Pelvic parameters as prognostic factors of radiographic progression in classical Ankylosing Spondylitis: A prospective follow-up data.

Radiographic progression in Ankylosing spondylitis (AS) is driven by mechanical strain. A well-balanced spine provides a favorable weight distribution across the entheses. Pelvic parameters are useful in assessing the shape of the spine. The present study aimed to prospectively investigate the predictive value of pelvic parameters for radiographic progression in AS. This non-interventional, observational, and prospective study enrolled AS patients fulfilling the modified New York criteria (mNY) currently under follow-up in the MARS (MARmara Spondyloarthritis) outpatient clinics. The primary objective was to investigate the relationship between the baseline pelvic parameters and radiographic progression in the spine. Two trained radiologists (EB, OB) independently assessed the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). An orthopedic surgeon (AHA) and a radiologist (EB) derived the pelvic parameters. Patients with no bridging or bamboo spine were included in the final analysis. Risk assessment for radiographic progression, defined as a two-unit increase in mSASSS or developing a new syndesmophyte every two years, was done using uni- and multivariate logistic regression analyses. Radiographs of 69 AS patients were analyzed. The median (IQR 25-75) prospective follow-up was 47.7 (34.6-52.8) months. Only 33.3% (23/69) had radiographic progression. The pelvic tilt (PT) was lower in patients with radiographic progression (p = 0.037) and each degree of decrease in PT provided a 9% increase in risk for radiographic progression. Male patients were 7.5 times more likely to progress. Pelvic parameters provide a prognostic insight into the radiographic progression in AS. Our observations may aid in selecting patient-specific interventions in addition to anti-inflammatory treatments.

Clinical and laboratory factors associated with bamboo spine in patients with axial spondyloarthritis: are there clues for bamboo spine?

OBJECTIVES: To analyse the clinical and laboratory factors associated with bamboo spine. METHODS: Data of patients fulfilling the 2009 ASAS classification criteria for axial spondyloarthritis, registered in the national, multicentre, longitudinal, and observational database of TReasure was analysed. Radiographs were assessed using the Bath Ankylosing Spondylitis Radiologic Index (BASRI). Data of patients with a bamboo spine (Group 1) was compared to data derived from patients with a longstanding disease of at least 15 years but no syndesmophytes (Group 2). RESULTS: Out of the 5060 patients, 1246 had eligible radiographs. There were 111 patients (8.9%) with a bamboo spine. Male sex was more common among patients with bamboo spine. The median BMI of 27.7 (25.8-31.1) in Group1 was higher than the BMI of 25.9 (22.9-29.2) in Group 2 (p<0.001). Hip arthritis, present or documented by a physician, was more common in Group 1 [(58/108 (53.7%) vs. 35/103 (34%), p=0.004]. There was a tendency towards a more prevalent enthesitis in these patients [29.1% (25/86) vs. 15.9%(11/69), p=0.054]. HLA-B27 status did not differ between groups. Smoking was more prevalent in Group 1. Multivariate logistic regression analysis revealed that male sex, body mass index, hip arthritis, and enthesitis are associated with bamboo spine in axSpA. CONCLUSIONS: Bamboo spine was more common in the male sex and associated with a delay in diagnosis, high BMI, hip involvement, and enthesitis. The constellation of increased body weight, hip arthritis, and enthesitis may imply that mechanical stress contributes to radiographic damage in the presence of chronic inflammation.

Tuberculin skin test before biologic and targeted therapies: does the same rule apply for all?

This study aimed to compare Tuberculin Skin Test (TST) and QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients scheduled for biological and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) in a Bacillus Calmette-Guérin-vaccinated population. Adult RA (n = 206) and SpA (n = 392) patients from the TReasure database who had both TST and QFT-GIT prior to initiation of biological and targeted synthetic DMARDs were included in the study. Demographic and disease characteristics along with pre-biologic DMARD and steroid use were recorded. The distribution of TST and performance with respect to QFT-GIT were compared between RA and SpA groups. Pre-biologic conventional DMARD and steroid use was higher in the RA group. TST positivity rates were 44.2% in RA and 69.1% in SpA for a 5 mm cutoff (p < 0.001). Only 8.9% and 15% of the patients with RA and SpA, respectively, tested positive by QFT-GIT. The two tests poorly agreed in both groups at a TST cutoff of 5 mm and increasing the TST cutoff only slightly increased the agreement. Among age, sex, education and smoking status, pre-biologic steroid and conventional DMARD use, disease group, and QFT-GIT positivity, which were associated with a 5 mm or higher TST, only disease group (SpA) and QFT-GIT positivity remained significant in multiple logistic regression. TST positivity was more pronounced in SpA compared to that in RA and this was not explainable by pre-biologic DMARD and steroid use. The agreement of TST with QFT-GIT was poor in both groups. Using a 5 mm TST cutoff for both diseases could result in overestimating LTBI in SpA.

Physicians' Biological Drug Preference in Patients With Rheumatoid Arthritis and Spondyloarthritis With a History of Malignancy: Perspectives From the Treasure Database.

OBJECTIVE: Because of concerns about malignancy risks, using biological disease-modifying antirheumatic drugs (bDMARDs) in patients with a history of malignancy remains a challenging issue in rheumatology practice. This study aimed to investigate bDMARD preferences of physicians when treating of rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients with a history of malignancy. METHODS: The data for this cross-sectional study were gathered from the TReasure database using a date range of December 2017 and January 2020. Biological disease-modifying antirheumatic drug preferences were analyzed for 40 RA patients and 25 SpA patients with a history of malignancy. RESULTS: The most frequently prescribed bDMARD was rituximab, which was given to 28 RA patients (70%). For 25 patients (62.5%), the time between the diagnosis of malignancy and starting on a bDMARD regimen was less than 60 months, with a median interval of 43.5 months. Among SpA patients, the preferred bDMARDs were secukinumab and etanercept, which were each administered to 7 patients (28%). For 13 SpA patients (52%), the time between the diagnosis of malignancy and starting on bDMARDs was less than 60 months, with a median interval of 97 months. CONCLUSIONS: The observed bDMARD preferences may be related to the therapeutic effects of rituximab on lymphoproliferative malignancies, the protective effects of secukinumab on tumor progression, and the short half-life of etanercept. Biological disease-modifying antirheumatic drugs should be used in RA and SpA patients with malignancy in case of high inflammatory activity.

Hemophagocytic lymphohistiocytosis: a review inspired by the COVID-19 pandemic.

Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis (HLH) is an acute and rapidly progressive systemic inflammatory disorder characterized by cytopenia, excessive cytokine production, and hyperferritinemia. Common clinical manifestations of HLH are acute unremitting fever, lymphadenopathy, hepatosplenomegaly, and multiorgan failure. Due to a massive cytokine release, this clinical condition is considered as a cytokine storm syndrome. HPS has primary and acquired (secondary, reactive) forms. Its primary form is mostly seen in childhood and caused by various mutations with genetic inheritance and, therefore, is called familial HLH. Secondary HLH may be caused in the presence of an underlying disorder, that is, secondary to a malignant, infectious, or autoimmune/autoinflammatory stimulus. This paper aims to review the pathogenesis and the clinical picture of HLH, and its severe complication, the cytokine storm, with a special emphasis on the developed classification criteria sets for rheumatologists, since COVID-19 infection has clinical symptoms resembling those of the common rheumatologic conditions and possibly triggers HLH. MED-LINE/Pubmed was searched from inception to April 2020, and the following terms were used for data searching: "hemophagocytic syndrome" OR "macrophage activation syndrome" OR "hemophagocytic lymphohistiocytosis", OR "cytokine storm". Finally, AND "COVID-19" was included in this algorithm. The selection is restricted to the past 5 years and limited numbers of earlier key references were manually selected. Only full-text manuscripts, published in an English language peer-reviewed journal were included. Manuscript selection procedure and numbers are given in Fig. 2. Briefly, the database search with the following terms of "Hemophagocytic syndrome" OR "Macrophage activation syndrome" OR "Hemophagocytic lymphohistiocytosis" OR "Cytokine storm" yielded 6744 results from inception to April 2020. The selection is restricted to the past 5 years and only limited numbers of earlier key references were selected, and this algorithm resulted in 3080 manuscripts. The addition of (AND "COVID-19") resulted in 115 publications of which 47 studies, together with four sections of an online book were used in the final review. No statistical method was used. HLH is triggered by genetic conditions, infections, malignancies, autoimmune-autoinflammatory diseases, and some drugs. In COVID-19 patients, secondary HLH and cytokine storm may be responsible for unexplained progressive fever, cytopenia, ARDS, neurological and renal impairment. Differentiation between the primary and secondary forms of HLH is utterly important, since primary form of HLH requires complicated treatments such as hematopoietic stem cell transplantation. Further studies addressing the performance of HScore and other recommendations in the classification of these patients is necessary.

The assessment of malnutrition and severity of gastrointestinal disease by using symptom-based questionnaires in systemic sclerosis: is it related to severe organ involvement or capillary rarefaction at microcirculation?

OBJECTIVES: Gastrointestinal (GI) system is commonly affected in sytemic sclerosis (SSc) patients who are also known to be at risk for malnutrition. We aimed to investigate the relationship between severity of GI disease, malnutrition and severity of organ involvement including microvasculopathy. METHODS: A hundred and thirty-four SSc patients were included into the study; disease activity and severity, the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Scleroderma Gastrointestinal scale 2.0 (UCLA SCTC GIT 2.0) and malnutrition universal screening tool (MUST) were cross-sectionally assessed. Nailfold video-capillaroscopy(NVC) was performed to evaluate microvasculopathy. RESULTS: SSc patients who are at medium to high risk for malnutrition (n=20); had more frequently limited pulmonary function, lung involvement, pulmonary hypertension, capillary rarefaction and NVC late pattern than those at low risk for malnutrition. Capillary rarefaction (≤6/mm) was shown to be independently associated with medium to high risk for malnutrition defined by using MUST. Capillary rarefaction and severe skin involvement were found to be independently related to 'severe' or 'very severe' GI disease defined by using UCLA SCTC GIT 2.0. UCLA SCTC GIT 2.0 scores were not found to be good discriminative in patients at risk for malnutrition allowing for a ROC curve of area under the curve (AUC)<0.8). CONCLUSIONS: Assessment of gastrointestinal complaints and nutritional status by using symptom based questionnaires reflected the severity of GI disease and malnutrition including some limitations. Capillary rarefaction and severe skin involvement might be determining factors for malnutrition risk and severe GI disease.

An Assessment in SpondyloArthritis International Society (ASAS)-endorsed definition of clinically important worsening in axial spondyloarthritis based on ASDAS.

INTRODUCTION: In a previous phase, 12 draft definitions for clinically important worsening in axial spondyloarthritis (axSpA) were selected, of which 3 were based on absolute changes in Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP (ASDAS). The objective here was to select the best cut-off for ASDAS for clinically important worsening in axSpA for use in clinical trials and observational studies. METHODS: An international longitudinal prospective study evaluating stable patients with axSpA was conducted. Data necessary to calculate ASDAS were collected at two consecutive visits (spaced 7 days to 6 months). Sensitivity and specificity of the three cut-offs for change in ASDAS were tested against the patient's subjective assessment of worsening as the external standard (ie, the patient reporting that he had worsened and felt a need for treatment intensification). Final selection was made by a consensus and voting procedure among Assessment of SpondyloArthritis International Society (ASAS) members. RESULTS: In total, 1169 patients with axSpA were analysed: 64.8% were male and had a mean age of 41.7 (SD 12.4) years. At the second visit, 127 (10.9%) patients judged their situation as worsened.Sensitivity and specificity for an increase of at least 0.6, 0.9 and 1.1 ASDAS points to detect patient-reported worsening were 0.55 (Se) and 0.91 (Sp), 0.38 (Se) and 0.96 (Sp), and 0.33 (Se) and 0.98 (Sp), respectively. The ASAS consensus was to define clinically important worsening as an increase in ASDAS of at least 0.9 points. CONCLUSION: This data-driven ASAS consensus process resulted in an ASDAS-based cut-off value defining clinically important worsening in axSpA for use in trials.

Limited reliability of radiographic assessment of spinal progression in ankylosing spondylitis.

Objectives: Conventional radiography is key to assessing AS-related spinal involvement and has become increasingly important given that spinal fusion may continue under biologic therapy. We aimed to compare the reliability of radiographic scoring of the spine by using different approaches to understand how different readers agree on overall scores and on individual findings. Method: Six investigators scored 68 plain radiographs of the cervical and lumbar spine of 34 patients with a 2-year interval, for erosions, sclerosis, squaring, syndesmophytes and ankyloses using the Spondyloarthritis Radiography (SPAR) module. The intraclass correlation coefficients were calculated compared with two gold standards. The reproducibility of each finding in 1632 vertebral corners and new syndesmophytes in each corner was calculated by kappa analysis and positive agreement rates. Results: The intraclass correlation coefficients mostly revealed good to excellent agreement with the gold standards (0.69-0.95). The kappa analysis showed worse agreement, being relatively higher for syndesmophytes (0.163-0.559) and ankylosis (0.48-0.95). Positive agreement rates showed that erosions were never detected at the same vertebral corner by two readers (positive agreement rate: 0%). The mean (range) positive agreement rates were 10.1% (0-27.7%) for sclerosis and 19.2% (0-59.7%) for squaring, and were higher for syndesmophytes [38.8% (21.4-62.5%)] and ankylosis [77.3% (64-95.3%)]. Conclusion: Our results show that there is a poor agreement on the presence of grade 1 lesions included in the Modified Stoke Ankylosing Spondylitis Spine Score-mostly for erosions and sclerosis-which may increase the measurement error. The currently used definitions of reliability have a risk of overestimating reproducibility.

The 2013 ACC/AHA 10-year atherosclerotic cardiovascular disease risk index is better than SCORE and QRisk II in rheumatoid arthritis: is it enough?

OBJECTIVE: To determine the ability of the new American College of Cardiology and American Heart Association (ACC/AHA) 10-year atherosclerotic cardiovascular disease (ASCVD) risk algorithm in detecting high cardiovascular (CV) risk, RA patients identified by carotid ultrasonography (US) were compared with Systematic Coronary Risk Evaluation (SCORE) and QRisk II algorithms. METHODS: SCORE, QRisk II, 2013 ACC/AHA 10-year ASCVD risk and EULAR recommended modified versions were calculated in 216 RA patients. In sonographic evaluation, carotid intima-media thickness >0.90 mm and/or carotid plaques were used as the gold standard test for subclinical atherosclerosis and high CV risk (US+). RESULTS: Eleven (5.1%), 15 (6.9%) and 44 (20.4%) patients were defined as having high CV risk according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. Fifty-two (24.1%) patients were US + and of those, 8 (15.4%), 7 (13.5%) and 23 (44.2%) patients were classified as high CV risk according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. The ACC/AHA 10-year ASCVD risk index better identified US + patients than SCORE and QRisk II (P < 0.0001). With EULAR modification, reclassification from moderate to high risk occurred only in two, five and seven patients according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. CONCLUSION: The 2013 ACC/AHA 10-year ASCVD risk estimator was better than the SCORE and QRisk II indices in RA, but still failed to identify 55% of high risk patients. Furthermore adjustment of threshold and EULAR modification did not work well.

A relationship between spinal new bone formation in ankylosing spondylitis and the sonographically determined Achilles tendon enthesophytes.

Spinal new bone formation is a major but incompletely understood manifestation of ankylosing spondylitis (AS). We explored the relationship between spinal new bone formation and ultrasound (US)-determined Achilles enthesophytes to test the hypothesis that spinal new bone formation is part of a generalized enthesis bone-forming phenotype. A multicenter, case control study of 225 consecutive AS patients and 95 age/body mass index (BMI) matched healthy controls (HC) was performed. US scans of Achilles tendons and cervical and lumbar spine radiographs were obtained. All images were centrally scored by one investigator for US and one for radiographs, blinded to medical data. The relation between syndesmophytes (by modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and the number of syndesmophytes) and enthesophytes (with a semi-quantitative scoring of the US findings) was investigated. AS patients had significantly higher US enthesophyte scores than HCs (2.1(1.6) vs. 1.6(1.6); p = 0.004). The difference was significant in males (p = 0.001) but not in females (p = 0.5). The enthesophyte scores significantly correlated with mSASSS scores (ρ = 0.274, p < 0.0001) with the association even stronger in males (enthesophyte scores vs. mSASSS ρ = 0.337, p < 0.0001). In multiple regression analysis, age, BMI, enthesophyte scores and disease duration were significantly associated with syndesmophytes in males, and keeping all other variables constant, increasing US enthesophyte scores increased the odds of having syndesmophytes by 67%. Male AS patients that have more severe US-determined Achilles enthesophyte also associated spinal syndesmophytes suggesting a bone-forming gender-specific phenotype that could be a useful marker predicting of new bone formation.

Epidemiological characteristics of hepatitis B and C in patients with inflammatory arthritis: Implications from treasure database.

Objectives: This study aimed to evaluate the hepatitis B (HBV) and C (HCV) frequency and clinical characteristics among patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) who receive biological treatments. Patients and methods: The observational study was conducted with patients from the TReasure database, a web-based prospective observational registry collecting data from 17 centers across Türkiye, between December 2017 and June 2021. From this database, 3,147 RA patients (2,502 males, 645 females; median age 56 years; range, 44 to 64 years) and 6,071 SpA patients (2,709 males, 3,362 females; median age 43 years; range, 36 to 52 years) were analyzed in terms of viral hepatitis, patient characteristics, and treatments used. Results: The screening rate for HBV was 97% in RA and 94.2% in SpA patients. Hepatitis B surface antigen (HBsAg) positivity rates were 2.6% and 2%, hepatitis B surface antibody positivity rates were 32.3% and 34%, hepatitis B core antibody positivity rates were 20.3% and 12.5%, HBV DNA (deoxyribonucleic acid) positivity rates were 3.5% and 12.5%, and antibody against HCV positivity rates were 0.8% and 0.3% in RA and SpA patients, respectively. The HBsAg-positive patients were older and had more comorbidities, including hypertension, diabetes, and coronary artery disease. In addition, rheumatoid factor (RF) positivity was more common in HBsAg-positive cases. The most frequently prescribed biologic disease-modifying antirheumatic drugs were adalimumab (28.5%), etanercept (27%), tofacitinib (23.4%), and tocilizumab (21.5%) in the RA group and adalimumab (48.1%), etanercept (31.4%), infliximab (22.6%), and certolizumab (21.1%) in the SpA group. Hepatitis B reactivation was observed in one RA patient during treatment, who received rituximab and prophylaxis with tenofovir. Conclusion: The epidemiological characteristics of patients with rheumatic diseases and viral hepatitis are essential for effective patient management. This study provided the most recent epidemiological characteristics from the prospective TReasure database, one of the comprehensive registries in rheumatology practice.

Recent advances in the diagnosis and therapy of large vessel vasculitis.

Large vessel vasculitis (LVV), including Takayasu arteritis (TAK) and giant cell arteritis (GCA), causes granulomatous vascular inflammation mainly in large vessels, and is the most common primary vasculitis in adults. Vascular inflammation may evoke many clinical features including vision impairment, stroke, limb ischemia, and aortic aneurysms. The best way to diagnose LVV is to combine medical history, physical examination, various laboratory tests, and imaging modalities. Progress in imaging modalities facilitated early diagnosis and follow­up of the disease activity. Conventional angiography is no longer the gold standard for the diagnosis of TAK. Similarly, temporal artery biopsy is no longer the only tool for diagnosing cranial GCA. In selected cases, color Doppler ultrasound may be used for this purpose. Despite some similarities, TAK and GCA differ in many aspects and they are different diseases. They also have different clinical subtypes. The presence of aortitis does not always implicate the diagnosis of TAK or GCA; infectious aortitis, as well as noninfectious aortitis associated with other autoimmune rheumatic diseases should be excluded. Treatment of LVV includes glucocorticoids (GCs), conventional immunosuppressive agents, and biological drugs. Tumor necrosis factor inhibitors are ineffective in GCA but effective in TAK. On the other hand, tocilizumab may be used to treat both diseases. Promising targeted therapies evaluated in ongoing clinical trials include, for example, anti­IL­12/23 (ustekinumab), anti­IL­17 (secukinumab), anti­IL­1 (anakinra), anti­IL­23 (guselkumab), anti­cytotoxic T­lymphocyte antigen 4 (abatacept), Janus kinase inhibitors (tofacitinib and upadacitinib), anti­granulocyte / macrophage colony­stimulating factor (mavrilimumab), and endothelin receptor (bosentan) therapies.

Pathogenesis and treatment of cytokine storm in COVID-19.

COVID-19 is a viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that killed a large number of patients around the world. A hyperinflammatory state resulting in a cytokine storm and adult respiratory distress syndrome seems to be the major cause of the death. Many mechanisms have been suggested in the pathogenesis of COVID-19 associated cytokine storm (COVID-CS). Insufficient viral clearance and persistence of a strong cytokine response despite inadequate antiviral immunity seem to be the main mechanisms underlying the pathogenesis. The diagnosis of COVID-19 is based on relatively constant clinical symptoms, clinical findings, laboratory tests, and imaging techniques, while the diagnosis of COVID-CS is a rather dynamic process, based on evolving or newly emerging findings during the clinical course. Management of COVID-19 consists of using antiviral agents to inhibit SARS-CoV-2 replication and treating potential complications including the cytokine storm together with general supportive measures. COVID-CS may be treated using appropriate immunosuppressive and immunomodulatory drugs that reduce the level of inappropriate systemic inflammation, which has the potential to cause organ damage. Currently corticosteroids, IL-6 blockers, or IL-1 blockers are most widely used for treating COVID-CS.

Interleukin-1 Inhibitors and Vaccination Including COVID-19 in Inflammatory Rheumatic Diseases: A Nonsystematic Review.

Newly emerging variants of coronavirus 2 (SARS-CoV-2) raise concerns about the spread of the disease, and with the rising case numbers, the Coronavirus disease 2019 (COVID-19) remains a challenging medical emergency towards the end of the year 2021. Swiftly developed novel vaccines aid in the prevention of the spread, and it seems that a specific cure will not be at hand soon. The prognosis of COVID-19 in patients with autoimmune/autoinflammatory rheumatic diseases (AIIRD) is more severe when compared to the otherwise healthy population, and vaccination is essential. Evidence for both the efficacy and safety of COVID-19 vaccination in AIIRD under immunosuppression is accumulating, but the effect of Interleukin-1 on vaccination in general and in AIIRD patients is rarely addressed in the current literature. In light of the current literature, it seems that the level of agreement on the timing of COVID-19 vaccination is moderate in patients using IL-1 blockers, and expert opinions may vary. Generally, it may be recommended that patients under IL-1 blockade can be vaccinated without interrupting the anti-cytokine therapy, especially in patients with ongoing high disease activity to avoid disease relapses. However, in selected cases, after balancing for disease activity and risk of relapses, vaccination may be given seven days after the drug levels have returned to baseline, especially for IL-1 blocking agents with long half-lives such as canakinumab and rilonacept. This may help to ensure an ideal vaccine response in the face of the possibility that AIIRD patients may develop a more pronounced and severe COVID-19 disease course.

A practical approach for vaccinations including COVID-19 in autoimmune/autoinflammatory rheumatic diseases: a non-systematic review.

The COVID-19 pandemic has occupied the world agenda since December 2019. With no effective treatment yet, vaccination seems to be the most effective method of prevention. Recently developed vaccines have been approved for emergency use only and are currently applied to large populations. Considering both the underlying pathogenic mechanisms of autoimmune/autoinflammatory rheumatological diseases (AIIRDs) and the immunosuppressive drugs used in treatment, vaccination for COVID-19 deserves special attention in such patients. In this article, we aimed to give simple messages to the clinicians for COVID-19 vaccination in patients with AIIRDs based upon the current evidence regarding the use of other vaccines in this patient group. For this purpose, we conducted a "Pubmed search" using the following keywords: Influenza, Hepatitis B, Pneumococcal, and Shingles vaccines and the frequently used conventional and biologic disease-modifying antirheumatic drugs (DMARDs). Likewise, an additional search was performed for the COVID-19 immunization in patients with AIIRDs and considering such drugs. In summary, patients with AIIRDs should also be vaccinated against COVID-19, preferably when disease activity is under control and when there is no concurrent infection. Low-degree immunosuppression does not appear to decrease antibody responses to vaccines. Ideally, vaccinations should be done before the initiation of any biological DMARDs. Patients receiving rituximab should be vaccinated at least 4 weeks before or 6 months after treatment. Since tofacitinib may also reduce antibody responses, especially in combination with methotrexate, it may be appropriate to discontinue this drug before vaccination and to restart after 14 days of immunization. Key points • COVID-19 vaccinations should preferably be made during remission in patients with autoimmune/autoinflammatory rheumatological diseases. • Low-degree immunosuppression may not interfere with antibody response to vaccines. • Ideally, vaccinations should be made before the initiation of any biological DMARDs. • Timing of vaccination is especially important in the case of rituximab.

Uveitis-related Factors in Patients With Spondyloarthritis: TReasure Real-Life Results.

PURPOSE: Spondyloarthritis (SpA) is a group of diseases with overlapping skeletal and extra-articular features. Acute anterior uveitis (AAU) is the most common extra-articular manifestation of SpA. The relation between AAU and SpA is well defined in the current literature. Our study aims to analyze the frequency and factors associated with AAU in different forms of SpA in a large nationwide cohort of Turkish SpA patients. DESIGN: Retrospective cohort study. METHODS: The data were obtained from the TReasure database, which compiles data from records of the web-based Rheumatoid Arthritis (RA) and SpA patients treated with biological disease-modifying anti-rheumatismal drugs from different regions of Turkey. The clinical characteristics of SpA and uveitis are recorded. RESULTS: Data of the 4,297 SpA patients were included in the study. Overall, 475 of 4,297 patients (11.0%) had experienced 1 or more episodes of uveitis. SpA patients with older age (P < .001), a smoking history (P = .004), delayed diagnosis (P = .001), longer disease duration (P < .001), arthritis (P < .001), positive HLA-B27 (P < .001), a family history of SpA (P < .001), and radiographic damage (presence of sacroiliitis, syndesmophytes, bamboo spine, hip involvement) (P < .001 for all) more commonly had uveitis. On the other hand, uveitis was less prevalent in patients with psoriasis and psoriatic arthritis (P < .001 for both). CONCLUSION: Uveitis may be the key feature leading to SpA diagnosis. Patients with radiographic damage and long disease duration have an increased risk for uveitis in both male and female SpA patients. Patients with uveitis should be referred to a rheumatologist for a thorough evaluation of SpA.

Validation of ultrasound imaging for Achilles entheseal fibrocartilage in bovines and description of changes in humans with spondyloarthritis.

BACKGROUND: Entheseal fibrocartilage (EF) derangement is hypothesised to be pivotal to the pathogenesis of spondyloarthritis. Ultrasound is useful for visualisation of the enthesis but its role in EF visualisation is uncertain. This work aimed to demonstrate face and content validity of ultrasound for EF visualisation both by bovine histological evaluation and EF imaging in spondyloarthritis. METHODS: Achilles enthesis of 18 bovine hindfeet was visualised using a MyLab 70 ultrasound machine. The presence of tissue with EF characteristics was documented and histological confirmation was performed on five randomly selected sections using Masson trichrome staining. Ultrasound of the Achilles tendon (AT) was performed in 19 patients with spondyloarthritis and 21 healthy controls (HC). RESULTS: The bovine EF could be visualised in all cases and seen as a thin, uncompressible, well-defined, anechoic layer between the hyperechoic bone and the hyperechoic fibrils of the enthesis both in longitudinal and transverse scans. This region corresponded to EF on histological examination. The same pattern of low signal corresponding to EF location was seen in 17/19 patients and all HC. Discontinuities of the anechoic layer around the erosions and enthesophytes were observed in the spondyloarthritis group. The thickness of the anechoic layer was not significantly different in spondyloarthritis and HC (0.5 ± 0.1 vs 0.5 ± 0.2 mm, p=0.9) whereas the thickness of the EF was greater in men (0.6 ± 0.2 vs 0.5 ± 0.1 mm; p=0.009) compared with women. CONCLUSION: Ultrasound can visualise EF of the AT insertion, which can be abnormal in cases of spondyloarthritis. This has implications for a better understanding of enthesopathy.

Monitoring Achilles enthesitis in ankylosing spondylitis during TNF-alpha antagonist therapy: an ultrasound study.

OBJECTIVE: Enthesitis is considered as the primary anatomical lesion in ankylosing spondylitis (AS). Therapeutic effects of TNF-alpha antagonist treatments for enthesitis on imaging changes are still limited to case reports or small sample-sized trials. We aimed to investigate the potential of ultrasonography (US) to detect early changes after TNF-alpha antagonist therapy of Achilles enthesis of AS patients. METHODS: Forty-three AS patients with active disease, requiring TNF-alpha antagonist therapy, were included. Physical examination was performed to detect Achilles enthesitis and/or retrocalcaneal bursitis. US of the Achilles tendon was performed bilaterally. Grey-scale (GS) and power Doppler (PD) scores on a 0-2 semi-quantitative scale and total additive scores (TS) were calculated. Follow-up US examinations were performed 2 months after the initiation of therapy. RESULTS: At baseline, 11 patients (26.2%) were symptomatic in physical examination for either Achilles enthesitis or retrocalcaneal bursitis, whereas 36 (83%) had GS US pathological findings and 10 (23.3%) had PD signal. GS score and TS decreased significantly [3.6 (3.0) vs 2.3 (2.2), P < 0.001 and 4.7 (4.9) vs 2.7 (3.3), P < 0.001, respectively], whereas the decrease in PD score was not significant after 2 months of follow-up. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), ESR and CRP levels also showed significant improvements. CONCLUSIONS: Subclinical Achilles enthesitis, detected only with GS US, is present in a subset of AS patients and a significant improvement can be demonstrated after 2 months of TNF-alpha antagonist therapy. In addition to standard outcome measures, US might be an additional useful tool to monitor therapy in SpA patients with Achilles enthesitis.