Primary Raynaud's Syndrome Research Articles

OA17 An evolving case of Anti PM/Scl Anti body associated Aggressive Systemic Sclerosis

OA17 An evolving case of Anti PM/Scl Anti body associated Aggressive Systemic Sclerosis

Abnormality Detection in MRI as a Diagnostic Tool for Raynaud's Phenomenon

Background Raynaud's phenomenon (RP), a disorder of episodic vasospasms found in the digits, is triggered by exposure to cold or stress. Typically, RP presents as a triphasic color pattern from pallor to cyanosis to rubor. Current diagnostic tools include nailfold capillaroscopy, thermography, color doppler ultrasound, cold stimulation test, and clinical findings. Due to expense, lack of availability, and reproducibility of results, there is no present universal, gold standard diagnostic method. Magnetic Resonance Imaging (MRI) has been used for diagnosis or prognosis, with associated abnormalities in RP patients. This research analyzes the potential use of MRI as an accurate and universal diagnostic tool for RP. Methods A search of PubMed and Google Scholar databases was conducted using the search terms: “Abnormal MRI, Raynaud's”, “MRI, Raynaud's Syndrome”, “Magnetic resonance, Raynaud's”, “Magnetic resonance angiography, Raynaud's”. A total of 13 papers were found, including 99 cases of Raynaud's patients, for analysis and incorporation into this review. Articles presenting cases of Raynaud's symptoms secondary to tumors or cysts were excluded. Results 99 patients (average age = 39.58 years old, age range = 18-80; gender = 54 female, 12 male, 33 unspecified), presented with RP with 98 MRIs completed. 30 patients presented with Primary Raynaud's Syndrome (PRS) and 69 presented with Secondary Raynaud's Syndrome (SRS). 88.78% of MRIs were abnormal. 84.06% of SRS patients had abnormal MRI results. SRS patients with normal results were limited to scans of the brain (3 with underlying systemic lupus erythematosus; 8 with systemic sclerosis). 100% of the PRS patients had abnormal MRI results. Conclusion Majority of MRIs identified abnormalities associated with RP, suggesting its potential as a diagnostic tool for RP. Abnormal MRI results were more accurate in identifying RP for PRS (100%) compared to SRS (84.06%). MRIs were found to be applicable in large patient populations, non-restrictive of age or gender. A limitation to the study included multiple, overlapping terms (RP, Raynaud's disease and Raynaud's syndrome) found in manuscripts, which contribute to confounding of results. Additionally, the various MRI locations (eg., extremity, heart, brain) could impact findings.

Finger blood flow after the cold challenge with primary Raynaud's syndrome: a case report.

Background Raynaud’s syndrome is a commonly encountered disorder. The relationship between the grade of Raynaud’s phenomenon and severity of vasoconstriction is unclear. Recently, various methods including colour Doppler ultrasonography have been used for assessment of vascularity of the extremities including fingers.Case summary A 53-year-old man had a 6-year history of Raynaud’s phenomenon with typical tri-coloured changes proceeding from white, blue to red and slight pain and slight paresthaesia in the fingers of both hands when his fingers were exposed to cold. He was diagnosed with primary Raynaud’s syndrome. After treatment with the calcium channel blocker amlodipine (5 mg once daily), a cold challenge did not induce Raynaud’s phenomenon on the fingers in the present patient. After the cold challenge, colour Doppler ultrasonography showed that vascularity was markedly decreased or was absent, whereas there was little difference in skin colour of the fingers.Discussion In Raynaud's phenomenon, vasospasm may occur even if the symptoms are well-controlled with a calcium channel blocker. It is unlikely that clinical symptoms in patients with Raynaud’s syndrome always reflect the severity of vasoconstriction in their fingers.

Targeted high concentration botulinum toxin A injections in patients with Raynaud's phenomenon: a retrospective single-centre experience.

Raynaud's phenomenon is a vasospastic condition affecting hands and feet which may lead to rest pain, ischemic ulcers and gangrene. Botulinum toxin A has been shown to improve peripheral circulation and relieve vasospastic symptoms. Our aim wasto assess our treatment outcomes following Botulinum toxin A injections in patients with Raynaud's phenomenon and to explore the importance of toxin concentration and injection sites. Retrospective chart review of patients with primary and secondary Raynaud's syndrome treated with Botulinum toxin A injections and a literature review was conducted. The toxin dose, injection sites, symptom relief, healing of ulcers and complications were assessed. A total of 30 treatment episodes over a 7½year period were included. All patients had failed medical management. Botulinum toxin A injection was injected primarily in the vicinity of the palmar digital neurovascular bundle. The average total Botulinum toxin A dose injected was 156U and the concentration was 50U/ml. All patients reported an improvement in symptoms and healing of digital ulcers. One patient reported a temporary muscle weakness. Six patients had a single treatment episode with long term benefit. Systemic sclerosis patients had an average of 6-month interval between treatment episodes. Higher doses of Botulinum toxin A has been well tolerated with no long term adverse effects. Our study shows that targeted low volume higher concentration Botulinum toxin A injections are effective in treating Raynaud's phenomenon.

Management of mild, primary Raynaud Syndrome: supplementation with Pycnogenol®.

Raynaud syndrome (RS) is associated with vasospasm of the hand and fingers as a response to cold or stress. RS may cause discomfort and color changes (pallor, cyanosis, erythema, as single symptoms, but usually in combination, localized to one or more fingers). The aim of this 4-week registry study was the evaluation of subjects with mild, primary RS and their treatment with a standard management (SM) plan in comparison with SM associated with supplementation with Pycnogenol®. A group of 67 females with mild, primary RS was included. All subjects were working in shops with refrigerators. No skin lesions were present. The age range was between 30 and 40; the vasospastic changes were symmetrical; no other physical findings were present. The two groups, receiving standard management (N.=33) or SM+Pycnogenol®, 100 mg/day, (N.=34) were comparable at inclusion. Considering the main symptoms, the decrease in coldness, burning pain, paresthesias and irregular color changes was more significant with Pycnogenol® (P<0.05) at 4 weeks. At thermography, low temperature areas and discrepancies in temperature and color were decreased with Pycnogenol® more than in controls (P<0.05). In the Pycnogenol® group, one subject (2.94%) decided to use drug treatment (PGE1) in 4 weeks in comparison with 5 controls (15.15%). The lowest finger temperature improved from 20.3° C at inclusion to 26.4° C at 4 weeks (+30.04%) with Pycnogenol® in comparison with lower values (from 20.5 to 23.1 [+12.7%] in controls [P<0.05]). The fingertip skin flux increased significantly (+ 1.55 flux units) with Pycnogenol® (P<0.05), in controls just by +0.14 (ns). Supplementation with Pycnogenol® decreased oxidative stress and increased transcutaneous oxygen pressure (TcPO2) more than in controls. Compliance and tolerability were optimal. This pilot registry study suggests that Pycnogenol® may be used with significant advantages in primary, mild RS. Subjects using Pycnogenol® may control their symptoms and may avoid the need for more complex and, potentially dangerous or expensive treatments.

Viscum album and a concomitant integrative medical therapy in a patient suffering from primary Raynaud syndrome and primary breast cancer – A 10-year follow-up case report

Viscum album and a concomitant integrative medical therapy in a patient suffering from primary Raynaud syndrome and primary breast cancer – A 10-year follow-up case report

Microcirculation of the fingers in Raynaud's syndrome: (99m)Tc-DTPA imaging.

We investigated the circulatory characteristics of patients suffering of primary and secondary Raynaud's syndrome. We examined 106 patients presenting with the classical symptoms of Raynaud's syndrom (47 primary, 59 secondary) by hand perfusion scintigraphy developed by our Department of Nuclear Medicine. After visual evaluation we analyzed the images semiquantitatively, using the finger to palm ratio. We statistically compared the patients with primary and those with secondary Raynaud's syndrome. By visual evaluation we constated regional perfusion disturbances in 42 from 59 patients with secondary Raynaud's syndrome. However, this was observed in only 3 from 47 patients with the primary form of this disease. This difference was statistically significant (p<0.001). Semiquantitative analysis showed that the finger/palm ratios (FPR) were significantly lower (p<0.05) for the patients with primary Raynaud's syndrome. No differences in the FPR values concerning sex or right and left side. The hand perfusion scintigraphy with (99m)Tc-DTPA is a noninvasive, cost effective diagnostic tool, which objectively reflects the global and regional microcirculatory abnormalities of the hands, and provides quantitative data for follow-up.

Nailfold capillaroscopy assessment of microcirculation abnormalities and endothelial dysfunction in children with primary or secondary Raynaud syndrome.

Raynaud syndrome (RS) manifests as episodes of transient spasms of peripheral blood vessels, most often in response to cold. The reason of that symptom (primary RS (pRS)) usually cannot be found but may be accompanied by some autoimmune diseases (secondary RS (sRS)). In this study, we assessed microcapillary status and serum concentrations of chosen cytokines, adhesive molecules, and nitric oxide (NO) in patients with pRS and sRS in comparison with healthy children. Eighty-six patients with RS were enrolled into the study, including 52 with pRS and 34 with sRS. The control group consisted of 29 healthy children. A decrease in myorelaxative and anticoagulant abilities was observed, with simultaneous prevalence of vasopressor substances and procoagulative activity. Therefore, several important factors such as endothelin-1 (ET-1), E-selectin (E-sel), interleukin-18 (IL-18), and nitrogen oxide (NO) were also analyzed. Two types of capillaroscopy status were determined: normal and microangiopathic. There was a significant relationship between presence of microangiopathy and higher serum ET-1 (p = 0.018) and E-sel (p = 0.021) levels. Similarly, we have found a correlation between presence of ANA and higher ET-1 (p = 0.005), but not E-sel (p = 0.241). In patients with pRS, we found significant relationship between ANA and higher ET-1 (p = 0.008). No such relations were observed in sRS patients. Our data indicates that external factor-induced vasoconstrictive effects dominated in pRS, whereas in sRS in the course of connective tissue diseases, it was accompanied by coexistent vasodilation due to endothelial dysfunction. The latter phenomenon is at least partially dependent on insufficient NO release.

SP0116 How to Select the Most Appropriate Capillaroscopic Device: PROS and Cons

One of the most important indications for performing a capillaroscopy is the differentiation between primary and secondary Raynaud's Syndrome. It is possible to examine with different kind of microscopes, which...

Acro-osteolysis

A 71-year-old man hospitalised with tracheobronchitis, complained of hand discolouration. His hands showed the three-phases of skin colour changes (white, blue, and red) and a diagnosis of Raynaud's syndrome was established. When questioned about the first time he had these symptoms, the patient noted that they had been recurrent for about 20 years. He had relatively short fingers, particularly of the thumbs, and no bone was palpable in most of the distal phalanges (figure A). Radiography of his hands showed bone resorption of almost all terminal phalanges of both hands, so-called acro-osteolysis (figure B). Immunological investigations and clinical features excluded several diseases commonly associated with Raynaud's syndrome. Nailfold capillaroscopy was done and showed no changes, supporting the diagnosis of primary Raynaud's syndrome. The most common causes of acro-osteolysis include scleroderma, psoriatic arthritis, occupational causes, injury (eg, thermal burn), and hereditary syndromes (eg, Hadju-Cheney syndrome). In patients with long-standing primary Raynaud's syndrome, chronic vascular deficiency may lead to acro-osteolysis. A 71-year-old man hospitalised with tracheobronchitis, complained of hand discolouration. His hands showed the three-phases of skin colour changes (white, blue, and red) and a diagnosis of Raynaud's syndrome was established. When questioned about the first time he had these symptoms, the patient noted that they had been recurrent for about 20 years. He had relatively short fingers, particularly of the thumbs, and no bone was palpable in most of the distal phalanges (figure A). Radiography of his hands showed bone resorption of almost all terminal phalanges of both hands, so-called acro-osteolysis (figure B). Immunological investigations and clinical features excluded several diseases commonly associated with Raynaud's syndrome. Nailfold capillaroscopy was done and showed no changes, supporting the diagnosis of primary Raynaud's syndrome. The most common causes of acro-osteolysis include scleroderma, psoriatic arthritis, occupational causes, injury (eg, thermal burn), and hereditary syndromes (eg, Hadju-Cheney syndrome). In patients with long-standing primary Raynaud's syndrome, chronic vascular deficiency may lead to acro-osteolysis.

Gefäßsonographie

Vascular ultrasound plays an important role in the visual depiction of arteries, veins, and changes of tissue in lymphatic diseases. In the case of arteries, this ranges from endothelial dysfunction over measuring the increase of intima media thickness to the detection of stenoses, occlusion, or aneurysm. Ultrasound helps to differentiate in functional arterial diseases such as primary and secondary Raynaud's syndrome as well as arterial compression syndromes like entrapment syndrome of different arterial regions or the chronic exceptional compartment syndrome of the lower leg. Ultrasound plays a central role in the diagnosis of rare arterial diseases like large vessel vasculitis, arterial dissection, cystic adventitial degeneration, and the differentiation of vascular malformation especially in children, thus, permitting ultrasound-guided intervention and follow-up controls. In venous thrombosis, sonography is the primary imaging method, while follow-up controls help in the prediction of recurrent venous thrombosis. Ultrasound is a tool to determine the cause and severity of chronic venous insufficiency and allows different therapeutic procedures for the treatment of varicose veins to be visually monitored.

The effect of metoprolol alone and combined metoprolol–felodipin on the digital microcirculation of patients with primary Raynaud's syndrome

Objectives Calcium channel inhibitors have beneficial impact on microcirculation, but beta-blocker effect is controversial. Clinicians still do not agree on beta-blocker combination with other treatments in the management of impaired microcirculation. The aim of the present study was to describe the effects of beta-blocker metoprolol monotherapy and combined with calcium channel inhibitor felodipin on digital microcirculation in primary Raynaud's syndrome. Methods We enrolled in this study 46 patients suffering from both hypertension and primary Raynaud's syndrome. Fifteen patients were treated with beta-blocker monotherapy (metoprolol), 13 received combined beta-blocker and calcium channel blocker therapy (felodipin and metoprolol), while 18 patients without any medications served as controls. Measurement of digital microcirculation was carried out with laser Doppler scanner. Results and conclusions Our investigation concludes that the concurrent administration of beta-blockers with calcium channel inhibitors positively reduces symptoms in patients suffering from Raynaud's syndrome.

FP20-TU-03 Evaluation of peripheral nervous system in patients with primary Raynaud's syndrome and dysautonomia

FP20-TU-03 Evaluation of peripheral nervous system in patients with primary Raynaud's syndrome and dysautonomia

Abordaje electroterápico en la enfermedad de Raynaud: a propósito de un caso

Introduction Primary Raynaud's syndrome consists in a symptomatic complex secondary to peripheral vasospasm in response to cold thermal stimulus and/or emotional stimulus in the distal parts of the body whose prevalence in adults varies from 3.7% to 13%. Objectives To analyze the symptoms and topography of the manifestation of Raynaud's syndrome, as well as the achieving of normal sweating by the treatment protocol designed. Results There is a significant reduction of perspiration, that is 66%, with a decrease in the number of episodes and increase of the periods between episodes, achieving normochromic coloring with the disappearance of the phases of chromatic change. Conclusions The thermohygrometric and colorimetric findings lead us to consider iontophoresis electrotherapy with running water as a long-term effective procedure that makes it possible to achieve hidrosis of the affected area and improvement in the vascular changes associated to Raynaud's disease.

Circulating nerve growth factor in primary and secondary Raynaud’s syndrome – Results of a pilot study

In this pilot study we examined circulating concentrations of nerve growth factor (NGF) in controls and patients suffering from primary or secondary Raynaud's syndrome and determined their relation to digital vasospasm. Eighteen controls, 16 patients with primary RP and 19 patients with systemic sclerosis (SScl) were included. Degree of vasospasm was graduated according to the degree of plethysmographically measured vasospastic reaction after cold test. A diary was handed out for documentation of the daily number and duration of RP during a period of 16 days. Circulating NGF levels were analysed by a commercial ELISA (Promega Inc., USA). SScl-patients were significantly older (p < 0.0001) and more severely affected by spontaneously occurring RP (p = 0.03), whereas the severity of the vasospastic reactions after a standard cold test were not significantly different between the groups (p = 0.09). Within each study group and between the study groups elevated NGF levels were observed only in SScl-patients after thermal provocations (p = < 0.05). In a correlation analysis restricted to patients with PRP or SRP, the degree of vasospasm after cold testing as well as the intensity of Raynaud's symptoms were not correlated with NGF-levels (p = n.s.). Our results do not support the hypothesis that NGF plays a major role in the generation of vasospasm in Raynaud's phenomenon.

Plasma-Endothelinkonzentration unter Kälteprovokation bei primärem Raynaud-Syndrom*

Plasma endothelin concentration was measured separately in each hand before and after unilateral whole-hand cooling in 23 patients (5 men, 18 women; mean age 35.2 [19-52] years) thought to have primary Raynaud's syndrome (Raynaud's disease). The diagnosis was confirmed, after excluding other causes, by strain-gauge plethysmography demonstrating cold-induced vasospasm in 8, disproved in 15. In the Raynaud patients (but not in the others) the plasma concentration of endothelin on the cooled side increased from 5.13 +/- 0.18 to 6.34 +/- 0.35 pg/ml (P < 0.05). On the non-cooled side there occurred a brief rise in endothelin concentration from 5.10 +/- 0.18 to 6.23 +/- 0.35 pg/ml (P < 0.05), although there had been no evidence of vasospasm. There had been no difference between the two sides in endothelin concentration before the cold provocation. The results suggest that cold provocation in primary Raynaud's syndrome causes an increase in endothelin liberation and that this plays a role in the pathogenesis of the vasospasms. Apparently not only local but also reflex mechanisms contribute to this.

Functional and morphological evaluation of hand microcirculation with nailfold capillaroscopy and laser Doppler imaging in Raynaud's and Sjögren's syndrome and poly/dermatomyositis

Objectives: Nailfold capillaroscopy is widely used in autoimmune patients to determine capillary morphology. Laser Doppler imaging (LDI) is a relatively new method for measuring the microcirculation of cutaneous perfusion. The aim of this study was to investigate the capillary morphology and microcirculation among patients with Sjögren's syndrome (SS) and poly/dermatomyositis (PM/DM) with these two non‐invasive methods and to detect secondary Raynaud's syndrome (SRS) in these autoimmune diseases.Methods: Thirty patients with primary SS, 30 patients with PM/DM, 30 patients with primary Raynaud's syndrome (PRS), and 30 healthy volunteers were included in the study. Nailfold capillaroscopy and LDI were performed on each patient.Results: A comprehensive analysis was performed among the patients and healthy individuals. Among SS patients avascularity and among PM/DM patients avascularity and capillary morphology changes were most often detected by capillaroscopy. With LDI the mean steady‐state cutaneous perfusion was 1.25 perfusion units (PU) in region of interest 1 (ROI1), 1.22 in ROI2, and 1.49 at the fingertips in PRS patients; the corresponding values were 1.2, 1.03, and 1.48 PU in SS, 0.91, 0.76, and 1.19 PU in PM/DM, and 1.79, 1.62, and 2.2 PU in the controls. The differences were significant between each autoimmune group compared to the control group (p<0.02, p<0.001, and p<0.001, respectively).Conclusions: By using nailfold capillaroscopy, abnormalities in capillary morphology can be detected, and by using LDI, the reduced blood flow in the capillaries can be detected. These investigations can be useful in the detection of SRS, or in distinguishing whether the reduced blood flow is due to primary/systemic autoimmune diseases.

P35.11 In patients with primary Raynaud syndrome there is prolonged cutaneous vasoconstriction and abnormal vasodilatation with exposure to cold

P35.11 In patients with primary Raynaud syndrome there is prolonged cutaneous vasoconstriction and abnormal vasodilatation with exposure to cold

Evidenzbasierte Therapie des Raynaud-Syndroms

Raynaud's syndrome has a prevalence of 3-5% in the general population. Despite its high frequency, the majority of available therapies have not been validated in randomized controlled trials. Effective therapies with a high level of evidence include the calcium channel blocker nifedipine. As analyzed by meta-analyses, nifedipine showed improvement of the peripheral circulation, as well as reduction of both the intensity and frequency of attacks in patients with primary and secondary Raynaud's syndrome as compared to placebo. Similar results in a metaanalysis were obtained for intravenous infusions of iloprost in patients with secondary Raynaud's phenomenon associated with systemic sclerosis. In addition, intravenous infusions of iloprost improved healing of fingertip ulcers in patients with systemic sclerosis. Therapies with significant effects in single randomized controlled trials include angiotensin II-receptor type 1 antagonists (losartan), the calcium channel blockers felodipine und amlodipine, serotonin-reuptake-inhibitors (fluoxetine) und phosphodiesterase-V-inhibitors (sildenafil, vardenafil). However, the results for these promising substances have to be confirmed in long-term trials with larger patient numbers.

Effects of cilostazol in patients with Raynaud's syndrome

Raynaud's syndrome (RS), which is characterized by recurrent episodes of vasospasm with exposure to cold, may occur alone (primary RS) or in association with connective tissue diseases or other underlying conditions (secondary RS). We investigated the effect of cilostazol on vessel wall responses in RS. Patients were diagnosed (primary or secondary RS associated with connective tissue diseases) and randomized to placebo or cilostazol 100 mg twice daily for 6 weeks in a double-blind manner. Brachial artery vasoreactivity, laser Doppler fluxmetry, and cold pressor testing (CPT) were performed at study initiation and completion. Symptoms were assessed using standardized questionnaires. Forty subjects completed the study (19 with primary RS and 21 with secondary RS). Cilostazol significantly increased the mean brachial artery diameter at 6 weeks (primary RS, p = 0.006; secondary RS, p = 0.06). There was no change in median flow-mediated dilation (FMD) with cilostazol in primary RS (25th, 75th percentiles) (4.06% [2.5, 6.1] to −0.77% [−2.4, 3.4] or secondary RS (2.2% [0.05, 6.3] to 2.95% [1.7, 7.4]). There were no changes in nitroglycerin-mediated dilation or microvascular flow indexes in either cohort. In patients with primary RS, cilostazol treatment yielded a positive change in the slope of brachial responsiveness to CPT (increase of 0.32 mm/min; p = 0.002 vs placebo). Cilostazol treatment remained significantly associated with increased brachial artery diameter when controlling for baseline values (p = 0.018). Cilostazol increased conduit vessel diameter in patients with primary and secondary RS, with a favorable impact on conduit vessel responsiveness to cold in patients with primary RS without affecting microvascular flow or symptoms.