Prevalence of symptoms of Raynaud's phenomenon in general practice.

OBJECTIVE--To investigate the prevalence of Raynaud''s phenomenon in the populations of five general practices. DESIGN--Two populations studied. A questionnaire was given to all new patients attending five general practices over four weeks, and the same questionnaire was sent by post to a random sample of adults from two of the practices. SETTING--General practices in inner London, Merseyside, and Cheshire. SUBJECTS--1532 Patients who completed questionnaires (1119 who attended the surgeries (response rate unknown) and 413 respondents to the postal survey (response rate 69%)). MAIN OUTCOME MEASURES--Response to questionnaire on symptoms of Raynaud''s phenomenon: patients were regarded as having the disease if they had episodes of blanching of the fingers that were precipitated by cold and accompanied by sensory symptoms (pins and needles or numbness). Subsequent interview and clinical appraisal of patients with the disease according to their responses to the questionnaire. RESULTS--The prevalence of Raynaud''s phenomenon was 11% (26/231) and 19% (34/182) respectively in men and women who completed the postal questionnaire and 16% (56/357) and 21% (157/762) respectively in those who completed the questionnaire when attending their general practice. Thus the overall rates were slightly higher in women, but there was no effect of age even after adjustment of the rates for practice and method of survey. CONCLUSION--The prevalence of Raynaud''s phenomenon is high compared with the low number of patients who seek treatment for the disease.     

Exaggerated postural vasoconstrictor reflex in Raynaud's phenomenon.

The central and local regulation of capillary blood flow in the finger was studied by the local xenon-133 washout technique in women with primary Raynaud''s phenomenon, men with vibration induced white finger, and their respective sex matched controls. The vasoconstrictor response to venous stasis of 40 mm Hg elicited by local reflex was normal in both types of Raynaud''s phenomenon. Change in posture from lying to sitting induced vasoconstriction in all groups, which was abolished by proximal nervous blockade. The vasoconstrictor response to sitting was augmented in both groups of subjects with Raynaud''s phenomenon compared with their sex matched controls. These results show the existence of central and local postural vasoconstrictor reflexes in normal fingers. In both types of Raynaud''s phenomenon there was hyperreactivity of the central sympathetic nervous system to orthostatic stress and normal function of digital arterioles and postganglionic sympathetic nerve fibres.     

Controlled trial of plasma exchange in treatment of Raynaud's syndrome.

Twenty-seven patients with Raynaud''s syndrome had their digital vessel patency assessed by Doppler ultrasound after different thermal stresses. Digital vessel patency rates differed significantly after stresses at 15 degrees C and 45 degrees C. In a randomised controlled trial placebo and heparin had no effect either on patients'' symptoms or on the patency of their digital vessels. Plasma exchange improved both symptoms and vessel patency rates at 15 degrees C and 21 degrees C. Improvement in seven out of eight of these patients has been maintained for six months. Assessing digital vessel patency by Doppler techniques allow continuous, atraumatic, and safe evaluation of the effects of different methods of treatment on the patency of the digital vessels and has helped to indicate that plasma exchange is a useful adjunct in the management of patients with severe Raynaud''s syndrome.     

Cutaneous microcirculation in systemic sclerosis and response to intra-arterial reserpine.

The cutaneous microcirculation in the hand was measured in 23 patients with systemic sclerosis, 19 with Raynaud''s phenomenon and four without Raynaud''s phenomenon, and 20 controls. The patients with Raynaud''s phenomenon had a reduced basal blood flow and an exaggerated further reduction on local cold stimulation, though both were normal in patients without Raynaud''s phenomenon. Reflex-induced vascular changes by cold stimulation of the contralateral hand showed no differences between the three groups. The blood flows were similar in the affected skin of the anterior chest wall in four patients with systemic sclerosis and peripheral Raynaud''s phenomenon and matched controls. In the seven most severely affected patients 1 mg of intra-arterial reserpine produced a prompt improvement in the cutaneous microcirculation which usually lasted one to three weeks but occasionally much longer. By judicious use of repeated injection guided by measurements of the microcirculation it was possible to heal indolent ulcers of the fingers. The results indicate that vascular changes are common in systemic sclerosis but are not fundamental in the pathogenesis of the disease. More probably there is a general soft tissue abnormality that usually but not necessarily affects the vessels.     

Treatment of Raynaud's phenomenon by fibrinolytic enhancement.

Twenty patients with advanced Raynaud''s phenomenon, in 14 of whom it was secondary to scleroderma, were treated with stanozolol, an anabolic steroid that enhances natural fibrinolysis. All showed an increase in hand blood flow and a reduction in symptoms during treatment. This response may have been caused by the lysis of fibrin deposited in the digital arteries and the reduction of plasma viscosity. Stanozolol is a useful addition to the treatment of patients with advanced Raynaud''s phenomenon who have trophic changes.     

Treatment of Raynaud's phenomenon with ketanserin in patients with connective tissue disorders.

The serotonin receptor blocker ketanserin was given orally in a double blind crossover study to 10 patients with connective tissue disorders and Raynaud''s phenomenon. Eight of the 10 patients improved clinically on ketanserin and none on placebo. Digital blood flow was assessed with laser Doppler flowmetry (LDF), photoplethysmography, and skin temperature measurements. Laser Doppler flowmetry was the most useful method, showing a significant reduction in recovery time after a standard cold provocation. Although the resting flow was not significantly improved, digital ulcers healed in four out of five patients, providing evidence of increased nutritive flow. The results of this study suggest that orally administered ketanserin may be an effective and well tolerated treatment for Raynaud''s phenomenon associated with connective tissue disorders, especially scleroderma.     

Haemorrheological response to plasma exchange in Raynaud's syndrome.

Eight patients with Raynaud''s syndrome were treated by weekly plasma exchange for four weeks using a Haemonetics Model 30 Blood Processor. The mean whole-blood viscosity at a shear rate of 0.77/s was significantly lower after treatment, and the mean index of red-cell deformability was significantly improved. In four patients studied serially the mean percentage fall in whole-blood viscosity after a single plasma exchange was 49% at 0.77/s but only 14% at 91/s. All patients noticed symptomatic improvement including healing of ischaemic digital ulcers. In six patients the number of digital arterial segments containing detectable blood flow was measured by directional Doppler; in all six the number increased. It is concluded that plasma exchange is an effective means of haemorrheological treatment and may be beneficial in patients with digital ischaemia.     

Raynaud's phenomenon in forestry workers in Quebec.

A survey of 1540 forestry workers in Quebec found a prevalence of Raynaud''s phenomenon of 30.5% among chain-saw users and 8.7% among nonusers. Prevalence was related directly to duration of use of the chain-saw. The mean interval (+/- the standard deviation) between the time the chain-saw was first used and the onset of Raynaud''s phenomenon was 7.8 +/- 5.6 years. After 20 years of chain-saw use over 50% of the population had Raynaud''s phenomenon. Relative risks among those using a chain-saw for more than 10 years were 3.60 for nonsmokers and 6.55 for smokers. Other factors associated with the phenomenon included a family history of nonoccupational Raynaud''s phenomenon, previous injuries to the arms, climate and type of residence during the wood-cutting season. Decreased work capacity, interference with leisure activities and changes in professional orientation often resulted from this disease. These problems should be taken into account when disability compensation is being considered.     

Treatment of Raynaud's phenomenon with the 5-HT2-receptor antagonist ketanserin.

The selective 5-hydroxytryptamine2-(5-HT2)-receptor-blocking agent ketanserin was given in a dose of 10 mg intravenously to nine patients with Raynaud''s phenomenon. The effect on blood flow was assessed by photopletysmography and measurments of skin temperature. Digital blood flow and skin temperature increased significantly after ketanserin injection, whereas the placebo (saline 9 g/l) had no such effect. This study suggests that ketanserin may be useful in the treatment of Raynaud''s phenomenon.     

Traumatic vasospastic disease in chain-saw operators.

Raynaud''s phenomenon is commonly induced in chain-saw operators by vibration; the hand guiding the tool is the more severely affected. The condition tends to persist after use of the chain-saw is stopped but compensation is rarely sought. Among 17 cases of Raynaud''s phenomenon in lumberjacks the condition was found to be related to use of the chain-saw in 14, 10 of whom had to give up their work in colder weather because the disease was so disabling. Two criteria essential to establish the condition as vibration-induced Raynaud''s phenomenon are the presence of symptoms for at least 2 years and a history of at least 1 year''s constant use of the chain-saw. Careful physical examination and simple tests of vascular function will provide objective evidence of permanent damage by which the patients may be classified and compensated.     

Raynaud's phenomenon and thermal entrainment: an objective test.

A new objective test for diagnosing Raynaud''s phenomenon was assessed in practice. The test is based on entrainment of the thermal vasomotor control system and entails non-invasive measurement of blood-flow responses in one hand while alternating thermal stimuli are applied to the contralateral hand. A significant (p less than 0.001) abnormality of vasomotor control was found in patients with Raynaud''s phenomenon compared with normal subjects. When applied clinically this test is diagnostic and indicates the severity of the disease and the effect of treatment.     

Thermal entrainment methods for studying Raynaud's phenomenon

Entrainment occurs when an externally applied periodic temperature stimulus forces the peripheral bloodflow component of thermoregulation to oscillate at the same frequency. This phenomenon can be demonstrated using frequency transforms to analyse the spectral content of the bloodflow, and can be used as a diagnostic test for Raynaud's phenomenon. Correlations were performed between the clinical diagnosis and the objective tests. The average inter-clinical correlation coefficient was r = 0.66. When the average clinical diagnosis was compared with a combination of thermal entrainment and digital patency testing the correlation coefficient rose to r = 0.68. These results highlight the difficulties encountered when assessing patients with Raynaud's phenomenon and the necessity of applying both physiological and clinical techniques.     

Low Molecular Weight Dextran Infusions in Systemic Sclerosis with Raynaud's Phenomenon: A Report of Nine Cases

Two litres of low molecular weight dextran in normal saline were given intravenously over 48 hours to 10 patients with systemic sclerosis and Raynaud''s phenomenon. The finger temperatures of nine were recorded under standardized conditions. One patient had lowered temperatures of the fingers, two had a rise in temperature, and six had no change. There were no side effects of the treatment. None of the 10 patients showed any clinical improvement.     

Raynaud's phenomenon as side effect of beta-blockers in hypertension.

A series of 102 hypertensive patients were assessed for the frequency of symptoms of Raynaud''s phenomenon and absent peripheral pulses. Out of 21 patients receiving methyldopa alone only one had cold hands and feet whereas among patients on beta-blockers the incidence was 50%. The frequency of both symptoms and absent pulses was highest in patients taking propranolol compared with those taking atenolol or oxprenolol. Patients without a foot pulse were much more likely to have cold hands. A change from propranolol to oxprenolol in some symptomatic patients resulted in improvement. In two patients the skin temperature fell after an 80-mg dose of propranolol. The mechanism by which beta-blockers induce Raynaud''s phenomenon is still not clear.     

Fibrinolytic activity of prostacyclin and iloprost in patients with peripheral arterial disease

We studied the effect of prostacyclin /PGI₂/ and its stable analog, iloprost, on blood fibrinolytic activity in 33 patients with peripheral arterial disease. Ten subjects /group A/ received three 5-hour infusions of iloprost on three consecutive days. The remaining 23 patients received three different 5-hour infusions /placebo, iloprost 2 ng/kg/min, PGI₂ 5 ng/kg/min/. Tissue plasminogen activator /t-PA/, total plasma fibrinolytic activity and euglobulin clot lysis time /ECLT/ were determined in patients before and after each infusion, both in freely flowing blood samples and following 10 min venous occlusion. In patients of group A, ECLT at rest was significantly shortened after all three iloprost infusions /on average by about 5–11%/. First and third infusions produced also shortening of ECLT after venostasis /by 21 and 32%/. Statistically significant rise in t-PA activity /by about 68% on average/ accompanied only the first infusion. In patients of the group B iloprost provoked significant fall in ECLT at rest /by about 19% on average/ only. PGI₂ shortened ECLT both at rest and after venous occlusion /by about 17% and 20% on average, respectively/ and led to a rise in t-PA activity after venous occlusion by about 33% on average. Our results indicate that prostacyclin and its stable analog, iloprost, enhance fibrinolytic activity in man by releasing or facilitating the release of tissue plasminogen activator from the vessel wall.     

Anticentromere antibody positive Sj?gren's Syndrome: a retrospective descriptive analysis

Introduction

A subgroup of patients with primary Sjögren''s Syndrome (SS) and positive anticentromere antibodies (ACA) were recognized as having features intermediate between SS and systemic sclerosis (SSc). Our goal was to describe this group clinically and serologically and define its tendency to evolve to full blown SSc.

Methods

Among 535 patients with primary SS we identified 20 ACA positive (ACA+/SS). We compared them to 61 randomly selected ACA negative SS patients (ACA-/SS), 31 ACA positive SSc patients with sicca manifestations [SSc/(+) sicca] and 20 ACA positive SSc patients without sicca manifestations [SSc/(-) sicca].

Results

Prevalence of ACA among SS patients was 3.7%. Cases and controls did not differ in sex ratio and age at disease onset. ACA+/SS patients had a lower prevalence of dry eyes, hypergammaglobulinaemia, anti-Ro and anti-La antibodies and a higher prevalence of Raynaud''s phenomenon and dysphagia compared to ACA-/SS patients. They also had lower prevalence of telangiectasias, puffy fingers, sclerodactyly, Raynaud''s phenomenon, digital ulcers and gastroesophageal reflux in comparison to both of the SSc subgroups and a lower prevalence of dyspnoea and lung fibrosis compared to the SSc/(+) sicca subgroup. Two patients originally having ACA+/SS evolved to full blown SSc. Four deaths occurred, all among SSc patients. Kaplan Meier analysis showed a significant difference between cases and controls in time from disease onset to development of gastroesophageal reflux, telangiectasias, digital ulcers, arthritis, puffy fingers, xerostomia, hypergammaglobulinaemia and dysphagia.

Conclusions

ACA+/SS has a clinical phenotype intermediate between ACA-/SS and SSc and shows little tendency to evolve to SSc.     

Fibrinolytic activity of prostacyclin and iloprost in patients with peripheral arterial disease

We studied the effects of prostacyclin (PGI2) and its stable analog, iloprost, on blood fibrinolytic activity in 33 patients with peripheral arterial disease. Ten subjects (group A) received three 5-hour infusions of iloprost on three consecutive days. The remaining 23 patients received three different 5-hour infusions (placebo, iloprost 2 ng/kg/min, PGI2 5 ng/kg/min). Tissue plasminogen activator (t-PA), total plasma fibrinolytic activity and euglobulin clot lysis time (ECLT) were determined in patients before and after each infusion, both in freely flowing blood samples and following 10 min venous occlusion. In patients of group A, ECLT at rest was significantly shortened after all three iloprost infusions (on average by about 5-11%). First and third infusions produced also shortening of ECLT after venostasis (by 21 and 32%). Statistically significant rise in t-PA activity (by about 68% on average) accompanied only the first infusion. In patients of the group B iloprost provoked significant fall in ECLT at rest (by about 19% on average) only. PGI2 shortened ECLT both at rest and after venous occlusion (by about 17% and 20% on average, respectively) and led to a rise in t-PA activity after venous occlusion by about 33% on average. Our results indicate that prostacyclin and its stable analog, iloprost, enhance fibrinolytic activity in man by releasing or facilitating the release of tissue plasminogen activator from the vessel wall.     

Vascular adhesion molecule-1 and markers of platelet function before and after a treatment with iloprost or a supervised physical exercise program in patients with peripheral arterial disease.

Platelet function and levels of vascular adhesion molecule-1 (VCAM-1) were investigated in 24 patients with peripheral arterial disease at Fontaine stage II undergoing a 2 weeks treatment with iloprost (0.5-2 ng/kg/h i.v. infused, 6 h/day) or a 2 weeks supervised physical training, randomly assigned. Patients were studied before (T0) and after (T14) treatments and 10 days later (T24). The adhesion of washed platelets to fibrinogen coated microwells was reduced after treatment both with iloprost (1.9+/-0.4 vs 6.8+/-0.7%; T24 vs T0; M+/-SEM; p<0.05) and physical exercise (3.0+/-1.0 vs 6.7+/-0.7; p<0.05) while adhesion to human plasma coated microwells was reduced only after treatment with iloprost (1.9+/-0.8 vs 5.8+/-0.9; p<0.05). The expression of fibrinogen receptor (glycoprotein IIb/IIIa) on platelets, measured by flow-cytometry was also reduced after iloprost treatment (17.1+/-1.5 vs 31.8+/-4.8 AU; p<0.05) and physical exercise (14.6+/-1.5 vs 34.0+/-3.3; p<0.05). Theurinaryexcretion of platelet thromboxane A2 metabolite 2,3-dinor-thromboxane B2 decreased only in patients treated with iloprost (154.7+/-97.9 vs 256.2+/-106.4 pg mg creatinine(-1); p<0.05). Similarly plasma VCAM-1 was lower in patients who were treated with iloprost (827.7+/-77.4 vs 999.0+/-83.8 ng ml(-1); p<0.05). In conclusion, both iloprost and physical exercise seem to act on reversible phenomena such as the expression of adhesion molecules or ex vivo adhesion, whereas only iloprost reduces thromboxane A2 biosynthesis in vivo. This anti-platelet activity seems to be extended in time and to be associated with an improvement in vascular function.     

Microcirculation and tolerability following i.v. infusion of PGE1 and iloprost: a randomized cross-over study in patients with critical limb ischemia

In a randomized cross-over study, the effect of PGE(1) and iloprost on microcirculation as well as the tolerability was investigated in 36 patients with peripheral arterial occlusive disease stage III and IV according to Fontaine. Patients received PGE(1) and iloprost by single 3-h i.v. infusions on two different days at doses recommended by the manufacturers or in previous studies (PGE(1): first hour 20 microg, next 2h 30 microg each. Iloprost: first hour 0.5 ng/kg/min, next 2h 1.0 ng/kg/min). Transcutaneous oxygen pressure (tcPO(2)) values increased much more with PGE(1). Median tcPO(2) increase over baseline 30 min after the end of infusion was 9 and 2 mmHg for PGE(1) and iloprost, respectively, corresponding to median AUC differences from baseline of 1050 and 210 min mmHg. Because of its exploratory character, the study was not powered to test for significance. Adverse effects occurred in 19.4% (PGE(1)) and 30.6% (iloprost) of patients. Dose reduction was required in 3 patients receiving iloprost (hypotension, nausea, irritation of the infused vein), and in none receiving PGE(1).     

Para-Clinical and Immunological Evaluation in Buerger's Disease as a Suspected Autoimmune Disease: Case Series

Background:Autoimmunity causes the loss of normal immune homeostasis and involves the presence of autoantibodies and inflammation. Thromboangiitis obliterans or Buerger''s disease (BD) refers to a type of vascular obstructive syndrome, with tobacco exposure accounting for disease formation and progression. However, the current understanding of autoimmunity is unclear in the context of BD, and the scientific findings are not enough to support autoimmune mechanisms. This study was aimed at investigating autoimmunity factors in patients with BD.Methods:Clinical and experimental examinations were performed on 80 patients with BD. The diagnostic work-up for autoimmunity was composed of IgM rheumatoid factor (RF), anti-nuclear antibodies (ANA), The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (CCP) antibodies, Antiphospholipid antibodies (APA), Anti-cardiolipin antibodies (ACLA), anti-double-stranded DNA (ds-DNA), and extractable nuclear antigen (ENA) profile. Immunomarkers were detected using the quantitative enzyme-linked immunosorbent assay (ELISA).Results:Raynaud''s phenomenon (84.93%), cold sensitivity (76.25%), and claudication (73.75%) were the most common symptoms in the BD patients. Also, 64.29% represented with high ANA levels and positive RF, while 42.11% were found with increased ANA and ESR levels. The ANA/RF positive BD patients had ESR> 15 mm/hr and a high prevalence of cold sensitivity, claudication, and Raynaud''s phenomenon (p> 0.05).Conclusion:There is a possibility of a non-specific autoimmune disposition among BD patients. RF and ANA could be considered for predicting disease progression.Key Words: Antibodies, Autoimmunity, Buerger''s Disease, Immune System