identify predictive factors associated with pain catastrophizing in women with systemic lupus erythematosus (SLE). METHODS: A total of 104 volunteered women with a diagnosis of systemic lupus erythematosus participated in the study. Pain Catastrophizing Scale, Body Awareness Questionnaire, Tampa Scale of Kinesiophobia, and Beck Depression Inventory were used to assess patients. Correlations between pain catastrophizing (dependent variable) and independent variables (age, body mass index, disease activity, organ damage, depression, kinesiophobia, and body awareness) were analyzed with Pearson's rho correlation analysis. The multiple stepwise linear regression models with R2 were used to compare across the models and explain the total variance. The significance level of a p-value was considered significant if p≤0.05. RESULTS: There were no correlations between Pain Catastrophizing Scale and age, Beck Depression Inventory, disease activity, and organ damage (p>0.05). Pain Catastrophizing Scale was correlated with Tampa Scale of Kinesiophobia (r=0.585; p<0.001), Beck Depression Inventory (r=0.511; p<0.001), and Body Awareness Questionnaire (r=0.277; p<0.005). The regression analysis showed that the predictor factors of pain catastrophizing in women with systemic lupus erythematosus were TSK (B 0.411; p<0.001), Beck Depression Inventory (B 0.363; p<0.001), Body Awareness Questionnaire (B 0.273; p<0.001), and body mass index (B -0.169; p=0.02) (Nagelkerke R2=0.52). CONCLUSIONS: As a result, the most related factors on pain catastrophizing were kinesiophobia, depression, body awareness, and body mass index in women with systemic lupus erythematosus. We suggest assessing these parameters as predictive of pain catastrophizing throughout systemic lupus erythematosus management.

Indications and risk factors for hospitalization in patients with primary Sjögren syndrome: experience from a tertiary center in Turkey.

OBJECTIVE: In this study, it was aimed to reveal the hospitalization reasons for patients diagnosed with primary Sjögren syndrome (pSS) and potentially associated factors in a tertiary health center. METHOD: One hundred and sixty-three pSS patients who regularly attended their follow-ups between January 2010 and May 2021 were included in the study. These patients' reasons for hospitalization, duration of hospitalization, and numbers of presenting to the hospital were recorded. The demographic, clinical and serological characteristics of the hospitalized and non-hospitalized patients were compared. RESULTS: Hospitalization occurred in 22.7% of the patients, and the total number of hospitalizations was 79. The hospitalization incidence density rate was 6.21 per 100 patient-years. The most frequently encountered reason for hospitalizations was pSS-related organ involvement (44.3%). Infections (17.7%), malignancy (16.5%), endocrine, and various other reasons were the other indications for hospitalization. While male sex (p = 0.005), the presence of extra-glandular involvement (p < 0.001), and interstitial lung disease (p = 0.001) were more common in the hospitalized patients, anti-nuclear antibody positivity was less frequent (p = 0.032). The usage rate of hydroxychloroquine (p = 0.022) was lower in the hospitalized patients, whereas the use of glucocorticoids (p < 0.001) and azathioprine (p = 0.005) was more frequent. The multivariable analyses revealed a relationship between extra-glandular involvement (OR: 4.57 [1.05-19.84], p = 0.043), glucocorticoid use (OR: 3.23 [1.13-9.21], p = 0.028) and hospitalization. CONCLUSION: pSS-related system involvement and infection accounted for the majority of hospitalizations of the pSS patients. The presence of extra-glandular involvement and glucocorticoid use were found to be associated with hospitalization. Key Points • pSS-related system involvement and infection accounted for the majority of hospitalizations of pSS patients. • The presence of extra-glandular involvement was found to be associated with hospitalization.

Interstitial Lung Disease in Systemic Sclerosis: A Single-center Retrospective Analysis.

BACKGROUND: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by microangiopathy, inflammation, fibrosis. Interstitial lung disease (ILD) is common among SSc patients. OBJECTIVE: This study aims to define the clinical, laboratory, and serologic characteristics of SSc patients with ILD and to present the frequency of chest computed tomography features. METHODS: Two hundred twenty-six SSc patients who applied to the Rheumatology Department between January 2007 and August 2019 were retrospectively examined. A total of 100 SSc patients with ILD (44.2%) were determined. Clinical, laboratory, and serological features of SSc patients with and without ILD were compared. RESULT: Both groups had similar characteristics in terms of age and sex. The duration of disease (p=0.001) and follow-up time (p=0.001) were longer in SSc patients with ILD. Multivariable logistic regression analysis indicated that the duration of disease (OR: 1.06 (1.01-1.13), p=0.029), presence of gastrointestinal system involvement (OR: 3.29 (1.28-8.46), p=0.013) and anti-SCL70-positivity (OR: 6.04 (2.35-15.49), p <0.001) were associated with ILD. There was an inverse relationship between Anti-CENP-B positivity and the presence of ILD (p=0.001). The assessment regarding the chest computed tomography characteristics of interstitial pneumonia patterns were as follows: 82.5% non-specific interstitial pneumonia, 14.4% usual interstitial pneumonia, and 2.1% desquamative interstitial pneumonia. The most frequent abnormal findings included ground-glass opacification (88.7%), reticulation (64.9%), traction bronchiectasis (57.7%), septal thickening (52.6%) and honeycombing (28.9%). CONCLUSION: We have shown a relationship between anti-SCL70, disease duration, gastrointestinal system involvement, and ILD in SSc patients.

Causes of severe infections in patients with systemic sclerosis and associated factors.

BACKGROUND: Systemic sclerosis (SSc) is a chronic systemic disease characterized by vascular damage, autoimmunity, and fibrosis in the skin and internal organs. In this study, we tried to determine the causes of severe infection in patients with SSc and to reveal the factors associated with severe infection. METHODS: We retrospectively examined 214 SSc patients between January 2010 and August 2020. Forty-seven patients with at least one severe infection and 167 patients without severe infection were compared. RESULTS: A total of 76 episodes of severe infections were detected in 47 (22%) patients. Common infections included pneumonia, infected digital ulcer, urinary tract infections, and osteomyelitis. Female patients had a higher frequency in the group without severe infection (91.6% vs. 80.9%, p = 0.035). Patients with severe infections had a higher frequency of digital ulcers (p < 0.001), cardiac (p = 0.002), and GIS involvement (p < 0.001). In multivariable analysis, digital ulcer presence (OR: 2.849 [1.356-5.898] (p = 0.006) and cardiac involvement (OR: 2.801 [1.248-6.285]) were associated with severe infection. Of the patients with severe infections, 34% had recurrent severe infections. There was no difference in demographic and clinical characteristics between patients with recurrent and nonrecurrent severe infections. DISCUSSION: The presence of digital ulcer and cardiac involvement seem to be associated with a severe infection in patients with systemic sclerosis. In patients with cardiac involvement and digital ulcers, more careful attention may be required for the development of severe infections.

Rituximab experience from a single centre for patients with rheumatoid arthritis-related interstitial lung disease.

Objective: To demonstrate the effects of rituximab (RTX) in patients with rheumatoid arthritis-related interstitial lung disease (RA-ILD). Methods: A total of 165 patients who used RTX for the management of rheumatoid arthritis were retrospectively scrutinised. Among these, 26 patients diagnosed with RA-ILD were analysed (61.5% male, mean age at RTX infusion 61.4 ± 6.5 years). To evaluate the efficacy of RTX on lung response, patients with pulmonary function test results and/or thorax computed tomography (chest-CT) of pre- and post-RTX were compared. Disease progression was defined as either a decline of ≥10% in forced vital capacity (FVC) and/or a decline of ≥15% in diffusion capacity of carbon monoxide (DLCO), or an increase of parenchymal involvement on chest-CT images according to the radiologists' assessment. Results: Among 26 patients, the most common radiologic pattern was usual interstitial pneumonia (42.3%), followed by non-specific interstitial pneumonia (38.5%). Data for lung response was available in 20 patients. Median pre- and post- RTX DLCO values were 71.0% (60.0-77.0) and 63.0% (47.0-74.0), respectively (p= 0.06). Median pre- and post-RTX FVC values were 74.0% (61.0-99.0) and 84.0% (63.0-100.0), respectively (p= 0.28). Overall, stabilization or regression of RA-ILD was provided in 13 (65.0%) patients, whereas 7 patients had progressive RA-ILD. Post-RTX, 5 patients were diagnosed with RA-ILD. Conclusion: Our results suggest that RTX is effective in achieving stabilization or even improvement of RA-ILD. However, considering that it does not cause regression in every patient and some develop RA-ILD under RTX, we still need more effective treatment options.

Analysis of vascular involvement in 460 patients with Behçet's syndrome: Clinical characteristics and associated factors.

OBJECTIVES: To describe demographic and clinical characteristics of vascular involvement in patients with Behçet's syndrome (BS) and to evaluate associations with such involvement. METHODS: We retrospectively evaluated records of 2118 BS patients. In total, 460 patients diagnosed with superficial thrombophlebitis (ST) and/or major vascular events (venous and/or arterial involvements) were included in current analysis. Isolated ST with no accompanying deep venous thrombosis might be accepted as part of skin involvement; therefore, we defined two different outcomes for vascular involvement ("any vascular event" and "major vascular events") and performed univariable and multivariable logistic regression to assess factors associated with these outcome variables. RESULTS: Overall, 68 (14.8%) patients had isolated ST, and 392 (85.2%) had major vascular events. The mean age of vascular BS was 33.8 (SD: 10.5) years and median follow-up was 13.9 (Q1-Q3: 8.3-22.9) years. The primary sites of major vascular events were deep venous thrombosis (n=358, 77.8%), pulmonary arterial involvement (n=66, 14.3%), extrapulmonary arterial involvement (n=52, 11.3%), and intracardiac thrombosis (n=14, 3.0%), respectively. Male sex was significantly associated with a higher risk for both outcome variables. When it was added to analysis, ST itself was the strongest explanatory variable that was associated with major vascular events in all multivariable models (ORs=11.9, 12.0, 13.0, and 18.9). While HLA-B51 was significantly associated with any vascular event, there was no similar observation for major vascular events. CONCLUSION: Male sex is a well-known risk factor for major vascular events in BS, but our study established that presence of ST was the strongest risk factor.

Can Subclinical Atherosclerosis Be Assessed More Precisely in Behçet Syndrome Patients by Using a Particular Cutoff Value for Carotid Intima Media Thickness?

OBJECTIVE: Behçet syndrome (BS) is a multisystemic chronic vasculitic disease. Among previous studies, although there are some that showed increased risk of subclinical atherosclerosis in BS, there are also others that showed the opposite. The objective of this study is to evaluate subclinical atherosclerosis in BS by using the cutoff value for intima-media thickness in the 2013 European Society of Cardiology/European Society of Hypertension guideline. METHODS: We conducted a cross-sectional analysis of 100 BS patients and 30 healthy volunteers at a single center in a 4-month period. All ultrasound scans were performed in a blind manner to the clinical assessment, and they were carried out by the same researcher by a B-mode ultrasonography. RESULT: When we grouped the patients based on the presence of subclinical atherosclerosis, the frequency of subclinical atherosclerosis in the BS patients was found to be higher than that in the healthy controls (32% and 7%, respectively; p = 0.006). When a cutoff is used for carotid intima-media thickness, increased atherosclerosis risk is observed in BS patients with vascular involvement (p = 0.043). CONCLUSIONS: Although higher inflammation and increased atherosclerosis in vascular BS patients were expected, this situation was not supported much in previous studies. We think that this may have been caused by mere comparison of numerical data, and usage of a cutoff value could be more significant in distinguishing what is normal and what is abnormal as in several medical parameters.

Disseminated Nocardiosis with Ocular Involvement in a Patient with Anca-associated Vasculitis.

A 62-year male patient, diagnosed with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), developed proptosis and decrease in visual acuity while on rituximab treatment. As the ophthalmological examination and imaging studies could not exclude tumour of the orbit, enucleation of the orbit was performed. The histopathology displayed necrosis and inflammation. Because the clinical, laboratory and pathological findings of the patient suggested a vasculitis exacerbation, the immunosuppressive treatment was continued. However, the patient developed confusion and hemiplegia with cerebral mass lesions on imaging. The subsequent report of the pathology revealed a nocardial infection of the eye. The patient was diagnosed with nocardiosis with ocular and cerebral involvement. Despite efficient antimicrobial therapy, the disease progressed rapidly causing death. This case is unique as it describes disseminated nocardiosis with ocular and cerebral involvement in an AVV patient. Key Words: Immunosuppression, Nocardiosis, ANCA-associated vasculitis, Proptosis.

Serum Calprotectin is Indicating Clinical and Ultrasonographic Disease Activity in Rheumatoid Arthritis, even with Normal C-Reactive Protein Levels.

OBJECTIVE: Calprotectin is an inflammatory biomarker which assesses disease activity in rheumatoid arthritis (RA). The objective of this study was to test whether serum calprotectin is associated with clinical and ultrasonographic disease activity in patients with RA, and to analyse its predicting value for disease activity evaluation despite normal C-Reactive protein (CRP) levels. METHODS: We included 80 patients with RA and 30 healthy subjects. Patients were examined clinically and by ultrasound, (US7 score) along with laboratory parameters (calprotectin, CRP, erythrocyte sedimentation rate [ESR]). Disease activity scores (DAS28) were calculated to assess disease activity. Firstly, patients were divided into four subgroups according to the DAS28-ESR (high, moderate, low disease activity, and remission), then into two subgroups; group-1 (DAS-28≤3.2) and group-2 (DAS28>3.2). The predicting value of calprotectin for disease activity in patients with normal CRP was analysed with univariate and multivariate analysis and receiver operating characteristic curves. RESULTS: Calprotectin levels were higher in RA patients than controls (96.3±45.9 ng/ml, 54.7±50.0 ng/ml, respectively; p<0.001). Calprotectin levels were 74.8±45.5 ng/ml in group-1 (n=37) and 114.7±37.9 ng/ml in group-2 (n=43) (p<0.001). In univariate analyses, calprotectin was significantly correlated with clinical, laboratory, and ultrasound parameters (p<0.05), and was a better predictor of power doppler synovitis than CRP in multivariate analysis (OR=1.014; 95%CI 1.002-1.027; p=0.024). The discriminatory capacity for calprotectin to distinguish ultrasonographically active disease in patients with normal CRP levels using AUC was 0.75 (95%CI 0.56-0.90, p=0.023). CONCLUSIONS: Calprotectin represents disease activity, even in patients who are clinical and ultrasonographical active but have normal CRP levels.

High mobility group box-1 levels may be associated with disease activity of Behcet's disease

BACKGROUND: High mobility group box- 1 (HMGB- 1) is a nuclear protein acting as a proinflammatory molecule. The serum HMGB- 1 levels were found elevated in chronic inflammatory diseases. In this cross-sectional study, serum HMGB- 1 levels in Behcet's disease (BD) patients and healthy controls (HC) were studied. Also, its association with disease activity scores and clinical findings were evaluated. METHODS: Ninety BD patients and 50 age-sex matched HC were included in the study. Disease activity scores were assessed by Behcet Disease Current Activity Form (BDCAF) and Behcet Syndrome Activity Score (BSAS). Serum HMGB- 1 levels were measured using a commercial ELISA kit. A p value of < 0.05 was considered to be statistically significant. RESULTS: Serum HMGB- 1 levels were significantly higher in BD than in HC (43.26 pg/mL and 16.73 pg/mL; p < 0.001, respectively). Serum HMGB- 1 levels were statistically significantly associated with presence of erythema nodosum (EN) and genital ulcers in the last one month prior to recruitment (p = 0.041 and p < 0.001, respectively). BDCAF and BSAS scores were positively correlated with serum HMGB- 1 level ( p = 0.03 and p = 0.02, respectively). DISCUSSION: HMGB - 1 may play a role in the development of BD. Also, due to its positive correlation with disease activity indices, it can be used as a novel disease activity parameter in BD.

Clinical characteristics of pulmonary artery involvement in patients with Behçet's syndrome: single-centre experience of 61 patients.

OBJECTIVE: To report the clinical characteristics of pulmonary artery involvement (PAI) in patients with Behçet's syndrome (BS) and to define the predictors of relapses. METHODS: We performed retrospective analysis of BS patients with PAI who fulfilled international study group criteria. Among 460 patients with vascular Behçet's syndrome (VBS), 66 were diagnosed with PAI. For final analyses, 61 patients with PAI were included who had at least 2 follow-up visits (72.1% male, mean age at BS diagnosis 29.34 ± 10.1 years). The patient data were recorded. Relapse was defined as the reoccurrence of vascular event in any vascular structure. Factors associated with relapse were assessed by logistic regression analysis. RESULTS: There were no differences considering demographic and clinical features of the patients with and without PAI in the VBS group, except that intracardiac thrombosis was more common in the patients with PAI (19.7% vs 0.3%). Among 61 patients, 50 (82.0%) had isolated pulmonary artery thrombosis (PAT), whereas 11 (18.0%) had pulmonary artery aneurysm with or without PAT. Twenty-four (39.3%) patients experienced vascular relapse during median follow-up of 65.9 (Q1-Q3: 20.1-109.0) months. To define the factors associated with relapses, patients with isolated PAT were analysed. On multivariable logistic regression analysis, older age at BS diagnosis and anticoagulation usage seemed to be protective (OR: 0.92, 95% CI 0.86-1.02, OR: 0.34, 95% CI 0.09-1.33, respectively). CONCLUSION: Our results indicate a higher frequency of intracardiac thrombosis in BS patients with PAI and possible efficacy of anticoagulation usage in preventing relapses. Key Points • This study shows that intracardiac and intracranial thromboses are seen more frequently in patients with PAI and the prevalence of pulmonary artery thrombosis has been increasing in the case of PAI. Furthermore, our report indicates that anticoagulation might be effective in preventing further vascular relapses.

Early onset primary Sjögren syndrome, clinical and laboratory characteristics.

INTRODUCTION/OBJECTIVES: Primary Sjögren syndrome (pSS) is usually encountered between the fourth and sixth decades. It is known that the age of onset in autoimmune diseases may affect the clinical features. In this study, we aimed to investigate the clinical and laboratory characteristics of early onset pSS patients. METHOD: The data of 352 pSS patients were analyzed retrospectively. The patients were divided into two groups as those with the onset age of 35 or younger (early-onset) and those with the onset age of older than 35. The clinical, laboratory, and serological characteristics of the two groups were compared. p < 0.05 was considered statistically significant. RESULTS: Forty patients in the group with an onset age of 35 or younger (11.4%) and 312 patients with an onset age of older than 35 (88.6%) were analyzed. The frequency of skin (22.5% vs 1.9%, p < 0.001) and renal involvement (10% vs 2.2%, p = 0.026) was significantly higher in the early-onset group than the late-onset group. There was no significant difference between the two groups in terms of xerostomia, eye dryness, arthritis, and other systemic involvement. Anti-Ro52 positivity (p = 0.04), elevated serum IgG levels (p = 0.004), and low C4 (p = 0.002) presence were more frequent in the early-onset group. CONCLUSIONS: Consequently, it is seen that the clinical phenotype of early-onset pSS patients may be different to those with later onset. Especially the more frequent observation of poor prognostic factors at early-onset ages shows the necessity to monitor these patients more regularly. KEY POINTS: • The clinical and laboratory features of patients with early-onset primary Sjogren syndrome may differ from late-onset patients.

Association of simple hematological parameters with disease manifestations, activity, and severity in patients with systemic sclerosis.

INTRODUCTION/OBJECTIVES: Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), mean platelet volume (MPV), and red cell distribution width (RDW) may potentially reflect inflammatory status in systemic autoimmune diseases. The aim of this study is to investigate the association between these proposed markers and disease manifestations, activity, and severity in systemic sclerosis (SSc). METHOD: We conducted a cross-sectional study of 69 systemic sclerosis (SSc) patients and 50 healthy volunteers in a single center. Adult patients with SSc and healthy controls were compared in terms of NLR, MLR, MPV, RDW, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Venous blood samples were drawn after at least 8 h of fasting in the morning. Extension of skin fibrosis was evaluated by using modified Rodnan skin score (mRSS). Disease severity and activity were assessed by Medsger disease severity and European Scleroderma Trials and Research Group (EUSTAR) disease activity scores, respectively. Associations of disease manifestations, clinical, laboratory, and capillaroscopic findings, mRSS, and the disease activity and severity scores with the proposed hematological markers were evaluated. Multiple regression models were generated for significant associations. RESULTS: The neutrophil number was higher (p = 0.004) and lymphocyte number was lower (p < 0.001) in SSc group compared to controls. SSc group also had higher NLR, MLR, and RDW. In multiple logistic regression, only the NLR (regression coefficient = 3.49, p = 0.031) and CRP (regression coefficient = 0.17, p = 0.037) remained significantly different between SSc and healthy control groups (Cox and Snell R2 = 0.243, Nagelkerke R2 = 0.337, p < 0.001). NLR and MLR positively correlated with mRSS, EUSTAR score, and CRP. MLR also positively correlated with Medsger score. Higher monocyte counts independently predicted higher EUSTAR and Medsger scores in multiple linear regressions. Patients with digital ulcers had higher NLR and MLR. We did not find any difference in MPV values between SSc and healthy control groups. CONCLUSIONS: Globally available and inexpensive hematological tests, particularly the NLR and MLR, may be associated with vascular and cutaneous manifestations as well as disease activity and severity in SSc.Key Points• Monocyte count itself independently predicted higher activity and severity scores in SSc.• Globally available and inexpensive hematological markers, particularly the NLR and MLR, may have an association with vascular and cutaneous manifestations as well as disease activity and severity in patients with SSc.

Serum Interleukin 35 Levels in Systemic Sclerosis and Relationship With Clinical Features.

BACKGROUND/OBJECTIVE: Interleukin (IL) 35 is a member of the IL-12 family. Studies show that IL-35 is an important anti-inflammatory cytokine and suppresses effector T-cell activity. In this study, we aimed to evaluate serum IL-35 levels in systemic sclerosis (SSc) patients and its potential relation with clinical findings. METHODS: We conducted a cross-sectional analysis of 70 SSc patients and 29 healthy volunteers in a single center in 5 months' period. Extension of skin fibrosis was evaluated by using modified Rodnan skin score. Disease severity was assessed by Medsger disease severity scores. Serum IL-35 was measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit (Cloud-Clone Corp, Wuhan, China). The relationship between IL-35 levels and clinical and laboratory parameters was investigated. Mann-Whitney U test was used to compare parameters among the groups. Correlation was tested by Spearsman correlation coefficient. RESULTS: Serum IL-35 levels was significantly higher in SSc patients (8.69 [interquartile range, 29.33] pg/mL) than in healthy controls (7.11 [interquartile range 7.53] pg/mL; p < 0.001). There was no significant relationship between serum IL-35 levels and organ involvement. There was a negative correlation between serum IL-35 levels and Medsger disease severity score (Rho, -0.333; p = 0.006), modified Rodnan skin score (Rho, -0.307; p = 0.010), and C-reactive protein (Rho, -0.294; p = 0.015). There was no relationship between IL-35 and disease duration and erythrocyte sedimentation rate. CONCLUSIONS: Our study revealed that IL-35 levels were higher in SSc patients, and in contrast to previous studies, it was the first study that showed that IL-35 levels did not increase in SSc patients with pulmonary fibrosis.

Anti-interleukin-1 treatment in 26 patients with refractory familial mediterranean fever.

OBJECTIVE: To investigate the effect of anti-interleukin-1 (anti-IL-1) treatment on the frequency and severity of attacks and other disease-related clinical parameters and to evaluate the adverse effects associated with anti-IL-1 treatment in 26 patients with refractory familial mediterranean fever (FMF). METHODS: The study included 26 FMF patients followed up in our centre using colchicine for 4 months to 30 years. The treatment was switched to anti-IL-1 treatment for various reasons; 20 cases were resistant to colchicine, 8 were intolerant to colchicine, and 3 had prolonged arthritis under colchicine. Clinical response was monitored through the number of attacks, and laboratory inflammation was monitored through erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A concentrations. Colchicine resistance was defined as at least two attacks/month together with C-reactive protein and serum amyloid A levels above the normal range between attacks. The colchicine dose was increased to 2 mg/day before they were considered colchicine-resistant. RESULTS: 24 patients used anakinra (100 mg/day), and 2 used canakinumab (150 mg/month), for -36 months. Sixteen patients with colchicine resistance had no attacks under anti-IL-1 treatment, and 4 had decreased frequency and duration of attacks. Seven of 8 patients intolerant to colchicine used anakinra, and 6 were attack-free under treatment, while 1 using canakinumab had attacks under treatment. One patient with prolonged arthritis used canakinumab but arthritis showed progression and the treatment was changed to IL-6 inhibitor. Three patients had injection site erythema and one had fatigue with anti-IL-1 treatment. Topical steroids with systemic antihistaminics were sufficient for symptom control in two cases, but canakinumab treatment was given due to severe injection site erythema in one case. CONCLUSION: Anti-IL-1 agents are rational treatment modalities in patients resistant or intolerant to colchicine. Anti-IL-1 agents can control FMF attacks quite effectively and they have a promising role in the treatment of FMF.

Association between single nucleotide polymorphisms in prospective genes and susceptibility to ankylosing spondylitis and inflammatory bowel disease in a single centre in Turkey.

BACKGROUND/AIMS: To establish the prevalence of the single nucleotide polymorphisms (SNPs) of endoplasmic reticulum aminopeptidase 1 (ERAP1), IL-23 receptor (IL-23R), signal transducer and activator of transcription 3 (STAT-3) and Janus kinase 2 (JAK-2) in ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) in a Turkish population. MATERIALS AND METHODS: A total of 562 subjects who presented at the Ankara University internal medicine departments of rheumatology and gastroenterology outpatient clinics were recruited in this study, including 365 patients with AS, 197 patients with IBD and 230 healthy controls. ERAP1, IL-23R, STAT-3 and JAK-2) were genotyped in competitive allele-specific polymerase chain reactions. RESULTS: The ERAP1 (rs26653) polymorphism was found to increase the disease risk in patients with AS and IBD compared with the control group (p=0.02 and p=0.01, respectively). In addition, this polymorphism revealed a significant relationship with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI) in patients with AS (r=0.829, p < 0.001 and r=0.731, p < 0.001, respectively). CONCLUSION: The ERAP1 gene polymorphism might be a risk factor in the pathogenesis of AS and IBD. In contrast, IL-23R gene polymorphisms may serve a protective role in AS and IBD.