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systemic sclerosis ( ssc ) is an autoimmune connective tissue disease characterized by early impairment of the microvascular system , leading to functional and organic manifestations , including digital ulcers .
progressive deficiency in the vasodilatory capacity of the vessels , along with intimal fibroproliferation , thrombosis of the digital arteries , and tissue ischemia have been postulated as mechanisms explaining the persistent vascular involvement .
microvascular damage and dysfunction are the earliest morphological and functional markers of ssc and are correlated with prognosis and therapy planning .
the vascular changes occur during the early stage of ssc , with raynaud phenomenon ( rp ) as the clinical expression of abnormal blood flow regulation due to altered microvascular structure and function
. therefore , morphological and functional assessment of the peripheral microvasculature in ssc patients is a diagnostic necessity , with prognostic and therapeutic consequences .
laser doppler flowmetry ( ldf ) allows evaluation of the extent of perfusion in the peripheral microcirculation , while laser speckle contrast analysis ( lasca ) is a relatively new method that permits quantitative assessment of the peripheral perfusion in larger areas of different body sites .
this non - invasive , well - accepted , safe method makes use of a magnification system ( best at 200 magnification ) .
the video - capillaroscope has an optical / digital probe that can be moved over the surface of the fingernails from the second to the fifth digits .
nvc is used to evaluate the morphology of nailfold dermal papillary capillaries , thus allowing recognition of the qualitative , morphological patterns of microangiopathy ( early , active , and late ) ( fig .
the early ssc pattern is characterized by the presence of few giant capillaries , few capillary microhemorrhages , no evident capillary loss , and a relatively well - preserved capillary distribution .
it is characterized by frequent giant capillaries , frequent capillary microhemorrhages , moderate capillary loss , absent or mildly ramified capillaries , and a mild disorganization of the capillary architecture . in the late pattern , giant capillaries and microhemorrhages
are nearly absent , but there is severe capillary loss , with evident extensive avascular areas , ramified or bushy capillaries , and severe disorganization of the normal capillary array . in patients with rp , nvc can be used to distinguish the primary from the secondary forms of the disease . under normal conditions or in the presence of primary rp , nvc shows a regular array of capillary loops along the nailfold bed , no abnormal enlargements , and no capillary loss . in secondary rp , the morphological signs of giant capillaries , microhemorrhages , capillary loss , the presence of avascular areas , and angiogenesis are indicative of microvascular damage .
these sequential capillaroscopic changes are typical of the microvascular involvement observed in more than 95% of ssc patients and are described by the term " ssc pattern " .
nvc also provides a semiquantitative assessment of microvascular damage that can be used to follow its progression , based on a semiquantitative rating scale ( score 0 to 3 ) for the assessment of microvascular parameters .
the microangiopathy evolution score   is the sum of the three individual scores : capillary loss , disorganization of the microvascular array , and capillary ramifications .
qualitative and semiquantitative assessments also have been used to predict the clinical complications of ssc .
for example , patients with a reduced capillary density are at high risk of developing digital skin ulcers and pulmonary arterial hypertension .
inclusion of the nvc patterns in the diagnostic procedure could increase the sensitivity of the classification criteria for ssc , such as the new european league against rheumatism and american college of rheumatology criteria . moreover ,
nvc - based assessment of microvascular structure may be useful in the evaluation of drug effects during the treatment of ssc patients .
ldf is a user - friendly , well - accepted , and non - invasive assessment of microvascular flow at a single skin point .
it provides an index of skin perfusion by measuring the doppler shift induced by coherent light scattering caused by moving red blood cells .
an example of peripheral blood perfusion ( bp ) evaluated by ldf is shown in fig .
the instrument comprises a heatable probe , an optic fiber connector , an instrument that detects both tissue perfusion and skin temperature , and a computer to evaluate the data .
ldf measures local perfusion in a cubic millimeter of tissue ( capillaries , arterioles , venules , shunts ) , which is recorded in perfusion units ( pus ) , for example at the level of the fingertips .
basal finger temperature ( usually at the level of the fingertips , from the second to fifth digits of both hands ) is measured first , after which the probe is heated to 36 and capillary dilation capacity evaluated . in the study by binaghi et al .
, a significant correlation was found between the digital flow parameters and capillaroscopy score in ssc patients .
the results suggested the relevance of ldf in evaluating apparently primary rp during a standardized thermic test , because even in the absence of a definite scleroderma - like capillaroscopic pattern , flowmetry can be used to identify patients with secondary rp .
some studies have demonstrated that ssc patients have lower blood flow compared with healthy subjects , and that among the patients evaluated by nvc , those with a late ssc microangiopathy pattern have a lower rate of blood flow on ldf compared with those with the early or active pattern .
ssc patients were also shown to have abnormal microvascular regulatory responses to heat stimulation , suggesting that the degree of endothelial dysfunction is related to the degree of peripheral microvascular involvement .
in addition , ldf can assess changes in peripheral bp during treatment with vasodilator drugs either within a few days or over a period of years .
however , one problem with the technique is the large site - to - site variation , which limits its efficacy in comparing blood flow among sites and in monitoring changes over time . a new technique , laser doppler imaging , which evaluates flow over an anatomic area might overcome this problem .
this relatively new technique quantifies bp over an area rather than only at a single point , and thus it may obviate the problems that occur when a single probe is used , especially site - to - site variability .
lasca is based on the principle that when an object is illuminated by laser light , the backscattered light will form a random interference pattern made up of dark and bright areas .
this so - called speckle pattern is stationary , but when movement occurs , as in red blood cells within a tissue , the speckle pattern changes over time .
an advantage of lasca is that it allows commonly used settings ( e.g. , working distance , point density , frame rate resolution , and the width and height of the measurement area ) to be saved for repeated use .
moreover , lasca does not require direct contact between the probe and the skin , which might in itself affect blood flow .
it also evaluates the fluxes in different regions of interest ( rois ) and time regions of interest may also be created . using lasca , fingertip bp , during or after recording ( for example , at the fingertips and dorsum of the hand ) ,
the different values can be represented graphically , and the bp roi , whether depicted in color or as intensity images , are superimposed ( fig .
one such study demonstrated that peripheral bp , evaluated by ldf and lasca , correlates with the extent of the microangiopathy detected by nvc .
as noted above , when patients whose disease had been classified using nvc were then evaluated using ldf and lasca , those with the late ssc microangiopathy pattern had a lower blood flow than that of patients with early or active ssc patterns .
a very recent study showed that bp , when monitored by lasca , is significantly lower in ssc patients than in healthy subjects at the level of the fingertips , periungual areas , and palms of the hands .
in addition , in ssc patients , there is a statistically significant negative correlation between the extent of nailfold microangiopathy and bp at the level of those same skin areas .
similar combined investigations might optimize the follow - up of ssc patients . whether the combination of all three techniques ( nvc , ldf , and lasca ) improves the classification of ssc , including distinguishing patients with ssc from those with primary rp and from healthy controls , has yet to be confirmed by the appropriate studies .
however , thus far , when only a single microcirculatory tool is used , nvc seems to be the best discriminator .
peripheral microvascular morphology can be assessed using nvc , which also allows the classification and scoring of capillary abnormalities .
nvc is the best method to distinguish patients with secondary rp from those with primary rp and from healthy subjects .
nvc , ldf , and lasca together constitute an essential set of safe and noninvasive tools for the early diagnosis and reliable quantification of ssc , the response to therapy , and disease progression .
systemic sclerosis is a connective tissue disease characterized by alterations in microvascular structure and function . in these patients , 
 numerous studies have demonstrated a relationship between capillary morphology and peripheral blood perfusion . 
 nailfold videocapillaroscopy reveals the peripheral microvascular morphology and thus allows classification and scoring of capillary abnormalities with respect to different microangiopathy patterns ( early , active , and late ) . 
 laser doppler flowmetry and laser speckle contrast analysis can be used to estimate cutaneous blood flow through microvessels and to assess and quantify blood perfusion at peripheral sites . 
 these two methods are also used to identify changes in digital blood perfusion after the infusion of vasodilators .