Descriptive statistics of precipitation and temperature from WRF/SSiB with different microphysics and radiation schemes for June 2000 over 18°-52°N, 86°-136°E.
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During the past decades, the vegetation-climate interaction has been a research focus of meteorology, climatology, geography, and ecology. The contents mainly include the impact of climate change on ecosystem and the feedback of vegetation cover change to atmosphere. Investigation on the correlation between vegetation variation and climate change and its influencing mechanisms are the basis for the studies on climate change adaptation and mitigation.
\nThe response of terrestrial ecosystem to climate change, a complex issue in the field of global change, has been focused on in the last 30 years [1]. Vegetation cover has been proven to be governed by climatic factors, such as precipitation, temperature, solar radiation, and CO2 concentration. Therefore, variation in vegetation and its relationship with climatic factors reflected the sensitivity and vulnerability of the ecosystem to climate change (i.e., the responding processes) [2]. In many studies, the normalized difference vegetation index (NDVI) was selected to detect the impact of climate change on vegetation activity in Eurasia, [3–5]. Although the temperature increase was detected to dominate the vegetation cover and its dynamic in the northwestern China, western China, and the Tibetan Plateau, the impact of precipitation in the arid and semiarid regions may be more significant. The complicated and spatial heterogeneous effects of climate change on NDVI indicate the need to conduct further investigation at regional scales. Recently, in order to make clear the role of vegetation cover in the regional climate change, several studies on the feedback of land cover to atmosphere were conducted, especially after 1990s [6]. Land cover change (LCC) was documented as important as atmospheric circulation and solar orbit perturbations in climate change [7]. On the other hand, the feedback is regional-dependent due to the complicated climate and LCC in different regions.
\nThe Karst region in the southwest China presents the transformation from vegetation covered landscape to exposed basement rocks, which was defined as the Karst rock desertification (KRD). In this region, the natural ecosystem is vulnerable while the human disturbance is severe. Earlier studies mainly emphasized the impact of land use change on vegetation cover [8–10], lacking consideration of climate change impacts at large scales. Furthermore, it is unknown the climatic effects of land cover change in the Karst region, especially land degradation. Therefore, in this chapter, the southwestern Karst region of China was selected to conduct land-atmosphere interactions research.
\nThe southwestern Karst region of China, at 101°73\'–112°44\'E and 21°26\'–29°25\'N, and the Guizhou Karst Plateau, in the center of the southwestern Karst region (Figure 1), were selected to conduct research of climatic impacts on vegetation cover and climatic effects of vegetation degradation, respectively. They are located in the subtropical/tropical monsoon climate zone with annual precipitation of above 900 mm. The temperature and precipitation present great difference in spatial patterns, because of the typical topographical features with widely distributed mountains. Besides the Guizhou Karst Plateau, the southwestern Karst region, approximately 5.5 × 106 km2, includes Guangxi Zhuang Autonomous Region (GX) and eastern part of Yunnan Province (YN).
\nLocation of the southwestern Karst region of China and the Guizhou Province of China.
There are six vegetation types in the study area, including broadleaf forest, coniferous forest, shrub, grass, meadow, and cultural vegetation, with shrub covering the largest area. Because of the widely distributing bare limestone and the unsuitable land use since 1950s, KRD covers over 20% of the total area with the desertification rate of 2.5 × 104 km2 per year, and thus has become the most serious environmental problem in the study area. Rocky desertification in GKP exhibits three characteristics of severe degree, large area and high risk. However, litter research was carried out to assess the long-term vegetation dynamics and its influence on regional climate change.
\nThe NDVI trend from 1982 to 2013 at pixel scale was estimated using the ordinary least squares (OLS) based on the ArcGIS 10.1 platform:
\nwhere
Mann-Kendall analysis, applied as a nonparametric, rank-based method for evaluating trends in time-series data [11], was used to detect the changing trend because it is known as more resilient to outliers. A rank sequence (
where
Under the assumption of random and independent time series, the statistic
Moreover,
The positive
In order to compare the relative importance of temperature and precipitation for NDVI, the multivariate regression and the standardized coefficients were applied together. The higher standardized values mean important roles. The MATLAB 8.1 was used to establish multivariate linear model:\n
where
The GWR analysis, coupled in ArcGIS 10.1, was conducted to reveal the spatial variations in relationships between NDVI and climatic variables. Both the spatial distribution and the dynamics of NDVI were considered by the GWR model. GWR extends the traditional OLS to consider the spatial heterogeneity in climate-vegetation correlations by assigning weight values [12]:\n
where
The regression coefficients were estimated by:\n
The WRF-ARW was developed as the next generation for regional climate model. It includes different parameterization schemes for longwave and shortwave radiation, cloud microphysics, cumulus, and land surface processes. The simplified simple biosphere model (SSiB), coupled with WRF model, was selected to simulate land surface energy balance. According to the SSiB model description, there are 12 types of vegetation cover, while the vegetation and soil parameters were set for every types. Defining different vegetation cover types in this study enabled investigation of the impact of land degradation and Karst rocky desertification using the WRF-SSiB model. The domain for WRF model was set as follows: dimensions of 196 × 154 horizontal grid points with center at 35°N and 110°E. In this domain, the influencing factors for East Asian summer monsoon can be included, for example, the upper level westerly jet (ULJ) and low-level jet (LLJ), the Bay of Bengal and the southeast trade wind, and so on [13]. The WRF downscaling ability was assessed by comparing the simulations with different physical schemes (Table 1), and the optimal combination was concluded from the assessment. For the execution of the WRF, we used the NCEP DOE Reanalysis-2 [14], hereafter NCEP R-2, at 6-h intervals to provide initial conditions and lateral boundary conditions.
\n\nTwo experiments were done. One was the Case C, using the original SSiB vegetation map (as shown in Figure 2a), the other was Case D with the degraded land cover types (Figure 2b). The degraded types were decided based on the spatial pattern of different rocky desertification degrees [15]. For example, if the deserted areas accounted more than 30% of the corresponding counties, the SSiB vegetation was modified to bare soil (type 11 in SSiB model). The type 9 (broadleaf shrubs with bare soil) was used to replace original vegetation types in areas described as desert and potential desert areas larger than 45% of the counties and smaller than 30% of the counties, respectively. Based on the reset of vegetation cover types, two vegetation maps were used in WRF model, and was further used to conduct Case C and Case D.
\nCases | \nMicrophysics | \nLong-wave radiation | \nShort-wave radiation | \nFactors | \nR | \nBias | \nRMSE | \n
---|---|---|---|---|---|---|---|
1 | \nWSM 3 | \nRRTM | \nMM5(Dudhia) | \nPrecipitation | \n0.70 | \n1.68 | \n4.07 | \n
Temperature | \n0.89 | \n3.48 | \n4.65 | \n||||
2 | \nKessler | \nRRTM | \nMM5(Dudhia) | \nPrecipitation | \n0.37 | \n1.02 | \n5.50 | \n
3 | \nPurdue Lin | \nRRTM | \nMM5(Dudhia) | \nPrecipitation | \n0.65 | \n2.64 | \n6.28 | \n
4 | \nWSM5 | \nRRTM | \nMM5(Dudhia) | \nPrecipitation | \n0.67 | \n2.84 | \n6.58 | \n
5 | \nFerrier | \nRRTM | \nMM5(Dudhia) | \nPrecipitation | \n0.66 | \n2.81 | \n6.30 | \n
6 | \nWSM 3 | \nCAM | \nCAM | \nPrecipitation | \n0.65 | \n1.91 | \n4.33 | \n
Temperature | \n0.88 | \n2.97 | \n4.08 | \n||||
7 | \nWSM 3 | \nRRTMG | \nRRTMG | \nPrecipitation | \n0.67 | \n3.04 | \n5.41 | \n
Temperature | \n0.89 | \n2.24 | \n3.65 | \n
Descriptive statistics of precipitation and temperature from WRF/SSiB with different microphysics and radiation schemes for June 2000 over 18°-52°N, 86°-136°E.
Potential LCC based on the spatial pattern of KRD in GKP. (a) The percentage of areas with KRD for counties. (b) SSiB vegetation map for GKP and vegetation cover conversion.
As shown in Figure 3, the rate of 0.0015/year during 1982–2013 was estimated for the growing-season NDVI trend in the Karst region of southwest China. The maximum value can be found in 2009 with significant variations between different years. It is indicated in Figure 3(b) that the year of 1994 was a tipping point, which means that there were two states before and after this year for the NDVI anomaly. We observed decreasing trend for some years, although the overall trend was increasing. Furthermore, the M-K trend test showed significant increasing trend, especially after the year 2004. As for the variation in NDVI of different vegetation types, the increasing rate was highest for coniferous forest, and the smallest value for meadow (Table 2).
\nInterannual variations in growing-season NDVI (a) and NDVI anomaly (b) during 1982-2013 in the entire region, using the annual average growing-season NDVI.
Vegetation type | \nGrowing-season NDVI value | \nNDVI rate | \nCorrelation coefficients | \n|||
---|---|---|---|---|---|---|
Average | \nMaximum | \nMinimum | \nTemperature | \nPrecipitation | \n||
Broadleaf forest | \n0.7412 | \n0.8501 | \n0.5056 | \n0.0013 | \n0.315** | \n0.173** | \n
Shrub | \n0.6952 | \n0.8369 | \n0.4866 | \n0.0015 | \n0.149** | \n0.130** | \n
Grassland | \n0.6946 | \n0.8405 | \n0.4126 | \n0.0013 | \n0.493** | \n0.289** | \n
Coniferous forest | \n0.6871 | \n0.8270 | \n0.3932 | \n0.0016 | \n0.252** | \n0.063 | \n
Cultural vegetation | \n0.6706 | \n0.8398 | \n0.3576 | \n0.0015 | \n0.374** | \n0.182** | \n
Meadow | \n0.5910 | \n0.7319 | \n0.4741 | \n0.0008 | \n0.412** | \n−0.109 | \n
Statistical characteristics of growing-season NDVI for different vegetation types during 1982–2013.
Spatial patterns of average values in growing-season NDVI during 1982–2013.
Figure 4 shows the spatial distribution of NDVI values in the study area, ranging from 0.32 to 0.85. Due to higher temperature and more precipitation in Guangxi Zhuang Autonomous Region, there were high values of NDVI in the east part of the study area. Under the background of complex climate change, there was also spatial heterogeneity for the dynamical variation of NDVI. The higher increasing rate was observed in the northwest and the smaller values in the southeast (Figure 5).
\n\nSpatial patterns of temporal trend in growing-season NDVI during 1982–2013.
We observed warming rate of 0.018°C/year in the study area (Figure 6a). It fluctuated from −0.6 ∼ 0.8°C for average growing-season temperature. The year of 1995 was a tipping point for temperature and NDVI changes. Specifically, the average temperature for different months presented obvious variations with a maximum temperature (25.2°C) in July. For the changes in precipitation, Figure 6(c) shows a decrease of −1.21mm/year during 1982–2013. The dynamic processes for precipitation can be classified as falling under three stages: 1982–1992, 1993–2002, and 2003–2013 (Figure 6d). Additionally, the significant uptrend for temperature can be concluded from the Mann-Kendall test.
\nInterannual variations in average growing-season temperature trend and anomaly (
As shown in Figure 7(a), there was obvious synergy for NDVI and temperature, but the synergy for NDVI and precipitation was relatively weak (Figure 7b). The lower regression coefficients of precipitation indicated the weaker impact of precipitation on vegetation cover change. The reason may be that there was rich rainfall in the study area, and the annual variation cannot play significant roles. Moreover, the correlations between NDVI and climatic variables were different for different vegetation types (shown in Table 2). The largest regression coefficient was in grassland.
\nThe overall relationship between annual growing-season NDVI and temperature (
In most areas, the relationship between NDVI and temperature (Figure 8a) was positive due to the strengthened photosynthesis and vegetation activity by the increase in temperature. It should be pointed out that only within an appropriate range, the temperature rise can result in beneficial effects, and if the temperature is too high, it will cause negative impact on vegetation growth. Figure 8(b) shows the regression coefficient for NDVI and precipitation. Although the correlation was positive in most of the areas, there were some negative values in the northern part of the study area.
\n\nThe later one means applying the changing rate of NDVI (Figure 5) as the dependent variable of GWR while the changing rate of climatic factors as independent variables. Figure 9 lists the GWR regression coefficients, where colors ranging from blue to red represented values from low to high. Additionally, the standard errors were analyzed by the points with different sizes.
\n\nThere was positive relationships between multiyear average NDVI and temperature (Figure 9a), however, the regression coefficients for NDVI and precipitation contained both positive and negative values (Figure 9b). It was found that the positive values for NDVI and precipitation were mainly located in Yunnan Province, where the climate is more arid than other areas of the study area. The GWR regression coefficients for dynamic relationships were listed in Figure 9(c) and (d). The NDVI was lower with increasing surface temperature, which may be explained as more serious aridity due to the warming. On the other hand, the correlation between the changing rate of NDVI with precipitation were positive, meaning that the increase in NDVI during 1982–2013 could have been caused mainly by the precipitation variations.
\nMultivariate regression coefficients of temperature (
Geographically weighted regression analysis between NDVI and temperature and precipitation during 1982–2013. (
Additional to the uptrend of NDVI from 1982 to 2013, there were some years when the NDVI decreased, that is, from 2009 to 2012. The decreasing rate during this time was −0.017/year. The significant decline was mostly in Guizhou Province where a decreased rate less than −0.02/year was observed (Figure 10). Correlation analysis between NDVI and climate change, revealed that the impact of temperature on the decreased NDVI was more profound than that from precipitation (Figure 11). Furthermore, the negative relationships between NDVI and precipitation also indicated the indirect impact of precipitation on temperature change. The increase in precipitation with more cloud could have led to the decrease in solar radiation and temperature, thus inhibiting photosynthesis.
\nSpatial patterns of variations in growing-season NDVI during 2009–2012.
Uncertainty on the downscaling capability of regional climate model (RCM) has in most cases led to skepticism for its use. Despite the weakness, the RCM dynamic downscaling is better than the simulations from General Circulation Model (GCM) or reanalysis datasets [13]. Furthermore, the uncertainty increases when the RCM is used to simulate the impact of land cover change on regional climate. In this section, the state-of-the-art RCM\'s downscaling ability was evaluated first, and was followed by analysis of the climatic effects of land degradation.
\nTo reveal the improvement of WRF simulations over reanalysis dataset, daily rainfall, temperature, and other circulation factors from WRF and reanalysis were compared with the APHROD (Asian Precipitation-Highly-Resolved Observational Data) precipitation dataset, the GTS (Global Telecommunication System) temperature dataset, and the JRA-25 (Japanese 25-year Reanalysis) atmospheric variables dataset. The assessment was conducted from the viewpoint of correlation coefficient (R), bias and root mean square error (RMSE) over the years of 1998, 2000, and 2004 and over 18°–52°N, 86°–136°E (Table 3). The lower Bias and RMSE and the higher R values indicate better performance.
\nMultivariate regression coefficients of temperature (
Variables | \n\n | Bias | \nRMSE | \nR | \n
---|---|---|---|---|
Precipitation | \nNCEP R-2 | \n1.95 | \n4.22 | \n0.60 | \n
WRF/SSiB | \n1.57 | \n3.16 | \n0.78 | \n|
Temperature | \nNCEP R-2 | \n−1.93 | \n3.62 | \n0.86 | \n
WRF/SSiB | \n−2.29 | \n4.21 | \n0.85 | \n|
VQ700 | \nNCEP R-2 | \n2.89 | \n11.38 | \n0.65 | \n
WRF/SSiB | \n−1.37 | \n7.49 | \n0.70 | \n
Descriptive statistics of ensemble mean JJA daily precipitation, temperature and water vapor flux at 700 hpa from WRF/SSiB and NCEP R-2 over 18°-52°N, 86°-136°E.
We further observed that the phenomenon of most rainfall occurring in the south of China, especially in the south of Yangtze River, can be detected from both WRF simulation and APHROD dataset. From the WRF simulation, there was also an obvious increasing trend from the northwest to southeast in the south of about 38°N with the minimum temperature in Qinghai-Tibetan Plateau. The WRF simulation of precipitation out-performed NCEP R-2, and was probably caused by the improved simulations of low level water vapor flux (Table 3), a key factor influencing the atmospheric convection in East Asian summer monsoon. Although the simulated surface temperature from WRF was not improved over NCEP R-2, the clearer spatial information for temperature was presented from WRF output, which suggests that, it is also an applicable tool in downscaling temperature.
\nThe area over 20°–34°N, 104°–124°E was chosen to investigate the impact of Karst rocky desertification on precipitation and temperature, because the significant and consistent effects were located in this region. There was spatial variation in the precipitation changes among the regions (Figure 12a). The reduced rainfall was mainly observed in the middle of Guizhou Karst Plateau. The areas with increased precipitation, mainly the middle and lower parts of Yangtze River and the surrounding areas, were of much larger magnitude and extent than that with decreased rainfall. It can be inferred that the consistent but nonsignificant reduction in rainfall with Guizhou Karst Plateau was due to high moisture influence from the Bay of Bengal. The land surface warming mainly occurred in the areas where the original vegetation types were replaced with bare soil type (Figure 12b), while the rainfall changes not only occurred within the desertification area but also beyond the area.
\n\nAs shown in Figure 13, the substantial changes of surface energy components occurred in Guizhou Karst Plateau. In the degraded areas, the higher albedo (Figure 13a) led to more reflected shortwave radiation from the land surface (Figure 13b). Due to the higher surface skin temperature (Figure 12b), the outgoing longwave radiation increased significantly, which further caused the reduced net longwave radiation at the surface (Figure 13c). Both the reduction of the net shortwave radiation and the net longwave radiation certainly resulted in the decrease in land surface net radiation (Figure 13d). More sensible heat flux was also induced by the warmer surface (Figure 13e), however, the reduction in surface latent heat flux (Figure 13f) was much more than the sensible heat flux increase. The decrease in evaporation was probably contributed by changes in vegetation and soil properties, such as the lower LAI and roughness length, and the higher surface albedo. It can be concluded that evaporation decrease produced the most profound influence on the hydrological balance at land surface. Additionally, the above-mentioned higher temperature in the degraded areas was caused by the reduced evaporative cooling.
\nEnsemble mean differences in JJA
Ensemble mean differences in JJA
Consistent with the spatial changes in precipitation, there were areas with significantly changed energy budget extending beyond the degraded area. Outside the Guizhou Karst Plateau, the variations in sensible heat flux and latent heat flux were controlled by the precipitation differences. For example, in the areas between 30°–34°N, 112°– 120°E (i.e., the southeastern coastal area of China), the increased evaporation (Figure 13f) was caused by the increase in precipitation (Figure 12a), which further led to the lower temperature (Figure 12b), and the lower sensible heat flux (Figure 13e). The issue on the impact of atmospheric circulations on precipitation will be discussed in the next section.
\nFigure 13(g) shows the impacts of cloud albedo and land surface albedo on shortwave radiation. In the degraded areas within Guizhou Karst Plateau, the cloud fraction was reduced due to the less evaporation and moisture flux convergence after land degradation, and the reduced cloud fraction further led to more incoming shortwave radiation. However, the increase in upward shortwave radiation (Figure 13a) due to the higher land surface albedo was much more than the downward shortwave radiation, which resulted in the reduced net shortwave radiation (Figure 13b). Moreover, in the southeastern coastal areas of China, the increased cloud fractions, consistent with more rainfall, led to the decrease in incoming shortwave radiation, dominating the alteration in net shortwave radiation.
\nEnsemble mean differences in JJA wind vector (m/s) at 700 hPa between Case D and Case C.
The modified water and energy budget due to Karst rocky desertification was the first-order effects. Because of the different input of heat and moisture into atmospheric circulation, the large-scale circulation features were altered, resulting in climatic effects beyond the desertification area. As shown in Figure 14, the weakened 3-month mean wind vector at 700 hPa between Case D and Case C was caused by the lower surface heating in GKP (Figure 13d). The monsoon airflow from the Bay of Bengal, an important moisture source for the East Asia, was weakened from the degraded areas to the northeast. Furthermore, the weakened southwest airflow had significant impacts on the East Asian monsoon, especially, the anomaly cyclone (Figure 14) and the stronger horizontal convergence in the southeastern coastal area that led to the strengthened vertical ascending motion and the increase in precipitation.
\n\nOn the other hand, the longitude-height section of the composite difference of zonal circulation along 24°–30°N between Case D and Case C was plotted to conduct further analysis (Figure 15). After the land degradation in GKP, an anomalous descending motion appeared in both the upper and middle level of troposphere over GKP and the middle and lower troposphere of the adjacent regions to the east. Such circulation modification caused the strengthened ascending motion over 114°–122°E. Moreover, the stronger lifting over the coastal areas led to the increase in the vertically integrated moisture flux convergence (VIMFC) from 1000 to 300 hPa. Consequently, the different circulation and moisture flux reduced the rainfall over GKP and promoted the formation of clouds and the positive rainfall anomalies over southeastern coastal areas of China (Figure 12a). Also, in the southeast China, the surface cooling (Figure 12b) was induced by the increased amount of clouds and further a negative net cloud radiation forcing.
\nZonal-height cross sections of ensemble mean differences in JJA zonal (ms−1) and vertical (10–2 ms−1) winds averaged over 24°–30°N. Gray shading indicates topography.
The growing-season NDVI increased significantly during the last 30 years in the Karst region of the southwest China. There were also differences in the increase rate of vegetation types. The distribution of NDVI presented obvious spatial patterns, specifically, lower values in the western part and higher values in the east. The correlation between NDVI and climatic factors implied the limiting role of temperature for the vegetation growth and distribution in the study area, although the regression coefficients presented spatial heterogeneity. Additionally, the decreased NDVI was analyzed to detect the influencing mechanism. It was found that the increased cloud cover and rainfall led to the decrease in solar radiation and temperature, and further impeded photosynthesis.
\nWe also observed that after the land cover change, there is need to consider its climatic effects through the impact of LCC on land surface water and energy budget. Karst rocky desertification (i.e., extensive exposure of basement rocks, serious soil erosion, drastic decrease in soil productivity and appearance of desert-like landscape) can modify the energy budget at land surface and then the regional climate. Specifically, after land degradation, the higher surface albedo and temperature caused the reduced net shortwave radiation and net longwave radiation. The sensible heat flux was increased by the higher temperature. Specifically, the substantial increase in sensible heat flux from ground offset the decrease in that from canopy. Due to higher stomatal resistance and lower LAI, the latent heat flux in KRD was reduced significantly. Less atmospheric heating from degraded land resulted in relative subsidence and less moisture flux convergence (MFC). The decrease in rainfall was probably attributed by both the reduced MFC and the reduced evaporation. A feedback loop was activated when precipitation was affected, for example, the altered soil moisture, vegetation growth, and phenology can further result in less diabatic heating rates, less moisture flux convergence, and lower rainfall. Moreover, the changed rainfall beyond the degraded areas was more significant. The modified energy and water balance due to land degradation weakened the southwest monsoon flow and affected the atmospheric circulation and moisture flux. In the southeastern coastal areas, the precipitation increased due to two reasons: (1) the weaker low-layer anticyclone causing the stronger vertical ascending motion, (2) the air mass diverging in the lower troposphere accompanying rising up over southeastern China.
\nWe thank the National Basic Research Program of China (Grant No. 2015CB452702), the National Natural Science Foundation of China (Grant No. 41671098, 41301089), the National Science and Technology Support Program of China (Grant No. 2012BAC19B10, Grant No. 2013BAC04B02) for supporting this work.
\nThe technique of nailfold capillaroscopy (NFC) was first described almost 100 years ago by Brown and O’Leary, but its utility in connective tissue disease was first truly recognised and demonstrated through the work of Maricq et al. in the 1970s and 1980s [1, 2, 3]. It is now established as a low-cost, non-invasive, highly specific, reproducible, and rapid investigation in the diagnostic workup of scleroderma-spectrum disorders and, tellingly, was included in the most recent ACR/EULAR systemic sclerosis classification criteria [4]. As a consequence, there has never been more interest in capillaroscopy and contemporary research is actively evaluating both the additional utility of NFC within scleroderma-spectrum disorders as well as in other diseases characterised by microvasculopathy. This chapter will summarise the techniques and principles of NFC, its established role, and explore the emerging roles for NFC with a focus on connective-tissue diseases.
As the name implies, NFC involves visualising the nailfold capillaries. Capillaries are the smallest blood vessels, with a size that normally allows the passage of a single red blood cell at a time. They form a complex network of “loops” (U-shaped structures commonly compared to hairpins) with an afferent (arterial) and efferent (venous) limb and an apex connecting the two (see Figure 1). These small vessels aid the diffusion of gases and the movement of substrates for and non-essential by-products of cellular respiration. The skin has a rich network of capillaries which are usually orientated vertically, distributing blood from the deep cutaneous arterioles to the surface skin and then back down again to the venous plexus. In contrast, at the nailfolds, these capillary loops lie horizontally which allows a visualisation along the length of their course. To be strictly accurate, we are not able to visualise the capillaries themselves, the thin walls of which are essentially transparent, but instead the column of red blood cells. Over many years researchers have identified abnormalities in the structure and arrangement of these capillaries present in certain diseases characterised by microvasculopathy. These abnormalities are discussed in more detail later.
Normal nailfold capillaries. The typical appearance of capillary “loops”.
NFC consists of two interrelated elements, image acquisition and image interpretation, and these will be discussed in turn in this and the following sections.
For all techniques, there are a number of general principles that should be observed. Firstly, to minimise the potential for variability in findings due to vasoconstriction and altered digital perfusion, capillaroscopy should be performed in a warm environment, with most studies suggesting a 15–30 minute period of acclimatisation to “room temperature”, usually around 20°C. Subjects should be advised to avoid smoking, caffeine or medications (where possible) that could cause peripheral vasoconstriction immediately prior to the investigation. Secondly, visualisation of the nailfold capillaries is aided by the use of a gel or oil interface to reduce surface reflection from the device light source. The more commonly used substances are clear or lightly coloured oils (such as paraffin or light olive oil) or lubricant jellies, applied in the region of the nailbed and cuticle immediately prior to visualisation. There are an increasing number of differing techniques for acquiring images and we will discuss the most frequently employed.
Widefield stereomicroscopy (WSM; see Figure 2a) is the original technique pioneered by Maricq et al. and is still considered one of the two “gold-standard” techniques [2, 3, 5]. Each nailfold (usually of just the index-little finger of each hand, as thumbs can be difficult to orientate under the microscope) is examined at around 20-fold magnification which allows for a panoramic view of the entire nailfold. The microscope allows close control of depth of focus. The microscope can be combined with a camera and other digital equipment to allow recording of images and assist real-time explanation of investigation findings. The technique typically takes around 5 minutes to complete.
The different techniques for performing nailfold capillaroscopy. (a) Widefield microscopy; (b) videocapillaroscopy; (c) dermoscopy (with a smartphone attachment).
Nailfold videocapillaroscopy (NVC; see Figure 2b) is the other “gold-standard” technique and is now the most frequent technique used in capillaroscopy research. Either a fixed or handheld imaging device is used which, when combined with computer software, affords a highly magnified view of the nailfold at 200–300-fold. This technique allows for very detailed images but an important consequence is that not all the nailfold can be visualised at the same time. The impact of this can be particularly relevant to studies looking at longitudinal nailfold changes (see later), as it can be difficult at subsequent study visits to visualise the exact same region of the nailfold. There is software that can ‘stitch’ together images using digital picture recognition and therefore produce a panoramic nailfold image made up of smaller high magnification images, first used by Herrick et al., which can mitigate this issue [6]. NVC can take substantially longer than other techniques if all fingers are studied (20–30 minutes), and consequently many studies restrict image acquisition to a single finger in both hands (most commonly the ring finger). An important potential downside of this compromise is that nailfold changes can vary markedly between even adjacent fingers. NVC has been shown in multiple studies to have good intra- and inter-observer variability and/or concordance and correlates well with WSM [6, 7, 8, 9].
Two important factors that have limited accessibility to NFC and its use in the broader rheumatology community are the relative (expensive) cost and the lack of portability of the two gold-standard techniques. There are clear advantages to being able to take a test to the “bedside” rather than having to bring a patient to the test, which is often only currently available at a small number of specialist institutions. Fortuitously, there are a number of low cost and handheld devices such as dermatoscopes and ophthalmoscopes which achieve a good visualisation of the nailfolds at around 10–20-fold magnification (see Figure 2c). A number of studies directly comparing these techniques with WSM and NVC have found a reassuring concordance [10, 11, 12]. In particular, although the rate of “unclassifiable” images is higher, ample diagnostically relevant findings can be elicited, even if more subtle changes can be missed. Rapidly improving technology, particularly with the availability of USB microscopes or attachments for smartphones, can already achieve similar magnification to NVC and record images. This infers that these devices are going to become more commonplace [11]. An additional advantage with the handheld devices is that they can be easier to use in patients with finger deformities and in thumbs (or even toes) which are often not visualised in other techniques, although the additional information gleaned from these is not yet of clear clinical utility.
Before proceeding to discuss nailfold capillary abnormalities, it is important to note that there is a surprisingly broad range of capillary appearances between or even within ‘normal’ subjects and the disease controls used in research settings [13]. It can sometimes be difficult to be certain whether subtle changes are of significance or not but with increasing experience this distinction becomes somewhat easier. In practice, most examinations will clearly fall into a normal or definitely abnormal category and for those that do not there is usually extra information from a history, examination and additional diagnostic tests that can help contextualise the capillaroscopy results.
The abnormal features that originally defined Maricq’s “scleroderma-dermatomyositis pattern (SD-pattern) remain the most important to examine for [2]. These consist of giant (significantly enlarged) capillaries, avascular areas (also referred to as capillary “drop-out”), and microhaemorrhages. Other abnormalities are recognised and include excessively tortuous capillaries, unusually shaped capillaries (“bushy” or “arborized” capillaries) and cuticular hypertrophy, but their clinical significance especially in isolation is less well established.
There is no universally agreed definition of a “giant capillary” but one is by and large accepted as a capillary that is that is enlarged over four-fold normal diameter (and often >ten-fold) (see Figure 3). A normal adult capillary is somewhere between 25-50um and therefore generally anything over 150um is considered pathologic. Enlarged capillaries are somewhere in between giant capillaries and normal. A useful clinical tip is to compare capillaries within the same patient to first establish the appearances and dimensions of their “normal” capillaries and use these to compare the enlarged capillaries against, if present. The presence of even a single giant capillary is very suggestive of an underlying connective tissue disease.
A single giant capillary, in this example associated with a microhaemorrhage in the distal cuticle.
Avascular areas or areas of capillary “drop-out” are regions where there are no capillaries and in the absence of local nailfold trauma are highly specific for systemic sclerosis in particular (see Figure 4). Again, there is no internationally ratified definition but a working definition is a 1 mm region of the distal nailfold with no capillaries present. Another definition is the absence of two or more sequential capillary loops [14]. It can be difficult if there is not adequate visualisation of the nailfold for technical reasons or if it is difficult to get the appropriate depth of focus to bring all capillaries in to view. A simple tip is to compare within the same patients nailfolds to see if the usual density of capillaries (number within a defined width or area) is regionally varied.
Avascular areas, demonstrating areas of capillary “drop-out”. Note in the right-hand image the extensive associated microhaemorrhages and cuticle hypertrophy.
These are evidenced by reddish-brown punctate lesions (haemosiderin staining) in the cuticle (see Figure 5). They are often associated with regional capillary architectural abnormalities (such as a giant capillary) and sometimes recurrent haemorrhage can be deduced from lesions “growing-out” along the cuticle over time.
Nailfold microhaemorrhages.
It is difficult to define “bushy”, “arborized” or excessively tortuous capillaries as these are qualitative judgements and experience dependent (see Figure 6). In addition, although cuticle hypertrophy is well recognised (although not that prevalent) there is no established definition for it and it is based upon a subjective assessment.
Other abnormal capillary shapes. (a) A tortuous capillary; (b) elongated capillaries.
Recently, the reliability of simple capillaroscopic definitions to describe the different morphologies that can be seen in rheumatic diseases has been published and widely accepted [15]. Although there are a range of potential abnormalities which may seem relatively complex, there is actually very good intra- and inter-observer concordance in most studies and even only a short amount of training (for example an hour) can help complete novices make accurate assessments [16]. There has been encouraging results when capillaroscopy has been used in a primary care setting as well [17]. Two prospective studies in particular have elegantly demonstrated the prognostic significance of these abnormalities in patients with Raynaud’s phenomenon. Koenig et al. showed that giant capillaries and capillary loss strongly predict the evolution to a diagnosis of systemic sclerosis (then using the 1980 ACR criteria) and, when combined with a relevant positive autoantibody, had a positive predictive value of 79% and negative predictive value of 93% [18]. A second study, by Ingegnoli et al., found that the three capillary abnormalities that correlated with a later diagnosis of systemic sclerosis were giant capillaries, capillary density and microhaemorrhages [19].
There is no universally adopted consensus on exactly how the varying combination of above potential capillary abnormalities should be classified and this is an ongoing research priority. Classification criteria have many discrete purposes from diagnostic criteria and we will cover only a few illustrative examples as our intended focus is on the use of capillaroscopy in the clinical rather than research setting.
The first proposed classification criteria was that of Maricq et al. who classified patient’s nailfold capillaries as having either “normal” appearances, “non-specific” abnormalities or the “Scleroderma-Dermatomyositis (or SD-) pattern” [2, 5]. This latter category was defined by the presence of giant capillaries or avascular areas and could include the other capillary abnormalities described above. It is this pattern that has now been shown in numerous publications to help differentiate primary from secondary Raynaud’s syndrome and as the pattern present in around 90% of systemic sclerosis patients, often very early in the course of their disease [20]. In essence, therefore, it is these features that are of primary clinical significance as they strongly suggest an associated underlying connective-tissue disease. The “non-specific” group consists of individuals who have some definite capillary abnormalities (such as microhaemorrhages, enlarged or tortuous capillaries), but neither of the more specific features of giant capillaries or avascular areas. From a clinical perspective, the significance of an investigation with these findings should usually be interpreted as normal but it may have some suggestive relevance when considered in the context of a patient’s history, examination and other investigations as supportive of a scleroderma-spectrum disorder.
Because of the intrinsic issues with purely qualitative classification systems, especially when trying to compare or reproduce different study methodologies and research findings, there have been many efforts to develop a more structured and systematic approach into criteria. A Brazilian group developed the Maricq scoring system and incorporated a count of the total number of enlarged or giant capillaries as well as a measure of mean capillary density (capillaries per mm) [21]. Other early efforts at moving towards a more quantitative classification included those by the research group of Lee et al. [14]. More recently, the most widely adopted criteria is that of Cutolo et al. who described “early”, “active” and “late” categories (see Table 1) for individuals with definite capillary abnormal features [23]. Several studies have shown that the Cutolo criteria are associated with disease activity and severity. The “early” and “active” patterns are more common in limited SSc, whereas the “late” category is present more frequently in patients with diffuse SSc [24]. In the same study, the severity of organ involvement progressively increased across groups from “early” towards “late”. Other studies have reported the “late” pattern in older patients, in those with a longer disease duration, and in those with diffuse disease [15, 16]. Several studies have shown that the “late” pattern in particular predicts digital ulcers as well as more severe cutaneous, cardiac and pulmonary disease [24, 25, 26, 27]. The initial Cutolo criteria was later simplified into a score ranging from 0 to 9, correlating to the average score for each of three variables in each of eight examined nailfolds [28].
Classification | Description |
---|---|
Early | Few giant capillaries, few haemorrhages and no capillary loss |
Active | Numerous giant capillaries and microhaemorrhages, mild capillary architecture disturbance and moderate capillary loss |
Late | Severe capillary loss with extensive avascular areas, disorganised capillaries and ramified capillaries. |
The Cutolo classification criteria [22].
Certain components of the capillaroscopic assessment are well suited to quantitative assessment. Capillary density (by convention the number of capillaries within a 1 mm region of the distal nailfold) is the best example of this, with anything less than 6 per mm being pathologically abnormal. A quantitative method was employed in a recent multicentre study and involved counting all the microhaemorrhages, normal capillaries, enlarged capillaries, giant capillaries and other abnormal capillary shapes in the distal row within two 1 mm fields per finger [29]. The study concluded that the simple count of capillaries (i.e. capillary density) was sufficient to monitor the progression of scleroderma. Recently, some groups have used computer technology to count capillaries and automate this quantitative process with good reproducibility and obvious potential advantages for future work [30, 31]. Reduced capillary density has been associated with disease complications such as pulmonary hypertension, interstitial lung disease and digital ulcers. Many other capillary features have been measured and investigated including, for example, capillary length, angle and loop diameter, but the clinical relevance of these measurements is not well established.
The first clearly established clinically relevant role for capillaroscopy was in the assessment of patients with Raynaud’s symptoms. Abnormal nailfold capillaroscopy is strongly predictive of an underlying connective tissue disease (synonymous with “secondary” Raynaud’s syndrome) and, conversely, normal nailfold capillaroscopy is reassuring that an underlying connective tissue disease is unlikely (“primary” Raynaud’s syndrome). The early work into the importance of nailfold capillary changes in identifying patients with secondary Raynaud’s syndrome is well summarised in a systematic review from 1998, where abnormal capillaries had the highest odds ratio (OR) of any variable studied for progression to secondary diseases [32]. These findings have been replicated and enhanced in the prospective study of Koenig et al. over 3000 patient years, who found abnormal capillaries and systemic sclerosis-specific autoantibodies were both independent predictors of an underlying connective tissue disease [18]. Twenty-six percent of patients with capillary abnormalities at baseline (and 36% with a specific autoantibody) developed systemic sclerosis within follow up, which increased to 80% in subjects with both features. Conversely, only 1.8% of patients with neither present at baseline developed a connective tissue disease during follow up. Similarly, a study from Pavlov-Dolijanovic et al. found 45% of their 3029 consecutive patients with Raynaud’s syndrome and abnormal NFC went on to develop a connective tissue disease. The OR for being diagnosed with systemic sclerosis in patients with abnormal NFC compared to those with Raynaud’s syndrome without capillary abnormalities was 183 (95% confidence intervals 97.9–271.5) [33].
Abnormal capillaroscopy features are particularly useful in the diagnosis of systemic sclerosis (SSc) and are present in up to 90% of patients [34]. The work of Leroy and Medsger highlighted the importance of NFC in detecting early SSc in particular and much subsequent work has helped include capillaroscopy in the most recent SSc classification criteria (see Table 2) [4, 35]. Abnormal capillaroscopic findings contribute 2 points towards the 9 points necessary to establish a diagnosis of SSc. If combined with Raynaud’s symptoms, a common indication for the investigation, it contributes a total of 4 points towards the diagnosis. The addition of capillaroscopy to the new criteria have helped improve their sensitivity for early and very early SSc which is an area of great interest to researchers seeking to find interventions and treatments to improve long-term outcomes [36, 37]. It could be argued on the basis of these criteria that access to NFC should be a pre-requisite for all clinicians and researchers evaluating patients with potential SSc.
Item | Sub-item | Weight/score |
---|---|---|
Skin thickening of fingers of both hands extending proximal to the MCPs | – | 9 |
Skin thickening (only count the higher score) | Puffy fingers | 2 |
Sclerodactyly | 4 | |
Finger tip lesions (only count the higher score) | Digital tip ulcers | 2 |
Finger tip pitting scars | 3 | |
Telangiectasia | – | 2 |
Abnormal nailfolds | – | 2 |
Pulmonary arterial hypertension and/or interstitial lung disease (maximum of 2) | Pulmonary arterial hypertension | 2 |
Interstitial lung disease | 2 | |
Raynaud’s phenomenon | – | 2 |
SSc-related autoantibodies (maximum score is 3) | Anti-Scl70 (anti-topoisomerase I) | 3 |
Anti-centromere | ||
Anti-RNA polymerase III |
The 2013 classification criteria for systemic sclerosis [4].
Patients with a score of ≥9 are classified as having definite systemic sclerosis.
There is an accumulating literature on the association between capillaroscopic findings and certain organ-specific complications of SSc. In general, the more severe morphological changes correlate with more severe disease [34, 38]. The converse is also true, where patients with less marked NFC abnormalities have less severe cutaneous and pulmonary involvement [39].
Digital ulcers (DU) are a visible representation of peripheral vasculopathy, occurring in up to 50% of patients at some point in their illness [40]. It stands to reason that capillaroscopic abnormalities would correlate with their presence and there has been considerable interest in applying capillaroscopy as a predictor of digital ulcers in systemic sclerosis. The association of capillary loss and digital ischaemia was first established almost a decade ago with work by Herrick et al. and Ennis et al. [37, 41]. The more recent video CAPillaroscopy (CAP) study showed the mean number of capillaries in the dominant hand middle finger (per mm) was one of three predictors of DU (the two others being number of DUs at enrolment and critical digital ischaemia at enrolment) [29]. The “late” NFC pattern (see Table 1) has been shown in a prospective longitudinal study to be an independent predictor for DU in patients both with and without a history of DUs [42]. NFC findings may help in future target high risk patients for vascular remodelling and protective strategies. Indeed, a prognostic tool, the capillaroscopic skin ulcer risk index (CSURI), has been developed and demonstrated to help predict ulcers in the 3 months following assessment [43]. Another similar tool to predict digital trophic lesions intended for day-to-day clinical used based upon a simple capillary count has also been described [44].
Pulmonary hypertension affects around 15% of patients with systemic sclerosis and despite advances in therapy still accounts for substantial morbidity and mortality [45]. Because of its relatively lower prevalence than other organ specific manifestations, it is more difficult to explore the role of NFC in predicting its presence or severity but some studies have already shown some intriguing results. In a recent Dutch cohort of over 200 patients, NFC changes were independently predictive of cardio-respiratory complications and, notably, all patients with pulmonary hypertension had abnormal NFC [46]. The “late” pattern and reduced capillary density have both been associated with the presence and severity of pulmonary hypertension in SSc [47, 48].
Interstitial lung disease (ILD) is present in up to 80% of patients with systemic sclerosis and, although only around 25% develop progressive disease, this again contributes to substantial morbidity and mortality [35]. In a retrospective observational study an association was found between abnormal NFC and the presence of ILD [49]. Capillaroscopic abnormalities were associated with a mean 15% reduction in forced vital capacity and DLCO compared to participants with normal capillaroscopy findings. Multiple other studies have also found an association between abnormal capillaroscopy and the presence or severity of ILD [27, 34, 46].
Abnormal NFC has been associated with an increased mortality. A study of almost 3000 patients with Raynaud’s symptoms but without an established diagnosis of a CTD was conducted for a mean of 9.3 years. An increased all-cause mortality rate was found for females (HR 1.10; 1.07–1.77) but this association was interestingly not found for males, although the substantially fewer males with Raynaud’s syndrome and relatively short follow up for this outcome measure may have impacted [50]. A more recent study also found an association between capillary loss and mortality, although this did not remain significant after multi-variant adjustment [51].
There has never been more activity and interest in capillaroscopy and its applications are only likely to expand over time. Although its role in the diagnosis of SSc is well established, it is emerging as having a role in a variety of other CTDs such as the idiopathic inflammatory myopathies (IIM) and mixed connective tissue disease (MCTD). Even within SSc there is much ongoing work into further understanding the potential role for capillaroscopy in more accurately screening and monitoring for disease complications and as a putative biomarker. Others are evaluating the potential role of capillaroscopy in monitoring the efficacy of new therapies and as a trial outcome measure. Finally, it is likely that capillaroscopy can be combined with complementary technologies or investigations to better serve the need for progress in the understanding and management of CTDs.
Implicit in Maricq’s initial qualitative classification of the “scleroderma-dermatomyositis” pattern was a recognition that dermatomyositis (DM) had similar nailfold capillary changes to SSc. This perhaps is not surprising given, like SSc, DM is a condition characterised by microvasculopathy and, along with other IIM subtypes such as the anti-synthetase syndrome and overlap myositis, it shares many clinical manifestations such as Raynaud’s syndrome, myositis and cutaneous involvement [52]. NFC has not been as thoroughly evaluated in this patient group as in SSc but there are some interesting findings. An Italian study of 52 patients with IIM found nailfold changes were significantly more common in patients with DM versus polymyositis (PM) and that disease duration seemed to have an impact on the features, as patients with longer disease duration had less of the “late” features [53]. This may seem counter-intuitive and the opposite of the findings in SSc where there is a trend towards more “late” pattern changes with increasing disease duration, but the study was not controlled for the impact of treatment on the capillary features. In an earlier study from Spain, the combination of microhaemorrhages and capillary enlargement was found more frequently in patients with DM
Many patients with MCTD, which again shares considerable clinical manifestation overlap with SSc, will have NFC abnormalities although this has not been studied in isolation [33]. The recent study by Markusse et al. found that the “early” pattern was associated with a positive anti-RNP antibody, a hint that, similar to NFC in the IIM, MCTD may have differing underlying microvascular pathophysiology with less avascular areas or capillary drop-out compared to patients with SSc [46].
In a recent systematic review, Cutolo et al. have helped summarise the limited existing literature of NFC in systemic lupus erythematosus (SLE) [57]. Although differences in the prevalence of capillary abnormalities in patients with SLE compared to normal controls have been found (especially with increased capillary tortuosity, prominent venous plexus and elongated capillaries), these are usually subtle compared to the more marked findings in SSc and IIM. An increased NFC score did correlate with disease activity in the majority of the few studies that reported on this, especially with the frequency of Raynaud’s symptoms or digital gangrene.
Although the role of NFC in diagnosis is well established, its role, if any, in established disease is less clear – could serial examinations be used to screen for complications in much the same way as an annual echocardiogram and pulmonary function tests would do? Prospective longitudinal studies are required to properly address this question, and some are already completed or underway. A recent study by Avouac et al. followed patients prospectively over three years and found that changes in NFC over time (in particular a loss of capillary density to <4 per mm), which occurred in almost half of patients, was a strong marker of organ progression [58]. As mentioned above numerous studies have linked the “late” NFC pattern with SSc disease activity, digital ulcers, cutaneous, cardiac and pulmonary involvement, which suggests an evolution of NFC changes over time [24, 26, 27]. A study from Brazil looked at overall mortality within a group of patients with SSc and found an increased mortality in those with more marked capillary loss [59]. Longitudinal NFC assessments in patients with systemic sclerosis could become feasibly become a part of routine care [60]. The comprehensive review by Ingegnoli & Gualtierotti also summarises the literature to date on the association between abnormalities of NFC and other serum biomarkers such as endothelin-1 and VEGF, which offers an insight into a potential future where biomarkers could be combined to stratify patients and personalise management [9].
Another area that is being researched intensively is in the arena of monitoring effects of drugs on nailfold changes. If, as has been largely established, the structural microvascular changes in CTDs can associate with disease activity, it would also make sense that a successful treatment may reverse the microvascular changes. NFC could therefore be used as a measure of treatment efficacy or even a trial outcome measure. There have been reports of significant improvements in microangiopathy paralleling the substantial clinical improvement in patients after autologous haematopoeitic stem cell transplant (HSCT) for SSc as well as in a patient with anti-synthetase syndrome [61, 62, 63]. In one report (of two patients with SSc and MCTD respectively), progressive improvements in NFC were seen with the cyclophosphamide used for stem cell mobilisation and then the subsequent HSCT [63]. Despite the evidence that endothelin-1 inhibitors reduce the incidence of digital ulcer recurrence and Raynaud’s symptoms [64, 65, 66], two studies have failed to find significant changes in structural microvascular changes [67, 68]. However, the follow up of these studies was relatively short and it has been argued that the true impact of endothelin-1 antagonists on structural microvascular change may take longer to establish. Similarly, intravenous prostanoid therapy was not associated with NFC improvements at 12 months despite a statistically significant improvement in Raynaud’s symptoms [69]. Some researchers are already postulating that making an early diagnosis of SSc in patients with NFC abnormalities may allow for the early instigation of preventative therapies (e.g. endothelin-1 antagonists to prevent pulmonary hypertension, antifibrotic therapies to prevent ILD) and therefore help change the natural history of the disease [70].
As technology rapidly advances there may become available a variety of novel techniques that allow for image acquisition. Inexpensive USB microscopes are already available as are accessory equipment allowing the digital camera of a smart phone to take diagnostically useful images [11]. Technology could also be harnessed to allow for quicker and more reproducible image assessment, as in the case of the recent publication of automated capillary counting [30]. NFC is an excellent measure of structural microvascular changes in disease, but the role and assessment of functional changes may also add clinically useful information. Thermography, where the skin surface temperature is measured using thermal cameras, is already well established at some expert centres [20]. The equipment is relatively expensive and requires regular calibration but technology is advancing and soon thermal cameras may be available as smartphone attachments. Several studies have shown thermography to be able to differentiate between healthy controls and primary Raynaud’s and between primary Raynaud’s and Raynaud’s secondary to systemic sclerosis based upon an abnormal pattern (a persistent “distal-dorsal difference”) of rewarming [71, 72]. Although thermography as a stand-alone test has some utility, further work may help establish that, in time, assessments of patients with potential CTD may include both a structural assessment in the form of NFC and a functional assessment. Developing a standardised protocol for thermography with a plan to validate the protocol to assist ongoing research in thermography is already underway [39]. Another novel strategy for functional perfusion assessment is to use Laser technology. Techniques such as laser Doppler flowmetry and laser speckle contrast analysis (LASCA) have shown good reliability in patients with SSc [73, 74, 75, 76, 77]. Advances are occurring in parallel with advances in other non-invasive imaging techniques such as optical coherence tomography and photoacoustic imaging which allow the opportunity to view the skin and cutaneous vessels in three dimensions [20].
Despite the great progress made by research into NFC over the last 50 years there is much work that is still required to be done. There is a great need for a widely-accepted consensus classification criteria. Work needs to continue to improve awareness of and access to the investigation which will be aided by more convenient and cheaper technologies. Prospective longitudinal studies will allow for a better understanding of certain nailfold capillary abnormalities and their link with organ-specific complications, disease severity, disease activity and hopefully, in time, the efficacy of certain treatments. Further work will also target other related CTDs.
Nailfold capillaroscopy is a simple, non-invasive, and non-expensive investigation with established roles in the diagnosis of scleroderma-spectrum disorders as well as being linked to the presence and severity of a variety of serious organ-specific manifestations which account for substantial morbidity and mortality. Access to the investigation is likely to increase as technology makes equipment more user friendly, reproducible and inexpensive. Demand for the investigation is similarly going to increase substantially as it has been included in recent classification criteria for SSc and the potential clinical applications are only increasing in a wide range of conditions characterised by microangiopathy. Because microvascular change is often present very early in the clinical disease course, nailfold capillaroscopy may be a tool to identify a “window of opportunity”, in conditions which to date have proven largely refractory to the therapies employed with much greater success in other rheumatic and autoimmune disease. It may usher in a new era of preventative rather than reactionary therapy and may become a part of disease management decisions, perhaps in a similar way to the use of clinical ultrasound in patients with rheumatoid arthritis. It is of relevance to all clinicians seeing patients with suspected connective tissue diseases to stay abreast of the progress being made in nailfold capillaroscopy and the related investigations.
The authors would like to thank the patients of Royal Prince Alfred Hospital.
The authors declare no conflict of interests.
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Lauret",authors:[{id:"86588",title:"Prof.",name:"Jean Philippe",middleName:null,surname:"Gastellu-Etchegorry",slug:"jean-philippe-gastellu-etchegorry",fullName:"Jean Philippe Gastellu-Etchegorry"}]},{id:"28865",doi:"10.5772/30323",title:"3D Modelling from Real Data",slug:"3d-modeling-from-real-data",totalDownloads:3411,totalCrossrefCites:14,totalDimensionsCites:22,abstract:null,book:{id:"907",slug:"modeling-and-simulation-in-engineering",title:"Modeling and Simulation in Engineering",fullTitle:"Modeling and Simulation in Engineering"},signatures:"Gabriele Guidi and Fabio Remondino",authors:[{id:"81959",title:"Prof.",name:"Gabriele",middleName:null,surname:"Guidi",slug:"gabriele-guidi",fullName:"Gabriele Guidi"},{id:"89325",title:"Dr.",name:"Fabio",middleName:null,surname:"Remondino",slug:"fabio-remondino",fullName:"Fabio Remondino"}]},{id:"28868",doi:"10.5772/29744",title:"Open Source 3D Game Engines for Serious Games Modeling",slug:"open-source-3d-game-engines-for-serious-games-modeling",totalDownloads:5655,totalCrossrefCites:7,totalDimensionsCites:14,abstract:null,book:{id:"907",slug:"modeling-and-simulation-in-engineering",title:"Modeling and Simulation in Engineering",fullTitle:"Modeling and Simulation in Engineering"},signatures:"Andres Navarro, Juan Vicente Pradilla and Octavio Rios",authors:[{id:"79143",title:"Prof.",name:"Andres",middleName:null,surname:"Navarro Cadavid",slug:"andres-navarro-cadavid",fullName:"Andres Navarro Cadavid"},{id:"90462",title:"BSc.",name:"Juan Vicente",middleName:null,surname:"Pradilla",slug:"juan-vicente-pradilla",fullName:"Juan Vicente Pradilla"},{id:"90463",title:"BSc.",name:"Octavio",middleName:null,surname:"Rios",slug:"octavio-rios",fullName:"Octavio Rios"}]},{id:"28867",doi:"10.5772/31092",title:"Applications of Computational 3D–Modeling in Organismal Biology",slug:"applications-of-computational-3d-modeling-in-biological-sciences",totalDownloads:2977,totalCrossrefCites:5,totalDimensionsCites:12,abstract:null,book:{id:"907",slug:"modeling-and-simulation-in-engineering",title:"Modeling and Simulation in Engineering",fullTitle:"Modeling and Simulation in Engineering"},signatures:"Christian Laforsch, Hannes Imhof, Robert Sigl, Marcus Settles, Martin Heß and Andreas Wanninger",authors:[{id:"57406",title:"Prof.",name:"Christian",middleName:null,surname:"Laforsch",slug:"christian-laforsch",fullName:"Christian Laforsch"},{id:"114845",title:"MSc.",name:"Hannes",middleName:null,surname:"Imhof",slug:"hannes-imhof",fullName:"Hannes Imhof"},{id:"131512",title:"MSc.",name:"Robert",middleName:null,surname:"Sigl",slug:"robert-sigl",fullName:"Robert Sigl"},{id:"131514",title:"Mr.",name:"Marcus",middleName:null,surname:"Settles",slug:"marcus-settles",fullName:"Marcus Settles"},{id:"131516",title:"Prof.",name:"Martin",middleName:null,surname:"Heß",slug:"martin-hess",fullName:"Martin Heß"},{id:"131517",title:"Prof.",name:"Andreas",middleName:null,surname:"Wanninger",slug:"andreas-wanninger",fullName:"Andreas Wanninger"}]},{id:"28871",doi:"10.5772/25955",title:"Virtual Prototyping for Rapid Product Development",slug:"virtual-prototyping-for-rapid-product-development",totalDownloads:4287,totalCrossrefCites:3,totalDimensionsCites:5,abstract:null,book:{id:"907",slug:"modeling-and-simulation-in-engineering",title:"Modeling and Simulation in Engineering",fullTitle:"Modeling and Simulation in Engineering"},signatures:"S.H. Choi and H.H. Cheung",authors:[{id:"13664",title:"Dr.",name:"S.H.",middleName:null,surname:"Choi",slug:"s.h.-choi",fullName:"S.H. Choi"},{id:"13744",title:"Dr.",name:"H.H.",middleName:null,surname:"Cheung",slug:"h.h.-cheung",fullName:"H.H. Cheung"}]}],mostDownloadedChaptersLast30Days:[{id:"62639",title:"Reliability Evaluation for Mechanical Systems by Petri Nets",slug:"reliability-evaluation-for-mechanical-systems-by-petri-nets",totalDownloads:1120,totalCrossrefCites:4,totalDimensionsCites:5,abstract:"The current trend in mechanical engineering is to design mechanical systems with higher stability, reliability, availability and operability. In order to meet the requirement of high reliability for a machine, it is of great importance for designers to seek the weak links in the system and learn the state of the key subsystems, carrying out the remedial measures when necessary. Hence, behavior modeling and failure analysis are the two aspects seriously concerned in the reliability evaluation in mechanical systems. This chapter will introduce new methodologies that use the fuzzy reasoning Petri net (FRPN) models to evaluate the reliability of mechanical systems in reliability prediction, reliability apportionment and reliability analysis. Cases are proposed by analyzing a spacecraft solar array system using the proposed method. Results indicate that the Petri nets models can contribute to a higher accuracy in reliability evaluation for mechanical systems.",book:{id:"6715",slug:"petri-nets-in-science-and-engineering",title:"Petri Nets in Science and Engineering",fullTitle:"Petri Nets in Science and Engineering"},signatures:"Jianing Wu and Shaoze Yan",authors:[{id:"238979",title:"Dr.",name:"Jianing",middleName:null,surname:"Wu",slug:"jianing-wu",fullName:"Jianing Wu"}]},{id:"54600",title:"Textile Forms’ Computer Simulation Techniques",slug:"textile-forms-computer-simulation-techniques",totalDownloads:1617,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Computer simulation techniques of textile forms already represent an important tool for textile and garment designers, since they offer numerous advantages, such as quick and simple introduction of changes while developing a model in comparison with conventional techniques. Therefore, the modeling and simulation of textile forms will always be an important issue and challenge for the researchers, since close‐to‐reality models are essential for understanding the performance and behavior of textile materials. This chapter deals with computer simulation of different textile forms. In the introductory part, it reviews the development of complex modeling and simulation techniques related to different textile forms. The main part of the chapter focuses on study of the fabric and fused panel drape by using the finite element method and on development of some representative textile forms, above all, on functional and protective clothing for persons who are sitting during performing different activities. Computer simulation techniques and scanned 3D body models in a sitting posture are used for this purpose. Engineering approaches to textile forms’ design for particular purposes, presented in this chapter, show benefits and limitations of specific 3D body scanning and computer simulation techniques and outline the future research challenges.",book:{id:"5707",slug:"computer-simulation",title:"Computer Simulation",fullTitle:"Computer Simulation"},signatures:"Andreja Rudolf, Slavica Bogović, Beti Rogina Car, Andrej Cupar,\nZoran Stjepanovič and Simona Jevšnik",authors:[{id:"180695",title:"Prof.",name:"Simona",middleName:null,surname:"Jevšnik",slug:"simona-jevsnik",fullName:"Simona Jevšnik"},{id:"181508",title:"Prof.",name:"Zoran",middleName:null,surname:"Stjepanovič",slug:"zoran-stjepanovic",fullName:"Zoran Stjepanovič"},{id:"195721",title:"Dr.",name:"Andreja",middleName:null,surname:"Rudolf",slug:"andreja-rudolf",fullName:"Andreja Rudolf"},{id:"196110",title:"Dr.",name:"Slavica",middleName:null,surname:"Bogović",slug:"slavica-bogovic",fullName:"Slavica Bogović"},{id:"196111",title:"Ph.D.",name:"Beti",middleName:null,surname:"Rogina-Car",slug:"beti-rogina-car",fullName:"Beti Rogina-Car"},{id:"196113",title:"Dr.",name:"Andrej",middleName:null,surname:"Cupar",slug:"andrej-cupar",fullName:"Andrej Cupar"}]},{id:"59877",title:"Petri Networks in the Planning of Discrete Manufacturing Processes",slug:"petri-networks-in-the-planning-of-discrete-manufacturing-processes",totalDownloads:1044,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This chapter puts forward characteristics of selected issues of manufacturing processes planning using the Petri networks technique. It includes references to the extensive literature concerning the use of Petri networks in computer aided planning of discrete production processes. Diversity of these problems is high as it refers both to the methods of modeling and simulation of the course of manufacturing processes, the issue of optimizing these processes and production systems, representation of knowledge on production parts of equipment and integration of planning and production activities in general. The work puts forward example use of a temporary, priority Petri network for modeling and optimizing production systems and manufacturing operations as well as an example of fuzzy interference using the Petri network mechanism.",book:{id:"6715",slug:"petri-nets-in-science-and-engineering",title:"Petri Nets in Science and Engineering",fullTitle:"Petri Nets in Science and Engineering"},signatures:"Roman Stryczek",authors:[{id:"238376",title:"Ph.D.",name:"Roman",middleName:null,surname:"Stryczek",slug:"roman-stryczek",fullName:"Roman Stryczek"}]},{id:"60326",title:"Performance Analysis of Shared-Memory Bus-Based Multiprocessors Using Timed Petri Nets",slug:"performance-analysis-of-shared-memory-bus-based-multiprocessors-using-timed-petri-nets",totalDownloads:956,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In shared-memory bus-based multiprocessors, the number of processors is often limited by the (shared) bus; when the utilization of the bus approaches 100%, processors spend an increasing amount of time waiting to get access to the bus (and shared memory) and this degrades their performance. The limitations imposed by the bus depend upon many parameters, and different parameters affect the performance in different ways. This chapter uses timed Petri nets to model shared-memory bus-based multiprocessors at the instruction execution level and shows how the performance of processors and the system are affected by different modeling parameters. Discrete-event simulation of the developed net models is used to get performance results.",book:{id:"6715",slug:"petri-nets-in-science-and-engineering",title:"Petri Nets in Science and Engineering",fullTitle:"Petri Nets in Science and Engineering"},signatures:"Wlodek M. Zuberek",authors:[{id:"146442",title:"Dr.",name:"Wlodek",middleName:null,surname:"Zuberek",slug:"wlodek-zuberek",fullName:"Wlodek Zuberek"}]},{id:"55001",title:"Computer Simulation of Bioprocess",slug:"computer-simulation-of-bioprocess",totalDownloads:1724,totalCrossrefCites:1,totalDimensionsCites:4,abstract:"Bioprocess optimization is important in order to make the bioproduction process more efficient and economic. The conventional optimization methods are costly and less efficient. On the other hand, modeling and computer simulation can reveal the mechanisms behind the phenomenon to some extent, to assist the deep analysis and efficient optimization of bioprocesses. In this chapter, modeling and computer simulation of microbial growth and metabolism kinetics, bioreactor dynamics, bioreactor feedback control will be made to show the application methods and the usefulness of modeling and computer simulation methods in optimization of the bioprocess technology.",book:{id:"5707",slug:"computer-simulation",title:"Computer Simulation",fullTitle:"Computer Simulation"},signatures:"Jianqun Lin, Ling Gao, Huibin Lin, Yilin Ren, Yutian Lin and\nJianqiang Lin",authors:[{id:"16729",title:"Dr.",name:"Jianqun",middleName:null,surname:"Lin",slug:"jianqun-lin",fullName:"Jianqun Lin"},{id:"16857",title:"Prof.",name:"Ling",middleName:null,surname:"Gao",slug:"ling-gao",fullName:"Ling Gao"},{id:"16859",title:"Dr.",name:"Jianqiang",middleName:null,surname:"Lin",slug:"jianqiang-lin",fullName:"Jianqiang Lin"},{id:"205062",title:"Mrs.",name:"Yutian",middleName:null,surname:"Lin",slug:"yutian-lin",fullName:"Yutian Lin"},{id:"205111",title:"Prof.",name:"Yilin",middleName:null,surname:"Ren",slug:"yilin-ren",fullName:"Yilin Ren"},{id:"205113",title:"Prof.",name:"Huibin",middleName:null,surname:"Lin",slug:"huibin-lin",fullName:"Huibin Lin"}]}],onlineFirstChaptersFilter:{topicId:"559",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:320,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:13,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:114,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:7,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:17,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},{id:"11",title:"Cell Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/11.jpg",isOpenForSubmission:!0,editor:{id:"133493",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/133493/images/3091_n.jpg",biography:"Prof. Dr. Angel Catalá \r\nShort Biography Angel Catalá was born in Rodeo (San Juan, Argentina). He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). 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