How to treat patients with thrombotic antiphospholipid syndrome in 2024?

Antiphospholipid syndrome encompasses a range of clinical conditions, particularly thrombotic or obstetrical manifestations, associated with the presence of antiphospholipid antibodies. Managing thrombotic antiphospholipid syndrome in daily clinical practice can be challenging and requires thorough risk stratification and tailored treatment strategies. Primary prophylaxis focuses on improving traditional thrombosis risk factors and, in certain situations, may include low-dose aspirin and / or prophylactic anticoagulants (e.g., low-molecular-weight heparin). The treatment of thrombotic antiphospholipid syndrome primarily involves long-term anticoagulation with vitamin K antagonists. In some cases, a combination of vitamin K antagonists and low-dose aspirin, vitamin K antagonists with international normalized ratio target >3 or a switch to therapeutic doses of low-molecular-weight heparin might be employed. The use of hydroxychloroquine is essential for patients with secondary systemic lupus erythematosus and may be considered for patients with recurrent thrombosis. In other selected situations, the use of immunomodulatory agents can be considered.

Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis.

OBJECTIVES: To analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). METHODS: For the present study, the following variables were selected for harmonization and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD. RESULTS: The results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. CONCLUSIONS: For the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.

Influence of exposure to climate-related hazards in the phenotypic expression of primary Sjögren's syndrome.

OBJECTIVES: To analyse how the key components at the time of diagnosis of the Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards. METHODS: For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure. RESULTS: After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries. CONCLUSIONS: Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjögren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.

Criteria and Non-Criteria Antiphospholipid Antibodies in Antiphospholipid Syndrome: How Strong Are They Correlated?

The place of non-criteria antiphospholipid antibodies (aPLs) in the diagnosis of antiphospholipid syndrome (APS) is still debatable. The aim of this research was to evaluate the correlations between the titres of non-criteria aPLs (anti-phosphatidylethanolamine (aPE), anti-phosphatidylserine (aPS), and anti-prothrombin (aPT) antibodies), and the ones of the already studied criteria aPLs (anti-cardiolipin (aCL) and anti-ß2 glycoprotein I-aß2GPI antibodies). Altogether, 72 APS (30 primary and 42 secondary) patients were included in our study. High correlation coefficients (rs) were found between aPS IgM and aCL IgM, overall (0.77, p < 0.01), as well as in the primary (0.81, p < 0.01), and secondary (0.75, p < 0.01) APS subgroups. Low or statistically insignificant correlations were observed between IgG/IgM isotypes of aPT and aCL, or aß2GPI, in the entire study population, and when evaluating the subgroups. Therefore, moderate correlations were mainly identified between the tested non-criteria antibodies and the criteria ones, suggesting little added value for the use of the tested non-criteria aPLs, with the exception of aPT, which seems to have different kinetics and might be a promising APS diagnostic tool.

Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study.

Background: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score. Methods: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables. Findings: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27-2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22-2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01-1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22-1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16-2) were independent predictors of SjS-related death. Interpretation: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS. Funding: Novartis.

The Spectrum of Extraglandular Manifestations in Primary Sjögren's Syndrome.

Extraglandular manifestations (EGMs) in primary Sjogren's syndrome (pSS) represent the clinical expression of the systemic involvement in this disease. EGMs are characterized by a wide heterogeneity; virtually any organ or system can be affected, with various degrees of dysfunction. The existing gaps of knowledge in this complex domain of extraglandular extension in pSS need to be overcome in order to increase the diagnostic accuracy of EGMs in pSS. The timely identification of EGMs, as early as from subclinical stages, can be facilitated using highly specific biomarkers, thus preventing decompensated disease and severe complications. To date, there is no general consensus on the diagnostic criteria for the wide range of extraglandular involvement in pSS, which associates important underdiagnosing of EGMs, subsequent undertreatment and progression to severe organ dysfunction in these patients. This review article presents the most recent basic and clinical science research conducted to investigate pathogenic mechanisms leading to EGMs in pSS patients. In addition, it presents the current diagnostic and treatment recommendations and the trends for future therapeutic strategies based on personalized treatment, as well as the latest research in the field of diagnostic and prognostic biomarkers for extraglandular involvement in pSS.

Comparative Analysis of Hematological and Immunological Parameters in Patients with Primary Sjögren's Syndrome and Peripheral Neuropathy.

BACKGROUND: Primary Sjögren syndrome (pSS) is a multisystem disorder of autoimmune etiology, frequently involving peripheral nerves. Early detection of peripheral neuropathy (PN) manifestations might improve prognosis and disease control. The purpose of the study was to evaluate the predictive potential of hematological and immunological parameters associated with PN development in pSS patients. METHODS: This single-center retrospective study included patients with pSS who were divided into two groups, according to the occurrence of neurological manifestations throughout the follow-up period. RESULTS: From the total of 121 pSS patients included in the study, 31 (25.61%) developed neurological manifestations (PN+ group) during the follow-up period. At the moment of pSS diagnosis, 80.64% of PN+ patients exhibited increased disease activity, with ESSDAI scores above 14 (p = 0.001), and significantly higher values for VASp score (p = 0.001), with a mean value of 4.90 ± 2.45, compared to 1.27 ± 1.32 in the PN- group. The hematological assessment at the moment of pSS diagnosis revealed that neutrophils and neutrophil-to-lymphocyte ratio (NLR) were significantly higher in the PN+ group (p = 0.001), while lymphocytes, monocytes and monocyte-to-lymphocyte ratio (MLR) were significantly lower (p = 0.025, p = 0.13 and p = 0.003, respectively). Immuno-inflammatory parameters-gammaglobulins, complement fractions C3, C4, total proteins and vitamin D were significantly lower in the PN+ patients' group. In multivariate analysis, the independent predictive character for PN development in pSS patients was confirmed for NLR (95% CI 0.033 to 0.263, p = 0.012), MLR (95% CI -1.289 to -0.194, p = 0.008), gammaglobulins (95% CI -0.426 to -0.088, p < 0.003), complement fraction C4 (95% CI -0.018 to -0.001, p < 0.030) and vitamin D (95% CI -0.017 to -0.003, p < 0.009). CONCLUSIONS: Readily available and frequently used hematological and immunological markers, such as NLR, MLR, gammaglobulins, C4 and vitamin D could be helpful in predicting the neurological involvement in pSS patients. These biological parameters might become useful tools for clinicians to monitor disease progression and identify potentially severe extraglandular manifestations in pSS patients.

The Predictive Role of Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Monocytes-to-Lymphocyte Ratio (MLR) and Gammaglobulins for the Development of Cutaneous Vasculitis Lesions in Primary Sjögren's Syndrome.

Background: In primary Sjögren's Syndrome (pSS), cutaneous vasculitis lesions (CVL) are extraglandular manifestations with an important clinical and prognostic impact and their early detection might contribute to the improvement of disease control and even patients' survival. The aim of this study was to evaluate the predictive potential of hematological elements in the development of CVL in pSS patients. Methods: In this single center, retrospective study, a total of 245 participants were included (124 pSS patients and 121 healthy controls). Complete blood count, inflammatory and immunological parameters were determined at the initial visit. pSS patients underwent a periodical follow-up program, when disease progression and response to therapy was monitored, including the emergence of CVL. Results: In pSS, leucocytes, lymphocyte, neutrophil, monocyte, erythrocyte and platelet counts are significantly decreased compared to healthy subjects (p < 0.001), whereas cellular ratios: NLR, PLR, MLR, and immunological and inflammatory parameters are significantly increased (p < 0.001). A total of 34 patients with pSS (27.41%) developed CVL during the follow-up period. The occurrence of CVL was positively correlated with neutrophil and platelet counts (p < 0.001), while for lymphocytes the correlation was negative (p < 0.001). Cellular ratios: NLR, PLR and MLR, and gammaglobulins also revealed significant positive correlations with the emergence of CVL in pSS (p < 0.001). The multivariate analysis confirmed the independent predictive character for CVL emergence in pSS for NLR (CI95% 0.053−0.2, p < 0.002), PLR (CI95% 0.001−0.003, p < 0.003), MLR (CI95% 0.086−0.935, p < 0.019), and gammaglobulins (CI95% 0.423−0.688, p < 0.001). Conclusions: Standard hematological parameters, widely used in the assessment of pSS patients, such as NLR, PLR, MLR and gammaglobulins could become valid elements that might be used for the early detection of patients at risk for the development of CVL.

Inclusion Body Myositis and Neoplasia: A Narrative Review.

Inclusion body myositis (IBM) is an acquired, late-onset inflammatory myopathy, with both inflammatory and degenerative pathogenesis. Although idiopathic inflammatory myopathies may be associated with malignancies, IBM is generally not considered paraneoplastic. Many studies of malignancy in inflammatory myopathies did not include IBM patients. Indeed, IBM is often diagnosed only after around 5 years from onset, while paraneoplastic myositis is generally defined as the co-occurrence of malignancy and myopathy within 1 to 3 years of each other. Nevertheless, a significant association with large granular lymphocyte leukemia has been recently described in IBM, and there are reports of cancer-associated IBM. We review the pathogenic mechanisms supposed to be involved in IBM and outline the common mechanisms in IBM and malignancy, as well as the therapeutic perspectives. The terminally differentiated, CD8+ highly cytotoxic T cells expressing NK features are central in the pathogenesis of IBM and, paradoxically, play a role in some cancers as well. Interferon gamma plays a central role, mostly during the early stages of the disease. The secondary mitochondrial dysfunction, the autophagy and cell cycle dysregulation, and the crosstalk between metabolic and mitogenic pathways could be shared by IBM and cancer. There are intermingled subcellular mechanisms in IBM and neoplasia, and probably their co-existence is underestimated. The link between IBM and cancers deserves further interest, in order to search for efficient therapies in IBM and to improve muscle function, life quality, and survival in both diseases.

Cardiovascular Disease in Primary Sjögren's Syndrome: Raising Clinicians' Awareness.

In the ever evolving landscape of systemic immune mediated diseases, an increased awareness regarding the associated cardiovascular system impairment has been noted in recent years. Even though primary Sjögren's Syndrome (pSS) is one of the most frequent autoimmune diseases affecting middle-aged individuals, the cardiovascular profile of this specific population is far less studied, at least compared to other autoimmune diseases. Traditional cardiovascular risk factors and disease specific risk factors are inextricably intertwined in this particular case. Therefore, the cardiovascular risk profile in pSS is a multifaceted issue, sometimes difficult to assess. Furthermore, in the era of multimodality imaging, the diagnosis of subclinical myocardial and vascular damage is possible, with recent data pointing that the prevalence of such involvement is higher in pSS than in the general population. Nevertheless, when approaching patients with pSS in terms of cardiovascular diseases, clinicians are often faced with the difficult task of translating data from the literature into their everyday practice. The present review aims to synthesize the existing evidence on pSS associated cardiovascular changes in a clinically relevant manner.

Relapse of cryoglobulinemic vasculitis with new-onset severe renal involvement in two patients following mRNA COVID-19 vaccination: A case report.

RATIONALE: Since mass-scale severe acute respiratory syndrome coronavirus 2 vaccination, there have been case reports of several immune-mediated reactions, including new-onset and flares of glomerular disorders following immunization with mRNA coronavirus disease 2019 vaccines. Here, we report two cases, the first to our knowledge, of relapsing cryoglobulinemic vasculitis with new-onset severe renal involvement following mRNA coronavirus disease 2019 vaccination. PATIENT CONCERNS: The relapse of the cutaneous and the new onset of severe renal involvement of cryoglobulinemic vasculitis occurred three weeks after the second dose of the mRNA Moderna coronavirus disease 2019 vaccination and two days after the first dose of mRNA Pfizer coronavirus disease 2019 vaccination in the first and second patient, respectively. DIAGNOSIS: Kidney biopsies were performed. The first pacient's kidney biopsy showed a membranoproliferative pattern of glomerular injury with extensive mesangial and endocapillary hypercellularity, while severe endothelial swelling, loss of fenestrations and widening of subendothelial space were identified by electron-microscopy. The second patient's kidney biopsy was consistent with cryoglobulin associated membrano-proliferative pattern of glomerular injury. INTERVENTIONS: Our patients were managed with a combination of immunosuppressants consisting of corticosteroids, Cyclophosphamide and Rituximab with a favourable outcome at the end of the induction period. OUTCOMES: Clinical and immunological response was achieved in both patients after four months of follow-up. LESSONS: The temporal association of the relapse of the cryoglobulinemic vasculitis to mRNA coronavirus disease 2019 vaccination suggest that the vaccine might have been a trigger for the reactivation of the disease in our cases. This possible association should be acknowledged by physicians in order to provide optimal monitoring and treatment in case of reactivation of the disease post-immunization.

Sclerodermic Cardiomyopathy-A State-of-the-Art Review.

Systemic sclerosis (SSc) is a chronic autoimmune disorder with unknown triggering factors, and complex pathophysiologic links which lead to fibrosis of skin and internal organs, including the heart, lungs, and gut. However, more than 100 years after the first description of cardiac disease in SSc, sclerodermic cardiomyopathy (SScCmp) is an underrecognized, occult disease with important adverse long-term prognosis. Laboratory tests, electrocardiography (ECG) and cardiovascular multimodality imaging techniques (transthoracic 2D and 3D echocardiography, cardiac magnetic resonance (CMR), and novel imaging techniques, including myocardial deformation analysis) provide new insights into the cardiac abnormalities in patients with SSc. This state-of-the-art review aims to stratify all the cardiac investigations needed to diagnose and follow-up the SScCmp, and discusses the epidemiology, risk factors and pathophysiology of this important cause of morbidity of the SSc patient.

Hydroxychloroquine in systemic lupus erythematosus: overview of current knowledge.

The antimalarial hydroxychloroquine (HCQ) has demonstrated several crucial properties for the treatment of systemic lupus erythematosus (SLE). Herein, we reviewed the main HCQ pharmacologic features, detailed its mechanism of action, and summarized the existing guidelines and recommendations for HCQ use in rheumatology with a systematic literature search for the randomized controlled trials focused on lupus. HCQ has been shown to decrease SLE activity, especially in mild and moderate disease, to prevent disease flare and to lower the long-term glucocorticoid need. The numerous benefits of HCQ are extended to pregnancy and breastfeeding period. Based on cohort studies, antithrombotic and metabolic HCQ's effects were shown, including lipid-lowering properties, which might contribute to an improved cardiovascular risk. Moreover, early HCQ use in antinuclear antibodies positive individuals might delay the progression to SLE. Finally, HCQ has a significant favorable impact on long-term outcomes such as damage accrual and mortality in SLE. Based on these multiple benefits, HCQ is now the mainstay long-term treatment in SLE, recommended by current guidelines in all patients unless contraindications or side effects. The daily dose associated with the best compromise between efficacy and safety is matter of debate. The concern regarding retinal toxicity rather than proper efficacy data is the one that dictated the daily dosage of ⩽5 mg/kg/day actual body weight currently agreed upon.

Physicians' Experience with COVID-19 Vaccination: A Survey Study.

BACKGROUND: COVID-19 vaccine hesitancy remains high in the general population and is the main determinant of low vaccination rates and of the fourth pandemic wave severity in Romania. Additional information is needed to raise awareness over vaccine efficiency and the safety profile. OBJECTIVE: To assess self-reported experience related to COVID-19 vaccination in Romanian physicians. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional, self-administered questionnaire-based survey, distributed online in the period 24 March to 24 May 2021. The survey included 30 cascade questions with skip logic filters. All physicians included filled in the questionnaire voluntarily and anonymously. Not all respondents filled in all questions. Main outcome and measure: Primary outcomes addressed were related to the COVID-19 vaccine safety profile. RESULTS: 407/467 (87.15%) of the respondents' physicians were fully vaccinated, mostly with the Pfizer-BioNTech (Comirnaty)-BNT162b2 vaccine, with the peak of immunization in January 2021, with almost four-fifths of the study participants. Regarding COVID-19, almost 20% physicians had the infection and one declared COVID-19 re-infection. A number of 48/420 (11.42%) and 47/419 (11.22%) of the vaccinated physicians did not report any side effects after the first or second vaccine dose. However, most of the side effects reported were minor. Only 50/360 (13.88%) physicians reported the vaccine side effects on the dedicated online national platform. Approximately 40% respondents checked the anti-spike SARS-CoV2 antibodies' titer after complete vaccination, of which two cases reported indeterminate levels. Lower anti-spike SARS-CoV2 antibodies' titer of 100-1000 times the laboratory limit was more frequent in naive physicians (36.95% versus 14.28%, p = 0.012), moderate titers were similar, while very high levels, more than 10,000 times laboratory limit, were more frequent in physicians with previous COVID-19 infection (2.17% versus 42.85%, p < 0.001). CONCLUSIONS AND RELEVANCE: In this cross-sectional survey study on the COVID-19 vaccination among Romanian physicians, we describe a safety vaccination profile among Romanian physicians.

Successful Treatment of Catastrophic Antiphospholipid Syndrome Using Rituximab: Case Report and Review of the Literature.

BACKGROUND: Kidney involvement is a frequent complication of systemic lupus erythematosus (SLE) and kidney biopsy is essential in differentiating lupus nephritis (LN) from thrombotic microangiopathy (TMA) secondary to antiphospholipid autoantibodies (aPL). Association between antiphospholipid syndrome (APS) and acquired hemophilia due to inhibitors was very rarely described in SLE patients. CASE PRESENTATION: We present the case of a 61-year-old male diagnosed with SLE who acquired deficiency of clotting factor VIII due to circulating inhibitors, admitted for acute kidney injury (AKI), microangiopathic hemolytic anemia, thrombocytopenia, and diplopia. Kidney biopsy showed TMA due to APS, but no signs of LN. Head computed tomography identified low dense areas in the white matter, suggesting small blood vessels' involvement. A diagnosis of probable catastrophic antiphospholipid syndrome (CAPS) was established and treatment with low molecular weight heparin, intravenous methylprednisolone, plasmapheresis, and rituximab was initiated, followed by resolution of AKI, diplopia, and TMA with complete depletion of CD19+B-lymphocytes (CD19+B-Ly) after one month. We further review the current knowledge regarding pathogenesis and management of CAPS in SLE patients. CONCLUSIONS: Targeted therapy was possible after kidney biopsy, improving renal and general prognosis. CD19+B-Ly repopulation preceded biological relapse, so monitoring of CD19+B-Ly may serve as a tool to predict relapses and guide rituximab therapy.

The impact of the COVID-19 pandemic on patients with primary Sjögren syndrome.

The aim of this study was to investigate the perspective of Romanian patients with Sjögren syndrome (SS) on various aspects of the disease during the SARS-CoV-2 outbreak, including both the impact of COVID-19 on the disease itself as well as the effects of vaccination against SARS-CoV-2 in this group of patients. The study is an online questionnaire-based survey. We received responses from 137 SS patients. Regarding the general emotional status, 33 patients (24.0%) and 47 patients (34.3%) declared to have been sadder/depressive and more agitated/anxious during the SARS-CoV2 outbreak, respectively. During the lockdown, 49 (33.7%) patients strictly and 77 patients (56.2%) did their best to respect the home isolation measures. The income was unchanged for most of the patients (94 patients, 68.6%). Regarding access to healthcare providers, 27 patients (18.7%) postponed the consultation for fear of getting SARS-CoV2. In our study group, 31 patients (22.6%) responded that they have had COVID-19. Only one patient was completely asymptomatic, while the most frequently declared symptom was weakness (84.0%). In 17 patients among the respondents (68%) the symptoms lasted for at least 2 weeks; the most frequent long-lasting symptoms were fatigue (40.0%) and weakness (36.0%). Out of all the respondents, 53 patients (41.4%) were vaccinated against SARS-CoV2 with at least one dose. After the first dose, the most prevalent side effect was pain at the site of injection (89.2%), followed by weakness (25.0%) and myalgias (21.4%). This information will be useful for developing special programs dedicated to SARS-CoV2 infection and vaccination in patients with SS and other autoimmune diseases.

Perceptions of Romanian Physicians on Lockdowns for COVID-19 Prevention.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) was declared a pandemic in March 2020, triggering important changes for the entire society and healthcare systems, as well as significant lockdown measures aimed to limit the disease spread. We herein intended to catch the dynamic of Romanian physicians' perceptions of COVID-19 impact. For this purpose, after a literature review, a 30-item questionnaire was designed. The questionnaire was twice distributed online, about 1 month apart, during which partial relaxation measures were decreed in Romania. The questionnaire was voluntarily filled in by Romanian physicians who were willing to participate in the study. A total of 214 physicians answered the questionnaire upon its first release, and 199 respondents were registered upon its second release, most of whom (94.9%) were involved in clinical work, with one-third working in units dedicated to COVID-19 patients. In parallel with the relaxation of lockdown measures, along with increased confidence in the efficiency of protective measures (46.7% vs. 31.3%), separation from household members decreased from 36.9% to 22.1%. Nevertheless, the feeling of rejection felt by doctors remained similar (22.4% vs. 24.6%). Furthermore, answers regarding the clinical picture, diagnostic approach, and treatment options are discussed. Most of therapeutic options considered for SARS-CoV-2 treatment (e.g., lopinavir/ritonavir, oseltamivir, hydroxychloroquine, azithromycin, tocilizumab, and convalescent plasma) failed to confirm significant efficiency. On the contrary, vaccines for widescale use are already available despite the initial skepticism. In the beginning of the pandemic, 25.2% (18.2% vs. 32.2%) considered that there will not be an effective COVID-19 vaccine, while 41.6% (43.0% vs. 40.2%) thought that a vaccine would be available after at least 12 months. In conclusion, initially, following only a 1 month period, Romanian physicians' intention to consider treatments such as hydroxychloroquine or lopinavir/ritonavir for COVID-19 decreased significantly. Moreover, confidence in the efficiency of available protective measures increased, and the rates of separation from household members decreased.

Hydroxychloroquine in systemic and autoimmune diseases: Where are we now?

Hydroxychloroquine (HCQ), one of the oldest drugs used in rheumatology, came recently into attention as one of the potential therapies tested for the severe acute respiratory syndrome coronavirus-2 disease treatment. Used initially as an antimalarial, then translated to rheumatic diseases, HCQ has been used in a wide range of pathologies, including infectious diseases, immune disorders, diabetes, dyslipidemia, or neoplasia. Regarding systemic diseases, HCQ is the mainstay treatment for systemic lupus erythematosus (SLE), where, according to last European guidelines, it is proposed to all SLE patients unless contraindicated or with side effects. HCQ proved positive impact in SLE on robust outcomes, such as accrual damage, disease activity and survival, but also pleiomorphic effects, including decrease in the need for glucocorticoids, reduction in the risk of neonatal lupus, lower fasting glucose and protection against diabetes, thrombotic risk, dyslipidemia, infections, etc. Moreover, HCQ can be used during pregnancy and breast-feeding. Besides SLE, the role for HCQ in the anti-phospholipid syndrome and Sjögren's disease is still under debate. On the contrary, recent advances showed only limited interest for rheumatoid arthritis, especially due the lack of structural damage prevention. There are still no strong data to sustain the HCQ use in other systemic diseases. In this review, we summarised the utility and efficacy of HCQ in different clinical conditions relevant for rheumatology practice.

Systemic lupus erythematosus-related acute pancreatitis.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a complex autoimmune pathology that can involve any organ. Lupus-related acute pancreatitis (AP) is, together with lupus mesenteric vasculitis, an important cause of SLE-induced acute abdominal pain. METHODS: A literature search was conducted using the terms "Pancreatitis" and "Lupus Erythematosus, Systemic" on PubMed/Medline and Web of Science from January 2007 to January 2020. Clinical characteristics, diagnostic approach, and treatment principles in SLE-related AP are presented in this review. RESULTS: Mainly retrospective reports were identified. The reported incidence of SLE-associated AP ranges from 0.9 to more than 5% of patients. A total of 264 SLE patients were found in the selected research, with a net female predominance (sex ratio 9:1) and mean age of 31.4 years. Abdominal pain was virtually present in all cases. AP occurrence was more frequent in SLE patients with short disease duration, high activity scores, and multiorgan involvement. The AP definition was based on currently available guidelines and after exclusion of any other known causes (including iatrogenic, i.e. drugs), a diagnosis of "idiopathic" SLE-related AP might be sustained. Management is difficult, as there is no standardized therapeutic approach. Of note, glucocorticoid use remains still controversial as, especially for high doses, subsequent pancreatic injury may occur. Monitoring serum lipase levels after high dose steroids might be considered. One study reported beneficial prognostic effect of plasma exchange. Moreover, AP in SLE might raise awareness about macrophage activation syndrome association. Mortality up to one third of AP cases in SLE was reported. CONCLUSION: The SLE-related AP is a rare, but severe, life-threatening complication. Corticosteroids must be used with caution. Plasma exchange could be considered in selected cases.

Celiac disease and Sjögren's syndrome: A case report and review of literature.

BACKGROUND: Celiac disease (CD) is a systemic, chronic immune-mediated disease triggered by gluten ingestion in genetically-susceptible individuals, with a prevalence of 1% worldwide. Sjogren's syndrome (SS) is also a systemic autoimmune disease, mainly characterized by ocular and oral sicca symptoms and signs. Sharing a common genetic background, CD and SS are known associated autoimmune diseases, but currently available guidelines are not reporting it. CASE SUMMARY: We report the case of a 39-year-old woman, who was in the care of her rheumatologist for 2 years with SS. On routine follow-up she was found to have iron deficiency, without anemia. She had no gastrointestinal complaints and denied any obvious source of blood loss. IgA tissue transglutaminase antibodies were positive and endoscopy with duodenal biopsies revealed crypt hyperplasia and villous atrophy. A diagnosis of CD was set and gluten-free diet was recommended. CONCLUSION: We present a review of existing data in the literature regarding the association of the two diseases, summarizing prevalence studies of CD in SS patients and the other way around. Screening recommendations and future research perspectives are also discussed, highlighting clinically relevant unanswered questions with respect to the association of CD with SS.