The association between sonographic enthesitis with sonographic synovitis and tenosynovitis in psoriatic arthritis patients.

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 (ß = 0.18, P = 0.008) and between sonographic enthesitis and sonographic tenosynovitis (ß = 0.06, P = 0.02). These associations were derived from the enthesitis inflammatory subcategory of the MASEI (P < 0.05). Associations between enthesitis and synovitis were also demonstrated on the level of the elbow, knee and ankle joints (P < 0.05). In addition, sonographic enthesitis was significantly associated with older age, male sex, swollen joint count, CRP level and physical occupation. 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.

Effect of Secukinumab and Tumor Necrosis Factor Inhibitors on Humoral Response to BNT162b2 mRNA Vaccine in Patients With Spondyloarthritis Compared to Immunocompetent Controls.

OBJECTIVE: To assess the humoral response to the BNT162b2 mRNA vaccine among patients with spondyloarthritis (SpA) receiving secukinumab (SEC) compared to those receiving tumor necrosis factor inhibitors (TNFi) and immunocompetent controls. METHODS: Consecutive patients with psoriatic arthritis or axial SpA receiving SEC (n = 37) or TNFi (monotherapy, n = 109; + methotrexate [MTX], n = 16), immunocompetent controls (n = 122), and patients with rheumatoid arthritis (RA) receiving TNFi therapy (controls, n = 50) were vaccinated with 2 or 3 doses of the BNT162b2 vaccine. We evaluated humoral response, adverse events, and disease activity, and monitored for breakthrough coronavirus disease 2019 (COVID-19) postvaccination. RESULTS: The 2-dose vaccine regimen induced a comparable seropositive response in all study groups. S1/S2 antibody titers (in binding antibody units/mL; mean [SD]) were higher in the SEC group vs the TNFi + MTX-SpA and TNFi-RA groups (192.5 [68.4] vs 104.6 [46.9], P < 0.001, and 143.1 [81.9], P = 0.004). After 6 months, 96.3%, 96.6%, and 80.9% of the SEC, immunocompetent, and TNFi monotherapy-SpA groups (P = 0.10), respectively; 66.7% of the TNFi + MTX-SpA group (P = 0.03); and 63% of the TNFi-RA group (P = 0.004) remained seropositive. S1/S2 antibody titer decline was steeper in the TNFi groups than the SEC group. After the third dose, 100% of the SpA and immunocompetent and 88.9% of the TNFi-RA (P = 0.25) groups were seropositive. Rate of breakthrough COVID-19 infection was higher in the TNFi groups than in the SEC group (36-37.5% vs 10.8%). No significant between-group differences were observed for postvaccination disease activity and adverse events. CONCLUSION: SEC did not interfere with the immunogenic response to BNT162b2 vaccine in patients with SpA; however, TNFi therapy was associated with lower S1/S2-antibody titers, faster decline, and higher rate of breakthrough infections.

Systemic Lupus Erythematous and Obstructive Sleep Apnea: A Possible Association.

Marked fatigue is common in patients with systemic lupus erythematosus (SLE). This study aimed to assess the association of sleep disorders, including obstructive sleep apnea (OSA), with SLE. Forty-two consecutive patients with SLE and 20 healthy controls were recruited and underwent a one-night ambulatory sleep examination. They completed questionnaires, including the Pittsburgh Sleep Quality Index (PSQI) and Functional Assessment of Chronic Illness Therapy (FACIT). SLE disease activity and damage were assessed by the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI). A significantly increased apnea/hypopnea index was noted in the SLE group compared to healthy controls (p = 0.004). SLE patients had higher rates of moderate-to-severe OSA (p = 0.04), PSQI (p = 0.001), and FACIT scores (p = 0.0008). Multivariate analysis revealed that the SDI was associated with OSA (p = 0.03). There was a positive association between SLEDAI-2K and moderate-to-severe OSA (p = 0.03). Patients with SLE had an increased prevalence of OSA and poorer quality of sleep compared to healthy controls. Our findings suggest that active disease and accumulated damage may be associated with OSA. These findings highlight the importance of identifying the presence of OSA in patients with SLE.

Sex-Based Differences in Sonographic and Clinical Findings Among Patients With Psoriatic Arthritis.

OBJECTIVE: To investigate sex-based sonographic differences in patients with psoriatic arthritis (PsA). METHODS: The 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). RESULTS: The 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 and P = 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). CONCLUSION: Sonographic 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.

Immunogenicity induced by two and three doses of the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases and immunocompetent controls: a longitudinal multicentre study.

OBJECTIVES: To evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls. METHODS: A 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. RESULTS: The two-dose vaccine regimen induced a higher humoral response in controls compared with patients, postvaccination seropositivity rates of 100% versus 84.72%, p<0.0001, and 96.55% versus 74.26%, p<0.0001 at 2-6 weeks and at 6 months, respectively. The third vaccine dose restored the seropositive response in all controls and 80.47% of patients with AIIRD, p=0.0028. All patients treated with methotrexate monotherapy, anticytokine biologics, abatacept and janus kinase (JAK) inhibitors regained the humoral response after the third vaccine, compared with only a third of patients treated with rituximab, entailing a 16.1-fold risk for a negative humoral response, p≤0.0001. Cellular immune response in rituximab-treated patients was preserved before and after the third vaccine and was similar to controls. Breakthrough COVID-19 rate during the Delta surge was similar in patients and controls, 1.83% versus 1.43%, p=1. CONCLUSIONS: The 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.

Predictors of Immunogenic Response to the BNT162b2 mRNA COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases Treated with Rituximab.

Treatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral response. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX). We analyzed 108 AIIRD-RTX patients and 122 immunocompetent controls vaccinated with BNT162b2 mRNA participating in a multicenter vaccination study. Immunogenicity was defined by positive anti-SARS-CoV-2 S1/S2 IgG. We used a stepwise backward multiple logistic regression to identify predicting factors for a positive immunogenic response to vaccination and develop a predicting calculator, further validated in an independent cohort of AIIRD-RTX BNT162b2 mRNA vaccinated patients (n = 48). AIIRD-RTX patients who mounted a seropositive immunogenic response significantly differed from patients who did not by a lower number of RTX courses (median (range) 3 (1-10) vs. 5 (1-15), p = 0.007; lower cumulative RTX dose (mean ± SD) 6943.11 ± 5975.74 vs. 9780.95 ± 7240.12 mg, p = 0.033; higher IgG level prior to last RTX course (mean ± SD), 1189.78 ± 576.28 vs. 884.33 ± 302.31 mg/dL, p = 0.002), and extended interval between RTX treatment and vaccination, 469.82 ± 570.39 vs. 162.08 ± 160.12 days, p = 0.0009, respectively. Patients with ANCA-associated vasculitis and inflammatory myositis had a low likelihood of a seropositive immunogenic response compared to patients with rheumatoid arthritis, odds ratio (OR) 0.209, 95% confidence interval (CI) 0.046-0.96, p = 0.044 and OR 0.189, 95% CI 0.036-0.987, p = 0.048, respectively. Based on these findings, we constructed a calculator predicting the probability of a seropositive immunogenic response following BNT162b2 mRNA vaccination which performed with 90.5% sensitivity, 59.3% specificity, and 63.3% positive and 88.9% negative predictive values. In summary, the predicting calculator could guide clinicians for optimal timing of BNT162b2 mRNA vaccination in AIIRD-RTX patients.

Association of a Third Dose of BNT162b2 Vaccine With Incidence of SARS-CoV-2 Infection Among Health Care Workers in Israel.

Importance: Administration of a BNT162b2 booster dose (Pfizer-BioNTech) to fully vaccinated individuals aged 60 years and older was significantly associated with lower risk of SARS-CoV-2 infection and severe illness. Data are lacking on the effectiveness of booster doses for younger individuals and health care workers. Objective: To estimate the association of a BNT162b2 booster dose with SARS-CoV-2 infections among health care workers who were previously vaccinated with a 2-dose series of BNT162b2. Design, Setting, and Participants: This was a prospective cohort study conducted at a tertiary medical center in Tel Aviv, Israel. The study cohort included 1928 immunocompetent health care workers who were previously vaccinated with a 2-dose series of BNT162b2, and had enrolled between August 8 and 19, 2021, with final follow-up reported through September 20, 2021. Screening for SARS-CoV-2 infection was performed every 14 days. Anti-spike protein receptor binding domain IgG titers were determined at baseline and 1 month after enrollment. Cox regression with time-dependent analysis was used to estimate hazard ratios of SARS-CoV-2 infection between booster-immunized status and 2-dose vaccinated (booster-nonimmunized) status. Exposures: Vaccination with a booster dose of BNT162b2 vaccine. Main Outcomes and Measures: The primary outcome was SARS-CoV-2 infection, as confirmed by reverse transcriptase-polymerase chain reaction. Results: Among 1928 participants, the median age was 44 years (IQR, 36-52 years) and 1381 were women (71.6%). Participants completed the 2-dose vaccination series a median of 210 days (IQR, 205-213 days) before study enrollment. A total of 1650 participants (85.6%) received the booster dose. During a median follow-up of 39 days (IQR, 35-41 days), SARS-CoV-2 infection occurred in 44 participants (incidence rate, 60.2 per 100 000 person-days); 31 (70.5%) were symptomatic. Five SARS-CoV-2 infections occurred in booster-immunized participants and 39 in booster-nonimmunized participants (incidence rate, 12.8 vs 116 per 100 000 person-days, respectively). In a time-dependent Cox regression analysis, the adjusted hazard ratio of SARS-CoV-2 infection for booster-immunized vs booster-nonimmunized participants was 0.07 (95% CI, 0.02-0.20). Conclusions and Relevance: Among health care workers at a single center in Israel who were previously vaccinated with a 2-dose series of BNT162b2, administration of a booster dose compared with not receiving one was associated with a significantly lower rate of SARS-CoV-2 infection over a median of 39 days of follow-up. Ongoing surveillance is required to assess durability of the findings.

Ultrasound, magnetic resonance imaging and radiography of the finger joints in psoriatic arthritis 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 < 0.001). The absolute agreement between US and MRI was good-to-very good for synovitis (85-96%, PABAK = 0.70-0.92), flexor tenosynovitis (93-98%, PABAK = 0.87-0.96) and extensor paratenonitis (95-98%, PABAK = 0.90-0.97). Agreement between US, MRI and radiography was 96-98% (PABAK = 0.92-0.97) for erosions and 71-93% (PABAK = 0.47-0.87) for bone proliferations. Sensitivity of US with MRI as gold standard was higher for synovitis (0.5-0.86) and extensor paratenonitis (0.63-0.85) than for flexor tenosynovitis (0.1-0.75), while the specificity was high for each pathology (0.89-0.98). 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.

Seroprevalence of SARS-CoV-2 antibodies in patients with autoimmune inflammatory rheumatic diseases.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

High Body Mass Index is Associated with Shorter Retention of Tumor Necrosis Factor-Alpha Blocker Treatment in Rheumatoid Arthritis.

PURPOSE: To evaluate the association between body mass index (BMI) and tumor necrosis factor α (TNF-α) blockers retention in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: This prospective cohort study analyzed data about patients with RA who initiated TNF blockers from the Israeli registry of inflammatory diseases from 2011 to 2019. Patients were grouped by BMI: normal (BMI <24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), obese (BMI 30-34.9 kg/m2) and morbid obese (BMI ≥35 kg/m2). Treatment cessation due to inefficacy was defined as an "event" and therapy with a drug above 3 months was defined as a "course." Kaplan-Meier survival curve was used to describe drug survival. Event-free survival was calculated using Cox regression with a hazard ratio and confidence interval of 95%. RESULTS: The final analysis included 521 RA patients (80% females) treated with etanercept, infliximab, adalimumab or golimumab. Eight hundred and eighteen treatment initiations were included in the final analysis, 334 (41%) in the normal weight group, 261 (32%) in the overweight, 144 (17%) in the obese and 79 (10%) in the morbid obesity group. Three hundred and twenty-six (40%) treatment initiations were with etanercept, 215 (26%) with adalimumab 197 (24%) with infliximab, and 80 (10%) with golimumab. BMI was inversely associated with drug survival. Morbid obese patients were more likely to discontinue treatment compared with normal weight patients HR 2.28 (95% CI 1.67-3.10, p<0.01). This association remained significant for each drug type (except for golimumab) in a subgroup analysis. Adalimumab switch rate was higher compared to etanercept with HR =1.51 (95% CI 1.20-1.91, p<0.01), no other significant differences were noted between the other drugs. CONCLUSION: Morbid obese RA patients have lower TNF-α blocker retention compared to normal weight patients.

Role of ultrasound for assessment of psoriatic arthritis patients with fibromyalgia.

OBJECTIVE: To investigate whether ultrasonography (US), as an objective imaging modality, can optimise the evaluation of disease activity in psoriatic arthritis (PsA) patients with concomitant fibromyalgia syndrome (FMS). METHODS: The study population included 156 consecutive PsA patients who were recruited prospectively and fulfilled the ClASsification criteria for Psoriatic ARthritis criteria. The patients underwent complete clinical evaluation including assessment of fulfilment of the 2016 fibromyalgia classification criteria. All of the patients underwent US evaluation including 52 joints, 40 tendons and 14 entheses. The US score was based on the summation of a semiquantitative score (including synovitis, tenosynovitis and enthesitis). Scoring was performed by a sonographer blinded to the clinical data. Spearman's correlation coefficient and multivariate linear regression models were used to examine the association of FMS with clinical and the US scores. RESULTS: Forty-two patients (26.9%) with coexisting PsA and FMS were compared with 114 (73.1%) PsA patients without FMS. Patients with PsA and FMS had significantly increased scores for clinical composite indices, including non-Minimal Disease Activity, Composite Psoriatic Disease Activity Index (CPDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS) (p<0.001). In contrast, the total US score and its subcategories were similar for those with and without FMS. The total US score significantly correlated with CPDAI, DAPSA and PASDAS (p<0.001) in the PsA without FMS but not in the PsA with FMS group. FMS was significantly associated with higher clinical scores (p<0.001) but not with the US score (multivariable linear regression models). CONCLUSIONS: US has significantly greater value than composite clinical scores in the assessment of disease activity in PsA patients with FMS.

Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study.

INTRODUCTION: Vaccination 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. METHODS: A 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. RESULTS: Following vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, p<0.0001 and 132.9±91.7 vs 218.6±82.06 BAU/mL, p<0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Postvaccination disease activity remained stable in the majority of patients. CONCLUSION: mRNA 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.

Prevalence of COVID-19 and seroprevalence to SARS-CoV-2 in a rheumatologic patient population from a tertiary referral clinic in Israel.

BACKGROUND: It is unclear if the prevalence of COVID-19 in rheumatologic patients is similar to that of the general population. There are no reports of seroprevalence of SARS-CoV-2 in these patients. AIMS: To investigate prevalence of COVID-19 cases and seroprevalence among rheumatologic patients and the risk factors for infection. METHODS: A cross-sectional study in a rheumatologic population. An online questionnaire was sent on 31 April 2020. Blood samples from 20% sample of patients were drawn for SARS-CoV-2 antibodies. Patients were divided based on autoimmune (AI) diagnosis. Prevalence of COVID-19 by nasopharyngeal swab and by serology (seroprevalence) was compared to national data. Risk factors for infection of SARS-CoV-2 were assessed. RESULTS: The study group included 1204 patients, 74.5% had an AI diagnosis. The prevalence of COVID-19 was 0.16% in the rheumatologic patient population and 0.22% in the AI group, which was not different from prevalence in Israel on 4 May 2020 (0.18%, P = 0.912 and P = 0.759 respectively). Serologic tests were performed in 242 patients, of which five were found positive pointing to a seroprevalence of 2.07%. Exposure to a known COVID-19 patient was the only significant risk factor for being positive by swab or by serology. AI diagnosis, immunosuppression, corticosteroid, hydroxychloroquine did not influence the risk. CONCLUSIONS: The prevalence of COVID-19 in a population of rheumatologic patients was similar to that of the general population. Mild/asymptomatic cases may be prevalent according to serologic tests. The major risk factor for infection is exposure to a known case of COVID-19, and immunosuppression did not play a role in the risk of infection.

Prevalence of Nonradiographic Sacroiliitis in Patients With Psoriatic Arthritis: A Real-life Observational Study.

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.

Mortality in psoriatic arthritis: Risk, causes of death, predictors for death.

BACKGROUND/OBJECTIVES: Mortality studies in psoriatic arthritis (PsA) have provided inconsistent results. This study aimed to: 1) Estimate trends in mortality rates among PsA patients over calendar time; 2) Evaluate cause-specific mortality rates in patients with PsA compared to the general population; 3) Identify predictors for mortality in PsA. METHODS: The study was carried out at the University of Toronto Psoriatic Arthritis Clinic where patients are followed prospectively according to a standard protocol at 6- to 12- month intervals. Standardized mortality ratios (SMRs) were calculated overall, by age, and by sex with reference to the Ontario population. Causes of death were recorded by ICD9 and ICD10 codes and cause-specific SMRs were computed. Cox regression models were used to identify predictors for mortality among PsA patients. RESULTS: Among 1490 patients followed over 15062.8 patient-years, 225 (15%) confirmed deaths were recorded (111 females, 114 males). The overall SMR was 0.92 (95% CI: 0.81-1.05), the sex-specific SMRs were 1.08 (95% CI: 0.89-1.30) for females and 0.81 (95% CI: 0.66-0.97) for males. The age-specific SMRs were 3.36 (95% CI: 1.61-6.18), 0.97 (95% CI: 0.68-1.34), 0.88 (95% CI: 0.73-1.06) and 0.86 (95% CI: 0.66-1.11) for 20-39, 40-59, 60-79 and above 80 years of age, respectively. Major causes of death included malignant neoplasms (n=61; SMR=0.97, 95% CI: 0.72-1.28), acute myocardial infarction (n=32; SMR=1.11, 95% CI: 0.74-1.58), and pneumonia (n=14; SMR=2.46, 95% CI: 1.27-4.31). Factors found to be associated with increased mortality include elevated acute phase reactants, presence of comorbidities such as heart disease and cancer, and lower education level. CONCLUSION: Young patients with PsA are at increased mortality risk. Better control of comorbidities may reduce this risk.

Chronic schistosomiasis in African immigrants in Israel: Lessons for the non-endemic setting.

To study the clinical presentation of Chronic Schistosomiasis (CS) in immigrants from East Africa to Israel and the tests that were useful in confirming the diagnosis.A retrospective study of all medical notes pertaining to hospitalized patients who were immigrants from East Africa with a pathological or microscopic confirmation of CS. Literature review was also conducted focusing on diagnosis of schistosomiasis among immigrants from endemic countries.We identified 32 suspected and 11 confirmed cases of CS. Most of the patients (82%) presented with gastrointestinal symptoms. Sensitivity of stool smear, serology and tissue diagnosis (by histopathology or microscopy) were 14%, 100%, 89%, respectively. Patients have undergone extensive diagnostic evaluation with long hospitalization stays (median 10 days, range 4 to 33 days).CS has multiple presentations and is seen in Israel among refugees from Eritrea and Sudan. Most of the manifestations are gastrointestinal, suggestive of infection with Schistosoma mansoni (S. mansoni). Standard diagnostic techniques used in endemic countries, such as microscopy for ova and parasites were unhelpful, necessitating more advanced procedures like colonoscopic or liver biopsy. We propose a diagnostic algorithm for CS in this patient population in order to make an accurate diagnosis and avoid unnecessary invasive procedures.

Psoriatic Arthritis Sonographic Enthesitis Instruments: A Systematic Review of the Literature.

OBJECTIVE: As part of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) ultrasound working group, we performed a systematic review of the literature to assess the evidence and knowledge gaps in scoring instruments of enthesitis in psoriatic arthritis (PsA). METHODS: A systematic search of PubMed, EMBase, and Cochrane databases was performed. The search strategy was constructed to find original publications containing terms related to ultrasound, enthesitis, spondyloarthritis (SpA) or PsA. Data extraction focused on the properties of the sonographic enthesitis instruments used in each study following components of the Outcome Measures in Rheumatology (OMERACT) filter: feasibility, test-retest reliability, construct validity as related to clinical assessment of enthesitis, biomarkers of inflammation and imaging of enthesitis by other modalities, discriminative validity, and responsiveness to treatment. RESULTS: Fifty-one of 310 identified manuscripts were included. Only 1 scoring instrument of enthesitis was specifically developed and validated in patients with PsA. Only 18 (35%) of the studies involved patients with PsA, while the remaining studies focused on SpA. In PsA, construct validity was assessed using biomarkers and clinical examination in 1 (2%) and 11 (21.5%) of the studies, respectively, whereas no studies used imaging for the same purpose. Only 2 (4%) of the studies assessed discriminative validity in PsA. Responsiveness to treatment was assessed in 7 studies, none of which included patients with PsA. CONCLUSION: Although sonographic enthesitis scoring instruments have been developed for SpA, only a few have been validated in PsA. None of them passed the OMERACT filter in patients with PsA. Additional research is required before endorsing a specific instrument for the assessment of enthesitis in patients with PsA.

The skin microbiome in psoriatic disease: A systematic review and critical appraisal.

BACKGROUND: Psoriasis affects 1-3% of the Canadian population. Psoriatic arthritis (PsA), the most common comorbidity of psoriasis, affects up to 30% of psoriasis patients. The skin microbiome is hypothesized to play a role in the pathogenesis of psoriatic disease (PsD-psoriasis and PsA). OBJECTIVE: To summarize the current state of literature on the skin microbiome in PsD. METHODS: A systematic review was performed using searches in Ovid, Medline, Embase, Medline Epub Ahead of Print and In-Process & Other Non-Indexed Citations, and Cochrane Central Register of Controlled Trials (CENTRAL). Search was limited to humans and English language, with no limits for date or publication type. RESULTS: Of 4,032 citations identified, 9 studies met inclusion criteria (7 on psoriasis only and 2 studies compared the microbiome characteristics between psoriasis and PsA). Compared to healthy controls, lesions demonstrated a decreased alpha diversity, higher relative abundances of Firmicutes, and lower relative abundances of Actinobacteria. Less conclusive were genus-level results, which nonetheless demonstrated trends towards increased Streptococcus, Staphylococcus, and Corynebacterium and decreased Propionibacterium in lesions vs. control. LIMITATIONS: Study designs were heterogeneous, including sampling technique and exclusion criteria. CONCLUSIONS: Phyla- and selected genus-level characteristic of the psoriatic microbiome are presented; further research is warranted.

Subcutaneous belimumab in the treatment of systemic lupus erythematosus.

Systemic lupus erythematosus is a chronic autoimmune disease with various clinical manifestations, organ involvement and laboratory findings. The disease can involve any organ including skin, joints, kidneys, central and peripheral nervous system, cardiovascular system and more. Currently, the cornerstone of treatment includes antimalarial and immunosuppressive medications and glucocorticosteroids. Recently, great effort has been invested in finding more targeted drugs for achieving better control of the disease with less adverse events. Intravenous belimumab was the first and only biologic drug to be approved by the US FDA and Health Canada for lupus over the last 50 years, and recently was studied in subcutaneous form. This paper will review the major belimumab trials with a focus on the subcutaneous form.

Novel Therapeutics in Psoriatic Arthritis. What Is in the Pipeline?

PURPOSE OF REVIEW: To highlight the recently approved therapeutic agents in psoriatic arthritis (PsA), drugs in the pipeline, as well as to discuss efficacy with regard to different clinical domains of PsA. RECENT FINDINGS: More than 15 years ago, tumor necrosis factor inhibitors (TNFi) were the first biologic disease modifying anti-rheumatic drugs (bDMARDs) that were approved for the treatment of PsA. Since then, multiple new therapeutic agents inhibiting other targets have emerged including biologics targeting interleukin (IL) 12/23, and IL 17 and oral agents targeting phosphodiesterase 4 (PDE4) and Janus kinases (JAKs). Many new agents with various modes of action including selective inhibition of IL 23, therapies promoting activated T cell apoptosis, inhibition of tyrosine kinase 2 (TYK2), and more are under active assessment in ongoing clinical trials. Effective therapies for treating PsA have emerged over the last 15 years and newer agents continue to be discovered, allowing greater therapeutic options for controlling psoriatic disease activity and preventing joint damage and disability. Personalized therapy for patients with PsA is now a possibility.