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

Curtiss, Paul; Schwager, Zachary; Cobos, Gabriela; Sicco, Kristen Lo; Franks, Andrew G.

doi:10.1016/j.jaad.2018.01.043

Cited by 34 publications

(23 citation statements)

References 36 publications

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“…18 Topical approaches to treatment also merit revisiting, as such, a 'local' approach to treatment could be better tolerated compared with systemic therapies for RP (and also digital ischaemic complications). [65][66][67]…”

Section: Unmet Needs and Challengesmentioning

confidence: 99%

Raynaud's phenomenon

Haque

Hughes

2020

Clinical Medicine

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Section: Unmet Needs and Challengesmentioning

confidence: 99%

Raynaud's phenomenon

Haque

Hughes

2020

Clinical Medicine

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“…While primary Raynaud syndrome is related to functional vascular aterations alone, in secondary Raynaud syndrome structural microvascular damage also occurs. Pathogenic mechanisms include an unbalance between vasodilatory and vasoconstrictor mediators, with increased levels of angiotensin II and decreased levels of nitric oxide, neural abnormalities with overactivity of α2c-adrenoreceptors and increased levels of neuropeptide Y that contribute to vasoconstriction, as well as intravascular abnormalities with increased production of platelet thromboxane A2, a potent vasoconstrictor, as well as oxidative stress [11,13,14].…”

Section: Resultsmentioning

confidence: 99%

“…Topical nitroglycerin is indicated in several dermatologic disorders with vasoconstriction as a common pathogenic mechanism, but with variable clinical manifestations, such as Raynaud syndrome, chondrodermatitis nodularis helicis, cutaneous ulcers, pernio erythema, alopecia areata, tissular necrosis after dermal filler injections [11,12].…”

Section: Experimental Partmentioning

confidence: 99%

Nitroglycerin in Dermatology

Toader¹,

Mocanu²,

Iancu³

et al. 2020

Rev. Chim.

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Nitroglycerin has traditionally been used in medicine for over 130 years for its potent dilator effect on both venous and arterial blood vessels. Cardiovascular ischemic diseases are among the classic indications. However, the possibility to incorporate nitroglycerin in different galenic forms renders it new therapeutic potential through topical application, both in surgery and in dermatology (Raynaud syndrome, chondrodermatitis, pernio erythema, alopecia areata, ulcers of different etiologies). Nitroglycerin is used for topical treatment as 0.5%, 1% or 2% ointment, lower concentrations limiting the probability of systemic adverse effects occurence.

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“…Topical nitrates provide exogenous NO after metabolism by mitochondrial aldehyde dehyrogenase . A recent meta_analysis conducted by our research group demonstrated the effectiveness of locally applied topical nitrates in treating RP . Alternatively, local NO production may be increased through l _arginine supplementation .…”

Section: Role Of No In Secondary Rp and Systemic Sclerosismentioning

confidence: 95%

“…31 A recent meta-analysis conducted by our research group demonstrated the effectiveness of locally applied topical nitrates in treating RP. 32 Alternatively, local NO production may be increased through L-arginine supplementation. 33 Developments in the biochemical understanding of ADMA and its effect on this pathway are critical in understanding which RP patients may benefit from L-arginine treatments (Fig.…”

Section: Role Of No In Secondary Rp and Systemic Sclerosismentioning

confidence: 99%

The clinical effects of l_arginine and asymmetric dimethylarginine: implications for treatment in secondary Raynaud's phenomenon

Curtiss

Schwager

Sicco

et al. 2018

Acad Dermatol Venereol

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Secondary Raynaud's phenomenon (RP) is often the sentinel clinical finding in systemic sclerosis and may precede systemic disease by several years. Altered nitric oxide metabolism plays a critical role in both fibrosis and severe secondary RP phenotypes in these patients. Increased flux through inducible nitric oxide synthase (iNOS) drives cutaneous fibrosis. Failure of flux through endothelial nitric oxide synthase (eNOS) contributes to increased vasoconstriction and decreased vasorelaxation. The underproduction of nitric oxide by eNOS is in part due to increased levels of asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase. The inhibitory effects of increased ADMA levels may be counteracted increasing serum l-arginine, which is often an effective treatment strategy in these patients. As such, l-arginine-based therapies should be considered in managing secondary RP, particularly given their favourable safety and tolerability profile. While there is no established dosing regimen, studies of oral l-arginine in secondary RP suggest that divided dosing may begin at 1-2 g/day and may be titrated up to 10 g/day. Conversely, primary RP is not associated with increased ADMA production which likely accounts for the failure of l-arginine trials to show benefit in primary RP.

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

Cited by 34 publications

References 36 publications

Raynaud's phenomenon

Raynaud's phenomenon

Nitroglycerin in Dermatology

The clinical effects of l_arginine and asymmetric dimethylarginine: implications for treatment in secondary Raynaud's phenomenon

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