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Objective: To assess the relationship between smoking exposure and organ damage accrual measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for Systemic Lupus Erythematosus score (SLICC-SDI) in consecutive patients with systemic lupus erythematosus (SLE) from Argentina., Methods: 623 consecutive SLE patients (fulfilling ≥4, 1997 ACR criteria) were included in this cross-sectional study. Sociodemographic and disease related variables including SLICC-SDI score and smoking status were collected. Patients currently smoking were considered "smokers", and "non-smokers" those who never smoked and former smokers. SLICC-SDI was divided into two categories: <3 and ≥3 was defined as severe damage., Results: Six hundred and 23 patients were included in the analysis, 89% women. Eighty-four per cent were non-smokers and 16 % were current smokers 83 percent of patients had SLICC-SDI <3 and 17 % had SLICC-SDI ≥3. Twenty one percent of patients with SLICC-SDI ≥3 and 15% with <3 SLICC-SDI were current smokers ( p 0.081). In the multiple regression analysis, current smoking (OR 1.82, CI 95% 1.01-3.31, p 0.046), older age (OR 1.04, CI 95% 1.00-1.05, p 0.034), disease duration (OR 1.03, CI 95% 1.00-1.07, p 0.021) and cyclophosphamide exposure (OR 2.97, CI 95% 1.49-5.88, p 0.002) were related to SLICC-SDI ≥3., Conclusion: In our sample of patients, current smoking, older age, disease duration and cyclophosphamide were related to severe damage (SLICC-SDI ≥3)., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To describe characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) from Argentina, Mexico and Brazil, and to assess factors associated with mortality in this population., Methods: Data from 3 national registries, SAR-COVID (Argentina), CMR-COVID (Mexico), and ReumaCoV-Brasil (Brazil), were combined. Adult patients with IMIDs and SARS-CoV-2 infection were recruited. Sociodemographic data, comorbidities, IMID clinical characteristics and treatment, and SARS-CoV-2 infection presentation and outcomes were recorded., Results: A total of 4827 individuals were included: 2542 (52.7%) from SAR-COVID, 1167 (24.2%) from CMR-COVID, and 1118 (23.1%) from ReumaCoV-Brasil. Overall, 82.1% were female with a mean age of 49.7 (SD, 14.3) years; 22.7% of the patients were hospitalized, and 5.3% died because of COVID-19 (coronavirus disease 2019). Argentina and Brazil had both 4% of mortality and Mexico 9.4%. In the multivariable analysis, older age (≥60 years; odds ratio [OR], 7.4; 95% confidence interval [CI], 4.6-12.4), male sex (OR, 1.5; 95% CI, 1.1-2.1), living in Mexico (OR, 3.0; 95% CI, 2.0-4.4), comorbidity count (1 comorbidity: OR, 1.5; 95% CI, 1.0-2.1), diagnosis of connective tissue disease or vasculitis (OR, 1.8; 95% CI, 1.3-2.4), and other diseases (OR, 2.6; 95% CI, 1.6-4.1) compared with inflammatory joint disease, high disease activity (OR, 4.2; 95% CI, 2.5-7.0), and treatment with glucocorticoids (OR, 1.9; 95% CI, 1.4-2.5) or rituximab (OR, 4.2; 95% CI, 2.7-6.6) were associated with mortality., Conclusions: Mortality in patients with IMIDs was particularly high in Mexicans. Ethnic, environmental, societal factors, and different COVID-19 mitigation measures adopted have probably influenced these results., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background/objective: This study describes the impact of immunomodulatory and/or immunosuppressive (IM/IS) drugs in the outcomes of COVID-19 infection in a cohort of patients with immune-mediated inflammatory diseases (IMIDs)., Methods: Adult patients with IMIDs with a confirmed SARS-CoV-2 infection were included. Data were reported by the treating physician between August 13, 2020 and July 31, 2021. Sociodemographic data, comorbidities, and DMARDs, as well as clinical characteristics, complications, and treatment of the SARS-CoV-2 infection, were recorded. Descriptive analysis and multivariable logistic regression models were carried out., Results: A total of 1672 patients with IMIDs were included, of whom 1402 were treated with IM/IS drugs. The most frequent diseases were rheumatoid arthritis (47.7%) and systemic lupus erythematosus (18.4%). COVID-19 symptoms were present in 95.2% of the patients. A total of 461 (27.6%) patients were hospitalized, 8.2% were admitted to the intensive care unit, and 4.4% died due to COVID-19.Patients without IM/IS treatment used glucocorticoids less frequently but at higher doses, had higher levels of disease activity, were significantly older, were more frequently hospitalized, admitted to the intensive care unit, and died due to COVID-19. After adjusting for these factors, treatment with IM/IS drugs was not associated with a worse COVID-19 outcome (World Health Organization-Ordinal Scale ≥5) (odds ratio, 1.24; 95% confidence interval, 0.73-2.06)., Conclusions: SAR-COVID is the first multicenter Argentine registry collecting data from patients with rheumatic diseases and SARS-CoV-2 infection. After adjusting for relevant covariates, treatment with IM/IS drugs was not associated with severe COVID-19 in patients with IMIDs., Study Registration: This study has been registered in ClinicalTrials.gov under the number NCT04568421., Competing Interests: Conflicts of interest: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SAR-COVID is a multisponsor registry, where Pfizer, Abbvie, and Elea Phoenix had provided unrestricted grants. None of them has participated or influenced the development of the project, data collection, analysis, and interpretation, or the drafting of this report. They do not have access to the information collected in the database., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background/objective: This study aims to describe the course and to identify poor prognostic factors of SARS-CoV-2 infection in patients with rheumatic diseases., Methods: Patients ≥ 18 years of age, with a rheumatic disease, who had confirmed SARS-CoV-2 infection were consecutively included by major rheumatology centers from Argentina, in the national, observational SAR-COVID registry between August 13, 2020 and July 31, 2021. Hospitalization, oxygen requirement, and death were considered poor COVID-19 outcomes., Results: A total of 1915 patients were included. The most frequent rheumatic diseases were rheumatoid arthritis (42%) and systemic lupus erythematosus (16%). Comorbidities were reported in half of them (48%). Symptoms were reported by 95% of the patients, 28% were hospitalized, 8% were admitted to the intensive care unit (ICU), and 4% died due to COVID-19. During hospitalization, 9% required non-invasive mechanical ventilation (NIMV) or high flow oxygen devices and 17% invasive mechanical ventilation (IMV). In multivariate analysis models, using poor COVID-19 outcomes as dependent variables, older age, male gender, higher disease activity, treatment with glucocorticoids or rituximab, and the presence of at least one comorbidity and a greater number of them were associated with worse prognosis. In addition, patients with public health insurance and Mestizos were more likely to require hospitalization., Conclusions: In addition to the known poor prognostic factors, in this cohort of patients with rheumatic diseases, high disease activity, and treatment with glucocorticoids and rituximab were associated with worse COVID-19 outcomes. Furthermore, patients with public health insurance and Mestizos were 44% and 39% more likely to be hospitalized, respectively., Study Registration: This study has been registered in ClinicalTrials.gov under the number NCT04568421. Key Points • High disease activity, and treatment with glucocorticoids and rituximab were associated with poor COVID-19 outcome in patients with rheumatic diseases. • Some socioeconomic factors related to social inequality, including non-Caucasian ethnicity and public health insurance, were associated with hospitalization due to COVID-19., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background/objective: To evaluate the efficacy and safety of SARS-CoV-2 vaccine in patients with rheumatic and immune-mediated inflammatory diseases (IMIDs) in Argentina: the SAR-CoVAC registry., Methods: SAR-CoVAC is a national, multicenter, and observational registry. Adult patients with rheumatic or IMIDs vaccinated for SARS-CoV-2 were consecutively included between June 1 and September 17, 2021. Sociodemographic data, comorbidities, underlying rheumatic or IMIDs, treatments received, their modification prior to vaccination, and history of SARS-CoV-2 infection were recorded. In addition, date and place of vaccination, type of vaccine applied, scheme, adverse events (AE), disease flares, and new immune-mediated manifestations related to the vaccine were analyzed., Results: A total of 1234 patients were included, 79% were female, with a mean age of 57.8 (SD 14.1) years. The most frequent diseases were rheumatoid arthritis (41.2%), osteoarthritis (14.5%), psoriasis (12.7%), and spondyloarthritis (12.3%). Most of them were in remission (28.5%) or low disease activity (41.4%). At the time of vaccination, 21% were receiving glucocorticoid treatment, 35.7% methotrexate, 29.7% biological (b) disease modifying anti-rheumatic drugs (DMARD), and 5.4% JAK inhibitors. In total, 16.9% had SARS-CoV-2 infection before the first vaccine dose. Most patients (51.1%) received Gam-COVID-Vac as the first vaccine dose, followed by ChAdOx1 nCoV-19 (32.8%) and BBIBP-CorV (14.5%). Half of them (48.8%) were fully vaccinated with 2 doses; 12.5% received combined schemes, being the most frequent Gam-COVID-Vac/mRAN-1273. The median time between doses was 51 days (IQR 53). After the first dose, 25.9% of the patients reported at least one AE and 15.9% after the second, being flu-like syndrome and local hypersensitivity the most frequent manifestations. There was one case of anaphylaxis. Regarding efficacy, 63 events of SARS-CoV-2 infection were reported after vaccination, 19% occurred during the first 14 days post-vaccination, 57.1% after the first dose, and 23.8% after the second. Most cases (85.9%) were asymptomatic or mild and 2 died due to COVID-19., Conclusions: In this national cohort of patients, the most common vaccines used were Gam-COVID-Vac and ChAdOx1 nCoV-19. A quarter of the patients presented an AE and 5.1% presented SARS-CoV-2 infection after vaccination, in most cases mild., Study Registration: This study has been registered in ClinicalTrials.gov under the number: NCT04845997. Key Points • This study shows real-world data about efficacy and safety of SARS-CoV-2 vaccination in patients with rheumatic and immune-mediated inflammatory diseases. Interestingly, different types of vaccines were used including vector-based, mRNA, and inactivated vaccines, and mixed regimens were enabled. • A quarter of the patients presented an adverse event. The incidence of adverse events was significantly higher in those receiving mRAN-1273 and ChAdOx1 nCoV-19. • In this cohort, 5.1% presented SARS-CoV-2 infection after vaccination, in most cases mild., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background/objective: Data on IgG4-related disease (IgG4-RD) come almost exclusively from cohorts from Asia, Europe, and North America. We conducted this study to describe the clinical presentation, phenotype distribution, and association with sex, ethnicity, and serological markers in a large cohort of Latin American patients with IgG4-RD., Methods: We performed a multicenter medical records review study including 184 Latin American IgG4-RD patients. We assigned patients to clinical phenotypes: group 1 (pancreato-hepato-biliary), group 2 (retroperitoneal/aortic), group 3 (head and neck-limited), group 4 (Mikulicz/systemic), and group 5 (undefined). We focused the analysis on how sex, ethnicity, and clinical phenotype may influence the clinical and serological presentation., Results: The mean age was 50.8 ± 15 years. Men and women were equally affected (52.2% vs 48.8%). Fifty-four patients (29.3%) were assigned to group 1, 21 (11.4%) to group 2, 57 (30.9%) to group 3, 32 (17.4%) to group 4, and 20 (10.8%) to group 5. Male sex was associated with biliary tract (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.36-8.26), kidney (OR, 3.4; 95% CI, 1.28-9.25), and retroperitoneal involvement (OR, 5.3; 95% CI, 1.45-20). Amerindian patients presented more frequently with atopy history and gallbladder involvement. Group 3 had a female predominance., Conclusions: Latin American patients with IgG4-RD were younger, and men and women were equally affected compared with White and Asian cohorts. They belonged more commonly to group 1 and group 3. Retroperitoneal and aortic involvement was infrequent. Clinical and serological features differed according to sex, ethnicity, and clinical phenotype., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally., Methods: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death., Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 μg/m 3 [95% CI 1·01-1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10-1·30]; p<0·0001), and population mobility (1·03 per 1% increase in number of visits to grocery and pharmacy stores [1·02-1·05]; p<0·0001 and 1·02 per 1% increase in number of visits to workplaces [1·00-1·03]; p=0·032) were independently associated with higher odds of mortality. Number of hospital beds (0·94 per 1-unit increase per 1000 people [0·88-1·00]; p=0·046), human development index (0·65 per 0·1-unit increase [0·44-0·96]; p=0·032), government response stringency (0·83 per 10-unit increase in containment index [0·74-0·93]; p=0·0018), as well as follow-up time (0·78 per month [0·69-0·88]; p<0·0001) were independently associated with lower odds of mortality. These factors sufficiently explained country-level variations in death attributable to COVID-19 (intraclass correlation coefficient 1·2% [0·1-9·5]; p=0·14)., Interpretation: Our findings highlight the importance of environmental and societal factors as potential explanations of the observed regional disparities in COVID-19 outcomes among people with rheumatic disease and lay foundation for a new research agenda to address these disparities., Funding: American College of Rheumatology and European Alliance of Associations for Rheumatology., Competing Interests: MID reports research support from Pfizer for unrelated work. AS reports grants from a consortium of 13 companies (AbbVie, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Lilly, Mylan, Hexal, Merck, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB) supporting the German RABBIT register, and personal fees from lectures for AbbVie, Merck, Roche, Bristol Myers Squibb, and Pfizer, outside of the submitted work. EFM reports that the Portuguese League Against Rheumatic Diseases received support for specific activities: grants from Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal SA, Merck, Celgene, Medac, Pharmakern, the Global Alliance for Patient Access; grants and non-financial support from Pfizer; and non-financial support from Grünenthal GmbH, outside of the submitted work. KLH reports receiving speaker fees from Abbvie and grant income from Bristol Myers Squibb, UCB, and Pfizer, unrelated to this work. KLH is also supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre. LG reports research grants from Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz, and Sanofi; and consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Biogen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, and UCB, all unrelated to this work. LC has not received fees or personal grants from any laboratory, but her institute works by contract for laboratories among other institutions, such as Abbvie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, SA Pharma, Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi, Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal GmbH, and UCB Pharma. JAS has performed consultancy for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, and Optum, unrelated to this work. LW has received consulting or speaking fees from Aurinia Pharma, outside of the submitted work. MFU-G reports grant or research support from Jannsen and Pfizer, unrelated to this work. The Swedish Rheumatology Quality Register, with LL as register holder, has agreements with Abbvie, Amgen, Eli Lilly, Gilead, Novartis, Pfizer, Sanofi, Sobi, and UCB for register data analyses, unrelated to this work. CR has received consulting or speaker fees from Abbvie, Amgen, AstraZeneca, BMS, Biogen, Eli Lilly, Glenmark, GlaxoSmithKline, Merck, Mylan, and Pfizer; and grants from Biogen, Lilly, and Nordic Pharma, all unrelated to this work. MJS has received speaker fees from Abbvie, AstraZeneca, Novartis, and Pfizer. AR has received speaker fees from Janssen, Pfizer, and Novartis. GP-E reports reports personal consulting fees, speaking fees, or both from Pfizer, GlaxoSmithKline, Janssen, Sandoz, and Sanofi, outside of the submitted work. PCR reports personal consulting fees, speaking fees, or both from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and travel assistance from Roche. PMM has received consulting fees, speaker fees, or both from Abbvie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, and UCB, unrelated to this work. PMM is supported by the NIHR University College London Hospitals Biomedical Research Centre. ES is a Board Member of the Canadian Arthritis Patient Alliance, a patient-run, volunteer-based organisation whose activities are largely supported by independent grants from pharmaceutical companies. JWL has received research funding from Pfizer, outside of the submitted work. JSH is supported by grants from the Rheumatology Research Foundation and has salary support from the Childhood Arthritis and Rheumatology Research Alliance. JSH has performed consulting for Novartis, Sobi, and Biogen, unrelated to this work. PS reports honorarium for doing social media for American College of Rheumatology journals. RG reports personal fees, speaking fees, or both from Abbvie, Janssen, Novartis, Pfizer, and Cornerstones; and travel assistance from Pfizer. SB reports non-branded consulting fees for AbbVie, Horizon, and Novartis; and is employed by Pfizer. ZSW reports grant support from Bristol Myers Squibb and Principia–Sanofi; and performed consultancy for Viela Bio and MedPace, outside of the submitted work. ZSW's work is supported by grants from the National Institutes of Health. JY has performed consulting for Eli Lilly, Pfizer, Aurinia, and AstraZeneca, outside of the submitted work. All other authors declare no competing interests., (Published by Elsevier Ltd.)

Competing Interests: The authors declare no conflict of interest.

Objectives: Methotrexate (MTX) has been studied with conflicting results in patients with polymyalgia rheumatica (PMR). Our objective was to evaluate the effectiveness of MTX to reduce relapses and recurrences in patients with PMR., Methods: This observational longitudinal cohort study included 94 consecutive patients with PMR. Patients were assigned to 3 groups according to the prescribed treatment: group 1, treated with glucocorticoids (GCs) alone; group 2, treated with GCs initially plus MTX after a relapse or recurrence; and group 3, treated with GCs plus MTX since diagnosis.Factors associated with a first relapse were studied in the population. To evaluate MTX effect, patients from group 2 were evaluated comparing results from the first treatment period (GCs alone) to the second treatment period with GCs plus MTX., Results: Ninety-four patients were included. The median follow-up time was 21.3 months (interquartile range [IQR], 11.7-56.2). Fifty-three patients (56.4%) were in group 1, 33 (35.1%) in group 2, and 8 (8.5%) in group 3. We found that female sex had a tendency to be associated with a first relapse (p = 0.07).In group 2, 35 relapses were identified during the first treatment period and only 8 relapses during the combined treatment period (p < 0.001). In this group, after the addition of MTX, the GCs dose at relapse was lower (5.1 vs 3 mg/d, p = 0.02) and the time to accomplish remission was shorter (22.9 vs 8.7 months, p = 0.01). There were no differences in the number of recurrences., Conclusions: The use of MTX in PMR patients who already had a relapse reduced the number of future relapses and decreased the time to achieve remission. Adding MTX allowed a reduction of GCs dose at relapse.

Objective: To assess the association between the HLA-B*51 allele and Behçet Disease (BD) in Argentinean patients., Methods: We enrolled 34 consecutive Argentinean patients with definitive diagnosis of BD between October 2016 and March 2017. None of the patients had the HLA-B*51 allele determined at study entry. Unrelated controls (n=240) were randomly obtained from the national cadaveric donor database. Demographic and clinical features of the patients were recorded by attending physicians through a questionnaire., Results: Mean age of cases was 42 years old. Nineteen (55.8%) were male, and the mean age at diagnosis was 35 years old; twenty (58.8%) were Mestizos, 8 (23.5%) were Caucasian, and 6 (17.6%) were Amerindians. Thirteen (38.2%) of 34 cases were HLA-B*51 allele positive; 11 were heterozygous and 2 homozygous for the allele. Thirty-four (14.2%) of 240 controls were positive for the HLA-B*51 allele. The association between BD and HLA-B*51 allele was greater than that of control group (OR=3.75; p=0.0012)., Conclusions: The HLA-B*51 allele is strongly associated with BD in Argentinean patients. Our finding is consistent with previous studies indicating that the HLA-B*51 allele is an important susceptibility gene in BD regardless the geographical region and ethnicity., (Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Introduction: Giant cell arteritis (GCA) is the most frequent systemic vasculitis in patients older than 50 years. The diagnosis is based on the clinical history, laboratory findings and imaging studies associated with a temporal artery biopsy (TAB). However, the biopsy result could be inconclusive in up to 40% of the cases. The aim of this study was to review the current management of the patients with clinical suspect of GCA in the university hospital CEMIC in Buenos Aires, Argentina, and correlate the disease behavior with the TAB result., Methods: Retrospective study that reviewed consecutive patients to whom a TAB was made in an 11-year period (2005-2016). Clinical and pathology reports were reviewed. Descriptive statistics were performed. Quantitative variables were described as mean (S.D.) or median [range or inter- quartile range (IQR)] and qualitative variables as number (%). To compare the characteristics of the groups, bivariate analyzes were performed using contingency tables and logistic regression models if necessary., Results: Sixty three patients were included, 68% women. The mean age was 72 years old (SD 8.4). Seventeen biopsies (26.9%) were positive for GCA. The average post fixation length was 1.68 cm (SD 1.2). Patients were divided into 3 groups taking into account the result of the TAB, the ACR criteria and the imaging studies. We could not identify predictors of biopsy positivity. The group of patients with GCA and negative TAB showed a higher percentage of patients with abnormal temporal artery at physical examination., Conclusion: The TAB positive percentage (26.9%) was similar to the reported in other series as well as the post fixation length. We could not identify predictors of biopsy positivity., (Universidad Nacional de Córdoba)

The cytoplasmic discrete dot (CDD) pattern is an unusual finding in indirect immunofluorescence, and its clinical value is unknown. To describe the clinical characteristics of patients with CDD pattern on indirect immunofluorescence (IIF) from our laboratory database and to evaluate possible associations with other autoantibodies and autoimmune diseases. This is a retrospective descriptive study. We included all patients with CDD pattern on IIF in HEp-2 cells with a titer equal or greater than 1/80, using a database of all IIF performed in a reference immunology and rheumatology laboratory between 2007 and 2015. Data on demographics, past medical history, and relevant laboratory findings were recorded and analyzed. We performed 13.056 IIF on HEp-2 cells tests between January 1, 2007 and December 31, 2015, with 6075 positive results. Among them, 5447 had nuclear pattern, 55 had both nuclear and cytoplasmic pattern, and 573 had cytoplasmic pattern. Only 21 showed a CDD pattern. Four patients were excluded since they did not have medical records at the institution. The prevalence of the CDD pattern in our laboratory was 0.35%. The median age was of 62.3 years (SD 9.16) and 100% were female. Fifty-three percent (9/17) had an autoimmune disease, Hashimoto's thyroiditis (4/9) being the most frequent one. In conclusion, cytoplasmic discrete dot pattern is an uncommon finding and its clinical value is uncertain. However, in our study, 53% of the patients had an autoimmune disease.

Objective: To study the prevalence and the associated factors of work disability (WD) in systemic lupus erythematosus (SLE) patients., Methods: A sample of 419 SLE patients from an observational cross-sectional multicenter study was included. Sociodemographic features, disease characteristics, comorbidities, quality of life, unhealthy behaviors, and work-related factors were measured in a standardized interview. Work disability was defined by patient self-report of not being able to work because of SLE. To identify variables associated with work disability, two different multivariate regression models using a stepwise backward method were performed., Results: Prevalence of WD due to SLE was 24.3%. Eighty-nine percent were female and 51% were Caucasians. Mean disease duration was 8.9 ± 7.2 years, and median System Lupus International Collaborating Clinics/American College of Rheumatology damage index SLICC-SDI was 1.5 (range 0-17). In stepwise multivariate logistic regression, living below the poverty line (odds ratio [OR] = 4.65), less than 12 years of education (OR = 2.84), Mestizo ethnicity (OR = 1.94) and SLICC-SDI (OR = 1.25) were predictors of WD. A second model was performed including patient-derived measures; in this model sedentary lifestyle (OR = 2.69) and lower emotional health domain score of the Lupus Quality of Life (LupusQoL) questionnaire (OR = 1.03) were found to be associated to WD and a higher score in LupusQoL physical health domain (OR = 0.93) was protective., Conclusion: The prevalence of WD in Argentinian SLE patients was 24.3%. WD was associated with ethnic (Mestizo), socioeconomic (poverty) and disease-related factors. Patient-related outcomes such us sedentary lifestyle and poor emotional quality of life were also associated with WD., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective The aim of this study was to measure presenteeism (productivity impairment while the patient is at work) and the related risk factors in patients with systemic lupus erythematosus (SLE) from Argentina. Methods A total of 130 consecutive (1997 American College of Rheumatology (ACR) criteria) working patients with SLE were assessed using a standardized data collection form. Sociodemographic, disease and work-related variables were collected. The Work Productivity and Activity Impairment (WPAI) questionnaire was performed. Results Overall, 130 patients were included in the analysis; 91% were women, and the mean age was 39 years (range 19-77). A total of 43% were White, 43% Mestizo and 13% Amerindian. Overall, 38% were single and 38% were married. A total of 75% had more than 12 years of formal education. The median disease duration was 7 years (interquartile range 25-75 (IQR) 4-13). Median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 0 (IQR 0-2), and median Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC-SDI) score was 0 (IQR 0-1). Lupus quality of life (LupusQoL) domains scores were: physical health 87 (IQR 70-96), emotional health 78 (IQR 54-91), burden to others 75 (IQR 50-92), intimate relationships 87 (IQR 50-100), and body image 85 (IQR 70-100). Absenteeism was 8%, presenteeism was 19%, and overall work impairment (absenteeism + presenteeism) was 26%. In the multiple regression analysis, considering presenteeism as dependent variable, (adjusting by age, disease duration, >12 years of education, Non-white race, Visual Analogue Scale (VAS) pain, VAS fatigue, SLICC-SDI, LupusQoL, physical and emotional domains), we found that SLICC-SDI (odds ratio (OR) 1.68, confidence interval (CI) 1-2.7) and Non-white race (OR 3.27, CI 1.04-10) were related to presenteeism and >12 years of education (OR 0.30, CI 0.09-0.98) and higher scores of LupusQoL emotional health domain (OR 0.95, CI 0.92-0.98) were protective. Conclusions organ damage and Non-white race were significantly associated with presenteeism while >12 years of education and higher scores of LupusQoL emotional health domain were protective.

Non Hodking´s lymphoma (NHL) may involve bones but synovial involvement is uncommon. We describe a patient who presented with polyarthritis, sicca symptoms and rash suggestive of rheumatoid arthritis. An atypical skin rash prompted skin and synovial biopsies. A diagnosis of synovial and skin malignant large B-cell lymphoma anaplastic subtype was performed. Chemotherapy with dexamethasone, vincristine and rituximab was started. Following treatment the patient had complete resolution of cutaneous and articular lymphoma manifestations.

Objectives: Patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) have increased IL-1β levels. IL-1β and other pro-inflammatory cytokines have a modulating activity on cardiac ion channels and have been associated with increased arrhythmic risk in rheumatoid arthritis patients. Likewise, adult patients with connective tissue diseases (CTDs) may have prolonged QTc intervals associated with the presence of anti-Ro/SSA antibodies. Our objective was to evaluate the presence of serum IL-1β in subjects with CTDs, in relation to the presence of anti-Ro/SSA antibodies and QTc interval duration., Methods: 12-lead electrocardiograms (ECG) were performed and blood was withdrawn, measuring electrolytes, IL-1β anti-Ro/SSA antibodies by ELISA in 73 patients with CTDs., Results: 55 patients were anti-Ro/SSA positive and 18 were anti-Ro/SSA negative. Patients with anti-Ro/SSA positive antibodies had a significantly greater median IL-1β serum level: 7.29 (range: 0.17-17.3 pg/ml) compared to patients with anti-Ro/SSA negative antibodies whose median was: 1.67 (range 0.55-4.12 pg/ml) p<0.001. The mean QTc interval values obtained in both groups were not significantly different (417.7±23.1 vs. 414.7±21.2, p=0.63). The QTc interval was prolonged in 11 (20%) patients, who were all anti-Ro/SSA positive versus 0 (0 %) in anti-Ro/SSA negative patients p=0.05. Median IL-1β levels were: 8.7 (range: 2.69-15.1 pg/ml) in patients with prolonged QTc interval versus median: 5.0 (range: 0.17-17.3 pg/ml) in those with normal QTc interval values (<440ms) p=0.006., Conclusions: IL-1β is elevated in patients with CTDs that have both anti-Ro/SSA antibodies and prolonged QTc intervals.

Objective: To investigate the prevalence and associations with clinical manifestations of anti- P ribosomal antibodies in patients with juvenile-onset and adult-onset systemic lupus erythematosus (SLE)., Methods: Clinical and serological data of 30 patients with juvenile-onset SLE (age at onset younger than 16 years old) were compared with data of 92 patients with adult-onset SLE. Symptoms occurring during the entire disease course were considered. Anti- P ribosomal antibodies were tested by ELISA., Results: Anti- P ribosomal antibodies were found significantly more often in pediatric-onset SLE patients (26.7% vs. 6.5%; OR=5.21 [CI95%=1.6-16.5], p=0.003). Alopecia (OR=10.11, CI 95%=1.25-97) and skin rash (non discoid) (OR=4.1, CI 95%=1.25-13.89) were significantly associated with anti- P ribosomal antibodies., Conclusion: Anti-ribosomal P antibodies are more often found in patients with juvenile SLE. Alopecia and skin rash were the only clinical manifestations associated to anti-ribosomal P antibodies., (Copyright © 2013 Elsevier España, S.L.U. All rights reserved.)

A 55-year-old man with granulomatosis with polyangiitis (GPA) developed continuous parietal headache, malaise, nasal crusting and dry cough. Neurological exam revealed only left hand hypoesthesia in 4th and 5th finger. Brain MRI showed enlarged right choroid plexus, hyperintense periventricular white matter, thalami and right side of corpus callosum. The suspected diagnosis was ependimoplexitis due to GPA, the patient received three 500 mg methylprednisolone pulses followed by 1 mg/kg of meprednisone with gradual tapering and was switched to oral cyclophosphamide. He had complete resolution of headache. An MRI following this treatment for relapse revealed only minimal ependimal changes.

Background: A recent case-control study suggested a benefit of hydroxychloroquine (HCQ) in lowering the risk of cardiac manifestations of neonatal lupus (cardiac-NL) in pregnancies of anti-SSA/Ro-positive patients with systemic lupus erythematosus. A historical cohort assembled from 3 international databases was used to evaluate whether HCQ reduces the nearly 10-fold increase in risk of recurrence of cardiac-NL independently of maternal health status., Methods and Results: Two hundred fifty-seven pregnancies of anti-SSA/Ro-positive mothers (40 exposed and 217 unexposed to HCQ) subsequent to the birth of a child with cardiac-NL were identified from 3 databases (United States, England, and France). Exposure was defined as the sustained use of HCQ throughout pregnancy with initiation before 10 weeks of gestation. The recurrence rate of cardiac-NL in fetuses exposed to HCQ was 7.5% (3 of 40) compared with 21.2% (46 of 217) in the unexposed group (P=0.050). Although there were no deaths in the exposed group, the overall case fatality rate of the cardiac-NL fetuses in the unexposed group was 21.7%. In a multivariable analysis that adjusted for database source, maternal race/ethnicity, and anti-SSB/La status, HCQ use remained significantly associated with a decreased risk of cardiac-NL (odds ratio, 0.23; 95% confidence interval, 0.06-0.92; P=0.037). Similar results were obtained with propensity score analysis, an alternative approach to adjust for possible confounding by indication., Conclusion: Aggregate data from a multinational effort show that in mothers at high risk of having a child with cardiac-NL, the use of HCQ may protect against recurrence of disease in a subsequent pregnancy.

Objective: Congenital heart block (CHB) is presumed to be caused by transplacental passage of maternal immunoglobulin against Ro and La ribonucleoproteins. The recurrence rate in subsequent pregnancies following the birth of a child with CHB is approximately 19%. The purpose of this study was to determine whether intravenous immunoglobulin (IVIG) therapy could prevent the development of CHB in the fetuses of high-risk pregnant women., Methods: A total of 24 pregnancies in 22 women who had a previous pregnancy in which CHB developed, were over the age of 18 years, were <12 weeks pregnant, and had anti-Ro, anti-La, or both antibodies were monitored in this multicenter, prospective, observational study. Fifteen patients received infusions of IVIG. The 9 pregnancies in the remaining 7 patients served as controls. IVIG was administered at a dose of 400 mg/kg at weeks 12, 15, 18, 21, and 24 of pregnancy. Echocardiograms were performed at least every 3 weeks from week 15 to week 30 of gestation. Electrocardiograms were obtained at birth. The outcome measure was the development of third-degree CHB detected by fetal echocardiogram., Results: CHB developed in 3 babies among the 15 pregnancies in the treatment group (20%) and in 1 baby among the 9 pregnancies in the control group (11%). CHB was detected at weeks 18, 23, and 26, respectively, in the 3 babies in the treated group and at week 19 in the baby in the control group. Three of the affected pregnancies ended in termination; 2 for reasons related to the fetal disease and 1 for reasons related to both maternal (severe pulmonary hypertension) and fetal disease (at 21 weeks of gestation)., Conclusion: IVIG at the dose and frequency used in this study was not effective as prophylactic therapy for CHB in high-risk mothers.

Objectives: To identify the main causes of morbidity and mortality in patients with antiphospholipid syndrome (APS) during a 5-year period and to determine clinical and immunological parameters with prognostic significance., Methods: The clinical and immunological features of a cohort of 1000 patients with APS from 13 European countries who had been followed up from 1999 to 2004 were analysed., Results: 200 (20%) patients developed APS-related manifestations during the 5-year study period. Recurrent thrombotic events appeared in 166 (16.6%) patients and the most common were strokes (2.4% of the total cohort), transient ischaemic attacks (2.3%), deep vein thromboses (2.1%) and pulmonary embolism (2.1%). When the thrombotic events occurred, 90 patients were receiving oral anticoagulants and 49 were using aspirin. 31/420 (7.4%) patients receiving oral anticoagulants presented with haemorrhage. 3/121 (2.5%) women with only obstetric APS manifestations at the start of the study developed a new thrombotic event. A total of 77 women (9.4% of the female patients) had one or more pregnancies and 63 (81.8% of pregnant patients) had one or more live births. The most common fetal complications were early pregnancy loss (17.1% of pregnancies) and premature birth (35% of live births). 53 (5.3% of the total cohort) patients died. The most common causes of death were bacterial infection (21% of deaths), myocardial infarction (19%) and stroke (13%). No clinical or immunological predictor of thrombotic events, pregnancy morbidity or mortality was detected., Conclusion: Patients with APS still develop significant morbidity and mortality despite current treatment (oral anticoagulants or antiaggregants, or both).

There have been significant advances in the treatment of SLE, which have produced major impacts on morbidity and in some cases mortality. The major drugs of the last three decades in treatment of SLE have been corticosteroids, AZA, MTX and cyclophosphamide. However, these drugs have considerable toxicities, and with the increasing knowledge of the immune system, and further understanding of SLE immunopathogenesis, many groups are seeking to identify and trial novel immunotherapeutic strategies. These have included therapies aimed at influencing particular immune cells (e.g. B cells) and molecules (e.g. costimulatory molecules, cytokines) which are thought to be important in disease pathogenesis. The advantage of such therapies is that efficacy may be achieved with lower toxicity, and without wide-ranging suppression of the immune system. Success has not always been achieved by specific design of immunotherapies for SLE, and the best recent example has been the use of B-cell depletion therapy, a concept derived from its successful use in RA. In this article, we discuss those immunotherapeutic strategies that have arrived as far as clinical trials in human subjects. In addition to these relatively specific immunotherapies, we also highlight the use of mycophenolate mofetil, an anti-proliferative immunosuppressant which has had good success over the last 10 yrs, with similar early efficacy to cyclophosphamide when used as induction therapy for lupus nephritis. Data are presented on more generalized immune strategies, such as the use of stem cell transplantation and intravenous immunoglobulin.

Objectives: To assess the efficacy and tolerability of mycophenolate mofetil (MMF) in six patients with myositis refractory to conventional immunosuppressive therapy., Methods: Six patients were identified from hospital notes. All had previously failed to respond to other immunosuppressive treatments. Efficacy was measured as changes in muscle strength, creatine kinase (CK) levels and prednisolone dose., Results: The mean age of the group was 49.8 +/- 9.1 yrs, 6 (100%) were female and Caucasian. Patients had failed to respond to a median of 3 (range 1-3) immunosuppressive drugs. They received MMF for a mean of 22.3 +/- 18.9 months with a mean MMF dose of 1.6 +/- 0.5 g/day. The mean initial prednisolone dose was 13.7 +/- 7.7 mg and the mean follow up dose was 8.5 +/- 4.9 mg/day (P = 0.03). CK levels were reduced from mean 2395 IU/l +/- 1202.8 to 746.6 +/- 555.8 IU/l (P = 0.03)., Conclusion: Our data demonstrate that MMF may be effective in myositis, previously unresponsive to conventional immunosuppressive drugs.

Menorrhagia is common in women receiving oral anticoagulation. In healthy women, reductions of up to 90% of menstrual loss have been described with the levonorgestrel releasing intrauterine device (LNG-IUS). However there is no data about the use of LNG-IUS in women receiving oral anticoagulation and so we assessed the efficacy and safety of LNG-IUS in this setting. Patients with menorrhagia who used LNG-IUS and warfarin were contacted by post and asked to complete a questionnaire assessing the extent and duration of menstrual bleeding, quality of life and treatment satisfaction. The questionnaire was sent to 23 patients and returned by 17. The amount of bleeding was reduced with the LNG-IUS in 10 (58.8%) women; amenorrhea occurred in four (23.5%), no change in blood loss in one (5.9%) and greater blood loss in two (11.8%) patients. The number of sanitary pads used was less in 12 (70.6%) patients; same in one (5.9%) patient, more in two (11.8%) patients and two (11.8%) did not remember. Five patients (29.4%) had shorter duration of bleeding, four (23.5%) had amenorrhoea, four (23.5%) had longer periods and four (23.5%) had same duration by subjective assessment. Eight (47.1%) patients felt very satisfied, four (23.5%) felt satisfied, two (11.8%) felt dissatisfied with the treatment, one felt very dissatisfied (5.9%) and two (11.8%) did not respond to the question. This small study suggests LNG-IUS is effective in reducing the duration and amount of menstrual bleeding in women with menorrhagia associated with oral anticoagulation. We feel the use of LNG-IUS is a major advance in reducing menorrhagia in women on oral anticoagulation as the previous alternative--hysterectomy--is associated with an increased risk of thrombosis and bleeding.

Introduction: Lupus membranous nephropathy (LMN) presents a difficult clinical problem as no particular treatment has been proven to be effective. Studies have shown good results with mycophenolate mofetil (MMF) in proliferative lupus nephropathy (LN) (WHO class III and IV disease)., Objectives: To study whether MMF treatment was effective in membranous predominant LN in patients resistant to or intolerant of other immunosuppressive agents., Patients and Methods: We retrospectively studied 10 patients with systemic lupus erythematosus who had biopsy-proven predominant LMN (six Vc patients and four Va or Vb patients). Previous treatments included cyclophosphamide, azathioprine, ciclosporin and corticosteroids. The following parameters were recorded at baseline and follow-up: blood pressure, ECLAM, proteinuria, serum albumin and creatinine, routine haematology and immunology., Results: The study included eight women and two men, mean age 38.4 +/- 7.1 yr (range 30-49 yr). The racial distribution was as follows: five Caucasian, and five Black patients. The mean treatment time with MMF was 18.8 +/- 15.4 months (range 3-52 months). Twenty-four-hour urinary protein excretion was reduced from median 2.26 g (range 0-7.92 g) to median 0.66 g (range 0.08-3.85 g) at follow-up (P = 0.0039). Serum albumin increased significantly after treatment from median 29.5 g/l (range 14.0-42.0 g/l) to 33.5 g/l (range 23.0-40.0 g/l) at follow-up (P = 0.04). There were no significant changes in serum creatinine (P = 0.55)., Conclusion: MMF is a potentially useful immunosuppressive agent in reducing the proteinuria associated with membranous predominant LN.

Objective: To assess the indications, efficacy, and tolerability of mycophenolate mofetil (MMF) in patients with systemic lupus erythematosus (SLE) resistant to other immunosuppressive therapy., Methods: Records of 93 patients with SLE were retrospectively reviewed. Seven patients were excluded. The remaining 86 patients received other immunosuppressive drugs before MMF. Efficacy was measured by changes in daily oral prednisolone dose, European Consensus Lupus Activity Measurement Index (ECLAM), erythrocyte sedimentation rate (ESR), C-reactive protein, and dsDNA antibody titer. In renal patients, changes in serum creatinine, creatinine clearance, chromium-51 EDTA glomerular filtration rate (EDTA-GFR), and 24 hour urine protein excretion were also evaluated., Results: Indications for MMF were mainly renal involvement (59% of patients), uncontrolled disease activity (14%), and other SLE related manifestations (13%). Overall, we found a significant reduction in the steroid dosage, ECLAM, ESR, and anti-dsDNA antibody titer. Renal patients (n = 35) showed a significant reduction in urinary 24 hour protein excretion. Levels of serum creatinine, creatinine clearance, and EDTA-GFR showed no significant change during treatment. Thirty-seven patients (42.8%) developed adverse events. Gastrointestinal intolerance in 25 (29%) and infections in 20 (23.2%) were the most frequent. The drug was discontinued in 14 (16.3%) patients due to side effects and 6 patients discontinued MMF because they achieved disease remission and were trying to conceive. MMF was stopped due to lack of efficacy in 12 patients., Conclusion: Our data suggest that MMF is a good therapeutic alternative for patients with SLE and renal involvement or refractory disease activity.

Objective: Skin disease can be one of the most refractory clinical manifestations of systemic lupus erythematosus (SLE). The standard therapy consists of sunscreens, topical corticosteroids and antimalarials. However in difficult cases a variety of other drugs have been tried. Here we describe our clinical experience with mycophenolate mofetil (MMF) in patients with cutaneous manifestations of SLE., Methods: Seven patients with SLE and skin involvement (including acute cutaneous lupus, subacute cutaneous lupus, discoid lupus erythematosus, vasculitis, urticarial rash and chilblain lupus) who had received treatment with MMF were included. The clinical characteristics, serologicalfindings and response to treatment were recalledfrom retrospective review of the files., Results: Our results showed no response in 5 patients, partial response in 1 patient and initial response but skin flare whilst on MMF in 1 patient. The median dose of MMF was 2 g (range 2-3 g). Adverse events on MMF were mild, mainly gastrointestinal and occurred in 5 patients. No patients discontinued MMF due to adverse events., Conclusions: MMF appears not to be particularly effective in the treatment of skin disease in SLE. It should be noted that our group of patients had previously failed to respond to a median of 4 (range 2-10) different drugs used to treat SLE skin disease. Thus, the patients in the study could be considered at the severe end of skin disease spectrum.

Mycophenolate mofetil (MMF) is an immunosuppressive agent used in transplantation, with evidence of superior protection against acute transplant rejection compared to azathioprine-containing regimens. Subsequently MMF has been used in a variety of autoimmune conditions. The major experience in systemic lupus erythematosus (SLE) has focused on proliferative lupus nephritis. Following its success in the treatment of lupus nephritis, MMF is now being used to control other SLE manifestations such as, lupus disease activity, haematological manifestations and resistant skin lupus. In this review, we discuss our own experience and the literature report about the use of MMF in SLE.

A 36 year-old woman with systemic lupus erythematosus was admitted to our hospital with headache, brachiocrural hemiparesis and hemianesthesia. She had been treated with prednisone and cyclophosphamide. CT scan and MRI revealed a 15 mm nodular mass enhanced with gadolinium in left frontal convexity. CNS biopsy was performed and a diffuse large B-cell lymphoma was diagnosed. She was treated with radiation therapy without response and died. There are few reports of erythematosus systemic lupus associated with primary central nervous system lymphoma.