Outcomes of COVID-19 re-infections: a single-center cohort of 167 patients with systemic rheumatic diseases.

Data on COVID-19 re-infections in patients with systemic rheumatic diseases (SRDs) are lacking. We aimed to describe the course and outcomes of COVID-19 re-infections in these patients versus controls. In this single-center retrospective study, we included 167 consecutive SRD patients with at least one COVID-19 re-infection (mean age 47.3 years, females 70.7%). SRD patients were compared in terms of patient-perceived COVID-19 re-infection severity and hospitalizations/deaths with 167 age/sex-matched non-SRD controls. Logistic regression analysis was performed to assess potential milder re-infection versus primary infection severity, adjusting for study group, demographics (age, sex), vaccination status, body mass index, smoking, and comorbidities. 23 and 7 out of 167 re-infected SRD patients experienced two and three re-infections, respectively, which were comparable to the re-infection rates in controls (two: 32; and three: 2) who also had comparable COVID-19 vaccination history (89% and 95% vaccinated, respectively). In the initial infection, patients with SRDs were hospitalized (7.2% versus 1.8%, p = 0.017), and had received antiviral treatment (16.1% versus 4.7%, p < 0.001) more frequently than controls. However, hospitalizations (1.8% vs 0.6%) and antiviral treatment (7.8% vs 3.5%) did not differ (p > 0.05) between patients and controls at the first re-infection, as well as during the second and third re-infection; no deaths were recorded. Perceived severity of re-infections was also comparable between patients and controls (p = 0.847) and among those on biologic DMARDs or not (p = 0.482). In multivariable analysis, neither SRDs presence nor demographics or comorbidities were associated with COVID-19 re-infection severity. COVID-19 re-infection severity (patient-perceived/hospitalizations/deaths) did not differ between SRDs and controls.

Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study.

OBJECTIVES: A reduced adrenal reserve-associated cortisol production relative to the enhanced needs of chronic inflammation (disproportion principle) has been observed in rheumatoid arthritis (RA). We examined the possible clinical value of diurnal cortisol measurements in active RA on treatment response prediction. METHODS: Diurnal cortisol production (measured at: 08-12:00/18:00-22:00) was assessed by electrochemiluminescence immunoassay in 28 consecutive patients with moderately/highly active RA, as well as 3 and 6 months after treatment initiation or/escalation. Twenty-eight COVID-19 patients and 28 age-matched healthy individuals (HC) served as controls. RESULTS: Saliva diurnal cortisol production in patients with RA was similar to that of HC, despite 12-fold higher serum C reactive protein (CRP) levels, and lower than COVID-19 patients (area under the curve: RA: 87.0±37.6 vs COVID-19: 146.7±14.3, p<0.001), having similarly high CRP. Moreover, a disturbed circadian cortisol rhythm at baseline was evident in 15 of 28 of patients with RA vs 4 of 28 and 20 of 28 of HC and COVID-19 patients, respectively. Treatment-induced minimal disease activity (MDA) at 6 months was achieved by 16 of 28 patients. Despite comparable demographics and clinical characteristics at baseline, non-MDA patients had lower baseline morning cortisol and higher adrenocorticotropic hormone (ACTH) levels compared with patients on MDA (cortisol: 10.9±4.0 vs 18.4±8.2 nmol/L, respectively, p=0.005 and ACTH: 4.8±3.3 vs 2.4±0.4 pmol/L, respectively, p=0.047). Baseline morning cortisol <13.9 nmol/L predicted non-MDA at 6 months (75% sensitivity, 92% specificity, p=0.006). Prospective measurements revealed that individualised diurnal cortisol production remained largely unchanged from baseline to 3 and 6 months. CONCLUSIONS: An impaired adrenal reserve is present in patients with RA. Further studies to confirm that assessment of diurnal cortisol production may be useful in guiding treatment decisions and/or predicting treatment response in RA are warranted. TRIAL REGISTRATION NUMBER: NCT05671627.

Omicron variant dominance and anti-SARS-CoV-2 vaccination are key determinants for a milder course of COVID-19 in patients with systemic autoimmune rheumatic diseases.

INTRODUCTION: This study aimed to determine whether the introduction of anti-SARS-CoV-2 vaccines and the dominance of the omicron variant had a significant impact on the outcome of COVID-19 in patients with systemic autoimmune rheumatic diseases (SAIRDs). METHODS: Using data entered to the Greek Rheumatology Society COVID-19 registry, we investigated the incidence of hospitalization and death due to COVID-19, during the successive periods of the pandemic according to the prevalent strain (wild-type, Alpha, Delta, Omicron) in vaccinated and unvaccinated patients. Variables independently associated with hospitalization and death were explored using multivariate regression analyses, while Kaplan-Meier curves were used to depict survival data. RESULTS: From August 2020 until June 30, 2022, 456 cases (70.2% females) of COVID-19 with a mean age (± SD) of 51.4 ± 14.0 years were reported. In unvaccinated patients, the proportions of hospitalization and death were 24.5% and 4%, compared to 12.5% and 0.8% in the vaccinated group (p < 0.001 for both comparisons). The rates of hospitalization for the wild-type, Alpha, Delta, and Omicron periods were 24.7%, 31.3%, 25.9%, and 8.1% respectively (p < 0.0001), while the case fatality rates were 2.7%, 4%, 7%, and 0%, respectively (p = 0.001). Using multivariable regression analysis, factors independently associated with hospitalization were infection by a non-Omicron variant, being non-vaccinated, exposure to rituximab, older age, and respiratory and cardiovascular disease. Independent predictors for death were contracting COVID-19 during the Alpha or Delta period, pulmonary disease, and older age, while being vaccinated was protective. CONCLUSIONS: In this 2-year analysis, the rates of hospitalization and death among patients with SAIRDs have declined significantly. Vaccination and the dominance of the Omicron variant appear to be the major determinants for this shift. Key points • During the late phase of the pandemic, the proportion of severe COVID-19 cases, defined as requiring hospitalization or resulting in death, in patients with systemic autoimmune rheumatic diseases has declined. • Anti-SARS-CoV-2 vaccination and the dominance of the Omicron strain are the key factors that have independently contributed to this shift.

Does the Impact of COVID-19 on Patients With Systemic Sclerosis Change Over Time?

OBJECTIVE: The outcome of patients with COVID-19 improved over the pandemic, including patients with systemic rheumatic diseases. However, data on patients with systemic sclerosis (SSc) are lacking. This study aimed to assess the outcome of patients with both SSc and COVID-19 over several waves. METHODS: Patients with both SSc and COVID-19 who were registered in the European Scleroderma Trials and Research group (EUSTAR) were collected between April 2020 and April 2021. Patients were assigned to waves 1, 2, or 3 depending on the date of their COVID-19 diagnosis. Primary endpoints were death, intensive care unit stay, or ventilatory support (severe outcome). Subgroup analyses of patients who were hospitalized or died were conducted. General and SSc-specific characteristics and treatment were compared over the waves. Descriptive statistics and multivariate logistic regression were applied. RESULTS: A total of 333 patients were included; 57 patients (17%) had a severe outcome, and 30 patients (9%) died. Compared to wave 1, significantly fewer patients with SSc suffered from severe COVID-19 in waves 2 and 3 (28.2% vs 9.8% and 12.7%; P < 0.001), fewer patients required hospitalization (46.7% vs 19.6% and 25.5%; P < 0.001) or ventilatory support (24.0% vs 8.7% and 10.9%; P = 0.001), and fewer patients died (15.7% vs 5.0% and 7.5%; P = 0.011). Patients were significantly younger, more often men, had less frequent arterial hypertension, and less SSc cardiac involvement over waves 1 to 3. Patients received significantly less medium to high doses of corticosteroids as they did SSc treatment. CONCLUSION: The outcome of patients with both SSc and COVID-19 improved significantly over time because of intrinsic and extrinsic factors.

COVID-19 and protection of vaccination in patients with systemic sclerosis-associated interstitial lung disease.

Objectives: Data on COVID-19 in patients with interstitial lung disease are scarce and whether SARS-CoV-2 may trigger interstitial lung disease progression remains unknown. We aimed to analyze outcomes of COVID-19 in patients with systemic sclerosis-associated interstitial lung disease, including possible thoracic radiographic progression. Patients and Methods: All 43 patients with systemic sclerosis-associated interstitial lung disease followed in our center (mean ± SD, 55.2 ± 11.6 years, 36 female) with confirmed SARS-CoV2 infection up to 1 September 2022 were analyzed. Individual interstitial lung disease extent on high resolution CT (HRCT) performed before (up to 3 months) and after COVID-19 (2-5 months) was compared. Results: At SARS-CoV-2 infection, 9/43 patients were unvaccinated, whereas 5, 26, and 3 had received 2, 3, or 4 doses of an mRNA vaccine, respectively. Thirty-one patients were either on monotherapy with immunosuppressives (mycophenolate, n = 7; cyclophosphamide, n = 2; methotrexate, n = 10; tocilizumab, n = 7; rituximab, n = 1; etanercept, n = 1), or their combinations (n = 3). Eight patients (20%), of whom four unvaccinated, required hospitalization for pneumonia and three (7%) died of acute respiratory failure (n = 2, both unvaccinated) or cardiac arrest. Lack of vaccination was the only independent predictor for hospitalization (OR = 7.98, 95% CI: 1.25-51.09) and marginally for death (OR = 32.7, 95% CI: 0.97-1110.98), regardless of the presence of diffuse systemic sclerosis, interstitial lung disease extent greater than 20% or immunosuppressive treatment. In 22 patients with available HRCT pairs (vaccinated = 20), the interstitial lung disease extent before COVID-19 (20.4%± 17.8%) remained unchanged (22.4% ± 18.5%) in all but one patient. Conclusion: SARS-CoV-2 vaccination is of outmost importance for every systemic sclerosis patient with interstitial lung disease. COVID-19 does not seem to promote progression of systemic sclerosis-associated interstitial lung disease in vaccinated patients, but further studies are warranted.

Chronological Age and DNA Damage Accumulation in Blood Mononuclear Cells: A Linear Association in Healthy Humans after 50 Years of Age.

Aging is characterized by the progressive deregulation of homeostatic mechanisms causing the accumulation of macromolecular damage, including DNA damage, progressive decline in organ function and chronic diseases. Since several features of the aging phenotype are closely related to defects in the DNA damage response (DDR) network, we have herein investigated the relationship between chronological age and DDR signals in peripheral blood mononuclear cells (PBMCs) from healthy individuals. DDR-associated parameters, including endogenous DNA damage (single-strand breaks and double-strand breaks (DSBs) measured by the alkaline comet assay (Olive Tail Moment (OTM); DSBs-only by γH2AX immunofluorescence staining), DSBs repair capacity, oxidative stress, and apurinic/apyrimidinic sites were evaluated in PBMCs of 243 individuals aged 18-75 years, free of any major comorbidity. While OTM values showed marginal correlation with age until 50 years (rs = 0.41, p = 0.11), a linear relationship was observed after 50 years (r = 0.95, p < 0.001). Moreover, individuals older than 50 years showed increased endogenous DSBs levels (γH2Ax), higher oxidative stress, augmented apurinic/apyrimidinic sites and decreased DSBs repair capacity than those with age lower than 50 years (all p < 0.001). Results were reproduced when we examined men and women separately. Prospective studies confirming the value of DNA damage accumulation as a biomarker of aging, as well as the presence of a relevant agethreshold, are warranted.

Generic and disease-adapted cardiovascular risk scores as predictors of atherosclerosis progression in SLE.

OBJECTIVE: Studies show that generic cardiovascular risk (CVR) prediction tools may underestimate CVR in SLE. We examined, for the first time to our knowledge, whether generic and disease-adapted CVR scores may predict subclinical atherosclerosis progression in SLE. METHODS: We included all eligible patients with SLE without a history of cardiovascular events or diabetes mellitus, who had a 3-year carotid and femoral ultrasound follow-up examination. Five generic (Systematic Coronary Risk Evaluation (SCORE), Framingham Risk Score (FRS), Pooled Cohort Risk Equation, Globorisk, Prospective Cardiovascular Münster) and three 'SLE-adapted' CVR scores (modified Systematic Coronary Risk Evaluation (mSCORE), modified Framingham Risk Score (mFRS), QRESEARCH Risk Estimator V.3 (QRISK3)) were calculated at baseline. The performance of CVR scores to predict atherosclerosis progression (defined as new atherosclerotic plaque development) was tested with Brier Score (BS), area under the receiver operating characteristic curve (AUROC) and Matthews correlation coefficient (MCC), while rank correlation was tested with Harrell's c-index. Binary logistic regression was also applied to examine determinants of subclinical atherosclerosis progression. RESULTS: Twenty-six (21%) of 124 included patients (90% female, mean age 44.4±11.7 years) developed new atherosclerotic plaques after a mean of 39.7±3.8 months' follow-up period. Performance analysis showed that plaque progression was better predicted by the mFRS (BS 0.14, AUROC 0.80, MCC 0.22) and QRISK3 (BS 0.16, AUROC 0.75, MCC 0.25). c-Index showed no superiority for discrimination between mFRS and QRISK3. In the multivariate analysis, QRISK3 (OR 4.24, 95% CI 1.30 to 13.78, p=0.016) among the CVR prediction scores and age (OR 1.13, 95% CI 1.06 to 1.21, p<0.001), cumulative glucocorticoid dose (OR 1.04, 95% CI 1.01 to 1.07, p=0.010) and antiphospholipid antibodies (OR 3.66, 95% CI 1.24 to 10.80, p=0.019) among disease-related CVR factors were independently associated with plaque progression. CONCLUSIONS: Application of SLE-adapted CVR scores such as QRISK3 or mFRS, as well as monitoring for glucocorticoid exposure and the presence of antiphospholipid antibodies, can help to improve CVR assessment and management in SLE.

Cardiac magnetic resonance imaging before and after therapeutic interventions for systemic sclerosis-associated myocarditis.

OBJECTIVES: Cardiac magnetic resonance imaging (CMRI) is increasingly used to evaluate cardiac involvement in SSc. We assessed changes, including inflammatory and/or fibrotic myocardial lesions detected by CMRI, following therapeutic interventions for SSc-associated symptomatic myocarditis. METHODS: In this retrospective study, myocarditis was diagnosed by CMRI (2018 revised Lake Louise criteria) in 14 diffuse and 4 limited SSc patients [16/18 women, age 56 years (s.d. 11), disease duration 8 years (s.d. 11), 17/18 with lung involvement] with cardiac symptoms and abnormal findings on echocardiography (4/18) and/or in 24-hour Holter monitoring (12/14). CMRI was repeated after 8 months (s.d. 3) following administration of cyclophosphamide (n = 11, combined with corticosteroids in 3 and rituximab in 1), mycophenolate (n = 1), tocilizumab (n = 1), methotrexate/corticosteroids (n = 2), corticosteroids (n = 1) or autologous stem cell transplantation (n = 2). RESULTS: Functional cardiac improvement was evident by increases in left [by 5.8% (s.d. 7.8), P = 0.006] and right ventricular ejection fraction [by 4.5% (s.d. 11.4), P = 0.085] in the second CMRI compared with the first. Notably, late gadolinium enhancement, currently considered to denote replacement fibrosis, decreased by 3.1% (s.d. 3.8; P = 0.003), resolving in six patients. Markers of myocardial oedema, namely T2 ratio and T2 mapping, decreased by 0.27 (s.d. 0.40; P = 0.013) and 6.0 (s.d. 7; P = 0.025), respectively. Conversely, both T1 mapping, considered to reflect acute oedema and diffuse fibrosis, and extracellular volume fraction, reflecting diffuse fibrosis, remained unchanged. CONCLUSIONS: CMRI may distinguish between reversible inflammatory/fibrotic and irreversible fibrotic lesions in SSc patients with active myocarditis, confirming the unique nature of primary cardiac involvement in SSc. Whether, and how, CMRI should be used to monitor treatment effects in SSc-associated myocarditis warrants further study.

Impaired adrenal cortex reserve in patients with rheumatic and musculoskeletal diseases who relapse upon tapering of low glucocorticoid dose.

OBJECTIVES: To examine adrenal cortex reserve in patients with rheumatic and musculoskeletal diseases (RMD) who relapse upon tapering of low glucocorticoid dose, despite concomitant treatment with disease-modifying anti-rheumatic drugs (DMARDs). METHODS: A morning standard dose of 250 mcg tetracosactide (Synacthen test) was given in 25 consecutive patients (13 rheumatoid arthritis, 2 psoriatic arthritis, 5 systemic lupus erythematosus, 2 dermatomyositis, 1 systemic sclerosis, 2 temporal arteritis) at the time of relapse upon small reductions (1-2 mg daily) of low prednisolone dose (<7.5 mg daily), while being on stable concomitant treatment with methotrexate, leflunomide, hydroxychloroquine, azathioprine, mycophenolate, tofacitinib, belimumab, anti-TNF, anti-IL-6 or anti-IL-1 regimens (n=14; 3; 9; 1; 2; 1; 1; 5; 2; 1, respectively). Sex-matched apparently healthy individuals (n=45) served as controls. RESULTS: Baseline cortisol levels and time-integrated cortisol response to tetracosactide were lower in patients than controls (12.01±4.47 vs. 15.63±4.16 mcg/dl, p=0.001, and 1050±286 vs. 1284±182, p<0.001, respectively). No significant associations were observed between the cortisol response to tetracosactide and age, duration of disease or glucocorticoid treatment. An abnormal Synacthen test, indicative of adrenal insufficiency, presumably secondary to chronic glucocorticoid administration, was noted in 5/25 patients. The remaining 20 patients (80%) had normal Synacthen test demonstrating, however, lower cortisol response than controls, independently of age (ß-coefficient=-0.373, p=0.033). CONCLUSIONS: Patients with RMD in remission under DMARDs who relapse upon concomitant low glucocorticoid dose tapering should be tested for iatrogenic adrenal insufficiency. Whether a marginally normal Synacthen test should discourage further attempts to withdraw glucocorticoid treatment in these patients warrants further investigation.

Update on assessment and management of primary cardiac involvement in systemic sclerosis.

Primary cardiac involvement is a common and severe complication of systemic sclerosis, which may affect all of the hearts' structural components, including pericardium, myocardium, endocardium, cardiac valves, and conduction system. While cardiac disease can be clinically silent and only diagnosed in autopsy, new imaging modalities such as speckle-tracking echocardiography and cardiovascular magnetic resonance may reveal various abnormal findings in the majority of patients. Cardiovascular magnetic resonance evaluation should include assessment of left and right ventricular function, inflammation (STIR T2-weighted sequences (T2-W) for edema detection), and fibrosis (T1-weighted sequences 15 min after Gd-DTPA contrast medium injection (late-gadolinium enhancement). Notably, cardiac disease is responsible for about one-fourth of systemic sclerosis-related deaths. Systematic studies for the assessment and therapy of systemic sclerosis-related cardiac complications, as well as relevant guidelines from the European League Against Rheumatism and the American College of Rheumatology, are currently lacking. However, research advances reviewed herein allow for a better understanding of the mechanisms that alter cardiac function. Implementation of such knowledge should reduce cardiac morbidity and mortality in systemic sclerosis patients.

Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases.

OBJECTIVE: Τo report outcomes of breakthrough COVID-19 in comparison with COVID-19 in unvaccinated patients with systemic rheumatic diseases (SRDs). METHODS: Patients with SRD with COVID-19 (vaccinated and unvaccinated) were included by their rheumatologists in a registry operated by the Greek Rheumatology Society in a voluntarily basis. Type, date and doses of SARS-CoV-2 vaccines were recorded, and demographics, type of SRD, concurrent treatment, comorbidities and COVID-19 outcomes (hospitalisation, need for oxygen supplementation and death) were compared between vaccinated and unvaccinated patients. RESULTS: Between 1 March 2020 and 31 August 2021, 195 patients with SRD with COVID-19 were included; 147 unvaccinated and 48 vaccinated with at least one dose of a SARS-CoV-2 vaccine (Pfizer n=38 or AstraZeneca n=10). Among vaccinated patients, 29 developed breakthrough COVID-19 >14 days after the second vaccine dose (fully vaccinated), while 19 between the first and <14 days after the second vaccine dose (partially vaccinated). Despite no differences in demographics, SRD type, treatment or comorbidities between unvaccinated and vaccinated patients, hospitalisation and mortality rates were higher in unvaccinated (29.3% and 4.1%, respectively) compared with partially vaccinated (21% and 0%) or fully vaccinated (10.3% and 0%) patients. CONCLUSIONS: Vaccinated patients with SRD with breakthrough COVID-19 have better outcomes compared with unvaccinated counterparts with similar disease/treatment characteristics.

COVID-19 vaccine safety and nocebo-prone associated hesitancy in patients with systemic rheumatic diseases: a cross-sectional study.

OBJECTIVE: To describe the rate and type of adverse effects (AEs) and the frequency of disease flares after COVID-19 vaccination and to assess the reasons for vaccination hesitancy (non-vaccination) in SRD patients. METHODS: Telephone interviews were conducted of SRD patients consecutively enrolled (15/06/2021-1/7/2021). Participants were asked about the type of AEs and disease flare after vaccination. Reasons for vaccination hesitancy were recorded. Univariate and mutivariable analyses examined associations of demographic, clinical and other features, with occurrence of AEs, disease flare and non-vaccination. For the latter, association with negative vaccination behaviour (not influenza vaccinated for the last 2 years) and nocebo-prone behaviour (denoting AEs attributed to negative expectations [Q-No questionnaire]) was also tested. RESULTS: 561 out of 580 contacted patients were included in the study. 441/561 (78.6%) patients were vaccinated [90% (Pfizer, Moderna), 10% (Astra-Zeneca)]. AEs were reported by 148/441 (33.6%), with rates being comparable between the three vaccines. AEs were more common in females and those with chronic obstructive pulmonary disease [OR, 95% CI; females: 2.23 (1.30-3.83); COPD: 3.31 (1.24-8.83)]. Disease flare was reported in 9/441 (2%) patients. For those unvaccinated, fear that the vaccine would be harmful (53.3%), could cause disease flare (24.2%) and/or could cause thrombosis (21.7%) were the main reasons to do so. Multivariable analysis identified as independent variables for non-vaccination: nocebo-prone behaviour (OR; 95% CI, 3.88; 1.76-8.55), negative vaccination behaviour (6.56; 3.21-13.42) and previous COVID-19 infection (2.83; 1.13-7.05). Higher educational status was protective (0.49; 0.26-0.92). CONCLUSION: No new safety signals for COVID-19 vaccination were observed. Vaccination campaign should target SRD patients with nocebo-prone and negative influenza vaccination behaviour.

Anti-interleukin 6 Therapy Effect for Refractory Joint and Skin Involvement in Systemic Sclerosis: A Real-world, Single-center Experience.

OBJECTIVE: To examine the efficacy and safety of interleukin-6 inhibition by tocilizumab (TCZ) in difficult-to-treat, real-world patients with systemic sclerosis (SSc). METHODS: Twenty-one patients (20 women; 16 diffuse cutaneous SSc; mean age: 52 ± 10 yrs; 10 with early disease [< 5 yrs]; and 11 with long-standing disease [mean disease duration 6.4 ± 3.7 yrs]) with active joint and/or skin involvement refractory to corticosteroids (n = 21), methotrexate (n = 19), cyclophosphamide (n = 10), mycophenolate mofetil (n = 7), rituximab (n = 1), leflunomide (n = 2), hydroxychloroquine (n = 2), and hematopoietic stem cell transplantation (n = 2), who received weekly TCZ (162 mg subcutaneously) in an academic center, were monitored prospectively. Changes in modified Rodnan skin score (mRSS), Disease Activity Score in 28 joints (DAS28), lung function tests (LFTs), and patient-reported outcomes (PROs) were analyzed after 1 year of treatment and at end of follow-up. RESULTS: One patient discontinued TCZ after 3 months due to inefficacy. During the first year of treatment, improvement was evident in the remaining 20 patients regarding skin involvement (mean mRSS change: -6.9 ± 5.9, P < 0.001), polyarthritis (mean DAS28 change: -1.9 ± 0.8, P < 0.001), and PROs (all P < 0.001); LFT stabilization was observed in 16/20 patients. During the second year, 3 patients discontinued TCZ (cytomegalovirus infection in 1, inefficacy in 2) and 1 died. Beneficial effects were sustained in all 16 patients at end of follow-up (2.2 ± 1.1 yrs), except LFT deterioration in 3 patients. Apart from recurrent digital ulcer infection in 3 patients, TCZ was well tolerated. CONCLUSION: TCZ was effective in refractory joint and skin involvement regardless of SSc disease duration or subtype. Long-term retention rates and disease stabilization for most real-world patients suggest that TCZ might be a valuable choice for difficult-to-treat SSc.

Psoriasis as an adverse reaction to biologic agents beyond anti-TNF-α therapy.

New onset or exacerbation of pre-existing psoriasis after therapeutic TNF-α inhibition is a well-described phenomenon. Over the last two decades, similar cases of paradoxical psoriasis have been reported following the administration of other biologic agents. We aimed to review all published cases of induced or exacerbated psoriasis after biologic therapy other than anti-TNF-α agents in order to further elucidate the pathophysiology of this phenomenon. A systematic literature review in the Medline database regarding any relevant case series or case reports on new onset or exacerbation of psoriasis after the administration of biologic agents targeting B cells, T cell co-stimulation, interleukin-1, interleukin-6, interleukin-17 and interleukin-12/23 was performed using appropriate key words. The literature search revealed nine articles (nine cases) of paradoxical psoriasis after ustekinumab and eight articles (nine cases) after secukinumab administration, both of which are approved therapies for psoriasis Moreover, 15 articles (23 cases) for rituximab, nine articles (12 cases) for abatacept, eight articles (nine cases) for tocilizumab, and one case report for anakinra have been published. In the majority of cases, patients had no prior history of psoriasis while 18 patients presented with exacerbation of pre-existing psoriatic lesions. Paradoxical psoriasis is not a specific adverse event of TNF-α inhibitors but is a possible side effect of any biologic agent interfering with the immune system. Awareness among physicians regarding early recognition is mandatory. Further clinical and experimental data are needed in order to unravel the pathophysiology of this unexpected phenomenon.

Cardiopulmonary exercise testing and prognosis in patients with systemic sclerosis without baseline pulmonary hypertension: a prospective cohort study.

Cardiopulmonary Exercise Testing (CPET) is a standardized, non-invasive procedure assessing pulmonary, cardiovascular, hematopoietic, and skeletal muscle functions during a symptom-limited test. Few studies have examined whether CPET is of prognostic value in Systemic Sclerosis (SSc), a disease characterized by highly increased cardiorespiratory morbidity and mortality. To examine the prognostic value of CPET in SSc patients without baseline pulmonary hypertension (PH). Sixty-two consecutive SSc patients underwent CPET, Pulmonary Function Tests (PFTs) and echocardiography at baseline. Four patients with Right Ventricular Systolic Pressure ≥ 40 mmHg, were excluded. Participants repeated PFTs approximately every 3 years. At the end of the follow-up period [median (IQR): 9.79 (2.78) years] patient vital status was recorded. Cox Regression analysis was used to identify predictors of deterioration of PFTs and 10-year survival. Median (IQR) age of 58 patients (90% women) at baseline was 54.0 (15.0) years, whereas 10-year survival was 88%. Baseline respiratory Oxygen uptake (VO2max) predicted PFT deterioration, defined either as a decline in FVC ≥ 10% or a combined decline in FVC 5%-9% plus DLCO ≥ 15%, during follow-up, after correction for age, gender and smoking status (HR: 0.874, 95%CI: 0.779-0.979, p = 0.021). In addition, lower baseline VO2max (HR = 0.861, 95%CI:0.739-1.003, p = 0.054) and DLCO (HR = 0.957, 95%CI: 0.910-1.006 p = 0.088), as well as male gender (HR = 5.68, 95%CI: 1.090-29.610 p = 0.039) and older age (HR = 1.069, 95%CI: 0.990-1.154, p = 0.086) were associated, after adjustment, with an increased risk for death. In the absence of baseline PH, CPET indices may predict pulmonary function deterioration and death in SSc patients during a nearly 10-year follow-up period.

Increased influenza vaccination rates in patients with autoimmune rheumatic diseases during the Covid-19 pandemic: a cross-sectional study.

To assess non-compliance and potential changes in seasonal flu vaccination coverage before and during the Covid-19 pandemic in patients with autoimmune rheumatic diseases (ARDs). Consecutive patients with ARDs followed-up in 2 tertiary hospitals were telephone-interviewed (December 12-30, 2020) regarding seasonal flu vaccination during the 2019/20 and 2020/21 time periods. Self-reported disease flares that occurred after flu vaccination, as well as reasons for non-vaccination were recorded. One thousand fifteen patients were included. The rate of flu vaccination increased from 76% before to 83% during the COVID-19 pandemic (p = 0.0001). The rate of self-reported disease flares was < 1% among vaccinated patients. Reasons for not vaccination in both periods, respectively, included: 'was not recommended by their rheumatologists' (35.0vs.12.2%, p < 0.0001), 'did not feel that they would have any benefit' (36.9 vs. 32.6%), felt unsafe to do so (27.5 vs. 30.2%), or other reasons (18.9 vs. 23.8%). By multivariate analysis, age [OR = 1.03 (95% CI 1.02-1.04)] vs. [1.04 (95% CI 1.02-1.05)] and treatment with biologics [OR = 1.66 (95% CI 1.22-2.24) vs. [1.68 (95% CI 1.19-2.38)] were independent factors associated with vaccination in both periods. These findings, although are temporally encouraging, emphasize the need for continuous campaigns aiming at increasing patients' and physicians' awareness about the benefits of vaccination.

Higher depression rates and similar cardiovascular comorbidity in psoriatic arthritis compared with rheumatoid arthritis and diabetes mellitus.

BACKGROUND: We explore the spectrum of comorbidities in psoriatic arthritis (PsA) patients in comparison with other high comorbidity-burden diseases like rheumatoid arthritis (RA) and diabetes mellitus (DM). METHODS: Two hundred and fifteen PsA patients, cross-sectionally collected from two tertiary hospitals, were compared with 215 RA and 215 DM patients (age/sex-matched, similar disease duration). Cardiovascular risk factors [hypertension, current smoking, hyperlipidaemia, obesity (body mass index (BMI) ⩾30)], coronary artery disease (CAD), stroke, major adverse cardiac events (MACEs; combined CAD and stroke), depression, osteoporosis and malignancies were recorded. Odds ratios (ORs) for stroke, CAD and MACE were adjusted for age, sex, hypertension, smoking, hyperlipidaemia, BMI, glucocorticoids use and those for depression were adjusted for age, sex, disease duration, skin involvement and smoking. Within the PsA group, associations between comorbidities and demographic/clinical features were assessed. RESULTS: Depression [OR (95% confidence interval (CI)): 3.02 (1.57-5.81)], obesity [OR (95% CI): 2.83, (1.65-4.86)] and hyperlipidaemia [OR (95% CI): 1.96 (1.32-2.90)] were more prevalent in PsA compared with RA, while no differences were observed for CAD, stroke, MACE and malignancies. Depression [OR (95% CI): 4.85 (2.37-9.93)] and osteoporosis [OR (95% CI): 6.22 (1.33-29.2)] were more common in PsA than in DM. Hypertension, but not the other cardiovascular risk factors, was more frequent in DM [OR (95% CI) 0.49 (0.33-0.74)]. However, prevalence of stroke, CAD and MACE did not differ between PsA and DM. Within PsA group, depression was associated with age [OR (95% CI): 1.03 (0.99-1.06)], female sex [OR (95% CI): 3.47 (1.51-7.99)] and smoking [OR (95% CI): 2.78 (1.31-5.88)] while MACEs were associated with age [OR (95% CI): 1.08 (1.00-1.17)], male sex [OR (95% CI) for females: 0.26 (0.06-1.23) and hypertension [OR (95% CI): 6.07 (1.12-33.0)]. No differences were recorded in comorbidities between the different PsA phenotypes. CONCLUSION: Depression was more prevalent in PsA compared with RA and DM, while cardiovascular comorbidity was comparable to both groups, supporting the need for their assessment and management.