Correlations between skin blood perfusion values and nailfold capillaroscopy scores in systemic sclerosis patients

doi:10.1016/j.mvr.2016.02.007

Microvascular Research

Volume 105, May 2016, Pages 119-124

https://doi.org/10.1016/j.mvr.2016.02.007 Get rights and content

Highlights

•
Blood perfusion is reduced in SSc patients only in those areas usually affected by Raynaud's phenomenon.
•
SSc patients blood perfusion correlates with the severity of nailfold microvascular damage
•
The low perfusion observed in these areas supports the higher risk and prevalence of local digital ulcers in SSc patients

Abstract

Objectives

To correlate blood perfusion (BP) values assessed by laser speckle contrast analysis (LASCA) in selected skin areas of hands and face with nailfold capillary damage scores in systemic sclerosis (SSc) patients.

Methods

Seventy SSc patients (mean SSc duration 6 ± 5 years) and 70 volunteer healthy subjects were enrolled after informed consent. LASCA was performed at different areas of the face (forehead, tip of nose, zygomas and perioral region) and at dorsal and volar regions of hands. Microvascular damage was assessed and scored by nailfold videocapillaroscopy (NVC) and the microangiopathy evolution score (MES) was calculated.

Results

SSc patients showed a significantly lower BP than healthy subjects at fingertips, periungual areas and palm of hands (p < 0.0001), but not at the level of face and dorsum of hands. A gradual decrease of BP at fingertips, periungual and palm areas, was found in SSc patients with progressive severity of NVC patterns of microangiopathy (“early”, “active”, or “late”) (p < 0.01). A negative correlation was observed between MES and BP values, as well as between loss of capillaries and BP, at the same areas (p < 0.001 and p < 0.01, respectively). Patients with diffuse cutaneous SSc (dcSSc) showed lower BP than those with limited cutaneous SSc (p < 0.04).

Conclusions

LASCA detects a significant reduction of BP only in those areas usually affected by Raynaud's phenomenon (fingertips, periungual and palm areas), especially in dcSSc patients, and BP values significantly correlate with the nailfold capillaroscopy scores of microangiopathy.

Introduction

Systemic sclerosis (SSc) is characterized by early impairment of the microvascular system and decreased peripheral blood perfusion together with progressive tissue fibrosis (Cutolo et al., 2010a, Cutolo et al., 2010b, Herrick, 2008, Rosato et al., 2011).

Nailfold videocapillaroscopy (NVC) is a safe and validated technique to assess and quantify morphological capillary alterations, while laser speckle contrast analysis (LASCA) is a non-invasive method to evaluate and quantify blood perfusion (BP) at different skin sites, especially in SSc patients (Smith et al., 2010, Sulli et al., 2014a, Ruaro et al., 2014). Compared to the limits of the contact and single point technique Laser Doppler flowmetry, LASCA allows analysis of BP on different and larger skin areas of the body, with a more reproducible and safer non-contact approach (i.e. face or legs) (Ruaro et al., 2014). Furthermore, LASCA is less prone to movement artifacts.

Limited information is available about BP at specific body sites in SSc, like either dorsum of hands or face, usually spared by Raynaud's phenomenon, with the exception of nose (Cutolo et al., 2010b, Rosato et al., 2011, Ruaro et al., 2014, Murray et al., 2006). The aim of this study was to assess by LASCA the BP in different skin areas of hands and face in SSc patients, and to search for correlations with nailfold capillary damage extent as detected by NVC.

Section snippets

Patients and methods

During their regular followup, seventy consecutive SSc patients (mean age 63 ± 12 SD years, 63 women and 7 men, mean Raynaud's phenomenon duration 12 ± 11 years, mean SSc duration 6 ± 5 years), according to the new ACR/EULAR criteria and 70 healthy subjects (mean age 63 ± 15 years, 62 women and 8 men), were enrolled and after informed consent (van den Hoogen et al., 2013).

Assessments were carried out after a treatment-free period of at least one month from prostanoids, calcium channel blockers,

Results

Clinical characteristics of SSc patients and healthy subjects are reported in Table 1.

SSc patients showed a significant lower median BP than healthy subjects at the level of fingertips (86 and 189 PU, respectively, p < 0.0001), periungual areas (69 and 140 PU, respectively, p < 0.0001) and palm of hands (77 and 111 PU, respectively, p < 0.0001) (see Table 1 for interquartile ranges).

No significant difference in BP values was observed between SSc and healthy subjects at the level of dorsum of hands,

Discussion

This study reports, for the first time in SSc patients, significant correlations between BP values in different body areas and nailfold microangiopathy severity, as respectively detected by LASCA and NVC.

BP was found lower in SSc patients than in healthy subjects at fingertips, confirming previous results obtained by single laser Doppler flowmetry (Cutolo et al., 2010b, Cutolo et al., 2014, Ruaro et al., 2014, Sulli et al., 2014b). In addition, this study showed lower BP in SSc patients than in

Funding

This study was supported by funding from the Research Laboratory and Academic Division of Rheumatology of the University of Genova, Italy (UGE001-15).

Disclosure statement

The authors have declared no conflict of interest.

Contributorship

The manuscript has been seen and approved by all the authors that have given necessary attention to ensure the integrity of the work.

Ethical approval

Local institutional review board approval.

Acknowledgments

Authors are members of the EULAR Study Group on Microcirculation in Rheumatic Diseases.

V. Smith is senior clinical investigator of the Research Foundation Flanders (Belgium) (FWO).

References (17)

A. Herrick
Diagnosis and management of scleroderma peripheral vascular disease
Rheum. Dis. Clin. N. Am.
(2008)
F. Ingegnoli et al.
Nailfold capillaroscopy in systemic sclerosis: data from the EULAR scleroderma trials and research (EUSTAR) database
Microvasc. Res.
(2013)
M. Cutolo et al.
Assessing microvascular changes in systemic slerosis diagnosis and management
Nat. Rev. Rheumatol.
(2010)
M. Cutolo et al.
Peripheral blood perfusion correlates with microvascular abnormalities in systemic sclerosis: a Laser-Doppler and nailfold videocapillaroscopy study
J. Rheumatol.
(2010)
M. Cutolo et al.
Longterm treatment with endothelin receptor antagonist bosentan and iloprost improves fingertip blood perfusion in systemic sclerosis
J. Rheumatol.
(2014)
H. Ennis et al.
A prospective study of systemic sclerosis-related digital ulcers: prevalence, location, and functional impact
Scand. J. Rheumatol.
(2013)
L. Guillevin et al.
Functional impairment of systemic scleroderma patients with digital ulcerations: results from the DUO Registry
Clin. Exp. Rheumatol.
(2013)
A.K. Murray et al.
Abnormal microvascular response is localized to the digits in patients with systemic sclerosis
Arthritis Rheum.
(2006)

There are more references available in the full text version of this article.

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Systemic sclerosis (SSc), also referred to as systemic scleroderma or scleroderma, is a rare, complex immune-mediated connective tissue disease characterized by progressive skin fibrosis and other clinically heterogenous features. The etiopathogenesis of SSc involves vasculopathy and immune system dysregulation occurring on a permissive genetic and epigenetic background, ultimately leading to fibrosis. Recent developments in our understanding of disease-specific autoantibodies and bioinformatic analyses has led to a reconsideration of the purely clinical classification of diffuse and limited cutaneous SSc subgroups. Autoantibody profiles are predictive of skin and internal organ involvement and disease course. Early diagnosis of SSc, with commencement of disease-modifying treatment, has the potential to improve patient outcomes. In SSc, many of the clinical manifestations that present early signs of disease progression and activity are cutaneous, meaning dermatologists can and should play a key role in the diagnosis and management of this significant condition. The first article in this continuing medical education series discusses the epidemiology, clinical characteristics, and pathogenesis of SSc in adults, with an emphasis on skin manifestations, the important role of dermatologists in recognizing these, and their correlation with systemic features and disease course.
Definition and application of proximal-distal gradient finger perfusion in systemic sclerosis by laser speckle contrast analysis
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In patients with systemic sclerosis (SSc) the perfusion of the fingers shows an alteration of the physiological proximal-distal gradient (PDG). The aim of this study is to provide a generalizable definition of PDG, applying it in a cohort of SSc patients and healthy controls (HC) using laser speckle contrast analysis (LASCA).
Adult consecutive SSc patients and HC were enrolled. Peripheral blood perfusion of the hands was evaluated by LASCA, subsequently obtaining 3 different regions of interest: from the distal interphalangeal joint to the fingertip (DIST), from the metacarpophalangeal joint to the distal interphalangeal joint (PROX), and of the whole finger (TOT). A PDG formula independent of both intra- and inter-personal factors was then built. The PDG formula so obtained was: [(DIST × 2.63) − PROX]/TOT.
Ninety-four SSc patients (79.8% female, mean age 58.7 years) were enrolled. Applying the PDG formula, SSc patients revealed mean PDG values significantly lower than HC (1.82 ± 0.44 PU vs 2.70 ± 0.38 PU; p < 0.0001). Patients with a previous history of digital ulcers presented significant lower PDG values (p = 0.002). The ROC curve analysis identified in 2.28 PU the best PDG cut-off value between SSc and HC, with 86% sensibility and 90% specificity.
This study provided a PDG formula generalizable to all kind of subjects, applying it in SSc with great sensibility and specificity using LASCA, the best non-invasive imaging technique for the dynamical evaluation of peripheral perfusion. LASCA-PDG appears also as a tool able to identify a subclinical microangiopathic impairment.
Nailfold capillaroscopic changes of sleep apnea patients
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Citation Excerpt :
The density, dimension, morphology of capillaries and presence of hemorrhages can be evaluated in order to examine microvascular circulation (Smith et al., 2020). Morphological changes observed through the dermoscope are used; in Raynaud's phenomenon (RP), which can be the first manifestation of systemic sclerosis (SSc) or other connective tissue diseases (Gualtierotti et al., 2017; Pizzorni et al., 2017), in SSc patients to identify the proper pattern of microvascular damage (Ruaro et al., 2016) and patterns of microangiopathy (Ruaro et al., 2018), in the diagnosis of autoimmune connective tissue diseases and in evaluating the systemic effects of the disease (Aytekin et al., 2011). Not only dermatological and rheumatic diseases but also diabetes, hypertension (Junqueira et al., 2018), normotensive glaucoma, non-rheumatic conditions (like radiation exposure, being musician or athletes) have been studied with dermoscope (Aytekin et al., 2011; Sontheimer, 2004a; Sirufo et al., 2021).
Obstructive Sleep Apnea Syndrome (OSAS) have frequent association with comorbidities and this makes it an independent risk factor for cardiovascular disease. Not only endothelial dysfunction, but also arterial stiffening, increased inflammatory mediators, oxidative stress after hypoxemia that develops due to OSAS, cause vascular pathologies in all diameters of vessels. Nail bed capillaroscopy is a simple, noninvasive, useful method to examine microcirculation and evaluate nail bed capillary abnormalities in diseases that cause vascular damage. The aim of this study is to examine microvascular changes in the nail bed of OSAS patients by capillaroscopy.
59 OSAS patients and 60 healthy cases (totally 119) were included. One single attended polysomnography was applied with Embla N7000 series (RemLogic Eastmed, Natus); and apnea-hypopnea index (AHI), oxygen de-saturation index >4% (ODI4%), minimum oxygen saturation (SaO2 Min.), total duration of oxygen desaturation, comorbidities, body mass index (BMI), smoking habit, sleep questionnaire applications were analyzed. Nailfold capillaroscopy was performed using a digital dermoscope (Molemax II, X30) and all images were evaluated for capillary density, capillary loop enlargement, capillary tortuosity, branching vessels, micro hemorrhages, avascular areas and splinter hemorrhages.
The prevalence rates of all capillaroscopy findings were significantly higher in the patient group (p < 0.05). There was an inverse and moderate relationship between AHI and mean saturation (p < 0.05). A statistically significant correlation was detected between the presence of hypertension (HT) and the severity of capillary tortuosity (CT) (p = 0.002), avascular area (AA) (p = 0.004), and periungual cyanosis (PUC) (p = 0.042); also between smoking habit and intensity of capillary dilatation, enlargement dilatation-enlarged giant capillaries (CELON) (p = 0.004), CT (p = 0.018) findings. Capillary distribution (CD), CELON, CT and AA findings were significantly higher in the group with low mean saturation (p < 0.05). DM was found to be significantly higher in individuals with high Epworth Sleep Scale (ESS) (p = 0.035).
In this study; 1) the nail bed capillaroscopy was used to examine vascular damage in OSAS, and 2) irregularities detected in the distal nail bed specific to a disease have been mentioned for the first time. It has been shown that endothelial damage is particularly related to the severity of hypoxia. HT and smoking history causes endothelial damage independent of the severity of the disease and hypoxia. Also, ESS may be more determinant in the screening of sleep disorders in diabetic patients.
State-of-the-art technologies provide new insights linking skin and blood vessel abnormalities in SSc-related disorders
2020, Microvascular Research
A key unanswered question in systemic sclerosis (SSc) is how microvascular abnormality and fibrosis inter-relate. Our aim was to use state-of-the-art non-invasive imaging methods to gain new insights into pathophysiology, comparing patients with different subtypes of SSc, including early dcSSc, not only to healthy controls but also to patients with causes of Raynaud's phenomenon not progressing to fibrosis.
Laser Doppler imaging, nailfold capillaroscopy, spectroscopy, and ultrasound measured (respectively) perfusion, microvascular structure, oxygenation/oxidative stress, and skin thickening in the hands of 265 subjects: 31 patients with primary Raynaud's phenomenon (PRP), 35 with undifferentiated connective tissue disease (UCTD), 93 with limited cutaneous SSc (lcSSc), 46 with diffuse cutaneous SSc (dcSSc, including 27 ‘early’) and 60 healthy controls.
Mean perfusion was reduced in SSc groups compared to controls (lcSSc 172 perfusion units [standard deviation 157], late-dcSSc 90 [145], early-dcSSc 68 [137] vs. controls 211 [146]; p = 0.0002) as was finger-oxygenation (lcSSc 12.1 [13.6] arbitrary units [AU], late-dcSSc 12.2 [8.4], early-dcSSc 11.1 [11.3] vs controls 14.9 [10.5]; p = 0.0049). Oxidative stress was increased at the hand-dorsum in SSc groups (p = 0.0007). Perfusion positively correlated with oxygenation (r = 0.23, p < 0.001), and capillary density negatively with skin thickness (r = −0.26, p < 0.001).
Our findings lend support to the hypothesis that in SSc, particularly early dcSSc, (but not in PRP or UCTD), reduced perfusion (together with structural microvascular abnormality) associates with reduced oxygenation, with oxidative stress and with skin thickening/fibrosis, most likely driving a vicious cycle which ultimately results in irreversible tissue injury. Findings in skin may mirror alterations in internal organs.
Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud's phenomenon and systemic sclerosis
2020, Autoimmunity Reviews
Citation Excerpt :
Especially, the absence of a mean capillary diameter of ≥30 μm in patients with RP is predictive of non-occurrence of a secondary RP due to SSc. Interestingly, a correlation between qualitative and quantitative NVC assessment and functional correlations (i.e. peripheral blood flow changes) have also been clearly shown [71–73,83]. Of note, scoring per linear mm of the individual parameters which characterize the different qualitative NVC patterns has been attested to be reliable for the following characteristics: capillary density, giants (i.e. capillary dimension) and presence/absence of haemorrhages, but not for “ramifications” (i.e. capillary morphology) [17].
Capillaroscopy is a non-invasive and safe tool which allows the evaluation of the morphology of the microcirculation. Since its recent incorporation in the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for systemic sclerosis together with its assessed role to monitor disease progression, capillaroscopy became a ‘mainstream’ investigation for rheumatologists. Given its increasing use by a variety of physicians internationally both in daily practice to differentiate primary from secondary Raynaud's phenomenon, as well as in research context to predict disease progression and monitor treatment effects, standardisation in capillaroscopic image acquisition and analysis seems paramount. To step forward to this need, experts in the field of capillaroscopy/microcirculation provide in this very consensus paper their view on image acquisition and analysis, different capillaroscopic techniques, normal and abnormal capillaroscopic characteristics and their meaning, scoring systems and reliability of image acquisition and interpretation.
Correlations between nailfold microvascular damage and skin involvement in systemic sclerosis patients
2019, Microvascular Research
The aim of this study was to identify any correlations between microvascular damage, assessed by nailfold videocapillaroscopy and skin impairment, evaluated by three different methods, the modified Rodnan skin score (mRSS), skin high-frequency ultrasound (US) and the plicometer skin test (PST) in systemic sclerosis (SSc) patients.
Sixty-three SSc patients and 63 healthy subjects were enrolled. Nailfold videocapillaroscopy (NVC) was used to assess the nailfold capillaroscopy pattern (“Early”, “Active” or “Late”), according to the Cutolo classification. All subjects were assessed by mRSS, US and PST to evaluate their dermal thickness (DT) in the seventeen skin areas of the body usually evaluated by mRSS (zygoma, fingers, hands, dorsum of hands, forearms, arms, chest, abdomen, thighs, legs, feet). Statistical evaluation was performed by nonparametric tests.
All the three methods demonstrated progressively higher values of skin impairment in patients with “Early”, “Active” or “Late” pattern of nailfold microangiopathy (for mRSS p < 0.01, US p < 0.02 and PST p < 0.02). A positive correlation was also observed in SSc patients between the three methods used to evaluate skin involvement (mRSS vs US, mRSS vs PST, PST vs US, p < 0.0001 respectively).
This study demonstrates that there is a correlation between two of the most important aspects to classify and monitor the SSc patients, i.e. microvascular damage progression (evaluated by NVC) and skin damage (assessed by mRss, US and PST).

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Correlations between skin blood perfusion values and nailfold capillaroscopy scores in systemic sclerosis patients

Highlights

Abstract

Objectives

Methods

Results

Conclusions

Introduction

Section snippets

Patients and methods

Results

Discussion

Funding

Disclosure statement

Contributorship

Ethical approval

Acknowledgments

Rheum. Dis. Clin. N. Am.

Microvasc. Res.

Assessing microvascular changes in systemic slerosis diagnosis and management

Nat. Rev. Rheumatol.

Peripheral blood perfusion correlates with microvascular abnormalities in systemic sclerosis: a Laser-Doppler and nailfold videocapillaroscopy study

J. Rheumatol.

Longterm treatment with endothelin receptor antagonist bosentan and iloprost improves fingertip blood perfusion in systemic sclerosis

J. Rheumatol.

A prospective study of systemic sclerosis-related digital ulcers: prevalence, location, and functional impact

Scand. J. Rheumatol.

Functional impairment of systemic scleroderma patients with digital ulcerations: results from the DUO Registry

Clin. Exp. Rheumatol.

Abnormal microvascular response is localized to the digits in patients with systemic sclerosis

Arthritis Rheum.