Nailfold capillaroscopy in systemic sclerosis: Data from the EULAR scleroderma trials and research (EUSTAR) database
Introduction
Systemic sclerosis (SSc) is a severe connective tissue disease in which vascular dysfunction, tissue fibrosis and immune dysregulation are key events. SSc has a heterogeneous clinical presentation, but skin and vascular changes are the hallmark of the disease (Geyer and Muller-Ladner, 2011, Herrick, 2012). Pathological microvascular findings in SSc document a significant loss of the peripheral vascular network, with loss of capillaries, deficient vascular repair and the absence of new vessel growth, and subsequent tissue ischemia and fibrosis (Brown and O'Leary, 1925, Herrick and Cutolo, 2010, Kuwana et al., 2004).
The sequence of these alterations in the microcirculation can be observed using a reliable, rapid, non-invasive examination such as nailfold capillaroscopy, which can be regarded as the most valuable technique for assisting the early diagnosis of SSc and monitoring the evolution of microangiopathy in overt SSc (Avouac et al., 2011, Cutolo et al., 2010). Capillaroscopy is a powerful in vivo tool not only in screening patients with Raynaud's phenomenon for underlying scleroderma spectrum disorders (Ingegnoli et al., 2008, Ingegnoli et al., 2010, Nagy and Czirjak, 2004, Vayssairat et al., 1982), but also in detecting the progressive microvascular damage during the course of SSc (Herrick and Cutolo, 2010).
The distinctive and identifiable morphological nailfold changes observed in patients with SSc have been extensively studied; they include enlarged loops, giant capillaries, neovascularization, capillary loss, and disrupted architecture of the nailfold microvascular network (Bukhari et al., 1996, Herrick and Cutolo, 2010, Herrick et al., 2010, Maricq and LeRoy, 1973, Maricq et al., 1980, Maricq et al., 1983). These microvascular scleroderma specific capillaroscopy abnormalities were initially described by Maricq (Maricq et al., 1980, Maricq et al., 1983) and called “scleroderma patterns”; subsequently they were classified into 3 different patterns, which include an “early” pattern (i.e. few enlarged/giant capillaries, few capillary hemorrhages, no evident loss of capillaries), an “active” pattern (i.e. frequent giant capillaries, frequent capillary hemorrhages, mild disorganization of the capillary network), and a “late” pattern (i.e. irregular enlargement of the capillaries, few or absent giant capillaries, hemorrhages, and extensive avascular areas) (Cutolo et al., 2000).
In order to clarify with further aspects the reported associations between nailfold capillary abnormalities and clinical and/or laboratory features (Bredemeier et al., 2004, Caramaschi et al., 2007, Chen et al., 1984, Cutolo et al., 2004, Hofstee et al., 2009, Lovy et al., 1985, Smith et al., 2012, Sulli et al., 2012) it was decided to evaluate a large multi-national group of patients with SSc such as the international multicenter cohort of the EULAR Scleroderma Trials And Research (EUSTAR) registry.
Therefore, the steps of this cross-sectional study were:
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To ascertain the use of capillaroscopy in everyday practice in the EUSTAR centers. Due to the fact that data on capillaroscopy were not mandatory points in the database, a lot of missing data on this topic were present. Therefore, EUSTAR centers were invited to give additional information by a short survey for assessing whether and how capillaroscopy is performed.
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To define a proper target population and to evaluate if the sample of patients in the study was representative of the population. After completing as much as possible the missing information, the target population was identified with inclusion and exclusion criteria. The representativity of the sample studied was evaluated comparing the characteristics of patients with and without information on capillaroscopy.
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To determine the frequency of capillaroscopic patterns (i.e. scleroderma pattern vs non-scleroderma pattern) in adult SSc patients, and to identify disease-phenotype associations. For this purpose clinical and demographic characteristics of patients with and without scleroderma pattern were compared.
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To examine the prevalence of the three different scleroderma patterns (i.e. early, active or late) and to better characterize these patterns in terms of their association with disease measurements, clinical and laboratory features. With this aim clinical and demographic characteristics of patients with early, active or late scleroderma pattern were compared.
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To evaluate jointly the association between clinical/laboratory information and capillaroscopic patterns. For this purpose, firstly groups (profiles) of patients which were homogeneous for their clinical/laboratory characteristics were obtained by cluster analysis; thus, these patients' profiles were related with capillaroscopy data.
Section snippets
The EUSTAR database
This EUSTAR study on capillaroscopy is based on data collected from the SSc patients entered in the EUSTAR registry. This database was launched in June 2004 and documents a multi-national, prospective and open SSc cohort. Participating medical centers have entered the data of consecutive patients into a specific database, which was definitely locked for this study in October 2011. The structure and minimal essential dataset (MEDS) of the EUSTAR database have been previously described (Tyndall
Use of nailfold capillaroscopy
A short survey was undertaken to collect information on capillaroscopy and response rate was 33.6% (37 of 110 centers), of whom 91.4% are European centers. In 18.9% (7 of 37) capillaroscopy was not routinely assessed, whereas in the 67.6% (25 of 37) of cases capillaroscopy was performed but data were not reported in the EUSTAR database. In 10 of 37 (27.0%) centers, capillaroscopy technique had been recently introduced and a videocapillaroscopic equipment was available only in 26 of 37 (70.3%)
Discussion
In the context of a constant chase for identifying a useful non-invasive tool to monitor SSc, the results of this large study on capillaroscopy add important information concerning the actual role of capillaroscopy.
The first part of this study aimed to depict the use of capillaroscopy in clinical practice. A low adherence to the survey was observed, but the collected data confirm that this technique is particularly used in European countries. This diagnostic tool was only recently introduced in
Acknowledgment
László Czirják Department of Immunology and Rheumatology, Faculty of Medicine, University of Pécs, Akác u.l., Hungary; Montecucco, Unita' Operativa e Cattedra di Reumatologia IRCCS Policlinico S Matteo, Pavia, Italy; Eugene J. Kucharz Department of Internal Medicine and Rheumatology, Medical University of Silesia, Katowice, Poland; Blaz Rozman University Medical Center Ljublijana, Division of Internal Medicine, Department of Rheumatology, Ljubliana, Slovenia; Armando Gabrielli Istituto di
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