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PubMed2003

Systemic scleroderma patients have improved skin perfusion after the transdermal application of PGE1 ethyl ester.

BACKGROUND: Patients with systemic scleroderma exhibit a noticeable slowing of blood cell velocities or even stasis in the capillaries of the skin. In this study the effects of transdermally applied prostaglandin PGE1 ethyl ester on nutritive cutaneous perfusion and on Raynaud's symptoms were investigated. PATIENTS AND METHODS: 24 patients with systemic scleroderma were treated transdermally over a period of 14 days with prostaglandin E1 ethyl ester patches. The response of blood cell velocity in the nailfold capillaries to cold exposure was tested in 20 patients, and all of the patients recorded the number of Raynaud's episodes in a journal over a period of two weeks. RESULTS: After the transdermal application of prostaglandin E1 ethyl ester there was an increase in blood cell velocity in the nutritive capillaries of systemic scleroderma patients (increase from 0.35 +/- 0.14 mm/s to 0.47 +/- 0.11 mm/s, (p < 0.05)). At the same time there was a decrease in the number of Raynaud's episodes (2.9 +/- 2.4 per day to 2.6 +/- 2.0 per day (p < 0.05)). CONCLUSION: The transdermal application of prostaglandin E1 ethyl ester was shown to have a favourable effect on nutritive blood flow in the capillaries of the skin in systemic scleroderma patients.

Administration, Cutaneous↗
PubMed2000

Capillaroscopy and the measurement of capillary pressure.

Capillaries play a critical role in cardiovascular function as the point of exchange of nutrients and waste products between the tissues and circulation. Studies of capillary function in man are limited by access to the vascular bed. However, skin capillaries can readily be studied by the technique of capillaroscopy which enables the investigator to assess morphology, density and blood flow velocity. It is also possible to estimate capillary pressure by direct cannulation using glass micropipettes. This review will describe the techniques used to make these assessments and will outline some of the changes that are seen in health and disease.

Age Factors↗
PubMed2000

Nailfold video capillaroscopy in psoriasis.

Changes in the microvasculature are considered to play an important part in the pathogenesis of psoriasis and its associated arthritis. The novel method of nailfold video capillaroscopy is an extension of the technique of widefield nailfold microscopy which has been of diagnostic and predictive use in the in vivo study of the microcirculation in systemic sclerosis and other connective tissue disorders. However, similar studies in patients with psoriasis and psoriatic arthritis and/or nail changes have produced conflicting results. We tested the hypothesis that any abnormalities in nailfold capillaries of either a quantitative or qualitative nature might be observed more readily in subjects with pathology adjacent to the nailfold, i.e. distal interphalangeal (DIP) joint changes and/or nail dystrophy, when using this technique. Forty-four patients with psoriasis were recruited (21 males, 23 females). Twelve patients had psoriasis alone, 13 had psoriasis and nail changes, six had DIP joint involvement with changes of psoriasis elsewhere, and 13 had psoriasis, DIP arthritis and nail changes. Capillary density and standard capillary dimensions were studied and compared with those of 44 age- and sex-matched control subjects. There was a significant (P < 0.05) decrease in capillary loop density in patients with either psoriasis plus nail disease (14.5 +/- 5.7 capillaries per 3 mm field) or psoriasis plus nail and DIP joint disease (14.3 +/- 5. 0) when compared with controls (19.2 +/- 3.8). In patients with psoriatic arthritis affecting the DIP joints, there was a statistically significant (P < 0.05) decrease in arterial and venous capillary limb diameters, and this was also seen in those with arthritis associated with nail changes. However, there was no difference in capillary dimensions between patients with psoriasis and/or nail changes when compared with normal controls. Morphological abnormalities previously described in the literature were not noted in any of our four patient groups. Our findings of diminution in both nailfold capillary bed density and dimensions of the arterial and venous capillary limbs suggest that vascular injury, previously noted in ultrastructural studies, may play a part in the pathogenesis of psoriatic arthritis. However, in contrast to previous studies, we found no specific pattern of a morphological nature of nailfold capillaries in patients with psoriasis with or without nail changes, when compared with normal controls.

Adult↗
PubMed1999

Visualization of dermal blood vessels--capillaroscopy.

Intravital capillaroscopy is the only noninvasive method available that visualizes directly the nutritional dermal capillaries. It can determine (in vivo): capillary morphology, including size, shape and tortuosity; capillary density; intercapillary distance; volume fraction (the percentage of skin occupied by microvessels); and changes in red cell velocity within capillaries. When capillaroscopy is performed using a video recording system, this permits real-time imaging of the cutaneous capillaries with retrospective analysis of capillary dynamics. Furthermore, when fluorescent dyes are injected intravenously, plasma-perfused capillaries are delineated allowing the calculation of several perfusion indices. Intravital capillaroscopy therefore permits the assessment of static as well as dynamic aspects of the skin microcirculation.

Aging↗
PubMed2002

Dextran sulfate (Selesorb) plasma apheresis improves vascular changes in systemic lupus erythematosus.

Apheresis has been effective as rescue therapy in patients with severe, therapy-resistant, systemic lupus erythematosus (SLE). Its benefit in patients with less severe but therapy-resistant SLE is not known. Dextran sulfate apheresis was applied as a rescue therapy for therapy-resistant vasculitic skin lesions in a 30 year old female patient with a 9 year history of SLE in combination with antiphospholipid syndrome and Raynaud's phenomenon. Partial remission was achieved after 9 immunoadsorption sessions, as documented by marked improvement of skin lesions and an increase of capillary density in the nailfold area. Further improvement was noted with maintenance therapy using mycophenolate mofetil. Dextran sulfate apheresis can be applied safely in patients with moderate therapy-resistant SLE disease activity when severe immunodeficiency and cytotoxic adverse effects should be avoided.

Adsorption↗
PubMed2001

Rarefaction of skin capillaries in patients with anginal chest pain and normal coronary arteriograms.

AIMS: Patients with arterial hypertension often have a reduction in capillary density (rarefaction) and a reduction in coronary flow reserve because of functional and structural alterations of the coronary microcirculation. Patients with chest pain and normal coronary arteriograms may have coronary microvascular dysfunction, but it is not known whether capillary rarefaction plays a role in the pathogenesis of this syndrome. The aim of this study was to compare capillary density in hypertensive and normotensive subjects with anginal chest pain and normal coronary arteriograms vs asymptomatic hypertensives and healthy controls. METHODS AND RESULTS: We studied 49 patients with typical anginal chest pain, positive exercise testing and normal coronary arteriograms; 22 were hypertensive and 27 were normotensive. We used intra-vital video-microscopy to examine the skin of the dorsum of the middle finger of the non-dominant hand before and after maximization of perfused capillaries with venous congestion. Mean capillary density was significantly lower in patients with chest pain and normal coronary arteriograms independent of their blood pressure level, compared to normotensive healthy controls. Differences were found both at baseline [51+/-2 (hypertensive) and 52+/-2 (normotensive) vs 65+/-2 (controls) per 0.56 mm(2) respectively], (P<0.0001) and after maximization [57+/-3 (hypertensive) and 59+/-2 (normotensive) versus 75+/-3 (controls) respectively] (P<0.0001). CONCLUSIONS: Skin capillary density is significantly lower in patients with chest pain and normal coronary arteriograms compared to normotensive controls. The pathophysiological importance of capillary rarefaction in patients with chest pain and normal coronary arteriograms remains unknown. Further studies are needed to determine whether the abnormality is associated with myocardial flow disturbances such that the findings can be extended to the heart.

Capillaries↗
PubMed2002

Morphologic changes in the microcirculation induced by chronic smoking habit: a videocapillaroscopic study on the human labial mucosa.

BACKGROUND: Cigarette smoking has been identified as a major risk factor for cardiovascular and pulmonary diseases. Although an impressive literature does exist on the subject, no evidence is available on morphologic changes induced with chronic smoking habit in the human microcirculation. SUBJECTS AND METHODS: One hundred healthy subjects, 50 smokers and 50 nonsmokers, underwent videocapillaroscopy of the labial mucosa. For each subject, the caliber of capillary loops, the number of visible capillary loops, the background optical transmittance, the tortuousness of capillary loops, the presence of microaneurysms, the presence of microhemorrhages, and the cumulative smoking habit (pack-year index) were noted. RESULTS: Smokers had a lower caliber of capillary loops (P <.001), with a higher number of visible capillary loops (P <.001), a lower background optical transmittance (P <.001), and a more marked tortuousness of capillary loops (P <.001). Microaneurysms and microhemorrhages were absent in nonsmokers, and 1 smoker of 3 had microaneurysms alone, and 1 smoker of 3 had both microaneurysms and microhemorrhages. A significant correlation was found between cumulative smoking habit and tortuousness of capillary loops (P <.001) and between cumulative smoking habit and total score (tortuousness score + microaneurysm score + microhemorrhage score; P <.005). CONCLUSION: Chronic smoking habit does induce significant morphologic changes in the microcirculation of the human labial mucosa, and these changes can be easily and comfortably recorded with videocapillaroscopy.

Adult↗
PubMed2000

Quantitative nailfold capillary microscopy findings in patients with acrocyanosis compared with patients having systemic sclerosis and control subjects.

BACKGROUND: The morphologic capillary microscopy (capillaroscopy) pattern of acrocyanosis is characterized by hemorrhages, pericapillary edema, and widened capillaries. These findings can result in a difficult differential diagnosis with systemic sclerosis (SSc). OBJECTIVE: We sought to quantify the characteristics of the capillaroscopy pattern that distinguishes patients with acrocyanosis from patients with SSc and control subjects. METHODS: A videomicroscope with fiberoptic illumination and personal computer-based image processing was used to measure capillary density, giant capillaries, loop width, and arterial and venous limbs in 10 patients with acrocyanosis, 10 patients with SSc, and 10 healthy control subjects. RESULTS: Acrocyanotic patients differed in every quantitative parameter both from control subjects and patients with SSc. In particular, capillary density, which was reduced compared with that of control subjects, was much higher than that of patients with SSc: one giant capillary per finger was observed in 2 patients with acrocyanosis, whereas more than 2 giant capillaries per finger were observed in each patient with SSc. CONCLUSION: These differences may aid in making the distinction between the capillaroscopy patterns in acrocyanosis and SSc.

Adult↗
PubMed2002

Recombinant human erythropoietin influences revascularization and healing in a rat model of random ischaemic flaps.

In order to ascertain whether erythropoietin plays a role in early and late repair processes following ischaemic skin flap injury, a dorsal, caudally based skin flap was created in rats. The rats were successively divided into four groups. Group 1 was not treated. The other groups were treated with a subcutaneous administration of 0.9% NaCl saline solution (group 2), a subcutaneous administration of vehicle (group 3) or a subcutaneous administration of 300 IU/kg/day of recombinant human erythropoietin (group 4). We evaluated the possible relationships between neutrophil accumulation, myeloperoxidase activity and content in flap tissue, flap survival, flap temperature (using telethermography) and flap revascularization (using videocapillaroscopy). Necrosis in the flap was significantly less extensive in group 4 than in groups 1, 2 and 3. A significant increase in neutrophil infiltration occurred between the 1st and 24th hour in these groups, but this was not observed in group 4. These findings were confirmed by biochemical data of myeloperoxidase activity and malonyldialdehyde content. Between the 1st and 7th days, we recorded an increase of about 20% in flap temperature in groups 1, 2 and 3, whereas no significant variation was observed in group 4. On the 7th day, videocapillaroscopic findings showed an increase in the mean vascularization index in group 4. Our findings suggest that recombinant human erythropoietin administration can improve the wound healing process, in both early and late stages of injury, by reducing inflammatory response, increasing the density of capillaries in ischaemic flaps and allowing earlier repair of a damaged area.

Animals↗
PubMed2002

Post-occlusive reactive hyperemia in single nutritive capillaries of the nail fold: methodological considerations.

Endothelial function at the arterial level has been extensively assessed by a non-invasive method using flow-mediated dilatation (FMD) of the brachial artery. Early disturbances have been found in patient groups prone to later development of manifest macrovascular atherosclerosis. A possible non-invasive means of studying blood-flow regulation and function at the microcirculatory level is through videophotometric capillaroscopy. The most stable variable in such an investigation is the time-to-peak (TtP) flow after a brief arterial occlusion. The short-term reproducibility of such assessments is excellent but the coefficient of variation (CV) in long-term studies is reported to be in the order of slightly less than 20%. The aim of the present methodological study was to evaluate different sources of variations in such microcirculatory assessments in order to be able to propose design recommendations that minimize the number of patients and recordings needed to achieve sufficient statistical power in longitudinal studies. We used a symmetric design with 144 recordings of TtP after a one-minute arterial occlusion in healthy volunteers. We did six occlusions each time in the capillaries of two fingers on each occasion, and repeated the procedure three times with an interval of at least one week between each investigation. All recordings were analyzed off-line using a cross-correlation technique with the Capiflow system. Each analysis was performed at least three times, giving a total of slightly less than 500 assessments. In our material (n = 10) TtP had a mean of 6.3 s (95% confidence interval 5.2-7.4). The correlation between repeated measurements in a single capillary during a single session was r > 0.91 (CV 6%). The between-finger CV was 8% (r = 0.84). The CV of measurements between different days was about 20% when single measurements were compared. However, the CV decreased to less than 13% when the mean of at least two time-to-peak assessments on each occasion was used. In conclusion, the methodological error including day-to-day variation could be minimized using the mean of at least two repeated assessments of post-occlusive hyperemia at each time point in a longitudinal study. This finding should be taken into consideration in the design of future longitudinal studies.

Blood Flow Velocity↗
PubMed2005

Capillaroscopy of the dorsal skin of the hands in hereditary hemorrhagic telangiectasia.

BACKGROUND: Cutaneous telangiectases are manifestations of hereditary hemorrhagic telangiectasia (HHT), a dominantly inherited disorder. Telangiectases have been studied by skin biopsy, and recently by nailfold capillaroscopy. AIM: To confirm the diagnostic role of nailfold capillaroscopy, and assess the value of skin capillaroscopy of the dorsum of the hands in HHT. DESIGN: Prospective clinical investigation. METHODS: Using a Wild Heerbrugg-M650 microscope, we studied the nailfolds and dorsum of the hands of 88 patients (37 females, 51 males, mean age 39.7 +/- 18.4 years), including 85 with positive genetic testing and three with clinical diagnosis (at least three clinical criteria but a negative genetic test) and 27 controls (13 females, 14 males, mean age 38.6 +/- 19.6 years). RESULTS: Microscopic telangiectases were observed on the dorsum of the hands in 80/88 patients (91%): 77 with positive and three with negative genetic tests. No control showed vascular abnormalities. In six patients (7%), nailfold capillaroscopy showed pseudo-megacapillaries and megacapillaries; the remaining 82 (93%) and all controls, had normal capillaroscopic patterns. DISCUSSION: HHT can induce morphological changes in microcirculation that are more easily detectable on the dorsum of the hands than in the nailfold. Microscopic lesions without macroscopic telangiectases were also noted, suggesting the need for further research. Capillaroscopy may provide an additional non-invasive diagnostic criterion for HHT.

Adolescent↗
PubMed2000

Quantitation of microcirculatory abnormalities in patients with primary Raynaud's phenomenon and systemic sclerosis by video capillaroscopy.

OBJECTIVE: : To assess nailfold capillary density and dimensions in patients with primary Raynaud's phenomenon (PRP), limited cutaneous systemic sclerosis (LSSc) and diffuse cutaneous SSc (DSSc), and healthy control subjects. METHODS: : Using the technique of nailfold video capillaroscopy, capillary density and dimensions were averaged from all visible capillaries in a 3 mm length of the nailfold from right and left ring fingers of each subject. Twenty healthy control subjects, 15 patients with PRP, 13 patients with DSSc and 21 patients with LSSc were examined. Intra-observer and inter-observer variability were calculated in 18 and 23 patients, respectively. RESULTS: : There were significant trends for capillary density to fall and for all dimensions to rise across the four groups (P < 0. 0001 for density and all dimensions, order healthy controls, PRP, DSSc and LSSc). Intra- and inter-observer reproducibility studies showed that although there was good correlation between and within observers, the limits of agreement were between +/-25-50% indicating lack of reproducibility. CONCLUSIONS: : Microcirculatory abnormalities can be quantified using the technique of video capillaroscopy and were most marked in patients with LSSc.

Adult↗
PubMed2004

Nailfold videocapillaroscopic patterns and serum autoantibodies in systemic sclerosis.

BACKGROUND: Microvascular lesions are a predominant feature in systemic sclerosis (SSc) and seem to play a central pathogenetic role. Recently, we graded scleroderma microangiopathy by nailfold videocapillaroscopy (NVC) into three NVC patterns (early, active and late). The aim of the present study was to confirm, in a larger number of SSc patients, the presence of three patterns of microvascular damage, and to detect any possible relationship between these patterns and both specific serum autoantibodies and the subsets of cutaneous involvement. METHODS: Two hundred and forty-one consecutive patients (227 women and 14 men) affected by SSc were recruited. One hundred and forty-eight patients were affected by limited cutaneous SSc (lSSc) and 93 patients by diffuse cutaneous SSc (dSSc). The ages at onset of Raynaud's phenomenon (RP) and SSc, the durations of RP and SSc, ANA and antitopoisomerase I (anti-Scl70) and anticentromere (ACA) antibodies were investigated in all patients. The SSc patients were subdivided on the basis of the NVC pattern into three groups. RESULTS: A statistically significant correlation was found between the NVC patterns and the durations of both RP and SSc (P<0.001). Enlarged and giant capillaries, together with haemorrhages, constituted the earliest NVC finding in SSc (early NVC pattern). These abnormalities were mostly expressed in the active NVC pattern. Loss of capillaries, ramified capillaries and vascular architectural disorganization were increased in the late NVC pattern. Age and the duration of both RP and SSc were lower in 24 patients complaining of RP alone. Anti-Scl70 antibodies were statistically less frequent in the early vs both the active and the late NVC pattern, whereas no significant correlation was found between the presence of anti-Scl70 antibodies and the duration of either RP or SSc. ACA positivity was more frequent in patients with longer RP duration. Patients with lSSc had shorter SSc duration and showed the early or active NVC pattern more frequently. Conversely, patients with dSSc showed longer disease duration and mostly showed the late NVC pattern. CONCLUSIONS: NVC is an appropriate tool for differential diagnosis between primary and secondary RP through the clear recognition of the early NVC scleroderma pattern. This study confirms, in a large number of SSc patients, the existence of three distinct NVC patterns that might reflect the evolution of SSc microangiopathy. The presence of anti-Scl70 antibodies seems be related to earlier expression of the active and late NVC patterns of SSc microvascular damage. The presence of ACA seems to be related to delayed expression of the late NVC pattern.

Adult↗
PubMed2005

Classification of systemic sclerosis. Visions and reality.

Systemic sclerosis, scleroderma (SSc) is a disabling condition that shortens life expectancy. Disease heterogeneity and difficulties separating SSc from SSc-like conditions make classification an important issue. Limited cutaneous and diffuse cutaneous SSc, with different severity and survival, have been recognized for several years as distinct subsets. Some authors have suggested an intermediate cutaneous form with intermediate survival. This issue remains unsettled, however. The technique of capillaroscopy is helpful as an adjunct diagnostic tool to separate idiopathic Raynaud's phenomenon from SSc. Digitized video-capillaroscopy is developing as a powerful new method to assess individual capillaries over time. Using the simpler techniques of video-capillaroscopy, different patterns have been described and named 'early', 'active', 'late' and 'slow'. The value of nailfold video-capillaroscopy to distinguish different subsets or provide prognostic information for use in daily practice remains to be assessed. The features of CREST (calcinosis, Raynaud's, oesophagus dysmotility, sclerodactyly, telangiectasias) are not confined to single subsets of SSc. There is no convincing evidence of any advantage for distinguishing the limited, intermediate and diffuse forms of SSc rather than only the limited and diffuse forms.

CREST Syndrome↗
PubMed2005

Levels of F2-isoprostanes in systemic sclerosis: correlation with clinical features.

OBJECTIVE: Oxidative stress may be one of the important complex pathogenetic mechanisms that lead to damage in scleroderma; free radicals may provoke endothelial injury, fibroblast proliferation and fragmentation of autoantigens favouring induction of autoantibodies. The present study investigates the oxidant status in scleroderma patients by measuring the urinary concentration of 8-isoprostaglandin-F2alpha, an F2-isoprostane, and a product of free radical-mediated peroxidation of arachidonic acid. METHODS: Forty-three scleroderma patients (42 women and 1 man, mean age 54.1 yr, mean disease duration 9.0 yr) underwent clinical evaluation and instrumental investigations in order to assess skin, vascular, lung and heart involvement. Von Willebrand factor was evaluated as marker of vascular dysfunction in 36 out of the 43 cases. The urinary level of 8-isoprostaglandin-F2alpha was measured in all scleroderma patients and in the 43 age- and sex-matched healthy controls. RESULTS: Urinary levels of 8-isoprostaglandin-F2alpha were higher in scleroderma patients than in the healthy control group (341.7 vs 147.6 pg/mg creatinine; P < 0.001). Values of 8-isoprostaglandin-F2alpha were strongly correlated with the nailfold videocapillaroscopy pattern and lung involvement (P = 0.002 and 0.003, respectively), showing increasing levels with the progression of pulmonary severity. Correlation between 8-isoprostaglandin-F2alpha level and von Willebrand factor narrowly failed to reach statistical significance (P = 0.05). There was no correlation between 8-isoprostaglandin-F2alpha concentration and disease activity, vascular, skin and heart involvement, disease pattern or autoantibody profile. CONCLUSIONS: Our study further supports the role of oxidant stress in the pathogenesis of scleroderma, showing a strong correlation between a marker of free radical damage with both the severity of lung involvement and the videocapillaroscopic patterns.

Adult↗