Nailfold Capillary Microscopy Research Articles

AB0501 Systolic blood pressure, not nailfold capillary microscopic finding, is the most important factor of arterial stiffness in systemic sclerosis patients

ObjectivesTo find the determinants of pulse wave velocity (PWV) and evaluate the association between degree of capillary microscopic changes and PWV in systemic sclerosis (SSc) patients.MethodsForty-five systemic sclerosis patients were...

Raynaud-Phänomen bei einer beruflichen Vibrationsbelastung

A 34-year-old female stonemason was referred for expert opinion. The question at issue was, whether she suffered from vibration-induced white finger disease. She was exposed to high-frequency hand-arm vibrations for many years. She reported white finger attacks at the long fingers, which were associated with cold weather. Until this point, physical findings were normal. The cold water provocation test showed a slight delay of the rewarming for the long fingers of the right hand. The nailfold capillary microscopy was normal. The slight Raynaud's phenomenon was recognized as an occupational disease with a diagnosis of vibration-induced white finger disease. About three years later, the symptoms of the Raynaud's phenomenon had deteriorated, although the patient had finished working with vibrating tools. The cold water provocation test confirmed the deterioration. At this time, the patient had inflamed swellings of some joints caused by rheumatoid arthritis. The differential diagnosis of a Raynaud's phenomenon should include occupational causes. Occupational history is diagnostically indicative. If an occupational disease is assumed, a report must be filed. With respect to German social law, the deterioration of the Raynaud's phenomenon was caused by the rheumatoid arthritis, which is regarded as independent from the job.

Reduction of the Nailfold Capillary Blood Velocity in Cigarette Smokers

BackgroundCigarette smoking causes cardiovascular disease and activates markers of endothelial dysfunction or injury. We investigated the nailfold capillary blood velocity (NCV) in cigarette smokers compared to non-smokers.MethodsForty-eight men (eighteen non-smokers and thirty smokers) were recruited. We measured NCV using nailfold capillary microscopy and exhaled carbon monoxide (ECO) concentration three times (before smoking; NCV0min and ECO0min, and after smoking; NCV5min, ECO5min, NCV30min, and ECO30min), in a condition of fasting in the case of smokers. In non-smokers, the same measurements were taken without smoking. Additionally, personal cigarette smoking and alcohol drinking history were acquired by a self-administrated questionnaire.ResultsMean age, waist circumference, ECO0min, ECO5min, and ECO30min was higher and NCV5min and NCV30min were significantly lower in smokers compared to non-smokers. Total smoking years were negatively correlated with NCV5min. Average pack of the daily smoking, total pack-years, as well as total smoking years were also negatively correlated with NCV30min by regression analysis. After adjustment of significantly different variables, NCV30min was significantly lower in smokers. In the subgroup analysis, the interleukin-6 level was significantly increased in subjects with a long period of cigarette smoking compared with non-smokers.ConclusionReduction of NCV in smokers is associated with personal smoking history, not with body composition or certain oxidative stress markers.

Actualités du 45e Congrès du Collège Français de Pathologie Vasculaire (CFPV) Paris, 16–18 mars 2011

The 45(th) Congress of the French College of Vascular Disease (CFPV) has been held in Paris in March 2011. Scientific sessions covered many fields of vascular diseases. A short synthesis is proposed there. A large part of the programme is related to new treatments for venous thrombo-embolic disease, healing factors of chronic leg ulcers, medical networks, hormones and atherothrombosis, cardiovascular risk in connective tissue diseases, vascular treatment and elderly, vascular compression syndromes, nailfold capillary microscopy.

Diabetic foot in the elderly: Capillaroscopic findings

Microangiopathy is the most frequent complication of diabetes mellitus. It frequently precedes metabolic and biohumoral pathology. The diabetic foot is a particular aspect of the disease. Capillary videomicroscopy has proven to be a valuable technique for detecting early morpho-functional changes in the microcirculation in vivo. It is performed at the fingers' nailfold, at conjunctiva, and on the skin. This study aims to propose a qualitative assessment of microvascular complications in elderly patients with diabetes mellitus by toe nailfold capillary microscopy.

Morphologic Classification of Nailfold Capillary Microscopy in Workers Exposed to Hand-arm Vibration

The aim of this study was to investigate the association between the morphologic classification of nailfold capillary microscopy and the clinical and demographic findings in workers exposed to hand-arm vibration. The subjects were 44 male forestry workers (average age; 51.9 ± 14.8 yr). The nailfold capillaries (NC) and the mean blood flow velocity were measured on the middle finger of the dominant side by a peripheral capillary observer. The analyses were made using 39 subjects after excluding five subjects who received medication for hypertension. The observed NC were classified into 5 types according to Kusumoto's classification: Type I, n=5; Type II, n=15; Type III, n=8; Type IV, n=5; and Type V, n=6. After excluding the subjects in the Type V, we divided the subjects into two groups: Type I/II group, n=20; and Type III/IV group, n=13. In the Type III/IV group, the operating year of handheld vibrating tools was relatively longer, the mean blood flow velocity was significantly slower, and the body mass index was relatively higher as compared to the Type I/II group. These results suggested that the nailfold capillary microscopy may reflect the effect of the vibration exposure.

Primary Raynaud phenomenon and small-fiber neuropathy: is there a connection? A pilot neurophysiologic study

The pathophysiologic factors of primary Raynaud phenomenon (RP) are unknown. Preliminary evidence from skin biopsy suggests small-fiber neuropathy (SFN) in primary RP. We aimed to quantitatively assess SFN in participants with primary RP. Consecutive patients with an a priori diagnosis of primary RP presenting to our outpatient rheumatology clinic over a 6-month period were invited to participate. Cases of secondary RP were excluded. All participants were required to have normal results on nailfold capillary microscopy. Assessment for SFN was accomplished with autonomic reflex screening, which includes quantitative sudomotor axonal reflex test (QSART), and cardiovagal and adrenergic function testing, thermoregulatory sweat test (TST), and quantitative sensory test (QST) for vibratory, cooling, and heat-pain sensory thresholds. Nine female participants with a median age of 38 years (range 21-46 years) and a median symptom duration of 9 years (range 5 months-31 years) were assessed. Three participants had abnormal results on QSART, indicating peripheral sudomotor autonomic dysfunction. Two participants had evidence of large-fiber involvement with heat-pain thresholds on QST. Heart rate and blood pressure responses to deep breathing, Valsalva maneuver, and 70° tilt were normal for all participants. Also, all participants had normal TST results. In total, three of the nine participants had evidence of SFN. The presence of SFN raises the possibility that a subset of patients with primary RP have an underlying, subclinical small-fiber dysfunction. These data open new avenues of research and therapeutics for this common condition.

No effects of bosentan on microvasculature in patients with limited cutaneous systemic sclerosis

The endothelium-derived vasoconstrictor molecule endothelin-1 (ET-1) has been suggested to play a role in the pathogenesis of Raynaud’s phenomenon (RP) and systemic sclerosis (SSc). We studied the effect of bosentan on microvascular structure and function in patients with RP secondary to limited cutaneous SSc in a mechanistic pilot study. In this single center, open study, 15 patients with limited cutaneous SSc were treated with bosentan for 16 weeks with a follow-up period of 4 weeks. Changes in microvascular structure and function were studied with assessment of vasodilatory microvascular responses using laser Doppler fluxmetry combined with iontophoresis, capillary permeability using fluorescence videomicroscopy, nailfold capillary microscopy, and serological markers of endothelial activation. No significant changes were seen in vasodilator responses to acetylcholine and sodium nitroprusside following bosentan treatment. No effect was noted on capillary permeability during treatment. The number of nailfold capillaries remained unchanged. The endothelial activation marker vascular cell adhesion molecule did not change during treatment, but levels of thrombomodulin significantly decreased after 12 weeks of treatment. Bosentan did not induce significant changes in vasodilator responses, capillary permeability, and capillary density during treatment, so no evidence was obtained for structural improvement of microvascular structure and function in this short-time mechanistic pilot study in patients with lcSSc.

Flickerlichtprovokation bei Vasospastikern verglichen mit gesunden Kontrollpersonen

Vascular dysregulation is considered to be a risk factor in several ophthalmic diseases. The purpose of this study was to evaluate the reaction of retinal vessels to flicker light in otherwise healthy subjects with a vasospastic propensity. Thirty healthy Caucasians, aged between 18-35 years were recruited for this study and grouped into vasospastics, based on a history of frequent cold hands, even in summer, with concordant findings in nailfold capillary microscopy, or as controls, if such a history was absent. The reaction of the retinal vascular diameter to flicker light was observed in a distance of two to three discs diameters away from the optic nerve head with the retinal vessel analyser. Three phases of flicker light of twenty seconds followed by baseline light phases of eighty seconds were recorded. The maximal vasodilatory amplitude of each flicker phase was determined and the results averaged. The maximal average dilatory amplitude at the arterial side reached (mean +/- SD) 2.9 +/- 1.7 % and 4.8 +/- 2.6 % of the baseline amplitude respectively in vasospastic subjects and in healthy controls (t = 2.34; p = 0.025). The reaction at the venous side was statistically comparable in both groups. Otherwise healthy, vasospastic subject disclosed an altered reaction of the retinal vasculature to flicker light in this study.

Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: A twenty‐year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis

To identify in patients with Raynaud's phenomenon (RP) independent markers that predict progression to definite systemic sclerosis (SSc) and to determine in patients with progression to SSc the type and sequence of microvascular damage and its relationship to SSc-specific autoantibodies. Consecutive patients referred for evaluation of RP who had no definite connective tissue disease were evaluated for microvascular damage by nailfold capillary microscopy (NCM) and for anticentromere (anti-CENP-B), anti-Th/To, anti-topoisomerase I, and anti-RNA polymerase III (anti-RNAP III) autoantibodies by specific assays. Patients were studied prospectively. Of the 586 patients who were followed up for 3,197 person-years, 74 (12.6%) developed definite SSc. A characteristic sequence of microvascular damage was identified, starting with enlarged capillaries, followed by capillary loss, and then by capillary telangiectases. Definite SSc was diagnosed in close temporal relationship to capillary loss. Enlarged capillaries, capillary loss, and SSc-specific autoantibodies independently predicted definite SSc. Anti-CENP-B and anti-Th/To antibodies predicted enlarged capillaries; these autoantibodies and anti-RNAP III predicted capillary loss. Each autoantibody was associated with a distinct time course of microvascular damage. At followup, 79.5% of patients with 1 of these autoantibodies and abnormal findings on NCM at baseline had developed definite SSc. Patients with both baseline predictors were 60 times more likely to develop definite SSc. The data validated the proposed criteria for early SSc. In RP evolving to definite SSc, microvascular damage is dynamic and sequential, while SSc-specific autoantibodies are associated with the course and type of capillary abnormalities. Abnormal findings on NCM at baseline together with an SSc-specific autoantibody indicate a very high probability of developing definite SSc, whereas their absence rules out this outcome.

Cardiac function and the skin microcirculation in acromegaly

The microcirculation was measured by nail-fold capillary video microscopy in 21 patients (12 men, 9 women; mean age 54.7 [29-74] years) with acromegaly. Levels of growth hormone (12.0-71.7 microU/ml) and of somatomedin C (2.4-10.5 IU/ml) were elevated in 10 patients, despite preceding treatment. Eleven patients had an increase in myocardial thickness and nine had impairment of left ventricular function, although only slight in most. Left ventricular hypertrophy was demonstrable even in the absence of hypertension. No patient had evidence of coronary heart disease. Nail-fold capillary video microscopy (capillary density, torque index, reactive hyperaemia, epidermal blood flow) failed to distinguish between successfully treated patients and those with persistently elevated growth hormone concentrations or disease duration of over 5 years. There was no evidence of inadequate capillary blood flow as a cause of abnormal function in hypertrophied organs.

Cutaneous microcirculatory function predicts the responsiveness to tadalafil in patients with erectile dysfunction and coronary artery disease

Despite the proven clinical efficacy of phosphodiesterase inhibitors in the treatment of erectile dysfunction (ED), some patients do not respond to the medication. By means of nailfold capillary microscopy in patients with concomitant coronary artery disease (CAD) and ED, it was evaluated whether the extent of microvascular dysregulation predicts the responsiveness to tadalafil (TAD) in terms of erectile function. The ED of each patient was assessed by the International Index of Erectile Function (IIEF). Patients presenting both, documented CAD and ED, showed a significantly reduced capillary red blood cell velocity (v(RBC)) at rest and after 3 min of ischemia compared with age-matched controls. At 2 h after intake of 20 mg of TAD, a significant increase of v(RBC) at rest as well as during postischemic hyperemia was found. Patients who reported no improvement of their ED after the use of TAD demonstrated no changes in the duration of postischemic (DpH) hyperemia, or even a reduction of the DpH. The majority of the patients, who reported at least one successful sexual intercourse due to TAD, had a prolongation of DpH. We conclude that assessment of microvascular regulation by nailfold capillary microscopy can predict the probability of a treatment failure with phosphodiesterase inhibitors in patients with ED. Moreover, as endothelial dysfunction is the common underlying pathophysiological process of ED and cardiovascular diseases, the test may help to identify patients at risk for the development of atherosclerosis and following cardiovascular events.

Macro- and microcirculatory assessment of cold sensitivity after traumatic finger amputation and microsurgical replantation

Finger replantations after traumatic amputation are associated with good prognosis and acceptable functional results. However, cold sensitivity is a common and sometimes disabling sequelae after digital replantation. The exact causes of cold intolerance are still unclear; neural as well as vascular mechanisms have been discussed. We examined the macro- and microvascular performance of replanted fingers using high-resolution color-coded sonography for the assessment of skin vessel density of the fingertips as well as nailfold capillary microscopy and laser Doppler anemometry. Subsequently, we correlated these findings with the presence of cold sensitivity of the replanted digits. Thirty-seven patients (mean age 45 years; range 19-72) with 40 traumatic finger amputations and microsurgical replantations were studied. The mean time interval between amputation and examination was 57.7 months (range 13-95). Macro- and microvascular examination consisted of electronic oscillograms of both arms, photoplethysmograms of all fingers before and after cold test, duplex ultrasound of the finger arteries, high-resolution color-coded sonography of the fingertips and nailfold capillary microscopy with laser Doppler anemometry. Cold sensitivity was present in 33 (83%) of the 40 replanted fingers. Peripheral arterial disease of the upper extremity could be excluded as all oscillograms showed normal findings. A vasospastic reaction after cold test was documented in 74% (30 of 38) of the replanted fingers, compared to 24% (9 of 38) of the contralateral uninjured fingers. Raynaud's phenomenon was restricted to replanted fingers and occurred in 10 of 40 patients (25%). Compared with the contralateral fingertips, reduced skin vessel density was found in 27 of 36 (75%) replants. Nailfold capillary microscopy revealed uncharacteristic morphologic patterns. The capillary flow velocity was 0.28 +/- 0.12 mm/s in the replanted fingers and 0.48 +/- 0.23 mm/s in their unaffected counterparts (P < 0.001). Correlating these findings with the presence of cold intolerance, reduced skin vessel density in the fingertips was significantly different between cold-sensitive replants and those without cold sensitivity (P = 0.05). Reduced skin vessel density was not related to the extent of reconstruction of nerves (P = n.s.), arteries (P = n.s.) and veins (P = n.s.). Our results do not confirm hypotheses that cold sensitivity after finger replantations is caused by macrovascular problems nor do they support assumptions of a primary capillary microcirculatory failure. Our findings of reduced vessel density point towards diminished thermoregulatory capacities in the fingertips of cold-sensitive replanted digits.

Simple counting of nailfold capillary density in suspected systemic sclerosis – 9 years' experience

Objectives: Capillary damage is a characteristic feature of systemic sclerosis (SSc). This work aimed to explore the potential clinical value of simple microscopic counting of capillary density.Methods: In 325 patients admitted because of a clinical suspicion of SSc and in 80 healthy controls, nailfold capillary microscopy (NCM) was performed using a stereo‐zoom microscope in 20× magnification and with a transparent ruler in one of the eyepieces. Capillaries were counted within 3 mm in the centre of the nailfold in eight fingers.Results: Capillary density (loops/mm) was decreased in patients with diffuse cutaneous SSc [median 4.7 (range 2.2–7.3)], limited cutaneous SSc [4.9 (2.0–7.3)], earlySSc [4.7 (2.8–7.3)], and preSSc [5.9 (4.3–8.2)] compared to healthy controls [7.2 (5.8–9.0)]. Patients with morphea and with primary Raynaud's phenomenon had normal numbers of capillaries [7.0 (6.2–7.2) and 7.0 (5.3–8.7), respectively]. In only 21/325 (6%) patients was it not possible to count the capillaries because of insufficient transparency of the skin. There was no discrepancy in capillary density based on counts of two or eight fingers. When 43 patients were reassessed after 1 to 4 years, there was no difference between the two assessments.Conclusion: Determination of capillary density by direct microscopy counts, a simple, inexpensive and rapid method, helps to identify patients with SSc, early in the disease course and in patients with very limited skin involvement.

Towards design of a nailfold capillary microscopy image analysis and diagnosis framework using grid technology

Nailfold capillary microscopy examination has been used since late 1950s as a non-invasive in-vivo technique for diagnosing and monitoring connective tissue disease in adults. Disorders such as Pri...

Systemische Sklerose – Diagnose und Klassifikation

Systemic sclerosis (SSc) is a polymorphic and heterogenic systemic disorder with inflammation, fibrosis and vascular damage. Early diagnosis and classification may be difficult if disease expression is oligosymptomatic (undifferentiated), presenting with only Raynaud's phenomenon or limited scleroderma. Scleroderma specific antinuclear autoantibodies, which are present early and persistently in about 90% of the patients with SSc, play an important taxonomic role. Scleroderma specific findings in nailfold capillary microscopy are sensitive and predictive for evolving SSc. An algorithm will be presented for the diagnosis and classification of SSc using clinical, capillaroscopic and serologic criteria, which are also useful for mixed or special forms of SSc. The 6th Outcome Measures in Rheumatology Clinical Trials (OMERACT) conference proposed different outcome measurements for clinical studies, however, for daily clinical practice there is as yet no consensus on status indices for disease activity, disease related damage or suitable prognostic criteria.

Laser Doppler anemometry distinguishes primary Raynaud phenomenon from VWF syndrome

Objectives We evaluated two microcirculatory function-tests, the Laser Doppler (LD)-Anemometry and the Laser Doppler Imager (LDI)-Flowmetry in their value to further elucidate functional behavior of the “Vibration-induced white finger syndrome” (VWF) and to distinguish between Raynaud's phenomenon (RP) of idiopathic or vibration origin. Participants and Methods Ninety-four patients, suffering from RP were studied (78 patients with primary RP and 16 patients with VWF). Measurement of blood cell velocity (BCV) before and after provocation was obtained by nailfold capillary microscopy and an included Laser detector (“Anemometry“). Digital blood flux was recorded by LDI-Flowmetry during a standardized cooling and rewarming thermal challenge. Results “Time to peak” of BCV, a measure of maximal reactive hyperemia was longer in VWF in comparison to primary RP (30.37 versus 19.29 sec P < 0.02), respectively. Conclusion Based on the fact, that prolongation of reactive hyperemia, an indicator of impaired endothelium-dependent vasodilation is also frequently found in peripheral arterial occlusive disease, it is hypothesized that VWF is not only a microcirculatory vasospastic disorder, but may also be related to atherosclerosis. Anemometry, in association with an appropriate provocation-test, could represent a useful non-invasive method for objectifying diagnosis of VWF in patients with RP.

The effect of polyneuropathy on foot microcirculation in Type II diabetes.

The aim of this study was to investigate the influence of peripheral polyneuropathy (PNP) on skin microcirculation and foot swelling rate in the feet of patients with Type II (non-insulin-dependent) diabetes mellitus. 38 Type II diabetic patients, 24 with PNP (PNP+), 14 without PNP (PNP-), and 16 healthy control subjects were studied, first supine and subsequently sitting with the foot dependent for 50 mn. In patients with PNP, foot skin temperature was higher, (p<0.04) and capillary blood cell velocity (CBV, nailfold capillary microscopy), was lower compared to patients without PNP (222 vs 313 micro m/s respectively, p<0.03). Compared to the control subjects, the percentage reduction in skin blood flux, (LDF, laser-Doppler fluxmetry), after 10 min was higher in the PNP- and PNP+ patients (3% vs 18% and 26% respectively, p<0.02). These disturbances were most pronounced in PNP+ patients with a history of a foot ulcer. Foot swelling rate (mercury strain gauge plethysmography) in the first 10 min of dependency, was lower in patients with PNP+ compared to the control subjects (0.00165 vs 0.00286 ml.100 ml(-1)s respectively, p<0.01). In addition, we found a negative correlation (r=-0.41; p<0.01) between Valk-score (severity of PNP) and FSR. Type II diabetes PNP is associated with multiple abnormalities in the (skin) microcirculation of the foot, characterised by reduced capillary blood flow, an enhanced reduction in skin blood flux and impaired fluid filtration after sitting up. The most severe abnormalities were observed in patients with a history of foot ulceration.

Predicting Mortality in Systemic Sclerosis

Predicting Mortality in Systemic Sclerosis

Microvascular involvement in systemic sclerosis: Capillaroscopic findings

Objective: To show the most representative capillaroscopic findings in patients with systemic sclerosis (SSc). Method: Capillaroscopic evaluation was performed with a videomicroscope at 100 times and 200 times magnification. Representative images of the nailbed microcirculation were obtained in 20 healthy subjects and in 75 patients with SSc. Results: Capillary abnormalities were seen at the nailfold in more than 90% of patients with SSc. Capillary involvement included several morphologic changes, which are easily distinguished from the pattern of healthy controls. Architectural disruption of the nailfold microvascular network, enlarged loops, neoformation of capillaries, loss of capillaries, and avascular areas are the main abnormalities detected in SSc patients. Conclusions: Nailfold capillary microscopy is one of the most valuable tools for the early diagnosis of SSc and related disorders. Rheumatologists and internists should be able to recognize these abnormalities because of their diagnostic relevance. Semin Arthritis Rheum 30:397-402. Copyright © 2001 by W.B. Saunders Company