COVID-19: autoimmunity, multisystemic inflammation and autoimmune rheumatic patients.

Coronavirus disease 2019 (COVID-19) is associated with autoimmunity and systemic inflammation. Patients with autoimmune rheumatic and musculoskeletal disease (RMD) may be at high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, based on evidence from the literature, as well as international scientific recommendations, we review the relationships between COVID-19, autoimmunity and patients with autoimmune RMDs, as well as the basics of a multisystemic inflammatory syndrome associated with COVID-19. We discuss the repurposing of pharmaceutics used to treat RMDs, the principles for the treatment of patients with autoimmune RMDs during the pandemic and the main aspects of vaccination against SARS-CoV-2 in autoimmune RMD patients.

Ligation of TLR Homologue CD180 of B Cells Activates the PI3K/Akt/mTOR Pathway in Systemic Sclerosis and Induces a Pathological Shift in the Expression of BAFF Receptors.

The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) pathways are known to play a key role in B-cell activation and fibrosis in systemic sclerosis (SSc). Receptors of B-cell activator factor (BAFF) utilize these pathways, which can be influenced by Toll-like receptors (TLRs), as TLRs can alter the expression of BAFF-binding receptors. Our results show that B-cell stimulation via TLR homologue CD180 phosphorylates Akt in diffuse cutaneous SSc (dcSSc) to a lower extent than in healthy controls (HCs). We found basal downregulated BAFF receptor (BAFF-R) and enhanced transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) expression in dcSSc B cells, which might enhance the formation of autoantibody-secreting plasma cells. Moreover, this pathological shift was observed in naive B cells, emphasizing the importance of their increase in SSc. Additionally, we measured higher serum levels of autoantibodies to BAFF in dcSSc patients, suggesting that an imbalance in the complex system of BAFF/anti-BAFF autoantibodies/BAFF-binding receptors may contribute to the development of SSc. Anti-CD180 antibody treatment had opposite effects on the expression of BAFF-R and TACI in HC B cells, resulting in similar levels as observed in SSc B cells without stimulation, which argues against the usefulness of such therapy in SSc.

European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance.

BACKGROUND/OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. METHODS: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. RESULTS: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. CONCLUSIONS: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.

Sensitivity to change of joint count composite indices in 72 patients with systemic sclerosis.

OBJECTIVES: We validated the responsiveness of joint count composite indices (JCCIs) in 72 patients with systemic sclerosis (SSc). METHODS: Changes in Disease Activity Score of 28 Joints using ESR and CRP (DAS28-ESR, DAS28-CRP), Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) were evaluated in a one-year follow-up study. Charts of patients including swollen/tender joint counts, laboratory signs of inflammation, and visual analogue scales referring to disease activity, severity and pain were also blindly categorized by two rheumatologists as improved, unchanged or deteriorated. These categories were used as references for the determination of effect size (ES) and standardised response mean (SRM). RESULTS: Articular inflammation improved in 15, deteriorated in 12, and remained unchanged in 45 (63%) patients with SSc based on the concordant opinion of two clinical investigators. All four JCCIs were sensitive to changes (ES>1; SRM>1). The correlation between changes in JCCIs and the physicians' evaluation was high (r >0.68; p<0.001). Arthritis was predominantly prone to change in patients with high JCCIs, impaired functional status, anti-RNA polymerase III antibodies and patients on DMARD therapy. Synovitis was more prevalent in patients with early diffuse SSc, and tended to improve during the follow-up. CONCLUSIONS: All four JCCIs were sensitive to changes, if tender/swollen joints were present at baseline. Articular inflammation was most prone to change in patients with high JCCIs, impaired functional status and already decreased health-related quality of life at baseline.

Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities.

OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). CONCLUSIONS: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.

2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus.

OBJECTIVE: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. RESULTS: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. CONCLUSION: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.

Assessment of skin involvement in systemic sclerosis.

Skin involvement in SSc is an important marker of disease activity, severity and prognosis, making the assessment of skin a key issue in SSc clinical research. We reviewed the published data assessing skin involvement in clinical trials and summarized the major conclusions important in SSc clinical research. A systematic literature review identified randomized controlled trials using skin outcomes in SSc. Analysis examined the validity of the different skin measures based on literature findings. Twenty-two randomized controlled trials were found. The average study duration was 10.2 (s.d. 4.5) months, mean (s.d.) sample size 32.4 (32.6) and 26.7 (27.8) in intervention and control arms, respectively. The 17-site modified Rodnan skin score is a fully validated primary outcome measure in diffuse cutaneous SSc. Skin histology seems to be an appropriate method for evaluation of skin thickness. These findings have important implications for clinical trial design targeting skin involvement in SSc.

The presence of small joint contractures is a risk factor for survival in 439 patients with systemic sclerosis.

OBJECTIVES: Analysis of risk factors and mortality of 439 patients with systemic sclerosis (SSc) in a tertiary care centre. METHODS: The mean follow up time was 8.4±5.6 years. Lost to follow up rate was 6.4%. Female to male ratio was 366 to 73. Two hundred sixty patients had limited and 179 diffuse cutaneous SSc (dcSSc). A standard protocol including musculoskeletal examinations was used for the assessment of patients. RESULTS: By Kaplan-Meier analysis the overall 5-, 10- and 15 year survival were 88.2%, 79.9% and 73.6%, respectively. Univariate analysis showed that dcSSc, male gender, presence of small joint contractures, pulmonary interstitial, cardiac, oesophageal involvement, scleroderma renal crisis, arterial hypertension, anti-topoisomerase antibody, anemia, hypalbuminemia, coexistent malignancies and elevated erythrocyte sedimentation were associated with poor survival. Lack of giant capillaries, avascular zones or neo-angiogenesis on capillaroscopy, and presence of anti-centromere antibodies were associated with favourable outcome. Multivariate regression analysis showed presence of small joint contractures, history of arterial hypertension, male gender, diffusing capacity of carbon monoxide <50%, right ventricular pressure >40 mmHg on echocardiography, less than 50% ejection fraction, anti-topoisomerase I positivity, anemia, and serum albumin concentration < 35 g/l as well as current or history of coexistent malignancy were independent poor prognostic factors. CONCLUSIONS: In addition to well-known factors predicting poor outcome in SSc, the presence of small joint contractures was a newly identi ed independent risk factor of mortality. Our data also confirmed a recent finding showing that history of arterial hypertension was also a poor prognostic factor.

Validation of disease activity indices using the 28 joint counts in systemic sclerosis.

OBJECTIVES: To validate the Disease Activity Score 28 using ESR (DAS28-ESR) and CRP (DAS28-CRP), the Simplified Disease Activity Index and the Clinical Disease Activity Index used in RA for SSc patients. METHODS: Seventy-seven SSc patients, 40 RA patients, 20 patients with primary RP (PRP) and 28 healthy volunteers were assessed. Besides the disease activity composite indices, the European Scleroderma Study Group Activity Index (EScSG-AI), the HAQ-DI, the Cochin Hand Function Scale and the Short Form Health Survey (SF36) were evaluated. The validation procedure included the assessment for truth, discrimination and feasibility. RESULTS: DAS28-ESR, DAS28-CRP, Simplified Disease Activity Index and Clinical Disease Activity Index showed significant correlation with EScSG-AI, HAQ-DI, Cochin Hand Function Scale and the physical component of SF36 (P < 0.001). All four indices discriminated patients with SSc from RA, PRS and healthy controls, respectively (P < 0.01). With the exception of DAS28-CRP, the other three indices also discriminated between subgroups of SSc based on value of EScSG-AI (⩽3 and >3) (P < 0.05). All four disease activity composite indices showed a good inter- and intraobserver reliability based on repeated measures of two independent investigators (P < 0.001). CONCLUSION: All four disease activity composite indices were found to be valid measures for assessing arthritis in SSc. DAS28-ESR showed the best performance regarding reliability and construct validity.

A Clinical Picture of Unselected Patients with Systemic Lupus Erythematosus in a Tertiary Hungarian Center-A Spectrum Ranging from Pure Lupus to Overlap Syndromes.

Introduction: Systemic lupus erythematosus (SLE) is a multidimensional disease; however, the association of another systemic autoimmune disease further complicates its clinical presentation. Aim: We decided to investigate whether the association of overlap syndromes is linked with a different clinical picture compared to pure lupus and whether this association changes the sensitivity of the following commonly used criteria: the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR), the ACR-1997 and the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria. Method: We performed a retrospective observational study among 382 patients afflicted with lupus: we measured as much of the full clinical and laboratory picture as possible in an unselected cohort. The diagnosis of SLE and other systemic autoimmune diseases was established by the rheumatologist in routine care and then the authors compared the characteristics of patients with pure lupus and those with overlapping pathologies. The diagnosis rates were compared to those that were determined based on the three classification criteria in order to identify various sensitivities and whether the existence of an overlap affects their rates. The fulfillment of each set of criteria was calculated using an Excel-based automatic calculation. Results: Among the patients, the ACR 1997's sensitivity was 81.2% (310 patients), and the SLICC 2012 criteria achieved 94.5% sensitivity (361 patients). The 2019 EULAR/ACR classification criteria resulted in a slightly lower sensitivity (90.3%-345 patients) when compared to the original publication (96%) due to the lower sensitivity of our anti-nuclear antibody (ANA) test (measured via enzyme-linked immunosorbent assay (ELISA)). Nearly all ANA-negative (21/22-95%) patients showed a positive lupus-associated antibody test. The proportion of ANA-negative cases showed no significant difference among pure and overlap patients. No significant difference was found between patients with overlap (138 patients-36%) and pure SLE (244 patients-64%) through the use of these criteria, with the exception of the SLICC criteria (ACR: 80.4% vs. 81.6%; SLICC: 97.4% vs. 92.6%, p = 0.035; EULAR/ACR 2019: 91.4% vs. 89.6%). Patients with an overlap syndrome were significantly older (55 vs. 50 years, p = 0.001), more likely to suffer from interstitial lung disease (ILD: 20% vs. 11%, p = 0.0343) and less frequently showed class III/IV lupus nephritis (7% vs. 14%, p = 0.029) when compared with their pure lupus counterparts. Conclusion: All investigated criteria regarding sensitivity were similar to the original publication's findings. The sensitivity of the EULAR/ACR 2019 classification criterion in cases with overlap syndrome proved excellent, with results very similar to patients afflicted with pure SLE. In the presence of an overlap syndrome, we found significantly fewer patients with lupus nephritis III/IV but no differences in other typical lupus organ manifestation beyond the kidney, whereas we found a higher proportion of ILD in patients with an overlap, indicating that the presence of an overlap syndrome significantly influences the observed clinical picture in real-world conditions.

Temporal Recall Strategies in Rheumatoid Arthritis Patients' Emotionally Intense Life Events.

BACKGROUND: Rheumatoid arthritis (RA) patients often encounter psychological challenges due to chronic pain, fatigue, side effects of medications, and disability. This study examines the relationship between autobiographical narratives and recollection patterns in RA patients. We investigated how different recall strategies for positive life events affect the emotional processing of negative episodes. We hypothesized that vividly recalling positive life events provides psychological resources that support a more intense emotional elaboration of stressful memories, allowing individuals to delve deeper into negative life experiences. Additionally, we explored the impact of these perspectives on self-reported well-being and physical health, proposing that re-living positive events improves overall well-being. METHODS: We collected and analyzed high-point and low-point life-story episodes from 60 RA patients (85% female; age mean 61 ± 11 years; range 37-79) using episodic narrative interviews and the Narrative Categorical Content Analysis algorithm (NarrCat). Participants were categorized into 2 clusters based on their temporal perspective during high-point episodes: 25 used a Retrospective viewpoint, while 35 employed a Re-experiencing strategy. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS), and functioning was measured using the Health Assessment Questionnaire (HAQ). RESULTS: The Re-experiencing group, which was more likely to articulate their high-point episode in vivid and real-time narrative, used more psychological perspectives (U(58) = 223, p < 0.01) and showed heightened emotional frequency (U(58) = 280, p < 0.05; positive: U(58) = 328, p < 0.05; negative: U(58) = 278, p < 0.05) in low-point episodes. No significant difference emerged between the two groups regarding psychological state (anxiety, depressive symptoms) and physical impairment. CONCLUSIONS: Vividly recalling positive events may facilitate a deeper exploration of negative memories. The Re-experiencing group showed increased positive emotions during low points, suggesting better emotion regulation. However, no significant association was found between recalling strategies, psychological state, and physical impairment. This indicates that further research is needed to determine whether re-experiencing positive life events is adaptive or maladaptive.

Clinical significance of coexisting antitopoisomerase I and anticentromere antibodies in patients with systemic sclerosis: a EUSTAR group-based study.

OBJECTIVES: To determine the clinical characteristics of simultaneous occurrence of antitopoisomerase (ATA) and anticentromere (ACA) autoantibodies in systemic sclerosis (SSc). METHODS: Data of patients (n=4,687) fulfilling the ACR criteria for SSc and followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. Sera from patients with simultaneous ATA and ACA were reanalyzed centrally by indirect immunofluorescence, enzyme immunoassay, and immunoblot to confirm antibody status. RESULTS: A total of 29 patients (0.6%) had been documented double-positive for both ATA and ACA in the EUSTAR database. Sera of 14 cases were available for central analysis, of which 8 were confirmed to unequivocally contain both antibodies. The double-positive patients were on average 52.4 years of age, 87.5% were female, and 62.5% had diffuse cutaneous (dc) SSc. Compared with matched ACA single-positive disease, cutaneous and visceral complications were more prevalent in double-positive cases, but this prevalence did not differ significantly in comparison to ATA single-positives. CONCLUSIONS: Coexistence of ATA and ACA can be found at low prevalence in SSc. The clinical features of double-positive patients are not clearly dissimilar to those of patients harbouring only ATA. The data do not support a direct involvement of these antibodies in the pathogenesis of established SSc, but may lack statistical power.

Characteristics of ScleroID highlighting musculoskeletal and internal organ implications in patients afflicted with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a multi-organ disease with impaired health-related quality of life (HRQoL). The EULAR SSc Impact of Disease (ScleroID) is a newly introduced SSc-specific patient-reported outcome to evaluate HRQoL in SSc. OBJECTIVE: To investigate the correlation between the ScleroID and the involvement of organ systems as well as disease activity/damage in a SSc cohort from a large tertiary care centre. PATIENTS AND METHODS: The ScleroID and clinical characteristics including internal organ involvement and hand function were investigated in 160 consecutive patients with SSc (median age 46 (43;56) years; diffuse cutaneous SSc 55%). RESULTS: A strong correlation was found between the ScleroID and articular disease activity scores (DAS28-CRP, DAS28-ESR, CDAI, SDAI), a hand function performance test, the Hand Anatomy Index and muscle strength tests. Additionally, a strong significant correlation was discovered using instruments representing hand function and musculoskeletal disability including the Cochin Hand Function Scale, the Quick Questionnaire of the Disability of the Hands, Arms and the Shoulders and the Health Assessment Questionnaire Disability Index. A significant negative correlation was found between the ScleroID score and the 6-min walking test (6MWT) (rho - 0.444, p < 0.001). Clinically mild lung/heart disease did not show increased ScleroID values. The Mouth Handicap in the Scleroderma Scale and the University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 also showed significant positive correlations to the ScleroID score (rho: 0.626, p < 0.001; rho: 0.646, p < 0.001, respectively). Patients experiencing oesophageal difficulties bore a significantly higher score compared to individuals with a normal functioning oesophagus (3.2/1.5;4.5/ vs. 2.2/1.0;3.2/, p = 0.011). Moreover, the ScleroID showed a significant positive correlation to the revised EUSTAR disease activity index and modified activity index. CONCLUSION: In a large single-centre cohort, the previously described ScleroID-related findings were confirmed. Furthermore, several organ involvement-related functional and performance tests showed a good correlation to the ScleroID including the 6MWT and gastrointestinal-related complaints. Many aspects of musculoskeletal damage, overall disease activity, pain and fatigue were also well represented in the ScleroID, which efficiently reflects the impact of organ involvement, disease activity and functional damage.

Significance of autoantibody assays in systemic lupus erythematosus / Az autoantitest-vizsgálatok jelentosége szisztémás lupus erythematosusban

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by pathological immune complexes and various autoantibodies. Detectable pathological autoantibodies produced by plasma cells differentiated from B cells play a significant role in the establishment of clinical diagnosis, classification, and differential diagnosis as well as assessing the disease activity during patients' follow-up. Autoantibody determination is very important in

Minimal Clinically Important Differences (MCID) for the Functional Assessment of Chronic Illness Therapy Fatigue Scale in Patients with Systemic Sclerosis.

(1) Background: Systemic sclerosis (SSc) is characterized by significant fatigue, causing diminished quality of life (QoL). The aim of this study was to examine fatigue levels and their associations with clinical factors and determine the minimal clinically important difference (MCID) value for the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-FS). (2) Methods: A total of 160 SSc patients and 62 individuals without SSc were followed-up over a 12-month period by measuring the FACIT-FS and the Visual Analogue Scale and the Short Form 36 Vitality Score analyzing changes in exhaustion. (3) Results: Fatigue was strongly correlated with HRQoL, level of pain, emotional disorders, physical capability and functionality. The MCID values for FACIT-FS were calculated as -3 for deterioration and +4 for improvement after a 12-month follow-up. The predictors of improvement of fatigue from baseline parameters were the significant disease activity, the patients' poorer functionality and the short disease duration. Patients with scleroderma-related interstitial lung disease at baseline had approximately tripled risks for worsening fatigue. The independent influential factors regarding the changing of FACIT-FS were improving or worsening in the same direction in reference to physical condition, gastrointestinal and emotional factors. (4) Conclusions: Fatigue is a multi-dimensional symptom, which is strongly correlated to HRQoL. MCID values of FACIT-FS can be useful tools in monitoring the changes of HRQoL in clinical trials and in daily practice among patients with SSc.

Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021.

Introduction: The J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI. Results: In this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients' data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174). Conclusions: 1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries.

Mechanism of coronary flow reserve reduction in systemic sclerosis: insight from intracoronary pressure wire studies.

OBJECTIVE: Functional impairment of coronary microcirculation is thought to be a major pathway in the development of primary cardiac involvement in SSc; however, the underlying mechanism is not fully understood. We aimed to investigate the mechanisms of coronary flow reserve (CFR) reduction in patients with SSc. METHODS: Seventeen SSc patients and 17 gender- and age-matched controls were enrolled. Coronary angiography and determination of coronary flow parameters including index of myocardial resistance (IMR) using intracoronary pressure wire at basal conditions and during vasodilator-induced maximal hyperaemia were performed. Transit times of repeated intracoronary saline injection were measured to evaluate the role of cold exposure. RESULTS: SSc patients with decreased CFR had accelerated basal coronary flow velocity (P < 0.05), and their IMR in hyperaemia (IMR(hyp)) did not differ from either SSc patients with normal CFR or from the controls (P = 0.292 and P = 0.308). The coronary flow velocity of SSc patients correlated with the IMR at baseline (IMR(bas)) (r = 0.56, P = 0.019). Injection of room temperature saline did not provoke changes in coronary transit times. CONCLUSIONS: The lack of decrease in the maximal vasodilatation response indicates that there is no irreversible functional damage at the level of the coronary arterioles. In patients with reduced CFR, the decreased basal IMR and higher velocity reflect compensatory vasodilatory mechanisms probably triggered by ischaemic signals deriving from abnormal myocardial microcirculation.

Patients with Systemic Sclerosis with and without Overlap Syndrome Show Similar Microvascular Abnormalities.

INTRODUCTION: Nailfold video capillaroscopy (NVC) is a useful tool for measuring capillary density (CD) and capillary morphology parameters and is mainly used in systemic sclerosis (SSc). OBJECTIVE: We aimed to assess the prevalence of an SSc pattern and CD in different connective tissue diseases (CTDs). METHODS: NVC was performed on 268 patients with CTDs. Control groups consisted of 104 healthy volunteers (HVs) and 36 primary Raynaud's patients (PRPs). RESULTS: Decreased CD was more prevalent in SSc, systemic lupus erythematosus (SLE), inflammatory myopathies (IIM), and overlap CTD patients compared with both controls. Average CD, the prevalence of decreased CD, and the prevalence of an SSc pattern did not differ significantly between SSc patients with (n = 39) and without (n = 50) overlap syndrome. An SSc pattern was significantly more prevalent in SLE (23%), SSc (82%), IIM (35%), and rheumatoid arthritis (17%) compared with both control groups. The prevalence of an elevated microangiopathy evaluation score (MES) was significantly higher in SLE, SSc, and IIM than in the HVs. CONCLUSION: The presence of another CTD in SSc did not influence CD or morphology. An SSc pattern may also be present in CTDs other than SSc. The MES is a useful instrument to distinguish between patients with CTDs and controls.

Nationwide epidemiological and health insurance disease burden of rheumatoid arthritis in Hungary / A rheumatoid arthritis okozta országos epidemiológiai és egészségbiztosítási betegségteher Magyarországon.

Összefoglaló. Bevezetés: A rheumatoid arthritisszel kapcsolatos szolgáltatások igénybevétele nagy teher az egészségügyi rendszerek számára. Célkituzés: Elemzésünk célja volt a rheumatoid arthritis okozta éves epidemiológiai és egészségbiztosítási betegségteher meghatározása Magyarországon. Adatok és módszerek: Az elemzésben felhasznált adatok a Nemzeti Egészségbiztosítási Alapkezelo (NEAK) finanszírozási adatbázisából származnak, és a 2018. évet fedik le. Meghatároztuk az éves betegszámokat, a prevalenciát 100 000 lakosra, továbbá az éves egészségbiztosítási kiadásokat korcsoportos és nemenkénti bontásban valamennyi egészségbiztosítási ellátás tekintetében. A rheumatoid arthritis kórképet fodiagnózisként a Betegségek Nemzetközi Osztályozása (BNO, 10. revízió) szerinti M0690-es kóddal azonosítottuk. Eredmények: Meghatározó betegforgalmat a gyógyszerek ártámogatása esetében találtunk: 7015 férfi, 23 696 no, együtt 30 711 fo. A gyógyszer-ártámogatás betegforgalmi adatai alapján a 100 000 fore eso prevalencia férfiaknál 150,2 fo, noknél 464,0 fo, együtt 314,1 fo volt. A rheumatoid arthritis kezelésére a NEAK 1,64 milliárd Ft-ot (6,07 millió USD, illetve 5,14 millió EUR) költött 2018-ban. A kiadások 19,3%-a férfiaknál, míg 80,7%-a noknél jelenik meg. A gyógyszer-ártámogatás (az összes kiadás 42,8%-a), a járóbeteg-szakellátás (21,9%) és az aktívfekvobeteg-szakellátás (12,4%) voltak a meghatározó költségelemek. Az egy betegre jutó átlagos éves egészségbiztosítási kiadás 53 375 Ft (198 USD/167 EUR) volt. Következtetés: A gyógyszerek ártámogatása bizonyult a fo költségtényezonek. A rheumatoid arthritis elofordulási gyakorisága 3,1-szer magasabb a nok esetében a férfiakhoz képest. Orv Hetil. 2021; 162(Suppl 1): 30-37. INTRODUCTION: Utilisation of services related to the treatment of rheumatoid arthritis poses a great burden for healthcare systems. Objecive: Our aim was to determine the annual epidemiological disease burden and the health insurance treatment cost of rheumatoid arthritis in Hungary. DATA AND METHODS: Data were derived from the financial database of the National Health Insurance Fund Administration (NHIFA) of Hungary, for the year 2018. The data analysed included annual patient numbers and prevalence per 100 000 population and annual health insurance treatment costs calculated for age groups and sex according to all health insurance treatment categories. Patients with rheumatoid arthritis were identified as main diagnosis with the following code of the International Classification of Diseases, 10th revision: M0690. RESULTS: We found a significant patient turnover in pharmaceutical reimbursement: 7015 men, 23 696 women, in total 30 711 patients. Based on patient numbers in pharmaceuticals, prevalence for 100 000 population among men was 150.2 patients, among women 464.0, in total 314.1 patients. In 2018, NHIFA spent 1.64 billion HUF (6.07 million USD, 5.14 million EUR) on the treatment of patients with rheumatoid arthritis. 19.3% of the costs was spent on the treatment of male, 80.7% on female patients. Pharmaceuticals (42.8% of the total expenditures), outpatient care (21.9%) and acute inpatient care (12.4%) were the main cost drivers. Average annual health insurance treatment cost per patient was 53 375 HUF (198 USD/167 EUR). CONCLUSION: Pharmaceutical reimbursement was the major cost driver. The prevalence of rheumatoid arthritis was by 3.1 higher in women compared to men. Orv Hetil. 2021; 162(Suppl 1): 30-37.

Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database.

OBJECTIVES: To determine the causes and predictors of mortality in systemic sclerosis (SSc). METHODS: Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan-Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality. RESULTS: Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities, 25% died of causes in which SSc-related complications may have participated (pneumonia, sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34), the presence of PAH based on echocardiography (HR 2.02), pulmonary restriction (forced vital capacity below 80% of normal, HR 1.64), dyspnoea above New York Heart Association class II (HR 1.61), diffusing capacity of the lung (HR 1.20 per 10% decrease), patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points). CONCLUSION: Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.