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- MATERIALS AND METHODS
- AUTHOR CONTRIBUTIONS
Nailfold capillaroscopy (NFC) is a well-established method that allows the assessment of microcirculation in patients with Raynaud's phenomenon (RP). It is extremely useful for differential diagnosis between primary and secondary RP and for early diagnosis of systemic sclerosis (SSc; scleroderma). Patients with SSc and scleroderma spectrum disorders exhibit a typical pattern at NFC designated “scleroderma pattern,” and characterized by enlarged capillary loops, loss of capillaries, areas of hemorrhages, disruption of the orderly appearance of the capillary bed, and distortion of capillaries (). These abnormalities can be recognized in early stages of SSc, even when clinical features of the disease are only limited to RP (). In addition, an improvement in the microangiopathic abnormalities characteristic of the scleroderma pattern was described after autologous hemopoietic stem cell transplantation in patients with severe SSc, suggesting a possible role of NFC for therapy monitoring as well ().
There are several methods and pieces of equipment for performing capillaroscopy, including the stereomicroscope, dermatoscope, ophthalmoscope, and videocapillaroscope. According to previous studies, dermatoscopes and ophthalmoscopes offer lower performances compared to stereomicroscopy and videomicroscopy ([4, 5]). Widefield NFC is a simple and low-cost method largely studied by Maricq et al 30–40 years ago. It is traditionally performed with a stereomicroscope at 10–40× magnification, allowing a global overview of the entire capillary network at the nailfold region (). By widefield NFC, capillary loops are evaluated using qualitative and semiquantitative approaches, as well as by means of quantitative measurement of the capillary density (). The videocapillaroscopy system is an extension of the panoramic capillaroscopy in which the magnification used is much higher (200–600× magnification) than the widefield technique (). Videocapillaroscopes are equipped with specific software that allows detailed measurement of specific parameters such as the dimensions of individual capillary loops, as well as the afferent and efferent luminal diameters ([8, 9]). However, only a restricted part of the nailfold region is assessed at a time, due to the high magnification power used in this technique.
Despite the increasing interest in NFC and its remarkable utility in clinical practice and research, there is no consensus or standardized approach to the evaluation of several capillaroscopic parameters. Recent studies have been published evaluating the reliability of videocapillaroscopy ([7, 10-12]), but studies comparing the performance of widefield NFC and videocapillaroscopy are scarce ([13, 14]). The present study aimed to evaluate and compare the diagnostic performance and reliability of different parameters evaluated by widefield NFC with those obtained by videocapillaroscopy in the assessment of microcirculation in patients with several forms of RP.
Box 1. Significance & Innovations
- Nailfold capillaroscopy (NFC) is an important tool for the investigation of patients with Raynaud's phenomenon (RP). Nevertheless, there is no guideline about the method and the parameters that should be evaluated.
- The performance for the diagnosis of systemic sclerosis (SSc) and the reliability of widefield NFC, a simple and low-cost method, were compared with those obtained by videocapillaroscopy, which is considered a more sophisticated method.
- Widefield NFC and videocapillaroscopy showed a similar performance in discriminating SSc patients from controls and RP patients. There was excellent intra- and interobserver agreement for all parameters evaluated by both methods.
- Widefield NFC and videocapillaroscopy were reliable methods, suggesting that both can be used equally for assessing peripheral microangiopathy in RP and SSc patients.
- Top of page
- MATERIALS AND METHODS
- AUTHOR CONTRIBUTIONS
NFC is considered one of the most important tools for the evaluation of microcirculation and early diagnosis of SSc. The present study originally performed a head-to-head comparison between 2 NFC methods (widefield NFC and videocapillaroscopy) that are widely used in clinical practice and research. The most important parameters related to the scleroderma pattern were analyzed by both methods. Both widefield NFC and videocapillaroscopy were equally able to discriminate SSc patients from healthy controls and from non-SSc patients with RP. The comparison between widefield NFC and videocapillaroscopy showed a strong and significant correlation in the evaluation of the number of capillaries/mm, enlarged capillaries, giant capillaries, and avascular areas. Finally, there was excellent intra- and interobserver reliability for all parameters evaluated either by widefield NFC or by videocapillaroscopy.
Widefield NFC is considered a classic approach based on the use of optical instruments (i.e., stereomicroscope) under low magnification. The advantage of this method is the panoramic view of the entire nailfold microvascular network, allowing the prompt identification of specific panoramic microangiopathic patterns and localization of isolated morphologic abnormalities ([6, 8]). Widefield NFC also has the advantage of being a lower-cost method, making it suitable for clinical use in smaller centers. On the other hand, it has been considered a more subjective method, with some limitations regarding reproducibility, especially when quantitative evaluation of the microangiopathy is required ([2, 23]). This could be explained by the fact that early widefield NFC descriptions were purely subjective and based only on specific pattern recognition. To reduce this limitation, several quantitative and semiquantitative techniques have been developed ().
Videocapillaroscopy is considered to be the most sophisticated method for nailfold capillary examination at present (). Due to special digital systems, this technique has been considered highly reliable and user friendly (). Because images are recorded and stored, it is possible to perform blind analysis of the data and to follow individual capillaries in the same patient, allowing the quantitation of microvascular disease progression over time, making this a great advantage in longitudinal studies and research. A limitation of this method is represented by the fact that the application of even minimal pressure to the skin by the probe can reduce or interrupt the blood flow in the capillaries and consequently impair the evaluation of the capillary loops along the nailfold margin ([6, 23]). In addition, the acquisition and posterior analysis of each image (32 images per patient) is extremely laborious and more time consuming compared to the widefield NFC method.
Although the sensitivity and specificity of NFC in the diagnosis of SSc have already been evaluated in previous studies ([13, 25]), this was the first study to perform a comparison of the sensitivity and specificity of different parameters as assessed by widefield NFC versus videocapillaroscopy in the same individuals. The most frequent parameters used in other studies, such as the number of capillaries/mm and devascularization ([9, 11, 26]), were evaluated. Both the avascular score and the number of capillaries/mm showed high sensitivity and specificity for SSc diagnosis using either videocapillaroscopy or widefield NFC. As expected, the performance of both methods was slightly higher when only healthy controls were compared to SSc patients, with excellent areas under the curve for both parameters analyzed (number of capillaries/mm and avascular score). However, when comparing SSc patients with the other 3 groups (controls and primary RP and UCTD patients), ROC curve analysis also showed an excellent AUC for the avascular score. In addition, the analyses of SSc patients with less than 4 years of disease showed a similar diagnostic performance, confirming the importance of the method for early diagnosis of the disease.
In a more synthetic approach, the most relevant NFC patterns were also evaluated by widefield NFC and videocapillaroscopy, again showing a similar diagnostic performance. An interesting finding was the presence of scleroderma pattern in 20–28% of the UCTD patients. These patients could also be classified as having early SSc according to the LeRoy and Medsger criteria from 2001 (), and are already being followed for monitoring of disease progression due to the high risk of developing SSc ([19, 28]).
An important aspect evaluated in the present study was the interobserver reproducibility and the intraobserver repeatability of both methods. Parameters with poor agreement in previous studies such as meandering, tortuous and bizarre capillaries, skin transparency, and intercapillary distance measurements were not evaluated ([29, 30]). The weighted kappa values showed excellent interobserver and intraobserver agreement on both methods, showing that both widefield NFC and videocapillaroscopy are highly reliable for the evaluation of different capillaroscopy patterns. Recently, Gutierrez et al (2012) evaluated the learning curve of rheumatologists with different background experience in videocapillaroscopy by means of a 1-week intensive training program focused on the interpretation of the main capillary nailfold abnormalities, including the normal and scleroderma patterns (). There was a progressive improvement in the interreader agreement from the beginning to the end of the training program. Nonetheless, we believe that more extensive training is necessary to deepen the knowledge of the wide range of normal findings as well as for research studies. In our study, the almost perfect agreement obtained can be explained by the long-term experience of both observers with NFC, and may not be similar for less experienced observers.
ICCs also showed high agreement in all parameters (number of capillaries/mm, enlarged capillaries, giant capillaries, microhemorrhages, and avascular score) evaluated by both methods. Recently, Wildt et al (2012) evaluated the capillary density (number of loops/mm) using a stereomicroscope and a videocapillaroscope in 40 patients with SSc and 21 controls. There was a good agreement rate between the methods, confirming the results found in the present study (). Moreover, 2 other studies evaluated inter- and intraobserver reliability of videocapillaroscopy only. Smith et al (2010) evaluated the inter- and intraobserver reliability of qualitative and 4 semiquantitative parameters (capillary loss, giant capillaries, microhemorrhages, and capillary ramifications) between 2 observers from 2 different centers in 71 SSc patients (). The inter- and intraobserver agreement rates for the semiquantitative scoring showed similar results compared to the present study. Another study found almost perfect inter- and intraobserver agreement for identification of major abnormalities (including giant capillaries) and good inter- and intraobserver agreement regarding analysis of the number of capillaries/mm, avascularity, and hemorrhages (). There was also good agreement in the evaluation of capillary disorganization, which was not evaluated in our study. Finally, Bland-Altman analysis also showed high agreement rates for all parameters evaluated by widefield NFC and videocapillaroscopy in the present study.
The present findings of high agreement rates for capillaroscopic parameters assessed by both methods suggest that, although widefield NFC measurements can be considered more subjective compared to videocapillaroscopy systems, both methods can be used in clinical practice in an accurate and reliable fashion. Nonetheless, it should be noted that the examinations were performed by 2 investigators from a single center and with long-term experience in widefield NFC. Therefore, we cannot extrapolate that such a good widefield NFC performance will be achieved in a scenario in which the investigators have modest experience with the method. Moreover, due to the high quality of the images, videocapillaroscopy can be more suitable for longitudinal followup and research ().
In conclusion, several recent studies have highlighted the importance of NFC for the investigation of patients with RP ([32-34]). In fact, NFC was included among the criteria for early diagnosis of SSc (), underlining the importance of the method for the identification of patients with SSc. In the present study, both widefield NFC and videocapillaroscopy were shown to be able to differentiate SSc patients from controls and patients with RP. Moreover, both methods showed excellent reliability, suggesting that both approaches can be used equally for assessing peripheral microangiopathy in RP and SSc patients. However, due to the operator-dependent characteristic of both methods, further multicenter and longitudinal studies are warranted in order to expand the present findings to other investigators in the clinical and research scenarios.