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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: a double blind randomised study.

OBJECTIVE--To compare the long term effects of short term intravenous infusions of iloprost with those of oral nifedipine in patients with Raynaud''s phenomenon associated with systemic sclerosis. DESIGN--Double blind, placebo controlled, randomised group comparison. SETTING--Dermatology outpatient clinic. PATIENTS--Twenty three patients with Raynaud''s phenomenon associated with well documented systemic sclerosis (American Rheumatism Association criteria) and with typical abnormalities in fingernail folds on capillaroscopy. INTERVENTIONS--Twelve patients were randomised to receive intravenous infusions of iloprost starting at 0.5 ng/kg/min and increased by 0.5 ng/kg/min every 15 minutes to a maximum of 2.0 ng/kg/min for eight hours on three consecutive days with a further single infusion at week 8. Placebo capsules were given concurrently. Eleven patients were randomised to receive nifedipine, starting at 30 mg daily and increased to 60 mg daily after four weeks for another 12 weeks. Infusions of placebo were given in the same manner as the infusions of iloprost. One patient from each group withdrew because of social reasons and three patients receiving nifedipine withdrew because of side effects. END POINT--Reduction in number, duration, and severity of attacks of Raynaud''s phenomenon, reduction in number of digital lesions, increase in digital blood flow. MEASUREMENTS AND MAIN RESULTS--Measurements were taken at 0, 4, 8, 12, and 16 weeks. Both regimens produced a reduction in the number, duration, and severity of attacks of Raynaud''s phenomenon. The mean (SE) number of digital lesions was reduced with iloprost (from 3.5 (1.6) to 0.6 (0.3] and with nifedipine (from 4.3 (0.8) to 1.4 (0.5] after 16 weeks. Hand temperature and digital and microcirculatory blood flow were increased with iloprost but not with nifedipine. CONCLUSION--Both iloprost and nifedipine are beneficial in the treatment of Raynaud''s phenomenon. With nifedipine, however, side effects are common. Short term infusions of iloprost provide longlasting relief of symptoms, and side effects occur only during the infusions and are dose dependent.     

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.     

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.     

Capillary blood flow imaging within human finger cuticle using optical microangiography

We report non‐invasive 3D imaging of capillary blood flow within human finger cuticle by the use of Doppler optical microangiography (DOMAG) and ultra‐high sensitive optical microangiography (UHS‐OMAG) techniques. Wide velocity range DOMAG method is applied to provide red blood cell (RBC) axial velocity mapping in capillary loops with ranges of ±0.9 mm/s and ±0.3 mm/s. Additionally, UHS‐OMAG technique is engineered to acquire high resolution image of capillary morphology. The presented results are promising to facilitate clinical trials of treatment and diagnosis of various diseases such as diabetes, Raynaud's phenomenon, and connective tissue diseases by quantifying cutaneous blood flow changes within human finger cuticle. (© 2013 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

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     

Scleroderma and Primary Biliary Cirrhosis

Two cases of scleroderma and primary biliary cirrhosis are described. One had systemic sclerosis with primary biliary cirrhosis of six years'' duration at the stage of ductular proliferation. The other had the C.R.S.T. syndrome (calcinosis, Raynaud''s phenomenon, sclerodactyly, and telangiectases) with primary biliary cirrhosis at the florid stage. Several similar cases were found in a review of other reports, and it is suggested that the association may be due to a common “autoimmune” process.     

Cryocrystalglobulinemia.

A 40-year-old woman had cryocrystalglobulinemia with IgG2(K1). To date, 27 other cases of spontaneous crystallization of a plasma protein have been reported. In all, the protein, a cryoglobulin, has been found to be an IgG molecule. The disease most commonly associated with this phenomenon has been multiple myeloma. None of the patients have had Raynaud''s phenomenon, but many have had purpuric skin lesions made worse by exposure to cold. In the two cases of essential cryocrystalglobulinemia, crystals were found in the peripheral blood film. Immunologic, biochemical and ultrastructural studies have so far not demonstrated any property common to all cryocrystalglobulins.     

Anti-Jo-1 antibody: a marker for myositis with interstitial lung disease.

An autoantibody known as anti-Jo-1 antibody is found in 25% of patients with myositis. Its prevalence in patients with both myositis and cryptogenic fibrosing alveolitis was 68% (13 out of 19 patients), compared with 7.5% in patients with myositis alone (four of 53) and 3% in patients with cryptogenic fibrosing alveolitis alone (two of 62). Anti-Jo-1 antibody may be useful in indicating patients with myositis and cryptogenic fibrosing alveolitis. Raynaud''s phenomenon, the sicca syndrome, and mild arthritis are also often part of the syndrome.     

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.     

A pyroelectric thermal imaging system for use in medical diagnosis

The value of infra-red thermography in a number of pathologies, notably rheumatology and vascular diseases, is becoming well established. However, the high cost of thermal scanners and the associated image processing computers has been a limitation to the widespread availability of this technique to the clinical community. This paper describes a relatively inexpensive thermographic system based on a pyroelectric vidicon scanner and a microcomputer. Sofware has been written with particular reference to the use of thermography in rheumatoid arthritis and vasospastic conditions such as Raynaud's phenomenon.     

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.