Prevalence and evolution of scleroderma pattern at nailfold videocapillaroscopy in systemic sclerosis patients: Clinical and prognostic implications☆
Introduction
Systemic sclerosis (SSc) is a connective tissue disease characterized by endothelial dysfunction, dysregulation of fibroblasts with collagen overproduction, and complex immune system abnormalities (Avouac et al., 2011, Ferri et al., 2014). A frequent consequence of this chronic disease is the multiple organ damage/failure responsible for marked impairment of the patient's quality of life and increased mortality (Avouac et al., 2011, Ferri et al., 2014). Vascular involvement plays a decisive role in SSc pathogenesis occurring early in the course of disease, typically with the appearance of Raynaud's phenomenon (Kahaleh, 2004). Microangiopathy is also directly responsible for some severe clinical manifestations, such as digital ulceration, pulmonary arterial hypertension and scleroderma renal crisis (Lambova and Müller-Ladner, 2010).
Capillaroscopy is an imaging technique, for the in vivo study of microcirculation, quick to perform, non-invasive, and not expansive (Grassi and De Angelis, 2007, Ingegnoli et al., 2013a). The first description of capillary abnormalities in systemic sclerosis (SSc) dates back to 1925 by Brown and O'Leary (1925) and these findings were thereafter called ‘scleroderma pattern’. In the last 3 decades many authors have investigated the scleroderma microangiopathy, and now the capillary abnormalities in SSc are well documented (Grassi and De Angelis, 2007, Ingegnoli et al., 2013a, Smith et al., 2012, Smith et al., 2013).
Recently, the presence of a scleroderma pattern has been included in classification criteria for SSc (van den Hoogen et al., 2013), but although it is detectable in a significant percentage of SSc patients, the prevalence of scleroderma pattern is highly variable in published studies (Bergman et al., 2003, Cutolo et al., 2006, Lambova and Müller-Ladner, 2011, Nagy and Czirják, 2004).
The aims of the study were to evaluate the prevalence and evolution of scleroderma pattern in a large cohort of SSc patients and analyze their demographic, clinical and prognostic characteristics in relation to the capillaroscopic features.
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Patients
Two hundred and seventy-five SSc patients, referred to our Rheumatologic Centre from February 2005 to October 2014, classified according to 2013 criteria (van den Hoogen et al., 2013), were retrospectively enrolled. All patients who underwent at least two nailfold videocapillaroscopy (NVC) during follow-up were enrolled in the study. Demographic, clinical, and serological data were collected for all patients at any NVC time. To calculate survival rates the vital status of all patients was
Results
Two hundred and twenty patients (80%) showed a scleroderma pattern at the moment of the first evaluation (group 1) (Fig. 1), while in 55 patients (20%) scleroderma pattern was not observed (group 2). Among group 2, 23 (41.8%) showed nonspecific alterations, while NVC was normal in the remaining 32 patients (58.2%).
Main clinical, serological and demographic features of the 275 SSc patients enrolled in the study are reported in Table 1.
No significant differences were observed for mean age at
Discussion
The present study evaluated for the first time the relationship between NVC features and clinical, demographic and laboratory characteristics on a large monocentric SSc population, although the retrospective collection of data may represent a limit.
Considering the whole follow-up, the frequency of scleroderma pattern in our population was 87.1%. Of interest, NVC pattern changed during follow-up in 11% of patients, confirming that microangiopathy is a dynamic process during the disease (Cutolo
References (27)
- et al.
Systemic sclerosis evolution of disease pathomorphosis and survival. Our experience on Italian patients' population and review of the literature
Autoimmun. Rev.
(2014) - et al.
Nailfold capillaroscopy in systemic sclerosis: data from the EULAR scleroderma trials and research (EUSTAR) database
Microvasc. Res.
(2013) - et al.
Nailfold capillary patterns in healthy subjects: a real issue in capillaroscopy
Microvasc. Res.
(2013) - et al.
Capillaroscopic pattern in systemic sclerosis—an association with dynamics of processes of angio- and vasculogenesis
Microvasc. Res.
(2010) - et al.
Measuring microangiopathy abnormalities in systemic sclerosis patients: the role of capillaroscopy-based scoring models
Am. J. Med. Sci.
(2014) Practical Statistics for Medical Research
(1991)- et al.
Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group
Ann. Rheum. Dis.
(2011) - et al.
The handheld dermatoscope as a nailfold capillaroscopic instrument
Arch. Dermatol.
(2003) - et al.
Skin capillaries in scleroderms
Arch. Intern. Med.
(1925) - et al.
Quantitation of microcirculatory abnormalities in patients with primary Raynaud's phenomenon and systemic sclerosis by video capillaroscopy
Rheumatology (Oxford)
(2000)
Serological markers in progressive systemic sclerosis: clinical correlations
Ann. Rheum. Dis.
Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis
J. Rheumatol.
Capillaroscopy and rheumatic diseases: state of the art
Z. Rheumatol.
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May capillaroscopy be a candidate tool in future algorithms for SSC-ILD: Are we looking for the holy grail? A systematic review
2020, Autoimmunity ReviewsCitation Excerpt :Though an important study, it was excluded from this very systematic review as the relationship between NVC and incident SSc-ILD had not been analysed separately from progressive SSc-ILD [21]. And lastly, the fourth longitudinal study by Ghizzoni et al., was excluded as the study population was enrolled retrospectively [56]. This systematic literature review, on behalf of the EULAR Study Group on Microcirculation in Rheumatic Diseases, is the first to investigate associations between NVC and SSc-ILD in a standardised way. (
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2019, Microvascular ResearchCitation Excerpt :It leads to loss of endothelium integrity with ECs detachment and in consequence to deformations of microvessels with significant enlargement of the capillaries followed by capillary collapse and rarefaction (Altorok et al., 2014; Cutolo and Sulli, 2015; Fleming and Schwartz, 2008; Freemont et al., 1992; Kahaleh, 2008; Manetti et al., 2010; Matucci-Cerinic et al., 2017). These specific sequential abnormalities in microcirculation are reflected by nailfold videocapillaroscopy (NVC) morphological changes in form of enlarged loops/giants, capillary crush with microhaemorrhages and capillary loss (Cutolo et al., 2004, 2013, 2018; Ghizzoni et al., 2015; Smith et al., 2016a, 2016b). Decreased blood flow and tissue hypoxia normally stimulates angiogenesis with the formation of new capillaries from pre-existing vessels; however in SSc subsequent proangiogenic efforts lead to chaotic and insufficient vascular regeneration that finally evolves towards progressive microvascular loss further exacerbated by extracellular matrix (ECM) accumulation and progressive fibrosis (Distler et al., 2006; Kuwana et al., 2004; Manetti et al., 2010, 2016; Matucci-Cerinic et al., 2017; Mulligan-Kehoe and Simons, 2008).
Does nailfold capillaroscopy help predict future outcomes in systemic sclerosis? A systematic literature review
2018, Seminars in Arthritis and RheumatismCitation Excerpt :Subsequent studies have identified associations between NC changes and a number of clinical features including cardiopulmonary disease [14], digital ulcers (DU) [15], calcinosis cutis [16], telangiectases [17], acro-osteolysis [16], and others [18]. A number of cross-sectional studies reporting associations between NC appearances and clinical phenotype have speculated about the prognostic and/or predictive value of NC in SSc but lacked longitudinal assessments to confirm this [14,15,18,19]. Prognostic studies seek to predict future outcomes in individuals based on clinical and non-clinical factors [20].
Capillary density: An important parameter in nailfold capillaroscopy
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The authors declare no financial support or other benefits from commercial sources for the work reported in the manuscript, or any other financial interests that any of the authors may have, which could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work.
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Cecilia Ghizzoni and Marco Sebastiani equally contributed to the article.