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 Table of Contents  
Year : 2018  |  Volume : 4  |  Issue : 2  |  Page : 178-183

Pathophysiology and management of Raynaud's phenomenon

1 Department of Medicine, St. Luke's Bethlehem, Bethlehem, PA, USA
2 Department of Medicine, Lake Erie College of Osteopathic Medicine, Erie, PA, USA
3 Department of Cardiology, Brigham and Women's, Boston, MA, USA
4 Department of Cardiology, Lehigh Valley Hospital, Allentown, PA, USA
5 Department of Cardiovascular Medicine, St. Luke's University Hospital Network, Fountain Hill, PA, USA

Date of Submission05-Nov-2017
Date of Acceptance14-Apr-2018
Date of Web Publication30-Aug-2018

Correspondence Address:
Dr. Sudip Nanda
Department of Cardiovascular Medicine, St. Luke's University Hospital Network, Fountain Hill, PA
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJAM.IJAM_78_16

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Raynaud's phenomenon (RP) is a multi-etiological vasospastic condition requiring individualized treatment. This case presents a patient with classic primary RP whose symptoms improved after being treated for depression. Her example demonstrates that medication regimen sometimes have unexpected, but positive outcomes.
The following core competencies are addressed in this article: Patient care, Medical knowledge.

Keywords: Polypharmacy, Raynaud's phenomenon, comorbidity management

How to cite this article:
Stone LE, Yellapu V, Ali F, Agrawal S, Singh A, Garg L, Longo S, Nanda S. Pathophysiology and management of Raynaud's phenomenon. Int J Acad Med 2018;4:178-83

How to cite this URL:
Stone LE, Yellapu V, Ali F, Agrawal S, Singh A, Garg L, Longo S, Nanda S. Pathophysiology and management of Raynaud's phenomenon. Int J Acad Med [serial online] 2018 [cited 2022 Jun 27];4:178-83. Available from: https://www.ijam-web.org/text.asp?2018/4/2/178/240142

  Introduction Top

Raynaud's phenomenon (RP) is defined as end-extremity pallor with subsequent purplish cyanosis and reactive hyperemic response to a trigger, such as cold exposure, emotional, or physical stress.[1],[2],[3] While the digits are the most commonly affected site, the toes, palms, soles, earlobes, and nose have also been indicated[4],[5] [Figure 1] and [Figure 2]. Other clinical symptoms during attacks can include loss of sensation and reperfusion pain depending on the severity and frequency of occurrences.[2],[4],[6] Frequent and prolonged attack can eventually lead to ulceration of the affected extremities.[7],[8],[9]
Figure 1: The patient's hands during a Raynaud's event. Note the purplish discoloration of the distal digits

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Figure 2: The most common sites of Raynaud's manifestations are the hands, feet, nose, and earlobes

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Although clinical presentation is relatively consistent, Raynaud's is divided into several categories by etiology.[10] Primary RP (PRP) is a diagnosis of exclusion[11] whose diagnosis requires the following criteria as follows: (1) normal nail-fold capillaroscopy, (2) absence of a positive antinuclear antibodies titer, and (3) absence of any other precipitating factors, that is, drugs, mechanical trauma, or nerve impingement.[9],[12],[13],[14] It is believed to be due to dysfunctional arteriovenous anastomoses (AVAs) in the palms and soles.[2],[15],[16] These anastomoses are unique in that they do not contain a capillary bed, allowing for rapid movement of blood to and from cutaneous circulation.[17],[18] This unique feature, when properly functioning, allows for efficient extremity thermoregulation.[17],[19] Several studies suggest that patients with PRP suffer from an increased number of AVAs with increased alpha-2 adrenergic receptors and sympathetic innervations.[20],[21] These innervations, which dilate and constrict vessels in response to various stimuli, mediate a reflexive vasoconstrictive response[9],[10],[22] [Figure 3]. In RP, the cold or stress acts as an aggravating factor, which promotes digital ischemia through an exaggerated sympathetic-induced vasoconstriction.[1],[2]
Figure 3: Mechanisms of smooth muscle modulation at the site of an arteriovenous anastomosis PIP2: phosphatidylinositol bisphosphate; IP3: Inositol Triphosphate; GMP: Guanosine monophosphate, AMP: Adenosine monophosphate, cGMP: Cyclic guanosine monophosphate, cAMP: Cyclic adenosine monophosphate, PKG: Protein kinase G, PKA: Protein kinase A

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Secondary RP (SRP) is multi-etiological.[11] Presentation is similar to primary Raynaud's; however, there are several factors that suggest PRP over SRP, including a milder, painless presentation, and onset of symptoms before the age of 20.[11],[23] [Table 1] shows the discussion of secondary Raynaud's etiologies.
Table 1: Etiology and mechanism

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Management of Raynaud's relies on addressing the underlying problem, lifestyle changes, and pharmacotherapy.[37] The latter involves several medications targeting the vascular endothelium and smooth muscle to promote blood flow to the compromised tissue.[5],[37] [Table 2] discusses the various drugs used in the treatment of both primary and secondary Raynaud's.
Table 2: Pharmacological agents for use in Raynaud's phenomenon

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  Case Report Top

The patient is a 59-year-old female that presented for evaluation of palpitations. She has a medical history of hyperparathyroidism status-postthymectomy, depression, hypertension, and cold-induced color changes to her fingertips (RP) for the past 30 years [Figure 1]. In the clinic, her vitals were within normal limits. Physical examination did not disclose any abnormalities and revealed no ulceration of her fingers. Her antinuclear antibody test was negative. There were no abnormalities in her complete blood panel or complete metabolic panel. Her electrocardiogram did not show any abnormalities and her tilt table test was negative for autonomic dysfunction. No abnormal rhythm other than sinus arrhythmia was identified.

The patient's long-term medications included losartan, quetiapine, and trazodone. The patient notes that after she was started on quetiapine, her Raynaud's symptoms decreased significantly.

  Discussion Top

The patient in this case report carries a diagnosis of Raynaud's and long-term depression. In the primary treatment of depression, she found relief of her Raynaud's symptoms without directly addressing this condition with pharmacotherapy. This unexpected result may be due to the mechanisms underlying her medications, which including losartan, quetiapine, and trazodone.

Losartan, an angiotensin-converting enzyme receptor blocker, increases circulating angiotensin II, leading to an increase in circulating blood volume, and decreased the effect of vasoconstriction in the extremities.[40],[41],[42],[43] Trazodone is a serotonin antagonist and reuptake inhibitor that increases serotonin concentration. Serotonin is a vasoactive substance that causes vasodilation.[44],[45] Quetiapine is a serotonin and adrenergic receptor antagonist causing vasodilation. The overall effect of these medication causes increased blood flow, increased vasodilation, and decreased platelet aggregation, mechanisms that parallel normal pharmacological interventions for Raynaud's symptoms.[46],[47],[48],[49] It is, therefore, quite possible that this patient's symptoms dramatically improved as an unexpected consequence of appropriately managing her other conditions. See [Figure 4] and [Figure 5] for a discussion of pertinent vascular receptors indicated in Raynaud's as well as management of both primary and secondary Raynaud's.
Figure 4: (a) Pharmacological and natural mediators of arterial endothelium and smooth muscle. (b) Key: 5-HT: 5-Hydroxytryptamine, AT-II: Angiotensin 36 37 Receptor

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Figure 5: Management for patients with primary and secondary Raynaud's phenomenon

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  Conclusion Top

Managing patients with multiple conditions present a challenge when determining efficient pharmacologic intervention. In conditions whose medication choices overlap, such as RP and depression, it is possible to treat all simultaneously or at least wisely choose medications that will reduce symptom burden across multiple conditions. This approach is ideal and avoids the complications and inconvenience of polypharmacy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

Ethical conduct of research

Established ethical guidelines for research were utilized during the conduct of this project.

  References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2]

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