Nailfold capillaroscopy assessment of microcirculation abnormalities and endothelial dysfunction in children with primary or secondary Raynaud syndrome.

Raynaud syndrome (RS) manifests as episodes of transient spasms of peripheral blood vessels, most often in response to cold. The reason of that symptom (primary RS (pRS)) usually cannot be found but may be accompanied by some autoimmune diseases (secondary RS (sRS)). In this study, we assessed microcapillary status and serum concentrations of chosen cytokines, adhesive molecules, and nitric oxide (NO) in patients with pRS and sRS in comparison with healthy children. Eighty-six patients with RS were enrolled into the study, including 52 with pRS and 34 with sRS. The control group consisted of 29 healthy children. A decrease in myorelaxative and anticoagulant abilities was observed, with simultaneous prevalence of vasopressor substances and procoagulative activity. Therefore, several important factors such as endothelin-1 (ET-1), E-selectin (E-sel), interleukin-18 (IL-18), and nitrogen oxide (NO) were also analyzed. Two types of capillaroscopy status were determined: normal and microangiopathic. There was a significant relationship between presence of microangiopathy and higher serum ET-1 (p = 0.018) and E-sel (p = 0.021) levels. Similarly, we have found a correlation between presence of ANA and higher ET-1 (p = 0.005), but not E-sel (p = 0.241). In patients with pRS, we found significant relationship between ANA and higher ET-1 (p = 0.008). No such relations were observed in sRS patients. Our data indicates that external factor-induced vasoconstrictive effects dominated in pRS, whereas in sRS in the course of connective tissue diseases, it was accompanied by coexistent vasodilation due to endothelial dysfunction. The latter phenomenon is at least partially dependent on insufficient NO release.

Symptoms of Raynaud's phenomenon (RP) in fibromyalgia syndrome are similar to those reported in primary RP despite differences in objective assessment of digital microvascular function and morphology.

Symptoms of Raynaud's phenomenon (RP) are common in fibromyalgia syndrome (FMS). We compared symptom characteristics and objective assessment of digital microvascular function using infrared thermography (and nailfold capillaroscopy where available) in patients with FMS (reporting RP symptoms) and primary RP. We retrospectively reviewed the outcome of microvascular imaging studies and RP symptom characteristics (captured using patient-completed questionnaire at the time of assessment) for patients with FMS (reporting RP symptoms) and patients with primary RP referred for thermographic assessment of RP symptoms over a 2-year period. Of 257 patients referred for thermographic assessment of RP symptoms between 2010 and 2012, we identified 85 patients with primary RP and 43 patients with FMS. There were no differences in RP symptom characteristics between FMS and primary RP (p > 0.05 for all comparisons). In contrast, patients with FMS had higher baseline temperature of the digits (32.1 vs. 29.0 °C, p = 0.004), dorsum (31.9 vs. 30.2 °C, p = 0.005) and thermal gradient (temperature of digits minus temperature of dorsum; +0.0 vs. -0.9 °C, p = 0.03) compared with primary RP. Significant differences between groups persisted following local cold challenge. In primary RP, patient reporting "blue" digits, bi-phasic and tri-phasic RP was associated with lower digital perfusion. In contrast, no associations between skin temperature and RP digital colour changes/phases were identified in FMS. Our findings suggest that symptoms of RP in FMS may have a different aetiology to those seen in primary RP. These findings have potential implications for both the classification of RP symptoms and the management of RP symptoms in the context of FMS. Digital colour changes reported by patients might reflect the degree of digital microvascular compromise in primary RP.

Raynaud’s phenomenon - assessment and differential diagnoses.

Raynaud’s phenomenon (RP) is characterised by paroxysmal reversible episodes of vasospasm, usually involving peripheral small vessels of the fingers or toes and resulting in a triple-colour change starting with pallor and followed by cyanosis and erythema. Attacks are typically triggered by cold or emotional stress. The diagnosis of RP can be made on the basis of the patient’s clinical symptoms. Primary RP occurs without underlying disease and is considered a benign condition. A normal erythrocyte sedimentation rate, negative testing for antinuclear antibodies, normal nailfold capillaries and the absence of structural micro- or macrovascular damage and other diseases lead to the diagnosis of primary RP. Digital photoplethysmography and pulse contour analysis can be used as an additional tool to exclude structural macro- or microvascular disease. In contrast, secondary RP is associated with other diseases, mainly connective tissue diseases such as systemic sclerosis. If there is a suspicion of secondary RP, a thorough laboratory and vascular assessment is required to make the diagnosis of underlying disease. Acrocyanosis and erythromelalgia are additional functional vascular disorders that can be easily distinguished when patients are carefully assessed for their history and clinical symptoms.

New insights into systemic sclerosis related microcirculatory dysfunction by assessment of sublingual micr\ocirculation and vascular glycocalyx layer. Results from a preliminary study.

BACKGROUND: Initial morphological and functional markers of systemic sclerosis (SSc) are evidenced in microvascular structural damage. However, nailfold videocapillaroscopy (NVC) explores only morphological abnormalities. Sidestream Dark Field (SDF) imaging of sublingual microcirculation enables assessment of both morphological and functional capillary impairment and allows measurement of the glycocalyx layer, which is an indicator of endothelial dysfunction. OBJECTIVE: To describe and validate sublingual abnormalities assessed by SDF device in comparison with NVC findings and to measure the thickness of the glycocalyx layer. METHODS: From February to May 2014, 26 subjects (16 SSc patients and 10 healthy controls) underwent standardised NVC and SDF imaging of sublingual microcirculation. Glycocalyx thickness was also measured. RESULTS: Capillary density and percentage of perfused vessels were significantly reduced in patients with SSc (n = 13) compared to controls. Correlation between nailfold capillary density assessed by NVC and sublingual capillary density assessed by SDF was observed (r(2) = 0.59; P = 0.023). According to the NVC pattern, patients with "active" disease experienced greater reduction in capillary density than patients with "late" disease as suggested by the de Backer score (9.17 ± 0.81 vs 10.86 ± 1.19; P = 0.03). Additionally, the decrease in glycocalyx thickness was measured in SSc patients (n = 13) compared to controls (n = 10) (0.41 ± 0.03 versus 0.76 ± 0.29 P = 0.003). CONCLUSION: Our results suggest for the first time in SSc, that sublingual microcirculation and glycocalyx are impaired and that SDF imaging findings correlate with those of NVC. Nevertheless, further studies are required for the validation of our preliminary results.

Reliability of widefield nailfold capillaroscopy and video capillaroscopy in the assessment of patients with Raynaud's phenomenon.

OBJECTIVE: To analyze the diagnostic performance and reliability of different parameters evaluated by widefield nailfold capillaroscopy (NFC) with those obtained by video capillaroscopy in patients with Raynaud's phenomenon (RP). METHODS: Two hundred fifty-two individuals were assessed, including 101 systemic sclerosis (SSc; scleroderma) patients,61 patients with undifferentiated connective tissue disease, 37 patients with primary RP, and 53 controls. Widefield NFC was performed using a stereomicroscope under 10­25 x magnification and direct measurement of all parameters. Video capillaroscopy was performed under 200 x magnification, with the acquirement of 32 images per individual (4 fields per finger in 8 fingers). The following parameters were analyzed in 8 fingers of the hands (excluding thumbs) by both methods: number of capillaries/mm, number of enlarged and giant capillaries, microhemorrhages, and avascular score.Intra- and interobserver reliability was evaluated by performing both examinations in 20 individuals on 2 different days and by 2 long-term experienced observers. RESULTS: There was a significant correlation (P < 0.000) between widefield NFC and video capillaroscopy in the comparison of all parameters. Kappa values and intraclass correlation coefficient analysis showed excellent intra- and interobserver reproducibility for all parameters evaluated by widefield NFC and video capillaroscopy. Bland-Altman analysis showed high agreement of all parameters evaluated in both methods. According to receiver operating characteristic curve analysis, both methods showed a similar performance in discriminating SSc patients from controls. CONCLUSION: Widefield NFC and video capillaroscopy are reliable and accurate methods and can be used equally for assessing peripheral microangiopathy in RP and SSc patients. Nonetheless, the high reliability obtained may not be similar for less experienced examiners.

Preliminary clinical evaluation of semi-automated nailfold capillaroscopy in the assessment of patients with Raynaud's phenomenon.

OBJECTIVES: Nailfold capillaroscopy is well established in screening patients with Raynaud's phenomenon for underlying SSc-spectrum disorders, by identifying abnormal capillaries. Our aim was to compare semi-automatic feature measurement from newly developed software with manual measurements, and determine the degree to which semi-automated data allows disease group classification. METHODS: Images from 46 healthy controls, 21 patients with PRP and 49 with SSc were preprocessed, and semi-automated measurements of intercapillary distance and capillary width, tortuosity, and derangement were performed. These were compared with manual measurements. Features were used to classify images into the three subject groups. RESULTS: Comparison of automatic and manual measures for distance, width, tortuosity, and derangement had correlations of r=0.583, 0.624, 0.495 (p<0.001), and 0.195 (p=0.040). For automatic measures, correlations were found between width and intercapillary distance, r=0.374, and width and tortuosity, r=0.573 (p<0.001). Significant differences between subject groups were found for all features (p<0.002). Overall, 75% of images correctly matched clinical classification using semi-automated features, compared with 71% for manual measurements. CONCLUSIONS: Semi-automatic and manual measurements of distance, width, and tortuosity showed moderate (but statistically significant) correlations. Correlation for derangement was weaker. Semi-automatic measurements are faster than manual measurements. Semi-automatic parameters identify differences between groups, and are as good as manual measurements for between-group classification.

Influence of the cold challenge on the discriminatory capacity of the digital distal-dorsal difference in the thermographic assessment of Raynaud's phenomenon.

OBJECTIVES: To investigate the influence of a standardised cold stress test (CST) on the thermographic 'distal-dorsal difference' (DDD) and its capacity to differentiate between disease states in the assessment of Raynaud's phenomenon (RP), and to compare the discriminatory capacity of the DDD of individual digits with composite indices of multiple digits. METHODS: Thermographic images of 55 patients with primary RP (PRP, n=27) and systemic sclerosis (SSc, n=28) who had undergone assessment of RP were retrospectively reviewed. The DDD for individual digits, and composite scores of multiple digits, were calculated at baseline (23°C), and at 10 min following CST. The discriminatory capacity of the mean DDD, and the proportion of patients with a clinically meaningful DDD of <-1°C, were assessed for individual digits and composite indices, at baseline and following cold challenge. RESULTS: There was a more pronounced decrease of the DDD (indicating reduced distal perfusion) following CST in patients with PRP compared to SSc. The disparity in response to CST between groups narrowed the differences that were present at baseline, reducing the discriminatory capacity of the DDD for all endpoints. Sparing of the thumbs occurs to a greater extent in SSc (P<0.005) compared with PRP (P<0.05) but does not facilitate differentiation between groups. Large variability of the DDD within groups precludes easy differentiation between disease states. Composite indices of multiple digits are preferable to individual digital assessment. CONCLUSIONS: The discriminatory capacity of the DDD is lost following CST. The CST may not be essential in the thermographic assessment of RP, potentially allowing greater use of thermography in clinical practise.

Early systemic sclerosis: assessment of clinical and pre-clinical organ involvement in patients with different disease features.

OBJECTIVE: To assess internal organ involvement in early SSc at presentation. METHODS: One hundred and fifteen patients admitted to a tertiary centre because of RP, who did not present any routinely detectable scleroderma-related internal organ involvement, were investigated for ANA and videocapillaroscopy, and underwent history and physical examination to detect symptoms/signs suggestive of SSc. Patients were then subdivided into three groups: (i) early SSc, constituted by patients without clinical manifestations other than RP, but with scleroderma marker autoantibodies and/or typical capillaroscopic abnormalities; (ii) probable SSc, constituted by patients with the same autoantibody and/or capillaroscopic status as early SSc patients, but with any of the following manifestations: digital ulcers/scars, puffy fingers, arthritis, telangiectasia, dysphagia/heartburn, shortness of breath; (iii) UCTD, constituted by patients with a specific (i.e. disease antibody marker) ANA and capillaroscopic findings plus any disease manifestation. All patients were investigated by lung functional study and B-mode echo-Doppler-cardiography. Patients who consented underwent oesophageal manometry. RESULTS: An inverted mitral E : A ratio (i.e. early scleroderma cardiac involvement) and/or a diffusing lung capacity for CO <80% of the predictive value (i.e. early lung involvement) and/or basal low oesophageal sphincter pressure <15 mmHg (i.e. early oesophageal involvement) were detected in 37/51 probable SSc patients (72%), 8/19 early SSc patients (42%) and 12/45 UCTD patients (27%). CONCLUSION: A scleroderma-related internal organ involvement was detected in patients from each group and, more importantly, was pre-clinical in a number of cases.

Comparison of laser Doppler imaging, fingertip lacticemy test, and nailfold capillaroscopy for assessment of digital microcirculation in systemic sclerosis.

INTRODUCTION: Laser Doppler imaging (LDI) is a relatively new method for assessing the functional aspect of superficial skin blood flow in systemic sclerosis (SSc) and Raynaud's phenomenon. The present study investigated the dynamic behavior of digital skin microvascular blood flow before and after cold stimulus (CS) in SSc patients and in healthy controls by means of a comprehensive approach of the functional (LDI), morphological (nailfold capillaroscopy (NFC)), and biochemical (fingertip lacticemy (FTL)) microcirculation components. METHODS: Forty-four SSc patients and 40 healthy controls were included. After acclimatization, all subjects underwent NFC followed by LDI and FTL measurement. NFC was performed with a stereomicroscope under 10× to 20× magnification in the 10 digits of the hands. Skin blood flow of the dorsum of four fingertips (excluding the thumb) of the left hand was measured using LDI at baseline and for 30 minutes after CS. The mean finger blood flow (FBF) of the four fingertips was expressed as arbitrary perfusion units. FTL was determined on the fourth left finger before (pre-CS-FTL) and 10 minutes after CS. RESULTS: LDI showed significantly lower mean baseline FBF in SSc patients as compared with controls (296.9 ± 208.8 vs. 503.6 ± 146.4 perfusion units; P < 0.001) and also at all time points after CS (P < 0.001). There was a significant decrease in mean FBF after CS as compared with baseline in SSc patients and in controls, followed by recovery of the blood flow 27 minutes after CS in healthy controls, but not in SSc patients. FBF tended to be lower in patients with digital scars and previous ulceration/amputation (P = 0.06). There was no correlation between mean baseline FBF and NFC parameters. Interestingly, there was a negative correlation between FTL and FBF measured by LDI in basal conditions and 10 minutes after CS in SSc patients. CONCLUSIONS: LDI showed lower digital blood flow in SSc patients when compared with healthy controls and correlated well with FTL both at baseline and after CS, allowing objective measurement of blood perfusion in SSc patients. The lack of correlation between functional and morphological microvascular abnormalities, measured by LDI and NFC, suggests they are complementary tools for evaluation of independent microangiopathy aspects in SSc patients.

Noninvasive imaging techniques in the assessment of scleroderma spectrum disorders.

OBJECTIVE: Systemic sclerosis (SSc) affects both microvascular structure and function. Laser Doppler imaging (LDI) and thermal imaging can be used to measure cutaneous blood vessel function. Nailfold capillaroscopy (NC) measures capillary morphology. The aim of this study was to investigate the relationship between capillary morphology and blood flow, and to determine which combination of techniques allows the best discrimination between patients with SSc, primary Raynaud's phenomenon (RP), and healthy controls. METHODS: NC was performed in 16 patients with SSc, 14 patients with primary RP, and 16 healthy controls. In addition, participants underwent cold stimulus with cold water. Hands were imaged to monitor rewarming and reperfusion. Nailfold morphologic features were measured and baseline images and rewarming curves were analyzed. RESULTS: Significant differences were found between groups (analysis of variance) for capillary morphologic features and rewarming curve characteristics. A correlation (P < 0.001) was found between LDI and thermal imaging at baseline (0.667) and maximum (0.729) blood flow and skin temperature, and for the areas under the rewarming curves (0.684). Receiver operating characteristic curves indicated that NC, thermal imaging, and LDI allowed 89%, 74%, and 72%, respectively, of SSc patient data to be correctly classified versus primary RP patients and controls. CONCLUSION: NC, LDI, and thermal imaging each independently provide good discrimination between patients with SSc and those with primary RP and healthy controls (NC being the most suitable technique for classifying patient groups). However, a combination of all 3 techniques improves classification. LDI and thermal imaging give equivalent information on dynamic changes in the cutaneous microcirculation; however, these only weakly correspond to capillary morphology.

Measurement, evaluation, and assessment of peripheral neurological disorders caused by hand-transmitted vibration.

Regular exposure to hand-transmitted vibration can result in symptoms and signs of peripheral vascular, neurological and other disorders collectively known as the hand-arm vibration syndrome. The measurement of the effects of hand-transmitted vibration involves converting the evidence of disorder (symptoms and signs) into information that can be stored. Evaluation requires the use of scales on which to indicate the severity of the various symptoms and signs. Assessment involves a judgement of severity relative to a criterion, usually for a specific purpose (e.g. to decide on removal from work or compensation). The measurement and evaluation of symptoms and signs is necessary when monitoring patient health and when performing epidemiological studies for research. The assessment of the severity of the hand-arm vibration syndrome is currently performed with staging systems, but the criteria are not clear and not related to defined methods for measuring or evaluating the symptoms and signs. Recognizing that similar symptoms can occur without injury from occupational exposures to hand-transmitted vibration, this paper attempts to define significant peripheral neurological symptoms caused by hand-transmitted vibration (i.e. 'unusual symptoms') and how these symptoms and related signs may be measured. Scales for evaluating the symptoms (e.g. their extent) and the related signs (e.g. their probability relative to the probability of the sign being present in persons not exposed to vibration) are defined. A method of relating unusual symptoms to both the signs of disorder and the pattern of vibration exposure is illustrated. Assessments of severity will vary according to the reasons for assessing the health effects of vibration, and will depend on local practice and convenience, but a way of combining evaluations of symptoms and signs is demonstrated in a staging system. Although inherently complex, the methods may assist the collection of data required to improve understanding of the effects of hand-transmitted vibration and also support a more complete reporting of the condition in those adversely affected by hand-transmitted vibration.

A cold-response index for the assessment of Raynaud's phenomenon.

BACKGROUND: Quantification of Raynaud's phenomenon (RP) is a prerequisite in the evaluation of novel therapeutic strategies. Fingertip rewarming in response to local cold provocation has been used in many studies but not been systematically validated. We have previously described the time elapsed before 63% of pre-cooling temperature is reached as a RP activity index. OBJECTIVE: A comprehensive evaluation of fingertip rewarming in primary and scleroderma-associated RP. METHODS: We defined a cold-response index (CRI) as the log transformation of the 63% rewarming time upon cold challenge. RESULTS: The CRI shows high intra-individual reproducibility. The mean CRI values were (mean+/-S.D.): 2.4+/-0.3 in controls (n=53) versus 2.7+/-0.3 in RP (n=50, p<0.0001 versus controls), and 2.7+/-0.3 in scleroderma patients (n=46, p<0.0001). In addition, baseline fingertip temperature was also found to be significantly reduced both in primary as well as scleroderma-associated RP. Kinetic analysis of rewarming temperature curves demonstrates that the CRI is independent of individual rewarming patterns. Finally, the CRI decreases significantly upon a single low-level systemic hyperthermia treatment in scleroderma patients (2.68+/-0.28 before versus 2.45+/-0.33 after, p=0.0003), while the extent of cooling remained unchanged, thus demonstrating sensitivity to change. CONCLUSION: Our results provide a solid basis for using the cold-response assay as an endpoint in addition to clinical activity scores in RP treatment trials.

Infrared-monitored cold response in the assessment of Raynaud's phenomenon.

BACKGROUND: Evaluation of treatments for Raynaud's phenomenon (RP) requires objective response parameters in addition to clinical activity scores. Thermographic monitoring of fingertip re-warming after cold challenge has been widely used but usually requires sophisticated equipment. We have previously shown that fingertip re-warming after cold challenge follows a first-order transient response curve that can be described by a single variable, designated tau. OBJECTIVES: Here, we describe a novel device termed a duosensor, which records the tau value upon cold challenge in an automated manner. METHODS: We determined tau values in healthy probands, patients with primary or secondary RP associated with autoimmune disease and patients with scleroderma-associated RP following cold challenge, to determine assay variability, sensitivity and specificity. RESULTS: Duosensor-based thermography exhibited low intraindividual variability in healthy probands. As expected, tau values in RP patients were significantly increased compared with controls (8.08 +/- 3.65 min vs. 3.23 +/- 1.65 min). The duosensor-determined tau value yielded a specificity of 94.6% and predictive value of 95.3% for the presence of RP in a retrospective analysis of 139 patients. Furthermore, in a cohort of scleroderma patients with RP, patient self-assessment of RP severity correlated with tau values. CONCLUSIONS: Taken together, the present data suggest that tau value determination provides a suitable outcome measure for clinical studies of novel RP treatments. As the duosensor is a simple stand-alone device requiring no supporting equipment and minimal personnel attention, it should allow RP activity monitoring even in clinical settings with minimal technical infrastructure.

Computerized nailfold video capillaroscopy--a new tool for assessment of Raynaud's phenomenon.

OBJECTIVE: To develop a computer based nailfold video capillaroscopy system with enhanced image quality and to assess its disease-subgroup resolving power in patients with primary and secondary Raynaud's phenomenon (RP). METHODS: Using frame registration software, digitized video images from the microscope were combined to form a panoramic mosaic of the nailfold. Capillary dimensions (apex, arterial, venous, and total width) and density were measured onscreen. Significantly, the new system could guarantee analysis of the same set of capillaries by 2 observers. Forty-eight healthy control subjects, 21 patients with primary RP, 40 patients with limited cutaneous systemic sclerosis (lcSSc), and 11 patients with diffuse cutaneous SSc (dcSSc) were studied. Intra- and interobserver variability were calculated in a subset of 30 subjects. RESULTS: The number of loops/mm was significantly lower, and all 4 capillary dimensions significantly greater, in SSc patients versus controls plus primary RP patients (p < 0.001 for all measures). When comparing control (+ primary RP) patients with SSc patients (lcSSc + dcSSc) the most powerful discriminator was found to be the number of loops/mm. Results for intra- and interobserver reproducibility showed that the limits of agreement were closer when both observers measured the same capillaries. CONCLUSION: The key feature of the newly developed system is that it improves reproducibility of nailfold capillary measurements by allowing reidentification of the same capillaries by different observers. By allowing access to previous measurements, the new system should improve reliability in longitudinal studies, and therefore has the potential of being a valuable outcome measure of microvessel disease/involvement in clinical trials of scleroderma spectrum disorders.

Assessment of digital ischaemia and evaluation of response to therapy by 99mTc sestamibi limb scintigraphy after local cooling of the hands in patients with vasospastic Raynaud's syndrome.

AIM: Cold induced arteriolar constriction in patients with vasospastic Raynaud's syndrome (VRS) produces temporary digital ischaemia. The aim of this study was to ascertain whether 99mTc sestamibi scintigraphy is useful in the diagnosis and the monitoring of treatment in VRS. METHODS: Fifteen patients with VRS and 20 matched normal controls underwent examination. Twelve patients with VRS received therapy. For each patient, one hand was immersed in iced water for 30s while the other hand served as a control. Ten minutes after cooling, 99mTc sestamibi was injected and imaging was performed 60min later. The per cent decrease of the perfusion (%DP) was calculated by semiquantitative analysis to determine the severity of hypoperfusion. RESULTS: In all patients with VRS, moderate or marked hypoperfusion were seen in 99mTc sestamibi images after exposure to the iced water, while there was minimal or mild hypoperfusion in the control groups. Values for %DP were 46.86 +/- 19.04 and 7.85 +/- 4.53 for the VRS group and normal subjects, respectively. The difference between both groups was statistically significant (P = 0.0000). In 12 treated patients with VRS, pre-treatment and post-treatment %DP values were 51.16 +/- 18.42 and 33.58 +/- 17.83, respectively, and a significant difference was seen between both values (P = 0.001). However, there was still a statistically significant difference between control subjects and post-therapy values (7.85 +/- 4.53 vs. 33.58 +/- 17.83, P = 0.0000). The +/- 95% confidence interval of DP for control subjects was 5.7-10% (chi-squared, P = 0.000). When a DP of 10% was used as a cut-off point, sensitivity, specificity and diagnostic accuracy were 100%, 70% and 83%, respectively, for the 99mTc sestamibi scan. There was also a strong correlation between %DP and the duration of the disease (r = 0.80, P = 0.0003). CONCLUSION: The results of this study indicate that a 99mTc sestamibi scan is a valuable imaging method for the determination of digital ischaemia in vasospastic Raynaud's syndrome, and may play a role in evaluating the response to therapy.

Quantitative assessment of peripheral arterial obstruction in Raynaud's phenomenon: development of a predictive model of obstructive arterial cross-sectional area and validation with a Doppler blood flow study.

The objective of this study was to develop a method for the analytical assessment of arterial obstruction in conditions of Raynaud's phenomenon capable of providing diagnostic criteria. Numerous attempts have been made to determine and quantify arterial obstruction in terms of Doppler ultrasound measurements of arterial blood velocity. Absent from these methods is a formulation that allows an assessment of arterial obstruction based on the obstructed area as derived from direct measurement. The authors used spectral analysis of velocity signals from a pulsed, range-gated Doppler ultrasonic instrument to make quantitative measurements of arterial blood flow velocity in hands of normal subjects and persons with Raynaud's phenomenon. They measured the peak and mean velocity during the cardiac cycle and the time integral of the velocity signal over the cardiac cycle. These measurements for two distinct hemodynamic states induced by temperature changes allowed them to calculate the fractional change in arterial cross-sectional area produced by the change in temperature through the application of a hydraulic model of digital arterial circulation. They found an equation expressing fractional obstructed area expressed as: dA/A = 2 (dD - taudv - vtau)/(D + vdtau), where D is the time integral of the velocity signal; tau is the blood flow interval, v is the blood velocity; and dD, dtau and dv are the differences in D, tau, and v at two different hemodynamic states produced by two different temperature states. Their findings suggest that over a temperature range of 35 degrees-25 degrees C, normal subjects experience 0.05/ degrees C reduction in cross-sectional area while Raynaud subjects experience a reduction of 5.8%/degrees C. The results, based on findings in 13 subjects, suggest that Doppler ultrasound can differentiate persons with Raynaud's phenomenon from normal subjects. Additionally, the hydraulic model appears to offer the potential of assessing relative stenotic area in other arterial obstructive diseases.

Non-invasive assessment of digital vascular reactivity in patients with primary Raynaud's phenonenon and systemic sclerosis.

OBJECTIVE: To examine digital microvascular responses in patients with primary Raynaud's phenomenon (PRP) and systemic sclerosis (SSc), and compare these to the responses in healthy control subjects. METHODS: Digital microvascular responses to repeated episodes of iontophoresis of acetylcholine chloride (endothelial-dependent), sodium nitroprusside (endothelial-independant) and adrenaline were measured using dual-channel laser Doppler in 8 healthy control subjects, 8 patients with PRP and 8 patients with SSc. RESULTS: There were no significant differences in responses between groups. For each chemical the greatest response was generally seen in period 7 of the protocol (after the third episode of iontophoresis). For acetylcholine chloride in period 7, the age and baseline adjusted ratio of the maximum response of PRP to control was 0.93, 95% CI (0.26, 3.38) and for SSc to control it was 0.60, 95% CI (0.13, 2.81). For sodium nitroprusside in period 7, this age and baseline adjusted ratio of the maximum response of PRP to control was 1.31, 95% CI (0.74, 2.32) and for SSc to control it was 1.35, 95% CI (0.68, 2.67). For adrenaline in period 7, the age and baseline adjusted ratio of PRP to control was 1.51, 95% CI (0.79, 2.89) and for SSc to control it was 2.18, 95% CI (1.01, 4.69). CONCLUSION: This study demonstrates the usefulness of iontophoresis of vasoactive chemicals, combined with laser Doppler blood flowmetry, in the non-invasive assessment of dermal microvascular responses. One possible explanation for the lack of difference in responses between groups is that vasoactive chemicals other than those discussed are important in the pathophysiology of primary and secondary Raynaud's phenomenon.

The poor man's capillary microscope. A novel technique for the assessment of capillary morphology.

OBJECTIVES: To evaluate a new method for rapid and efficient assessment of capillary morphology. METHODS: Nailfold capillary morphology in 18 patients with Raynaud's phenomenon was investigated with a new bedside test, based on a modified dermatoscope using a novel gel-immersion technique. These findings were compared with those obtained by standard capillary microscopy. RESULTS: With the standard microscope, six patients had dilated capillaries, six had mega-capillaries, seven had avascular fields, eight had ramified capillaries, six had contorted capillaries, and seven patients showed micro-haemorrhages, respectively. The dermatoscope identified exactly the same patients to have the same capillary abnormalities. One hundred and thirty six fingers were available for pairwise comparison: The kappa statistic was 0.93 for dilated capillaries, 0.97 for mega-capillaries, 0.93 for avascular areas, 0.78 for ramified capillaries, 0.81 for contorted capillaries, and 0.94 for micro-haemorrhages, respectively. The average examination time was 18 (range 8-30) minutes with the standard microscope and 4 (3-8) minutes with the dermatoscope. CONCLUSION: A new diagnostic tool for rapid and efficient examination of nailfold capillaries is described for circumstances when a standard microscope is not available. This study shows that the hand held device can be used in clinical routine with sufficient diagnostic efficacy and little expenditure, both timewise and financially.