Management Of Raynaud's Phenomenon Research Articles

G protein estrogen receptor as a potential therapeutic target in Raynaud's phenomenon.

Exaggerated cold-induced vasoconstriction can precipitate a pathogenesis called Raynaud's phenomenon (RP). Interestingly, RP is significantly more prevalent in females than age-matched men, highlighting the potential implication of 17β-estradiol (E2) in the etio-pathogenesis of this disease. Indeed, we have previously reported that E2 stimulates the expression of vascular alpha 2C-adrenoceptors (α2C-AR), the sole mediator of cold-induced constriction of cutaneous arterioles. This induced expression occurs through the cyclic adenosine monophosphate → exchange protein activated by cAMP→ Ras-related protein 1→ c-Jun N-terminal kinase→ activator protein-1 (cAMP/Epac/Rap/JNK/AP-1 pathway). On the basis that estrogen-induced rapid cAMP accumulation and JNK activation occurs so rapidly we hypothesized that a non-classic, plasma membrane estrogen receptor was the mediator. We then showed that an impermeable form of E2, namely E2:BSA, mimics E2 effects suggesting a role for the membranous G-protein coupled estrogen receptor (GPER) in E2-induced α2C-AR expression. Our current working hypothesis and unpublished observations further cement this finding, as G1, a GPER agonist, mimics while G15, a GPER antagonist, abrogates estrogen's effect on the expression of vascular α2C-AR. These, and other observations, highlight the potential of GPER as a tractable target in the management of RP, particularly in pre-menopausal women.

Raynaud Phenomenon

Raynaud phenomenon is an episodic, exaggerated vascular response to cold or emotional stimuli, typically involving the fingers. Raynaud phenomenon is classified as either primary or secondary which is often associated with autoimmune disease as described in this review. Clinical evaluation and diagnostic studies are discussed, including evaluation of digital pressure response to cooling, evaluation that differentiates Raynaud phenomenon from other ailments affecting perfusion to the digits, and nailfold capillaroscopy if secondary Raynaud phenomenon is suspected. Management of Raynaud phenomenon is discussed, including lifestyle modification and many different medical therapies that have been studied in this disease process. Interventional procedures are also discussed. Guidelines to assist in the treatment of both primary and secondary Raynaud phenomenon are provided. This review contains 2 figures, 2 tables, and 52 references. Key words: calcium channel blockers, capillaroscopy, cold intolerance, digits, discoloration, Raynaud phenomenon, vasospastic

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.

Raynaud’s phenomenon—an update on diagnosis, classification and management

Raynaud's phenomenon (RP) is used to describe a symptom complex caused by digital vascular compromise. RP is a clinical diagnosis. The typically episodic nature of RP has resulted in a reliance upon patient self-report for diagnosis. The term 'primary RP' is generally applied when no underlying pathology can be demonstrated. Whilst 'primary RP' is currently considered a distinct disorder, there is evidence that the term may comprise several entities that include a functional vasospastic disorder, a physiologically appropriate thermoregulatory response, subclinical atherosclerosis and 'cold intolerance'. Optimal management may differ depending on cause. The term 'secondary RP' encompasses a broad range of rheumatological, haematological, endocrinological and vascular pathology. RP can range from relatively benign but intrusive vasospasm, to the progressive obliterative microangiopathy of systemic sclerosis (SSc), in which severe digital ischaemia can threaten tissue viability. SSc has formed the focus of much of the research into RP but, consistent with most medical symptom complexes, the aetiopathogenesis of RP varies greatly dependent on cause. Vasospasm within the digital macro- and microvasculature occurs in SSc, but digital ischaemia is further compounded by a progressive obliterative microangiopathy. Recent work exploring the patient experience of SSc-RP is challenging the 'episodic' paradigm of 'Raynaud's', with important implications for clinical trials utilising diary-based patient-reported outcome instruments for assessing Raynaud's symptoms. This review shall examine the causes, pathogenesis, clinical features, classification and management of RP. A practical approach to the evaluation and management of RP is outlined, highlighting important knowledge gaps and unmet research needs where applicable. Key Points • Raynaud's phenomenon is a symptom complex related to digital vascular compromise secondary to broad-ranging pathology. • Raynaud's phenomenon, as currently classified, likely encompasses a number of aetiopathogenic processes. • Raynaud's phenomenon causes significant disease-related morbidity in autoimmune rheumatic diseases such as systemic sclerosis.

The role of the dermatologist in Raynaud's phenomenon: a clinical challenge.

Raynaud's phenomenon (RP) is a functional vascular disorder involving extremities. In his practice, the dermatologist may frequently encounter RP which affects mainly women and is categorized into a primary benign form and a secondary form associated with different diseases (infections, drugs, autoimmune and vascular conditions, haematologic, rheumatologic and endocrinologic disorders). Still today, the differential diagnosis is a clinical challenge. Therefore, a careful history and a physical examination, together with laboratory tests and nailfold capillaroscopy, is mandatory. RP is generally benign, but a scheduled follow-up for primary RP patients should be established, due to risk of evolution to secondary RP. A combination of conservative measures and medications can help in the management of RP. The importance of avoiding all potential physical, chemical and emotional triggers, as well as quitting smoking, should be strongly suggested to the patient. As first-line treatment, dihydropyridine calcium channel blockers should be used. If this approach is not sufficient, prostacyclin derivatives, phosphodiesterases inhibitors and endothelin receptor antagonists can be considered as second-line treatment. In cases of acute ischaemia, nifedipine and intravenous prostanoids are helpful. In refractory cases, botulinum injections have shown a significant benefit. The approach to the RP patients requires therefore a coordinated care of specialists together with the primary care physician.

Handy Hints About Raynaud's Phenomenon in Children: A Critical Review.

Raynaud's phenomenon (RP) is a vasospastic disorder characterized by recurrent self-limited episodes of skin pallor, cyanosis, and hyperemia caused by paroxysmal spasms in the small arteries of the fingers and toes and can occur in any age group. Hands, feet, nose, ears, and nipples can be affected. The diagnosis is made clinically, assessing varying degrees of ischemia in the involved areas of skin, but this transient ischemia may also herald the onset of connective tissue disease. Investigation is recommended when RP starts in childhood to exclude an underlying autoimmune condition and close follow-up for its development. Management of RP in children includes conservative and pharmacologic treatments.

E02 Pharmacological Management of Raynaud Phenomenon in a District General Hospital: An Audit

E02 Pharmacological Management of Raynaud Phenomenon in a District General Hospital: An Audit

SAT0321 The Absence of SSC Pattern at NFC Carries A 90% Negative Predictive Value for the Classification of Very Early or Established SSC in an Unselected Cohort of Patients with Raynaud's Phenomenon; Experience from A Single Tertiary Centre

BackgroundNail-fold capillaroscopy (NFC) patterns of vasculopathy have been well described in systemic sclerosis (SSc) but few studies have reported their predictive value in an unselected cohort of patients with Raynaud's...

Pharmacologie du phénomène de Raynaud

Raynaud's phenomenon (RP) is characterised by transient ischaemia in the extremities in response to cold or emotions. It can be primary (idiopathic) or secondary to an underlying disease. The pathophysiology of RP is multifactorial and complex. Microvascular impairment is a hallmark of the disease. The objective of this work is to review the different pharmacological treatments currently used in the management of RP, from their mechanism of action to the available evidence regarding their efficacy. We also propose to discuss potential pharmacological targets such as the potentiation of the nitric oxide pathway, or the inhibition of the RhoA-Rho kinase pathway. The last part of this review deals with drug-induced RP. Among various medications, beta-blockers, interferons, tyrosine-kinase inhibitors or cytotoxic agents such as bleomycin are involved.

Raynaud Phenomenon of the Nipple in Breastfeeding Mothers

To elucidate the diagnostic criteria of Raynaud phenomenon of the nipple that will aid in recognizing and treating Raynaud phenomenon in breast feeding mothers with chronic deep nipple pain during lactation. Retrospective review of a patient database composed of 22 cases of breastfeeding mothers who fit the diagnostic criteria for Raynaud phenomenon of the nipple. Menlo Dermatology Medical Group in Menlo Park, California, an academic-affiliated, private dermatologic referral center. All patients diagnosed as having Raynaud phenomenon of the nipple evaluated from January 1, 2004,through December 31, 2010. The rate of failed treatment for Candida mastitis, the rate of improvement of symptoms with nifedipine use, and the overall rate of improvement of symptoms with appropriate therapy involving treatment of Raynaud phenomenon. Among the 22 patients with Raynaud phenomenon of the nipple, previous treatment for Candida mastitis with oral or topical antifungals was ineffective in 20(91%). Of the 12 patients who tolerated a trial of nifedipine,10 (83%) reported decreased or resolved nipple pain. All patients experienced marked improvement of symptoms with appropriate therapy involving treatment of Raynaud phenomenon. Most patients were treated with antifungals before presentation without resolution of nipple pain. Nifedipine appears to be an effective medication for the treatment of Raynaud phenomenon of the nipple. With appropriate management of Raynaud phenomenon,breastfeeding mothers demonstrated improvement of nipple pain. Raynaud phenomenon of the nipple should be considered in the differential diagnosis of nipple pain during lactation.

Primary Raynaud's phenomenon in an infant: a case report and review of literature

Raynaud's phenomenon (RP) is an extremely unusual finding in early infancy. In the present report we describe a one-month-old previously healthy male infant who presented with unilateral acrocyanosis. Although infantile acrocyanosis is known to be a benign and self-resolving condition, it is generally bilateral and symmetric. The unilateral nature of the acrocyanosis was an atypical finding in this infant. Consequently, he was closely monitored to evaluate the progression of his acrocyanosis. Based on his benign clinical course and failure to demonstrate other etiologies contributing to his acrocyanosis, he was diagnosed to have primary RP. Due to the rarity of RP in children, we review the progress in understanding the pathophysiology, epidemiology and management of RP and additionally discuss the differential diagnosis of unilateral and bilateral acrocyanosis in infants.

Management of cutaneous vascular complications in systemic scleroderma: experience from the German network

Major cutaneous vascular complications of systemic sclerosis (SSc) are secondary Raynaud's phenomenon (RP) and digital ulcers. Even though SSc is a rare disease, timely and appropriate management of its vascular complications is mandatory for reducing the rate of major impairment. It should therefore be aware to physicians from different specialties. We evaluated the diagnostic and therapeutic approach toward secondary RP and ulceration in SSc patients at 28 German clinical centers at the time of initiation of the German network for Systemic Scleroderma (DNSS). We retrieved data via questionnaires and from the DNSS patient registry. Management of RP and ulcerations in SSc were heterogeneous at initiation of the network, reflecting a sometimes insufficient use of the diagnostic and therapeutic possibilities. As such, (1) calcium channel blockers were the first line therapy in most centers; but often in insufficient dosages, and (2) only 21.2% of patients with acral ulceration had received prostacyclins when recruited into the network. The sometimes insufficient care of vascular complications of SSc in Germany revealed the need for their standardized management, e.g. within a network for SSc and for consensus on a diagnostic or therapeutic algorithm.

Raynaud-Phänomen in der Dermatologie

While primary Raynaud phenomenon (RP) only rarely leads to complications, secondary RP when associated with systemic sclerosis (SSc) frequently results in necrosis, ulcers or even gangrene. Therefore timely therapeutic intervention is required. Management of RP includes physical therapy, avoidance of triggers, and a variety of medications, depending on the disease severity. On the basis of published studies and of our own experience we suggest: a) for primary and uncomplicated secondary RP, calcium channel blockers in adequate doses; b) for SSc-associated secondary RP with hypertension, cardial or renal involvement, drugs which interfere with angiotensin; c) in case of concomitant depression, exploitation of the vasodilatory effects of serotonin reuptake inhibitors, d) in presence of ulcers or marked trophic alterations, intravenous administration of iloprost, e) for recalcitrant cases and endangered digits, sildenafil, f) for prevention of severe relapses, the endothelin-receptor antagonist bosentan. The drugs mentioned in c-f are not approved for RP and used off-label. In patients with secondary SSc-associated RP, timely therapy can reduce the percentage of complications such as ulcers or amputations. In addition, timely treatment of RP possibly retards ensuing fibrotic processes.

Raynaud's phenomenon in older adults: diagnostic considerations and management.

Raynaud's phenomenon (RP) is characterised by sensitivity to cold temperatures associated with either biphasic or uniphasic change in colour of the digits. Since few studies are available which include older adults, the prevalence of RP in the older adult population is estimated from surveys or studies of the general population. The causes of RP in older adults may differ significantly from those in young adults and, therefore, so would the evaluation of RP. Because of comorbitis that accompany advancing age, the management of RP in older adult patients must take into consideration toxicity and adverse reactions that may develop, especially in the frail individual. Although nonpharmacological therapy is preferable, slow-release calcium antagonists provide a relatively well tolerated and effective treatment for moderate to severe RP in older adult patients. Aggressive treatment including hospitalisation is appropriate for older adult patients during periods of critical digital ischaemia associated with RP.

Hand warming as a treatment for Raynaud's phenomenon in systemic sclerosis

Twelve patients with Raynaud's phenomenon (RP) due to systemic sclerosis (SS) warmed their hands for 5 min in hand hot water every 4 h throughout the day during alternate weeks of a 6-week study. There was a statistically significant decrease in the number and duration of Raynaud's attacks in the weeks in which warming was performed compared with the intervening weeks. An increase in blood flow as measured by laser-Doppler flowmetry accompanied clinical improvement. Simple hand warming appears to be effective in the management of RP in patients with SS.