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.

Mottled Raynaud's phenomenon and hand-arm vibration syndrome: followed up for 10 years.

Vibration white finger is a form of secondary Raynaud's phenomenon (RP) caused by the use of handheld vibrating tools. RP usually appears on the extremities of the fingers, and its borders are well recognised. No reports have been published on 'mottled' RP in continuous observation from the onset to the disappearance of RP. A man in his 60s who had been using vibrating tools such as jackhammers and tampers for 30 years presented with sensations of coldness, burning and numbness. Whole-body cold exposure was performed outdoors in winter, and RP was photographed continuously. 'Mottled' RP can be defined as triphasic colour changes: white, blue and red. The patient was taken off work, kept warm and medicated. His symptoms improved slightly after 10 years of follow-up, but the RP did not disappear. 'Mottled' RP is rare and refractory and should be recognised as a form of RP.

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.

Association of Clinical Manifestations of Systemic Lupus Erythematosus and Complementary Therapy Use in Taiwanese Female Patients: A Cross-Sectional Study.

Background and Objectives: Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that affects predominantly women in the childbearing years. Patients may seek complementary therapies to manage their health and to reduce symptoms. However, to our knowledge, no studies have explored the association between clinical manifestations of SLE and complementary therapies. Therefore, this study aimed to investigate the association of complementary therapies with common clinical manifestations in Taiwanese female patients with SLE. Materials and Methods: A cross-sectional study was conducted at a regional teaching hospital in southern Taiwan. Outpatients from the rheumatology clinic who met the inclusion criteria were consecutively recruited. Demographic data, clinical manifestations of SLE, and types of complementary therapy use were determined using paper-based questionnaire. Multiple logistic regression analyses were conducted to investigate the use of complementary therapies associated with clinical manifestations of SLE. Results: Of the 317 female patients with SLE, 60.9% were 40 years or older. The five SLE clinical manifestations with the highest prevalence were Raynaud's phenomenon (61.2%), photosensitivity (50.2%), Sjögren's syndrome (28.4%), arthralgia and arthritis (22.1%), and renal involvement (14.5%). Multiple logistic regression analyses revealed that Raynaud's phenomenon was significantly associated with fitness walking or strolling (adjusted odds ratio [aOR] 1.77; p = 0.027) and fish oil supplements (aOR 3.55, p < 0.001). Photosensitivity was significantly and inversely associated with the use of probiotics (aOR 0.49; p = 0.019). Renal involvement was significantly associated with the use of probiotics (aOR 2.43; p = 0.026) and visit to the Chinese medicine department in a hospital (aOR 3.14, p = 0.026). Conclusions: We found that different clinical manifestations of SLE were associated with the use of different complementary therapies. Health care providers should have up-to-date knowledge of common complementary therapies and be ready to provide evidence-based advice to patients with SLE.

Serum vitamin B12 and D levels in children with Primary Raynaud Phenomenon: a retrospective cohort study.

Primary Raynaud phenomenon (RP) is resultant from transient vasospasm of peripheral arteries and arterioles, is usually precipitated by cold exposure or emotional stress, without any clue for autoimmune connective tissue diseases. We aimed to determine the frequency of vitamin D and B12 deficiencies in pediatric patients with primary RP, and to investigate their roles on the disease course. Vitamin B12 and D were supplemented if the patients had deficiencies. The study included 40 children with primary RP, 29 (72.5%) female and 11 (27.5%) male. The mean and median age were 15.1 ± 1.8 and 15.5 (range, 11.5-17.8) years. Symptoms were improved in 31 (77.5%) patients with warming procedures. Seventeen (41.5%) and 16 (39%) patients had low serum vitamin B12 and D levels, respectively. Vasodilator treatment requirement did not change by vitamin B12 status but was significantly lower in vitamin D deficient and replaced patients. Further studies are needed to clarify our results.

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.

The effect of vitamin D3 and thyroid hormones on the capillaroscopy-confirmed microangiopathy in pediatric patients with a suspicion of systemic connective tissue disease-a single-center experience with Raynaud phenomenon.

Raynaud phenomenon (RP) may be the first manifestation of a systemic connective tissue disease (SCTD). Early detection of dysfunction of small vessels called microangiopathy is essential for the diagnostic process. The focus of this single-center, retrospective study was to investigate the potential dependencies between microvascular image and laboratory markers measured in children with RP. The study analyzed the nail-fold video-capillaroscopy (NVC) findings and laboratory results of 81 children between the ages 6 and 17 who were referred to pediatric rheumatologist with a suspicion of SCTD. Out of 52 patients presenting with RP at the time of evaluation, abnormalities in capillary microscopic imaging were found in 34. NVC findings were then compared to levels of specific biomarkers in serum. Vitamin D3 serum levels have been significantly decreased in patients with RP (23.4 ng/mL ± 8.76 vs. 30.0 ng/mL ± 12.66, P = 0.0148). There were positive significant correlations between levels of vitamin D3 and acute-phase reactants in serum, such as C-reactive protein (P = 0.0292). Furthermore, free thyroxine levels (fT4) in patients with both RP (P = 0.0126) and micro-angiopathy (P = 0.05496) persisted in the lower range of the normal limit (< 1.0 ng/dL). Regular oral supplementation of vitamin D3 should be always considered in children with RP if deficiency is found. Additionally, low fT4 level (< 1.0 ng/dL) should be considered as an indication to perform NVC in patients suspected of SCTD even when they do not present RP.

Discovery of potential pharmacodynamic ingredients of Dang-Gui-Si-Ni decoction based on absorbed ingredients and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: The Dang-Gui-Si-Ni (DGSN) decoction as a classic prescription has been widely used for thousands of years in the clinical practice of traditional Chinese medicine (TCM). Especially in recent years, the potential efficacy of TCM for the treatment of Raynaud's syndrome has attracted great attention as there are still no specific remedies for this disease. However, the active constituents and underlying mechanisms responsible for the therapeutic benefits are not well understood, which makes it difficult to ensure quality control or to design research and drug development strategies. To identify the potential pharmacodynamic ingredients (PPIs) of TCM will help to achieve suitable process control procedures for industrial production and large-scale manufacturing. AIM OF THE STUDY: In the present study, we propose a multi-dimensional qualitative analysis method combining water-decoction spectra, in-vitro intestinal absorption spectra, in-vivo plasma spectra, and molecular docking of components to quickly identify the PPIs for the DGSN decoction of TCM. MATERIALS AND METHODS: Water-based decoctions of DGSN were prepared in accordance with the clinical use registered in ancient books. Ultra-high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q/TOF-MS) coupled with computerized modelling activity screening was used to quickly identify the PPIs of the DGSN decoction. Bioactive compounds absorbed in vitro were identified using the everted intestinal sac model from rats and compounds absorbed in vivo were confirmed in portal vein blood samples obtained following oral administration in rats. Molecular docking validation experiments were adopted to predict the binding activity to coagulation factors I, II, VII, X, and IX. The active components were further confirmed by pharmacodynamics analysis. The anticoagulant activity of the DGSN decoction was verified using rat models. RESULTS: Thirty-one compounds were identified in the DGSN decoction. According to the in vivo experiments, 22 compounds that could be absorbed in vivo were detected by the everted intestinal sac model in rats. This model greatly reduces the scope of PPIs and is easy to perform. Ten compounds were detected in the portal vein blood in rats. The compounds detected in plasma provide stronger evidence supporting the PPIs. Molecular docking in vitro experiments indicated that 7 compounds exhibited better binding activity with coagulation factors I, II, VII, X, and IX. The animal experiments confirmed that the DGSN decoction could improve the microcirculation, providing indirect proof of anticoagulant activity suggested by the molecular docking studies. Finally, based on the multi-dimensional methods, 9 potential compounds present in the DGSN decoction were identified as PPIs (i.e., ferulic acid, paeoniflorin, albiflorin, chlorogenic acid, cryptochlorogenic acid, liquiritin, liquiritin apioside, cinnamaldehyde and glycyrrhizic acid). CONCLUSION: Overall, this study combined the water-decoction spectra, intestinal absorption spectra in vitro, plasma spectra in vivo, and molecular docking studies to establish a multi-dimensional qualitative analysis method of the DGSN decoction. Meanwhile, 9 compounds in DGSN decoction were identified as PPIs using this method, and are proposed for application as quality standards for complex TCM prescriptions.

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.

Effectiveness of Chinese herbal medicine for primary Raynaud's phenomenon: a systematic review and Meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of Chinese herbal medicine for primary Raynaud's phenomenon (PRP). METHODS: The Cochrane Central Register of Controlled Trials, PubMed, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database were searched up to February 13, 2018. Randomized controlled trials (RCTs) on treatment of PRP with Chinese herbal medicine compared with placebo, blank control, lifestyle changes, or calcium antagonists were identified and reviewed. The quality of included trials was assessed using a risk of bias tool. RESULTS: Eight RCTs involving 674 participants were included. The methodological quality of the included trials was generally poor. Meta-analysis of two trials showed that Buyang Huanwu Tang plus Danggui Sini Tang produced greater improvement in global symptoms than nifedipine. One trial showed that Danggui Sini Tang and a self-composed Chinese herbal medicine decoction, respectively, produced greater improvement in global symptoms than nifedipine alone. In one trial, modified Danggui Sini Tang showed greater improvement in global symptoms and arterial peak systolic velocity compared with nifedipine. One trial showed that Jiejing Tongmi Tang produced greater improvement in global symptoms, plasma endothelin, and plasma nitric oxide than cinepazide maleate injection. However, Jiejing Tongmi Tang did not produce a significant difference in skin temperature and peripheral artery blood stream drawing after cold pressor testing compared with cinepazide maleate injection. None of the trials reported frequency of attacks, duration of attacks, participant preference scores, or adverse events. CONCLUSION: Chinese herbal medicine may have a positive effective on PRP. However, owing to weak methodology, the benefits of Chinese herbal medicine for PRP are inconclusive. More rigorously designed studies are needed to confirm these findings.

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.

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

BACKGROUND: 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®. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

"Beet" the cold: beetroot juice supplementation improves peripheral blood flow, endothelial function, and anti-inflammatory status in individuals with Raynaud's phenomenon.

Raynaud's phenomenon (RP) is characterized by recurrent transient peripheral vasospasm and lower nitric oxide (NO) bioavailability in the cold. We investigated the effect of nitrate-rich beetroot juice (BJ) supplementation on 1) NO-mediated vasodilation, 2) cutaneous vascular conductance (CVC) and skin temperature (Tsk) following local cooling, and 3) systemic anti-inflammatory status. Following baseline testing, 23 individuals with RP attended four times, in a double-blind, randomized crossover design, following acute and chronic (14 days) BJ and nitrate-depleted beetroot juice (NDBJ) supplementation. Peripheral Tsk and CVC were measured during and after mild hand and foot cooling, and during transdermal delivery of acetylcholine and sodium nitroprusside. Markers of anti-inflammatory status were also measured. Plasma nitrite concentration ([nitrite]) was increased in the BJ conditions (P < 0.001). Compared with the baseline visit, thumb CVC was greater following chronic-BJ (Δ2.0 flux/mmHg, P = 0.02) and chronic-NDBJ (Δ1.45 flux/mmHg, P = 0.01) supplementation; however, no changes in Tsk were observed (P > 0.05). Plasma [interleukin-10] was greater, pan endothelin and systolic and diastolic blood pressure (BP) were reduced, and forearm endothelial function was improved, by both BJ and NDBJ supplementation (P < 0.05). Acute and chronic BJ and NDBJ supplementation improved anti-inflammatory status, endothelial function and blood pressure (BP). CVC following cooling increased post chronic-BJ and chronic-NDBJ supplementation, but no effect on Tsk was observed. The key findings are that beetroot supplementation improves thumb blood flow, improves endothelial function and anti-inflammatory status, and reduces BP in people with Raynaud's.NEW & NOTEWORTHY This is the first study to examine the effect of dietary nitrate supplementation in individuals with Raynaud's phenomenon. The principal novel findings from this study were that both beetroot juice and nitrate-depleted beetroot juice 1) increased blood flow in the thumb following a cold challenge; 2) enhanced endothelium-dependent and -independent vasodilation in the forearm; 3) reduced systolic and diastolic blood pressure, and pan-endothelin concentration; and 4) improved inflammatory status in comparison to baseline.

Raynaud Phenomenon of the Nipple: An Under-Recognized Condition.

BACKGROUND: Obstetricians often feel ill-equipped to address the symptom of breast pain in pregnant and postpartum patients. CASES: In the first case, a 40-year-old woman in the second trimester of pregnancy reported nipple discoloration and severe pain. She was treated with nifedipine, and her symptoms decreased quickly and markedly. In the second case, a 32-year-old woman presented for a routine postpartum visit. She described breast pain and sporadic purple discoloration of the nipples, a finding confirmed on examination. Conservative measures of maintaining warmth were recommended. CONCLUSION: Raynaud phenomenon of the nipple is an underdiagnosed condition affecting women in both the prenatal and postpartum periods. A careful history and physical must be obtained in women presenting with breast pain, because diagnosis and treatment allows breastfeeding continuation and mitigation of symptoms.

Effect of topical rosemary essential oil on Raynaud phenomenon in systemic sclerosis.

INTRODUCTION: Raynaud's phenomenon is the earliest manifestation of systemic sclerosis. Nitroglycerin gel is the only proven topical therapy. METHODS: A 53-year-old woman with systemic sclerosis had topical Rosamarinus officinalis (rosemary) oil, often used in anthroposophic medicine, applied to her hands over 3days and then, separately, olive oil. RESULTS: Thermography images showed significant warming of fingers after rosemary oil, but not after olive oil, coinciding with the patient's subjective experience. CONCLUSIONS: Topical Rosamarinus officinalis oil had a vasodilator and warming effect in a patient with systemic sclerosis and Raynaud's phenomenon.

Herbal Medicines for Cold Hypersensitivity in the Hands and Feet: A Systematic Review and Meta-Analysis.

Objectives: Cold hypersensitivity in the hands and feet (CHHF) and Raynaud's phenomenon (RP) are prevalent among Asian populations, especially among women, who exhibit a higher rate of cold hypersensitivity that may be associated with gynecological problems. In several countries, herbal medicine has effectively treated cold hypersensitivity symptoms. This systematic review and meta-analysis of the literature was undertaken to evaluate the efficacy of herbal medicine for the treatment of CHHF in adults. Design: Through March 31, 2018, comprehensive databases were searched, including MEDLINE, EMBASE, Cochrane Library, Chinese Academic Journal, and Japanese National Institute of Informatics, to identify relevant studies and extract data. Outcome measures: Primary: total effective rate (TER); secondary: skin temperature, peripheral blood flow, adverse events. Results: Fourteen randomized controlled trials (n = 974) were included. Thirteen studies with dichotomous values showed a significant reduction in CHHF and RP (risk ratio 0.31, 0.24-0.40) when comparing herbal medicine with/without Western medicine, and no treatment or Western medicine alone. Reductions in CHHF and RP were also observed between herbal medicine plus Western medicine and Western medicine alone (risk ratio 0.45, 0.24-0.86), as well as between herbal medicine and Western medicine alone (risk ratio 0.30, 0.21-0.41). In the only study using a placebo arm, herbal medicine was found to be superior to placebo in increasing skin temperature and peripheral blood flow. Six participants exhibited minor adverse drug reactions. Herbal medicine showed a superior TER, especially when combined with Western medicine, to Western medicine alone or placebo. However, there was a high risk of bias within all studies. Conclusion: Although herbal medicine shows potential to be a safe and effective treatment for CHHF and RP, the high risk of bias in all studies prevents definitive conclusions; thus, higher quality studies must be performed.