Importance of identification and treatment of Raynaud’s phenomenon

Previous studies have shown that patients with Raynaud’s phenomenon secondary to systemic sclerosis present abnormal endothelial function; the mechanisms responsible for the endothelial dysfunction are unknown but increased vascular oxidative stress could be a possible cause. The hypothesis that a potent water-soluble antioxidant can reverse endothelial dysfunction in these patients was tested in the present study. We examined 11 female patients with Raynaud’s phenomenon secondary to systemic sclerosis and ten healthy control women by ultrasound imaging of the brachial artery to assess flow-mediated (endothelium-dependent) and nitrate-induced (endothelium-independent) vasodilatation. Flow-mediated dilatation and nitrate-induced dilatation were significantly reduced in patients with Raynaud’s phenomenon, indicating abnormal endothelial and smooth muscle cell function. Patients with Raynaud’s phenomenon entered a double-blind, randomized, crossover placebo-controlled trial and received orally 2 g of ascorbic acid or placebo; vascular studies were repeated two hours after ascorbic acid or placebo administration. Flow-mediated dilatation did not improve after ascorbic acid (1.6 ± 2.2% to 2.2 ± 2.5%, ns) or placebo administration (1.2 ± 1,9% to 1.7 ± 1.4%, ns); also nitrate-induced dilatation was similar after ascorbic acid or placebo (16 ± 7.4% vs 17 ± 8%, ns), suggesting no effect of ascorbic acid on endothelial and vascular smooth muscle function. In conclusion, ascorbic acid does not reverse endothelial vasomotor dysfunction in the brachial circulation of patients with Raynaud’s phenomenon secondary to systemic sclerosis. The use of different antioxidants or different dosing of ascorbic acid may be required to show a beneficial effect on endothelial vasodilator function.

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The response of skin perfusion and of rheological and immunological variables to intravenous prostanoid administration in Raynaud’s phenomenon secondary to collagenosis

VASA ◽

10.1024/0301-1526.34.4.243 ◽

2005 ◽

Vol 34 (4) ◽

pp. 243-249 ◽

Cited By ~ 2

Author(s):

Drinda ◽

Neumann ◽

Pöhlmann ◽

Vogelsang ◽

Stein ◽

...

Keyword(s):

Laser Doppler Flowmetry ◽

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

Plasma Viscosity ◽

Laser Doppler ◽

Erythrocyte Aggregation ◽

Control Group ◽

Long Term Effects ◽

Doppler Flowmetry

Background: Prostanoids are used in the treatment of Raynaud’s phenomenon and acral perfusion disorders secondary to collagenosis. In subjective terms, intravenous administration of these agents produces success in more than 50% of patients. The therapeutic outcome of clinical administration of alprostadil or iloprost may vary from individual to individual. Patients and methods: The following variables were analysed in a cross-over study in 27 patients with collagenosis and Raynaud’s phenomenon: plasma viscosity and erythrocyte aggregation (rheological variables), partial pressure of oxygen and laser Doppler flowmetry in the finger region, and lymphocyte phenotyping and interleukin (IL) determinations (immunological variables). Results: Laser Doppler flowmetry revealed significant differences between patients with secondary Raynaud’s phenomenon and a control group of 25 healthy subjects. Laser Doppler readings did not change significantly as a result of the treatments. Therapy with iloprost produced a reduction in IL-1beta, L-selectin (CD 62 L) and IL-6. Conclusion: The change in immunological variables due to iloprost may explain the long-term effects of prostaglandins in the treatment of Raynaud’s phenomenon. From our results it is not possible to infer any preference for iloprost or alprostadil.

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Raynaud’s phenomenon and digital ischaemia - pharmacologic approach and alternative treatment options

VASA ◽

10.1024/0301-1526/a000526 ◽

2016 ◽

Vol 45 (3) ◽

pp. 201-212 ◽

Cited By ~ 13

Author(s):

Birgit Linnemann ◽

Matthias Erbe

Keyword(s):

Quality Of Life ◽

Angiotensin Receptor Blockers ◽

Raynaud’S Phenomenon ◽

Treatment Options ◽

Raynaud's Phenomenon ◽

Tissue Loss ◽

Receptor Antagonists ◽

Skin Ulcers ◽

Digital Ischaemia

Abstract. The primary goal of therapy is to reduce the frequency and intensity of Raynaud’s attacks and to minimize the related morbidity rather than to cure the underlying condition. Treatment strategies depend on whether Raynaud’s phenomenon (RP) is primary or secondary. All patients should be instructed about general measures to maintain body warmth and to avoid triggers of RP attacks. Pharmacologic intervention can be useful for patients with severe and frequent RP episodes that impair the patient’s quality of life. Calcium channel blockers are currently the most prescribed and studied medications for this purpose. There has been limited evidence for the efficacy of alpha-1-adrenergic receptor antagonists, angiotensin receptor blockers, topical nitrates or fluoxetine to treat RP. The intravenously administered prostacyclin analogue iloprost can reduce the frequency and severity of RP attacks and is considered a second-line therapy in patients with markedly impaired quality of life, critical digital ischaemia and skin ulcers who are at risk for substantial tissue loss and amputation. Phosphodiesterase inhibitors (e.g., sildenafil) can also improve RP symptoms and ulcer healing whereas endothelin-1 receptor antagonists (e.g., bosentan) are mainly considered treatment options in secondary prevention for patients with digital skin ulcers related to systemic sclerosis. However, their use in clinical practice has been limited by their high cost. Antiplatelet therapy with low-dose aspirin is recommended for all patients who suffer from secondary RP due to ischaemia caused by structural vessel damage. Anticoagulant therapy can be considered during the acute phase of digital ischaemia in patients with suspected vascular occlusive disease attributed to the occurrence of new thromboses. In patients with critical digital ischaemia, consideration should be given to hospitalisation, optimisation of medical treatment in accordance with the underlying disease and evaluation for a secondary, possibly reversible process that is causing or aggravating the clinical symptoms.

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You’re the Flight Surgeon

Aerospace Medicine and Human Performance ◽

10.3357/amhp.5575.2020 ◽

2020 ◽

Vol 91 (5) ◽

pp. 459-461

Keyword(s):

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

Vibration Syndrome

Warneke JA, Pavelites JJ. You’re the flight surgeon: Raynaud’s phenomenon/hand arm vibration syndrome. Aerosp Med Hum Perform. 2020; 91(5):459–461.

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Antinuclear Antibodies in both Healthy Individuals and Subjects with Raynaud's Phenomenon.

Nishi Nihon Hifuka ◽

10.2336/nishinihonhifu.55.915 ◽

1993 ◽

Vol 55 (5) ◽

pp. 915-919 ◽

Cited By ~ 1

Author(s):

Yoko KOMURA ◽

Hideyo YOSHIDA ◽

Setsuya FUJITA ◽

Ryoichi INABA ◽

Hirotoshi IWATA

Keyword(s):

Antinuclear Antibodies ◽

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

Healthy Individuals

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Clinical and epidemiological characteristics and treatment of Raynaud's phenomenon in rheumatic diseases

Practical medicine ◽

10.32000/2072-1757-2018-16-6-178-184 ◽

2018 ◽

Vol 16 (6) ◽

pp. 178-184

Author(s):

Z. R. Bagautdinova ◽

◽

I. R. Gaysin ◽

L. V. Ivanova ◽

A. A. Trukhina ◽

...

Keyword(s):

Rheumatic Diseases ◽

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

Epidemiological Characteristics

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Faculty Opinions recommendation of Statins: potentially useful in therapy of systemic sclerosis-related Raynaud's phenomenon and digital ulcers.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1129797.586876 ◽

2008 ◽

Author(s):

Margitta Worm

Keyword(s):

Systemic Sclerosis ◽

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

Digital Ulcers

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Repurposing cilostazol for Raynaud's phenomenon

Current Medicinal Chemistry ◽

10.2174/0929867327666200903114154 ◽

2020 ◽

Vol 27 ◽

Author(s):

Nehme El-Hachem ◽

Manal M. Fardoun ◽

Hasan Slika ◽

Elias Baydoun ◽

Ali H. Eid

Keyword(s):

Color Change ◽

Angiotensin Receptor Blockers ◽

Raynaud’S Phenomenon ◽

Blood Perfusion ◽

Raynaud's Phenomenon ◽

Channel Blockers ◽

Phosphodiesterase Type 5 Inhibitors ◽

Receptor Blockers ◽

Phosphodiesterase Type ◽

Food And Drugs Administration

: Raynaud's Phenomenon (RP) results from exaggerated cold-induced vasoconstriction. RP patients suffer from vasospastic attacks and compromised digital blood perfusion leading to triple color change at the level the fingers. Severe RP may cause ulcers and threaten tissue viability. Many drugs have been used to alleviate the symptoms of RP. These include calcium-channel blockers, cGMP-specific phosphodiesterase type 5 inhibitors, prostacyclin analogs, and angiotensin receptor blockers. Despite their variety, these drugs do not treat RP but rather alleviate its symptoms. To date, no drug for RP has been yet approved by U.S Food and Drugs Administration. Cilostazol is a selective inhibitor of phosphodiesteraseIII, originally prescribed to treat intermittent claudication. Owing to its antiplatelet and vasodilating properties, cilostazol is being repurposed as a potential drug for RP. This review focuses on the different lines of action of action of cilostazol serving to enhance blood perfusion in RP patients.

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Clinical features and risk factors of Raynaud’s phenomenon in primary Sjögren’s syndrome

Clinical Rheumatology ◽

10.1007/s10067-021-05749-w ◽

2021 ◽

Author(s):

Wei Lin ◽

Zhifei Xin ◽

Xiaoran Ning ◽

Yang Li ◽

Xiuying Ren ◽

...

Keyword(s):

Risk Factors ◽

Disease Activity ◽

Raynaud’S Phenomenon ◽

Sjogren’S Syndrome ◽

Raynaud's Phenomenon ◽

Sjogren's Syndrome ◽

Primary Sjögren’S Syndrome ◽

Lung Involvement ◽

Primary Sjogren’S Syndrome ◽

Primary Sjögren's Syndrome

Abstract Objective The aim at the current study was to investigate the clinical characteristics and risk factors of Raynaud’s phenomenon (RP) in patients with primary Sjögren’s syndrome (pSS). Methods Retrospective analysis of the medical records of 333 new-onset pSS patients was performed. Demographic, clinical, and serological data were compared between individuals with and without RP. Logistic regression analysis was used to identify risk factors. Results RP was present in 11.41% of the pSS patients. pSS-RP patients were younger (49.74±14.56 years vs. 54.46±13.20 years, p=0.04) and exhibited higher disease activity (11 [5.75–15] vs. 7 [4–12], p=0.03) than those without. The prevalence of lung involvement was significantly higher in pSS patients with RP (60.53% vs. 17.29%; p<0.001). A significantly higher proportion of patients with pSS-RP tested positive about antinuclear (ANA), anti-RNP, and anti-centromere antibodies (ACA) compared to those without (p=0.003, <0.001, and 0.01, respectively). Multivariate analysis identified lung involvement (odds ratio [OR]=8.81, 95% confidence interval [CI] 2.02–38.47; p=0.04), anti-RNP positive status (OR=79.41, 95% CI 12.57–501.78; p<0.0001), as well as ACA (OR=13.17, 95% CI 2.60–66.72; p=0.002) as prognostic factors for pSS-RP. Conclusion The presence of RP defined a subset of pSS with a unique phenotype, manifesting as increased lung involvement and a higher frequency of anti-RNP antibodies and ACA, as well as greater disease activity. These results suggest that RP has clinical and prognostic value of pSS patients. Further prospective studies with a larger number of subjects are warranted to confirm our findings and assess the prognostic and treatment implications of RP in pSS patients. Key Points• Raynaud’s phenomenon (RP) was present in 38 (11.41%) of 333 patients with primary Sjögren’s syndrome (pSS), with patients with RP exhibiting a younger age and higher disease activity.• The presence of RP indicates a subset of pSS with a unique phenotype, with manifestations including increased lung involvement and a higher frequency of anti-RNP antibodies and anti-centromere antibodies.• Patients with pSS and RP need close follow-up and long-term observation (including assessment of microangiopathy), with specific attention paid to the possible development of clinical features of systemic sclerosis.

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