Effects of Audio‐Guided Imagery on Raynaud Phenomenon in Connective Tissue Disease

Abstract

Objective

To assess the physical, emotional, and mental impact of regular audio‐guided imagery (AGI) in patients with connective tissue disease (CTD)–associated Raynaud phenomenon (RP).

Methods

Sixteen adult patients with CTD‐associated RP were enrolled in an open‐label, single‐arm, eight‐week intervention with daily AGI at a single center. Patients completed surveys, including assessment of RP severity, depression/anxiety, and quality of life at baseline and the end of eight weeks.

Results

Study participants demonstrated significant improvement in all patient reported outcomes, except Generalized Anxiety Disorder 7, which showed improvement but was not statistically significant. This eight‐week intervention shows that patients with CTD‐associated RP had less severe RP episodes, as well as improved quality of life and depressive symptoms.

Conclusion

AGI significantly improved several domains of health, including physical, emotional, and mental, in patients with CTD‐associated RP who otherwise more commonly struggle with more RP attacks, lower quality of life, and depression. AGI is a low‐cost, low‐risk, and convenient therapy for CTD‐associated RP. A larger study studying the effects of this intervention is indicated.

INTRODUCTION

Raynaud phenomenon (RP) is characterized as episodic digital color changes—white, blue, and red—triggered by cold environments, sudden temperature decreases, and emotional stress. Not all attacks exhibit the full triphasic sequence. Most individuals have primary RP (PRP), which typically presents in young women, may be familial, and is not associated with tissue ischemia. In contrast, secondary RP (SRP) occurs in the setting of connective tissue diseases (CTDs), particularly in systemic sclerosis (SSc), and is associated with increased risk of digital ischemia and ulceration.

PRP, as defined by LeRoy and Medsger, includes episodic and symmetric digital pallor or cyanosis, absence of peripheral vascular disease or digital ulcers, normal nailfold capillaries, negative antinuclear antibodies, a normal sedimentation rate (erythrocyte sedimentation rate), and stability of RP for at least two years without progression. ¹ PRP reflects functional dysregulation of cutaneous thermoregulation, including exaggerated arteriolar vasoconstriction, increased sympathetic tone, and impaired vasodilation. ²

SRP has both functional and structural vascular abnormalities, including endothelial dysfunction, heightened sympathetic activity, platelet activation, and vascular remodeling. ² These patients are at higher risk for digital ischemia and ulceration. ² In SSc, for example, up to 95% of patients have RP. ³ For many, RP is a presenting symptom and can be severe and cause significant morbidity. Surveys have shown that RP is the highest ranked SSc‐specific symptom associated with impact on quality of life. ⁴ In SSc, RP can range from unsightly color changes to painful digits to ischemic digits, leading to digital ulcers, gangrene, secondary infection, or amputation.

The general approach to treating RP aims at minimizing attacks, reducing their severity, and, in patients with SRP, preventing tissue damage. Lifestyle changes are recommended, such as avoiding cold environments, tobacco cessation, ⁵ and keeping the core warm. If these measures are inadequate, then adding medication such as calcium channel blockers, phosphodiesterase type 5 inhibitors, alpha‐blockers, angiotensin‐receptor blockers, selective serotonin reuptake inhibitors, and topical nitrates is recommended. There are no US Food and Drug Administration–approved therapies for management of RP.

Although cold temperatures and thermal changes are the most common trigger for episodes of RP, emotional stress accounts for a third of attacks. ³ , ⁶ RP has been shown to lower quality of life, causing pain and frustration when symptoms limit daily tasks and fine motor skills, interfering with hobbies, and straining relationships. ⁷ Ischemic episodes are proposed to be a result of an overactive sympathetic nervous system and release of norepinephrine, which binds α‐adrenoreceptors on vascular smooth muscle, leading to excessive vasoconstriction. ³ Unsurprisingly, rates of depression, stress, and anxiety are higher in individuals with RP. ⁸ , ⁹ Anxiety and depression have been found to be more common in those with SRP compared to PRP. ¹⁰ Lacking coping mechanisms to address anxiety and stress may contribute to the excessive vasoconstriction. ¹¹

Mind–body techniques have been shown to address anxiety, depression, and emotional stress. Guided imagery is a form of meditation that uses internal focused visualization and imaginative content to evoke sensory perceptions to improve well‐being and reduce anxiety. ¹² It incorporates positive guided sentences, music, breathing, and relaxation training. ¹² The objective of our study was to evaluate the feasibility and efficacy of audio‐guided imagery (AGI) intervention on CTD‐associated RP.

PATIENTS AND METHODS

Study design

The study was an open‐label, single‐arm, eight‐week intervention at the University of Pittsburgh. Inclusion criteria were men and women aged 18 years and older who carried a diagnosis of CTD‐associated RP. CTD was diagnosed and treated by a rheumatologist at a university center. Daily doses of immunosuppressive agents, vasodilators, antidepressants, and anxiolytics were required for a patient to be stable for four weeks before baseline. Study patients who met inclusion and exclusion criteria were approached to participate following their regular clinical appointment. They needed a computer or smartphone with access to email to complete electronic surveys. Socioeconomic and educational backgrounds were not collected for this study. Patients already performing daily meditation practices were excluded. The study was approved by the University of Pittsburgh Institutional Review Board (STUDY 21100111).

Intervention

Participants were asked to complete a 10‐minute AGI intervention daily over eight weeks (Figure 1). This was accessed by web link, which recorded the number of minutes used daily.

Figure 1.

Study flow for data obtained during eight‐week audio‐guided imagery intervention. These data were designed to collect information about the patient's emotional and physical well‐being as well as the severity of RP before and after audio‐guided imagery intervention. ASRAP‐SF, Assessment of the Systemic Sclerosis–Associated RP Questionnaire‐Short Form; GAD‐7, Generalized Anxiety Disorder 7; QIDS, Quick Inventory of Depressive Symptomatology; RP, Raynaud phenomenon; SHAQ, Scleroderma Health Assessment Questionnaire.

Outcome measures

All outcome measures were collected at baseline, four weeks, and eight weeks. The primary objective was to assess the impact on RP symptoms. A smartphone app was used to keep an RP diary for one week, in which RP attack frequency, duration, and Raynaud condition score (RCS) were collected. ¹³ Attacks and duration could be collected in real time using a start and stop button. Daily reminders prompted patients to enter their RCS. The SSc‐Associated RP Questionnaire Short Form (ASRAP‐SF) is a validated tool that captures, in several domains, the impact of RP symptoms over the past seven days. ¹⁴ , ¹⁵ Quality‐of‐life secondary outcome measures were assessed using the Scleroderma Health Assessment Questionnaire (SHAQ). The RP visual analog scale (RP‐VAS) was assessed, which was embedded as a single question in the SHAQ. Anxiety was assessed using the Generalized Anxiety Disorder 7 (GAD‐7), ¹⁶ and depression was assessed using the Quick Inventory of Depressive Symptomatology (QIDS). ¹⁷

Statistics

Mean change of survey scores was compared from baseline to week eight in a repeated measures model (ASRAP‐SF and RCS). QIDS scores were compared and analyzed for change only between week zero and week eight with the paired t‐test. For nonparametric variables (SHAQ and GAD‐7), the Wilcoxon signed rank test was used.

RESULTS

Sixteen patients were enrolled (Table 1), with an average age of 55 years old, and 94% were women. Nearly all patients (14 of 16) had SSc‐RP. Of the 16 patients, 14 had consistent recorded meditation times. Two patients were excluded from the eight‐week analysis because they had no recorded meditations; however, their baseline surveys were included in the baseline analysis. All patients with recorded meditations had their baseline and eight‐week surveys analyzed. Study participants performed AGI an average of 42.3 ± 14.59 days and spent an average of 8.4 ± 1.1 minutes on daily AGI. The lowest participation was observed in a participant who practiced for eight days with an average daily duration of six minutes. Patients completed baseline questionnaires from February 7 to March 17, and eight‐week questionnaires were completed between April 1 and May 11, 2022. Of note, more than half the patients completed their questionnaires before April 9. With a small enrollment size and limited time to enroll, it was challenging to control for seasonality. Average monthly temperatures in Pittsburgh during this period were 33 °F in February, 44 °F in March, 50 °F in April, and 61 °F through May 11.

Table 1.

Demographics of enrolled patients with connective tissue disease–associated Raynaud phenomenon^*

Characteristic	n = 16
Age, mean (IQR), y	55 (39–60)
Sex, n (%)
Female	15 (94)
Male	1 (6.3)
Race, n (%)
Arabic	1 (6.3)
Black	1 (6.3)
White	14 (88)
Disease, n (%)
Mixed connective tissue disease	1 (6.3)
Scleroderma	14 (88)
Undifferentiated connective tissue disease	1 (6.3)

^*Characteristics of the study participant population were collected, and the averages were calculated. Most participants were White women with a diagnosis of systemic sclerosis. IQR, interquartile range.

Following eight weeks of the daily online AGI program, the median ASRAP‐SF score significantly decreased from 50.5 (interquartile range [IQR] 47.4–56.4) to 46.1 (IQR 38.6–53.0), with a P value of 0.02 (Table 2), suggesting reduction in RP severity. Similarly, the RCS and RP‐VAS scores also decreased from baseline to eight weeks, similarly suggesting improvement of RP symptoms. The means ± SDs decreased from 2.67 ± 2.44 to 1.54 ± 1.33 (P = 0.04) and from 3.57 ± 2.54 to 2.94 ± 2.23 (P = 0.04), respectively. The SHAQ score also significantly decreased after eight weeks from 0.44 (IQR 0.09–1.03) to 0.13 (IQR 0.00–1.00; P = 0.03). The QIDS score showed the greatest reduction, from 6.31 ± 3.91 to 3.64 ± 3.65 (P = 0.006). Although the GAD‐7 score decreased from a median of 3 (IQR 0–5) to 1 (IQR 0–5), it did not demonstrate a significant difference (P = 0.68).

Table 2.

Patient‐reported outcomes at baseline and eight‐weeks following auditory‐guided imagery^*

Outcome	Baseline (n = 16)	8‐week (n = 14)	Change (n = 14)	P value
ASRAP‐SF, median (IQR)	50.5 (47.4 to 56.4)	46.1 (38.6 to 53.0)	−4.36 (−7.88 to −0.85)	0.02
RCS, mean ± SD	2.67 ± 2.44	1.54 ± 1.33	−1.31 ± 2.10	0.04
RP‐VAS, mean ± SD	3.57 ± 2.54	2.94 ± 2.23	−1.29 ± 1.53	0.05
SHAQ, median (IQR)	0.44 (0.09 to 1.03)	0.13 (0.00 to 1.00)	0.00 (−0.125 to 0)	0.03
GAD‐7, median (IQR)	3 (0 to 5)	1 (0 to 5)	0.00 (−1.75 to 2.50)	0.68
QIDS, mean ± SD	6.31 ± 3.91	3.64 ± 3.65	−2.36 ± 2.71	0.006

^*Study participants demonstrated improvement in five of the six patient‐reported outcome measures in domains that assessed RP severity, participants’ mental health, and physical function. Sixteen patients were enrolled, and their baseline surveys were included. Two patients did not have recorded meditations, so only 14 patients had eight‐week surveys included in the analysis. Bold P values indicate statistical signifiance of < 0.05. ASRAP‐SF, Assessment of the Systemic Sclerosis–Associated RP Questionnaire‐Short Form; GAD‐7, Generalized Anxiety Disorder‐7; IQR, interquartile range; QIDS, Quick Inventory of Depressive Symptomatology; RCS, Raynaud condition score; RP‐VAS, Raynaud phenomenon visual analog scale; SHAQ, Scleroderma Health Assessment Questionnaire.

DISCUSSION

An AGI intervention to reduce the severity and frequency of RP attacks was performed in patients with CTD. Patients completed 10 minutes of AGI every day over an eight‐week period. A daily practice was introduced to help shift ingrained beliefs about RP that may worsen or prolong symptoms. Patients demonstrated significant improvement in all patient‐reported outcomes except GAD‐7. The ASRAP‐SF questionnaire probes the domains of physical symptoms, emotional impact, and impact of RP on daily life. RCS captures the frequency of RP attacks. RP‐VAS directly asks patients to rate their pain level on a numerical scale. SHAQ measures disease status and changes over time. GAD‐7 assesses the severity of anxiety. QIDS is a self‐assessment on depression symptoms. Not only did patients have improved RP episodes, but they also reported improved quality of life and depression, highlighting the strong correlation between less severe and frequent RP attacks and improved mental health. These changes were seen after two months of intervention, and we suspect anxiety would have also shown to be significantly better if the intervention occurred over a longer period.

Guided imagery has been used extensively in oncologic and psychiatric communities to reduce anxiety, depression, emotional stress, and fatigue but has not been systematically employed or studied in patients with autoimmune disease. Biofeedback, a method by which a person gauges their physiologic state to help regulate physical and mental processes, has been used, with most of the literature focusing on PRP. Thermal biofeedback (TBF) is the most studied behavioral treatment and consists of teaching hand‐warming relaxation techniques with the use of temperature sensors to provide real‐time feedback. ¹⁸ Freedman et al showed TBF reduced RP attacks of 67% in the first year and when coupled with cold exposure during training, up to 92% with effects lasting up to three years. ⁶ , ¹⁹ However, in a meta‐analysis looking at eight studies that used biofeedback to actively change behavior as treatment and one that implemented a behavioral intervention, a conclusion could not be reached about the efficacy of behavioral interventions for RP management due to missing data. ²⁰ Behavioral interventions may provide a low‐cost, low‐risk option for individuals with RP, especially in those in whom the standard medications are contraindicated. This study shows that the potential benefits of regular AGI therapy on RP are that it is low risk, low cost, and convenient to perform. In addition, these benefits may suggest improvement beyond the scope of disease and may have positive impact on personal well‐being.

In conclusion, daily AGI appeared to improve RP symptoms, quality of life, and depression in a small pilot study of 16 study patients. A larger study with more patients with CTD and longer duration of intervention is warranted because it would provide more insight between RP and relaxation techniques such as AGI. A limitation of the study is that it has a small sample size. Also, there were technical and logistical issues at the beginning of the study, and a couple of participants did not record their meditations, leading to inconsistency and reduced statistical power. Additional data were not obtained following the completion of the study to know the sustaining effects of AGI on RP, which we would obtain in a larger study. We would design the next study to include a larger enrollment size and consider the seasonality (colder vs warmer months) when implementing AGI with either staggered enrollment over the year or a crossover design.

AUTHOR CONTRIBUTIONS

All authors contributed to at least one of the following manuscript preparation roles: conceptualization AND/OR methodology, software, investigation, formal analysis, data curation, visualization, and validation AND drafting or reviewing/editing the final draft. As corresponding author, Dr. Padilla confirms that all authors have provided the final approval of the version to be published and takes responsibility for the affirmations regarding article submission (eg, not under consideration by another journal), the integrity of the data presented, and the statements regarding compliance with institutional review board/Declaration of Helsinki requirements.

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