Abstract
Objective To identify the frequency and relative importance of symptoms experienced by adults with fibromyalgia (FM) and determine factors associated with a higher disease burden.
Methods We conducted semistructured interviews with 15 participants with FM, collecting 1479 quotes regarding the symptomatic burden of FM. We then performed an international cross-sectional study involving 1085 participants with FM to determine the prevalence and relative importance (scale 0-4) of 149 symptoms representing 14 symptomatic themes. We performed subgroup analysis to determine how age, sex, disease duration, medication use, employment status, change in employment status, missing work due to FM, and ability level are related to symptomatic theme prevalence.
Results The symptomatic themes with the highest prevalence in FM were pain (99.8%), muscle tenderness (99.8%), and fatigue (99.3%). The symptomatic themes that had the greatest effect on patients’ lives were related to fatigue (2.88), pain (2.85), muscle tenderness (2.79), and impaired sleep and daytime sleepiness (2.70). Symptomatic theme prevalence was most strongly associated with the modified Rankin Scale level of disability, disability status, and change in employment status (on disability vs not on disability).
Conclusion Participants with FM identify a variety of symptoms that significantly affect their daily lives. Many of these symptoms, such as fatigue, sleep disturbance, and activity limitation, are life-altering and not related to traditional diagnostic criteria. Symptom prevalence in this population varies across subgroups based on demographic categories and disability status.
Although chronic, widespread pain is the defining feature of fibromyalgia (FM), the full impact of FM’s symptomatic burden includes a diffuse, multifocal spectrum of symptoms, such as sleep disturbances, fatigue, anxiety, depression, headaches, and reduced function.1 FM affects an estimated 2% to 4% of the general population, presenting in individuals of all ages and genders.2 However, like many chronic pain disorders, FM disproportionately affects women.2
The limited understanding of FM’s etiology and a lack of diagnostic biomarkers have impeded the development of objective testing and therapeutic innovation. An FM diagnosis is achieved based on a process of both exclusion and inclusion. Because FM symptoms overlap with multiple medical conditions for which there are verifiable pathology, a typical diagnostic journey begins with exhaustive “ruling out” testing.3 Consequently, FM often involves more frequent visits to general practitioners and specialists, and increased usage of laboratory and imaging tests and pain relief medications, compounding the economic and financial burden of individuals affected by FM.4 The mean total time to FM diagnosis is 6.42 (SD 3.57) years; however, the mean time when treated by the same primary physician as at diagnosis is 3.75 (SD 3.26) years.5 In addition to longer mean diagnosis times if seeing multiple medical practitioners, comorbidity, younger patient age, and older physician age have also been associated with longer time to diagnosis.5
In studies examining health-related quality of life, it has been shown that individuals with FM have a worse health status than those with other chronic diseases, such as osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus, myocardial infarction, and chronic obstructive pulmonary disease.6 A 2022 study exploring the most important influences on the quality of life of individuals with FM found that anxiety and depression had the most negative effect, followed by pain and sleep quality. Nearly 50% of the variance in their linear regression analysis was accounted for by anxiety and depression, highlighting psychological distress as a primary target for effective FM therapies.7
The specific objective of our research was to use direct patient input to determine the prevalence and relative importance of the varied symptoms and issues that occur in FM. In addition, we sought to determine how disability status and other demographic features are associated with the occurrence of these issues.
METHODS
Study participants. Participants consisted of individuals aged ≥ 18 years with FM. Participants were recruited from the Fibromyalgia Association registry. Participants had a clinical diagnosis of FM and had the capacity to give informed consent.
Study design
• Semistructured qualitative interviews. We conducted semistructured qualitative interviews with participants. Eligible individuals who were interested in participating were subsequently contacted by a member of the study team and gave consent by telephone. During the consent process, detailed information regarding the purpose of the study was provided, and the study team informed the participants that they would be asking questions to determine those symptoms that are most impactful to participants’ lives. Study interviews were performed by 1 of 2 clinical research coordinators with prior training in performing qualitative interviews and qualitative coding (JW and SR). Using open-ended questions from a comprehensive interview guide, participants with FM were asked to identify the symptoms that have the greatest effect on their lives. All interviews were conducted by telephone and were audio-recorded using Zoom (Zoom Video Communications), a Health Insurance Portability and Accountability Act (HIPAA)-compliant conferencing software that is licensed and approved by the University of Rochester’s IT security team. All interviews were then transcribed, coded, and analyzed using a qualitative framework technique, triangulation, and a multiple investigator consensus approach.8 Quotes that were common were used to ascertain potentially relevant symptoms in the FM population. These symptoms were then categorized into symptomatic themes (ie, concepts representing a group of like symptoms) using the World Health Organization’s framework of health and FM-specific health domains.9
• International cross-sectional survey study. We performed an online, international cross-sectional study to identify the symptoms and issues of greatest importance to adults with FM. We administered the cross-sectional survey electronically using Research Electronic Data Capture (REDCap), a HIPAA-compliant electronic data capture system. The survey link was distributed by the Fibromyalgia Association and made available online from February 25 to March 26, 2021. Respondents were asked to read an information letter before consenting to complete the survey.
The survey included questions regarding (1) demographics; (2) an individual’s clinical state; (3) potential symptoms of importance, as identified during qualitative interviews; and (4) more generalized symptomatic themes, as identified through analysis of the qualitative interviews.
The survey inquired about 149 symptoms, including 14 symptomatic theme questions and 15 demographic/clinical questions. Participant responses were included in the data analysis if the participant completed at least 1 demographic question and 1 survey question.
Question selection was established using a consensus approach by our research team. For each individual symptom question, the survey inquired, “How much does the following impact your life now?” Participants were provided a 6-point Likert-type scale with the following response options: (1) I do not experience this; (2) I experience this, but it does not affect my life; (3) it affects my life a little; (4) it affects my life moderately; (5) it affects my life very much; (6) it affects my life severely. Participants were given the option to decline answering any demographic or symptom questions. Upon completion of the survey, participants were asked to list and rate the severity of any symptoms that were not included in the survey. The format of this survey has previously been used and described during studies of other neurologic and nonneurologic populations.10-19
Standard protocol approvals, registrations, and patient consent. All aspects of this research were approved by the University of Rochester Research Subjects Review Board. Prior to their completion of the study interview or survey, all interview participants and survey participants were provided with a detailed information letter describing the research study. Qualitative interview participants provided verbal consent over the phone prior to participation, and cross-sectional survey study participants provided electronic consent through the online REDCap platform.
Statistical analysis. For the cross-sectional sample cohort, we calculated the prevalence of each symptom and theme. Life impact scores (a metric with a range of 0-4 that measures the relative importance of each symptom to a participant) were generated for each symptom and theme based on all participants who reported that they experience the symptom or theme. Numerical values were assigned to each response as follows: 0 = the patient experiences the symptom, but it does not affect the patient’s life; 1 = the symptom affects the patient’s life a little; 2 = the symptom affects the patient’s life moderately; 3 = the symptom affects the patient’s life very much; and 4 = the symptom affects the patient’s life severely. The responses from participants for a particular symptom or theme were averaged to get an average life impact score. Additionally, a population impact score for each symptom was generated by multiplying the prevalence and average life impact score of the symptom. The possible range for this score was also 0-4, with a value of 4 representing a symptom that affects all individuals with FM at the highest level of severity. We have previously described and used this methodology for other neurologic and nonneurologic conditions.10-19
We determined the prevalence and average life impact of each symptom and symptomatic theme for the entire sample as well as for select subgroups. We used Fisher exact test to compare the prevalence of each theme across the different subgroups. Statistical significance was defined as a value of P < 0.05. To correct for multiple comparisons, the Benjamini-Hochberg procedure was used with a false discovery rate of 0.05 and 238 test statistics. As outlined by this method, the P values for each data set were sorted from smallest to largest, and the largest value of i such that P(i) ≤ 0.05, i/238 was determined. The null hypotheses associated with the P values P(1), …, P(i) were rejected, resulting in 36 discoveries.
Subgroup analyses were conducted by employment status (on disability vs not on disability), belief of cause of FM (physical/emotional trauma vs not related to trauma, and not related to trauma vs I don’t know), change in employment status (yes vs no, and no vs I don’t know), modified Rankin Score (mRS) level of disability (moderate, moderately severe, or severe disability vs no significant or slight disability), patient age (above vs on or below the median), missed work due to FM (yes vs no), disease duration (above vs on or below the median), use of acupuncture therapy (yes vs no), use of aqua therapy (yes vs no), use of myofascial release therapy (yes vs no), use of physical therapy (yes vs no), use of medicine (yes vs no), use of antidepressants (yes vs no), use of antiinflammatories (yes vs no), and use of medicinal cannabis (yes vs no).
RESULTS
Semistructured qualitative interviews. We conducted interviews with 15 adults aged ≥ 18 years with FM who were identified and recruited by the Fibromyalgia Association. Five participants were male (33.3%) and 10 were female (66.7%). The mean age of the participants was 54 (SD 14) years, with a range from 20-76 years. From the participants with FM, we obtained and analyzed 1479 direct quotes identifying individual symptoms of importance. One hundred forty-nine symptoms of importance representing 14 symptomatic themes were selected to be included in a cross-sectional survey.
International cross-sectional study of individuals with FM. One thousand eighty-five participants with FM participated in our international cross-sectional survey study via REDCap. In total, participants answered > 172,000 questions regarding symptoms. Percentages of demographic and clinical characteristics of the study population were normalized based upon the number of participants who answered each question. The participant mean age was 58.5 (SD 11.1) years, with a range from 19 to 89 years. Participants were predominantly from the US (88.45%), female (95.28%), White (93.75%), non-Hispanic (95.12%), and had a mean age of diagnosis of 39.9 (SD 10.3) years. Approximately 60% of participants indicated they had experienced symptoms for > 20 years, > 56% cited missing work, and 89.41% reported having some level of disability due to their FM. Nearly 70% of the participants experienced an employment status change due to their FM, and more than one-third of participants indicated being on disability or not working. Approximately half of respondents (54.18%) attributed the onset of their FM to the experience of a trauma, with 51.03% of those participants citing a trauma that was both emotional and physical in nature. The majority of participants (80.15%) indicated they take medications for their FM, with antiinflammatories (36.90%), medicinal cannabis (17.84%), and antidepressants (10.22%) being the most prevalent medications taken. Over one-quarter of participants (27.67%) indicated engaging in aqua therapy, and 18.48% reported engaging in physical therapy. Collectively, only 27.3% of participants indicated using acupuncture, massage therapy, myofascial release therapy, occupational therapy, or attending a pain management clinic. Details regarding the demographics of the survey respondents are provided in Table 1.
Demographic and clinical characteristics of study participants.
Prevalence of symptomatic themes and symptoms. The symptomatic themes with the highest prevalence in our cross-sectional study sample were pain (99.8%), muscle tenderness (99.8%), and fatigue (99.3%; Figure 1). The symptoms with the highest prevalence were decreased energy (99.5%), sore or achy muscles (99.4%), and tired muscles (99.3%). A comprehensive list of the prevalence of each symptom is provided in Supplementary Table S1 (available from the authors upon request).
Prevalence and average impact of symptomatic themes in fibromyalgia.
Average life impact of symptomatic themes and symptoms. The symptomatic themes with the highest average life impact scores (range 0-4) in our cross-sectional study cohort were fatigue (2.88), pain (2.85), and muscle tenderness (2.79; Figure 1). The individual symptoms identified as having the highest average life impact scores were decreased energy (3.00), feeling worn out (2.96), and feeling drained (2.95). Average life impact scores for all symptoms are provided in Supplementary Table S1 (available from the authors upon request).
Population impact of symptomatic themes and symptoms. The symptomatic themes with the highest population impact scores reported by individuals with FM were fatigue (2.86), impaired sleep and daytime sleepiness (2.84), and muscle tenderness (2.79). The individual symptoms with the highest population impact scores were decreased energy (2.98), feeling worn out (2.93), and feeling drained (2.91).
Subgroup analysis of symptomatic theme prevalence by demographic and clinical characteristics in individuals with FM. After correcting for multiple comparisons, several symptomatic themes differed in prevalence between demographic and clinical subgroups. Participants younger than the median age of 59 years old were more likely to report headaches and difficulty thinking compared to older participants. Those with a disease duration less than the median of 40 years were more likely to have headaches than those whose disease duration was greater than the median (Table 2A).
Prevalence of symptomatic themes by demographic and clinical subgroups: age and duration of disease.
When analyzing the sample by disability status, those who were on disability reported a higher prevalence in 6 of 14 symptomatic themes: emotional issues, difficulty thinking, limitations with mobility or walking, decreased performance in social situations, numbness, and hearing difficulties. Level of disability, measured by mRS, was associated with the prevalence of 8 of 14 symptomatic themes. Individuals who reported having a moderate, moderately severe, or severe disability level indicated a higher prevalence of emotional issues, difficulty thinking, inability to do activities, gastrointestinal (GI) issues, limitations with mobility or walking, decreased performance in social situations, numbness, and hearing difficulties compared to those individuals who indicated having no significant disability or slight disability (Table 2B).
Prevalence of symptomatic themes by demographic and clinical subgroups: disability status and level of disability.
Participants who indicated experiencing an employment status change due to their FM reported a higher prevalence in 7 of 14 symptomatic themes: emotional issues, difficulty thinking, limitations with mobility or walking, decreased performance in social situations, numbness, inability to do activities, and GI issues. There were no statistically significant differences among those participants who did not experience an employment status change vs those who did not know if they had an employment status change. Missed work due to FM was associated with a higher prevalence of inability to do activities and decreased performance in social situations (Table 2C).
Prevalence of symptomatic themes by demographic and clinical subgroups: employment status change and missed work due to FM.
Individuals with FM reporting they used acupuncture did not reveal any statistically significant differences compared to those who did not use acupuncture. Those who participated in aqua therapy revealed a higher level of limitations with mobility and walking and decreased performance in social situations compared to those who did not do aqua therapy (Table 2D). There were no statistically significant differences between those who used myofascial release therapy vs those who did not and no difference in those who used physical therapy vs those who did not (Table 2E).
Prevalence of symptomatic themes by demographic and clinical subgroups: therapy use (acupuncture and aqua therapy).
Prevalence of symptomatic themes by demographic and clinical subgroups: therapy use (myofascial release and physical therapy).
The use of medication for FM symptoms was not associated with a higher or lower frequency of any symptomatic themes. Individuals with FM who took antidepressants indicated a higher level of difficulty thinking vs those who did not take antidepressants (Table 2F). There were no statistically significant differences between those who took antiinflammatories vs those who did not, or between those who used medicinal cannabis vs those who did not (Table 2G).
Prevalence of symptomatic themes by demographic and clinical subgroups: medication use (any medication and antidepressants).
Prevalence of symptomatic themes by demographic and clinical subgroups: medication use (antiinflammatories and medicinal cannabis).
Individuals who reported believing that their FM onset was due to a physical/emotional trauma vs those who did not believe their FM was due to trauma indicated experiencing emotional issues, GI issues, decreased performance in social situations, and numbness at a higher prevalence. Those who did not believe the onset of their FM was due to trauma revealed lower levels of GI issues, limitations with mobility and walking, and numbness than those who did not know if their FM was due to trauma (Table 2H).
Prevalence of symptomatic themes by demographic and clinical subgroups: belief in FM onset being due to physical or emotional trauma.
DISCUSSION
The Patient-Reported Impact of Symptoms in Fibromyalgia (PRISM-FM) study provides novel, large-scale patient data regarding the polysymptomatic disease burden faced by individuals with FM. The multisystem influence of this disease is demonstrated by the fact that over 98% of participants indicated experiencing 5 of the 14 symptomatic themes. Twelve of the 14 symptomatic themes were experienced by more than 90% of all participants, with only numbness and hearing difficulties experienced by fewer than 90% of participants. Symptoms experienced by over 99% of participants included decreased energy, tired muscles, feeling worn out, stiffness, and sore or achy muscles. Using a threshold of 98% prevalence or higher expands this list to 13 symptoms, including impaired endurance, fatigue interfering with activities, decreased stamina, exhaustion, muscle fatigue, feeling drained, back pain, and trigger points. The full burden of FM is not only measured by the quantity and intensity of these symptoms but also by their duration, as more than 60% of respondents indicated having experienced symptoms for greater than 20 years.
The debilitating nature of this disease can also be seen by nearly 70% of participants noting a change in employment status due to FM. Employment status change due to FM was associated with statistically significant higher prevalence of 7 symptomatic themes. Over 56% of participants indicated missing work each week due to their FM symptoms, with the majority of those who miss work (39.5%) missing up to 10 hours a week. Participants who reported missing work were further characterized by an inability to do activities and decreased performance in social situations.
The data from this research contributes to knowledge regarding participant beliefs on the cause of onset of FM as well as understanding participants’ family histories of FM. With over 40% of participants indicating having one or more blood relatives with FM, future research is needed to determine the role of family history on the risk of developing FM.
More than half of participants responded that they believe their FM onset was due to a physical, emotional, or physical and emotional trauma. Among those, just over 50% believed it was both a physical and emotional trauma. Subgroup analysis further demonstrated an association between those who believed their onset was due to trauma and higher rates of emotional issues, GI issues, decreased performance in social situations, and numbness.
A key inquiry made by our research was regarding the use of medication and therapy for FM symptoms. Over three-quarters of respondents (80.15%) reported taking medication to treat their FM, with 36.90% of those respondents using antiinflammatories, 17.84% using medicinal cannabis, and 10.22% taking antidepressants. Following our corrections for multiple comparisons, the use of medication (yes vs no) to treat FM symptoms did not reveal statistically significant reductions with any of the symptomatic themes. The use of antidepressants revealed an association with increased difficulty thinking, a common side effect for many medications in this class. Aqua therapy was the most commonly used therapy, used by 27.67% of participants, followed by physical therapy, used by 18.48% of respondents. An association was shown between those who use aqua therapy and a higher prevalence of limitations with mobility and walking and decreased performance in social situations. Although it is suspected that those with problems walking and/or social issues may seek out aqua therapy at a higher rate, additional research is needed to determine the exact relationship between these occurrences.
This research importantly provides patient-centered information on the most impactful therapeutic targets of a disease characterized by a multitude of symptomatic domains. We acknowledge several limitations associated with this research. Our large sample of people with FM who participated in this cross-sectional study may not fully represent the general population of those with FM. Prior research has shown that FM occurs in a clinical population at a female:male ratio of 8-10:1; however, our cross-sectional study sample was 95% female.20 Our sample indicated that participants had, on average, a higher education level: only 32.4% of our participants had not graduated from college, whereas 87.7% of people reporting an FM diagnosis had not graduated from college, according to data collected from the 2012 National Health Interview Study (NHIS).21 Further, 2012 NHIS data indicated 55.8% of their sample was unable to work, whereas only 35.23% of our sample reported being on disability or unable to work. Despite this discrepancy, 69.81% of our cross-sectional sample reported having experienced a change in their employment status due to their FM. Regardless of potential disagreement in the demographic characteristics of our cohort vs other FM study cohorts, it is worthwhile to point out that our sample size exceeded both comparator samples cited. Further, given the expense and complexity of achieving an FM diagnosis, it is possible that all our participants with self-reported FM would not have met formal diagnosis criteria for FM. Last, due to our survey being conducted online, it is possible that individuals with limited internet access due to technical or socioeconomic factors were underrepresented in our sample.
This research contributes novel, large-scale data that can meaningfully increase clinician knowledge regarding FM’s disease burden, which is critical to diagnostic advancement. These data can also guide therapeutic innovation that addresses the most impactful patient-identified symptoms. In the absence of verifiable pathology, it is imperative for the clinical and research community to both accept and value the experience and expertise of individuals with FM to inform effective treatments and reduce patient biopsychosocial distress caused by living with a medically unexplained condition.
Footnotes
CH receives royalties for the use of multiple disease specific instruments; has provided consultation to Biogen, Ionis, aTyr Pharma, AMO Pharma, Acceleron, Cytokinetics, Expansion Therapeutics, Harmony Biosciences, Regeneron, Astellas, AveXis, Recursion, IRIS Medicine, Takeda, Scholar Rock, Avidity Biosciences, Novartis, SwanBio Therapeutics, Neurocrine Biosciences, and the Marigold Foundation; receives grant support from the Department of Defense, Duchenne UK, Parent Project Muscular Dystrophy, Recursion, Swan Bio Therapeutics, National Institute of Neurological Disorders and Stroke, Muscular Dystrophy Association, the Friedreich’s Ataxia Research Alliance, Cure Spinal Muscular Atrophy, Michael J. Fox Foundation, and the Amyotrophic Lateral Sclerosis Association; and is the director of the University of Rochester Center for Health + Technology. The remaining authors declare no conflicts of interest relevant to this article.
- Accepted for publication December 19, 2023.
- Copyright © 2024 by the Journal of Rheumatology
REFERENCES
DATA AVAILABILITY
Additional anonymized data not included in the article or supplemental figures can be obtained through request to the corresponding author.
