Treatment Of Raynaud's Phenomenon Research Articles

Patients’ perspectives on systemic sclerosis-related Raynaud's phenomenon in the feet: A qualitative study from the OMERACT Foot and Ankle Working Group

ObjectiveTo explore, from patients’ perspectives, the symptoms and impact of Raynaud's phenomenon (RP) on the feet of patients with systemic sclerosis (SSc-RP), and to identify which foot-related domains are important to patients. MethodsForty participants (34 women) with SSc-RP took part in one of six focus groups held in the United Kingdom or United States. Participants were purposively sampled to ensure diversity in disease type, duration, and ethnicity. The topic guide included questions on RP impact, self-management, and treatment expectations. Qualitative content analysis was employed to identify key concepts in the data relating to foot-specific symptoms and their impact. Themes were organized by corresponding domains of potential importance. ResultsTwenty-eight participants (70 %) reported experiencing RP in their feet. Five themes were identified corresponding to domains of potential importance: temperature changes, pain, cramping and stiffness, numbness, and color changes. These issues negatively affected participants’ lives, impairing walking, driving, and socializing, and causing issues with footwear and hosiery. ConclusionsThis large qualitative study exploring the experiences of patients with SSc-RP in the feet identified several key domains of high importance to patients. SSc-RP is common in the feet, presents in several patterns, and impacts multiple aspects of patients’ lives. These findings indicate where future foot-specific interventions for RP could be targeted. Findings from this study improve understanding of what domains are important to patients with SSc-RP affecting the feet and will contribute to the development of a core outcome set for foot and ankle disorders in rheumatic and musculoskeletal diseases.

Botulinum Toxins for the Treatment of Raynaud Phenomenon: A Systematic Review With Meta-analysis.

Botulinum toxin (Btx) therapy has emerged as a potential treatment for patients with Raynaud phenomenon (RP) in recent years. This study aimed to investigate the efficacy and safety of Btx treatment for RP. Databases of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from their inception up to August 2022. Studies that reported Btx use for the treatment of RP were included. A meta-analysis was conducted for the Shortened version of the Disabilities of the Arm, Shoulder, and Hand (Quick DASH) score and visual analog scale pain score using a random-effects model. Thirteen full-text studies were included. The pooled standard mean changes for the visual analog scale pain score and QuickDASH score were -3.82 (95% confidence interval, -6.62 to -1.02) and 0.83 (95% confidence interval, -1.47 to -0.19), respectively. The 2 most common complications were injection site pain and intrinsic hand weakness. The effect of Btx treatment on RP is promising based on current evidence. Nevertheless, more studies and randomized clinical trials with larger sample sizes are needed to confirm the current results.

Efficacy of botulinum toxin type A injection for Raynaud's phenomenon and digital ulcers in patients with systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune, connective tissue disorder of unknown etiology which causes vasculopathy and fibrosis. Raynaud's phenomenon (RP) is a common complication of SSc, which leads to ischemia and gangrenes. Treatment of RP is a clinical problem and often remains insufficient.This study aimed to evaluate the therapeutic efficacy of local injections of botulinum toxin type A (BTX-A) in improving the symptoms of Raynaud's phenomenon (RP) secondary to scleroderma. This parallel single-blinded, placebo-controlled clinical trial enrolled 29 patients with scleroderma. Participants received BTX-A in the first, 2nd, 3rd, and 4th dorsal web spaces and the base of the thumb and small finger of the non-dominant hand and 2.5 ml of sterile normal saline in the opposite hand. Pre-injection measurements and post-injection follow-up evaluations at months 1 and 4 were performed. We compared the outcomes using the paired Student's t-test. The change in pain severity between pre-injection and month 1 follow-up was significantly larger in the BTX-A group (p-value = 0.04). Between pre-injection and month 1 and month 4, the changes in the Raynaud's condition score (RCS) (p-value = 0.02, 0.004, respectively) and the number of Raynaud's attacks (p-value = 0.006, 0.001, respectively) were significantly greater in the BTX-A group. No significant difference was found in terms of paresthesia, skin thickening, upper extremity function, ulcer diameter, number of ulcers, or Raynaud's attack duration between the two groups (p-value > 0.05). In time, the decrease in pain severity, paresthesia, RCS, number of ulcers, and ulcer diameter, and the increase in upper extremity function were significantly greater in the BTX-A group as compared to the placebo group (p < 0.05). Our study showed that local injection of BTX-A is safe and has beneficial therapeutic effects on RP and RP-related digital ulcers in SSc patients.

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.

Evaluation of Botulinum Toxin Type A and its Potential Effect on Exacerbated Raynaud's Phenomenon in Hospitalized Scleroderma Patients.

Raynaud's phenomenon by episodically reversible constriction of the arteries in the fingers and toes causes pain, numbness, sores, and gangrene. However, the treatment of Raynaud's phenomenon is one of the clinical issues. Recent studies have shown that botulinum toxin is considered a potential and effective therapeutic option for improving finger blood circulation in patients with Raynaud's syndrome. In this study, we sought to investigate the therapeutic effect of botulinum toxin type A on exacerbated Raynaud's phenomenon in patients with scleroderma. In this prospective study, 11 patients with systemic scleroderma who were referred due to aggravated Raynaud's were included. For all patients, questionnaires were filled up, and physical examination was performed separately for both treatment and control hands, and then similar volumes of botulinum toxin type A (Botox) and normal saline were randomly injected. The results showed that there was a significant difference in Raynaud's score (P = 0.001), Quick-Dash score (P = 0.01), Mc-Cabe cold score (P = 0.003), the mean frequency of recurrences arracks (P = 0.01), pain (0.005) (P = 0), skin color (P = 0.01), and duration of Raynaud's phenomenon (P = 0.006) between the intervention and control groups after two months. Following Botox injection, a significant improvement in terms of various Raynaud's parameters as well as the clinical manifestations was observed in the intervention group. Together, botulinum toxin type A could retrieve the hand function, the cold sensitivity, and the painful feeling caused by Raynaud's syndrome.

Botulinum toxin in the management of primary and secondary Raynaud's phenomenon.

Raynaud's phenomenon (RP) is common in rheumatic diseases. In the setting of systemic sclerosis (SSc), it can be complicated by digital ischemia that includes ulceration and gangrene. Systemic adverse effects may preclude the use of oral or topical vasodilators for the treatment of RP and its complications. In this article, we review effectiveness/efficacy of botulinum toxin injection in primary and secondary RP. We discuss botulinum toxin formulations, dosage, sites of administration, and adverse effects. The evidence for botulinum toxin in the treatment of primary and SSc-associated RP is promising. Consistency across patient populations, treatment options (botulinum serotype, dose, and injection site), and outcome measures will be essential for further research.

Raynaud's Phenomenon: A Vascular Acrosyndrome That Requires Long-Term Care.

Some 5-10% of the German population are affected by Raynaud's phenomenon (RP). In around 10-20% of cases RP arises from an underlying disease, most commonly a connective tissue disease. This review encompasses the diagnosis and differential diagnosis of RP and examines the efficacy of the currently available pharmaceutical and non-pharmaceutical treatment options. We conducted a selective literature search in PubMed using the search terms "Raynaud's phenomenon", "Raynaud's syndrome," "vasospasm," "vascular acrosyndrome," and "systemic sclerosis," together with a search of the Cochrane Database of Systematic Reviews up to April 2020. Raynaud's phenomenon mainly affects the fingers or toes and is typically triggered by cold or emotional stressors. The most important diagnostic steps are demonstration of a tendency towards digital vasospasm, exclusion of occlusions in the afferent arteries and acral vessels, nail-fold capillaroscopy, and determination of autoantibody status. Tumor screening should be arranged in the presence of B symptoms or first manifestation of RP in old age. The onset of RP in childhood is a rare occurrence and points to a secondary origin. The principal options for treatment are protection against cold and administration of calcium antagonists, which reduces the occurrence of RP by around 20-40 %. The treatment of RP in patients with systemic sclerosis is described in the recommendations of the European League Against Rheumatism (EULAR). At onset or after years of latency, patients with Raynaud phenomenon may have an underlying disease (most commonly a connective tissue disease). Long-term specialist care is necessary for asymptomatic patients with risk factors and for those with clinically manifest symptoms of an underlying condition alike.

BTX-A Promotes Expression of Angiogenesis-Associated Genes in Human Umbilical Vein Endothelial Cells.

Raynaud's phenomenon (RP) is an episodic vasospasm of the peripheral arteries caused by an exaggerated reaction to cold temperature or emotional stress. Restoring the angiogenesis capability of the acral lesional skin is a critical strategy to treat RP. Local injection of botulinum toxin-A (BTX-A) has also been reported for treatment of RP. However, since the exact mechanisms of BTX-A action are still unclear, its administration for treatment of RP is not widely used. In the present study, BTX-A was found to promote angiogenesis and relieve RP in the patient. To elucidate its mechanisms against angiogenesis, BTX-A was used to treat human umbilical vein endothelial cells (HUVECs), one of the most popular in vitro models of angiogenesis, and RNA sequencing was used to investigate differentially expressed genes. A total of 413 genes were upregulated, and 1634 were downregulated, with fold-changes >2.0 in HUVECs treated with BTX-A. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed BTX-A affected expression of angiogenesis-associated, angiogenesis-associated signaling pathway-related, metabolic pathway, and epigenetic regulation-related genes. These results demonstrate potential biomarkers of BTX-A action, thereby providing potential therapeutic mechanism(s) by which BTX-A relieves RP symptoms.

Drug Treatment of Raynaud's Phenomenon of the Nipple.

Drug Treatment of Raynaud's Phenomenon of the Nipple.

Estrogen increases expression of vascular alpha 2C adrenoceptor through the cAMP/Epac/JNK/AP-1 pathway and potentiates cold-induced vasoconstriction

Cutaneous cold-induced vasoconstriction is a normal physiological reaction mediated by alpha 2C-adrenergic receptors (α2C-ARs) expressed in vascular smooth muscle cells (VSMCs). When this reaction is exaggerated, Raynaud's phenomenon (RP) ensues. RP is more prevalent in females compared to age-matched men. We previously established that 17-β estradiol (estrogen) upregulates α2C-ARs in human VSMCs via a cAMP/Epac/Rap pathway. We also showed that cAMP acts through JNK to increase α2C-AR expression. However, whether estrogen employs JNK to regulate α2C-AR is not investigated. Knowing that the α2C-AR promoter harbors an activator protein-1 (AP-1) binding site that can be potentially activated by JNK, we hypothesized that estrogen regulates α2C-AR expression through an Epac/JNK/AP-1 pathway. Our results show that estrogen (10−10 M) activated JNK in human VSMCs extracted from cutaneous arterioles. Pretreatment with ESI09 (10 μM; an Epac inhibitor), abolished estrogen-induced JNK activation. In addition, pre-treatment with SP600125 (3 μM; a JNK specific inhibitor) abolished estrogen-induced expression of α2C-AR. Importantly, estrogen-induced activation of α2C-AR promoter was attenuated with SP600125. Moreover, transient transfection of VSMCs with an Epac dominant negative mutant (Epac-DN) abolished estrogen-induced activation of α2C-AR promoter. However, co-transfection of constitutively active JNK mutant overrode the inhibitory effect of Epac-DN on α2C-AR promoter. Moreover, estrogen caused a concentration-dependent increase in the activity of AP-1-driven reporter construct. Mutation of AP-1 site in the α2C-AR promoter abolished its activation by estrogen. This in vitro estrogen-increased α2C-AR expression was mirrored by an increase in the ex vivo functional responsiveness of arterioles. Indeed, estrogen potentiated α2C-AR-mediated cold-induced vasoconstriction, which was abolished by SP600125. Collectively, these results indicate that estrogen upregulates α2C-AR expression via an EPAC-mediated JNK/AP-1- dependent mechanism. These results provide an insight into the mechanism by which exaggerated cold-induced vasoconstriction occurs in estrogen-replete females and identify Epac and JNK as potential targets for the treatment of RP.

Recent advances in the workup and management of Raynaud’s phenomenon

Raynaud phenomenon (RP) is defined as recurrent, reversible episodes of vasospasm involving peripheral small vessels, typically in the fingers and toes. Primary (idiopathic) RP is common (it occurrs in about 5% of the general population) and is usually benign. Secondary RP accounts for 10% to 20% of all RP cases and may be associated with complications such as tissue loss, ulcers, and gangrene. Systemic sclerosis (SSc) or, more rarely, other connective tissue diseases are the main underlying conditions. A detailed clinical history and careful physical examination may be helpful in identifying the cause. Routine investigations include a full blood count, measurement of erythrocyte sedimentation rate, C‑reactive protein, antinuclear antibody levels, biochemical profile, thyroid function tests, protein electrophoresis, chest X‑ray, and nailfold capillaroscopy. Capillaroscopy can facilitate a very early diagnosis of SSc. Doppler ultrasound is recommended to evaluate the risk of pathologies in large to medium-sized arteries. Lifestyle modifications may be sufficient to control primary RP, but some patients, and most with secondary RP, require pharmacologic treatment. Several medications are proposed to manage RP and its complications, such as calcium channel blockers, phosphodiesterase type 5 inhibitors, intravenous prostanoids, and topical nitrates. However, scientific evidence for the use of these drugs is still weak to moderate. Despite the lack of efficacy of bosentan in RP treatment, this medication is approved for the secondary prevention of digital ulcers in patients with SSc. In conclusion, the management of RP still represents a challenge. Collaboration between healthcare professionals, patient organizations, and the society could encourage earlier medical assessment of people at risk of SSc.

Successful Treatment of medically refractory scleroderma digital gangrene with long-term continuous brachial plexus block

Raynaud’s phenomenon (RP) is the earliest and most common clinical manifestation of scleroderma, occurring in 90 to 98% of patients [1]. A combination of sympathetically mediated vasospasm and vasoocclusive disease has been implicated in the etiology of digital ischemic phenomenon [2,3], and treatment of RP is directed towards relieving vasospasm and restoring blood flow. Therefore, cervicothoracic or peripheral sympatholysis and digital artery reconstruction have been performed for medically refractory RP with scleroderma even though all procedures have some limitations. Thoracoscopic symapthectomy has recently been shown to have an initial improvement, although almost always relapses 6 months after the treatment [4,5]. Surgery of the hand, including digital sympathectomy and arterial reconstruction, for scleroderma might have favorable outcomes [6,7]. However, it would be a limited treatment option because of a recurrent ulcer after surgery [8], delayed wound healing [8,9], and development of complex regional pain syndrome [10]. Another alternative and less invasive treatment for blocking the sympathetic outflow would be a sympathetic block with local anesthetics [11,12]. These therapies are based on the premise that excessive sympathetic activity may be involved in the pathogenesis of digital ischemia.

Innovations in the Assessment of Primary and Secondary Raynaud's Phenomenon.

Objectives: Raynaud’s phenomenon (RP) is characterized by intense vasospasm of the digital arteries that causes characteristic color changes in fingers. There are two main types of RP: Primary RP (PRP) and Secondary RP (SRP). PRP is a benign condition. Whilst SRP is associated with several connective tissue diseases (CTD), in particular systemic sclerosis (SSc). The objectives of this report were: to present a short review on morphological (nailfold videocapillaroscopy, NVC) and functional techniques (laser tools and thermography) that allow for a correct diagnosis and treatment of RP and to investigate blood perfusion (BP) by laser speckle contrast analysis (LASCA) in different skin areas of hands and face in PRP, SRP to SSc, and healthy subjects (CNT).Methods: 31 PRP patients (LeRoy criteria), 70 SRP to SSc (ACR/EULAR criteria) and 68 CNT were enrolled. BP was assessed by LASCA at the level different areas of hands and face. NVC was performed to distinguish between PRP and SRP, and to detect the proper pattern of nailfold microangiopathy in SSc patients.Results: Both PRP and SRP showed a statistically significant lower BP than CNT at the level of fingertips (p < 0.0001), periungual (p < 0.0001), palmar aspect of 3rd finger (p < 0.0001), and palm areas (p < 0.0001). Moreover, BP was significantly lower in PRP than in SRP to SSc with the “Early” pattern of microangiopathy in the same areas as above (p < 0.04).Conclusion: By considering a small cohort of patients, BP of hands was found lower in PRP than in SSc patients with the “Early” NVC pattern of microangiopathy.

Iloprost use and medical management of systemic sclerosis-related vasculopathy in Italian tertiary referral centers: results from the PROSIT study.

Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud's phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of patients' life. The management of vascular disease can be challenging for the clinician because of the suboptimal tolerability of the treatments and lack of consensus on the best therapeutic approach. Intravenous iloprost, a synthetic analogue of prostacyclin, is broadly used for the treatment of RP and ischemic ulcers secondary to SSc. However, no standardized protocol on iloprost use is currently available and, consequently, the management of this treatment is largely based on the experience of each single center. The PROSIT project is an observational, multicenter study aiming to investigate the current treatments for SSc vasculopathy, the use of prostanoids, with special regard to iloprost, and the perception of the treatment from a patient's perspective. The study was conducted on a cohort of 346 patients from eight Italian centers and included a structured survey addressed to physicians, data collected from patient's medical records and two patient-administered questionnaires assessing the level of satisfaction, tolerability and perception of the efficacy of Iloprost. PROSIT data confirmed that in the contest of SSc iloprost represents the first-line choice for the management of severe RP and DU. Moreover, it is a well-tolerated treatment as reported by patients' experience. Although a standard protocol for the treatment of SSc-related vasculopathy is lacking, PROSIT study identified different therapeutic approaches largely supported by tertiary Italian centers. Further studies are needed in order to optimize the best treatment for SSc vascular diseases, in particular to improve the best iloprost schedule management.

In Raynaud phenomenon, on-demand sildenafil did not reduce disability or frequency or duration of attacks.

Source Citation Roustit M, Giai J, Gaget O, et al. On-demand sildenafil as a treatment for Raynaud phenomenon: a series of n -of-1 trials. Ann Intern Med. 2018;169:694-703. 30383134

Evaluation of clinical efficacy of prostanoid therapy for Raynaud’s phenomenon in rheumatic diseases

Aim. On the basis of clinical manifestations of Raynaud’s phenomenon (RP) to determine the RP expression level and to evaluate the long-term efficacy of treatment of RP in patients with rheumatic diseases (RD) with iloprost and alprostadil. Methods. Treatment for indications with prostanoids (intravenous iloprost, alprostadil or their combinations) was administered to 40 patients with secondary RP in RD. During 3-year follow up, clinical instrumental parameters (frequency of attacks of Raynaud's, digital ulcers (DU) formation, pain intensity on visual analogue scale (VAS) were evaluated. The control group included 30 patients with RP in RD who did not receive prostanoid therapy. The method of factor analysis was used to determine the index of generalized expression of RP, on the basis of which the expression levels of the RP were determined. Results. The “expression of RP” scale revealed in the course of factor analysis as an indicator of generalized manifestation of RP, is the average value of two subscales, the first one of which consisted of four indices - “digital ulcer”, “digital pitting scars”, “phalange amputation” and “Raynaud's attack frequency”, and the second one included “intensity of pain”, “duration of illness”, “whitening of fingers”. Verification of the correlation revealed during the study of subscales, showed its reliability (r = 0.294, p = 0.053). The final expression of RP was 1.51 ± 0.86. The low level of RP expression had values up to 0.65, high - over 2.37. When included in the study, a high level of RP expression was defined in 16 (22.9 %) patients, medium - in 43 (61.4 %), low - in 11 (15.7 %). The use of iloprost in the treatment of RP was effective for healing of DU and a statistically significant decrease of the generalized expression of RP from 2.25 [1; 3] to 1.75 [1; 2] (p = 0.012) was observed. On alprostadil treatment, statistically significantly decreased frequency of attacks from multiple daily (more than once a day) to once a month and reduced numbness during RP attack were observed as well as a decrease of the level of generalized index of RP expression from 1.26 ± 0.71 to 0.97 ± 0.57 (р = 0.038). The combination of prostanoids had a contradictory clinical effect: the pain and frequency of RP attacks decreased, but the formation of DU and new cases of amputations of phalanges were registered, the treatment had no effect on the value of RP expression. Conclusion. Based on the clinical manifestations of RP, a generalized index of RP severity was identified and the levels of RP severity were determined. Treatment with iloprost and alprostadil has a significant effect on reducing the clinical manifestations of RP with a corresponding decrease in its severity.

On-Demand Sildenafil as a Treatment for Raynaud Phenomenon: A Series of n-of-1 Trials.

Treatment of Raynaud phenomenon (RP) with phosphodiesterase-5 inhibitors has shown moderate efficacy. Adverse effects decrease the risk-benefit profile of these drugs, and patients may not be willing to receive long-term treatment. On-demand single doses before or during exposure to cold may be a good alternative. To assess the efficacy and safety of on-demand sildenafil in RP. Series of randomized, double-blind, n-of-1 trials. (ClinicalTrials.gov: NCT02050360). Outpatients at a French university hospital. Patients with primary or secondary RP. Each trial consisted of a multiple crossover study in a single patient. Repeated blocks of 3 periods of on-demand treatment were evaluated: 1 week of placebo, 1 week of sildenafil at 40 mg per dose, and 1 week of sildenafil at 80 mg per dose, with a maximum of 2 doses daily. Raynaud Condition Score (RCS) and frequency and daily duration of attacks. Skin blood flow in response to cooling also was assessed with laser speckle contrast imaging. Mixed-effects models were used and parameters were estimated in a Bayesian framework to determine individual and aggregated efficacy. 38 patients completed 2 to 5 treatment blocks. On the basis of aggregated data, the probability that sildenafil at 40 mg or 80 mg was more effective than placebo was greater than 90% for all outcomes (except for RCS with sildenafil, 80 mg). However, the aggregated effect size was not clinically relevant. Yet, substantial heterogeneity in sildenafil's efficacy was observed among participants, with clinically relevant efficacy in some patients. The response to sildenafil was substantially heterogeneous among patients. Despite a high probability that sildenafil is superior to placebo, substantial heterogeneity was observed in patient response and aggregated results did not show that on-demand sildenafil has clinically relevant efficacy. In this context, the use of n-of-1 trials may be an original and relevant approach in RP. GIRCI (Groupement Interrégional de Recherche Clinique et d'Innovation) Auvergne Rhône-Alpes (academic funding) and Pfizer.

Use of nitroglycerin ointment to treat primary and secondary Raynaud's phenomenon: a systematic literature review.

Raynaud's phenomenon (RP) is a microvascular condition in which reversible ischemic attacks occur in the extremities. Due to the unpredictable nature of these attacks, pharmacologic agents that can be administered on as-needed basis are currently being sought after. Topical nitrates are well suited for as-needed use, and several different formulations have been studied for the treatment of RP, including ointments, gels, patches, and tapes. However, these different dosage forms are not all equal in terms of safety and efficacy, and not every one is commercially available for use in clinical practice. Nitroglycerin ointment is commercially available, and it has less systemic side effects than other topical formulations. Since its role in the treatment of RP has not yet been completely established, we performed a systematic search of Medline, Embase, and the Cochrane Central Register of Controlled Trials to evaluate its safety and efficacy. A total of 1125 studies were identified, and 7 were included in our review. Although the included studies used different measures of efficacy, the majority reported positive responses to nitroglycerin ointment. The benefit of nitroglycerin ointment in the treatment of RP may be further realized through more robust investigation.

A systematic review and meta-analysis of the effects of topical nitrates in the treatment of primary and secondary Raynaud's phenomenon.

Multiple placebo-controlled trials have assessed locally applied topical nitrate preparations in treating Raynaud's phenomenon (RP). The objective of this meta-analysis was to assess the effects of local topical nitrates in primary and secondary RP with respect to a combined end point integrating parameters of digital blood flow and clinical severity. A systematic review was performed using MEDLINE, Embase, and the Cochrane library. Only trials comparing locally applied topical nitrates with placebo comparators were included. Studies were appraised for bias by 2 independent reviewers. A total of 7 placebo-controlled trials including 346 patients were used in the meta-analysis; 4 trials used nitroglycerin ointments, 2 used the nitroglycerin gel vehicle MQX-503, and 1 used compounded nitrite. The meta-analysis results supported a moderate-to-large treatment effect in RP (standardized mean difference [SMD]=0.70; 95% CI, 0.35-1.05; P<.0001). Subgroup analyses showed a large treatment effect in secondary RP (SMD=0.95; 95% CI, 0.25-1.65; P=.008) and moderate effect in primary RP (SMD=0.45; 95% CI, 0.05-0.85; P=.03). Limitations include the inclusion of multiple topical nitrate preparations and integration of different outcomes assessments. Local topical nitrates have significant efficacy in the treatment of both primary and secondary RP.

Клиническая и эпидемиологическая характеристика и лечение феномена Рейно при ревматических заболеваниях

Клиническая и эпидемиологическая характеристика и лечение феномена Рейно при ревматических заболеваниях