Relationship between nailfold capillaroscopy findings and the etiology and prognosis of interstitial lung disease.

OBJECTIVES: Connective tissue-associated interstitial lung diseases (CTD-ILD) are believed to be caused by microvascular damage. The objective of this study was to assess the nailfold capillaroscopy (NFC) pattern in patients diagnosed with both CTD-ILD and non-CTD-ILD to identify microvascular changes and determine the relation between capillaroscopic parameters, clinical variables, and disease-related measurements. PATIENTS AND METHODS: This cross-sectional study included 95 patients with interstitial lung disease who applied to our Rheumatology and Chest Clinics between September 2021 and July 2023. The patients were divided into two groups based on their diagnosis: non-CTD-ILD (group 1) and CTD-ILD (group 2). Nailfold capillaroscopy was performed. RESULTS: Ninety-five patients, 49 (51% female, mean age 62.31 ± 11.027 years) in group 1 and 46 (69.6% female, mean age 62.09 ± 10.887 years) in group 2, were included in the study. Abnormal capillary morphologies were both detected in the CTD-ILD group and the non-CTD-ILD groups. In patients with a usual interstitial pneumonia (UIP) pattern on chest computed tomography (CT), tortuosity was higher than in patients with non-specific interstitial pneumonia (NSIP) (P = 0.041), and the proportion of tortuosity increased significantly as the duration of the disease increased (P = 0.016). CONCLUSION: Our study highlights capillaroscopic abnormalities alone may not be sufficient to differentiate CTD-ILD (other than systemic sclerosis) from non-CTD-ILD. The presence of NFC abnormalities in non-CTD-ILD may suggest that fibrotic lung disease could potentially play a role in the deterioration of the microvascular structure or abnormal angiogenesis. Our study demonstrated that a multidisciplinary approach, incorporating clinical, morphological, pathological, and serological evaluations, is necessary for interpreting ILD. Key Points • Capillaroscopic abnormalities can also be seen in non-CTD-ILD. • Capillaroscopy findings do not distinguish the non-Ssc etiology of ILD. • Nailfold capillaroscopy may have the potential to serve as a useful tool in predicting prognosis and monitoring the disease progression in patients with idiopathic pulmonary fibrosis (IPF).

Baseline capillaroscopy provides no evidence of microvascular changes to predict long-COVID syndrome.

BACKGROUND: Long-COVID refers to a variety of symptoms that continue for at least 4 weeks following the onset of acute COVID-19 infection. "Microclots/microvasculopathy" is a potential cutting-edge theory. Nailfold capillaroscopy is a non-invasive method used to assess microvascularity. In this study, we aimed to compare baseline characteristics and capillaroscopic findings of patients with and without long-COVID syndrome. METHODS: Baseline clinical characteristics of 53 patients who tested positive for SARS-CoV-2 were recorded. At the time of COVID-19 diagnosis, patients underwent nailfold capillaroscopy. One year later, patients were rescreened for long-COVID symptoms. Comparisons were made between patients with and without long-COVID syndrome in terms of their baseline characteristics and capillaroscopic findings. RESULTS: There were 35 individuals (66%) with long-COVID syndrome. The most common symptoms related to long-COVID were fatigue (43.4%), myalgia (34%), arthralgia (20.8%), dyspnea (20.8%). In total, 22 patients (41.5%) had abnormal capillaroscopy findings. Like other baseline characteristics, the proportion of patients with abnormal capillaroscopic findings (40% vs 44%, p=0.76) was similar between patients with and without long-COVID syndrome. CONCLUSION: Microvasculopathy and microthrombotic vascular damage are among the strongest hypotheses discussed in this regard. Our results may suggest that factors, rather than baseline microvasculopathy, may drive pathophysiological mechanism underlying the poorly understood long-COVID syndrome (Tab. 2, Ref. 35).

Nailfold capillary measurements correlated to NOTCH3 R544C mutation in preclinical CADASIL patients.

BACKGROUND: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disease caused by NOTCH3 mutation. Nailfold capillaroscopy is a non-invasive technique typically used for rheumatic diseases. It has potential in other conditions linked to vascular pathology. However, capillaroscopy in CADASIL has not been explored. This study aims to investigate whether capillaroscopy measurements can correlate with brain vascular changes in preclinical CADASIL patients, specifically those with NOTCH3 mutation. METHODS: This study included 69 participants from the Taiwan Precision Medicine Initiative (TPMI) dataset who visited Taichung Veterans General Hospital from January to December 2022. All individuals underwent genetic studies, brain imaging and nailfold capillaroscopy. The Mann-Whitney U test was used to compare results of brain imaging between carriers and controls. It was also used to compare measurements in nailfold capillaroscopy within each group. Spearman Rank Correlation Analysis was used to explore the relationship between capillary measurements and brain MRI results. RESULTS: White matter hyperintensities (WMH) expression was positively correlated with capillary dimension and negatively correlated with density. Our results presented that R544C carriers exhibited a diffuse increase in WMH (p < 0.001) and a global reduction in gray matter volume but preserved in specific areas. The white matter lesion scores in all brain regions were higher in the mutation carriers than the controls. (p < 0.001). CONCLUSION: This research highlights the association of nailfold capillaroscopy findings with white matter lesions in preclinical CADASIL patients. Capillaroscopy guides an effective screening strategy in individuals with NOTCH3 mutations.

Dermatomyositis: nailfold capillaroscopy patterns and a general survey.

INTRODUCTION: Dermatomyositis (DM) is a group of autoimmune idiopathic inflammatory myopathies characterized by typical cutaneous signs and symptoms of muscle involvement. The diseases can be associated with cancer in the paraneoplastic syndrome, calcinosis, interstitial lung disease, other autoimmune connective tissue diseases (in overlap syndrome), and Raynaud's phenomenon. METHODS: Clinical and capillaroscopic data were gathered from 43 patients with DM. The diagnosis was based on the Bohan‒Peter and European League against Rheumatism / American College of Rheumatology (EULAR/ACR) classification criteria. In addition, nailfold capillaroscopy was performed in all patients. RESULTS: In our cohort, eight patients had overlap syndrome, six had paraneoplastic syndrome, eight presented with interstitial lung disease, and nine had calcinosis, two of whom also had a cancerous pathology. Raynaud's phenomenon was reported in 74% of patients. Upon nailfold capillaroscopy, 84% of patients presented giant capillaries, 81% ramified capillaries, and 70% both. The latter, notably giant ramified capillaries, could be considered specific for DM. The detection of prominent subpapillary venous plexuses was associated with pulmonary involvement. In contrast, alterations of the pericapillary spaces were associated with the severity and prognosis of DM. CONCLUSIONS: Our results underline the usefulness of nailfold capillaroscopy in the diagnosis and prognosis of DM. Based on the results and literature data, specific nailfold capillaroscopy features should be included in DM diagnostic criteria.

Nailfold Capillaroscopy: A Comprehensive Review on Its Usefulness in Both Clinical Diagnosis and Improving Unhealthy Dietary Lifestyles.

Since the 1970s, the utility of nailfold capillaroscopy (NFC) in diagnosing rheumatological disorders such as systemic sclerosis has been well established. Further studies have also shown that NFC can detect non-rheumatic diseases such as diabetes, glaucoma, dermatitis, and Alzheimer disease. In the past decade, nailfold capillary morphological changes have also been reported as symptoms of unhealthy lifestyle habits such as poor diet, smoking, sleep deprivation, and even psychological stress, all of which contribute to slow blood flow. Therefore, studying the relationships between the morphology of nailfold capillaries and lifestyle habits has a high potential to indicate unhealthy states or even pre-disease conditions. Simple, inexpensive, and non-invasive methods such as NFC are important and useful for routine medical examinations. The present study began with a systematic literature search of the PubMed database followed by a summary of studies reporting the assessment of morphological changes detected by NFC, and a comprehensive review of NFC's utility in clinical diagnosis and improving unhealthy dietary lifestyles. It culminates in a summary of dietary and lifestyle health promotion strategy, assessed based on NFC and other related measurements that indicate healthy microvascular blood flow and endothelial function.

"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.

Relationship between nailfold videocapillaroscopic findings and cardiovascular risk factors.

BACKGROUND: Nailfold Videocapillaroscopy (NVC) is a valuable tool in the differential diagnosis of Raynaud's phenomenon (RP), present in certain Rheumatic diseases (RD). Knowing that many people have cardiovascular risk factors (CVRF), the main objective was to demonstrate that CVRF and carotid plaques produce NVC alterations. METHODS: Cross-sectional unicentric study carried out from 2020 to 2023. Four groups were formed: subjects with RD and RP, participants with RD without RP, subjects with RP without RD and finally participants without RP or RD (study group). Each subject exhibiting CVRF presented only a single risk factor. The variables collected were: sociodemographic, CVRF (diabetes, tobacco, alcohol (ALC), obesity (OBE), dyslipidemia and arterial hypertension (AH)), diseases, RP, treatments, tortuosities and NVC alterations (ramified capillaries, enlarged capillaries, giant capillaries, haemorrhages and density loss) and carotid ultrasound (CU). RESULTS: 402 subjects were included (76 % women, mean age 51 ± 16 years), 67 % had CVRF, 50 % RP and 38 % RD. Tortuosities were present in 100 % of CVRF participants. A statistically significant association was found between the presence of CVRF and all the NVC alterations: ramified capillaries (OR = 95.6), enlarged capillaries (OR = 59.2), giant capillaries (OR = 8.32), haemorrhages (OR = 17.6) and density loss (OR = 14.4). In particular, an association was found between giant capillaries with AH (p = 0,008) and OBE (p ã€ˆ0,001), and haemorrhages and density loss with ALC and OBE (p < 0,001). On the other hand, 40 subjects presented CU plaques (9.9 %), associated with enlarged capillaries (OR = 8.08), haemorrhages (OR = 4.04) and ramified capillaries (OR = 3.01). The pathological intima-media thickness was also associated with haemorrhages (OR = 3.14). CONCLUSIONS: There is a clear association between CVRF and ultrasound atherosclerotic findings in carotid with NVC alterations. These findings are of special interest for a correct NVC interpretation and to avoid false positives in the diagnosis of primary and secondary RP.

Re-evaluation of nailfold capillaroscopy in discriminating primary from secondary Raynaud's phenomenon and in predicting systemic sclerosis: a randomised observational prospective cohort study.

BACKGROUND: Primary Raynaud's phenomenon (pRP) is difficult to distinguish from secondary (sRP). Although nailfold capillaroscopy (NFC) may detect early alterations, no universal criteria yet discriminate between pRP from sRP. OBJECTIVES: To create and validate two NFC scores that could distinguish pRP from sRP and that could predict systemic sclerosis (SSc), respectively. METHODS: We performed NFC on two separate cohorts with isolated RP, and recorded number of capillaries per field, enlarged/giant capillaries, crossed/bizarre patterns, microhemorrhages, neoangiogenesis, rarefaction, edema, blood flow velocity, stasis. By multivariate regression analysis, we evaluated the adjusted prognostic role of these features in a derivation cohort of 656 patients. Results were used to construct algorithm-based prognostic scores (A and B). These scores were then tested on a confirmation cohort of 219 patients. RESULTS: Score A was unable to discriminate sRP from pRP (low negative predictive values with high positive predictive values for any cut-point); score B was unable to discriminate progression to SSc or a SSc-spectrum disorder (low positive predictive values with high negative predictive values for lower cut-points). CONCLUSION: NFC patterns, believed as specific, showed low discriminatory power and on their own are unable to reliably discriminate sRP from pRP or predict evolution to SSc.

Improved nested U-structure for accurate nailfold capillary segmentation.

Changes in the structure and function of nailfold capillaries may be indicators of numerous diseases. Noninvasive diagnostic tools are commonly used for the extraction of morphological information from segmented nailfold capillaries to study physiological and pathological changes therein. However, current segmentation methods for nailfold capillaries cannot accurately separate capillaries from the background, resulting in issues such as unclear segmentation boundaries. Therefore, improving the accuracy of nailfold capillary segmentation is necessary to facilitate more efficient clinical diagnosis and research. Herein, we propose a nailfold capillary image segmentation method based on a U2-Net backbone network combined with a Transformer structure. This method integrates the U2-Net and Transformer networks to establish a decoder-encoder network, which inserts Transformer layers into the nested two-layer U-shaped architecture of the U2-Net. This structure effectively extracts multiscale features within stages and aggregates multilevel features across stages to generate high-resolution feature maps. The experimental results demonstrate an overall accuracy of 98.23 %, a Dice coefficient of 88.56 %, and an IoU of 80.41 % compared to the ground truth. Furthermore, our proposed method improves the overall accuracy by approximately 2 %, 3 %, and 5 % compared to the original U2-Net, Res-Unet, and U-Net, respectively. These results indicate that the Transformer-U2Net network performs well in nailfold capillary image segmentation and provides more detailed and accurate information on the segmented nailfold capillary structure, which may aid clinicians in the more precise diagnosis and treatment of nailfold capillary-related diseases.

Biomarkers of endothelial glycocalyx damage are associated with microvascular dysfunction in resuscitated septic shock patients.

BACKGROUND: Microvascular dysfunction plays a central role in organ dysfunction during septic shock. Endothelial glycocalyx (eGC) damage could contribute to impaired microcirculation. The aim was to assess whether several eGC-damaged biomarkers are associated with microvascular dysfunction in resuscitated septic shock patients. METHODS: This cross-sectional study included resuscitated septic shock patients (N = 31), and a group of healthy individuals (N = 20). The eGC damage biomarkers measured were syndecan-1 (SDC-1), soluble CD44 (CD44s), hyaluronic acid (HYAL) in blood sample; sulfated glycosaminoglycans (GAGs) in urine sample; and thrombomodulin (TBML) in blood sample as biomarker of endothelial cell damage. Microcirculation was assessed through sublingual videocapillaroscopy using the GlycoCheck™, which estimated the perfused vascular density (PVD); the perfused boundary region (PBR), an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). We defined a low MVHS (<50th percentile in septic patients) as a surrogate for more impaired microvascular function. RESULTS: The SDC-1, CD44s, TBML and GAGs levels were correlated with impaired microvascular parameters (PVD of vessels with diameter < 10 µm, MVHS and flow-adjusted PBR); p < 0.05 for all comparisons, except for GAGs and flow-adjusted PBR. The SDC-1 [78 ng/mL (interquartile range (IQR) 45-336) vs. 48 ng/mL (IQR 9-85); p = 0.052], CD44s [796ρg/mL (IQR 512-1995) vs. 526ρg/mL (IQR 287-750); p = 0.036], TBML [734ρg/mL (IQR 237-2396) vs. 95ρg/mL (IQR 63-475); p = 0.012] and GAGs levels [0.42 ρg/mg (IQR 0.04-1.40) vs. 0.07 ρg/mg (IQR 0.02-0.20); p = 0.024]; were higher in septic patients with more impaired sublingual microvascular function (low MVHS vs. high MVHS). CONCLUSION: SDC-1, CD44s, TBML and GAGs levels were associated with impaired microvascular function in resuscitated septic shock 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).

Nailfold capillaroscopy findings of a multicentric multi-ethnic cohort of patients with idiopathic inflammatory myopathies.

OBJECTIVES: To assess nailfold video capillaroscopic (NVC) abnormalities and their association with clinical features, myositis-specific autoantibodies (MSA), and myositis-associated antibodies (MAA) in a large multi-ethnic cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: We recruited 155 IIM patients from three centres in Mexico, Spain, and the USA. We evaluated the clinical and laboratory features of the patients and performed semiquantitative and quantitative analyses of the NVC. Each NVC study was defined as having a normal, non-specific, early systemic sclerosis (SSc), active SSc, or late SSc pattern. Twenty-three patients had at least one follow-up NVC when disease control was achieved. Quantitative variables were expressed as medians and interquartile range (IQR) and were compared with the Kruskal-Wallis, the Mann-Whitney U-test, and the Wilcoxon test for paired medians. Associations between qualitative variables were assessed with the χ2 test. RESULTS: Most patients were women (68.3%), Hispanic (73.5%), and had dermatomyositis (DM) (61.2%). Fourteen patients (9%) had a normal NVC. A non-specific abnormality pattern was the most frequent (53.9%), and was associated with joint involvement, interstitial lung disease, Jo1 autoantibodies, anti-synthetase syndrome, and immune-mediated necrotising myopathy. The SSc pattern was observed mostly in DM and overlap myositis and was associated with cutaneous features and anti-TIF-1g autoantibodies. After treatment, there was a decrease in the capillaroscopic score, the capillary diameter, and the number of avascular areas, and an increase in capillary density and bushy capillary number. CONCLUSIONS: NVC abnormalities are related to the diagnosis, clinical features, disease activity, and autoantibodies of patients with IIM.

Nailfold capillaroscopy abnormalities and pulmonary hypertension in mixed connective tissue disease and systemic sclerosis patients.

OBJECTIVE: Pulmonary arterial hypertension (PAH) represents an important vascular complication of mixed connective tissue disease (MCTD) and systemic sclerosis (SSc). Microvascular involvement in these diseases can be investigated by means of nailfold capillaroscopy (NFC). Microvascular involvement detected in the nailfold bed is the mirror of the microvascular damage occurring in the entire body, further indicating the involvement of the target organs. The aim of this study was to evaluate the microvascular involvement in MCTD patients with or without PAH, compared to that found in SSc patients with or without PAH. PATIENTS AND METHODS: This cross-sectional study was performed in the Department of Internal Medicine and Department of Rheumatology, Timișoara, Romania, during the time period between January 2017 and December 2022, on a group of 26 patients with MCTD and 26 SSc patients. Antinuclear antibodies, anti-U1-RNP, anti-Scl 70, anti-centromere, anti-cardiolipin antibodies (aCL) (IgM, IgG), anti-ß2-glycoprotein I (aß2GPI) (IgM, IgG) antibodies, and lupus anticoagulant (LAC) were determined in both the groups. PAH was evaluated through cardiac ultrasonography, determining the sPAP (systolic pulmonary artery pressure). Nailfold capillaroscopy was performed using a USB Digital Microscope and 2.0-megapixel digital camera recording capillaries density, giant capillaries, enlarged capillaries, capillaries hemorrhages, avascular areas, ramified/bushy capillaries scores. Data were recorded and presented as mean ± standard deviation. Statistical analyses were performed using the Student's t-test, ANOVA test, and Pearson's correlation. Differences were considered statistically significant if p-value < 0.05. RESULTS: Among the MCTD patients, PAH was identified in 12 patients (46.15%), while among the SSc patients PAH was identified in 14 patients (53.84%). Development of PAH in MCTD patients was associated with lower capillaries density (p-value < 0.00001), higher scores of giant capillaries, ramified/bushy capillaries, and capillary hemorrhages (p-value < 0.00001, for each of them). Anti-U1-RNP, aCL, aß2GPI antibodies and LAC were also found to be involved in PAH-associated MCTD development. Unlike MCTD patients, SSc patients with PAH presented with lower capillaries density and ramified/bushy capillaries scores (p-value < 0.05). CONCLUSIONS: The MCTD patients who presented significant NFC abnormalities (especially active and late scleroderma-like capillaroscopic pattern) are prone to PAH development. Capillary density reduction is the most important factor associated with the occurrence of PAH. Differences in NFC findings (especially capillary density and ramified/bushy capillaries) were detected among patients with MCTD and SSc having PAH.

Capillaroscopic differences between primary Raynaud phenomenon and healthy controls indicate potential microangiopathic involvement in benign vasospasms.

BACKGROUND: For primary Raynaud phenomenon (PRP), an otherwise unexplained vasospastic disposition is assumed. To test the hypothesis of an additional involvement of distinct ultrastructural microvascular alterations, we compared the nailfold capillary pattern of patients with PRP and healthy controls. METHODS: A total of 120 patients with PRP (with a median duration of vasospastic symptoms of 60 [IQR: 3-120] months) were compared against 125 controls. In both groups, nailfold capillaroscopy was performed to record the presence of dilatations, capillary edema, tortuous capillaries, ramifications, hemorrhages, and reduced capillary density and to determine a semiquantitative rating score. Further, the capacity of finger skin rewarming was investigated by performing infrared thermography in combination with cold provocation. RESULTS: Unspecific morphologic alterations were found in both, PRP, such as controls, whereby the risk for PRP was four times as high in the presence of capillary dilations (CI: 2.3-7.6) and five times as high if capillary density was reduced (CI: 1.9-13.5). Capillary density correlated with thermoregulatory capacity in both hands in the PRP group, but not in controls. In addition, a negative correlation between the microangiopathy score and the percentage degree of rewarming in both hands was found for patients with PRP only. CONCLUSION: We found specific differences within the microvascular architecture between patients with PRP and controls. As a conclusion, PRP may not be an entirely benign vasospastic phenomenon, but might be associated with subtle microcirculatory vasculopathy. In addition, we suggest that the implementation of a scoring system might serve as guidance in the diagnostic process at least of patients with long-standing PRP.

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.

Nailfold videocapillaroscopy in antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of illnesses that cause inflammation and alterations to small vessels in the body. Some of the most common and detrimental manifestations, including alveolar hemorrhage and glomerulonephritis, are caused by this capillary inflammation. We sought to clarify whether patients with AAV would have abnormal nailfold capillaries when evaluated with nailfold videocapillaroscopy. METHODS: Patients with a current diagnosis of AAV and a control group were identified for enrollment. Nailfold videocapillaroscopy images were used for a semiquantitative analysis on capillary density, morphology, dilation, and microhemorrhage after review by 2 rheumatologists. Disease characteristics, occurrence of recent disease flare, and presence of ANCA were recorded. RESULTS: Thirty-three patients with a diagnosis of AAV and 21 controls were recruited. The AAV group had a median age of 59 and 17 (52%) were women. Granulomatosis with polyangiitis was the most common diagnosis (19 [58%]), followed by eosinophilic granulomatosis with polyangiitis (7 [21%]) and microscopic polyangiitis (7 [21%]). Twenty-seven patients (82%) had positive ANCA tests. After assessment of capillary density, dilation, morphology, microhemorrhages, and disorganization, there were no statistically significant differences between the 2 groups. CONCLUSION: There was no evidence of differences in nailfold capillaroscopy abnormalities between those diagnosed with AAV and the control group. While this cohort was relatively small, we did not find a high enough prevalence or specific phenotype of capillary abnormalities that could aid in diagnosis or prognostication of these diseases in the clinical setting.

Analysis of microvascular pattern in diabetes mellitus condition using the nailfold capillaroscopy images.

Diabetes is often considered a vascular disease due to its impact on blood vessels, it is a complex condition with various metabolic and autoimmune factors involved. One of the long term comorbidities of diabetes includes microvascular complications. The microvascular complications can be analyzed using the Nailfold capillaroscopy, a non-invasive technique that allows for the visualization and analysis of capillaries in the proximal nailfold area. Using advanced video capillaroscopy with high magnification, capillary images can be captured from and processed to analyze their morphology. The capillary images of normal group and diabetic group are acquired from 118 participants using nailfold capillaroscopy and the obtained images are preprocessed using image processing filters. The identification and segmentation of the capillaries are the challenges to be addressed in the processing of the images. Hence segmentation of capillaries is done using morphological operations, thresholding and convolutional neural networks. The performance of the filters and segmentation methods are evaluated using Mean Square Error (MSE), Peak signal to Noise Ratio (PSNR), Structural Similarity Index Measure (SSIM), Jaccard Index and Sorensen coefficient. By analyzing the morphological features namely the capillary diameter, density, distribution, presence of hemorrhage and the shape of the capillaries from both the groups, the capillary changes associated with diabetic condition were studied. It was found that the non diabetic participants considered in this study has capillary diameter in the range of 8-14 µm and the capillary density in the range of 10-30 capillaries per mm2 whereas the diabetic participants has capillary diameter greater than 30 µm and the capillary density is less than 10 capillaries per mm2. In addition to capillary density and diameter, the presence of hemorrhage, the orientation and distribution of the capillaries are also considered to differentiate the diabetic group from the non diabetic group. The classification of the participants are validated with the clinical history of the participants.

Microvascular status in juvenile Sjögren's disease: the first nailfold videocapillaroscopy investigation.

INTRODUCTION: Juvenile Sjögren's disease (jSjD) is a rare autoimmune disease characterized by exocrine gland involvement and systemic manifestations, including small vessel vasculitis and Raynaud's phenomenon (RP). We aimed to investigate the microvascular status in jSjD patients by nailfold videocapillaroscopy (NVC) and the potential correlations with clinical and serological features. METHODS: Clinical data from thirteen consecutive jSjD patients (11 females and 2 males), with a mean age of 16 ± 4 years, diagnosed before 16 years of age (mean age at diagnosis 12 ± 3) according to the 2016 American College of Rheumatology/EULAR criteria for adult SjD, were collected including age- and sex-matched healthy controls (HCs). Clinical, laboratory, and instrumental data were collected, together with NVC examination. Non-specific and specific NVC parameters were investigated, such as capillary density, capillary dilations, giant capillaries, microhaemorrhages and abnormal shapes. Associations between NVC findings and clinical/serological features were explored and analysed using parametrical and non-parametrical tests. RESULTS: Capillary density reduction correlated significantly with articular involvement (arthralgias) (p = 0.024). Microhaemorrhages correlated with lower C3 levels (p = 0.034). No specific NVC pattern for jSjD was identified, whereas abnormal capillary shapes were significantly higher in jSjD patients than HCs (p = 0.005). NVC abnormalities were not associated with SjD-specific instrumental tests (biopsy, imaging, Schirmer's test). RP was present in 8% of jSjD patients. CONCLUSIONS: The reduction of capillary density, as well as microhaemorrhages at NVC analysis, are significantly associated with some clinical aspects like articular involvement and serum biomarkers (C3 reduction). The NVC is suggested as safe and further analysis in jSjD patients.

Treatment with mycophenolate mofetil is associated with improved nailfold vasculature in systemic sclerosis.

OBJECTIVE: To investigate the evolution of nailfold capillary density in patients with SSc in relation to immunosuppressive treatment and autoantibodies. METHODS: This was a prospective study cohort. Consecutive newly diagnosed SSc patients were included into this study who, in a retrospective review, had at least two nailfold capillary microscopy measurements performed during the first 48 months of follow-up. Capillary density per 3 mm was measured with widefield nailfold capillary microscopy. Improvement of capillary density per finger and mean capillary density were analysed. Longitudinal measurements of mean capillary density were analysed by generalized estimating equation. RESULTS: Eighty patients (68 women, 12 men) met the inclusion criteria. The median follow-up time was 27 months. Twenty-eight patients had an improved capillary density in per-finger analysis. MMF was associated with fewer numbers of fingers that had worsened in capillary density. Anti-topoisomerase antibodies were associated with low mean capillary density. Anti-RNA polymerase III antibodies were associated with improvement and anti-centromere antibodies with worsening of capillary density in per-finger analysis. MMF treatment was associated with less steep capillary density decline in a moderated generalized estimating equation model including presence of anti-topoisomerase antibodies and the interaction of MMF with follow-up time. CONCLUSION: Nailfold capillary density improved over time in a substantial proportion of SSc patients. MMF treatment had a positive impact on the evolution of capillary density in these patients. SSc autoantibody phenotype may affect the capillary density development. The data support previous hypotheses that early immunosuppression may favourably affect vascular regeneration in SSc.

Microvascular changes on nailfold capillaroscopy in acute stage of Kawasaki disease: a new diagnostic paradigm for an enigmatic condition.

OBJECTIVES: Kawasaki disease (KD) is a medium vessel vasculitis with a predilection to involve coronary arteries. However, there is a paucity of literature on microvascular changes in patients with KD. METHODS: Children diagnosed with KD based on American Heart Association guidelines 2017 were enrolled prospectively. Demographic details and echocardiographic changes in coronaries were recorded. Nailfold capillaries were assessed using Optilia Video capillaroscopy and data were analysed using Optilia Optiflix Capillaroscopy software at acute (prior to IVIG administration) and subacute/convalescent phase. RESULTS: We enrolled 32 children with KD (17 boys) with a median age of 3 years. Nailfold capillaroscopy (NFC) was performed in 32 patients in the acute phase (compared with 32 controls) and in 17 during the subacute/convalescent phase at a median follow-up of 15 (15-90) days after IVIG treatment. The following findings were seen in NFC in the acute phase of KD: reduced capillary density (n = 12, 38.6%), dilated capillaries (n = 3, 9.3%), ramifications (n = 3, 9.3%) and capillary haemorrhages (n = 2, 6.2%). Capillary density was reduced significantly in the acute phase of KD (38.6%) as compared with the subacute/convalescent phase (25.4%) (P-value <0.001) and controls (0%) (P-value = 0.03). We observed no correlation between coronary artery involvement and mean capillary density (P = 0.870). CONCLUSION: Results show that patients with KD have significant nailfold capillary changes in the acute phase. These findings may provide a new diagnostic paradigm for KD and a window to predict coronary artery abnormalities.