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.

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.

[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.

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.

ARTERIAL INSUFFICIENCIES: Hyperbaric Oxygen Therapy for Selected Problem Wounds.

The use of hyperbaric oxygen (HBO2) for the treatment of selected problem wounds has focused almost entirely on the diabetic foot ulcer (DFU) in recent years. The prevalence of DFUs in today's patient population and the reimbursement available for the treatment of DFUs have given it priority status in discussions about problem wounds, but there are sound fundamental reasons why additional oxygen may have benefits in the treatment of non-DFU wounds.

The complementary effects of galvanic current electrical stimulation associated with conservative treatment to increase vasodilation in patients with Raynaud's phenomenon: a randomized trial.

OBJECTIVE: To analyze the effectiveness of an electrotherapy intervention with galvanic current on symptoms associated with Raynaud's phenomenon. DESIGN: Single-blind randomized controlled trial, parallel design (1:1 ratio) and intention-to-treat analysis. SETTING: Virgen de las Nieves Hospital, Granada, Spain. SUBJECTS: Thirty-four participants with Raynaud's phenomenon, with a mean (SD) age of 43.43 (17.62) years. INTERVENTIONS: The patients were randomly assigned to a control group with conservative treatment (anti-inflammatory, vasodilatory and analgesic drugs) or an intervention group that received conservative treatment and vasodilatory electrical stimulation during seven weeks, three times/week for a total of 20 sessions. MAIN MEASURES: The primary outcome was the number of attacks. Secondary outcomes were pain, peripheral blow flow, oxygen saturation, upper limb disability, central sensitization, pain catastrophizing and temperature recovery. All outcomes were assessed at baseline, posttreatment and at two months of follow-up. RESULTS: The galvanic current electrotherapy group showed significantly greater improvements in the number of attacks (mean difference = 26.3, 95% confidence interval (CI) = 14.4 to 38.3), pre-cold stress pain (95% CI = 0.6 to 2.4), radial artery blood flow (95% CI = -7.8 ⩾ x ⩽ 1.3), ulnar artery blood flow (95% CI = -8.63 to 0.60), oxygen saturation (95% CI = -1.7 ⩾ x ⩽ -0.29), upper limb disability (95% CI = 1.1 to 22.3), central sensitization (95% CI = 6.7 to 18.2) and temperature recovery (95% CI = -5.7 ⩾ x ⩽ -0.32) than the conservative treatment group. CONCLUSION: This study suggests that a complementary treatment with galvanic current in combination to conservative approach is superior to conservative applied as isolate, in reducing the clinical manifestations and disability in Raynaud's phenomenon.

What is the Best Way to Treat Patients with Raynaud's Phenomenon and a Tendency towards Hypotension?

Episodes of excessive vasospasm are common in patients with Raynaud's phenomenon (RP). Pharmacological treatment may often result in side-effects such as hypotension, leading to discontinuation of treatment. Review of therapeutic interventions with regard to tendency towards hypotension was done in medical databases including PubMed, Scopus, and Medline to summarize the current state of the knowledge. Despite the episodes of blood pressure drops caused by hypotension, calcium channel blockers (CCB) have been widely used in RP as first-line treatment medication. The use of other CCB apart from nifedipine is controversial due to the variety of results in clinical trials. A clinical study comparing the efficacy and tolerability of losartan with nifedipine revealed a significant reduction in RP severity, frequency of episodes, and reported adverse effects. Application of oral sildenafil 100 mg/d as an add-on therapy increased microvascular blood flow in secondary RP, while being well-tolerated and with no withdrawal from the study. Topical vasodilators may be applied as an adjuvant therapy for patients with RP. Clinical studies approved 10% nifedipine cream and 10% nitroglycerine gel as an efficient RP therapy with side-effects comparable with placebo usage. Non-pharmacological interventions, such as cold avoidance, stress management, and smoking cessation are recommended in reducing episodes of RP. Calcium channel blockers, with a particular emphasis on nifedipine, in combination with non-pharmacological management seem to be the optimal way to treat the patients with a tendency to hypotension.

Raynaud's phenomenon: Current concepts.

Raynaud's phenomenon (RP) is a transient, acral, vasospastic phenomenon that manifests with characteristic color changes. This vasospasm, classically triggered by cold temperatures, may also be driven by shifts in temperature, climate, or emotional state. Primary RP (PRP) is a common condition without severe sequelae. Secondary RP (SRP), which may be driven by vascular, autoimmune, hematologic, or endocrine etiologies, can result in digital ulceration, irreversible ischemia and necrosis, and secondary infection. This review delineates the clinical manifestations of both primary and secondary RP, as well as the current understanding of RP epidemiology and pathogenesis. Proper examination, including nailfold capillary microscopy, and laboratory workup for secondary causes of RP are also discussed. The traditional armamentarium of therapies used for RP, as well as newer medical and surgical options, is also summarized with particular regard to the clinical evidence for their efficacy.

Difficulties in diagnosis and treatment of severe secondary Raynaud's phenomenon in a Cameroonian woman: a case report.

BACKGROUND: Raynaud's phenomenon is a microvascular disorder that results in exaggerated vasoconstriction over vasodilatation secondary to an alteration in autonomic control. Though benign, it can result in severe ulceration and ultimately gangrene associated with disfiguration and permanent deformity. We present a case of severe secondary Raynaud's phenomenon in a black-African patient from a resource-limited setting, with focus on the difficulties encountered in the diagnosis and treatment. CASE PRESENTATION: A 43-year-old female Cameroonian farmer with a 7-year history of episodic paresthesia in her fingers and toes (when exposed to cold) presented to our emergency department with severe pain, ulceration, and "darkening" of her fingertips over a period of 2 days. An examination revealed bilateral ulceration and dry gangrene of her fingers and toes, based on which a diagnosis of secondary Raynaud's phenomenon due to a connective tissue disease was proposed. Results of paraclinical investigations were normal. Lifestyle modification along with a calcium channel blocker and phosphodiesterase type 5 inhibitor provided significant relief. CONCLUSIONS: An early diagnosis and knowledge on appropriate treatment of Raynaud's phenomenon is of vital importance to prevent permanent tissue damage and disability. Relying on biphasic color change for the diagnosis of Raynaud's phenomenon in black Africans can be potentially misleading.

Raynaud's phenomenon, cytokines and acupuncture: a case report.

A 30-year-old African-American woman diagnosed in 2006 with primary Raynaud's phenomenon (RP) was seen in the clinic in 2010 and the diagnosis confirmed excluding underlying disorders. Acupuncture was administered bilaterally at the LI4 Hegu acupuncture points for 5 min twice weekly for 2 months, which resulted in improvement in pain severity, joint stiffness and the colour of her fingers and toes. The literature reveals that acupuncture is effective in improving pain severity and joint stiffness in RP. The patient's serum proinflammatory cytokines were compared with those from an ongoing study in our institution and the results indicated that acupuncture therapy might be anti-inflammatory. Acupuncture is relatively safe and should be considered as an alternative treatment or non-pharmacological therapy for pain associated with RP.

Modulation of somatosensory profiles by spinal cord stimulation in primary Raynaud's syndrome.

BACKGROUND AND GOAL: Spinal cord stimulation (SCS) is an effective antinociceptive treatment for various neuropathic pain syndromes. Apart from antinociceptive action, it may modulate overall somatosensory perception. This case report targets the question of whether SCS may alter quantitative sensory testing (QST) in a patient with primary Raynaud's syndrome. MATERIALS AND METHODS: We report on a 44-year-old female patient with primary Raynaud's syndrome who had SCS via cervical and lumbar electrodes. QST was performed in a standardized manner assessing cold detection threshold (CDT) and warm detection threshold (WDT), cold pain threshold (CPT) and heat pain threshold (HPT), mechanical detection threshold (MDT) and mechanical pain threshold (MPT) thresholds, and vibration detection threshold (VDT) and pressure pain thresholds (PPT). We tested at the dorsum of the right/left hand of the patient with engaged and disengaged SCS. Test results were compared with a control group of 80 subjects. RESULTS: Without SCS, the patient showed a sensory decrease in CDT, MDT, MPT, and VDT. SCS influenced the perception of cold, warm, and tactile detection thresholds, whereby CDT, WDT, and VDT were impaired and MDT was improved. CONCLUSION: SCS significantly modulated the somatosensory profile in a patient with primary Raynaud's syndrome. These effects were pronounced in qualities involving Aß, C, and A∂ nerve fibers. Further investigations may help to understand the mechanisms of action of SCS.

Effect of biofeedback and deep oscillation on Raynaud's phenomenon secondary to systemic sclerosis: results of a controlled prospective randomized clinical trial.

Our aim was to evaluate the effect of deep oscillation and biofeedback on Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). A prospective randomized study was performed in SSc patients receiving either deep oscillation (n = 10) or biofeedback (n = 8) thrice a week for 4 weeks, or patients were randomized into the waiting group untreated for vasculopathy (n = 10) in time of running the study interventions. Biofeedback resulted in an improvement of RP as determined by score reduction of visual analogue scale compared with patients of the control group (P < 0.05), whereas deep oscillation revealed a tendency for improvement (P = 0.055). The study underlines the beneficial role of physiotherapy for the treatment of SSc-related RP.

Spinal cord stimulation for Raynaud's syndrome: long-term alleviation of bilateral pain with a single cervical lead.

INTRODUCTION: Spinal cord stimulation (SCS) has been described in a variety of neuropathic and vasospastic pain conditions including Raynaud's syndrome. METHODS: We report here the outcome of single lead SCS in the case of a 49-year-old woman with severe Raynaud's syndrome, which had failed to respond to medical therapy. RESULTS: With a single quadripolar cervical lead in midline position at the C2/C3 level sustained pain relief of the bilateral pain was accomplished. Pain scores sank from 7/10 to 2-3/10 on the nominal analog scale and remained stable more than nearly four years by now. CONCLUSIONS: Treatment of bilateral pain in Raynaud's syndrome with SCS in a single technique is feasible. Advantages and disadvantages as compared with stimulation with bilateral leads are discussed.

Effectiveness of interventions for secondary Raynaud's phenomenon: a systematic review.

OBJECTIVES: To present an evidence-based overview of the effectiveness of (non)surgical symptomatic interventions to treat secondary Raynaud's phenomenon (RP). DATA SOURCES: The Cochrane Library, PubMed, Embase, PEDro, and CINAHL were searched for relevant systematic reviews and randomized controlled trials (RCTs). STUDY SELECTION: Two reviewers independently applied the inclusion criteria to select potential studies. DATA EXTRACTION: Two reviewers independently extracted data and assessed the methodologic quality. DATA SYNTHESIS: If pooling of data was not possible, a best-evidence synthesis was used to summarize the results. Of the 5 reviews and 19 RCTs included, 1 RCT studied acupuncture and another RCT reported on percutaneous radiofrequency thoracic sympathectomy. All others concentrated on the effectiveness of drugs (oral or intravenous [IV]). It appeared that calcium channel blockers significantly reduce the frequency and severity of Raynaud attacks, and are therefore effective in the treatment of secondary RP. Iloprost (oral and IV) was also found to be effective. Limited evidence was found for atorvastatin. For other traditional and more recently discovered interventions, no clear favorable effects were found. CONCLUSIONS: This review shows that there is clear evidence in favor of calcium channel blockers and iloprost (oral and IV) to treat secondary RP. For all other interventions, only limited, conflicting, or no evidence was found. More high-quality, well-designed RCTs are needed in this field, especially for new interventions based on recent knowledge about the pathophysiology of secondary RP.

25. Ischemic pain in the extremities and Raynaud's phenomenon.

Two important groups of disorders result from an insufficient blood supply to the extremities: critical vascular disease and the Raynaud's phenomenon. The latter can be subdivided into a primary and a secondary type. Critical ischemic disease is often caused by arteriosclerosis due to hypertension or diabetes. Primary Raynaud's is idiopathic and will be diagnosed as such if underlying systemic pathology has been excluded. Secondary Raynaud's is often a manifestation of a systemic disease. It is essential to try to establish a diagnosis as soon as possible in order to influence the evolution of the disease. A sympathetic nerve block can be considered in patients with critical ischemic vascular disease after extensive conservative treatment, preferably in the context of a study (2B±). If this has insufficient effect, spinal cord stimulation can be considered in a selected patient group (2B±). In view of the degree of invasiveness and the costs involved, this treatment should preferably be applied in the context of a study and with the use of transcutaneous pO(2) measurements. In case of primary Raynaud's, life style changes are the first step. Sympathectomy can be considered as a treatment of Raynaud's phenomenon (2C+), but only after multidisciplinary evaluation of the patient and in close consultation with the patient's rheumatologist, vascular surgeon or internist.

[The usefulness of capillaroscopy for the evaluation of pulsed magnetic field therapy in patients with primary and secondary Raynaud's phenomenon]. / Przydatnoc kapilaroskopii do oceny terapii impulsowym polem magnetycznym pacjentów z pierwotnym i wtórnym objawem Raynauda.

INTRODUCTION: Raynaud's phenomenon (RP) as a vasospastic response to cold and emotions has an impact on the quality of life. This also applies to patients with primary (idiopathic) RP. Moreover, RP may also be a factor of irreversible tissue injury manifested by ulceration or necrosis, especially in patients with connective tissue disease. Nailfold videocapillaroscopy (NVC) is a recognized method for diagnosing and monitoring of microvascular abnormalities in rheumatic diseases. The purpose of this study was to assess the usefulness of capillaroscopy for monitoring of the therapeutic effect of low-frequency pulsed magnetic field in 44 patients with RP. MATERIAL AND METHODS: Clinical examination and NVC were performed before and after 2 weeks of treatment. Low-frequency pulsed magnetic field was administered 5 days per week for 2 weeks with the Magnetronic MF-10 generator operating at 40 Hz frequency and 1.0-5.0 mT induction values. Each session lasted 10-20 minutes. RESULTS: Patients with primary and secondary RP experienced a significant decrease in the number and duration of RP episodes and reported a reduction in pain on the Visual Analog Scale. Moreover, an improvement in vascular flow and reduction in interstitial edema was seen with NVC. A correlation between capillaroscopic findings and severity of RP was also observed. CONCLUSIONS: Capillaroscopy is an effective method for evaluation of the effects of low-frequency pulsed magnetic field therapy on the microcirculation in patients with primary and secondary RP. Further prospective studies on the effect of this therapy on capillaroscopic abnormalities in RP patients are needed.