An Experimental Phototherapy Device for Studying the Effects of Blue Light on Patients with Raynaud's Phenomenon.

Raynaud's phenomenon (RP) is a condition that causes decreased blood flow to areas perfused by small blood vessels (e.g., fingers, toes). In severe cases, ulceration, gangrene, and loss of fingers may occur. Most treatments focus on inducing vasorelaxation in affected areas by the way of pharmaceuticals. Recently, animal studies have shown that vasorelaxation can be induced by non-coherent blue light (wavelength ~ 430-460 nm) through the actions of melanopsin, a photoreceptive opsin protein encoded by the OPN4 gene. To study this effect in humans, a reliable phototherapy device (PTD) is needed. We outline the construction of a PTD to be used in studying blue light effects on Raynaud's patients. Our design addresses user safety, calibration, electromagnetic compatibility/interference (EMC/EMI), and techniques for measuring physiological responses (temperature sensors, laser Doppler flow sensors, infrared thermal imaging of the hands). We tested our device to ensure (1) safe operating conditions, (2) predictable, user-controlled irradiance output levels, (3) an ability for measuring physiological responses, and (4) features necessary to enable a double-blinded crossover study for a clinical trial. We also include in the Methods an approved research protocol utilizing our device that may serve as a starting point for clinical study. We introduced a reliable PTD for studying the effects of blue light therapy for patients suffering from Raynaud's phenomenon and showed that our device is safe and reliable and includes the required measurement vectors for tracking treatment effects throughout the duration of a clinical study.

Cold Hands or Feet: Is It Raynaud's or Not?

Raynaud's phenomenon is an exaggerated response to cold stimuli that may be primary or secondary. The diagnosis relies on patient history and physical examination to distinguish RP from other vasomotor dysfunction (e.g. acrocyanosis, pernio, small fiber neuropathy with vasomotor symptoms, and complex regional pain syndrome). Achenbach syndrome, or spontaneous venous hemorrhage, may also be mistaken for RP but is a self-limiting phenomenon. Laboratory evaluation and vascular diagnostic testing may identify SRP causes. Regardless of etiology, treatment includes warming with trigger avoidance, and consideration of vasodilators (eg. calcium channel, alpha-1 blockers). SRP with digital ulceration may require PDE5i, endothelin-1 receptor blockers, and prostanoids. Refractory cases may require pneumatic arterial pumps, botulinum toxin administration, or surgical sympathectomy.

Adipose derived stromal vascular fraction and fat graft for treating the hands of patients with systemic sclerosis. A randomized clinical trial.

BACKGROUND: Systemic Sclerosis in the hand is characteristically evidenced by Raynaud's phenomenon, fibrosis of the skin, tendons, ligaments, and joints as well as digital ulcers with prolonged healing. Current medical treatment does not always cure these complications. Local adipose-derived stromal vascular fraction administration into the hands has been proposed as an emerging treatment due to its regenerative properties. The objective of this randomized controlled clinical trial was to evaluate the safety and clinical effects of fat micrografts plus adipose derived-stromal vascular fraction administration into the hands of patients with systemic sclerosis. METHODS: This was an open-label, monocentric, randomized controlled study. Twenty patients diagnosed with systemic sclerosis were assigned to the experimental or control group. Fat micrografts plus the adipose derived-stromal vascular fraction were injected into the right hand of experimental group patients. The control group continued to receive only medical treatment. Demographic, serologic data and disease severity were recorded. Digital oximetry, pain, Raynaud phenomenon, digital ulcers number, mobility, thumb opposition, vascular density of the nail bed, skin affection of the hand, serologic antibodies, hand function, and quality of life scores were evaluated in both groups. RESULTS: The results of the intervention were analyzed with the Wilcoxon rank test, and the differences between the control and experimental groups at 0 days and 168 days were analyzed with the Mann-Whitney U test. Adverse events were not observed in both groups. At the end of the study, statistically significant improvements were observed in pain levels (p<0.05) and number of digital ulcers (p<0.01) in the experimental vs control group. CONCLUSION: The injection of adipose derived-stromal vascular fraction plus fat micrografts is a reproducible, and safe technique. Pain and digital ulcers in the hands of patients with systemic sclerosis can be treated with this technique plus conventional medical treatment.

The use of acupuncture in patients with Raynaud's syndrome: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the effectiveness of acupuncture for the treatment of Raynaud's syndrome by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: Studies were identified from English and Chinese databases from their inception to September 2020. The outcomes of interest were remission incidence, number of daily attacks, incidence of positive cold stimulation tests and incidence of cold provocation tests. We conducted meta-analysis and network meta-analysis using meta and gemtc. RESULTS: Six trials (n = 272 participants) were included in the meta-analysis. Pairwise meta-analyses show that acupuncture was associated with increased remission incidence (risk ratio (RR) = 1.21, 95% confidence interval (CI) = 1.10 to 1.34), decreased daily number of attacks (weighted mean difference (WMD) = -0.57, 95% CI = -1.14 to -0.01), and increased incidence of positive cold stimulation tests (RR = 1.64, 95% CI = 1.27 to 2.11). There was not enough evidence to associate acupuncture with decreased incidence of positive cold provocation tests. The network meta-analyses did not demonstrate significant results for the effectiveness of any acupuncture treatments (electroacupuncture or manual acupuncture ± moxibustion), compared with controls, in terms of remission incidence or daily number of attacks, possibly due to small sample sizes and a lack of statistical power. CONCLUSION: The use of acupuncture may be effective for the treatment of Raynaud's syndrome in terms of increasing remission incidence, decreasing daily number of attacks and increasing incidences of positive cold stimulation tests. However, our findings should be interpreted with caution due to small sample sizes, very low quality of evidence and high risk of bias. Future large-scale RCTs are warranted.

Arm heating to relieve Raynaud's phenomenon in systemic sclerosis: A single-arm multicentre prospective clinical trial.

OBJECTIVES: Raynaud's phenomenon, one of the major symptoms of systemic sclerosis (SSc), is difficult to treat. Although it is empirically considered that warming is a beneficial technique, there is no supportive evidence. We conducted a multicentre study to evaluate whether continuous heating of the arm alleviates Raynaud's phenomenon in SSc. METHODS: A pair of disposable warmers was applied to the upper arm near the elbow of patients with SSc. Two weeks of non-warmer application were followed by 2 weeks of warmer application, which was repeated twice. The Raynaud Condition Score (RCS), number of episodes, and duration of Raynaud's phenomenon were recorded. The differences in the mean RCS, frequency, and duration of Raynaud's phenomenon between the warmer application and non-application periods were analysed. RESULTS: Twenty-eight patients were included in the analysis. The average RCS was 1.98 and 2.66 during the warmer application and non-application periods, respectively. The change between the two periods was statistically significant by paired t-test. In addition, the frequency and total duration of Raynaud's phenomenon in the warmer application period were significantly lower than those in the non-application period. CONCLUSIONS: Heating of the upper arm near the elbow is effective in alleviating Raynaud's phenomenon in SSc.

Raynaud's phenomenon.

Raynaud's phenomenon (RP) is a vasospastic condition of the extremities in response to cold or stress, affecting approximately 3% to 5% of the population. While most patients have primary RP, the condition can also occur secondary to a variety of underlying medical conditions. RP may be the presenting symptom of connective tissue diseases, especially systemic sclerosis, and RS may therefore provide an opportunity for early diagnosis and treatment. This review addresses the causes, clinical features, diagnostic workup, and treatment possibilities of RS.

Spinal cord stimulator for the treatment of ischemic pain-Burger's disease and Raynaud's disease: A report of two cases and literature review.

Ischemic pain is the main symptom of a group of diseases that result in inadequate blood flow to the extremities and ischemia. In this symptomatology, two major diseases are distinguished: Critical vascular disease and Raynaud's phenomenon. Critical vascular disease background of atherosclerosis caused by diabetes mellitus or hypertension. Raynaud phenomenon is divided into primary and secondary form. The primary form is due to vasospasm and there is no underlying cause. Secondary form is associated with underlying connective tissue or rheumatic diseases, peripheral vascular diseases such as thromboangitis obliterans (Burger's disease). Clinical findings in Raynaud's disease are vasomotor changes with cold exposure such as bruising, coldness, painful paresthesias, and ulcers due to chronic ischemia. Clinic presentation in critical ischemic disease is intermittent claudication for earlier stage and resting pain, gangrene, necrosis, and trophic changes were added in advanced stages. The treatment of the Raynaud 's disease in early stage is medical and conservative. In case of advanced stage ischemic vascular disease, medical treatment resistant pain, insufficient response to endovascular treatment, and inoperabl cases, interventions such as sympathectomy and spinal cord stimulation (SCS) can be applicable. SCS reduces vascular resistance through vasodilator mediators and increases blood flow. SCS also suppresses sympathetic vasoconstriction, increases tissue vascularity, reduces tissue damage, provides ulcer healing and pain reduction. In this report, we demonstrated that persistent Raynaud's disease and advanced stage Burger's disease were successfully treated with SCS.

Multidisciplinary Treatment for Severe Secondary Raynaud's Phenomenon: A Case Report.

Raynaud's phenomenon is a symptom complex manifested as intermittent fingertip ischemia caused by cold or other sympathetic drivers. Secondary Raynaud's phenomenon is often more severe and could even lead to finger ulceration, making it particularly complicated to treat. We describe a case of severe Raynaud's phenomenon secondary to subclinical hypothyroidism lasting for more than 6 hours in a 65-year-old woman. The patient was also diagnosed with hypothyroidism, epilepsy, and secondary soft tissue infection of the right middle and ring fingers. After careful multidisciplinary consultation and discussion, the patient received vasodilation, anticoagulation, thyroxine supplementation, stellate ganglion block, hyperbaric oxygen therapy and debridement. The patient responded well to the medication, avoiding amputation or obviously dysfunction. Multidisciplinary team gathering the doctors from different departments proposes appropriate strategies for patients with severe Raynaud's phenomenon and could improve the prognosis and satisfaction of patient effectively.

[Paroxysmal vascular acrosyndromes: Practical approach to diagnosis and management]. / Acrosyndromes vasculaires paroxystiques : démarche pratique de diagnostic et de prise en charge.

Paroxysmal vascular acrosyndromes are related to a peripheral vasomotor disorder and presented as paroxysmal color changes of the fingers. They include primary Raynaud's phenomenon (RP), which is the most common, secondary RP and erythermalgia. They are to be distinguished from non-paroxysmal acrosyndromes such as acrocyanosis and chilblains, which are very frequent and often associated with RP, digital ischemia and necrosis, spontaneous digital hematoma and acrocholosis. The challenge of a consultation for a vascular acrosyndrome is to make positive diagnosis through history and clinical examination, and to specify its nature, to prescribe complementary exams. In any patient consulting for RP, assessment includes at least an antinuclear antibody test and capillaroscopy. For erythermalgia, a blood count and even a search for JAK2 mutation are required. A thryoid-stimulating hormon assay, a test for antinuclear antibodies, and a search for small fiber neuropathy are also performed. The treatment of RP is essentially documented for secondary RP where calcium channel blockers are indicated in first line, and iloprost in severe cases. The treatment of primitive erythermalgia is based on sodium channel blockers such as mexiletine or lidocaine infusions, and on drugs effective on neuropathic pain, such as gabapentin or amitryptiline, in case of erythermalgia associated with small fiber neuropathy. The treatment of erythermalgia associated with myeloproliferative syndromes is based on etiological treatment and aspirin.

Practical management of Raynaud's phenomenon - a primer for practicing physicians.

PURPOSE OF REVIEW: Raynaud's phenomenon (RP) is a common vasospastic condition that results in digital hypoperfusion in response to cold and/or emotional stress and is associated with significant pain and disability. The aim of our review is to provide a practical approach for clinicians to inform assessment and management of patients with RP. RECENT FINDINGS: Autoantibodies and nailfold capillaroscopy are key investigations to stratify the risk of progression to systemic sclerosis (SSc) in patients RP, which was recently confirmed in the multicenter, very early diagnosis of systemic sclerosis (VEDOSS) project. Research has explored the complex lived-patient experience of RP including digital vasculopathy in SSc and has highlighted the need for outcome measure development to facilitate research in the field. Pharmacological treatment strategies vary significantly internationally and there is continued interest in developing surgical approaches. SUMMARY: We provide a practical and up-to-date approach to inform the assessment and management of patients with RP including guidance on drug initiation and escalation. Calcium channel blockers are first-line treatment and can be initiated by primary care physicians. We also highlight second-line drug therapies used for refractory RP and the potential role for surgical intervention.

Spinal cord stimulation for the treatment of pain and toe ulceration associated with systemic sclerosis: a case report.

Systemic sclerosis is a complex disease characterized by extensive fibrosis, microvascular alterations, and additional sequelae. Microvascular alterations can cause painful ulcers and necrosis; however, conservative or surgical treatment is often challenging in terms of healing. The study aimed to describe a toe ulcer with systemic sclerosis and its' successful treatment with spinal cord stimulation. An 83-year-old woman, who was diagnosed with systemic sclerosis over the past decade, was distressed by a non-healing toe ulcer for an extended period of time. The patient underwent spinal cord stimulation treatment with the expectation of pain relief and an improvement in microcirculatory insufficiency. Her pain scales and microcirculation improved, and the toe ulcer healed. Furthermore, the frequency of Raynaud's symptoms was reduced, and the patient's pain decreased. There was no recurrence of the ulcer and she no longer needed a cane for walking.

Evidence and consensus-based recommendations for non-pharmacological treatment of fatigue, hand function loss, Raynaud's phenomenon and digital ulcers in patients with systemic sclerosis.

OBJECTIVE: SSc is a complex CTD affecting mental and physical health. Fatigue, hand function loss, and RP are the most prevalent disease-specific symptoms of systemic sclerosis. This study aimed to develop consensus and evidence-based recommendations for non-pharmacological treatment of these symptoms. METHODS: A multidisciplinary task force was installed comprising 20 Dutch experts. After agreeing on the method for formulating the recommendations, clinically relevant questions about patient education and treatments were inventoried. During a face-to-face task force meeting, draft recommendations were generated through a systematically structured discussion, following the nominal group technique. To support the recommendations, an extensive literature search was conducted in MEDLINE and six other databases until September 2020, and 20 key systematic reviews, randomized controlled trials, and published recommendations were selected. Moreover, 13 Dutch medical specialists were consulted on non-pharmacological advice regarding RP and digital ulcers. For each recommendation, the level of evidence and the level of agreement was determined. RESULTS: Forty-one evidence and consensus-based recommendations were developed, and 34, concerning treatments and patient education of fatigue, hand function loss, and RP/digital ulcers-related problems, were approved by the task force. CONCLUSIONS: These 34 recommendations provide guidance on non-pharmacological treatment of three of the most frequently described symptoms in patients with systemic sclerosis. The proposed recommendations can guide referrals to health professionals, inform the content of non-pharmacological interventions, and can be used in the development of national and international postgraduate educational offerings.

Treatment of Raynaud phenomenon and ischemic ulcers associated to systemic sclerosis with hyperbaric oxygen.

We describe 4 patients with Raynaud's phenomenon associated with systemic sclerosis, 3 with ischaemic ulcers, successfully treated with hyperbaric oxygen. This therapy has been useful in the treatment of chronic wounds due to its anti-inflammatory, antimicrobial and angiogenic effects. Hyperbaric oxygen treatment could be a therapeutic option in patients with Raynaud's phenomenon refractory to conventional treatment.

Proximal heat stress up-regulates angiopoietin-1 in fingers and reduces the severity of Raynaud's phenomenon in systemic sclerosis: a single-centre pilot study.

OBJECTIVES: Raynaud's phenomenon (RP) is a peripheral vascular disorder that frequently occurs in systemic sclerosis (SSc). Although therapeutic heating seems reasonable given that RP is elicited by cold stimuli, the effects of heating are still unclear. We examined the effects of heating applied on various body parts in SSc patients with RP of fingers. METHODS: Fourteen SSc patients heated their neck, elbows, and wrists with disposable heating pads for 1 week each. The visual analogue scale (VAS) for RP during each heating period was compared with that of each 1-week pre-treatment interval. On the day after the expiration of each heating period, their finger temperature, the finger blood flow, and angiogenesis-related factors (vascular endothelial growth factor, endostatin, angiopoietin-1, and angiopoietin-2) obtained from the cubital vein and fingertip were measured. RESULTS: The mean VAS was significantly reduced during the heating of the neck and elbows. Fingertip blood samples showed significantly increased angiopoietin-1 after each of the heating periods and increased endostatin after wrist heating. After the termination of heating, changes in finger temperature or blood flow could not be detected. CONCLUSIONS: Heating the neck or elbows can alleviate RP in SSc. The heat up-regulates angiopoietin-1 in the fingers.

Raynaud Phenomenon and Other Vasospastic Disorders.

Vasospastic disorders are prevalent in the general population and can affect individuals of any age. Primary (or idiopathic) vasospastic disorders often have a benign course; treatment focuses on the control of symptoms. Secondary vasospastic disorders occur owing to an underlying condition and have an increased risk of complications, including tissue loss and digital ulcerations; treatment should focus on the underlying condition. In this review, we discuss the pathophysiology, clinical presentation, diagnosis, and management of vasospastic disorders, including Raynaud syndrome, acrocyanosis, livedo reticularis, and pernio.

Raynaud's phenomenon and digital ulcers: advances in evaluation and management.

PURPOSE OF REVIEW: The aim of this review is to give an update on advances in evaluation and management of systemic sclerosis (SSc)-related Raynaud's phenomenon and digital ulceration, focusing on reports from the last 18 months. The increasing recognition of the huge impact of Raynaud's phenomenon and of digital ulceration on the everyday lives of patients with SSc has sparked enthusiasm internationally to develop better outcome measures and better treatments, and so a review is timely. RECENT FINDINGS: There have been recent advances in the development of patient reported outcome instruments [e.g. the Hand Disability in Systemic Sclerosis-Digital Ulcers (HDISS-DU) instrument] and also in noninvasive imaging techniques, including thermography and laser Doppler methods. Improved outcome measures will facilitate future clinical trials, both early phase proof-of-concept and later phase trials. New insights have been gained into mechanisms of action and methods of administration of 'conventional' therapies, for example phosphodiesterase inhibitors and intravenous prostanoids. New treatment approaches are being investigated, including topical and procedural therapies. SUMMARY: Clinicians can look forward to seeing these advances translating into clinical benefit over the next 5 years. To help ensure this, they should strive whenever possible to recruit patients with SSc-related digital vasculopathy into observational studies and clinical trials.

Novel Combined Approach for Digital Necrosis Secondary to Raynaud's Phenomenon.

The presence of severe Raynaud's Phenomenon (RP), with permanent pain or digital necrosis is a rare condition. Cervical sympathectomy or distal sympathectomy or A botulinum toxin have demonstrated efficacy after medical treatment failure. We report the case of a 38-year-old female patient with an acute onset of severe RP in both hands secondary to systemic sclerosis. Medical treatment failed, so a novel approach by a combination of a modified distal sympathectomy and injection of A botulinum toxin on digital neuromuscular bundles was performed. Remission of the pain occurred immediately after the procedure and 45 days later she had complete healing of the digital wounds and recovered full mobilization of both hands. The patient remained asymptomatic 6 month after the procedure, and a Doppler ultrasound showed tri-phasic flows distal to the surgical site. This novel technique is described, and a brief review of the literature is performed.

Raynaud's phenomenon and related vasospastic disorders.

Raynaud's phenomenon, which is characterized by episodic digital pallor, cyanosis and rubor upon exposure to cold environment or to stress, is relatively common, although the prevalence depends on the climate. Still, it is under-diagnosed, under-treated, and often confused with other conditions. Primary Raynaud's phenomenon (i.e., Raynaud disease) must be distinguished from secondary Raynaud's phenomenon (i.e., Raynaud syndrome) as long-term morbidity and outcomes differ vastly between the two conditions. Additionally, the practitioner must differentiate between Raynaud's phenomenon and related vascular disorders, such as acrocyanosis, pernio, and livedo reticularis. In this article, we review differences between the conditions and suggest an approach to diagnosis and treatment strategy for these disorders.