Search

Objectives To examine the association between sonographic enthesitis with sonographic synovitis and tenosynovitis in PsA patients, and the association between sonographic enthesitis and clinical characteristics. Methods Consecutive PsA patients that fulfilled the ClASsification criteria for Psoriatic ARthritis (CASPAR) were prospectively recruited. Each patient was evaluated by comprehensive clinical and sonographic assessment (greyscale and Doppler), the latter including 52 joints, 40 tendons and 14 entheses [according to MAdrid Sonography Enthesitis Index (MASEI) plus lateral epicondyles] performed by an experienced sonographer blinded to the clinical data. The US enthesitis score was further categorized to inflammatory (hypoechogenicity, thickening, bursitis and Doppler) and structural (enthesophytes/calcifications and erosions) subcategories. Multivariate linear regression models assessed the association between enthesitis and the selected variables. Results A total of 158 PsA patients [mean (s.d.) age 52.3 (13) years, 88 (55.7%) females] were analysed. Multivariate linear regression analyses showed a significant association between sonographic enthesitis and sonographic synovitis (β = 0.18, P = 0.008) and between sonographic enthesitis and sonographic tenosynovitis (β = 0.06, P = 0.02). These associations were derived from the enthesitis inflammatory subcategory of the MASEI (P Conclusions Sonographic enthesitis is associated with sonographic synovitis and tenosynovitis. The severity of sonographic enthesitis may represent a marker for inflammatory activity in other musculoskeletal domains.

ObjectivesTo evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls.MethodsA prospective multicentre study investigated serum anti-SARS-CoV-2 S1/S2 IgG titre at 2–6 weeks (AIIRD n=720, controls n=122) and 6 months (AIIRD n=628, controls n=116) after the second vaccine, and 2–6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). T-cell immune response to the third vaccine was evaluated in a small sample.ResultsThe two-dose vaccine regimen induced a higher humoral response in controls compared with patients, postvaccination seropositivity rates of 100% versus 84.72%, pConclusionsThe two-dose BNTb262 regimen was associated with similar clinical efficacy and similar waning of the humoral response over 6 months among patients with AIIRD and controls. The third vaccine dose restored the humoral response in all of the controls and the majority of patients.

ObjectiveTo investigate sex-based sonographic differences in patients with psoriatic arthritis (PsA).MethodsThe study population included consecutive prospectively recruited patients with PsA, as determined by the CASPAR (Classification for Psoriatic Arthritis) criteria, who underwent clinical and physical examinations, followed by a detailed ultrasound (US) evaluation (greyscale and Doppler). US evaluation included 52 joints, 40 tendons, and 14 points of entheses (Modified Madrid Sonographic Enthesis Index [MASEI] plus lateral epicondyles) performed by an experienced sonographer blinded to the clinical data. The US score was based on the summation of a semiquantitative score for synovitis, tenosynovitis, and enthesitis. The US enthesitis score was categorized into inflammatory lesions (ie, hypoechogenicity, thickening, bursitis, and Doppler) and structural lesions (ie, enthesophytes/calcifications and erosions).ResultsThe study population of 158 patients included 70 males and 88 females. The males had higher rates of employment (P= 0.01), Psoriasis Area and Severity Index scores (P= 0.04), and mean swollen joint counts (P= 0.04). The total US score and its subcategory scores—the synovitis and tenosynovitis scores—were similar for both sexes, whereas the total enthesitis score and its subcategory score—the inflammatory enthesitis score—were significantly higher for the males compared to the females (P= 0.01 andP= 0.005, respectively). Hypoechogenicity, thickening, and enthesophytes were more prevalent in males compared to females (P< 0.05). Multivariate ordinal logistic regression models showed that male sex was associated with a higher US inflammatory enthesitis score compared to female sex (odds ratio 1.96,P= 0.02).ConclusionSonographic enthesitis was more prevalent in males compared to females with PsA. These differences were not reflected by enthesitis disease activity scores derived from clinical assessment.

Objective.To establish the prevalence of nonradiographic sacroiliitis within a real-life sample of patients with psoriatic arthritis (PsA), using pelvic radiographs and magnetic resonance imaging (MRI) of sacroiliac joints (SIJs).Methods.This cross-sectional study included 107 consecutive adults with PsA (Classification Criteria for Psoriatic Arthritis criteria). Participants completed clinical and laboratory evaluation, pelvic radiographs scored for radiographic sacroiliitis according to the modified New York (mNY) criteria, and noncontrast MRI of SIJs, scored by the Berlin score and categorized into active sacroiliitis using the 2016 Assessment of Spondyloarthritis international Society (ASAS) criteria and the presence of structural sacroiliitis.Results.Radiographic sacroiliitis/mNY criteria were detected in 28.7% (n = 29), confirmed by MRI-detected structural lesions in 72.4% (n = 21). Active sacroiliitis was detected by MRI in 26% (n = 28) of patients, with 11% (n = 11) qualifying for nonradiographic sacroiliitis. Patients with radiographic and nonradiographic sacroiliitis had similar clinical characteristics, except for a longer duration of psoriasis (PsO) and PsA in the radiographic subgroup (PsO: 23.8 ± 12.5 vs 14.1 ± 11.7 yrs, P = 0.03; PsA: 12.3 ± 9.8 vs 4.7 ± 4.5 yrs, P = 0.02, respectively). Inflammatory back pain (IBP) was reported in 46.4% (n = 13) with active sacroiliitis and 27% (n = 3) with nonradiographic sacroiliitis. The sensitivity of IBP for detection of nonradiographic sacroiliitis was low (27%) and moderate for radiographic sacroiliitis (52%), whereas specificity ranged from 72% to 79% for radiographic and nonradiographic sacroiliitis, respectively.Conclusion.The prevalence of active sacroiliitis among a real-life population of patients with PsA was 26%. However, the prevalence of nonradiographic sacroiliitis was low (11%) compared to the radiographic sacroiliitis (28.7%) seen in patients with longer disease duration. IBP was not a sensitive indicator for the presence of early-stage sacroiliitis that was commonly asymptomatic.

To assess the prevalence of anti-SARS-CoV-2 antibodies in autoimmune inflammatory rheumatic disease (AIIRD) patients, and to define clinical factors associated with seropositivity.A cross sectional study was conducted at a tertiary rheumatology department in Israel. Consecutive patients completed a questionnaire and were tested for SARS-CoV-2 anti-nucleoprotein IgG (N-IgG). If this was positive, an anti-S1/S2 spike IgG (S-IgG) test was done. If both were positive, the patient was considered seropositive. Seropositive patients were retested after 3 months.The study included 572 AIIRD patients. Thirty patients were found seropositive, for a seroprevalence of 5.24%. The seropositive rate was significantly lower for patients treated with immunosuppressive medications (3.55%, p≤0.01), and specifically for patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) (2.7%, p≤0.05). These associations remained significant in the multivariate regressions adjusting for age, sex and exposure to a known COVID-19 patient. A second serology test 3 months later was collected in 21 of the 30 seropositive patients. In a mean±standard deviation (SD) of 166.63±40.76 days between PCR and second serology, 85% were still positive for N-IgG, and 100% were still positive for S-IgG, with a higher mean±SD titre compared to the first S-IgG (166.77±108.77 vs. 132.44±91.18, respectively, p≤0.05).Humoral response to SARS-CoV-2 in AIIRD patients may be affected be immunosuppressive treatment, especially bDMARDs. In patients with AIIRD, titres of SARS-CoV-2 IgG antibodies, especially N-IgG antibodies, fade with time, while S-IgG antibodies persist.

IntroductionVaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.MethodsA multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2–6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose.ResultsFollowing vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, pConclusionmRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.

In view of the COVID-19 pandemic, there is an unmet clinical need for the guidelines on vaccination of patients with autoimmune inflammatory rheumatic diseases (AIIRD). This position paper summarises the current data on COVID-19 infection in patients with AIIRD and development of vaccines against COVID-19, discusses the aspects of efficacy and safety of vaccination, and proposes preliminary considerations on vaccination against COVID-19 in patients with AIIRD, mainly based on the expert opinion and knowledge on the use of other vaccines in this population of patients.

Objectives To report the discrepancies and agreements between US, MRI and radiography of the hand in PsA, and to compare the sensitivity and specificity of US and radiography to MRI as the gold standard imaging study in PsA. Methods All of the 100 prospectively recruited consecutive PsA patients underwent clinical assessment and concomitant radiographic, US and MRI studies of the MCP, PIP and DIP joints of one hand. Synovitis, flexor tenosynovitis, extensor paratenonitis, erosions and bone proliferations were identified and scored. All readers were blinded to clinical data, and agreement was calculated based on prevalence-adjusted bias-adjusted kappa (PABAK). Results The prevalence of synovitis, flexor tenosynovitis, extensor paratenonitis and erosions was similar for US and MRI, while that of bone proliferation was significantly increased in US and radiography compared with MRI (P Conclusion There is very good agreement between US and MRI for the detection of inflammatory changes in finger joints in PsA. US, radiography and MRI have a good-to-very good agreement for destructive changes.

The impact of biologics used in PsA management on T cells is unknown. This study evaluated the effect of tumour necrosis factor-alpha (TNFα), interleukin-17A (IL-17A), and IL-6 receptor (IL-6R) blockers on T cell function in PsA patients and healthy controls peripheral blood mononuclear cells (PBMCs).A total of 111 PsA patients and 32 healthy controls were recruited. PBMCs were co-cultured in presence of the biologics. T cell activation and proliferation were analysed by flow cytometry and cytokines in supernatants were measured by ELISA. The effect of biologics on lymphocyte proliferation was determined in response to phytohemagglutinin (PHA).Activated CD4+CD25+ T cells were significantly reduced by adalimumab (ADA) in PsA patients as compared to medium, ixekizumab (IXE), and tocilizumab (TCZ), while in healthy controls, ADA reduced the activated CD4+CD25+ T cells non-significantly. Elevated TNFα and IL-1β levels were produced in supernatants of PsA patients as compared to healthy controls. TNFα, IL-17A, IL-1β, and MMP-3 levels were reduced by ADA compared to medium (p0.0001, p0.0004, p0.04, p0.04, respectively). IXE reduced IL-17A (p0.0001) but not the other cytokines. ADA had higher susceptibility to inhibit PHA-induced proliferation in both PsA patients and healthy controls (p0.03) as compared to IXE and TCZ.Both TNF and IL-17A blockers are suitable for PsA treatment, but exhibit different activity on T cells. Moreover, the study reveals part of the mechanism exerted by ADA and provides a possible explanation for TCZ inefficacy in PsA.

Objective Subclinical myocardial dysfunction has been reported to occur early in systemic lupus erythematous (SLE). The study aim was to search for biomarkers of subclinical myocardial dysfunction which may correlate with disease activity in SLE patients. Methods This is a prospective, controlled, cross-sectional study of 57 consecutive patients with SLE and 18 controls. Serum samples were obtained to determine serum soluble ST2 (sST2), CXCL-10 and high-sensitivity troponin (hs-troponin) levels. All participants underwent an echocardiographic tissue Doppler study. Results sST2, CXCL-10 and hs-troponin levels were higher in patients with higher SLE disease activity (SLEDAI). sST2 and CXCL-10 levels were higher in patients with more disease damage as measured by the SLE damage index. Measures of diastolic dysfunction, as assessed by echocardiographic tissue Doppler negatively correlated with log CXCL-10: including E/A; E/e′lateral and E/e′septal, while E/e′ positively correlated with CXCL-10. Diastolic dysfunction parameters also correlated with log sST2 levels, a negative correlation was seen with E/e′lateral and a positive correlation was seen with E/e′. Systolic dysfunction parameters positively correlated with hs-troponin: LVED, LVES, IVS, LVMASS and LVMASS index. In a multivariate analysis, sST2 and CXCL-10 were found to be significantly different in SLE vs. healthy controls, independent of each other and independent of cardiovascular risk factors. Conclusions Soluble ST2 and CXCL-10 are markers of disease activity and accrued damage in SLE and may serve as sensitive biomarkers for detection of subclinical diastolic dysfunction, independent of traditional cardiovascular risk factors.

The clinical manifestations of the antiphospholipid syndrome (APS) are heterogeneous and related to anti-phospholipid antibodies (aPL). There is some evidence that B cells are involved in the pathogenesis of this condition. Thus the ability of rituximab (RTX) to deplete B cells makes it an appealing potential therapy for refractory antiphospholipid syndrome (APS). Real world data on RTX treatment of APS are still lacking. This study was conducted to report outcomes of RTX administration in the treatment of different aspects of APS.This is a retrospective case series study on APS patients from 3 medical centres in Israel who were treated with RTX during 2010-2019 for refractory manifestations of APS including diffuse alveolar haemorrhage, recurrent thrombosis, cytopenia, neurological and skin manifestations. Medical records were reviewed regarding the clinical indication for RTX treatment, concomitant medications, RTX protocol, aPL status and response to treatment. Outcomes were defined as complete response if full resolution of the "indicated manifestation" was achieved and maintained for at least 12 months, partial response or no response.We identified 40 APS patients who were treated with RTX for refractory manifestations of this condition, of whom, 24 patients (60%) were female with a mean age of 40 years, and 31 patients (78%) were diagnosed with primary APS. A favourable response to RTX was documented in 32 patients (80%) including a complete response in 22 patients (55%). Response to RTX treatment was associated with a rituximab protocol of 375mg/m2 x 4 compared to a fixed dose of 1000 mg x2 (100% vs. 65%; p=0.01). Complete response was associated with a decrease in aPL titres within 4-6 months post treatment, whereas no significant change in aPL titres was observed in patients with partial or no response.Consistent with previous small case series, we report a good therapeutic response to RTX in patients with difficult to treat manifestations of APS. In this cohort, treatment protocols were associated with outcomes. Although further studies are required to verify our observations, our data support a plausible role for B cell depletion in refractory APS.

Biologics have revolutionized the treatment of inflammatory arthritis, but their impact on T cell function is unknown. We evaluated the effect of tumor necrosis factor-alpha (TNF-α), interleukin-17A (IL-17A), and IL-6 receptor (IL-6R) blockers on T cell function in psoriatic arthritis (PsA) patients. Peripheral blood mononuclear cells (PBMCs) from PsA patients (n=111) and healthy controls (n=20) were co-cultured with adalimumab (ADA), ixekizumab (IXE), tocilizumab (TCZ), or medium alone for 5 days. T cell activation and proliferation were determined by flow cytometry and cytokines in supernatants were measured by ELISA. Activated CD4+CD25+ T cells were significantly down-regulated by ADA in naive, conventional disease-modifying anti-rheumatic drug (cDMARD)- and biologic-treated PsA patients compared to medium (p < 0.04, p < 0.01, respectively), IXE, and TCZ. In healthy, ADA reduced the activated CD4+CD25+ T cells proportion but non-significantly as compared to the other groups. Inhibition of PsA patients derived lymphocytes proliferation by the biologics was determined in response to phytohemagglutinin (PHA). The strongest ability to suppress the extent of PHA-induced proliferation was exerted by ADA (p < 0.01) compared to IXE and TCZ. IL-1β, IL-17A, and MMP-3 levels were down-regulated by ADA compared to medium (p < 0.02, p < 0.0001, p < 0.002, respectively). IXE reduced IL-17A (p < 0.0001) but not IL-1β or MMP-3 levels. TNF and IL-17A blockades are suitable for PsA treatment, but exhibit different activity on T cells. Moreover, the study reveals part of the mechanism exerted by ADA and provides a possible explanation for TCZ inefficacy in PsA.

Background Clinical manifestations of the antiphospholipid syndrome (APS) are heterogeneous and may be difficult to treat. Evidence that B cells and particularly anti-phospholipid antibodies (aPL) are involved in APS-clinical events has been documented. Thus, the ability of rituximab (RTX) to deplete B cells and possibly reduce aPL titers makes it an appealing potential therapy for this autoimmune disease. Real world data on the usefulness of RTX treatment for APS is scarce. In this study we report outcomes of RTX administration in treating different manifestations of APS. Methods In this retrospective case series, data from 3 medical centers in Israel was collected regarding the use of RTX to treat APS. Medical records were reviewed for clinical manifestations, indication for RTX treatment, concomitant medications, aPL status and the response to treatment. The latter was clinically defined as complete resolution of the indicated manifestation, partial improvement or no response. Results We included 40 APS patients in this case series, 31 primary-APS and 9 with APS secondary to SLE. Our cohort consisted of 16 males and 24 females, mean age 39±14 years, 29 were defined as triple-aPL positive. All patients presented with 1–2 difficult to treat manifestations including: diffuse alveolar hemorrhage (DAH-n=6), recurrent thrombosis despite anticoagulation (n=10), thrombocytopenia and/or hemolytic anemia (n=10), neurological manifestations (n=7), nephropathy (n=2) vasculitis/leg ulcers (Skin) (5p) and catastrophic-APS (n=2). Notably, 32 (80%) patients responded favorably (complete response - 22; partial improvement -10), 5 did not respond to RTX therapy and 3 patients died within 12 months (figure 1). Concomitant therapies (e.g. hydroxychloroquine, glucocorticoids, cyclophosphamide, plasmapheresis, azathioprine etc.) did not correlate with favorable responses, rather treatment with cyclophosphamide or plasmapheresis correlated with worse outcomes (p Conclusions Herein, consistent with previous small case series, we report a good therapeutic response to RTX in patients with difficult to treat manifestations of APS. The RTX treatment protocol may affect response to therapy and a decrease of aPL titers within 2–6 months following therapy may predict a better response. Larger studies are required to confirm these results.

Background SLE complexity and unpredictability challenge assessment of disease activity. Current scoring instruments are limited in ability to detect changes in activity over time and too cumbersome for daily practice. We constructed a new disease activity score, including physician and patient assessment, aiming to simplify and improve assessment in daily practice, and possibly serve as a tool for clinical studies. Methods The new instrument is comprised of 6 visual analogue scales, separately addressing the physician’s global assessment and 5 organ systems: mucocutaneous, musculoskeletal, cardiorespiratory, renal and neuropsychiatric systems, and 5 visual analogue scales addressing patients’ assessment of disease activity and adherence to therapy. Laboratory values and medications are recorded. Aiming to assess the reliability and validity of the new score, as well as it’s sensitivity to changes in disease activity, 4 paper cases, including 2 visits per case, were constructed. Each visit was scored by 5 experienced rheumatologists, using BILAG, SLEDAI, LFA-REAL and our proposed score. Results The inter-rater reliability of the new score was good for all systems, both for single visit scores and for change in disease activity between 2 consecutive visits (ICC [2,1] range 0.75–0.95), except for changes in activity in the renal system (0.59). The inter-rater reliability values of the new score were comparable with those of the BILAG and the LFA-REAL instruments. The construct validity of the new score was good for single visit scores (Spearman correlation coefficients range 0.48–0.94). Correlation of our proposed score with the BILAG, was good when scoring the mucocutaneous, musculoskeletal and cardiorespiratory systems (0.66, 0.75, 0.83, respectively) but poor when scoring the renal system (0.11). Conclusions This paper case evaluation of the new disease activity score suggests a promising and simple tool, with overall good reliability and construct validity.

Background:Immune responses in AIIRD patients may be reduced and influenced by immunosuppressive treatments[1].The effect of immunosuppression on the mounting of SARS-CoV-2 antibodies in AIIRD is not clear.Objectives:To assess the prevalence of SARS-CoV-2 antibodies in AIIRD patients and to define clinical factors affecting this prevalence.Methods:Consecutive consenting AIIRD patients from the Rheumatologic department in Tel Aviv Medical Center participated in the study.Patients answered a questionnaire and were tested for SARS-CoV-2 antibodies. A two stage antibody testing was done in order to increase specificity.Results:The study included 560 AIIRD patients (229 RA, 149 PsA, 84 SLE, 55 vasculitidies, 40 SpA, 3 other CTD), of them 26 patients were found to have SARS-CoV-2 IgG antibodies (4.6%) (Table 1). This was more than double than a previous prevalence in the same clinic population studied after the first wave of the pandemic in Israel, which was 2.07% (accepted for publication).A lower rate of immunosuppression was found for positive SARS-CoV-2 IgG patients compared to negative serology patients (Table 1, p=0.009). There was also a trend for the subgroup of patients on biologic DMARDS (26.92% vs. 47% respectively, p=0.06).Positive SARS-CoV-2 PCR test was reported and confirmed in 36 patients, of them 14 (38.89%) had negative serology. Patients who did not have antibodies had numerically more than double rates of glucocorticoids and bDMARDs treatment. The time between positive PCR test to positive serology test was significantly shorter (mean±standart deviation 75.57±40.44 days) than the time between positive PCR to negative serology test (130.79±86.47 (p=0.04) (Table 1 and Figure 1) suggesting a fading of the antibody response with time.Conclusion:The prevalence of SARS-CoV-2 IgG was 4.6% in a population of AIIRD patients from a single tertiary medical center in Israel. SARS-CoV-2 seroprevalence tended to be low among AIIRD patients on immunosuppressive treatment, including in patients with a confirmed history of positive SARS-CoV-2 PCR, similar to other studies [3].As in individuals without AIIRD, the mounting of SARS-CoV-2 IgG seems to fade with time.Larger studies are needed to confirm the potential effect of immunosuppression on the antibody response in AIIRDs.Table 1.Demographic and clinical characteristics of patients with negative and positive SARS-CoV-2 IgG, and in the subgroup with positive SARS-CoV-2 PCR testTotal population (n=560)Positive PCR population (n=36)Negative IgG(n=534)Positive IgG(n=26)PNegative IgG(n=14)Positive IgG(n=22)PFemale n (%)360 (67.42)22 (84.62)0.0810 (71.43)18 (81.82)0.68Age median (95% CI)57 (54.95-57.58)52.5 (46.55-58.6)0.2342 (35.46-53.11)52.5 (47.62-60.65)0.06No. of comorbiditiesmean±STD (95%CI)0.88±1.15 (0.78-0.98)0.92±1.2 (0.44-1.41)0.860.79±1.12 (0.14-1.43)0.96±1.3 (0.4-1.51)0.68AIIRD treatments n(%)Total immunosuppression401 (75.09)13 (50)0.00911 (78.57)12 (54.54)0.175GC113 (21.16)3 (11.54)0.325 (35.71)3 (13.64)0.32csDMARDS257 (48.13)13 (50)17 (50)13 (59.09)0.73bDMARDS251 (47)7 (26.92)0.069 (64.29)7 (31.82)0.09Anti CD-2036 (6.74)00.41 (7.14)00.39SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2; IgG, immunoglobulin G; PCR, polymerase chain reaction; n, number; 95%CI, 95% confidence interval; GC, glucocorticoids; csDMARDS, conventional synthetic disease modifying antirheumatic drugs; bDMARDS, biologic disease modifying antirheumatic drugs.References:[1]V. Furer et al., “Incidence and prevalence of vaccine preventable infections in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD): a systemic literature review informing the 2019 update of the EULAR recommendations for vaccination in adult patients wit,” RMD Open, vol. 5, no. 2, p. e001041, Sep. 2019.[2]D. Simon et al., “Patients with immune-mediated inflammatory diseases receiving cytokine inhibitors have low prevalence of SARS-CoV-2 seroconversion,” Nat. Commun., vol. 11, no. 1, pp. 1–7, 2020.Acknowledgements:This study was performed in collaboration with the Israeli Ministry of Health.Disclosure of Interests:None declared.

Background:Sleep disturbances are common in individuals with rheumatological diseases in general and systemic lupus erythematosus (SLE) in particular1. Studies suggest that obstructive sleep apnea (OSA) might correlate with SLE disease activity and the presence of additional symptoms such as pain, fatigue, affective symptoms and steroid use2. Sleep disturbances symptomatology such as fatigue and increased pain overlap with constitutional inflammatory symptoms of SLE and may mimic or mask disease related relapse3,4. Therein lies the importance of diagnosing and treating such disorders in SLE.Objectives:To determine whether patients with SLE have increased prevalence of OSA as assessed by the apnea hypopnea index (AHI) and to explore possible contributors to OSA including SLE disease activity and accrued damage, medications, secondary fibromyalgia and depression.Methods:42 consecutive patients with SLE (38 women, 4 men) and 20 healthy, sex, body mass index (BMI) and age matched controls (15 women, 5 men) were consecutively recruited and underwent an ambulatory sleep study using the WatchPAT device. All participants completed questionnaires including Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Functional Assessment of Chronic Illness Therapy (FACIT), Widespread Pain Index (WPI), Symptoms Severity Scale (SSS) and Beck Depression Inventory. SLE disease activity and damage were assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics (SLICC) damage index.Results:The mean AHI was 9.19 ± 6.79 in the SLE group and 3.95 ± 3.47 in the control group (p=0.004). Moderate-severe OSA (AHI≥15) was significantly more common in patients with SLE (23.6% vs. 0%, p=0.04). Patients with SLE had lower sleep efficiency (83.38 ± 6.15 vs. 87.22 ± 4.24, p=0.03), increased sleep arousals (7.72 ± 5.66 vs. 5.13 ± 2.29, p=0.01), higher PSQI and FACIT scores SLE (8.14 ± 3.47 vs. 5.10 ± 2.64, p=0.001, 16.89 ± 11.19 vs. 7.29 ± 5.93, p= 0.0008 respectively) and had more fibromyalgia as assessed by WPI and SSS (19.5% vs. 0%, p=0.04). BMI and the SLICC score were independent predictors of OSA (p=0.03 and p=0.02 respectively). A correlation between SLEDAI and moderate-severe OSA was found (p=0.03), although an association to medications, secondary fibromyalgia and depression was not found.Conclusion:Patients with SLE have increased prevalence of OSA with lower sleep quality compared to healthy controls. Our findings suggest a possible correlation between accrued damage as assessed by the SLE damage index and OSA.References:[1]Wu, L., Shi, P. L., Tao, S. S., Tao, J. H. & Wu, G. C. Decreased sleep quality in patients with systemic lupus erythematosus: a meta-analysis. Clin. Rheumatol. (2020) doi:10.1007/s10067-020-05300-3.[2]Palagini, L. et al. Sleep disorders and systemic lupus erythematosus. Lupus vol. 23 115–123 (2014).[3]Javaheri, S. & Javaheri, S. Update on Persistent Excessive Daytime Sleepiness in OSA. Chest vol. 158 776–786 (2020).[4]Mertz, P. et al. Towards a practical management of fatigue in systemic lupus erythematosus. Lupus Science and Medicine vol. 7 (2020).Table 1.WatchPAT sleep parameters analysisSLE groupn = 42Control groupn = 20P valueRDI ± SD13.52 ± 6.549.72 ± 3.600.04AHI ± SD9.19 ± 6.793.95 ± 3.470.004ODI ± SD2.54 ± 2.721.27 ± 1.450.04Sleep efficiency (%) ± SD83.38 ± 6.1587.22 ± 4.240.03Number of arousals ± SD7.72 ± 5.665.13 ± 2.290.01Saturation (%) ± SD96.10 ± 1.3795.75 ± 1.390.45Sleep latency ± SD21.25 ± 9.3318.46 ± 6.630.27REM latency ± SD87.88 ± 49.0673.60 ± 46.210.09REM ± SD25.35 ± 14.0327.32 ± 6.790.15Light sleep ± SD57.63 ± 12.3752.70 ± 11.630.18Deep sleep ± SD17.89 ± 5.5918.76 ± 6.700.54SLE, Systemic Lupus Erythematosus; RDI, Respiratory Disturbance Index; SD, Standard Deviation; AHI, Apnea Hypopnea Index; ODI, Oxygen Desaturation Index; REM Rapid Eye Movement.Disclosure of Interests:None declared

Background:The epidemiology of COVID19 among patients with AIIRD may be influenced by a dysregulated immune system, immunosuppressive therapies and behavioral patterns. Data regarding the epidemiology of COVID19 among patients with AIIRD is scarce.Objectives:To assess the pattern of COVID19 pandemic among patients with AIIRD compared to the general population in IsraelMethods:At the beginning of the COVID-19 pandemic, we established a national registry of patients with AIIRD, diagnosed with COVID-19, based on voluntary reporting by the treating rheumatologist. All the members of the Israeli Society of Rheumatology were encouraged to participate and repeatedly reminded to report any new cases. Rheumatology centers from 11 hospitals from the Northern and Central part of Israel participated in this study. The registry included demographic data, AIIRD diagnosis and duration, systemic organ involvement, co-morbidities, treatment (conventional synthetic disease modifying drugs (csDMARDs), biologic/targeted (b/ts) DMARDs, corticosteroids use, dose and treatment duration, date of COVID19 diagnosis, severity of the viral disease and complications, duration of hospitalization, if required, treatment for COVID 19, laboratory results and outcome. The diagnosis of COVID 19 was made by a positive SARS CoV2 PCR. The indications for SARS CoV2 PCR testing in Israel comprise clinical symptoms or exposure to a confirmed close contact. Severe illness was defined by SpO2 30 breaths/min, PaO2/FiO2 50% on chest imaging.The epidemiological data regarding the number of COVID19 confirmed patients, the number of severe cases and the rate of mortality among the general population per day and per week, were extracted from the data dashboard of the Israeli Ministry of Health. We analyzed data from 02.2020 to 15.01.2021.Results:During the study period we experienced 3 waves of COVID 19 pandemic. The governmental management of COVID19 spread, at the beginning of the pandemic, included inforcement of severe travel restrictions and social distancing, followed eventually by a preventive lockdown, in spite of the relatively low number of cases. Easing of the restrictions, lifting the travel ban, opening of the commerce and schools led to 2 much more severe waves, which triggered 2 new lockdowns. Up to January 2021, 549763 Israelis had confirmed COVID19, 30% of whom had severe disease, 0.84% died (30% of the patients with severe disease).We identified 190 AIIRD patients (mean(SD) age 52(18), 30% males) who had confirmed COVID19. The weekly incidence curve of patients with rheumatic diseases correlated with the curve of the general population (Figure 1).Sixty-one % of the patients with AIIRD received csDMARDs, 41% were on b/tsDMARDs, 39% on chronic corticosteroids, 12% on ≥10mg prednisone. Forty-seven% of patients required hospitalization, 20% had severe COVID19. Sixteen patients (42% of patients with severe COVID19) (mean(SD), median age 64.7(15.4),67)) died (systemic sclerosis-4 patients, rheumatoid arthritis – 6, systemic lupus erythematosus – 2, antiphospholipid syndrome-2, granulomatous polyangiitis -1, polymyalgia rheumatica-1). The AIIRD was active in 56% of them, 50% received csDMARDs, none of them were on b/tsDMARDs, 31% received chronic prednisone>10 mg. All patients who died had at least 2 comorbidities.Conclusion:The pattern of spread of COVID19 in AIIRD patients is similar to the general population despite repeated mass media alerts for enhanced social distancing for elderly and immune suppressed patients. The disease tends to be more severe with enhanced mortality, especially in those with active AIIRD disease and organ involvement (lungs, heart, renal), older age and co-morbidities. A reporting bias cannot be excluded.Figure 1.Acknowledgements:Both first authors contributed equally to the manuscript.Disclosure of Interests:None declared.

Objective To evaluate the prevalence of sacroiliitis, the radiographic hallmark of inflammatory spondyloarthropathy, among patients diagnosed with fibromyalgia syndrome (FMS), using the current Assessment of SpondyloArthritis International Society (ASAS) criteria and magnetic resonance imaging. Methods Patients experiencing FMS (American College of Rheumatology 1990 criteria) were interviewed regarding the presence of spondyloarthritis (SpA) features and underwent HLA–B27 testing, C-reactive protein (CRP) level measurement, and magnetic resonance imaging examinations of the sacroiliac joints. FMS severity was assessed by the Fibromyalgia Impact Questionnaire and the Short Form 36 health survey. SpA severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index. Results Sacroiliitis was demonstrated among 8 patients (8.1%) and ASAS criteria for diagnosis of axial SpA were met in 10 patients (10.2%). Imaging changes suggestive of inflammatory involvement (e.g., erosions and subchondral sclerosis) were demonstrated in 15 patients (17%) and 22 patients (25%), respectively. The diagnosis of axial SpA was positively correlated with increased CRP level and with physical role limitation at recruitment. Conclusion Imaging changes suggestive of axial SpA were common among patients with a diagnosis of FMS. These findings suggest that FMS may mask an underlying axial SpA, a diagnosis with important therapeutic implications. Physicians involved in the management of FMS should remain vigilant to the possibility of underlying inflammatory disorders and actively search for such comorbidities.

Background Cognitive impairment is frequent in systemic lupus erythematosus. Atrophy of the corpus callosum and hippocampus have been reported in patients with systemic lupus erythematosus, and diffusion tensor imaging studies have shown impaired white matter integrity, suggesting that white matter damage in systemic lupus erythematosus may underlie the cognitive impairment as well as other neuropsychiatric systemic lupus erythematosus manifestations. Retinal nerve fiber layer thickness, as assessed by optical coherence tomography, has been suggested as a biomarker for white matter damage in neurologic disorders such as multiple sclerosis, Alzheimer’s disease and Parkinson’s disease. Retinal nerve fiber layer thinning may occur early, even in patients with mild clinical symptoms. Aim The objective of this study was to assess the association of retinal nerve fiber layer thickness, as a biomarker of white matter damage in systemic lupus erythematosus patients, with neuropsychiatric systemic lupus erythematosus manifestations, including cognitive impairment. Methods Twenty-one consecutive patients with systemic lupus erythematosus underwent neuropsychological testing using a validated computerized battery of tests as well as the Rey-Auditory verbal learning test. All 21 patients, as well as 11 healthy, age matched controls, underwent optical coherence tomography testing to assess retinal nerve fiber layer thickness. Correlations between retinal nerve fiber layer thickness and results in eight cognitive domains assessed by the computerized battery of tests as well as the Rey-Auditory verbal learning test were assessed in patients with systemic lupus erythematosus, with and without neuropsychiatric systemic lupus erythematosus, and compared to retinal nerve fiber layer thickness in healthy controls. Results No statistically significant correlation was found between retinal nerve fiber layer thickness in patients with systemic lupus erythematosus as compared to healthy controls. When evaluating by subgroups, no correlation was found between patients with or without neuropsychiatric systemic lupus erythematosus or cognitive impairment and retinal nerve fiber layer thickness. Conclusion Retinal nerve fiber layer thickness of systemic lupus erythematosus patients was not found to be statistically different compared to controls. Within systemic lupus erythematosus patients there was no correlation between retinal nerve fiber layer thickness and cognitive impairment or other neuropsychiatric systemic lupus erythematosus manifestations.

Rituximab, a monoclonal antibody against CD20 positive B cell, depletes these cells peripherally, and is a successful treatment in rheumatoid arthritis (RA). It is the second efficacious biologic to be established in the treatment of RA after TNFα blockers. Eighteen years of global experience from diverse clinical trials and from "real world" data, have demonstrated clinical efficacy in various disease scenarios and patient populations - short and long disease duration, methotrexate naïve patients and those with incomplete response to methotrexate, biologic naïve patients and those with incomplete response to previous biologics. Moreover, it has demonstrated the inhibition of radiographic progression. It seems to be most efficacious in seropositive patients. Despite vast experience, the need for concomitant traditional disease-modifying anti rheumatic drugs (DMARD), the optimal retreatment dose, and the favored retreatment interval remain somewhat uncertain. The recommended dosage is 1000 mg, administered twice, with a 2 weeks interval, although in some cases, a reduced dosage of 500 mg, administered twice may be considered. The safety profile of rituximab includes mainly infusion-related reactions, which are usually mild. A small risk of major infections has remained stable over time and repeated courses. Opportunistic infections are infrequent. Nevertheless, reactivation of hepatitis B is still a concern. Tuberculosis, malignancies, cardiovascular events and deterioration of interstitial lung disease do not appear to be increased. Since rituximab severely impairs the humoral response to vaccinations, they should be administered prior to treatment whenever possible. Rituximab has been a powerful addition to the large armamentarium for the treatment of RA. Rituximab is indicated in Israel as a second line biologic treatment for active RA.

Patients with psoriatic arthritis (PsA) are at increased risk of cardiovascular disease (CVD). High-sensitivity cardiac troponin T (hs-cTnT) is a novel biomarker of CVD. The objective of this study is to determine the prevalence of circulating hs-cTnT in patients with PsA compared to the general population and to characterize a PsA subset with detectable hs-cTnT. A cross-sectional analysis of serum hs-cTnT levels was performed in 116 consecutive patients with PsA and the Tel-Aviv Medical Center Inflammatory Survey cohort of the general population (n = 6052) as a control group. The level and prevalence of hs-cTnT (ng/L) were similar in the entire study population: 4.94 ± 4.4, 30.2% in PsA, 5.17 ± 6.7, 34.2% and 5.38 ± 4.3, 37.9% in unmatched and matched control groups according to age, gender and cardiovascular risk factors, respectively. Factors associated with detectable hs-cTnT in PsA included male gender (p = 0.002), age (p = 0.007), hypertension (p

Background TNF-α blockers are effective drugs for the treatment of psoriatic arthritis (PsA) and rheumatoid arthritis (RA). On the other hand, while interleukin-6 receptor (IL-6R) blockers have emerged as effective drugs in the treatment of RA, their effect in PsA has been disappointing. We hypothesized that the differential effect of TNF-α and IL-6R blockers in PsA may be mediated by the effect of these drugs on IL-17 expression, a cytokine profoundly involved in PsA and by their influence on activated CD4+CD25+ T cells. Objectives To evaluate the differential effect of adalimumab (ADA) (representing TNF-α blockers) and tocilizumab (TCZ) (IL-6R blocker) on the expression level of IL-17 and on the frequency of activated CD4+CD25+ T cells. Methods Levels of IL-17 mRNA expression were measured following in vitro co-culture of peripheral blood mononuclear cells (PBMC) derived from PsA patients with, ADA, TCZ at 10ug/ml or with medium alone as control for 3 days. Next, RNA was extracted and real-time PCR for IL-17 mRNA expression was performed. In addition, after 5 days incubation with the biologic agents the frequency of activated CD4+CD25+ T cells were analyzed by flow cytometry. Results The differential effect of ADA and TCZ on IL-17 mRNA expression and modulation of activated CD4+CD25+ T cells in culture of PBMC derived from PsA patients is shown in Figure 1. We found that IL-17 mRNA expression in PsA patients derived PBMC (n=20) was down-regulated by ADA. This down grading was significant in comparison with TCZ and medium control respectively (p Conclusion Our data highlight the differential effect of ADA and TCZ on IL-17 expression level and on frequency of activated CD4+CD25+ T cells in culture of peripheral immune cells derived from PsA patients. This data suggest a new mechanism of action of ADA and provide a possible explanation of the inefficacy of TCZ in PsA. Disclosure of Interests None declared

Objective To assess the immunogenicity and safety of vaccination against seasonal influenza in psoriatic arthritis (PsA) patients treated with secukinumab versus healthy controls (HC). Methods PsA patients administered secukinumab for ≥3 months and HC received the Sanofi Pasteur vaccine composed of 3 antigens (H3N3, H1N1, and B) and underwent clinical and laboratory assessments on the day of vaccination and 4–6 weeks later. Immunogenicity of the vaccine was evaluated by hemagglutination inhibition assay against those 3 antigens. Responders to each antigen were defined by a 4-fold increase in the antigen titer or by seroconversion in patients whose baseline level was Results Thirty-two consecutive PsA patients treated with secukinumab for ≥3 months comprised the study group, 10 of whom received concomitant conventional synthetic disease-modifying drugs, mostly methotrexate. There were 17 age- and gender-matched HC (median age 48.5 years, 6 females). The geometric mean titers of each antigen increased significantly in both groups. The number of responders in each group was similar for H3N2 and H1N1, and significantly higher for B/Brisbane in the PsA group. The proportion of patients with a seroprotective level (a titer >1/40) was high and similar in both groups. There was no correlation between the response rate and age, gender, or selected parameters of disease activity (tender/swollen joint counts, Leeds enthesitis index, physician and patient global assessment, psoriasis area severity index, and C-reactive protein). No disease exacerbation was observed following the vaccination. No serious adverse effects were observed in both groups during the study period. Conclusion Secukinumab treatment does not affect the humoral response to influenza vaccine of patients with PsA.

BACKGROUND: Induced sputum is a noninvasive tool, aimed at collecting cellular and soluble materials from lung airways. Induced sputum sampling analysis has been validated in chronic obstructive lung diseases as well as in various diffuse interstitial lung disorders. Our objective was to evaluate the utility of induced sputum speciments of cellular and soluble materials noninvasively sampled from the lung airways of subjects with systemic sclerosis compared with healthy controls and determine possible correlation with disease manifestations. METHODS: The study population included 20 consecutive subjects with systemic sclerosis and 16 healthy volunteers (controls). All of the participants underwent pulmonary function testing (PFT), single-breath diffusion capacity of carbon monoxide, and induced sputum cytology analysis. RESULTS: The systemic sclerosis subjects' induced sputum samples contained a higher neutrophil count ( P = .09) and lower lymphocyte count ( P = .045) compared with the controls. Within the systemic sclerosis population, several clinical, PFT, and induced sputum findings were positively correlated: the modified Rodnan skin score score and CD3 ( P = .044), modified Rodnan skin score and CD4 ( P = .04), modified Rodnan skin score and percentage neutrophils ( P = .059), and total lung capacity (TLC) and percentage lymphocytes ( P = .02). Induced sputum neutrophil counts were inversely associated with TLC ( P = .02) and FVC ( P = .02). Induced sputum samples from the subgroup of systemic sclerosis subjects with PFT restrictive pattern contained a significantly lower percentage of lymphocytes ( P = .004) and lower CD4/CD8 ratio ( P = .028) compared with controls. In this subgroup, TLC also was negatively correlated with the neutrophil count ( P = .043), and positive correlations were found between TLC and CD3 ( P = .053), disease duration and CD4/CD8 ratio ( P = .033), TLC and FVC and percentage macrophages ( P = .033 and P = .052, respectively), diffusion per unit of alveolar volume, and percentage macrophages ( P = .032), and C-reactive protein and percentage lymphocytes, percentage macrophages, and neutrophil count ( P = .02, P = .008, and P = .006, respectively). CONCLUSIONS: Induced sputum analysis of subjects with systemic sclerosis, including those with restrictive lung disease, shows changes in cellular pattern and correlation with several highly relevant clinical and PFT parameters.

Objective.To study the effect of the presence of fibromyalgia (FM) on common clinical disease activity indices in patients with psoriatic arthritis (PsA).Methods.Seventy-three consecutive outpatients with PsA (mean age 51.7 yrs; 42 females, 57.5%) were enrolled in a prospective cross-sectional study. FM was determined according to American College of Rheumatism criteria (2010 and 1990). All patients underwent clinical evaluation of disease activity and completed the Health Assessment Questionnaire (HAQ), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Dermatology Life Quality Index, and the Leeds Enthesitis Index (LEI). Disease activity was evaluated using the Composite Psoriatic Disease Activity Index (CPDAI), minimal disease activity (MDA), and the Disease Activity Index for Psoriatic Arthritis (DAPSA) scores.Results.The overall prevalence of FM was 17.8% (13 patients), and all but 1 were women (12 patients, 92.3%, p = 0.005). CPDAI and DAPSA scores were significantly higher in patients with coexisting PsA and FM (9.23 ± 1.92 and 27.53 ± 19.23, respectively) than in patients with PsA only (4.25 ± 3.14 and 12.82 ± 12.71, respectively; p < 0.001 and p = 0.003). None of the patients with FM + PsA met the criteria for MDA, whereas 26 PsA-only patients did (43.3%, p = 0.003). HAQ, BASDAI, and LEI scores were significantly worse in patients with PsA and associated FM.Conclusion.Coexisting FM is related to worse scores on all tested measures in patients with PsA. Its influence should be taken into consideration in the treatment algorithm to avoid unnecessary upgrading of treatment.

Objective.To evaluate the effect of pregnancy on disease activity in psoriatic arthritis (PsA).Methods.This is a retrospective case series. Review of the medical files of all female patients followed at the PsA clinic of 2 medical centers identified those with at least 1 pregnancy during followup and 1 visit during or soon after pregnancy.Results.Twenty-five women with PsA (out of 107 women of reproductive age followed up in our PsA clinics) and 35 pregnancies were enrolled. Thirty-three pregnancies resulted in live healthy babies. In the whole group, there was no significant change in disease activity throughout pregnancy, while in 16 (48%) of pregnancies, patients worsened during the first postpartum year. In 15 out of 21 pregnancies, in which the women had been treated before conception with biologics, treatment was discontinued close to pregnancy or during the first trimester. Five of those 15 patients had been classified as having mild to severe PsA activity prior to pregnancy. That number increased to 8, 9, and 14 during the first and second trimesters and postpartum period, respectively. There was no significant change in degree of disease activity in 6 patients whose biologics were continued beyond the first trimester. Improvement in disease activity was observed during pregnancy among the nonbiologics-treated patients. Corticosteroids were initiated or the dosage was increased during 6 pregnancies, all involving patients whose biologics were stopped before pregnancy.Conclusion.Continuation of biologics therapy was associated with a low level of disease activity and a low probability of flare during pregnancy. Stopping treatment with biologics before pregnancy is associated with flare during pregnancy and the postpartum period.

Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients.To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs.In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment.The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data.Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported.

Rheumatoid arthritis (RA) patients have many therapeutic options; however, tools to predict individual patient response are limited. The Genefron personal diagnostic kit, developed by analyzing large datasets, utilizes selected interferon stimulated gene expressions to predict treatment response. This study evaluates the kit's prediction accuracy of individual RA patients' response to tumor necrosis alpha (TNFα) blockers.A retrospective analysis was performed on RA patients reported in published datasets. A prospective analysis assessed RA patients, before and 3 months after starting a TNFα blocker. Clinical response was evaluated according to EULAR response criteria. Blood samples were obtained before starting treatment and were analyzed utilizing the kit which measures expression levels of selected genes by quantitative real time polymerase chain reaction (PCR). ROC analysis was applied to the published datasets and the prospective data.The Genefron kit analysis of retrospective data predicted the response to a TNFα blocker in 53 of 61 RA patients (86.8% accuracy). In the prospective analysis, the kit predicted the response in 16 of 18 patients (89% accuracy) achieving a EULAR moderate response, and in 15 of 18 patients achieving a EULAR good response (83.3% accuracy). ROC analysis applied to the two published datasets yielded an AUC of 0.89. ROC analysis applied to the prospective data yielded an AUC of 0.83 (sensitivity - 100%, specificity - 75%) The statistical power obtained in the prospective study was .9.The diagnostic kit predicted the response to TNFα blockers in a high percentage of patients assessed retrospectively or prospectively. This personal kit may guide selection of a suitable biological drug for the individual RA patient.

The aim of this study was to evaluate the presence of autoantibodies to cyclic citrullinated synthetic peptides (ACPAs) in the sputum of patients with long-standing rheumatoid arthritis (RA).Nineteen consecutive RA patients and 16 age- and sex-matched control subjects participated in this cross-sectional study. All underwent complete lung function tests and provided induced sputum. Antibodies to citrullinated (CitP) and the corresponding norleucine-containing (NorP) peptides in the sputum of the RA patients and control subjects, as well as in the serum of the RA patients, were determined by enzyme-linked immunosorbent assay.Patients with RA had the following characteristics: mean disease duration of 12 years, Disease Activity Score for 28 joints of 3.44, and Sharp-van der Heijde score of 57.5. Ten of the 19 RA patients showed high titers of ACPAs in their sera. Four of the seropositive (40%), none of the seronegative RA patients, and only 1 of the control subjects showed detectable levels of ACPAs in their sputum. The ratio between the reactivity with CitP and NorP peptides in the sputum was significantly higher in RA sputum than in control sputum (1.33 ± 1.2 vs. 0.64 ± 0.14, P = 0.02). A positive correlation was found between sputum ACPAs and age, serum ACPAs, sputum anti-NorP, serum anti-CitP/NorP reactivity ratio, and the proportion of neutrophils and lymphocytes in the sputum. No significant correlation was found between sputum ACPAs and disease severity, history of smoking, lung function tests, or treatment for RA.Anticitrullinated protein/peptide antibodies can be detected in the sputum of RA patients and are correlated with the presence in the serum.

Objectives: Belimumab has recently been approved for the treatment of systemic lupus erythematosus (SLE) refractory to standard therapy. Following one case of an SLE flare after cessation of belimumab, we hypothesized that this might lead to a rebound phenomenon and possible exacerbation of SLE.Method: Members of the Israeli Society of Rheumatology were contacted by e-mail and asked to report cases of an SLE flare following cessation of belimumab treatment.Results: Three cases of SLE patients who experienced a severe SLE flare following cessation of belimumab therapy were reported. In all cases, belimumab was given as treatment for active mucocutaneous manifestations and/or polyarthritis with improvement in all three patients, one of whom achieved disease remission. In all three cases, patients experienced a severe flare in previously uninvolved major organ systems, including one case of class IV lupus nephritis accompanied by a new-onset severe headache with elevated cerebrospinal fluid (CSF) protein and...

Background Detection of axial disease has important implications. Data on the structural changes of the spine and SIJ in PsA is mainly based on plain XR and MRI of SIJ. The prevalence and distribution of spinal changes in PsA as detected by MRI is largely unknown. Objectives To evaluate acute and structural changes in spine and SIJ by whole spine MRI performed in a consecutive clinical cohort of PsA. Methods Adult PsA (CASPAR criteria) patients were enrolled in the study. All underwent clinical exam, CRP, HLA-B27 tests, and MRI of the entire spine and SIJ. Spinal sagittal T1-W, STIR and semi-coronal T1-W and T2-W with fat saturation sequences of the SIJ were performed. The spine was scored for the presence of syndesmophytes, bone marrow edema (BME)/fatty corners and enthesitis. SIJS were scored (Berlin score) for the presence of BME, fatty replacement, erosions, sclerosis, and ankylosis. Findings were further categorized into active sacroiliitis (ASAS1), structural sacroiliitis, and spinal findings compatible with SpA (≥3 BME or ≥4 fatty corners2). All MRIs were evaluated by an experienced musculoskeletal radiologist, blinded to clinical data. Data were analyzed by SPSS Version 20.0. Results Ninety six patients completed the study.(Table1) Active/structural/total sacroiliitis was detected in 26%/11.5%/37.5% of patients, respectively. Spinal SpA was demonstrated in 15.6%.(Table 2) Isolated spinal changes were detected in 2.1% of the cohort. Presence of inflammatory back pain (IBP) by ASAS correlated with the prevalence of active sacroiliitis (p 0.024) and SpA (axial/SIJ) (p 0.003). The extent of psoriasis severity (PASI) correlated with both SIJ and whole spine SpA changes. (p 0.02 for both) Gender differences or biologic therapy did not affect the prevalence of SIJ or spine involvement. Conclusions In the present PsA cohort, active and structural sacroiliitis was more prevalent vs typical spinal SpA changes. In particular, there was a paucity of SpA changes in the cervical spine. The most prominent axial findings included fatty corners and syndesmophytes. IBP presence and extensive skin disease correlated with SpA axial and SIJ changes. References Lambert RG. Ann Rheum Dis. 2016,75. Hermann KG. Ann Rheum Dis 2012.71. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) patients have many therapeutic options. However, there are limited tools to predict the individual patient9s response to therapy. The Genefron personal diagnostic kit (IFR 300) has been developed based on analysis of large databases to select interferon stimulated gene (ISG) expressions which could predict response to a biologic agent Objectives This study aims to evaluate the ability of the Genefron diagnostic kit to predict the individual RA patient response to TNFα blockers. Methods Two separate analyses were performed, one retrospective and one prospective analysis. The response of 61 RA patients reported in 2 published data sets was analyzed retrospectively utilizing the Genefron kit. In addition, 18 patients with RA were assessed prospectively, before and 3 months after starting treatment with a TNFα blocker. Clinical assessment included swollen and tender joint counts, patient and physician assessments of disease activity. Patients9 blood samples were obtained before administration of the TNFα blocker and were analyzed utilizing the Genefron diagnostic kit which measures expression levels of selected genes by quantitative real time PCR. Results Genefron kit analysis of retrospective data correctly predicted the response to a TNFα blocker in 53 of 61 RA patients (accuracy - 86.8%). In the prospective analysis 6 patients achieved a moderate EULAR response, 6 achieved a good EULAR response and 6 did not respond. According to the EULAR moderate response, the Genefron diagnostic kit predicted the response correctly in 16 of 18 patients (accuracy-89%, sensitivity -100%, specificity - 67%). According to the EULAR good response, the kit predicted the response correctly in 15 of 18 patients (accuracy - 83.3%, sensitivity - 100%, specificity - 75%). Conclusions The Genefron diagnostic kit predicted the response to TNFα blockers in a high percentage of RA patients assessed either retrospectively or prospectively in a real life setting. This personal diagnostic kit has the ability to guide selection of a suitable biological drug for the individual RA patient Disclosure of Interest None declared

The objective of the study was to combine ultrasonographic (US) with clinical findings for comparing the effect of adalimumab (ADA) to methotrexate (MTX) on the thickness of tendons and enthesis in psoriatic arthritis (PsA) patients. Forty-three consecutive PsA patients were examined at baseline and after 6 and 12 weeks of treatment with ADA or MTX. The US assessment included thickness measurement of the extensor (ET) and flexor tendons (FT) of the second and third finger of both hands, plantar aponeurosis (PA) and the Achilles tendon (AT) bilaterally. Disease activity (DA) was assessed by the number of tender (TJ) and swollen joints (SJ), the number of inflamed enthesis (IE), pain assessment (PAI), and patient (PDAI) and physician (PHDAI) disease activity evaluations by visual activity score (VAS). Nineteen patients received MTX and 24 patients received ADA. All DA parameters improved in both groups. A decrease in thickness of tendons and enthesis was observed only in the ADA group, reaching a level of significance for the left AT (p = 0.01), left PA (p = 0.007), the second left FT (p = 0.04) and the third ET (p = 0.04). ADA patients showed a trend towards a better response to treatment compared to MTX patients that reach significance at week 6 of treatment for the thickness of left AT (p = 0.04), left PA (p = 0.03), the number of TJ (p = 0.0136), PAI (p = 0.0028), and PDAI (p = 0.029). ADA treatment for PsA compared to MTX significantly improved signs of DA and several US parameters. US assessment of enthesis can be an additional useful tool in the monitoring of psoriatic enthesopathy.

Rituximab is a monoclonal antibody directed against the CD20 antigen on the surface of normal and malignant B lymphocytes. Its use in autoimmune conditions is rapidly expanding. Late-onset neutropenia (LON) is a well-recognized side effect of rituximab therapy in lymphoma patients. Only a small number of cases of LON have been reported in patients with autoimmune disorders. The aim of this work is to review cases in Israel and to compare them to published cases in the literature thus adding to the body of knowledge regarding this unusual phenomenon. Members of the Israeli Rheumatology Association were encountered by e-mail, requesting reports of cases of LON after therapy with rituximab. Submitted cases were reviewed, with demographics and clinical data collated and tabled. Current cases were compared to previously published rheumatology cases. Twelve episodes of LON following rituximab therapy were reported. All patients were female with an average age of 50 years (range 22-78). LON occurred at an average of 155 days after therapy (range 71-330). The average leukocyte count was 1,456 white cells, with an average of 413 neutrophils (range 0-1,170 neutrophils). Three of the patients underwent bone marrow biopsies which showed white cell line maturation arrest with an increased number of lymphocytes. No blasts were seen. Our results add support to the growing evidence that this adverse event usually follows a benign course and is not an absolute contraindication for repeat treatment if required in the future. However, vigilance is recommended with routine periodic blood counts, especially 5 months following rituximab administration when the risk is expected to be the highest.

BackgroundMemory impairment is prevalent in systemic lupus erythematosus (SLE); however, the pathogenesis is unknown.MethodsWe studied 12 patients with SLE without clinically overt neuropsychiatric manifestations and 11 matched healthy controls, aiming to characterize neural correlates of memory impairment, using structural and functional magnetic resonance imaging (MRI). The paradigm consisted of three encoding and free-recall cycles, allowing characterization of dynamics along consecutive retrieval attempts.ResultsDuring learning, patients with SLE and healthy controls showed brain activity changes in two principal networks, the default mode network (DMN) and the task-positive network (TPN). Patients with SLE demonstrated significantly less deactivation in the DMN and greater activation in the TPN, reflecting greater recruitment of both networks. The anterior medial prefrontal cortex (amPFC) of the DMN emerged as the only region where brain activity dynamics were altered both over the learning process ( p ConclusionsIncreased brain activation in patients with SLE during learning may reflect compensatory mechanisms to overcome memory impairment. Our findings localize this impairment to the amPFC, consistent with the behavioral pattern seen in SLE. Altered networking of the hippocampal subsystem of the DMN is consistent with hippocampal neuronal damage seen in SLE, and may reflect compensatory cortical reorganization to cope with dysfunction in these regions pivotal to mnemonic functions.

The American Academy of Ophthalmology published in 2011 revised recommendations regarding screening for hydroxychloroquine (HCQ) toxicity. We aimed to assess implementation of these recommendations by rheumatologists and ophthalmologists. A questionnaire regarding screening practices for HCQ toxicity was distributed among all members of the Israeli societies of Rheumatology and Ophthalmology. A total of 128 physicians responded to the questionnaire (rheumatologists: 60, ophthalmologists: 68). Only 5% of the rheumatologists and 15% of the ophthalmologists are aware of ophthalmologic assessments recommended for baseline and follow-up evaluation. When an abnormal test is detected, even if inappropriate for HCQ toxicity screening, 60% of the responders recommend cessation of therapy. Only 13% of the responders recommend first follow-up after five years for patients without risk factors; the remainder recommend more frequent testing. Ninety-six percent of the responders are not aware of all of the known risk factors for HCQ toxicity. Use of inappropriate tests to detect HCQ retinal toxicity may lead to unnecessary cessation of beneficial treatment with risk of disease flare, while lack of consideration of risk factors may put patients at risk for toxicity. These results emphasize the importance of implementing the recommendations to ensure safe and effective use of this drug.

To evaluate the prevalence of sacroiliitis, the radiographic hallmark of inflammatory spondyloarthropathy, among patients diagnosed with fibromyalgia syndrome (FMS), using the current Assessment of SpondyloArthritis International Society (ASAS) criteria and magnetic resonance imaging.Patients experiencing FMS (American College of Rheumatology 1990 criteria) were interviewed regarding the presence of spondyloarthritis (SpA) features and underwent HLA-B27 testing, C-reactive protein (CRP) level measurement, and magnetic resonance imaging examinations of the sacroiliac joints. FMS severity was assessed by the Fibromyalgia Impact Questionnaire and the Short Form 36 health survey. SpA severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index.Sacroiliitis was demonstrated among 8 patients (8.1%) and ASAS criteria for diagnosis of axial SpA were met in 10 patients (10.2%). Imaging changes suggestive of inflammatory involvement (e.g., erosions and subchondral sclerosis) were demonstrated in 15 patients (17%) and 22 patients (25%), respectively. The diagnosis of axial SpA was positively correlated with increased CRP level and with physical role limitation at recruitment.Imaging changes suggestive of axial SpA were common among patients with a diagnosis of FMS. These findings suggest that FMS may mask an underlying axial SpA, a diagnosis with important therapeutic implications. Physicians involved in the management of FMS should remain vigilant to the possibility of underlying inflammatory disorders and actively search for such comorbidities.

To assess the effect of the timing of vaccination in relation to administration of infliximab on the efficacy and safety of influenza vaccine in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS).The study population comprised 38 patients treated with infliximab at a mean dosage of 3 mg/kg (20 RA patients; 18 AS patients; 23 RA controls (treated with disease modifying antirheumatic drugs other than anti-tumor necrosis factor-alpha; and 17 healthy controls). Split-virion inactivated vaccine containing 15 mug hemagglutinin/dose of each of A/New Caledionan/20/1999 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004 (M) was used. Patients treated with infliximab were divided into 2 groups: 22 were vaccinated on the day of administration of infliximab, while 16 received the vaccine 3 weeks after infliximab. Baseline and 4- to 6-week clinical assessment of disease activity included erythrocyte sedimentation rate and C-reactive protein for all patients, the 28-joint disease-activity score for RA patients, and Bath Ankylosing Spondylitis Disease Activity Index for AS patients. Hemagglutination inhibition (HI) antibodies were tested by a standard World Health Organization procedure. Response was defined asor=4-fold rise in HI antibodies 4 to 6 weeks after vaccination, or seroconversion in patients with a nonprotective baseline level of antibodies (1/40). Geometric mean titers (GMT) were calculated to assess the immunity of the whole group.At baseline, RA patients and controls had similar occurrence of protective levels of HI antibodies and GMT, while AS patients had lower levels reflecting lower rates of previous vaccination. Four weeks after vaccination, a significant and similar increase in GMT for each antigen was observed in all groups (P0.004) except in the RA-infliximab group, vaccinated 3 weeks after administration of infliximab, in whom the increase in GMT was not significant for H1N1 (P = 0.12) and H3 (P = 0.06). AS patients demonstrated an increase in GMT, independently of the time of vaccination. The percentage of responders was similar in all groups. The response was not affected by variables such as age, gender, methotrexate, or prednisone use. Parameters of disease activity remained unchanged. No adverse effects other than injection site pain were recorded.Influenza virus vaccine generated a good humoral response in RA and AS patients treated with infliximab.

Earlier we showed the generation of tolerizing human monocyte-derived DC following interaction with iC3b-opsonized apoptotic cells. In this study we examine the generation of DC with our previously described tolerogenic phenotype in patients with the systemic autoimmune disease systemic lupus erythematosus (SLE). Monocyte-derived DC were generated in 71 SLE patients, characterized, and then tested for clearance of iC3b-opsonized 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate-stained apoptotic cells using flow cytometry, and for autologous T-cell activation using autologous mixed lymphocyte reaction (AMLR), at the same time as controls. Compared with healthy, age- and gender-matched controls, SLE patients showed upregulation of MHC class II, with a mean expression of 130.5%+/-36.8% (p0.007); CD86 in immature DC from SLE patients, generated in autologous human or control plasma, were also upregulated, with mean expression 106.6%+/-18.0% (p0.03). A significant (20%) reduction in iC3b-apoptotic cell uptake, together with increased autologous mixed lymphocyte reaction, was seen in 75% of SLE patients. Mean 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate-stained apoptotic cell acquisition was 70.0%+/-24% (p0.0001) compared with healthy controls. Altered generation of a tolerizing DC phenotype was seen in at least one third of SLE patients following interaction with iC3b-opsonized apoptotic cells. These results suggest that a substantial portion of SLE patients fail to generate DC with a tolerizing phenotype.

To present a case of severe interstitial nephritis with proteinuria in primary Sjögren's syndrome (pSS) and review the literature regarding renal disease and its management in pSS, aiming to suggest recommendations for treatment.A search of MEDLINE (PubMed) was performed for review articles and case reports using the MESH terms: Sjögren syndrome; renal disease; interstitial nephritis (IN); glomerulonephritis (GN).We describe a rare case of pSS presenting with hypokalaemic tetraparesis and proteinuria due to severe IN, successfully treated with high-dose steroids and azathioprine. Reviewing the literature, we identified 180 reported cases of renal involvement in pSS (selected based on the European criteria for pSS), 89 of which underwent renal biopsies revealing IN in 49 cases, GN in 33 samples, and both IN and GN in seven. Eighteen studies reported treatment experience of renal disease in 32 pSS cases. Seventeen patients were treated with corticosteroids and cyclophosphamide, and 15 patients received only steroids with improvement in the majority of cases.The present case, as well as the limited number of reports in the literature, suggest that renal involvement, including IN, in pSS may improve with immunosuppressive therapy. Further studies are required to determine indications for and dosages of immunosuppressive treatment in patients with renal involvement of pSS.