Capillaroscopic Pattern Research Articles

Disturbed microcirculation in the hands of patients with systemic sclerosis detected by fluorescence optical imaging: a pilot study

BackgroundUtilising fluorescence optical imaging (FOI), the distribution of an intravenously applied colouring agent indocyanine green (ICG) can be analysed with the potential to identify malperfusion by little to no tissue enhancement. Systemic sclerosis (SSc) is characterised by the presence of digital ulcers reflecting progressive vasculopathy.The objective was to investigate the potential of FOI in the detection of disturbed microcirculation in the hands and fingers of patients with SSc and to link FOI findings to clinical signs of ischemia such as digital ulcers and pitting scars.MethodsIn this cross-sectional study, 63 patients with SSc and 26 healthy subjects were examined. FOI was performed in all 89 individuals and compared to clinical data and capillaroscopic findings assembled for the SSc cohort.ResultsHealthy subjects showed initial ICG signals in their fingertips in 93.6%, SSc patients in 78.5% (limited SSc) and 43.2% (diffuse SSc). Moreover, in SSc patients, FOI findings were significantly associated with a late capillaroscopic pattern, disseminated SSc features, a diffuse SSc subtype, and the presence of digital ulcers or pitting scars. Intra- and inter-reader reliability for FOI amounted to κ = 0.786 and κ = 0.834, respectively.ConclusionsFOI is able to detect areas of reduced microcirculation in patients with SSc with high association to capillaroscopic findings. The results pave the way for future FOI investigations into its role in the prediction of complications due to an impaired acral perfusion.

Is there an association between glaucoma and capillaroscopy in patients with systemic sclerosis?

To evaluate the relationship between glaucoma diagnosis and the nailfold capillaroscopy pattern in patients with systemic sclerosis. An observational study in a cohort of patients with SSc was conducted. Patients with at least one nailfold videocapillaroscopy and one ophthalmology examination at the same year were included. Data collected were: age, sex; type of systemic sclerosis according to the degree of skin impairment, self-reported ethnicity, disease duration, current use and dosage of systemic corticosteroid, current use and dosage of bosentan®, intraocular pressure, central corneal thickness, diagnosis of glaucoma and capillaroscopy pattern. Thirty-one patients with systemic sclerosis were enrolled, 23% had glaucoma. There was no statistically significant association between glaucoma diagnosis and the capillaroscopic pattern (p=0.86). There was also no significant difference (p=0.66) regarding intraocular pressure between patients with mild (13.9±3.8mmHg) and severe capillaroscopic pattern (14.4±2.8mmHg). The odds ratio of glaucoma for severe capillaroscopic pattern compared to mild was 1.6 (95% confidence interval: 0.3-9.5). Up to 23% of patients with SSc have glaucoma. The high prevalence of glaucoma in SSc suggests a possible systemic vascular disturbance as the cause. However, there seems to be no significant association between the capillaroscopy pattern and glaucoma in systemic sclerosis. Further research is required to improve the understanding of glaucoma in the context of systemic sclerosis.

Coexistence of diabetes mellitus type 1 with diffuse systemic sclerosis - case report and literature review.

Diabetic sclerodactyly is a frequently recognized skin finding that may occur in patients with diabetes mellitus but coexistence of diabetes and systemic sclerosis is rare. We describe a case of coexistence of type 1 diabetes mellitus and systemic sclerosis in 42-year-old man with the history of Raynaud’s phenomenon, progressive diffuse hardening of the skin and sclerodactyly, slowly worsening with time. The medical history included type 1 diabetes since childhood with microvascular complications. The patient presented a typical capillaroscopic scleroderma-like pattern, antinuclear antibodies and sclerotic lesions in gastrointestinal system. Summing up, our case represents the rare coexistence of autoimmune diseases like diabetes mellitus type 1 and systemic sclerosis.

Detection of early endothelial damage in patients with Raynaud's phenomenon

ObjectivesRaynaud's phenomenon (RP) can be the first manifestation of systemic sclerosis (SSc) or other connective tissue diseases (CTDs), often preceding an overt disease by years. It is not known if markers of endothelial damage are detectable in those RP patients who subsequently develop a CTD. MethodsWe studied 82 RP patients at their first evaluation to correlate the levels of endothelial markers with the subsequent development of an overt disease 36months later. We measured plasma levels of tissue-type plasminogen activator (t-PA) and von Willebrand factor (vWF), two markers of endothelial damage, and interleukin-6 (IL-6), a pro-inflammatory cytokine. Thirty sex- and age-matched healthy subjects (HS) served as controls. ResultsAt baseline, 67 patients showed capillaroscopic normal pattern (CNP) and 15 patients, of which 11 were very early SSc, had capillaroscopic scleroderma pattern (CSP). Plasma levels of t-PA, vWF and IL-6 were higher in patients with CNP (p=0.0001) than in HS and even much higher in patients with CSP (p=0.0001). In patients with CNP and RP of recent onset (<18months), vWF plasma levels were higher when autoantibodies were present (p=0.020). After 36months, among 48 RP patients with CNP who remained in follow-up, 24 were diagnosed as primary and 24 as secondary RP. In secondary RP, basal levels of t-PA, IL-6 and particularly vWF were higher than in primary RP (p=0.005, p=0.004, p=0.0001 respectively) and HS (p=0.0001 for all). ConclusionsOur findings indicate that markers of endothelial damage are elevated in RP patients who subsequently develop SSc or other CTDs, even in the absence of capillaroscopic abnormalities.

Nailfold digital capillaroscopic findings in patients with diffuse and limited cutaneous systemic sclerosis

BackgroundSystemic sclerosis (SSc) is a chronic disease with microvascular damage. Nailfold capillaroscopy is a non-invasive method used for evaluating capillaries in SSc. Its findings could be related to the internal organ involvement and SSc course. In this study, we aimed to determine the association of the capillaroscopic patterns of nailfold capillaries with the disease subtypes of SSc, disease duration, and clinical manifestations.Material and methodsSeventy patients with SSc (15 cases with diffuse cutaneous SSc [DcSSc] and 55 patients with limited SSc [LcSSc]) were studied. The patients were classified into early and intermediate/late DcSSc and LcSSc regarding their disease duration. The capillaroscopy findings were classified into normal, ‘early’, ‘active’ and ‘late’ scleroderma patterns, and ‘non-specific’ changes. The association of the nailfold capillaroscopy changes and their components with clinical manifestations was also studied.ResultsWe studied 15 DcSSc and 55 LcSSc patients. No association was found between the patterns of capillaroscopic changes and these subtypes. There were 8 early DcSSc, 7 intermediate/late DcSSc, 34 early LcSSc, and 21 intermediate/late LcSSc patients. In patients with LcSSc, the ‘early’ scleroderma pattern of capillaroscopy was associated with early disease based on duration. We found a direct association between some capillary components and some clinical findings. Also, some capillaroscopic components had an inverse association with some clinical manifestations.ConclusionsWe found no association between the patterns of capillaroscopy and SSc subtypes; early scleroderma pattern of capillaroscopy was significantly associated with early LcSSc, compatible with the slower course of the disease in LcSSc. Subtle changes, capillary elongation, and capillary tortuosity had an inverse association with clinical manifestations and might be considered as good prognostic factors.

EXCELLENT RELIABILITY OF SEMI-QUANTITATIVE NAILFOLD CAPILLAROSCOPY IN PATIENTS WITH SYSTEMIC SCLEROSIS – A PILOT STUDY

Background. Semi-quantitative nailfold capillaroscopy (NFC) scoring represents a promising tool for assessing disease activity, severity and change in systemic sclerosis (SSc), however there is no consensus yet over which capillaroscopy abnormalities should be analyzed and how. Objective. Investigation of the reliability of the qualitative and semi-quantitative scoring of NFC assessment between two raters and test-retest for each rater in a SSc cohort. Methods. This is a single-center pilot study where 2 raters assessed the NFC images of 48 consecutive patients with SSc. Data were analyzed in 3 ways: 1. qualitatively by “normal”/“abnormal” category; 2. qualitatively by the following categories: “early”, “active”, “late” SSc patterns, “normal”, and unclassifiable in any pattern, and step; 3. Semi-quantitatively by calculating the mean score for capillary loss, disorganization of the microvascular array, giant capillaries, microhaemorrhages and capillary ramifications and combinations of giant capillaries and microhaemorrhages (as a surrogate for vascular activity). Disorganization and ramifications (surrogate for vascular damage) were also assessed. Variables for all steps were calculated for all fingers and for each finger. Inter-rater/intra-rater agreement was assessed by Cohen’s kappa coefficients for qualitative variables and by intraclass correlation coefficients (ICC) for mean score values of abnormalities. Results. Inter-rater reliability ranged from good to excellent agreement for mean score values of abnormalities in all fingers (ICC coefficients 0.745 to 0.897) and was excellent for activity (ICC coefficient of 0.923) and damage combinations (ICC coefficient of 0.918). Assessment of abnormalities in a qualitative manner (normal/abnormal or with capillaroscopy patterns) showed weaker inter-rater agreement than the semi-quantitative assessment (k coefficient &lt;0.7). Intra-rater variability was good to excellent for mean score values of abnormalities and activity and damage combinations in all fingers and separate fingers for both raters; for qualitative assessment, only one of the raters had good test-retest reliability. Conclusion. Reliability of NFC assessment is essential in SSc trials/clinical practice to ensure quality of data. This pilot study demonstrates very good reliability between raters of the semi-quantitative NFC assessment in a SSc cohort. Combinations of NFC abnormalities had very good reliability and might be preferred because they are less time consuming.

Prevalence of Systemic Sclerosis in Primary Biliary Cholangitis Using the New ACR/EULAR Classification Criteria.

Systemic sclerosis (SSc) is a well-established disease associated with primary biliary cholangitis (PBC). However, the original 1980 American College of Rheumatology (ACR) criteria have poor sensitivity, especially for the detection of earlier SSc in previous studies. The objective was to evaluate the prevalence of SSc in patients with PBC using more sensitive 2001 LeRoy and Medsger criteria and the 2013 ACR/European League Against Rheumatism (EULAR) classification criteria. The secondary objective was to evaluate the frequency of individual clinical features. One hundred consecutive patients with PBC without previously diagnosed SSc were recruited between 2005 and 2007 from a tertiary care gastroenterology clinic. All patients underwent a complete clinical examination, determination of SSc-specific antibodies, and a nailfold capillary microscopy. Fulfillment of the 3 different criteria sets was analyzed, along with individual disease features. Of 100 patients with PBC, 1% met the ACR 1980 criteria, 22% met the 2001 LeRoy and Medsger criteria for early SSc, and 17% the 2013 ACR/EULAR criteria. Raynaud phenomenon, SSc-related antibodies, and SSc capillaroscopic patterns were the most prevalent findings, with the highest sensitivities to help guide future screening. Our data show a high prevalence of SSc in patients with PBC with probable underestimation by previous studies using the original ACR criteria. Comorbid SSc should be actively searched for based on newly described criteria to improve detection and increase benefits of earlier treatment.

Capillaroscopy in systemic sclerosis: A narrative literature review

Abstract Nailfold capillaroscopy is relatively little known tool outside the areas of rheumatology and dermatology. It is used to observe the shape, number and organization of the capillaries in the nail bed. It has not been widely used in the past, partly as it required specialized training and equipment, as well as the poor standardization of this diagnostic method. However, in recent years, thanks to renewed interest and research effort of the academic community, these problems have been able to be overcome, turning capillaroscopy into real resource for the study of microcirculation, being especially useful in differentiating primary from secondary Raynaud's phenomenon. These benefits have enabled capillaroscopy to gain importance in the rheumatology field, specifically in the early diagnosis of systemic sclerosis, a disease with significant microcirculation involvement, where the change in capillaroscopy pattern also helps to predict the onset of complications, such as digital ulcers and organ compromise.

Nailfold capillaroscopy microscopy - an interdisciplinary appraisal.

Nailfold capillaroscopy is a method of great diagnostic value in the differential diagnosis of primary versus secondary Raynaud´s phenomenon, of systemic sclerosis versus other so called connective tissue diseases and of additional diagnostic value in other entities. Rheumatologists, dermatologists, and angiologists in Germany have convened in an interdisciplinary working group in which they synergistically combined their expertise to develop a common nomenclature and standards for the technical performance of nailfold capillary microscopy. The article gives an overview of historical and technical aspects of capillaroscopy, morphologic findings, and disease-specific patterns. It also provides a critical appraisal of its significance in the diagnosis and sequelae of these interdisciplinarily-managed diseases including its performance in children and gives an excursion in the potential perspectives of capillaroscopy in less common indications.

Capilaroscopia en esclerosis sistémica: una revisión narrativa de la literatura

Nailfold capillaroscopy is relatively little known tool outside the areas of rheumatology and dermatology. It is used to observe the shape, number and organisation of the capillaries in the nail bed. It has not been widely used in the past, partly as it required specialised training and equipment, as well as the poor standardisation of this diagnostic method. However, in recent years, thanks to renewed interest and research effort of the academic community, these problems have been able to be overcome, turning capillaroscopy into real resource for the study of microcirculation, being especially useful in differentiating primary from secondary Raynaud's phenomenon. These benefits have enabled capillaroscopy to gain importance in the rheumatology field, specifically in the early diagnosis of systemic sclerosis, a disease with significant microcirculation involvement, where the change in capillaroscopy pattern also helps to predict the onset of complications, such as digital ulcers and organ compromise.

Absence of Scleroderma pattern at nail fold capillaroscopy valuable in the exclusion of Scleroderma in unselected patients with Raynaud's Phenomenon.

BackgroundTo report the predictive value of nail-fold capillaroscopy (NFC) patterns of vasculopathy for systemic sclerosis (Scleroderma; SSc) in an unselected cohort of patients with Raynaud’s phenomenon (RP).MethodsPatients referred to a tertiary SSc clinic with RP were evaluated by light/video-NFC. Clinical diagnosis, details and serology were recorded. Primary RP was defined as RP with no features of connective tissue disease (CTD)/antibody. NFC patterns were determined: normal, non-specific, ‘early’, ‘active’ or ‘late’ SSc patterns. Fulfilment of the VEDOSS or 2013 ACR/EULAR criteria for SSc was determined following NFC assessment.ResultsThree hundred forty-seven patients were referred: mean (SD) age 47 (15.2) years. On clinical review, 54 (16 %) did not have RP, 69 (20 %) had primary RP, 52 (15 %) had SSc and 172 (50 %) had secondary RP. NFC SSc pattern was detected in 80 (23 %) patients; 37/52 with SSc, 30/172 with secondary RP, 9/69 with primary RP and 4/54 with no RP. For identifying patients who met either the VEDOSS or 2013 ACR/EULAR criteria for SSc, detection of a SSc NFC pattern had a sensitivity of 71 %, specificity 95 %, positive predictive value 84 % and negative predictive value 90 %.ConclusionsThe absence of SSc NFC pattern in patients with RP or suspected CTD is very valuable in the exclusion of SSc.

The Place of Nailfold Capillaroscopy Among Instrumental Methods for Assessment of Some Peripheral Ischaemic Syndromes in Rheumatology.

Micro- and macrovascular pathology is a frequent finding in a number of common rheumatic diseases. Secondary Raynaud's phenomenon (RP) is among the most common symptoms in systemic sclerosis and several other systemic autoimmune diseases including a broad differential diagnosis. It should be also differential from other peripheral vascular syndromes such as embolism, thrombosis, etc., some of which lead to clinical manifestation of the blue toe syndrome. The current review discusses the instrumental methods for vascular assessments. Nailfold capillaroscopy is the only method among the imaging techniques that can be used for morphological assessment of the nutritive capillaries in the nailfold area. Laser-Doppler flowmetry and laser-Doppler imaging are methods for functional assessment of microcirculation, while thermography and plethysmography reflect both blood flow in peripheral arteries and microcirculation. Doppler ultrasound and angiography visualize peripheral arteries. The choice of the appropriate instrumental method is guided by the clinical presentation. The main role of capillaroscopy is to provide differential diagnosis between primary and secondary RP. In rheumatology, capillaroscopic changes in systemic sclerosis have been recently defined as diagnostic. The appearance of abnormal capillaroscopic pattern inherits high positive predictive value for the development of a connective tissue disease that is higher than the predictive value of antinuclear antibodies. In cases of abrupt onset of peripheral ischaemia, clinical signs of critical ischaemia, unilateral or lower limb involvement, Doppler ultrasound and angiography are indicated. The most common causes for such clinical picture that may be referred to rheumatologic consultation are the antiphospholipid syndrome, mimickers of vasculitides such as atherosclerosis with cholesterol emboli, and neoplasms.

Digital ischaemia during cooling is independently related to nailfold capillaroscopic pattern in patients with Raynaud's phenomenon.

The aim of the study was to assess the association between plethysmographically measured vasospasms during stepwise cooling and recovery, as an index for digital ischaemia, and nailfold capillaroscopic pattern (NCP) severity in patients with primary or secondary RP, including SSc. In 381 consecutive patients with suspected RP without a history of digital ulcers, NCP (assessed by widefield videocapillaroscopy), fingertip photoelectric plethysmography during cooling and recovery and clinical characteristics were analysed. NCPs were graded as follows: normal, non-specific, early and active. The mean ischaemic time was defined as the mean time of perfusion loss during cooling and recovery of five fingers. In the patients with loss of perfusion during cooling and recovery, the NCP was normal in 152, non-specific in 96, early in 61 and active in 39 patients. The mean ischaemic time was positively associated with the severity of NCP, with P < 0.05 for each two- or three-grade increase and independent of underlying SSc. The difference was most pronounced during recovery. We demonstrate that the degree of vasospasm and ischaemia provoked by stepwise cooling and recovery are positively associated with NCP in patients with RP of different aetiologies and without a history of digital ulcers.

Post-occlusive reactive hyperaemia (POHR) in systemic sclerosis: very early disease (VEDOSS) represents a separate entity compared to established disease

Objectives: Vascular involvement is a key feature of systemic sclerosis (SSc). Vascular changes are central to the pathogenesis of the disease and the assessment of vascular involvement has a prognostic value. This assessment therefore has a pivotal role in the management of SSc patients. The aim of our study was to evaluate post-occlusive reactive hyperaemia (PORH) in consecutive SSc patients and to test whether a PORH test might be a useful tool for the early diagnosis of SSc.Method: Between April 2011 and April 2015, 60 consecutive SSc patients (mean age 56 ± 15 years, females:males = 18:1) were enrolled in the study. The patients were divided into those with full-blown SSc (n = 50) and those with very early diagnosis of SSc (VEDOSS) (n = 10) according to the literature. Laser speckle contrast analysis (LASCA) was used to assess PORH.Results: A statistically significant difference was detected in the post-ischaemic hyperaemic peak flow between VEDOSS and established SSc (424% vs. 137%, p = 0.0011). PORH peak flow decreased according to the capillaroscopic pattern (early = 419%, active = 163%, late = 145%, p = 0.0027). Moreover, a correlation between capillary density and peak flow was revealed (rho = 0.33, p < 0.01).Conclusions: These data show a different pattern of vascular involvement in VEDOSS compared to established disease that mirrors capillaroscopic changes. Functional features of very early and established disease seem to be the physiological counterpart of abnormalities detected by capillaroscopy. The POHR test might be a useful aid for further characterization of vascular involvement in SSc. In particular, blunted POHR might prove a tool to separate pre-clinical from full-blown SSc.

Quantitative Alterations of Capillary Diameter Have a Predictive Value for Development of the Capillaroscopic Systemic Sclerosis Pattern.

To quantify earlier capillary diameter abnormalities, observed by nailfold videocapillaroscopy (NVC), in primary Raynaud phenomenon (PRP) subjects compared with RP subjects later evolved to systemic sclerosis (SSc)-associated secondary Raynaud phenomenon (SRP). There were 6112 NVC images of 191 subjects analyzed at baseline and after a mean followup of 42.77 ± 35.80 months. We selected 48 patients affected by SRP and 143 matched controls confirmed with PRP. The diameter of the most dilated limbs (arterial, venous, and apical) was measured in 16 images per subject. Statistical analysis was performed using nonparametric tests. The threshold values for capillary diameters associated with the development of SSc-associated SRP were determined through receiver-operating characteristic curves. Mean capillary diameter values were significantly different for arterial, venous, and average diameters (mean value of arterial, venous, and apical) between patients with PRP and SRP (p < 0.0001). These alterations were found to be independent predictors for disease development (p = 0.015). Threshold values of 30 µm (area under the curve = 0.802, sensitivity/specificity = 0.85/0.63) to 31 µm were identified for average, arterial, and venous diameters, with a shortening effect on time to disease development. The study showed that capillary diameter is an independent predictor for development of SSc-associated SRP. Progression to SRP is unlikely for subjects affected by RP when average capillary diameter is under 30 μm. Subsequently, the execution of the qualitative/quantitative integrated analysis should be part of the NVC followup of RP subjects.

Usefulness of Α-Lipoc Acid, Leucoselect and Ginkgoselect Phytosoma in Chronic Venous Insufficiency

Background: Chronic venous insufficiency (CVI) is a frequent pathology that affects quality of life of the patients due to several symptoms such as pain, leg cramps, aching and itch. Our scope was to verify the usefulness of a supplement based on α-lipoc acid, Leucoselect® and Ginkgoselect® phytosome in patients with CVI. Methods: From July to November 2015, 30 consecutive patients with CVI received once a day a tablet containing the supplement for a period of 4 weeks. A control group of 30 subjects taking placebo and matched for CVI class, age and sex was also recruited. Clinical evaluation using VCSS and microcirculatory assessment with perimalleolar capillaroscopy were performed. A questionnaire consisting of two questions investigating presence of pain and itch/ paraesthesia was also given to the patients. Each question was scored on a dichotomous Likert scale (0=no; 1=yes). Results: A significant reduction of VCSS from baseline to 4-weeks was observed in the group of treatment respect to control group (2.70 ± 0.95 vs 0.93 ± 0.74 and 2.87 ± 0.86 vs 2.60 ± 0.81, p<0.0001). Itch and paresthesias resolved in 86.7% of patients vs 26.7% of control (p<0.0001) while leg pain improved in 70% of cases vs 23.3% of control (p<0.001). No significant changes were found between baseline and 4-weeks capillaroscopic pattern in both groups. Conclusions: After 4-weeks of treatment with α-lipoc acid, leucoselect and ginkgoselect phytosoma we observed clinical improvement of CVI symptoms, especially itch and paresthesias.

Combination therapy with Bosentan and Sildenafil improves Raynaud's phenomenon and fosters the recovery of microvascular involvement in systemic sclerosis.

The aim of this study was to evaluate in systemic sclerosis (SSc) retrospectively the effect of Bosentan and Sildenafil and their combination on Raynaud's phenomenon (RP), function, and capillaroscopic patterns. One hundred and twenty-three SSc patients (mean age ± sd, 57.69 ± 14.07 years) were retrospectively evaluated and divided into two groups according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification score: group 1 score < 10, group 2 score > 10. Each group was divided into three subgroups according to treatment: Bosentan, Sildenafil, and Bosentan + Sildenafil. Nailfold videocapillaroscopy (NVC), Scleroderma Health Assessment Questionnaire (SHAQ) and Raynaud Condition Score (RCS) were performed at baseline and after 3 and 6 months. In Bosentan (29 patients: 12, group 1; 17, group 2), NVC changed significantly in both groups, after 3 and 6 months (p = 0.00439, group 1; p = 0.00035, group 2). In group 1, the "active" and the "late" patterns reduced, and the "aspecific" increased. In group 2, there was a reduction of late patterns, a worsening of SHAQ (p < 0.005) and an improvement of RCS (p = 0.00014). In Sildenafil (63 patients: 35, group 1; 28, group 2), after 3 months, NVC patterns changed significantly in both groups(p = 0.042 group 1, p = 0.00089 group 2). In group 1, the late and early patterns increased, and the aspecific decreased. In group 2, a significant change of NVC pattern was observed also after 6 months (p = 0.00089): the late pattern increased while the active one reduced. After 6 months, SHAQ was significantly reduced in group 1 (p = 0.00027) and in group 2 (p = 0.0043). RCS improved in both groups (p = 0.0042, group 1; p = 0.0016, group 2). Combination therapy (Bosentan + Sildenafil) (31 patients: 14, group 1; 17, group 2) induced significant changes on NVC only in group 1 after 3 (p = 0.00256) and 6 months (p = 0.000349) with a reduction of the late and active patterns and an increase of the early pattern. In both groups, after 6 months, SHAQ (p < 0.05, group 1; p = 0.00049, group 2) and RCS significantly reduced (group 1, p = 0.00024; group 2, p = 0.0021). Patients treated with Bosentan + Sildenafil show a significant improvement of RCS and NVC. This combination therapy may exert a vascular activity achieving an amelioration of the structure of microvasculature in SSc.

Assessment of nailfold capillaries with a handheld dermatoscope may discriminate the extent of organ involvement in patients with systemic sclerosis.

To investigate whether nailfold capillaroscopy (NFC) patterns assessed through an in-office handheld dermatoscope may reflect the extent of disease severity in systemic sclerosis (SSc). NFC patterns were evaluated with a non-contact, polarized light dermatoscope in 40 consecutive patients with SSc and graded in sequence as 0 = normal, 1 = early, 2 = active, or 3 = late patterns. Disease severity was measured according to a modified Medsger severity scale (MSS). For comparisons, patients were grouped in tertiles according to disease severity, and a numerical correlation between the NFC patterns and the composite MSS score was assessed. Twenty patients had normal or early NFC patterns, most of them (17 individuals, 85 %) having low to moderate disease severity. In contrast, 18 out of 20 (90 %) patients with active or late NFC patterns had moderate to high disease severity. Accordingly, patients with normal/early NFC patterns had a median MSS score of 4 (interquartile range (IQR), 3-5) as compared with 7 (4-8; P = 0.02) in those with active/late patterns. A Spearman's rho coefficient of 0.45 (95 % CI, 0.15-0.67; P = 0.003) was found between the graded scale of NFC patterns and the composite MSS score. A handheld dermatoscope is useful to visualize the NFC patterns in SSc patients, and it is efficient enough to reflect the extent of disease severity.

In systemic sclerosis prolonged QTc interval is associated with reduced exercise tolerance

In systemic sclerosis (SSc) primary cardiac involvement may manifest as fibrosis of the conduction system, myocardial and pericardial involvement, arrhythmias, pacemaker and intracardiac defibrillator implantation, sudden death and autonomic dysfunction [ 1 Lambova S. Cardiac manifestations in systemic sclerosis. World J Cardiol. 2014; 6: 993-1005 Crossref PubMed Google Scholar , 2 Gigante Rosato E. Liberatori M. et al. Autonomic dysfunction in patients with systemic sclerosis: correlation with intrarenal arterial stiffness. Int J Cardiol. 2014; 177: 578-580 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ]. Recently, QTc interval prolongation was found in SSc patients without clinical cardiac involvement and in the absence of echographic abnormalities. In fact, in SSc patients has been observed that QTc interval prolongation correlate with capillaroscopic pattern, with digital ulcers and with skin thickening score [ [3] Rosato E. Gigante A. Liberatori M. et al. QTc interval prolongation in systemic sclerosis: correlations with clinical variables. Int J Cardiol. Mar 1 2015; 182: 20-22 Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar ]. Also, Rosato et al. showed in a cohort of SSc patients without cardiac and pulmonary involvement, a high prevalence of reduced exercise tolerance [ [4] Rosato E. Romaniello A. Magrì D. et al. Exercise tolerance in systemic sclerosis patients without pulmonary impairment: correlation with clinical variables. Clin Exp Rheumatol. 2014; 32 (S-103-8) PubMed Google Scholar ], while Gigante et al. for the first time have demonstrated that a correlation exists between increased intrarenal stiffness and pulmonary vasculopathy characterized by impairment of blood flow during exercise [ [5] Gigante A. Romaniello A. Magrì D. et al. Correlation between intrarenal arterial stiffness and exercise tolerance in systemic sclerosis patients without renal and cardiopulmonary impairment: the role of the microvascular damage. Int J Cardiol. 2015; 15: 122-124 Abstract Full Text Full Text PDF Scopus (6) Google Scholar ]. Accordingly, the aim of the present study is to assess QTc prolongation in SSc and evaluate correlations with cardiopulmonary exercise test (CPET) in patients without pulmonary and cardiac involvement.

T and NK Cell Phenotypic Abnormalities in Systemic Sclerosis: a Cohort Study and a Comprehensive Literature Review.

Scleroderma (SSc) is a rare and heterogeneous immune-mediated disease involving the connective tissue and microvasculature whose pathogenesis remains unclear. Data concerning T and natural killer (NK) cell abnormalities and cytokine levels in the peripheral blood (PB) from patients with SSc are scarce, and the results are contradictory. The present study aimed to analyze the changes of T lymphocytes, NK cells, and T helper (Th)-related cytokines in the PB of patients with SSc in comparison to healthy individuals and its relation to disease subtype and stage, organ involvement, and nailfold capillaroscopic changes. A non-random convenience sample of 57 scleroderma patients was utilized. Fifty-five out of the 57 patients studied were women (97 %); 10 patients presented pre-scleroderma (pre-SSc) and 47 SSc: 34 limited cutaneous SSc (lcSSc) and 13 diffuse cutaneous SSc (dcSSc). Patients with SSc were classified in early (n = 7), intermediate (n = 10), and late (n = 30) disease. Blood samples were analyzed by flow cytometry for total T cells, CD4+ and CD8+ T cell subsets, total NK cells, and CD56+low and CD56+high NK cell subsets. T cells were further analyzed for the expression of the CD56 adhesion molecule and activation-related markers (HLA-DR, CD45RO). In addition, the serum levels of Th1-, Th2-, and Th17-related cytokines were measured by flow cytometry. Twenty-five healthy individuals recruited from the blood bank were used as controls. Patients had lower numbers of total lymphocytes and T cells comparing to healthy controls. Both CD4+ and CD8+ T cells were decreased, but differences were statistically significant only for CD8+ and CD8+ CD45RO+ T cells. These alterations were seen in patients with SSc but not in patients with pre-SSc, and, in general, they were more pronounced in patients with dcSSc than in patients with lcSSc, in patients with vascular involvement than in those without, as well as in patients having active and late nailfold capillaroscopic patterns. CD56+ T cells were also decreased in SSc patients, especially in those with active/late capillaroscopic patterns or with severe lung disease. Diminished numbers of circulating NK cells were also observed in patients with lcSSc and in those with early disease. No statistically significant changes were found in serum cytokine levels, as compared with controls. Patients with SSc had major alterations in circulating CD8+ and CD56+ T cells, as well as in NK cells, suggesting that these cells may play a relevant role in SSc pathogenesis, probably operating at different phases and/or at different organs. In addition, the serum levels of Th1, Th2, and Th17 cytokines did not provide useful information for evaluating T cell polarization in SSc.