Modified-release sildenafil reduces Raynaud's phenomenon attack frequency in limited cutaneous systemic sclerosis

Herrick, Ariane L.; Hoogen, Frank van den; Gabrielli, Armando; Tamimi, Nihad; Reid, Carol; O’Connell, Damian P.; Vázquez-Abad, Maria Dolores; Denton, Christopher P.

doi:10.1002/art.30195

Cited by 95 publications

(50 citation statements)

References 31 publications

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“…These include phosphodiesterase-5 inhibitors (sildenafi l, tadalafi l, vardenafi l) [25] and phosphodiesterase-3 inhibitors such as cilostazol. However, phosphodiesterase-5 inhibitors are being increasingly used in systemic sclerosis-related RP, with a number of recent trials [26][27][28][29] and a meta-analysis [25] suggesting benefi t, although the trials were all of short duration and large, long duration controlled trials are required. Topical nitrates have recently been revisited.…”

Section: Drug Treatmentmentioning

confidence: 99%

ESVM guidelines – the diagnosis and management of Raynaud’s phenomenon

Belch

Carlizza

Carpentier

et al. 2017

Vasa

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Abstract. Regarding the clinical diagnosis of Raynaud’s phenomenon and its associated conditions, investigations and treatment are substantial, and yet no international consensus has been published regarding the medical management of patients presenting with this condition. Most knowledge on this topic derives from epidemiological surveys and observational studies; few randomized studies are available, almost all relating to drug treatment, and thus these guidelines were developed as an expert consensus document to aid in the diagnosis and management of Raynaud’s phenomenon. This consensus document starts with a clarification about the definition and terminology of Raynaud’s phenomenon and covers the differential and aetiological diagnoses as well as the symptomatic treatment.

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Section: Drug Treatmentmentioning

confidence: 99%

ESVM guidelines – the diagnosis and management of Raynaud’s phenomenon

Belch

Carlizza

Carpentier

et al. 2017

Vasa

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“…The major point to highlight in the last 18 months for the practising clinician has been the increased use of PDE5 inhibitors , and many clinicians are now very likely to use a PDE5 inhibitor as a second choice after a calcium channel blocker in patients with SScrelated RP. This is because (a) PDE5 inhibitors have now been shown to confer benefit in a number of randomised controlled trials [36,37,38,39], and in a recent meta-analysis [40] (although the trials were all short-term, with a treatment period of 6 weeks or less) and (b) reduced costs of PDE5 inhibition from previously. examine characteristics of 89 patients treated with bosentan in a 'real-world' setting: patients treated wth bosentan (median treatment duration until data collection was 17.5 months) had severe disease (61% with at least 2 previous digital ulcer episodes, and 63% had had previous intravenous iloprost infusions).…”

Section: Raynaud's Phenomenon (Which Has Not Progressed To Digital Ulmentioning

confidence: 99%

Recent advances in the pathogenesis and management of Raynaud's phenomenon and digital ulcers

Herrick

2016

Current Opinion in Rheumatology

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Purpose of review: Systemic sclerosis (SSc)-related digital vasculopathy can progress from severe Raynaud's phenomenon (RP) to digital ulceration, is a major cause of pain and disability, and impacts negatively on quality of life. Current treatments are often ineffective and poorly tolerated. This review summarises some of the progress which has been made in the last 12 to 18 months in terms of our understanding of disease process, measurement and treatment. Recent findings:The most important findings include that we can now better predict which patients with SSc are most likely to develop digital ulcers. In terms of treatment, a multicentre trial showed that the phosphodiesterase inhibitor sildenafil confers some benefit in SSc-related digital ulceration.Topical therapies are being explored: iontophoresis of vasodilators increases local blood flow, and in an avian model, VEGF 121 fibrin applied in a gel matrix improved wound healing. A number of challenges confront clinicians and scientists with an interest in SSc-related digital vasculopathy, specific questions being:1. What mechanisms drive the digital vasculopathy and lead to structural as well as functional change? 2. Can we predict which patients progress to digital ulceration? 3. Can we measure disease process reliably (in terms of both RP and digital ulcers), to provide outcome measures to facilitate clinical trials?4. Are we making progress in developing safe and effective treatments, for both severe RP and SScrelated digital ulceration?In this review I shall outline developments over the last 12-18 months in answering these four questions, under the headings of pathophysiology, predictors of digital ulceration, measurement of disease process, and management. Under each heading I shall consider firstly RP and secondly digital ulceration, although this is a false distinction because both are part of the spectum of SSc-digital vasculopathy. PATHOPHYSIOLOGY Raynaud's phenomenonThe pathophysiology of RP is complex and most likely involves an interplay between vascular factors, neural control mechanisms and intravascular factors [6]. Flavahan, in a recent review [7**], describes thermoregulatory mechanisms as central to an understanding of RP, highlighting the role of arteriovenous anastomoses, and how local cooling leads to increased activity of alpha 2 -adrenoceptors, resulting in reduced blood flow. In patients with SSc, structural microvascular changes mean that upstream vasoconstriction can irretrievably compromise nutritional blood flow and lead to tissue injury [7**,8]. The review also gives a framework for targetted therapeutic interventions [7**]. Digital ulcerationA commonly held view is that fingertip ulceration is ischaemic, whereas ulceration over the extensor surfaces of fingers is 'traumatic'. To date there has been very little direct evidence to support this theory. However, a study by Ruaro et al [9*] of 20 patients with SSc and fingertip ulcers demonstrated that blood flow is reduced at the site of fingertip ulcers (and improves wit...

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“…17 Sildenafil improves symptoms, ulcer healing, and capillary blood flow in patients with secondary RS. 18,19 Tadalafil and vardenafil have longer half-lives than sildenafil but have been less well studied in RS, although both have demonstrated symptom improvement in small clinical trials. 20,21 Nitrates…”

Section: Phosphodiesterase 5 Inhibitorsmentioning

confidence: 99%

Raynaud Syndrome

Valdovinos

Landry

2014

Techniques in Vascular and Interventional Radiology

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Raynaud syndrome (RS) was first described by the French physician Maurice Raynaud in 1862 with the characteristic tricolor change featuring pallor (ischemic phase), cyanosis (deoxygenation phase), and erythema (reperfusion phase) induced by cold or stress. Although the underlying pathophysiological mechanism is unclear, alterations in activity of the peripheral adrenoceptor have been implicated, specifically an enhanced smooth muscle contraction due to overexpression or hyperactivity of postsynaptic alpha 2 receptors. There are 2 ways that RS can appear clinically; isolated, formerly referred as Raynaud disease or now primary RS and in association with other conditions, usually connective tissue disorders (eg, Sjögren syndrome, systemic lupus erythematosus, scleroderma, and rheumatoid arthritis), frequently called Raynaud phenomenon or secondary RS. The estimated prevalence in the general population is 3%-5%, with a higher prevalence in women than in men. The diagnosis is mainly clinical, based on patient descriptions of skin changes. Upper extremity pulse-volume recording is used to rule out proximal arterial obstruction. The differentiation between a vasospastic vs and obstructive mechanism is made using digital pressures and photoplethysmography, where an obstructive mechanism has decreased pressures and blunted waveforms. Cold challenge testing, such as ice water immersion with temperature recovery, is highly sensitive but lack specificity. Serologic screening (antinuclear antibody and rheumatoid factor) is advocated to rule out associated connective tissue disorders. Most patients with RS can be managed conservatively, with avoidance of cold exposure or hand warming. For those in whom conservative management is inadequate, a number of pharmacologic and surgical therapies have been used. Owing to lack of complete understanding of the underlying pathophysiology, targeted therapy has not been possible; rather, therapy has been focused on the use of general vasodilation strategies. In this review, the diagnosis, natural history, and current medical and invasive therapy are summarized.

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Modified-release sildenafil reduces Raynaud's phenomenon attack frequency in limited cutaneous systemic sclerosis

Cited by 95 publications

References 31 publications

ESVM guidelines – the diagnosis and management of Raynaud’s phenomenon

ESVM guidelines – the diagnosis and management of Raynaud’s phenomenon

Recent advances in the pathogenesis and management of Raynaud's phenomenon and digital ulcers

Raynaud Syndrome

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