"Scleroderma" and "Scleroderma-like" Capillaroscopic Pattern-Differences and Similarities.

INTRODUCTION: The "scleroderma" type capillaroscopic pattern is a reference pattern in rheumatology that is a diagnostic sign for systemic sclerosis (SSc) in an appropriate clinical context and is observed in more than 90% of scleroderma patients. Similar microvascular changes, the so-called "scleroderma-like", have been described albeit in a lower proportion of patients with other rheumatic diseases, such as dermatomyositis (DM), undifferentiated connective tissue diseases (UCTD), systemic lupus erythematosus (SLE), etc. Three distinct stages of "scleroderma" pattern have been suggested by Cutolo et al., i.e., "early", "active", and "late". However, disease duration is just one of the factors that contributes to the progression of microvascular changes, and in this regard, "active" or even "late" pattern could be observed in patients with shorter disease duration. In addition, stable microvascular changes could be found for long periods in other cases. OBJECTIVE: The aim of the study was to assess the presence of differentiating features between "scleroderma" pattern in SSc and "scleroderma-like" pattern in other rheumatic diseases. METHODS: 684 capillaroscopic images demonstrating a "scleroderma" and "scleroderma-like" pattern have been analysed in the current retrospective cross-sectional study. 479 capillaroscopic pictures were obtained from 50 SSc patients, 105 from 7 DM patients, 38 from 10 rheumatoid arthritis (RA) patients, 36 images from 5 patients with SLE, and 26 images from 9 patients with UCTD. All capillaroscopic images used in the current analysis have fulfilled the criteria for "sclerderma/scleroderma-like" pattern, as the pathological changes in the capillaroscopic parameters have also been confirmed by quantitative measurement of capillary diameters, capillary density, and intercapillary distance. All the images have been categorized into one of the following groups, i.e., "early", "active" and "late" phases (according to the definition of Cutolo et al.), or "other" findings, the latter being specifically described as they could not be attributed to one of the other three categories. RESULTS: 479 capillaroscopic pictures were obtained from 50 scleroderma patients. 31 of them showed an "early", 391 an "active" phase, and 57 a "late" phase "scleroderma" type microangiopathy. In 69 images assessed as an "active" pattern, neoangiogenesis was found. In 43 out of 105 capillaroscopic pictures from DM patients, an "active" phase was detected; in 2 of the images, a "late" pattern was found, and in 60 capillaroscopic pictures, neoangiogenesis in combination with giant capillary loops was observed. Early microangiopathy was not found in this group. Among capillaroscopic images from SLE patients, "late" phase microangiopathy was not found. "Early" phase was present in 3 images, "active" phase in 29, neoangiogenesis in "active" phase in 4 pictures. Early microangiopathy was detected in 11 capillaroscopic pictures from RA patients (8 out of 9 patients), an "active" phase in 4 images (3 patients), and in 23 capillaroscopic images, neoangiogenesis with mild capillary derangement and capillary loss and single giant capillaries ("rheumatoid neoangiogenic pattern") were observed. Classic "late" type microangiopathy was not found in RA patients as well as among patients with UCTD. The predominant capillaroscopic pattern in UCTD patients was early microangiopathy (n = 23). The rest images from UCTD exhibited features of the "active" phase. CONCLUSION: In conclusion, early microangiopathy was observed in RA, SLE, and UCTD patients, but not in patients with DM. An "active" phase "scleroderma" type capillaroscopic pattern was detected in all patient groups other than SSc, i.e., DM, SLE, RA, and UCTD. "Late" phase "scleroderma" type microangiopathy was present in patients with scleroderma and DM and was not observed in SLE, RA, and UCTD. Despite the fact that in some cases, microangiopathy in scleroderma and other rheumatic diseases may be indistinguishable, the results of the current research have shown the presence of some differentiating features between "scleroderma" and "scleroderma-like" microangiopathy that might be a morphological phenomenon associated with differences in the pathogenesis and the degree of microvascular pathology in various rheumatic diseases.

The Value of Ultrasound for Detecting and Following Subclinical Interstitial Lung Disease in Systemic Sclerosis.

BACKGROUND: Interstitial lung disease (ILD) is a complication in patients with systemic sclerosis (SSc). Accurate strategies to identify its presence in early phases are essential. We conducted the study aiming to determine the validity of ultrasound (US) in detecting subclinical ILD in SSc, and to ascertain its potential in determining the disease progression. METHODS: 133 patients without respiratory symptoms and 133 healthy controls were included. Borg scale, Rodnan skin score (RSS), auscultation, chest radiographs, and respiratory function tests (RFT) were performed. A rheumatologist performed the lung US. High-resolution CT (HRCT) was also performed. The patients were followed every 12 weeks for 48 weeks. RESULTS: A total of 79 of 133 patients (59.4%) showed US signs of ILD in contrast to healthy controls (4.8%) (p = 0.0001). Anti-centromere antibodies (p = 0.005) and RSS (p = 0.004) showed an association with ILD. A positive correlation was demonstrated between the US and HRCT findings (p = 0.001). The sensitivity and specificity of US in detecting ILD were 91.2% and 88.6%, respectively. In the follow-up, a total of 30 patients out of 79 (37.9%) who demonstrated US signs of ILD at baseline, showed changes in the ILD score by US. CONCLUSIONS: US showed a high prevalence of subclinical ILD in SSc patients. It proved to be a valid, reliable, and feasible tool to detect ILD in SSc and to monitor disease progression.

Characterization of kidneys in patients with systemic sclerosis by multi-parametric magnetic resonance quantitative imaging.

PURPOSE: To determine the usefulness of multiparametric magnetic resonance (MR) quantitative imaging in characterizing the kidneys in systemic sclerosis (SSc) patients. MATERIAL AND METHODS: Forty-six SSc patients (47.9 ± 12.8 years, 40 females) and 22 age- and sex- matched healthy volunteers (46.1 ± 13.8 years, 20 females) were recruited and underwent renal MR imaging by acquiring blood oxygen level dependent and saturated multi-delay renal arterial spin labeling (SAMURAI) sequences. The T2* value, T1 value, renal blood flow (RBF), arterial bolus arrival time (aBAT), and tissue bolus arrival time (tBAT) of renal cortex were measured and compared among diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) groups and healthy controls using One-way ANOVA and analyzed by logistic regression. RESULTS: Compared to healthy volunteers, SSc patients with normal estimated glomerular filtration rate (n = 40) had significantly lower T2* value (P = 0.026) in the left renal cortex, longer T1 value (right: P = 0.015; left: P = 0.023), lower RBF (right: P < 0.001; left: P < 0.001), and shorter tBAT (right: P < 0.001; left: P = 0.005) in both right and left renal cortex after adjusting for demographics. The dcSSc patients (n = 23) had significantly lower RBF in both right (226.7 ± 65.2 mL/100 g/min vs. 278.2 ± 73.5 mL/100 g/min, P = 0.022) and left (194.5 ± 71.5 mL/100 g/min vs. 252.7 ± 84.4 mL/100 g/min, P = 0.020) renal cortex compared to the lcSSc patients (n = 23) after adjusting for demographics, but the significance of the difference was attenuated after further adjusting for modified Rodnan skin score and digital ulcers. CONCLUSION: Multi-parametric MR quantitative imaging, particularly multi-delay ASL perfusion imaging, is a useful technique for characterizing the kidneys and classification of SSc patients.

Naifold capillaroscopy in mixed connective tissue disease patients.

INTRODUCTION: Mixed connective tissue disease (MCTD) is a rare systemic disease characterized by overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermato-/polymyositis (DM/PM), and rheumatoid arthritis (RA). Naifold capillaroscopy (NFC) is a non-invasive test for evaluating the capillaries of the nail shaft used in the diagnosis of rheumatic diseases. OBJECTIVES: To determine whether there are characteristic abnormalities in NFC in MCTD patients, and whether the type of NFC lesions correlates with organ involvement in these patients. METHODS: Clinical picture and NFC patterns were analyzed in 43 patients with MCTD. Capillaroscopic images were divided into scleroderma-like pattern (SD-like pattern) according to the Cutolo classification, non-specific lesions, and normal images. Relationships between the clinical aspects considered in the MCTD classification criteria and the changes in the capillaroscopic images were evaluated. RESULTS: SD-like pattern was present in 20 MCTD patients (46.51%) with a predominance of the "early" pattern. Giant, branched, dilated capillaries and reduced capillary density were found more frequently in MCTD patients compared to the control group (p-values 0.0005, 0.005, 0.02, < 0.0001 respectively). There were associations found between the presence of a reduced number of vessels, avascular areas, and SD-like pattern with the presence of sclerodactyly in MCTD patients (p = 0.002, p = 0.006, p = 0.02, respectively), alongside an association between the presence of branched vessels and the subpapillary plexus with pulmonary arterial hypertension (PAH) (p = 0.04 and p = 0.005, respectively). CONCLUSIONS: MCTD patients are significantly more likely to have abnormalities upon NFC. It is worthwhile to perform capillaroscopic examination in MCTD patients. Key Points • Scleroderma-like pattern was found in more than half of the MCTD patients. • Reduced capillary density was found to be a significant predictor of the diagnosis of MCTD. • There were relationships between the presence of reduced capillary density, avascular areas, and SD-like with the presence of sclerodactyly in the MCTD patients. • There was an association between the presence of branched vessels and the visibility of the subpapillary plexus and pulmonary arterial hypertension (PAH).

Clinical course and factors associated with progressive acro-osteolysis in early systemic sclerosis: a retrospective cohort study.

To examine clinical course of early systemic sclerosis (SSc) and identify factors for progression of acro-osteolysis by a retrospective cohort study. Dual time-point hand radiography was performed at median interval (range 3.0 ± 0.4 years) in 64 recruited patients. Progressive acro-osteolysis was defined as the worsening of severity of acro-osteolysis according to rating scale (normal, mild, moderate, and severe). Incidence of the progression was determined. Cox regression was analyzed for the predictors. A total of 193.6 per 100 person-years, 19/64 patients had progressive acro-osteolysis with incidence of 9.8 per 100-person-years (95% CI 6.3-15.4). The median time of progressive acro-osteolysis was 3.5 years. Rate of progression increased from 1st to 3rd years follow-up with the progression rate at 1-, 2- and 3-years were 0, 2.0 and 18.3%, respectively. Patients with positive anti-topoisomerase I tended to have more progressive acro-osteolysis but no significant predictors on Cox regression. 44%, 18%, and 33% of who had no, mild, and moderate acro-osteolysis previously developed progression and 10 turned to be severe acro-osteolysis. In conclusion, the incidence of progressive acro-osteolysis was uncommon in early SSc but the rate of progression was pronouncedly increasing after three years follow-up. A half of the patients progressed to severe acro-osteolysis.

Dental Implants in 18 Patients with Systemic Scleroderma: A Retrospective Radiographic Analysis Over a 5-Year Period with Focus on Marginal Bone Loss.

PURPOSE: Patients with systemic scleroderma (SSc) often suffer from premature tooth loss. The aim of this study was to radiologically investigate bone loss at dental implants in patients with SSc and compare it with data from the literature on healthy patients. MATERIALS AND METHODS: Mesial and distal bone level changes at implants were independently determined on panoramic and intraoral radiographs. They were double-checked after determination of evaluability by three different raters. Cohen's kappa was used to test for interrater reliability. Mean bone loss was estimated using linear regression analysis considering the patient as a random-effect implant and performed separately in predefined implant regions for different time points and for the mesial and distal sides of the implants. RESULTS: Mesial and distal bone level changes were analyzed in 61 implants using periapical and panoramic radiographs. In total, 114 radiographs from 18 patients were evaluable in both the mesial and distal regions. After a maximum observation period of 60 months, the mean peri-implant bone loss was 1.68 mm (range: 0.83 to 2.54 mm) at the distal aspect and 1.65 mm (range: 0.81 to 2.48 mm) at the mesial aspect in the right posterior mandible (region 44 to 47 [FDI numbering system]), whereas in the left posterior maxilla (regions 24 to 27), the mean peri-implant bone loss was 0.61 mm (range: 0.32 to 0.91 mm) at the distal aspect and 0.59 mm (range: 0.16 to 1.03 mm) at the mesial aspect. The mean bone loss 60 months after surgery was 1.05 mm (range: 0.85 to 1.25 mm). CONCLUSIONS: Marginal bone loss at implants in patients with SSc is comparable to data from the literature collected in healthy subjects.

Histogram-Based Densitometry Index to Assess the Severity of Interstitial Lung Disease in Systemic Sclerosis in Standard and Low-Dose Computed Tomography.

OBJECTIVE: Mean lung attenuation, skewness, and kurtosis are histogram-based densitometry variables that quantify systemic sclerosis-associated interstitial lung disease (SSc-ILD) and were recently merged into a computerized integrated index (CII). Our work tested the CII in low-dose 9-slice (reduced) and standard high-resolution computed tomography (CT) scans to evaluate extensive SSc-ILD and predict mortality. METHODS: CT scans from patients with SSc-ILD were assessed using the software Horos to compute standard and reduced CIIs. Extensive ILD was determined following the Goh staging system. The association between CIIs and extensive ILD was analyzed with a generalized estimating equation regression model, the predictive ability of CIIs by the area under the receiver-operation characteristic curve (AUC), and the association between CIIs and death by Kaplan-Meier analysis. RESULTS: Among 243 patients with standard and reduced CT scans available, 157 CT scans from 119 patients with SSc-ILD constituted the derivation cohort. The validation cohort included 116 standard and 175 reduced CT scans. Both CIIs from standard (odds ratio [OR] 0.53, 95% CI 0.37-0.75; AUC 0.77, 95% CI 0.68-0.87) and reduced CT scans (OR 0.54, 95% CI 0.35-0.82; AUC 0.78, 95% CI 0.70-0.87) were significantly associated with extensive ILD. A threshold of CII ≤ -0.96 for standard CT scans and CII ≤ -1.85 for reduced CT scans detected extensive ILD with high sensitivity in both derivation and validation cohorts. Extensive ILD according to Goh staging (OR 2.94, 95% CI 1.10-7.82) and standard CII ≤ -0.96 (OR 1.78, 95% CI 1.24-2.56) significantly predicted mortality; a marginal P value was observed for reduced CII ≤ -1.85 (OR 1.27, 95% CI 0.93-1.75). CONCLUSION: Thresholds for both standard and reduced CII to identify extensive ILD were developed and validated, with an additional association with mortality. CIIs might help in clinical practice when radiology expertise is missing.

Evaluating Skin Involvement in Systemic Sclerosis Using High-Frequency Ultrasound and Virtual Touch Tissue Imaging.

OBJECTIVE: This study aimed to explore the diagnostic significance of high-frequency ultrasound combined with visual touch tissue imaging quantification (VTIQ) in the diagnosis and management of systemic sclerosis (SSc). METHODS: Patients diagnosed with SSc and normal volunteers were recruited and divided into an experimental group and a control group, with 30 cases in each group, respectively. The skin thickness at six sites was assessed using high-frequency ultrasound, and the shear wave velocity (SWV) was determined using the VTIQ method. The differences in skin thickness and SWV between the experimental group and the control group were compared and a receiver operating characteristic (ROC) curve was plotted. The value of high-frequency ultrasound, VTIQ, and high-frequency ultrasound combined with VTIQ for evaluating skin involvement in SSc was determined. RESULTS: The difference in SWV sum at six sites and the thickness sum was statistically significant (all p = 0.000 < 0.05) from that of the control group, and there was a strong association between the SWV sum, thickness sum, and Rodnan skin score at the six sites in the experimental group (p = 0.000, r = 0.726; p = 0.000, r = 0.679). Based on the ROC curve, the area under the curve (AUC) for high-frequency ultrasound examination was 0.789. The AUC for VTIQ examination was 0.893, while the AUC for high-frequency ultrasound combined with VTIQ examination was 0.923. The combined examination method showed the highest AUC, indicating the best diagnostic performance. CONCLUSION: The integration of high-frequency ultrasound and VTIQ provides a quantitative approach for assessing the extent of skin involvement in SSc patients, offering valuable insights for clinical diagnosis and treatment purposes.

KL6 and IL-18 levels are negatively correlated with respiratory function tests and ILD extent assessed on HRCT in patients with systemic sclerosis-related interstitial lung disease (SSc-ILD).

BACKGROUND: Interstitial lung disease (ILD) is one of the leading causes of mortality in patients with systemic sclerosis (SSc). Serum biomarkers have been suggested as indicators for pulmonary damage with clinical value in the diagnosis and prognosis of SSc-ILD. OBJECTIVES: To investigate the role of serum biomarkers (Krebs von den Lungen-6 KL-6, IL-18 and IL-18BP) as a potential biomarker reflecting the severity of SSc-ILD as assessed through high-resolution computed tomography (HRCT) and pulmonary function tests (PFT), including forced vital capacity (%FVC) and diffusing capacity of the lung for carbon monoxide (%DLCO). METHODS: A cross-sectional study including patients with SSc fulfilling the 2013 ACR/EULAR criteria was performed. Patients were classified according to disease duration and pulmonary involvement (presence of ILD). All SSc patients underwent chest HRCT scans and pulmonary function test at baseline. Serum concentration of KL-6, IL8 and IL18BP were determined using the quantitative ELISA technique, sandwich type (solid phase sandwich Enzyme Linked-Immuno-Sorbent Assay), with kits from MyBiosource for KL-6 and from Invitrogen for IL18 and IL18BP. A semiquantitative grade of ILD extent was evaluated through HRCT scan (grade 1, 0-20%; grade 2, >20%). Extensive disease was defined as >20% lung involvement on HRCT, and FVC <70% predicted and limited lung involvement as ≤20% ILD involvement on HRCT, and an FVC ≥70% predicted. RESULTS: 74 patients were included, 27% were male. The mean age at diagnosis was 57.5±15 years and the mean time since diagnosis was 7.67±8 years. 28 patients had ILD (38%). 64% of patients had <20% ILD extent classified through HRCT scan. SSc-ILD patients had elevated serum KL-6 and IL-18 levels compared to patients without ILD (p=0.003 and p=0.04), and those findings were preserved after adjusting for age and sex. Negative correlation between KL-6 levels and%FVC (ß=-0.25, p 0.037) and% DLCO (ß=-0.28, p 0.02) and between IL-18 levels and%FVC (ß=-0.38, p 0.001) and%DLCO (ß=-0.27, p 0.03) were found. Serum KL-6 and IL-18 levels successfully differentiated grades 1 and 2 of the semiquantitative grades of ILD extent (p = 0.028 and p = 0.022). Semiquantitative grades of ILD on the HRCT scan were significantly proportional to the KL-6 (p = 0.01) and IL-18 (p = 0.03). A positive correlation between extensive lung disease and KL-6 (ß=0.42, p = 0.007) but not with IL-18 was found. CONCLUSIONS: Serum KL-6 levels and IL-18 were increased in patients with SSc-ILD and showed a positive correlation with ILD severity as measured using a semiquantitative CT grading scale and negative correlation with PFT parameters. Serum KL-6 and IL-18 could be a clinically useful biomarker in screening and evaluating SSc-ILD.

Peripheral microvascular function is linked to cardiac involvement on cardiovascular magnetic resonance in systemic sclerosis-related pulmonary arterial hypertension.

AIMS: Systemic sclerosis (SSc) is characterized by vasculopathy, inflammation, and fibrosis, and carries one of the worst prognoses if patients also develop pulmonary arterial hypertension (PAH). Although PAH is a known prognosticator, patients with SSc-PAH demonstrate disproportionately high mortality, presumably due to cardiac involvement. In this cross-sectional study, the relationship between cardiac involvement revealed by cardiovascular magnetic resonance (CMR) and systemic microvascular disease severity measured with nailfold capillaromicroscopy (NCM) in patients with SSc-PAH is evaluated and compared with patients with idiopathic PAH (IPAH). METHODS AND RESULTS: Patients with SSc-PAH and IPAH underwent CMR, echocardiography, and NCM with post-occlusive reactivity hyperaemia (PORH) testing on the same day. CMR imaging included T2 (oedema), native, and post-contrast T1 mapping to measure the extracellular volume fraction (ECV, fibrosis) and adenosine-stress-perfusion imaging measuring the relative myocardial upslope (microvascular coronary perfusion). Measures of peripheral microvascular function were related to CMR indices of oedema, fibrosis, and myocardial perfusion. SSc-PAH patients (n = 20) had higher T2 values and a trend towards a higher ECV, compared with IPAH patients (n = 5), and a lower nailfold capillary density (NCD) and reduced capillary recruitment after PORH. NCD correlated with ECV and T2 (r = -0.443 and -0.464, respectively, P < 0.05 for both) and with markers of diastolic dysfunction on echocardiography. PORH testing, but not NCD, correlated with the relative myocardial upslope (r = 0.421, P < 0.05). CONCLUSION: SSc-PAH patients showed higher markers of cardiac fibrosis and inflammation, compared with IPAH patients. These markers correlated well with peripheral microvascular dysfunction, suggesting that SSc-driven inflammation and vasculopathy concurrently affect peripheral microcirculation and the heart. This may contribute to the disproportionate high mortality in SSc-PAH.

Umbilical cord mesenchymal stem cells transplantation in patients with systemic sclerosis: a 5-year follow-up study.

OBJECTIVE: To assess the long-term safety and efficacy of umbilical cord mesenchymal stem cells transplantation (UMSCT) in patients with systemic sclerosis (SSc). METHODS: Forty-one patients with moderate to severe SSc underwent UMSCT at the Affiliated Drum Tower Hospital of Nanjing University Medical School from 2009 to 2017. In this study, we conducted a longitudinal and retrospective analysis and compared the clinical and laboratory manifestations before and after UMSCT. The main outcome of the study was overall survival. We evaluated changes in the modified Rodnan Skin Score (mRSS), as well as the changes in the pulmonary examination by using high-resolution computed tomography (HRCT) and ultrasound cardiogram (UCG). Additionally, we assessed the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the severity of peripheral vascular involvement during the first year after treatment. RESULTS: The overall 5-year survival rate was 92.7% (38 out of 41 patients). Following UMSCT, the mean mRSS significantly decreased from 18.68 (SD = 7.26, n = 41) at baseline to 13.95 (SD = 8.49, n = 41), 13.29 (SD = 7.67, n = 38), and 12.39 (SD = 8.49, n = 38) at 1, 3, and 5 years, respectively. Improvement or stability in HRCT images was observed in 72.0% of interstitial lung disease (ILD) patients. Pulmonary arterial hypertension (PAH) remained stable in 5 out of 8 patients at the 5-year follow-up. No adverse events related to UMSCT were observed in any of the patients during the follow-up period. CONCLUSION: UMSCT may provide a safe and feasible treatment option for patients with moderate to severe SSc based on long-term follow-up data. The randomized controlled study will further confirm the clinical efficacy of UMSCT in SSc. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00962923. Key Point • UMSCT is safe and effective for SSc patients.

Prognostic value of automated assessment of interstitial lung disease on CT in systemic sclerosis.

OBJECTIVE: Stratifying the risk of death in SSc-related interstitial lung disease (SSc-ILD) is a challenging issue. The extent of lung fibrosis on high-resolution CT (HRCT) is often assessed by a visual semiquantitative method that lacks reliability. We aimed to assess the potential prognostic value of a deep-learning-based algorithm enabling automated quantification of ILD on HRCT in patients with SSc. METHODS: We correlated the extent of ILD with the occurrence of death during follow-up, and evaluated the additional value of ILD extent in predicting death based on a prognostic model including well-known risk factors in SSc. RESULTS: We included 318 patients with SSc, among whom 196 had ILD; the median follow-up was 94 months (interquartile range 73-111). The mortality rate was 1.6% at 2 years and 26.3% at 10 years. For each 1% increase in the baseline ILD extent (up to 30% of the lung), the risk of death at 10 years was increased by 4% (hazard ratio 1.04, 95% CI 1.01, 1.07, P = 0.004). We constructed a risk prediction model that showed good discrimination for 10-year mortality (c index 0.789). Adding the automated quantification of ILD significantly improved the model for 10-year survival prediction (P = 0.007). Its discrimination was only marginally improved, but it improved prediction of 2-year mortality (difference in time-dependent area under the curve 0.043, 95% CI 0.002, 0.084, P = 0.040). CONCLUSION: The deep-learning-based, computer-aided quantification of ILD extent on HRCT provides an effective tool for risk stratification in SSc. It might help identify patients at short-term risk of death.

Ultrasound assessment of diaphragm and quadriceps muscles and its relationship with handgrip and respiratory muscle strength in patients with systemic sclerosis: a cross-sectional study.

BACKGROUND: Muscle dysfunction may cause disability and reduce the quality of life of patients with systemic sclerosis (SSc) when compared to healthy individuals. However, the literature on the topic is scarce and uses several criteria for assessing muscle dysfunction in this population. OBJECTIVES: To compare diaphragm and quadriceps muscle thickness, diaphragm mobility, and handgrip strength between patients with SSc and healthy individuals. METHOD: This cross-sectional study included 16 patients with SSc and 16 self-reported healthy individuals matched for age. We assessed quadriceps and diaphragm thickness and diaphragmatic mobility (ultrasound), handgrip strength (hand-held dynamometer), and respiratory muscle strength (manovacuometer). Patients also responded to the Health Assessment Questionnaire Disability Index and the International Physical Activity Questionnaire. RESULTS: Patients with SSc presented lower quadriceps thickness (p < 0.0001), diaphragmatic mobility (p = 0.01), handgrip (p < 0.0001), and respiratory muscle strength (p < 0.0001) than healthy individuals. A moderate positive correlation was observed between handgrip strength and quadriceps thickness in patients with SSc (rho = 0.576; p = 0.02). CONCLUSIONS: Patients with SSc presented reduced quadriceps thickness, diaphragmatic mobility, handgrip, and respiratory muscle strength when compared to healthy individuals Also, handgrip strength was correlated with quadriceps thickness in patients with SSc, suggesting that loss of muscle mass accompanies loss of peripheral muscle strength group of patients. Key Points • SSc patients presented reduced quadriceps thickness and diaphragmatic mobility • SSc patients have reduced handgrip and respiratory muscle strength • Lower handgrip muscle strength correlated with lower quadriceps thickness.

Advanced and traditional chest MRI sequence for the clinical assessment of systemic sclerosis related interstitial lung disease, compared to CT: disease extent analysis and correlations with pulmonary function tests.

BACKGROUND: MRI is a radiation-free emerging alternative to CT in systemic sclerosis related interstitial lung disease (SSc-ILD) assessment. We aimed to compare a T2 radial TSE and a PD UTE MRI sequence with CT in SSc-ILD extent evaluation and correlations with pulmonary function tests (PFT). MATERIAL AND METHODS: 29 SSc-ILD patients underwent CT, MRI and PFT. ILD extent was visually assessed. Lin's concordance correlation coefficients (CCC) and Kruskal Wallis test (p-value < 0.05) were computed for inter-method comparison. Patients were divided in limited and extended disease, defining extended ILD with two methods: (A) ILD>30% or 10%20% or 20% with FVC%<70%. MRI Sensitivity, Specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and Accuracy were assessed. Pearson correlation coefficients r (p-value<0.025) were computed between ILD extents and PFT (FVC% and DLCO%). RESULTS: Median ILD extents were 11%, 11%, 10% on CT, radial TSE and UTE, respectively. CCC between CT and MRI was 0.95 for both sequences (Kruskal-Wallis p-value=0.64). Sensitivity, Specificity, PPV, NPV and Accuracy in identifying extended disease were: (A) 87.5 %, 100 %, 100 %, 95.5 and 96.6 % with radial TSE and 87.5 %, 95.2 %, 87.5 %, 95.2 and 93.1 % with UTE; (B) 86.7 %, 86.4 %, 66.7 %, 95.0 % and 86.2 % for both sequences. Pearson r of CT, radial TSE and UTE ILD extents with FVC were -0.66, -0.60 and -0.68 with FVC, -0.59, -0.56 and -0.57 with DLCO, respectively (p<0.002). CONCLUSIONS: MRI sequences may have similar accuracy to CT to determine SSc-ILD extent and severity, with analogous correlations with PFT.

The presence of abnormal septal motion on echocardiography is a predictor of abnormal cardiac magnetic resonance in systemic sclerosis.

OBJECTIVES: We aimed to perform a comprehensive analysis of the ECG, two-dimensional echocardiography (2DE) and cardiac MRI (CMR) findings in patients with systemic sclerosis (SSc), and also to investigate correlations between CMR findings and some ECG and echocardiography (ECHO) results. METHODS: We retrospectively analysed data from patients with SSc who were regularly seen at our outpatient referral centre, all assessed with ECG, Doppler ECHO and CMR. RESULTS: Ninety-three patients were included; mean (s.d.) age of 48.5 (10.3) years, 86% female, 52% diffuse SSc. Eighty-four (90%) of the patients had sinus rhythm. The most common ECG finding was the left anterior fascicular block, recorded in 26 patients (28%). The abnormal septal motion (ASM) was found in 43 (46%) patients on ECHO. Myocardial involvement (inflammation or fibrosis), as assessed by multiparametric CMR, was present in >50% of our patients. The age- and sex-adjusted model showed that ASM on ECHO increased significantly the odds of increased extracellular volume [odds ratio (OR) 4.43, 95% CI 1.73, 11.38], increased T1 Relaxation time (OR 2.67, 95% CI 1.09, 6.54), increased T2 Relaxation time (OR 2.56, 95% CI 1.05, 6.22), increased signal intensity ratio in T2-weighted imaging (OR 2.56, 95% CI 1.05, 6.22), presence of late gadolinium enhancement (OR 3.85, 95% CI 1.52, 9.76) and mid-wall fibrosis (OR 3.64, 95% CI 1.48, 8.96). CONCLUSION: This study indicates that the presence of ASM on ECHO is a predictor of abnormal CMR in SSc patients, and a precise assessment of ASM may serve as an important point for selecting the patients that should be evaluated by CMR for early detection of myocardial involvement.

The Value of Nailfold Capillaroscopy in the Classification and Differential Diagnosis of Raynaud's Phenomenon in Rheumatology.

Among instrumental techniques, nailfold capillaroscopy plays a leading role in the assessment of Raynaud's phenomenon (RP) patients because it is the only method that provides opportunities for morphological assessment of capillaroscopic findings in the nailfold area, with proven diagnostic and prognostic significance in rheumatology. The discussion about updating the classification of RP in rheumatology is interesting given the current understanding of capillaroscopic findings in rheumatic diseases and improvements in immunological diagnostics. The presence of dilation of the "true" capillary diameters in primary RP could be observed. There are some cases of primary RP where the capillaroscopic pattern is completely normal and there are no dilated capillaries present, which could be related to the duration and severity of the symptoms. It is possible that longer duration and greater severity are associated with the appearance of capillary dilations, but more research is needed to confirm it. Rarely, pathological capillaroscpic features of microangiopathy could be observed in RP patients in whom clinical, laboratory and immunological findings are compatible with the diagnosis "primary RP". These cases should be defined as "suspected secondary RP" and require closer follow-up for the assessment of symptom evolution. Abnormal "scleroderma" type capillaroscopic pattern has been established as a new classification criterion for systemic sclerosis (SSc) in 2013. Similar changes ("scleroderma-like" pattern) could be observed in other rheumatic diseases, i.e., undifferentiated connective tissue disease (UCTD), systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, including without evidence of overlap with scleroderma. The appearance of such microvascular abnormalities at disease presentation is less well studied in diseases different from SSc. However, "scleroderma-like" microangiopathy has also been reported as an initial sign in some systemic rheumatic diseases, such as UCTD and systemic lupus erythematosus. Thus, interpretation of capillaroscopic findings is performed in overall context, including clinical findings and laboratory and immunological test results.

CT evaluation of interstitial lung disease related to systemic sclerosis: visual versus automated assessment. A systematic review.

AIM: To identify similarities and differences between visual (VA) and automated assessment (AA) of systemic sclerosis-related interstitial lung disease (SSc-ILD) at chest computed tomography (CT) in terms of clinical applicability. MATERIALS AND METHODS: Medline, Embase, and Web of Science were searched to identify all studies investigating VA and AA for SSc-ILD assessment, from inception to 31 July 2022. Exclusion criteria were manuscripts not in English, absence of full-text, reviews, diseases other than ILD in SSc, CT not analysed with both VA and AA, VA and AA not adopted for the same purpose or not compared, overlap syndromes, SSc-ILD data not extractable, and studies with <10 patients. RESULTS: Ten full-text studies (804 patients) were included. The most adopted VAs were the Warrick or Goh score (four studies each), while densitometry (eight studies) or lung texture analysis (LTA, two studies) were utilised as AAs. The main field of investigation was the correlation with baseline pulmonary function tests (PFT, six studies). Warrick VA showed lower correlations compared to densitometry, while Goh VA demonstrated more heterogeneous results. Compared to LTA, Goh VA obtained lower correlations with lung volumes but similar or stronger coefficients with alveolar diffusibility. CONCLUSIONS: VA and AA may show heterogeneous results comparing their correlations with PFT, probably depending on the specific analysis adopted for each method. More data are needed on VA versus LTA. Comparisons between VA and AA regarding correlation with PFT follow-up and as prognostic elements, or for disease monitoring, are lacking. AAs in progressive fibrosis diagnosis remain to be tested.

Diagnosis of interstitial lung disease (ILD) secondary to systemic sclerosis (SSc) and rheumatoid arthritis (RA) and identification of 'progressive pulmonary fibrosis' using chest CT: a narrative review.

Interstitial lung disease (ILD) is a frequent manifestation of connective tissue diseases (CTDs), with incidence and prevalence variously assessed in the literature but reported in up to 30% of patients, with higher frequency in rheumatoid arthritis (RA) and systemic sclerosis (SSc). Recent years have seen a growing interest in the pulmonary manifestations of ILD-CTDs, mainly due to the widening of the use of anti-fibrotic drugs initially introduced exclusively for IPF, and radiologists play a key role because the lung biopsy is very rarely used in these patients where the morphological assessment is essentially left to imaging and especially HRCT. In this narrative review we will discuss, from the radiologist's point of view, the most recent findings in the field of ILD secondary to SSc and RA, with a special focus about the progression of disease and in particular about the 'progressive pulmonary fibrosis' (PPF) phenotype, and we will try to address two main issues: How to predict a possible evolution and therefore a worse prognosis when diagnosing a new case of ILD-CTDs and how to assess the progression of an already diagnosed ILD-CTDs.

Ultrasound abnormalities of the major salivary glands in Egyptian patients with systemic sclerosis.

INTRODUCTION/OBJECTIVES: systemic sclerosis (SSc) is an autoimmune disorder with multiple organs destruction. This study aimed to identify the ultrasonographic changes of major salivary glands in Egyptian scleroderma patients and to detect their association to different disease manifestations. METHODS: Forty-seven SSc patients and 43 apparent healthy volunteers were enrolled. Demographics, inflammatory markers, and autoimmune status were recorded. Ultrasound evaluation of salivary glands was performed. Salivary gland changes' associations were statistically examined with SSc susceptibility and disease manifestations. RESULTS: Thirty-one SSc patients exhibited glandular pathology (p < 0.0001), compared to controls. Of these abnormalities, SSc patients showed a total parotid gray scale of 2, total submandibular gray scale of 2, total glandular gray scale of 4, and total glandular Doppler signal of 1 at p < 0.0001, compared to the control group. Patients with SSc and glandular pathology had a higher prevalence of arthritis (p = 0.029) and ESR (p = 0.002) than those with normal glandular ultrasound. Significant associations were reported between gray scale ultrasound (GSUS) of total parotid (odds ratio "OR" = 0.4), total submandibular (OR = 0.36), and total glandular (OR = 0.53) with susceptibility to SSc at p < 0.0001. Total glandular GSUS (p = 0.039) and total submandibular power Doppler (p = 0.044) correlated with the SSc duration. Total parotid GSUS (p = 0.008) and total glandular GSUS (p < 0.0001) correlated with Schirmer's test. CONCLUSIONS: Major salivary glands are affected in SSc. Hence, scanning these glands with ultrasound is an additive tool besides the current practice. Key Points • Major salivary gland changes, observed by ultrasonography, are new findings in Egyptian SSc patients. • Ultrasound changes of major salivary glands are associated with inflammatory markers and clinical manifestations of SSc. • Scleroderma ultrasonography scans of the main salivary glands could be added to the routine work.