In systemic sclerosis macrovascular damage of hands digital arteries correlates with microvascular damage
Highlights
► Distal peripheral artery disease is present in the digits of systemic sclerosis patients. ► Ultrasonography damage of proper palmar digital arteries appears in late stages of microangiopathy. ► Blood flow dysfunction of digital arteries is already present in early disease. ► Macrovascular damage progresses with worsening of systemic sclerosis microangiopathy.
Introduction
Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by endothelial dysfunction and fibrosis of the skin and internal organs. Vascular dysfunction is one of the hallmarks of SSc and involves both the macro and microvasculature (Campbell and LeRoy, 1975).
In SSc patients ultrasonography (US) of digital arteries is characterized by smaller artery lumen, reduced pulsation, and thickened, slightly hyperechoic artery walls, increased resistive index (RI), low vessel compliance (Bregenzer et al., 2004, Schmidt et al., 2006). Color Doppler Ultrasonography (CDUS) of finger arteries is useful to differentiate between primary and secondary Raynaud's phenomenon (RP). It depicts the same anatomical structures as angiography, but it is cheaper, faster, and noninvasive (Keberle et al., 2000, Schmidt et al., 2008, Singh et al., 1991).
Nailfold videocapillaroscopy (NVC) is the most reliable way to distinguish between primary and secondary RP through identification of an early pattern of SSc (Cutolo et al., 2003, Maricq and LeRoy, 1973). Laser Doppler Perfusion Imaging (LDPI) is not an invasive technique on evaluating skin blood perfusion in patients with primary RP and SSc (Cutolo et al., 2010, Grattagliano et al., 2010, Rosato et al., 2009, Rosato et al., 2010a). Photoplethysmography (PPG) application in RP is restricted to evaluate the response of digital arteries to cold test and drugs. PPG improves the evaluation of vascular damage in patients with PRP and SSc (Rosato et al., 2010b).
Our aim was to assess in SSc patients macrovascular damage of hand digital arteries by CDUS and its relationship with microvascular damage, evaluated by NVC, LDPI and PPG.
Section snippets
Subjects
Thirty six patients (31 female and 5 male; mean age 46.1 ± 11.9 years) fulfilling the American College of Rheumatology preliminary criteria for the classification of SSc were enrolled in this study (ARA, 1980). SSc patients were divided into limited (lcSSc) and diffuse (dcSSc) cutaneous SSc groups (15). Disease activity and disease severity were measured by Valentini Disease Activity Index (DAI) and Medsger Disease Severity Scale (DSS), respectively (Medseger et al., 2003, Valentini et al., 2003).
CDUS
No significant differences of IMT were observed between SSc patients and healthy controls (0.61 ± 0.03 mm vs 0.58 ± 0.06 mm). CDUS of healthy controls showed normal US morphology of PPDA and normal blood flow with homogeneous pattern of waveform analysis. US pathologic findings of PPDA occurred in 69% of patients with SSc: 11 patients (31%) have an US type A pattern, 13 (36%) have an US type B pattern, 12 (33%) an US type C pattern and no one has a type D pattern (Fig. 1). In all ten fingers of each
Discussion
Microvascular dysfunction is already present in early disease. Microvascular abnormalities are well-known as major sites of pathology, but less attention has been paid to macrovascular abnormalities (Rollando et al., 2010).
In SSc macrovascular disease was considered extremely rare and the prevalence of vascular abnormalities has been considered to be inversely proportional to the size of blood vessels studied (Hettema et al., 2008). An increased prevalence of peripheral vascular disease in SSc
Conclusion
PPDA blood flow dysfunction is already present in early disease. Structural macrovascular damage progresses with worsening of SSc microangiopathy. Therefore, our findings should be confirmed in a multicenter study with a larger cohort of patients.
Author contribution
Edoardo Rosato: designed the research, performed the research, analyzed data, wrote the paper. Antonietta Gigante: designed the research, performed the research, analyzed data, wrote the paper; Biagio Barbano: performed the research, analyzed data, wrote the paper; Rosario Cianci: performed research; Ilenia Molinaro: analyzed data, wrote the paper; Simonetta Pisarri: performed the research; Felice Salsano: designed the research, wrote the paper.
Conflict of interest statement
The authors declare no conflicts of interest.
Submission declaration
The authors declare that the work described has not been published previously, that it is not under consideration for publication elsewhere, that its publication is approved by all authors.
- SSc
systemic sclerosis
- US
ultrasonography
- RI
resistive index
- CDUS
Color Doppler Ultrasonography
- RP
Raynaud's phenomenon
- NVC
nailfold videocapillaroscopy
- LDPI
Laser Doppler Perfusion Imaging
- PPG
photoplethysmography
- IMT
intima-media thickness
- PIP
proximal interphalangeal joints
- DIP
distal interphalangeal joints
- PI
pulsatility index
Abbreviations
References (34)
- et al.
Pathogenesis of systemic sclerosis: a vascular hypothesis
Semin. Arthritis Rheum.
(1975) Digital laser doppler flowmetry may discriminate “limited” from “diffuse” systemic sclerosis
Microvasc. Res.
(2010)The different photoplethysmographic patterns can help to distinguish patients with primary and sclerodermic raynaud phenomenon
Am. J. Med. Sci.
(2010)Endothelial dysfunction precedes atherosclerosis in systemic sclerosis — relevance for prevention of vascular complications
Rheumatology
(2007)Doppler ultrasound identifies increased resistive indices in SSc
Ann. Rheum. Dis.
(2004)Doppler spectral waveform analysis of arteries of the hand in patients with Raynaud's phenomenon as compared with healthy subjects
AJR Am. J. Roentgenol.
(1999)Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis
J. Rheumatol.
(2000)Raynaud's phenomenon and the role of capillaroscopy
Arthritis Rheum.
(2003)Peripheral blood perfusion correlates with microvascular abnormalities in systemic sclerosis: a laser-Doppler and nailfold videocapillaroscopy study
J. Rheumatol.
(2010)Digital arteries in patients with scleroderma. Arteriographic and plethysmographic study
Arch. Intern. Med.
(1972)
Arteriographic evaluation of vascular changes of the extremities in patients with systemic sclerosis
Br. J. Dermatol.
Macrovascular disease and atherosclerosis in SSc
Rheumatology
Assessment of microvascular changes in Raynaud's phenomenon and connective tissue disease using colour doppler ultrasound
Rheumatology
Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis
Arthritis Rheum.
Increased thickness of the arterial intima-media detected by ultrasonography in patients with rheumatoid arthritis
Arthritis Rheum.
Scleroderma (systemic sclerosis): classification, subsets and pathogenesis
J. Rheumatol.
Patterns of finger capillary abnormalities in connective tissue disease by “wide-field” microscopy
Arthritis Rheum.
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