Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study.

OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.

Identification and characteristics of patients with potential difficult-to-treat Psoriatic Arthritis: exploratory analyses of the Greek PsA registry.

OBJECTIVE: To present the characteristics of patients with potential difficult-to-treat (D2T) psoriatic arthritis (PsA). METHODS: We used data from the Greek multicentre registry of PsA patients. D2T-PsA was defined as follows: patients with at least 6-months disease duration, who have failed to at least 1 csDMARD and at least 2 bDMARDs/tsDMARDs with a different mechanism of action and have either at least moderate disease activity (MODA) defined as DAPSA > 14, and/or are not at minimal disease activity (MDA). Demographic and clinical characteristics were compared between D2T and non-D2T PsA patients. In two sensitivity analyses, patients classified as D2T solely according to the MODA or MDA criterion were examined separately. RESULTS: Among 467 patients included, 77 (16.5%) were considered D2T and 390 non-D2T PsA. Compared with non-D2T, patients with D2T PsA presented more commonly with extensive psoriasis (p< 0.0001) and were more likely to have higher BMI (p= 0.023) and a history of inflammatory bowel disease (p= 0.026). In the MODA and MDA sensitivity analyses, 7.5% and 12.5% of patients were considered D2T, respectively. In both sensitivity analyses, extensive psoriasis was again identified as an independent variable for D2T PsA (p= 0.001 and p= 0.008, respectively). Moreover, female gender (p= 0.034) in the MODA analysis and axial disease (p= 0.040) in the MDA analysis were independent variables for D2T PsA. CONCLUSION: Despite the availability of therapies, D2T PsA is common in real-life cohorts of patients with PsA and extensive psoriasis. High BMI, female gender, axial-disease, and history of IBD were also associated with D2T PsA.

"Long-term MRI findings in Ankylosing spondylitis patients treated with TNF inhibitors for a decade".

OBJECTIVE: This study aims to evaluate the active and chronic lesions in sacroiliac joints and lumbar spine over a decade of TNFi therapy in patients with AS. METHODS: The study enrolled patients with AS under treatment with a TNFi for over a decade. The patients underwent a new MRI scan of their lumbar spine and sacroiliac joint (SIJ). Two readers evaluated all images. Inflammation of SIJ (SIS), SIJ structural damage (SSS) including Fat Metaplasia, Erosions, Backfill and Ankylosis, and Spondyloarthritis Research Consortium of Canada Bone marrow edema (SPARCC) spine score were recorded. RESULTS: In the study, 15 patients were included, with 80% being male. The mean age during their first MRI was 38.1 (± 11.9) years old, and the majority (86.7%) tested positive for HLA-B27. While TNFi improved both BASDAI and BASFI scores, there was a noticeable increase in MRI acute lesions in the SIJ over time, where the median score increased from 0 (0-4) to 3 (0-10) after ten years (p = 0.028). After a decade of treatment, the median SPARCC spine score also increased from 0 (0-9) to 5 (0-16), p = 0.093. Finally, it was observed that there was a significant positive correlation between ESR and SIS erosions in cases of chronic lesions (r = 0.819, p < 0.001). CONCLUSIONS: While TNFi have significantly improved the treatment of AS, this study shows that acute lesions can still develop despite treatment. A personalized approach that adapts MRI assessment to each patient's specific requirements may help detect changes early and enable doctors to intervene promptly to prevent further damage.

TNFα inhibitor biosimilar associated with polychondritis. A case-based review.

Relapsing polychondritis (RP) is a rare autoimmune disease characterized by inflammation of the cartilage structures of the body with typical features of auricular chondritis, nasal and ocular inflammation, audio-vestibular damage, as well as respiratory tract manifestations. It is associated with several autoimmune diseases and many other disorders. Tumor necrosis factor alpha (TNFα) inhibitors treat many chronic inflammatory disorders. They have proven effective and relatively safe in many clinical trials and observational studies. However, several autoimmune phenomena and paradoxical inflammation have been described with TNFα inhibitors, among them RP. This report presents a 43-year-old man with psoriatic arthritis treated with ABP-501 (Amgevita), an adalimumab (ADA) biosimilar and who developed RP, 8 months after the initiation of the treatment. This, is the first report of RP development during TNFα inhibitors biosimilar. We concluded that rheumatologists dealing with patients treated with TNFα inhibitors (originators or biosimilars), should be aware of several paradoxical reactions which may emerge and RP, is one of them.

Perceived treatment satisfaction in patients with systemic rheumatic diseases treated with biologic therapies: results of a self-reported survey.

Biological agents are widely used for the management of systemic rheumatic diseases (SRDs) and their therapeutic implications have been expanded beyond inflammatory arthropathies to more complicated autoimmune disorders, such as systemic lupus erythematosus, vasculitis, and systemic sclerosis. The aim of this study was to investigate treatment satisfaction and overall experience of SRDs' patients receiving biologics as well as to explore patient's perspectives on the quality of services provided by rheumatology departments and to determine factors related to the level of satisfaction. We performed a synchronous correlation study. Patients with SRDs answered an anonymous questionnaire assessing their satisfaction and how treatment with biologics has affected their quality of life and functionality. Sample consisted by 244 patients (65.2% women), with mean age of 50.4 years, and the most common diagnosis was rheumatoid arthritis (37.3%). Sixty one percent of patients received intravenous therapy and 39% subcutaneously. Overall, 80.5% of the patients reported a positive/very positive effect of their treatment on their life. The average total patient satisfaction from the unit was 79.8%. The presence of mental disease was significantly associated with less positive impact of the treatment on patients' life, worse quality of life, and greater pain. In conclusion, patients with a broad spectrum of SRDs were generally satisfied and treatment with biologic regimens appeared to have a positive impact on several aspects of their life. The majority of patients were at least satisfied with all the characteristics of the unit staff and better quality of life was associated with greater satisfaction about the Unit and more positive affect of the treatment in patients' life.

Prevalence of rheumatoid arthritis in Greece: results from the national health examination survey EMENO.

Rheumatoid arthritis (RA) is considered the most common form of autoimmune arthritis. The disease's prevalence is around 0.5-1% worldwide, but it seems to vary among different populations. The aim of this study was to estimate the prevalence of self-reported diagnosed RA in the general adult population in Greece. The data were derived from the Greek Health Examination Survey EMENO, a population-based survey performed between 2013 and 2016. Of the 6006 participants (response rate 72%), 5884 were eligible for this study. Prevalence estimates were calculated according to the study design. Prevalence of self-reported RA was estimated to be overall 0.5% (95% CI 0.4-0.7) being approximately three times higher in women than in men (0.7% vs 0.2%, p value = 0.004). A decrease in the prevalence of RA was observed in urban areas of the country. In contrast, higher disease rates were reported in individuals with lower socioeconomic status. Multivariable regression analysis showed that gender, age, and income were related to the occurrence of the disease. Osteoporosis and thyroid disease were the two comorbidities observed at statistically significant higher rates in individuals with self-reported RA. The prevalence of self-reported RA in Greece is similar to that reported in other European countries. Gender, age, and income are the main factors related to the disease's prevalence in Greece.

Apremilast for biologic-naïve, peripheral psoriatic arthritis, including patients with early disease: results from the APROACH observational prospective study.

To evaluate the effect of the phosphodiesterase 4 inhibitor apremilast in biologic-naïve patients with early peripheral PsA in terms of disease activity, clinical manifestations, patient-perceived outcomes, as well as apremilast's safety profile in routine care settings of Greece. Non-interventional, multicenter, 52-week prospective cohort study, enrolling biologic-naïve patients with early active peripheral PsA who started apremilast after intolerance or inadequate response (within the first 12 months of treatment) to an initial conventional synthetic (cs)DMARD treatment. Non-responder imputation was applied for missing data.In total, 167 consecutive patients (mean age: 52.5 years; median PsA duration: 0.9 years) were analyzed. At baseline, the median (interquartile range) clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score was 22.0 (16.0-29.0), with 86.8% of patients having at least moderate (29.3% high) disease activity; 87.4% had skin psoriasis, 37.7% nail psoriasis, 30.7% enthesitis, and 12.4% dactylitis. At 16, 24, and 52 weeks, 28.7, 42.5, and 48.5% of patients, achieved ≥ 50% improvement in their baseline cDAPSA score, respectively. At week 52, 55.6, 50, and 26.8% of evaluable patients achieved complete resolution of enthesitis, dactylitis and nail psoriasis, respectively. Improvements were also observed in patient's health state assessed by the Psoriatic Arthritis Impact of Disease 12-item questionnaire, and health-related quality of life. The 52-week drug survival rate was 75%, while 13.8% of patients experienced at least one adverse drug reaction.Biologic-naïve patients with early PsA, treated with apremilast experienced significant improvements in disease activity, extra-articular manifestations and patient-centered outcomes, accompanied by a favorable tolerability profile.

The large Hellenic Study of Uveitis: epidemiology, etiologic factors and classification.

PURPOSE: To analyse the demography, etiology, and classification of uveitis at a tertiary academic referral center. METHODS: An observational study was conducted on the archives of uveitic patients at the Ocular Inflammation Service of the Department of Ophthalmology at the University Hospital of Ioannina (Greece) from 1991 to 2020. This study aimed to investigate the epidemiological profile of patients, including their demographics and the main etiologic factors of uveitis. RESULTS: Out of 6191 cases with uveitis, 1925 were infectious, 4125 were non-infectious, and an overall of 141 masquerade syndromes were recorded. Among these cases, 5950 patients were adults, with a slight female predominance, while 241 were children (< 18 years old). Interestingly, 24.2% of cases (1500 patients) were associated with 4 specific microorganisms. Herpetic uveitis (HSV-1 and VZV/HZV) was the most common cause of infectious uveitis (14.87%), followed by toxoplasmosis (6.6%) and tuberculosis (2.74%). In 49.2% of non-infectious uveitis cases, no systematic correlation was found. The most frequent causes of non-infectious uveitis included sarcoidosis, white dot syndromes, ankylosing spondylitis, lens-induced uveitis, Adamantiades-Behçet disease, and idiopathic juvenile arthritis. Infectious uveitis was more common in the rural population, whereas non-infectious uveitis was more frequently recorded in the urban population CONCLUSIONS: Although our study was conducted on a predominantly white Caucasian population, it also reflects the effect of increasing immigration, improvements of diagnostic techniques, changes in referral patterns, and various actual changes in disease incidence.

Clinical features and diagnostic tools in idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIMs) are rare autoimmune disorders affecting primarily muscles, but other organs can be involved. This review describes the clinical features, diagnosis and treatment for IIMs, namely polymyositis (PM), dermatomyositis (DM), sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myopathy (IMNM), and myositis associated with antisynthetase syndrome (ASS). The diagnostic approach has been updated recently based on the discovery of circulating autoantibodies, which has enhanced the management of patients. Currently, validated classification criteria for IIMs allow clinical studies with well-defined sets of patients but diagnostic criteria to guide the care of individual patients in routine clinical practice are still missing. This review analyzes the clinical manifestations and laboratory findings of IIMs, discusses the efficiency of modern and standard methods employed in their workup, and delineates optimal practice for clinical care. Α multidisciplinary diagnostic approach that combines clinical, neurologic and rheumatologic examination, evaluation of electrophysiologic and morphologic muscle characteristics, and assessment of autoantibody immunoassays has been determined to be the preferred approach for effective management of patients with suspected IIMs.

COVID-19: Clinical features and outcomes in unvaccinated 2-dose and 3-dose vaccinated against SARS-CoV-2 patients with systemic autoimmune and autoinflammatory rheumatic diseases.

Clinical data on vaccinated patients with coronavirus disease 2019 (COVID-19) who have systemic autoimmune and autoinflammatory rheumatic diseases (SAARD) are limited. This observational study aimed to report the clinical features and outcomes of COVID-19 among cases with SAARD that were unvaccinated or were 2- and 3-dose vaccinated against SARS-CoV-2 and were consecutively recorded by the treating physician. Unvaccinated and 2- and 3-dose vaccinated patients were compared in terms of COVID-19 symptomatology, hospitalizations, oxygen supplementation requirements, and death rates. From the beginning of the pandemic to February 15, 2022, 134 vaccine-naïve COVID-19 cases were recorded among our study cohort. From March 1, 2021 to February 15, 2022, 89 2-dose vaccinated and 105 3-dose vaccinated patients who were infected with SARS-CoV-2 ≥14 days after the second dose were included. The hospitalization rate was higher in the unvaccinated (n = 36, 26.9%) than in the 2-dose (n = 13, 14.6%, p = 0.03) or 3-dose (n = 5, 4.8%, p < 0.001) vaccinated patients. Severe/critical COVID-19 cases requiring oxygen supplementation were the least among 3-dose vaccinated (n = 4, 3.8%) compared to both 2-dose vaccinated (n = 12, 13.5%, p = 0.018) and unvaccinated (n = 25, 18.7%, p < 0.001) patients. ICU admission and death rates were similar among unvaccinated (n = 5, 3.7% and n = 3, 2.2%, respectively) and 2-dose vaccinated patients (n = 4, 4.5%; and n = 2, 2.2%, respectively), while no 3-dose vaccinated patients died or required ICU admission. Logistic regression analysis revealed a significant inverse association between 3-dose vaccination and severe/critical COVID-19 (OR = 0.078, 95% CI: 0.022-0.273, p < 0.001). In conclusion, these findings argue in favor of booster vaccination against SARS-CoV-2 in patients with SAARD.

Clinical and laboratory findings of primary Sjögren's syndrome patients without sicca symptoms.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by oral and eye dryness. A minority of patients can present without dryness but studies on their clinico-laboratory manifestations are scarce. Our purpose was to describe the clinical phenotype of pSS patients lacking sicca symptoms. METHODS: From a total of 1738 consecutive pSS patients fulfilling the 2016 ACR-EULAR criteria, those who presented without sicca symptoms were identified (non-dryness group). Their medical data was collected and compared with 2 control groups: a) the remaining unmatched sicca pSS patients with both oral and eye dryness (unmatched dryness group) and b) matched sicca pSS patients according to age, sex, and disease duration, in 1:2 ratio (matched dryness group). RESULTS: Thirty-eight (2.19%) patients lacked sicca manifestations presenting mainly with arthralgias (47%), parotid enlargement (24%), Raynaud's phenomenon (11%) and persistent lymphadenopathy (11%) that led them to be evaluated for pSS. Non-dryness pSS patients were younger than the unmatched sicca controls, displaying a higher frequency of anti-Ro/SSA antibodies (100% vs. 79.7%, p<0.001), ANA positivity (100% vs. 90.4%, p<0.001), neutropenia (20.8% vs. 7.5%, p=0.04) and thrombocytopenia (13.8% vs. 4.2%, p=0.04). They also had lower frequency of positive ocular tests compared to both unmatched and matched dryness patients. No differences were found between non-dryness pSS patients and both control groups regarding focus score or any other extraglandular manifestation. CONCLUSIONS: pSS patients without sicca complaints constitute a distinct phenotype involving younger patients, sharing common immunopathologic mechanisms with typical sicca patients.

Hepatitis B, C and human immunodeficiency virus knowledge among the general greek population: results from the Hprolipsis nationwide survey.

BACKGROUND: Although several studies on hepatitis B (HBV), C (HCV) and human immunodeficiency virus (HIV) infection have been conducted in Greece, little is known on the knowledge level of the Greek population towards these three infections. Our aim was to assess the knowledge level of the adult Greek general population about the HBV, HCV and HIV. METHODS: Data were derived from the first general population health survey, Hprolipsis. The sample was selected by multistage stratified random sampling. A standardized questionnaire was administered by trained interviewers during home visits. A knowledge score was constructed based on responses to 17 per infection selected items and categorized in three levels; high (12-17 correct replies) medium (6-11) and low (0-5). Among 8,341 eligible individuals, 6,006 were recruited (response rate: 72%) and 5,878 adults (≥ 18 years) were included in the analysis. The statistical analysis accounted for the study design. RESULTS: Only 30.4%, 21.6%, and 29.6% of the participants had a high overall knowledge level of HBV, HCV and HIV, respectively. These low percentages were mainly attributed to the high levels of misconception about transmission modes (65.9%, 67.2%, and 67.9%, respectively). Results showed that increasing age and living out of the big metropolitan cities were associated with decreased odds of having higher knowledge. Female gender, higher education level, higher monthly family income, higher medical risk score, history of testing and being born in Greece or Cyprus, were associated with increased odds of having higher knowledge. CONCLUSIONS: There are significant knowledge gaps in the Greek general population regarding modes of transmission, preventive measures and treatment availability for HBV, HCV and HIV. There is an urgent need for large scale but also localized awareness activities targeted to less privileged populations, to fill the gaps in knowledge and increase population engagement in preventive measures.

A biomarker for lymphoma development in Sjogren's syndrome: Salivary gland focus score.

The aim of this study is to explore the role of labial minor salivary gland (LMSG) focus score (FS) in stratifying Sjögren's Syndrome (SS) patients, lymphoma development prediction and to facilitate early lymphoma diagnosis. Ιn an integrated cohort of 1997 patients, 618 patients with FS ≥ 1 and at least one-year elapsing time interval from SS diagnosis to lymphoma diagnosis or last follow up were identified. Clinical, laboratory and serological features were recorded. A data driven logistic regression model was applied to identify independent lymphoma associated risk factors. Furthermore, a FS threshold maximizing the difference of time interval from SS until lymphoma diagnosis between high and low FS lymphoma subgroups was investigated, to develop a follow up strategy for early lymphoma diagnosis. Of the 618 patients, 560 were non-lymphoma SS patients while the other 58 had SS and lymphoma. FS, cryoglobulinemia and salivary gland enlargement (SGE) were proven to be independent lymphoma associated risk factors. Lymphoma patients with FS ≥ 4 had a statistically significant shorter time interval from SS to lymphoma diagnosis, compared to those with FS < 4 (4 vs 9 years, respectively, p = 0,008). SS patients with FS ≥ 4 had more frequently B cell originated manifestations and lymphoma, while in patients with FS < 4, autoimmune thyroiditis was more prevalent. In the latter group SGE was the only lymphoma independent risk factor. A second LMSG biopsy is patients with a FS ≥ 4, 4 years after SS diagnosis and in those with FS < 4 and a history of SGE, at 9-years, may contribute to an early lymphoma diagnosis. Based on our results we conclude that LMSG FS, evaluated at the time of SS diagnosis, is an independent lymphoma associated risk factor and may serve as a predictive biomarker for the early diagnosis of SS-associated lymphomas.

A prospective multicenter study assessing humoral immunogenicity and safety of the mRNA SARS-CoV-2 vaccines in Greek patients with systemic autoimmune and autoinflammatory rheumatic diseases.

OBJECTIVES: To investigate humoral responses and safety of mRNA SARS-CoV-2 vaccines in systemic autoimmune and autoinflammatory rheumatic disease (SAARD) patients subjected or not to treatment modifications during vaccination. METHODS: A nationwide, multicenter study, including 605 SAARD patients and 116 controls, prospectively evaluated serum anti-SARS-CoV-2 S1-protein IgG antibody titers, side-effects, and disease activity, one month after complete vaccination, in terms of distinct treatment modification strategies (none, partial and extended modifications). Independent risk factors associated with hampered humoral responses were identified by data-driven multivariable logistic regression analysis. RESULTS: Patients with extended treatment modifications responded to vaccines similarly to controls as well as SAARD patients without immunosuppressive therapy (97.56% vs 100%, p = 0.2468 and 97.56% vs 97.46%, p > 0.9999, respectively). In contrast, patients with partial or without therapeutic modifications responded in 87.50% and 84.50%, respectively. Furthermore, SAARD patients with extended treatment modifications developed higher anti-SARS-CoV-2 antibody levels compared to those without or with partial modifications (median:7.90 vs 7.06 vs 7.1, p = 0.0003 and p = 0.0195, respectively). Mycophenolate mofetil (MMF), rituximab (RTX) and methotrexate (MTX) negatively affected anti-SARS-CoV-2 humoral responses. In 10.5% of vaccinated patients, mild clinical deterioration was noted; however, no differences in the incidence of deterioration were observed among the distinct treatment modification SAARD subgroups. Side-effects were generally comparable between SAARD patients and controls. CONCLUSIONS: In SAARD patients, mRNA SARS-CoV-2 vaccines are effective and safe, both in terms of side-effects and disease flares. Treatment with MMF, RTX and/or MTX compromises anti-SARS-CoV-2 antibody responses, which are restored upon extended treatment modifications without affecting disease activity.

Incidence, risk factors and validation of the RABBIT score for serious infections in a cohort of 1557 patients with rheumatoid arthritis.

OBJECTIVES: Predicting serious infections (SI) in patients with rheumatoid arthritis (RA) is crucial for the implementation of appropriate preventive measures. Here we aimed to identify risk factors for SI and to validate the RA Observation of Biologic Therapy (RABBIT) risk score in real-life settings. METHODS: A multi-centre, prospective, RA cohort study in Greece. Demographics, disease characteristics, treatments and comorbidities were documented at first evaluation and one year later. The incidence of SI was recorded and compared with the expected SI rate using the RABBIT risk score. RESULTS: A total of 1557 RA patients were included. During follow-up, 38 SI were recorded [incidence rate ratio (IRR): 2.3/100 patient-years]. Patients who developed SI had longer disease duration, higher HAQ at first evaluation and were more likely to have a history of previous SI, chronic lung disease, cardiovascular disease and chronic kidney disease. By multivariate analysis, longer disease duration (IRR: 1.05; 95% CI: 1.005, 1.1), history of previous SI (IRR: 4.15; 95% CI: 1.7, 10.1), diabetes (IRR: 2.55; 95% CI: 1.06, 6.14), chronic lung disease (IRR: 3.14; 95% CI: 1.35, 7.27) and daily prednisolone dose ≥10 mg (IRR: 4.77; 95% CI: 1.47, 15.5) were independent risk factors for SI. Using the RABBIT risk score in 1359 patients, the expected SI incidence rate was 1.71/100 patient-years, not different from the observed (1.91/100 patient-years; P = 0.97). CONCLUSION: In this large real-life, prospective study of RA patients, the incidence of SI was 2.3/100 patient-years. Longer disease duration, history of previous SI, comorbidities and high glucocorticoid dose were independently associated with SI. The RABBIT score accurately predicted SI in our cohort.

Incidence of spondyloarthritis subtypes: a systematic review.

OBJECTIVES: Several epidemiologic studies of spondylarthritis (SpA) and its subtypes have been reported during the last decades. The majority of these studies provided prevalence estimates and showed a considerable variation in the reported frequency of SpA subtypes. Most systematic reviews published in this field aimed to summarise the results of prevalence studies, however, incidence studies are important for an accurate picture of a disease occurrence in a defined population. We conducted a systematic review regarding the incidence of SpA subtypes on studies published during the last 25 years, to compare their methodology and summarise their results. METHODS: A systematic literature search of PubMed was performed to identify all published studies on the incidence of SpA subtypes between 1/1/1995 and 31/12/2019. Studies were considered eligible if the incidence of one or more SpA subtypes was measured in the general population, and met concrete inclusion criteria. Incidence rates (IR) were summarised using a random effect model. RESULTS: A total of 24 publications fulfilled the inclusion criteria. Most of them included results for two or more SpA subtypes. Sixteen studies presented the incidence of psoriatic arthritis, which gave an overall IR estimate of 9.7 cases per 100.000 person-years. Thirteen studies presented the incidence of ankylosing spondylitis with an overall IR estimate of 4.8, and eight studies presented reactive arthritis incidence with an overall IR estimate of 3.4. A small number of studies referred to the incidence of enteropathic arthritis or undifferentiated spondyloarthritis. CONCLUSIONS: Incidence studies of SpAs differ considerably in their methods, and result in a wide variation of the IRs for all SpA subtypes. Methodological differences may only partly explain the differences in disease occurrence observed among studies. More studies from different populations based on specific classification criteria are needed for a more accurate picture of SpA epidemiology.

Combined seronegativity in Sjögren's syndrome.

OBJECTIVES: To describe the clinical spectrum of Sjögren's syndrome (SS) patients with combined seronegativity. METHODS: From a multicentre study population of consecutive SS patients fulfilling the 2016 ACR-EULAR classification criteria, patients with triple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(+)] and quadruple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(-)] were identified retrospectively. Both groups were matched in an 1:1 ratio with 2 distinct control SS groups: i) classic anti-Ro/SSA seropositive patients [SS(+)] and ii) classic anti-Ro/SSA seropositive patients with negative rheumatoid factor [SS(+)/RF(-)] to explore their effect on disease expression. Clinical, laboratory and, histologic features were compared. A comparison between triple and quadruple seronegative SS patients was also performed. REESULTS: One hundred thirty-five SS patients (8.6%) were identified as triple seronegative patients and 72 (4.5%) as quadruple. Triple seronegative patients had lower frequency of peripheral nervous involvement (0% vs. 7.2% p=0.002) compared to SS(+) controls and lower frequency of interstitial renal disease and higher prevalence of dry mouth than SS(+)/RF(-) controls. Quadruple seronegative patients presented less frequently with persistent lymphadenopathy (1.5% vs. 16.9 p=0.004) and lymphoma (0% vs. 9.8% p=0.006) compared to SS(+) controls and with lower prevalence of persistent lymphadenopathy (1.5% vs. 15.3% p=0.008) and higher frequency of dry eyes (98.6% vs. 87.5% p=0.01) and autoimmune thyroiditis (44.1% vs. 17.1% p=0.02) compared to SS(+)/RF(-) SS controls. Study groups comparative analysis revealed that triple seronegative patients had higher frequency of persistent lymphadenopathy and lymphoma, higher focus score and later age of SS diagnosis compared to quadruple seronegative patients. CONCLUSIONS: Combined seronegativity accounts for almost 9% of total SS population and is associated with a milder clinical phenotype, partly attributed to the absence of rheumatoid factor.

COVID-19 in patients with gout on colchicine.

Current data demonstrated that severe cases of coronavirus-disease-19 (COVID-19) require treatment with antiviral therapy, dexamethasone, supportive care, as well as some anti-rheumatic drugs, among them, cytokine inhibitors and colchicine. Colchicine is an anti-inflammatory drug that is being used in rheumatology for many years to treat mostly gout, calcium pyrophosphate deposition disease, and Familial Mediterranean Fever. Here, we present for the first time, two patients suffering from gout being treated with colchicine, who were affected from severe acute respiratory coronavirus-2 (SARS-CoV-2) syndrome. Both patients presented with mild symptoms of COVID-19 expressed with myalgias, arthralgias, and sore throat, while laboratory investigations showed only high acute phase reactants. Four weeks later, both patients were free of symptoms with negative SARS-CoV-2 tests and without any complications. To our knowledge, there are no other studies of gout arthritis and SARS-CoV-2 infection published so far. Thus, our preliminary conclusion is that chronic use of colchicine may mitigate the clinical picture and disease course of COVID-19 in gout arthritis patients. Further studies with a large number of patients are needed to confirm the above beneficial effect of colchicine.

Calcified constrictive pericarditis resulting in tamponade in a patient with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan involvement, including heart. Pericarditis-the most common cardiac manifestation-occurs in up to 50% of cases, resulting in positive treatment outcomes. Rarely, it evolves to hazardous complications. A 50-year-old woman with SLE in clinical remission, receiving hydroxychloroquine 400 mg/day, presented to us with severe chest pain and low-grade fever. Physical examination revealed a friction rub and decreased breath sounds at the right lung base. Laboratory evaluation demonstrated leukopenia, thrombocytopenia, low C4 levels, and high acute phase reactants. Chest X-ray exhibited cardiomegaly, calcified pericardium, and right pleural effusion, confirmed by CT scan. PPD skin test and IGRA were both negative. Pericardial fluid, blood, and urine cultures for bacteria and fungi, as well as Gram and Ziehl-Neelsen stains were negative. Serological tests for viruses were also negative. The patient was diagnosed with calcified constrictive pericarditis (CP) due to SLE. She was treated with cyclophosphamide and methylprednisolone pulses, without improvement. Her clinical condition deteriorated, developing signs and symptoms compatible with cardiac tamponade (TMP), which was confirmed by Doppler echocardiography. The patient underwent pericardiectomy. A dramatic response was noted and she was discharged with prednisone 50 mg/day and azathioprine 100 mg/day. Thus, we review and discuss the relevant literature of SLE cases with CP or TMP. When an SLE patient presents with CP, infectious causes should be excluded first. To the best of our knowledge, this is the only case of SLE and calcified CP leading to TMP, hence physicians should be aware of this complication.

Use of conventional synthetic and biologic disease-modifying anti-rheumatic drugs in patients with rheumatic diseases contracting COVID-19: a single-center experience.

To examine whether patients with inflammatory arthritis (IA) treated with conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) and/or biologic (b) DMARDs, could be affected from SARS-CoV-2 infection and to explore the COVID-19 disease course and outcome in this population. This is a prospective observational study. During the period February-December 2020, 443 patients with IA who were followed-up in the outpatient arthritis clinic were investigated. All patients were receiving cs and/or bDMARDs. During follow-up, the clinical, laboratory findings, comorbidities and drug side effects were all recorded and the treatment was adjusted or changed according to clinical manifestations and patient's needs. There were 251 patients with rheumatoid arthritis (RA), 101 with psoriatic arthritis (PsA) and 91 with ankylosing spondylitis (AS). We identified 32 patients who contracted COVID-19 (17 RA, 8 PsA, 7 AS). All were in remission and all drugs were discontinued. They presented mild COVID-19 symptoms, expressed mainly with systemic manifestations and sore throat, while six presented olfactory dysfunction and gastrointestinal disturbances, and all of them had a favorable disease course. However, three patients were admitted to the hospital, two of them with respiratory symptoms and pneumonia and were treated appropriately with excellent clinical response and outcome. Patients with IA treated with cs and/or bDMARDs have almost the same disease course with the general population when contract COVID-19.