Calcinosis in Rheumatic Disease Is Still an Unmet Need: A Retrospective Single-Center Study.

Patients with immune-mediated rheumatic disease-related calcinosis comprise a subgroup at risk of encountering a more severe clinical outcome. Early assessment is pivotal for preventing overall disease progression, as calcinosis is commonly overlooked until several years into the disease and is considered as a 'non-lethal' manifestation. This single-center retrospective study explored the prevalence, clinical associations, and impact on survival of subcutaneous calcinosis in 86 patients with immune-mediated rheumatic diseases (IMRD). Calcinosis predominantly appeared in individuals with longstanding disease, particularly systemic sclerosis (SSc), constituting 74% of cases. Smaller calcinosis lesions (≤1 cm) were associated with interstitial lung disease, musculoskeletal involvement, and digital ulcerations, while larger lesions (≥4 cm) were associated with malignancy, severe peripheral artery disease, and systemic arterial hypertension. The SSc calcinosis subgroup exhibited a higher mean adjusted European Scleroderma Study Group Activity Index score than those without. However, survival rates did not significantly differ between the two groups. Diltiazem was the most commonly used treatment, and while bisphosphonates reduced complications related to calcinosis, complete resolution was not achieved. The findings underscore current limitations in diagnosing, monitoring, and treating calcinosis, emphasizing the need for further research and improved therapeutic strategies to improve patient care and outcomes.

Do We Have Good Activity Indices in Systemic Sclerosis?

BACKGROUND: No fully validated index is available for assessing overall disease activity in systemic sclerosis (SSc). OBJECTIVES: To estimate the effect of disease activity as measured by different disease activity indices on the risk of subsequent organ damage. METHODS: The European Systemic sclerosis study group activity index (EScSG AI), the European Scleroderma Trials and Research Group Activity Index (r-EUSTAR AI), 12 point activity index proposed by Minier (12point AI) were calculated for 91 patients; the CRISS (The Composite Response Index for Systemic Sclerosis) for patients included after 2016. Data were analysed by parametric and non-parametric tests and logistic regression. RESULTS: EscSG AI, r-EUSTAR AI and 12point AI correlated with lung involvement. EScSG AI and r-EUSTAR AI correlated with diffuse skin involvement. EscSG AI correlated with digital ulcers and diffuse cutaneous involvement and r-EUSTAR AI with a renal crisis. Bivariate analysis showed an inverse correlation between the three disease activity scores and forced vital capacity (FVC) (p<0.001) and diffusing capacity for carbon monoxide (DLCO) (p<0.001) and positive correlation with pulmonary fibrosis (p<0.001), modified Rodnan skin score (mRSS) (p<0.001), health assessment questionnaire (HAQ) (p<0.001), systolic pulmonary pressure (sPAP) (p<0.001), C-reactive protein (CRP) (p<0.001) and capillaroscopy scoring (p<0.001) at both baseline visit and the 3-year follow-up visit. Logistic regression revealed that baseline EScSG AI adjusted for gender and age and that baseline 12-point AI both adjusted and unadjusted predicted worse skin involvement at 3-year follow-up; while adjusted EScSG AI predicted decreasing DLCO. Also, 12-point AI predicted a decline of FVC and higher HAQ scores at 3-year follow up; while baseline r-EUSTAR AI was able to predict muscular deterioration, decline of FVC and the increase of HAQ score during 3 years of following. An active disease according to EScSG AI at first visit predicted progression of joint involvement while an active disease at baseline showed by r- EUSTAR AI predicted muscular deterioration, FVC and DLCO worsening, as well as an increase in HAQ score during the follow-up period. r-EUSTAR AI was the only score to predict the decrease of FVC in a multiple regression prediction model (OR= 1.306 (1.025, 1.665), p=0.31) while baseline EScSG AI best predicted worsening of DLCO (OR=1.749 (1.104, 2.772), p=0.017). CONCLUSION: Our study could not establish a gold standard to assess disease activity in SSc; especially EscSG AI and r-EUSTAR AI could quantify and predict major organ involvement in daily practice. CRISS can be useful as an outcome measure for patients with short disease duration included in clinical studies.

Quantitative Doppler in musculoskeletal ultrasonography - suboptimal performance of both experienced and in-training sonographers in selection of the highest Doppler signal image from cine-loops.

AIMS: Doppler ultrasonography assessment is mandatory nowadays for the complete description of rheumatic disease activity. Initially it was performed in semi quantitative way but recently the (fully) quantitative assessment is gaining more interest. In quantitative assessment, the ratio between total colorized and total pixels (CTR) is computed for the whole image or just for the region of interest (ROI). The frame with the highest amount of Doppler signal (also called worst case scenario image - WCSI) is usually the only one analyzed. The technique requires a very precise identification of WCSI from a certain number of consecutive frames, captured from the same position of the US probe, (and in most cases this is done manually). Our study examined the ability of both experienced and in-training sonographers to identify WCSI using a computerized analytical system as the gold standard. MATERIALS AND METHODS: The study analyzed 480 frame selections done in two distinct exercises. The WCSI and other 3 images with a 5%, 10% and respectively 20% lower level of CTR compared with WCSI were packed in one selection. All frames emerging from the same video clip were randomly presented to six experienced and six in training sonographers; the request was to select the frame with the highest CTR (WCSI) from each package (twenty packages in total). A similar exercise was performed with CTRs decreasing in steps of 2%. RESULTS: In the first exercise the WCSI was correctly identified in 79.1% cases and in 67% of cases in the 2nd exercise. The interobserver agreement between experienced and in-trainer evaluators for the 1st exercise was 0.78 and 0.4 in the 2nd exercise. CONCLUSION: Using computerized analysis as the gold standard, we demonstrated a large heterogeneity across sonographers regarding their ability to identify the best Doppler image even from a small group of frames.

Clinical Phenotype of Endothelial Dysfunction in Romanian Scleroderma Patients.

OBJECTIVE: To identify the particularities of the clinical phenotype of endothelial dysfunction in a lot of Romanian patients from a reference center and compare it to data reported by international registries. MATERIAL AND METHODS: 51 patients were included in a cross-sectional study. The patients were evaluated for the pattern of disease, main visceral involvement, serum markers of disease. RESULTS: 41.2% patients had history of digital ulcers, 27.45% had pulmonary arterial hypertension; cardiovascular involvement also included: diastolic dysfunction in 31.1% of the patients, global systolic dysfunction in 9.8%, rhythm and conduction disturbances in 19.6%, peripheral vascular disease in 19.6%. Scleroderma renal crisis was identified in 2 patients. CONCLUSION: Vascular complications are a major cause of morbidity and mortality in systemic sclerosis. Earlier therapeutic intervention demands improved screening and diagnosis in all cases.

Low vitamin D status in systemic sclerosis and the impact on disease phenotype.

OBJECTIVE: Vitamin D has pleiotropic effects including immunomodulatory, cardioprotective, and antifibrotic properties and is thus able to modulate the three main links in scleroderma pathogenesis. The aim of the study was to evaluate the level of vitamin D in patients with systemic sclerosis and to analyze the associations between the concentration of vitamin D and the features of systemic sclerosis. MATERIAL AND METHODS: Fifty-one consecutive patients were evaluated for visceral involvement, immunological profile, activity, severity scores, and quality of life. The vitamin D status was evaluated by measuring the 25hydroxy-hydroxyvitamin D serum levels. RESULTS: The mean vitamin D level was 17.06±9.13 ng/dL. Only 9.8% of the patients had optimal vitamin D levels; 66.66% of them had insufficient 25(OH)D levels, while 23.52% had deficient levels. No correlation was found between vitamin D concentration and age, sex, autoantibody profile, extent of skin involvement, or vitamin D supplementation. Vitamin D levels were correlated with the diffusing capacity of the lung for carbon monoxide (p=0.019, r=0.353), diastolic dysfunction (p=0.033, r=-0.318), digital contractures (p=0.036, r=-0.298), and muscle weakness (p=0.015, r=-0.377) and had a trend for negative correlation with pulmonary hypertension (p=0.053, r=-0.29). CONCLUSION: Low levels of vitamin D are very common in systemic sclerosis. Poor vitamin status seems to be related with a more aggressive disease with multivisceral and severe organ involvement, especially pulmonary and cardiac involvement.

Clinical Phenotype of Endothelial Dysfunction in a Lot of Romanian Scleroderma Patients.

OBJECTIVES: to identify the particularities of the clinical phenotype of endothelial dysfunction in a lot of Romanian patients from a reference center and compare it to data reported by international registries. MATERIALS AND METHODS: 51 patients were included in a cross sectional study. The patients were evaluated for the pattern of disease, main visceral involvement, serum markers of disease. RESULTS: 41.2% patients had history of digital ulcers, 27.45% had pulmonary arterial hypertension; cardiovascular involvement also included: diastolic dysfunction in 31.1% of the patients, global systolic dysfunction in 9.8%, rhythm and conduction disturbances in 19.6%, peripheral vascular disease in 19.6%. Scleroderma renal crisis was identified in 2 patients. CONCLUSION: Vascular complications are a major cause of morbidity and mortality in systemic sclerosis. Earlier therapeutic intervention demands improved screening and diagnosis in all cases.

Monitoring drug and antidrug levels: a rational approach in rheumatoid arthritis patients treated with biologic agents who experience inadequate response while being on a stable biologic treatment.

Clinical response in patients with rheumatoid arthritis (RA) treated with biologic agents can be influenced by their pharmacokinetics and immunogenicity. The present study evaluated the concordance between serum drug and antidrug levels as well as the clinical response in RA patients treated with biological agents who experience their first disease exacerbation while being on a stable biologic treatment. 154 RA patients treated with rituximab (RTX), infliximab (IFX), adalimumab (ADL), or etanercept (ETN) were included. DAS28, SDAI, and EULAR response were assessed at baseline and reevaluated at precise time intervals. At the time of their first sign of inadequate response, patients were tested for both serum drug level and antidrug antibodies level. At the next reevaluation, patients retreated with RTX that had detectable drug level had a better EULAR response (P = 0.038) with lower DAS28 and SDAI scores (P = 0.01 and P = 0.03). The same tendency was observed in patients treated with IFX and ETN regarding EULAR response (P = 0.002 and P = 0.023), DAS28 score (P = 0.002 and P = 0.003), and SDAI score (P = 0.001 and P = 0.026). Detectable biologic drug levels correlated with a better clinical response in patients experiencing their first RA inadequate response while being on a stable biologic treatment with RTX, IFX, and ETN.