Coronavirus Disease 2019 Outcomes in Amyloid A Protein Amyloidosis Secondary to Rheumatic Conditions and Signs of Post- Coronavirus Disease 2019 Proteinuria Progression.

BACKGROUND: We aimed to investigate coronavirus diease 2019 (COVID-19) outcomes in patients with amyloid A protein (AA) amyloidosis secondary to rheumatic diseases and discuss factors associated with disease course. METHODS: A retrospective cohort was formed from adult patients with a diagnosis of AA amyloidosis. In patients with a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR) test, rates of hospitalization, intensive care unit admission and mortality due to COVID-19 were collected from medical records. Data regarding to demographics, comorbidities, laboratory tests, medical treatments, adherence to previous treatments during COVID-19 and treatment administered for COVID-19 were collected from hospital databases and patient reviews. RESULTS: In 96 patients with AA amyloidosis, 16 had COVID-19 with a positive PCR. Ten (62.5%) patients were hospitalized, 2 (12.5%) were admitted to ICU, 1 (6.25%) was died. Hospitalized patients tended to be older. Comorbidities seemed to be more frequent in hospitalized patients. None of the patients had rapid progression to end-stage renal disease post-COVID-19. Seven patients had pre-COVID-19 and post-COVID-19 proteinuria levels. Three had notable increase in proteinuria after COVID-19 in 2 of which amyloidosis treatment was revised accordingly. CONCLUSION: Despite high rates of hospitalization in AA amyloidosis patients, mortality was observed only in 1 patient. Progression of proteinuria requiring treatment adjustment may be an issue in these patients. Cite this article as: Güven SC, Erden A, Küçük H, et al. Coronavirus disease 2019 outcomes in amyloid A protein amyloidosis secondary to rheumatic conditions and signs of post-coronavirus disease 2019 proteinuria progression. Eur J Rheumatol. Published online April 4, 2024. DOI:10.5152/eurjrheum.2024.23050.

Unveiling cancer risk in ANCA-associated vasculitis: result from the Turkish Vasculitis Study Group (TRVaS).

To investigate cancer incidence in patients with ANCA-associated vasculitis (AAV), compare it with the age/sex-specific cancer risk of the Turkish population, and explore independent risk factors associated with cancer. This multicenter, incidence case-control study was conducted using the TRVaS registry. AAV patients without cancer history before AAV diagnosis were included. Demographic and AAV-related data of patients with and without an incident cancer were compared. Standardized cancer incidence rates were calculated using age-/sex-specific 2017 Turkish National Cancer Registry data for cancers (excluding non-melanoma skin cancers). Cox regression was performed to find factors related to incident cancers in AAV patients. Of 461 AAV patients (236 [51.2%] male), 19 had incident cancers after 2022.8 patient-years follow-up. Median (IQR) disease duration was 3.4 (5.5) years, and 58 (12.6%) patients died [7 with cancer and one without cancer (log-rank, p = 0.04)]. Cancer-diagnosed patients were older, mostly male, and more likely to have anti-PR3-ANCA positivity. The cumulative cyclophosphamide dose was similar in patients with and without cancer. Overall cancer risk in AAV was 2.1 (SIR) ((1.3-3.2), p = 0.004); lung and head-neck [primary target sites for AAV] cancers were the most common. In Cox regression, male sex and ≥ 60 years of age at AAV diagnosis were associated with increased cancer risk, while receiving rituximab was associated with decreased cancer risk. Cancer risk was 2.1 times higher in AAV patients than the age-/sex-specific cancer risk of the Turkish population population, despite a high rate of rituximab use and lower dose of cyclophosphamide doses. Vigilance in cancer screening for AAV patients covering lung, genitourinary, and head-neck regions, particularly in males and the elderly, is vital.

Effects of intrauterine device use on attack frequency and severity in woman of reproductive age with familial Mediterranean fever.

AIM: Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease in the world. There are known triggers to initiate an FMF attack, yet potential effects of intrauterine devices (IUD) in women of reproductive age have not been evaluated before. METHOD: Consecutive female patients with FMF who ever used IUD over the age of 18 were enrolled. Female patients with FMF were sub grouped according to the type of IUD they use. FMF attack frequency, severity, duration, presence of dysmenorrhea, severity of dysmenorrhea, having attacks during menstruation before and after IUD use were questioned. Demographic and clinical data were collected from hospital database. RESULTS: When all patients with IUD use were evaluated, it was found that the frequency of attacks increased after IUD insertion at 3rd and 12th months (median [min-max] attack frequency at 3rd month, 1 (0-3) vs 1 (0-6), p = 0.002, median [min-max] attack frequency at 12th month, 2 (0-12) vs 3.5 (0-18), p = 0.028). Attack severity measured by VAS pain was also significantly increased. Attack duration and menstrual pain was similar before and after IUD use. Attack frequency at 3rd and 12th months, attack severity and menstrual pain was all increased significantly in Cu-IUD users, whereas none of these parameters deteriorated in LNG-IUD group. CONCLUSION: IUD use, especially Cu-IUD, may increase the frequency and severity of attacks in female patients with FMF. Clinicians may benefit from considering LGN-IUD if IUDs are preferred as contraception in women of childbearing age with FMF.

Non-criteria autoantibodies in antiphospholipid syndrome may be associated with underlying disease activity.

BACKGROUND: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by persistent antiphospholipid antibodies (aPLs) with arterial and venous thrombosis and/or pregnancy morbidity. In recent years, several studies have highlighted the potential role of non-criteria aPL in diagnosing APS patients. AIM: This study aimed to determine the association of the presence of non-criteria aPL antibodies to the clinical and laboratory features of patients with a diagnosis of APS. METHODS: Eighty patients diagnosed with APS and under observation in the rheumatology clinic of Ankara City Hospital were assessed. Patient demographic and clinical features were meticulously recorded. Non-criteria antibodies tested in our center included antiphosphatidylserine IgA, antiphosphatidylserine IgM, beta 2 glycoprotein IgA, anti-cardiolipin IgA, antiphospholipid antibody IgG, and antiphospholipid antibody IgM. Antibodies from patients who were tested for at least one non-criteria antibody were documented. RESULTS: Out of 80 patients, 55 (68.8%) were tested for at least one non-criteria antibody, and 29 of those patients (52.7%) tested positive for at least one non-criteria antibody. The antiphospholipid antibody IgM and the beta 2 glycoprotein IgA were the most commonly tested non-criteria antibodies. Patients with non-criteria antibody positivity had a higher frequency of Ds DNA positivity and low complement (62.0% vs. 35.0%, p = 0.042; 69.0% vs. 38.0%, p = 0.023), respectively. In addition, positivity for anti-cardiolipin IgG and b2 glycoprotein IgG was significantly higher in the group positive for non-criteria antibodies (79% vs. 31%, p ≤ 0.001; 72.0% vs. 19%, p ≤ 0.001). There was no significant difference between the clinical features of patients with at least one positivity for non-criteria antibodies and those without. CONCLUSION: Systemic lupus erythematosus (SLE) is the most commonly associated disease with APS, being present in approximately 35% of cases [1]. Since the majority of the patient group in our study had APS that was secondary to SLE, non-criteria antibody positivity may be linked to the immunological activity of SLE. Large multicenter studies are necessary to investigate the clinical significance of isolated/combined positivity for criterion/non-criteria aPLs.

Low relapse rate in patients with giant cell arteritis in a multi-centre retrospective Turkish Registry.

OBJECTIVES: Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only protocol arms in controlled trials of tocilizumab and abatacept in 12-24 months. Herein, we aimed to assess the real-life relapse rates retrospectively in patients with GCA from Turkey. METHODS: We assembled a retrospective cohort of patients with GCA diagnosed according to ACR 1990 criteria from tertiary rheumatology centres in Turkey. All clinical data were abstracted from medical records. Relapse was defined as any new manifestation or increased acutephase response leading to the change of the GC dose or use of a new therapeutic agent by the treating physician. RESULTS: The study included 330 (F/M: 196/134) patients with GCA. The mean age at disease onset was 68.9±9 years. The most frequent symptom was headache. Polymyalgia rheumatica was also present in 81 (24.5%) patients. Elevation of acute phase reactants (ESR>50 mm/h or CRP>5 mg/l) was absent in 25 (7.6%) patients at diagnosis. Temporal artery biopsy was available in 241 (73%) patients, and 180 of them had positive histopathological findings for GCA. For remission induction, GC pulses (250-1000 methylprednisolone mg/3-7 days) were given to 69 (20.9%) patients, with further 0.5-1 mg/kg/day prednisolone continued in the whole group. Immunosuppressives as GC-sparing agents were used in 252 (76.4%) patients. During a follow-up of a median 26.5 (6-190) months, relapses occurred in 49 (18.8%) patients. No confounding factor was observed in relapse rates. GC treatment could be stopped in only 62 (23.8%) patients. Additionally, GC-related side effects developed in 64 (24.6%) patients, and 141 (66.2%) had at least one Vasculitis Damage Index (VDI) damage item present during follow-up. CONCLUSIONS: In this first multi-centre series of GCA from Turkey, we observed that only one-fifth of patients had relapses during a mean follow-up of 26 months, with 76.4% given a GC-sparing IS agent at diagnosis. At the end of follow-up, GC-related side effects developed in one-fourth of patients. Our results suggest that patients with GCA had a low relapse rate in real-life experience of a multi-centre retrospective Turkish registry, however with a significant presence of GC-associated side effects during follow-up.

Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis.

OBJECTIVES: To analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). METHODS: For the present study, the following variables were selected for harmonization and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD. RESULTS: The results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. CONCLUSIONS: For the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.

Influence of exposure to climate-related hazards in the phenotypic expression of primary Sjögren's syndrome.

OBJECTIVES: To analyse how the key components at the time of diagnosis of the Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards. METHODS: For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure. RESULTS: After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries. CONCLUSIONS: Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjögren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.

Neurological Involvement in Patients with Primary Sjögren's Syndrome: A Retrospective Cross-Sectional Study.

Background: To determine the rate and types of neurological involvement in patients with primary Sjögren's syndrome (pSS) and to evaluate predictive clinical and immunologic features of neurological involvement. Methods: We retrospectively assessed 2127 patients with an ICD-10 code for Sjögren recorded in the hospital database. Among these patients, those meeting the pSS classification criteria and having neurological symptoms and an objective evaluation accordingly were enrolled. After comparing the patients with and without neurological involvement, peripheral and central involvement subtypes were also compared within themselves. Results: A total of 199 pSS patients were enrolled and neurological involvement was found in 31.6%. Peripheral nervous system (PNS) involvement was found in 23.5% of the patients, and central nervous system (CNS) involvement was found in 34.3%. Patients with neurological involvement had a higher frequency of Schirmer's test, anti-Ro/SS-A and anti-La/SS-B positivity and the presence of interstitial lung disease, articular involvement, lymphadenopathy, anemia and hypocomplementemia than patients without those. In multivariate regression analysis, only articular involvement had a higher risk for the development of neurologic involvement [OR 10.01 (4.18-23.97), P 0.0001]. Among the patients with PNS, the frequency of anti-Ro/SS-A positivity, low C3 and Schirmer's test positivity were statistically increased compared to those who were not in PNS (P = 0.032, P = 0.044, and P = 0.029, respectively). When compared in terms of CNS involvement, patients with CNS involvement were younger, had a shorter disease duration, and had a higher frequency of anti-Ro/SS-A positivity than patients without those (P = 0.041, P = 0.027, and P = 0.046, respectively). Conclusions: In our study, it was shown that one third of the symptomatic pSS patients had objective neurological involvement. The presence of neurological symptoms should be considered, especially in patients with articular involvement in pSS.

Does decision tree analysis predict oral ulcer activity-related factors in patients with Behçet's syndrome?

OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.

The Possible Relation of Demodex and Facial Erythema in Connective Tissue Diseases.

Background: We aimed to investigate the frequency of Demodex infestation and clinical implications in connective tissue disease patients with facial erythema. Methods: Patients diagnosed with a connective tissue disease and had facial erythema were consecutively enrolled in the study from 2019-2020. An age and gender matched control group was formed from healthy volunteers. Presence of Demodex was investigated by standardized skin surface biopsy. Number of Demodex mites over 5 per centimeter square was considered meaningful for infestation. Topical or systemic metronidazole treatment was given to the connective tissue disease patients with Demodex infestation. Facial erythema visual analog scale was questioned in patients at treatment onset and one month after. Results: A total of 31 connective tissue disease patients with facial erythema were enrolled. Control group included 31 healthy volunteers. Demographics and comorbidities were similar between groups. Demodex infestation was present in 58.1% of the disease group and in 25.8% of the control group (P=0.01). Pruritus was the most common symptom in patients with infestation. Median (IQR) facial erythema visual analog scale score was 6 (3) at treatment onset and was 2 (2.5) one month later (P<0.001). Conclusion: When evaluating facial cutaneous lesions, Demodex infestation should not be overlooked in a patient group like connective tissue diseases with dysfunctional immune system.

Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study.

Background: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score. Methods: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables. Findings: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27-2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22-2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01-1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22-1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16-2) were independent predictors of SjS-related death. Interpretation: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS. Funding: Novartis.

Long-Term Results of Immunogenicity of Booster Vaccination against SARS-CoV-2 (Hybrid COV-RAPEL TR Study) in Turkiye: A Double-Blind, Randomized, Controlled, Multicenter Phase 2 Clinical Study.

The immunogenicity of vaccines decreases over time, causing a need for booster doses. This study aimed to present the long-term (Day 84) immunogenicity results of the double-blind, randomized, controlled, phase II Hybrid COV-RAPEL TR Study (NCT04979949), in which the TURKOVAC or CoronaVac vaccines were used as a booster after the second dose of primary vaccination with CoronaVac. A total of 190 participants from the Hybrid COV-RAPEL TR Study, who had both Day 28 and Day 84 immunogenicity results, were included. The immunogenicity on Day 84, regarding the neutralizing antibody positivity (Wuhan and Delta variants) and anti-spike immunoglobulin (Ig) G (IgG) antibody positivity, was compared between TURKOVAC and CoronaVac vaccine arms according to sex and age groups. Overall, antibody positivity showed a slight decrease on Day 84 vs. Day 28, but was not different between TURKOVAC and CoronaVac arms either for sexes or for age groups. However, TURKOVAC produced better antibody response against the Delta variant than CoronaVac, while CoronaVac was superior over TURKOVAC regarding neutralizing antibody positivity in the 50-60 years age group, regardless of the variant. A single booster dose, after the completion of the primary vaccination, increases antibody positivity on Day 28 which persists until Day 84 with a slight decrease. However, an additional booster dose may be required thereafter, since the decrease in antibody titer may be faster over time.

Pulmonary hypertension in Behçet's disease: echocardiographic screening and multidisciplinary approach.

BACKGROUND: Little is known about the prevalence and causes of pulmonary hypertension (PH) in Behçet's disease (BD). This study was conducted to determine the prevalence and causes of PH in BD. METHODS: In this descriptive study, we screened 154 patients with BD for PH using transthoracic echocardiography between February 2017 and October 2017. An estimated systolic pulmonary arterial pressure (sPAP ≥ 40 mmHg) was used as the cutoff value to define PH. Patients with BD were categorized into 5 groups according to organ involvement including mucocutaneous/ articular, ocular, vascular, gastrointestinal, and neurologic involvement. Additional laboratory and imaging results were obtained from hospital file records to determine the causes of PH. RESULTS: PH was detected in 17 (11%) patients. Nine (52.9%) of these patients had group II PH (due to left heart disease), 4 (23.5%) had IV PH (due to pulmonary arterial involvement), and 1 had III PH (due to chronic obstructive lung disease). The frequency of PH was higher in BD patients with vascular involvement than those without (52.9% vs 28.5%; p = 0.04). Among 10 patients with pulmonary artery involvement (PAI) 4 (40%) had PH. Although the vascular BD group had the highest rate of PH, we observed no statistically significant difference in the frequency of PH between the predefined BD subgroups. DISCUSSION: : PH is not rare in patients with BD. The majority of BD patients with PH are in group II or IV PH. Patients with vascularinvolvement carry a higher risk for the development of PH. Monitoring BD patients with PAI should be considered for the development of group IV PH.

Rheumatology experience with FDG PET / CT in inflammation of unknown origin: a single - centre report for determining factors associated with diagnostic precision.

BACKGROUND / AIM: The use of PET / CT is becoming more common in the elucidation of inflammatory processes in which the underlying cause cannot be determined by conventional examinations. Although PET / CT is an effective method for detecting inflammatory foci, the precise diagnosis may not be obtained in all cases. In addition, considering factors such as radiation exposure and cost, it becomes important to identify patients who can get results with PET / CT. In this study, it was aimed to examine the factors that can predict the differential diagnostic value of PET / CT by retrospectively scanning patients who underwent PET / CT for inflammation of unknown origin (IUO) in rheumatology practice. METHODS: Demographic, clinical and laboratory information of the patients followed up in our clinic and who underwent PET / CT for differential diagnosis were enrolled. Whether they were diagnosed after PET / CT and during the follow - up period, and their diagnoses were examined. RESULTS: A total of 132 patients were included in the study. A previous diagnosis of rheumatic disease was present in 28.8 % of the patients, and a history of malignancy was present in 2.3 % . The patients were divided into three groups: group 1 patients with increased FDG uptake in PET / CT and diagnosis confirmed by PET / CT, group 2 patients with increased FDG uptake in PET / CT but diagnosis was not confirmed, and group 3 patients without increased FDG uptake in PET / CT. Increased FDG uptake in PET / CT was detected in 73 % of the patients. While PET / CT helped the diagnosis in 47 (35.6 %) patients (group 1), it did not help the diagnosis in 85 (64.4 %) (groups 2 and 3). Thirty - one (65.9 %) of the diagnosed patients were diagnosed with a rheumatologic disease. When the 3 groups were compared, male gender, advanced age, CRP levels, presence of constitutional symptoms, SUVmax values and number of different organs with increased FDG uptake were higher in Group 1. Sixty - six percent and 74 % of the patients in groups 2 and 3 were not diagnosed during the follow - up period. No patient in group 3 was diagnosed with malignancy during follow - up. CONCLUSION: PET / CT has high diagnostic value when combined with clinical and laboratory data in the diagnosis of IUO. Our study revealed that various factors can affect the diagnostic value of PET / CT. Similar to the literature, the statistically significant difference in CRP levels shows that patients with high CRP levels are more likely to be diagnosed with an aetiology in PET / CT. Although detection of involvement in PET / CT is not always diagnostic, there was an important finding that no malignancy was detected in the follow - up in any patient without PET / CT involvement. Key points • PET / CT is an effective method for detecting inflammatory foci. • PET / CT has proven to be effective in the diagnosis of rheumatological diseases, the extent of disease and the evaluation of response to treatment. • Indications for the use of PET / CT in the field of rheumatology and the associated factors and clinical features supporting the diagnosis with PET / CT are still to be fully clarified. • In routine practice, with PET / CT, both delays in diagnosis and examinations performed during diagnosis and the cost can be reduced.

Tofacitinib experience in patients with enteropathic arthritis.

Background/aim: The JAK-STAT pathway is involved in the pathogenesis of both the inflammatory bowel disease (IBD) and spondyloarthropathy group of diseases. The purpose of this study was to evaluate the effectiveness of tofacitinib, a Janus kinase inhibitor, in the treatment of enteropathic arthritis (EA). Materials & methods: The study included seven patients, four from the authors' follow-up and three from the literature. All cases were recorded for demographic characteristics, comorbidities, IBD and EA symptoms, medical treatments and changes in clinical and laboratory results with treatment. Results & conclusion: Clinical and laboratory remission in terms of IBD and EA was achieved in three patients after tofacitinib treatment. For both spondyloarthritis spectrum diseases and IBD, tofacitinib may be an appropriate choice, as its efficacy has been shown in both conditions.

Tofacitinib, which inhibits the JAK enzyme, is an oral, nonbiologic, disease-modifying drug used in the treatment of rheumatologic diseases. Tofacitinib modulates the immune response and reduces or prevents inflammation. There are limited data on the efficacy of tofacitinib for the treatment of enteropathic arthritis. This study aimed to evaluate the efficacy of tofacitinib in the treatment of enteropathic arthritis. Seven patients, four from the authors' follow-up and three from the literature, were included in the study. All cases were recorded in terms of demographic characteristics, comorbidities, symptoms of inflammatory bowel disease and enteropathic arthritis, medical treatments and changes in treatment and clinical and laboratory results. After tofacitinib treatment, clinical and laboratory improvement was achieved in three patients. As a result, tofacitinib may be a suitable choice for enteropathic arthritis.

Semaphorin 3A levels in vascular and nonvascular phenotypes in systemic sclerosis.

OBJECTIVE: Semaphorin 3A (Sema3A) plays a regulatory role in immune responses. The aim of this study was to evaluate Sema3A levels in patients with systemic sclerosis (SSc), especially in major vascular involvements such as digital ulcer (DU), scleroderma renal crisis (SRC), pulmonary arterial hypertension (PAH), and to compare Sema3A level with SSc disease activity. METHODS: In SSc patients, patients with DU, SRC, or PAH were grouped as major vascular involvements and those without as nonvascular, and Sema3A levels were compared between the groups and with a healthy control group. The Sema3A levels and acute phase reactants in SSc patients, as well as their association with the Valentini disease activity index and modified Rodnan skin score, were evaluated. RESULTS: The Sema3A values (mean ±â€…SD) were 57.60 ±â€…19.81 ng/mL in the control group (n = 31), 44.32 ±â€…5.87 ng/mL in patients with major vascular involvement SSc (n = 21), and 49.96 ±â€…14.00 ng/mL in the nonvascular SSc group (n = 35). When all SSc patients were examined as a single group, the mean Sema3A value was significantly lower than controls (P = .016). The SSc with major vascular involvement group had significantly lower Sema3A levels than SSc with nonmajor vascular involvement group (P = .04). No correlation was found between Sema3A, acute phase reactants, and disease activity scores. Also, no relationship was observed between Sema3A levels and diffuse (48.36 ±â€…11.47 ng/mL) or limited (47.43 ±â€…12.38 ng/mL) SSc types (P = .775). CONCLUSION: Our study suggests that Sema3A may play a significant role in the pathogenesis of vasculopathy and can be used as a biomarker in SSc patients with vascular complications such as DU and PAH.

Ustekinumab in enteropathic arthritis.

Objective: The aim of this study was to evaluate the efficacy of ustekinumab in the treatment of enteropathic arthritis. Materials & methods: A systematic literature search was performed in the Pubmed database of publications between January 2010 and October 2021. Demographic characteristics, comorbidities, inflammatory bowel disease and enteropathic arthritis symptoms, other extraintestinal findings, medical treatments and clinical and laboratory findings for all cases were recorded. Results: A total of 11 patients were included. While clinical and laboratory remission was achieved in terms of inflammatory bowel disease in all patients and enteropathic arthritis in nine patients after ustekinumab treatment, other extraintestinal findings for all patients completely regressed after treatment. Conclusion: Ustekinumab may be an appropriate treatment option for this patient group, considering both pathogenesis and successful treatment responses.

Treatments targeting the IL-23 pathway are highly effective in psoriasis, psoriatic arthritis and inflammatory bowel diseases. However, their efficacy in patients with enteropathic arthritis with peripheral and/or axial joint involvement is unclear. Ustekinumab may be a valuable option for patients who cannot adhere to other treatment options due to side effects or ineffectiveness. Considering its positive effects on joint involvement in patients with psoriatic arthritis, the current work was designed to investigate the efficacy of ustekinumab in patients with enteropathic arthritis on both gut and extraintestinal involvement, particularly musculoskeletal symptoms.

The impact of antiphospholipid antibodies in Takayasu arteritis.

BACKGROUND: The significance of antiphospholipid antibodies (aPL) is controversial in Takayasu arteritis (TA). This study was conducted to explore the frequency of aPL and their association with disease-related complications in TA. METHODS: : This cross-sectional study was conducted to investigate the presence of anti-cardiolipin (aCL), anti-beta 2 glycoprotein- 1(aß2G1) antibodies, and lupus anticoagulant (LA) in TA patients. TA patients admitted to the Department of Rheumatology of Hacettepe University Faculty of Medicine between December 2015 and September 2016 who fulfilled the American College of Rheumatology (ACR) classification criteria for TA were consecutively enrolled in the study. Patients were grouped according to aPL positivity and compared in terms of disease manifestations, type of vascular involvement at diagnosis, and vascular complications/interventions attributable to TA. RESULTS: Fifty-three TA (49 female) patients were enrolled in the study. We detected 9 (16.9%) patients with IgM and/or IgG aß2G1 and/or LA positivity. There were no patients with positive aCL. All aß2G1 titers were low. There were no differences in terms of symptoms, signs, type of vascular involvement, the number of patients with disease-related complications or vascular interventions/surgery between aPL (+) and aPL(-) groups (p > 0.05 for all). The number of patients with thrombotic lesions was similar between the groups (p > 0.05). There were no patients with a history of venous thrombosis or on anticoagulant treatment in the aPL(+) group. Only 1 patient with IgM aß2G1 (+) had a history of pregnancy loss. DISCUSSION: Our results indicate that aPL positivity is not rare in TA. On the other hand, all aPL titers were low and no differences were found in the frequency of disease-related complications between aPL(+) and aPL(-) patient groups. Only TA patients with atypical manifestations with high suspicion of aPL-related complications should be considered to be investigated for aPL.

Effects of breast milk on Behçet's disease clinical features.

BACKGROUND: The etiology of Behçet's disease (BD) is not clearly known, however, abnormal activity in T helper (Th) 1, Th 17, and regulatory T cells (Treg) has critical importance in pathogenesis. It has been shown that the intestinal microbiome can be effective in the modulation of these immune abnormalities in BD patients. Breastfeeding increases the maturation of the infant's intestinal permeability by affecting the newborn's immature intestinal microbiome and metagenome. We aimed to examine the effects of breastfeeding on disease related symptoms, organ involvements and course of the disease in BD patients. METHODS: This study was designed as a cross-sectional study in Ankara City Hospital rheumatology clinic between December 2021 and March 2022. Patients who were diagnosed with BD by meeting the criteria of the 'International Study Group' and whose information we could access by agreeing to participate in the study were enrolled. The mothers of the patients were also contacted and asked whether these patients were breastfed, the duration of breastfeeding, and the mode of birth. Demographic and clinical data of the patients, comorbid diseases, and drugs used for BD were collected from the records in the hospital database. The presence of sacroiliitis in patients was evaluated with sacroiliac X-ray and/or magnetic resonance imaging (MRI), which was requested because of low back pain symptoms and only patients with previous sacroiliac imaging for low back pain were included in the study. BD-related organ damage was measured by the Vasculitis Damage Index (VDI) and Behçet's syndrome Overall Damage Index (BODI) scores. RESULTS: : A total of 304 patients were included in the study. The percentage of patients who were reported to have ever breastfed (median duration (IQR): 12(12) months, 33.5% < 6 months, 66.4% ≥ 6 months, and 59.6% ≥ 12 months) is 92%. When the breastfed and nonbreastfed patients were compared, 6.8% of the breastfed patients needed TNF-i against 18.2% of the nonbreastfed patients (p = 0.052). While the rate of having at least one comorbidity was 26.4% for those who were breastfed, this rate was 50% for those who had never been breastfed. When the organ and system involvements of the patients were compared, the incidence of sacroiliitis was statistically significantly higher in the nonbreastfed group (p = 0.025). Patients who were breastfed for less than 6 months were diagnosed with BD at an earlier age than those who were breastfed for more than 6 months, and those who were breastfed for less than 12 months compared to those who were breastfed for more than 12 months (respectively, p = 0.039, p = 0.035). DISCUSSION: Our results imply that history of breastfeeding may have some positive effects on the course of the disease in BD patients.

COVID-19 disease frequency, risk factors, and re-infection rates in patients with autoimmune rheumatic disease receiving rituximab.

INTRODUCTION: Rituximab, which is used in autoimmune rheumatic diseases (ARD), can cause both an increased risk of development of COVID-19 disease and re-infection due to its potent and long-acting immunosuppression. So, we aimed to evaluate the frequency, risk factors and re-infection rates of COVID-19 in ARD patients receiving rituximab. METHODS: A single-center retrospective study was performed with patients receiving rituximab for ARD in 12 months before the onset of COVID-19 in Turkey. The data regarding severe acute respiratory syndrome-coronavirus 2 reverse transcription polymerized chain reaction (RT-PCR) test, clinical, laboratory, and mortality data of all patients were collected from medical records. Logistic regression analysis was used for predictors of COVID-19 disease. COVID-19 re-infection was defined as RT-PCR positivity and recurrence of acute COVID-19 symptoms after at least 1 negative RT-PCR in patients with clinical improvement. RESULTS: Ninety-eight ARD patients with rituximab were evaluated and 23 (23%) of them had COVID-19. The presence of hypogammaglobulinemia increased the risk of COVID-19 disease 8-fold. COVID-19 pneumonia occurred in 13 (57%) and these patients' age was higher than those without pneumonia (59.6 ± 11.8 vs 44.9 ± 14.2 years, P = 0.013). Mortality due to COVID-19 was 13% and COVID-19 re-infection was seen in 20% of survivors. CONCLUSION: Regardless of the underlying rheumatic disease and organ involvements, hypogammaglobulinemia in ARD could be a risk factor for COVID-19 development, and advanced age could be for COVID-19 severity. Moreover, COVID-19 re-infection rates are high.