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Interleukin-13 in systemic sclerosis: relationship to nailfold capillaroscopy abnormalities.

The aim of this study was to investigate whether interleukin-13 (IL-13) serum levels correlate to different nailfold capillaroscopy (NC) findings in patients with systemic sclerosis (SSc). IL-13 serum levels were measured using an ELISA method. The following NC abnormalities were considered: the presence of giant loops, haemorrhages, loss of capillaries, disorganisation of the vascular array, ramified/bushy capillaries and sludging of blood. A semiquantitative rating scale was adopted to score these changes, as well as a rating system for avascular areas and three morphological NC patterns ('early', 'active' and 'late'). Mean capillary density was determined by counting the total number of capillaries in a 1 mm length, and the arterial and venous diameters of the capillary as well as the total loop diameter were measured. In SSc patients IL-13 serum levels were significantly higher than in controls ( P < 00.1), whereas in patients with ( n=8) and without ( n=24) abnormal IL-13 serum levels (>17 pg/ml) the comparison of the NC features showed significantly relevant differences concerning a more frequent 'active' NC pattern ( P < 0.02), the presence of haemorrhages ( P < 0.0037) and sludging of blood ( P < 0.038), as well as larger total loop ( P < 0.036) and arterial ( P < 0.03) diameters, in those patients with elevated IL-13 serum levels. The study confirmed that IL-13 serum levels are higher in the sera of patients with SSc, and shows for the first time the significant correlations between this serological finding and some of the main relevant SSc capillaroscopic features, leading us to believe that this cytokine not only seems to sustain the immunological and fibrotic process of SSc, but might have a role in determining the more severe microvascular lesions in this disease.

Adult↗

Multiple avascular necrosis in a patient with systemic lupus erythematosus/systemic sclerosis overlap syndrome.

A white female patient developed overlapping features of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) with severe pulmonary compromise. She was treated with steroids and azathioprine, which improved her clinical condition and spirometric status. In May 2002 she presented with continuous pain in her left ankle that continued even during rest and under treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). Magnetic resonance imaging (MRI) showed multiple avascular necrosis (AVN). Rest and kinesitherapy were indicated for 1 year, and gradually an orthosis was introduced allowing the patient to walk normally.

Adult↗

The usefulness of power Doppler ultrasonography in differentiating primary and secondary Raynaud's phenomenon.

The objectives of this study were to assess a usefulness of power Doppler ultrasonography (PDU) and compare the diagnostic value of PDU to nailfold capillaroscopy (NFC) in the patients with clinically diagnosed Raynaud's phenomenon (RP) and healthy controls. Forty-one patients with primary (n=19), secondary RP (n=22), and ten healthy controls underwent PDU and NFC examinations on the same day. Microvascularity was evaluated using PDU before and after cold challenges, and the PDU signals were qualitatively graded on a scale of 1-4. According to the change of microvascularity before and after cold challenges, the findings of PDU were classified into three groups: (1) 'pattern I' (normal microvascularity over grade 3 both before and after cold challenges), (2) 'pattern II' (decreased microvascularity to grade 1 or 2 only after cold challenge), and (3) 'pattern III' (decreased microvascularity of grade 1 or 2 both before and after cold challenges). PDU confirmed the presence of RP in all patients with clinically diagnosed RP and yielded a correct classification in 88.9% of the all persons analyzed (normal=100%, primary RP=89.5%, secondary RP=77.3%). The analysis was performed to assess the degree of agreement between the final diagnoses obtained by PDU and NFC. A good correlation rate was observed between PDU and NFC examinations in differentiating primary from secondary RP (Kappa=0.658, p<0.01). In conclusion, PDU examination with a cold challenge is a useful and reliable method to diagnose RP and discriminate between primary and secondary RP.

Adult↗

Predictive value of nailfold capillaroscopy in patients with Raynaud's phenomenon.

The objective of this study was to evaluate the long-term follow-up of patients with Raynaud's phenomenon (RP) and pathological nailfold capillaroscopy (NC) in order to analyse the predictive value of specific features of capillaroscopy for the development of a connective tissue disease (CTD). From 1992 to 2002, NC alone or combined with fluorescence videomicroscopy with sodium fluorescein (NaF) was performed in 1024 consecutive patients because of RP. We analysed the follow-up and pathological features of NC in all patients who had neither clinical nor serological signs of a CTD at the time of NC. Of 308 patients with neither serological findings nor clinical signs of CTD but with RP and pathological features in NC suspicious for CTD, follow-up data were available for 133 patients. An additional NaF test had been performed in 51 (38.4%) patients. After a mean follow-up of 6.5 years (range: 1-15 years), 109 patients had developed a CTD and 24 patients did not show any clinical signs or serological markers for a CTD after a mean follow-up of 8.5 years (range: 2-15 years). There were no differences in age, duration of RP or of follow-up in patients who developed a CTD compared to patients who did not. Significantly more giant capillaries (p=0.0001), avascular fields (p=0.02) and irregular architecture (p=0.0001) had been observed in patients who had developed a CTD during the follow-up of 6.5 years. The presence of giant capillaries, avascular fields and irregular architecture of nailfold capillaries is predictive for the development of a CTD in patients with RP.

Adolescent↗

Correlation between homocysteine plasma levels and nailfold videocapillaroscopic patterns in systemic sclerosis.

The aim of the study is to investigate the relationship between microangiopathy as assessed by nailfold videocapillaroscopy (NVC) and plasma level of homocysteine (Hcy) in systemic sclerosis (SSc). As known, Hcy is a nonessential amino acid that interferes with normal properties of a vascular tree. Sixty patients affected by SSc (4 men and 56 women, mean age 54.6) underwent the determination of plasma Hcy level; at the same time, NVC was performed. Hcy level was also determined in 30 sex- and age-matched controls. In patients affected by SSc the plasma Hcy level was significantly higher than in healthy controls (11.8 and 6.5 micromol/l, respectively; p < 0.001). A significant correlation was found between plasma Hcy concentration and the pattern of NVC with a progressive increase from early to active and above all to late pattern (10.7, 11.8, and 17.4 micromol/l, respectively; p < 0.001). Subjects with high Hcy level (i.e., >75th percentile of Hcy level in controls and in patients considered altogether) were mostly represented in the scleroderma patients with late nailfold videocapillaroscopic pattern; the crude odds ratio was 9.0 (significant; 95% CI from 2.1 to 38.8). In conclusion, Hcy plasma level is related to microvascular involvement in patients affected by SSc; the concentration increases with the progression of the nailfold videocapillaroscopic pattern. Hyperhomocysteinemia may represent an aggravating factor among the complex mechanisms involved in scleroderma damage contributing to the injury of endothelium.

Adult↗

Office capillaroscopy in systemic sclerosis.

The aims of this study are to assess the reliability of two office techniques, the ophthalmoscope and the Dermlite dermatoscope, and to detect nailfold capillaroscopy abnormalities in systemic sclerosis (SSc). Two separate studies were performed. In the first, the nailfolds of two fingers on one hand of 13 SSc patients and two normals were examined by four rheumatologists using an ophthalmoscope. In the second, the nailfolds of the two fingers of each hand of six SSc patients and two normals were examined by six rheumatologists with a Dermlite dermatoscope. Widefield capillary microscopy was performed by one observer in the ophthalmoscope study to assess validity. The examiners determined the presence or absence of dilated loops, giant capillary loops, and/or avascular areas on each digit. The kappa coefficient was calculated to demonstrate agreement. With the ophtalmoscope, the inter-observer kappa coefficients were 0.43, 0.54, and 0.19; the average intra-observer agreements were 0.61, 0.56, and 0.31; and the ophthalmoscope-microscope agreement were 0.63, 0.52, and <0.1 for dilated capillaries, giant capillaries, and avascular areas, respectively. With the dermatoscope, the kappa values for inter-observer reliability were 0.63, 0.40, and 0.20; and intra-observer reliability was 0.71, 0.55, and 0.40 for dilated capillaries, giant capillaries, and avascular areas, respectively. The ophthalmoscope and the dermatoscope provide moderate to substantial reliability to detect the presence of giant and dilated capillaries but poor inter-observer agreement for avascular areas. The ophthalmoscope is valid when compared to the microscope for detecting giant or dilated capillaries. We conclude that these techniques are useful office tools to detect capillary abnormalities in SSc.

Dermoscopy↗

Capillaroscopic findings in erosive and nodal osteoarthritis of the hands.

Osteoarthritis of the hands is a very common disease that can present a large number of different clinic pictures, such as nodal (NOA) and erosive (EOA) forms. EOA in particular is a rare subset of hand osteoarthritis characterised by faster destructive changes involving the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints. In the early stages of the disease the differential diagnosis from other arthritides, such as rheumatoid or seronegative arthritis, may pose a challenge. Nailfold capillaroscopy is a non-invasive technique that allows the in vivo study of the microvascular environment. In this study the authors have compared the capillaroscopic microvascular patterns in 56 patients with EOA, in 46 patients with NOA, and in 50 normal controls. The abnormalities that could be found in EOA patients were similar to those described by some authors in patients with psoriatic arthritis. The authors discuss the significance of these abnormalities and the possible relationship between EOA and psoriatic arthritis.

Aged↗

The effect of cigar smoking on the lingual microcirculation.

The aim of this study was to analyze the lingual microcirculation in vivo and to evaluate the effects on it of cigar smoking, using computerized videocapillaroscopy. Twenty-five healthy nonsmokers and 25 healthy smokers were examined. For each subject we evaluated the visibility, course, tortuosity, and any images characteristic of capillary loops, as well as the possible presence of microhemorrhages, the average caliber of the capillary loops, and the number of capillary loops visible per square millimeter. The investigation of the lingual mucosa revealed capillary loops with a course parallel to the surface. In smokers, capillary loops had a smaller caliber (P < 0.001) and there was a higher number of detectable capillary loops (P < 0.001). An important correlation between capillary tortuosity and cigar smoking (P < 0.001) was observed. Our research shows that chronic smoking induces significant changes in lingual capillary morphology, caliber, and number.

Adult↗

Capillaroscopy.

Raynaud's phenomenon (RP) is the most common and significant clinical condition with an indication for a microvascular analysis to be carried out as soon as possible. Microvascular involvement is a key feature of RP and several rheumatic diseases are characterised by the presence of RP. Nailfold capillary microscopy shows an impressive cost/effectiveness ratio: it is simple, non-invasive and inexpensive. Well recognised nailfold videocapillaroscopic patterns (NVC) have been described mainly in systemic sclerosis (SSc) patients with secondary RP. The peripheral microvascular damage in SSc is characterised by increasing structural alterations of the capillaries (giant capillaries and microhaemorrhagies) with a progressive decrease in their density. The detection of the scleroderma NVC pattern allows an early distinction between the primary RP (functional, not disease associated) and the secondary RP (disease associated). Other major NVC patterns have been described in the field of rheumatic diseases. Interestingly, correlations are evident between the NVC and the clinical symptoms, severity of the disease and the laboratory findings.

Clinical Trials as Topic↗

Videocapillaroscopic alterations in erythematotelangiectatic rosacea.

BACKGROUND: Rosacea is a common chronic dermatosis that involves the cutaneous microvasculature of the face. There are no objective measures for assessing the severity of erythematotelangiectatic rosacea. OBJECTIVE: Our purpose was to characterize and provide objective measures of vessel changes in erythematotelangiectatic rosacea by videocapillaroscopy. METHODS: We compared 30 patients with erythematotelangiectatic rosacea with 30 age- and sex-matched patients with facial seborrheic dermatitis and 30 healthy control subjects. Videocapillaroscopy was performed both on the cheeks and on the nailfold region. The analyzed parameters of the face were morphological (background color, vessel irregularities) and quantitative (polygonal net perimeter, telangiectasia, and vessel diameters). RESULTS: Characteristic alterations of skin vessels were observed in facial rosacea, with a pattern distinct from that of facial seborrheic dermatitis. In particular, rosacea showed neoangiogenesis and significantly larger polygons (13.21 +/- 3 vs 7.8 +/- 3 mm; mean +/- standard deviation, P < .001), more prominent telangiectases (267.8 +/- 108 vs 118.2 +/- 35 microm; P < .001) and larger mean vessel diameter (46.71 +/- 9 vs 24 +/- 10 microm; P < .001) compared with seborrheic dermatitis. Seborrheic dermatitis displayed more polygon irregularities and vessel tortuosity. In contrast, no differences were found in the nailfold region. LIMITATIONS: Vessel irregularities and overall erythema may be difficult to quantify. CONCLUSIONS: Videocapillaroscopy may represent a valid adjunctive method in the early diagnosis and measurement of erythematotelangiectatic rosacea.

Adult↗

Structural and functional abnormality of systemic microvessels in cardiac syndrome X.

BACKGROUND AND AIM: Microvascular damage of coronary bed has been considered the main pathogenetic factor of cardiac syndrome X (chest pain, exercise-induced ischemic ST-segment changes and angiographically normal coronary arteries). Previous studies have demonstrated that vascular abnormalities are not confined to the heart, suggesting a peripheral vascular dysfunction. On the hypothesis of a generalized microvascular disturbance in cardiac syndrome X, we performed a morphologic and functional study of systemic microcirculation in patients with syndrome X compared to normal subjects. METHODS AND RESULTS: Microvessels were evaluated with intravital videocapillaroscopy (VCP) executed in peripheral and conjunctival observation sites which explore micro and paramicrocirculation; biohumoral study included markers of inflammation and of endothelial function, coagulative-fibrinolytic system and lipid metabolism. Videocapillaroscopy showed several morphologic changes (present in high percent of patients with syndrome X and not in controls) and significant quantitative alterations (capillary density, granular flow score, alterations of vessel profile, length of capillary loop branches and of arteriole/venule diameter) which indicated a severe alteration of whole vessel structure and an important rearrangement of microvascular disposition. In a similar way, the humoral study showed some significant changes of endothelial (vWF, ICAM-1, E-sel, PAI-1), inflammatory (C-reactive protein (CRP), fibrinogen) and metabolic factors (HDL-chol) which are commonly associated with inflammatory response. CONCLUSIONS: We conclude that patients with cardiac syndrome X exhibited some structural and functional alterations of systemic microvasculature; the pattern is similar to that detected in systemic inflammatory diseases and suggests a vascular lesion of inflammatory type. The same changes could be operating also in coronary microvessels of patients with syndrome X.

Angina Pectoris↗

Non-invasive methods and stimuli for evaluating the skin's microcirculation.

Vessels in the skin are arranged into superficial and deep horizontal plexuses and they are involved in thermoregulation, oxygen and nutritional support. The skin has a large number of functions and broad appeal spanning basic mechanistic and clinical research. Indeed, the skin can be used as a marker of normal and impaired vascular control and, owing to its accessibility and frequent involvement, is easy to investigate non-invasively. A large number of non-invasive methods are available for investigating the skin, ranging from those that permit the visualisation of microvessels, to those that monitor blood flow or one of its derivatives (e.g., skin temperature and transcutaneous oxygen). Such methods can be combined with non-invasive, dynamic stimuli (e.g., the use of cold or warm stimuli, activation of the peripheral nervous system or local neuronal systems, and the topical application of vasoactive drugs) and this potentially enables the differentiation of underlying disorders (e.g., primary from secondary Raynaud's phenomenon) and also to quantify changes over time or following intervention. The present article outlines the non-invasive methods and dynamic tests that can be used to investigate the microcirculation of the skin.

Animals↗

Effect of beta-blockers on peripheral skin microcirculation in hypertension and peripheral vascular disease.

OBJECTIVE: This study was undertaken to investigate the possible negative effect of beta-blockers on skin microcirculation in patients with intermittent claudication and hypertension. Methods and materials In this clinical crossover study, 20 patients with mild to moderate hypertension, treated with long-term beta-blockade, and intermittent claudication or ischemic rest pain, underwent assessment of peripheral circulation before and after 2-week withdrawal of beta-blocking therapy and again 2 weeks after restarting therapy. Replacement therapy (calcium antagonist) was given if considered necessary to control hypertension. Skin microcirculation was assessed with three noninvasive techniques: capillary microscopy of the hallux nailfold, transcutaneous oximetry of the forefoot, and laser Doppler fluxmetry of the great toe. RESULTS: Mean initial blood pressure was 163/81 mm Hg. Mean heart rate significantly increased with withdrawal of beta-blocker, from 65 bpm to 85 bpm. No significant differences in skin microcirculation and blood pressure were found between measurements obtained before, during, and after withdrawal of beta-blocking therapy. Patients experienced no change in symptoms during the study. CONCLUSION: beta-Blockers do not appear to have a negative effect on peripheral skin microcirculation and are therefore not contraindicated to treat hypertension when intermittent claudication or ischemic rest pain is also present.

Adrenergic beta-Antagonists↗

[Raynaud's syndrome in children. Study of 23 cases].

AIM OF THE STUDY: To analyze the epidemiological characteristics of Raynaud's syndrome in childhood. PATIENTS AND METHODS: We conducted a nine-year-retrospective survey of children up to 17 y seen with Raynaud's syndrome. Charts were retrieved from pediatrics and dermatology outpatient units, and from the registry of capillaroscopy. A specific questionnaire was designed and missing data were completed after a phone interview of the parents. RESULTS: A definite diagnosis of Raynaud's syndrome was ascertained in 23 patients with marked female predominance (SR = 0.27). Triggering factors were essentially a cold environment and emotions. The mean age at the diagnosis was 11 y (5 to 16 y) with an onset after ten years in 65% of cases. Eleven of these Raynaud's syndromes were secondary with ten connectivitis, eight remained essential and four were suspected to be secondary. DISCUSSION: This series of pediatric Raynaud's syndromes was important according to scarcity of literature on this topic. The diagnosis is made upon exclusive clinical basis and we underline the high frequency of serious underlying conditions. Further etiologic investigations are mandatory for any pediatric patient with Raynaud's syndrome. The sensitivity (78%) and specificity (80%) of capillaroscopy were of interest in our patients; its prognosis value needs to be evaluated in a larger group of patients.

Adolescent↗

Fludrocortisone in the treatment of systemic hypotension in primary open-angle glaucoma patients.

BACKGROUND: Fludrocortisone is a potent mineralocorticoid, which has no known direct vasoactive properties, and is the first-line drug for treatment of orthostatic hypotension. The present study evaluated the systemic hemodynamic effects of fludrocortisone treatment in glaucoma patients. PATIENTS AND METHODS: A retrospective analysis of the charts of glaucoma patients of the University Eye-Clinic Basel was performed. Twenty-two patients with open-angle glaucoma under treatment with fludrocortisone were selected. The selected patients had one 24-h blood pressure recording immediately prior to treatment with fludrocortisone and one recording at least 2 months after starting the treatment. Parallel to blood pressure recordings, diurnal intraocular tension curve recordings and visual field testings were carried out. In addition, twelve patients also had nail-fold video-capillaroscopy. RESULTS: IOP and visual fields remained stable. The average values for all systemic blood-pressure readings showed an improvement in the follow-up compared to primary examination. Mean (+/- SD) night-to-day ratio ('nocturnal dips') of systolic, diastolic and mean arterial blood pressure decreased from 13.6 +/- 4.3%, 16.9 +/- 5.2% and 15.9 +/- 3.5%, respectively, to 9.9 +/- 5.9% (p = 0.01), 13.2 +/- 4.3% (p = 0.044) and 11.7 +/- 3.9% (p = 0.0004). Baseline capillary blood-flow velocity increased and capillary blood-flow standstill time after cold provocation decreased significantly under fludrocortisone therapy. CONCLUSION: Hemodynamic parameters show a tendency towards improvement in a magnitude which might be of clinical relevance.

Blood Flow Velocity↗

Effects of vacuum compression therapy on skin microcirculation in patients suffering from lower limb ischaemia.

BACKGROUND: We investigated the short-term effect of vacuum compression (VC) treatment on skin microcirculatory perfusion in the foot of patients with lower limb ischaemia and healthy controls. PATIENTS AND METHODS: Ten patients with intermittent claudication or rest pain and 5 healthy controls underwent vacuum-compression treatment for half an hour. The leg was positioned in an air-tight plexiglass cylinder in which hypobaric (-115 mm Hg) and hyperbaric (75 mm Hg) pressure could be generated alternately, in order to improve peripheral circulation. The effect on skin microcirculation was investigated using nailfold capillary microscopy (measuring nutritive perfusion), laser Doppler fluxmetry (LDF) (total skin perfusion) and transcutaneous oxygen tension measurements (TcpO2). RESULTS: A few patients experienced ischaemic symptoms during VC, probably because the leg was pinched off through inflation of the cuff. In both patients and controls capillary microscopic parameters did not change significantly. In some cases, microcirculatory perfusion decreased because the leg had cooled during the treatment. Application of a heating matrass annihilated this effect. Only in the patient group a few LDF- and TcpO2 parameters improved slightly, but significantly. CONCLUSION: Vacuum-compression therapy only slightly improves total skin perfusion and oxygenation, but not the nutritive microcirculation, being an essential factor in the occurrence of ischaemic symptoms. We therefore conclude that this instrument in its present form is not an aid in the treatment of lower limb ischaemia.

Aged↗

Evaluation of clinical tests to assess perfusion in chronic critical limb ischemia.

BACKGROUND: Evaluation of macro- and microcirculatory tests to confirm diagnosis, and recognize perfusion changes in chronic critical limb ischemia (CLI). PATIENTS AND METHODS: Forty-two consecutive patients with CLI examined at the University Hospital Bern, with 21 included in this prospective follow-up analysis. Patients underwent serial clinical examinations, and assessment of the macro- (ankle arterial pressure [AP], great toe pressure [TP], oscillography) and microcirculation (transcutaneous partial oxygen pressure [tcPO2] recumbent, sitting, O2-inhalation; capillary microscopy) at baseline, 6 weeks after revascularization (group 1; [n = 11]), or after 10 weeks in patients unsuitable for revascularization (group 2; [n = 10]). Clinical improvement was considered to indicate increased perfusion. RESULTS: Eleven patients with revascularization (11/11), and 2 without revascularization (2/10) showed clinical improvement. AP measurements were not reliable or feasible in 9 (43%), TP in 4 patients (19%), respectively. All measurable pressures were in accordance to clinical course. Oszillography gave a moderate perception of perfusion changes. Baseline tcPO2 levels were critical (< 30 mmHg) in all 21 patients, whereas follow-up gave poor correlation with the clinical course. Reliability to detect perfusion changes increased by adding provocation manoeuvers in patients with clinical improvement (39% [5/13] recumbent, 77% [10/13] sitting, 85% [11/13] O2-inhalation). Capillary microscopy revealed a relevant pathology at the forefoot level in all patients with feasible examinations (18/21), and significant improvements according to the clinical course in 92% of patients (12/13). CONCLUSIONS: TP measurements represented most reliable test to confirm diagnosis and disclose improved perfusion in CLI. TcPO2 measurements in recumbent position gave unreliable results, improved by provocation manoeuvers. Capillary microscopy was reliable, but time consuming and limited by anatomical restrictions.

Aged↗