Fibromyalgia: one year in review 2022.

Fibromyalgia syndrome (FM) is a chronic widespread pain syndrome characterised by fatigue, sleep disturbances and many idiopathic pain symptoms. The aim of this review is to describe and summarise the most recent findings concerning the diagnosis, aetiopathogenesis and treatment of fibromyalgia syndrome published between January 2021 and January 2022 and appearing on PubMed database. In particular, last year's literature focused on the impact of COVID-19 pandemic on FM patients, on new aetiopathogenetic horizons and the last conclusions about pharmacological and non-pharmacological interventions.

Blood transcriptome and machine learning identified the crosstalk between COVID-19 and fibromyalgia: a preliminary study.

OBJECTIVES: The COVID-19 pandemic caused by SARS-CoV-2 has seriously threatened the human health. Growing evidence shows that COVID-19 patients who recovery will persist with symptoms of fibromyalgia (FM). However, the common molecular mechanism between COVID-19 and FM remains unclear. METHODS: We obtained blood transcriptome data of COVID-19 (GSE177477) and FM (GSE67311) patients from GEO database, respectively. Subsequently, we applied Limma, GSEA, Wikipathway, KEGG, GO, and machine learning analysis to confirm the common pathogenesis between COVID-19 and FM, and screened key genes for the diagnosis of COVID-19 related FM. RESULTS: A total of 2505 differentially expressed genes (DEGs) were identified in the FM dataset. Functional enrichment analysis revealed that the occurrence of FM was intimately associated with viral infection. Moreover, WGCNA analysis identified 243 genes firmly associated with the pathological process of COVID-19. Subsequently, 50 common genes were screened between COVID-19 and FM, and functional enrichment analysis of these common genes primarily involved in immunerelated pathways. Among these common genes, 3 key genes were recognised by machine learning for the diagnosis of COVID-19 related FM. We also developed a diagnostic nomogram to predict the risk of FM occurrence which showed excellent predictive performance. Finally, we found that these 3 key genes were closely relevant to immune cells and screened potential drugs that interacted with the key genes. CONCLUSIONS: Our study revealed the bridge role of immune dysregulation between COVID-19 and fibromyalgia, and screened underlying biomarkers to provide new clues for further clinical research.

The possible onset of fibromyalgia following acute COVID-19 infection.

INTRODUCTION: The exact pathogenesis of fibromyalgia (FM) syndrome is unclear. However, various infectious have been implicated with the development of FM after their acute phase. We aimed to investigate the incidence of FM syndrome among convalesced individuals following hospitalization for Acute Coronavirus Disease-2019 (COVID-19). METHODS: We performed a cross-sectional study on patients who were discharged after COVID-19 hospitalization from the Sheba Medical Center, Israel, between July 2020 to November 2020. A phone interview was performed consisting of the following questionnaires: the Fibromyalgia Survey Diagnostic Criteria Questionnaire, Sense of Coherence Questionnaire to evaluate resilience, and the Subjective Traumatic Outlook Questionnaire to assess the associated psychological aspects of the trauma. The incidence of post-COVID FM was calculated and regression models were performed to identify predictors. RESULTS: The study population consisted of 198 eligible patients who completed the phone interview. The median age was 64 (52-72) and 37% were women. The median follow-up was 5.2 months (IQR 4.4-5.8). The incidence of FM was 15% (30 patients) and 87% (172 patients) had at least one FM-related symptom. Female gender was significantly associated with post-COVID FM (OR 3.65, p = 0.002). In addition, high median Subjective Traumatic Outlook scores and low median Sense of Coherence scores were both significantly associated with post-COVID FM (OR 1.19, p<0.001 and OR 0.92, p<0.001, respectively). CONCLUSIONS: FM is highly prevalent among COVID-19 convalescent patients. Our finding suggests that a significant subjective traumatic experience and a low resilience are highly associated with post-COVID FM.

The effect of novel coronavirus disease-2019 (COVID-19) on fibromyalgia syndrome.

OBJECTIVES: Fibromyalgia syndrome (FM) is a complex disease that is mainly characterised by chronic widespread pain, fatigue and sleep disturbances and may be precipitated or worsened by many stressors. The aim of this study was to observe the behaviour of FM symptoms during the course of coronavirus disease 2019 (COVID-19). METHODS: Patients who had been diagnosed as having FM for ≥3 months were recruited between February and May 2020. The collected data were age, sex, educational level and marital status; height and weight; and the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Status 2019 (FASmod), and the Polysymptomatic Distress Scale (PDS). The patients were divided into those with or without concomitant COVID-19 infection. RESULTS: Eight hundred and ninety-seven (93%) of the 965 patients (881 women [91.3%] and 84 men [8.7%]) were followed up on an outpatient basis because of FM and 68 (7.0%) were either followed up as out-patients or hospitalised because of COVID-19. There was no difference in the sociodemographic data of the two groups, but there were statistically significant between-group differences in the results of the clinimetric tests. The major differences between the score of the items (those with the greatest disease impact) were the following related symptoms: sleep quality (FIQR15), fatigue/energy (FIQR13), pain (FIQR12), stiffness (FIQR14). CONCLUSIONS: The mean total and subdomain scores of all the tests were significantly higher in the patients with COVID-19, which suggests that global FM symptoms are more severe in patients with infection. Further studies of the post-COVID19 patients are being carried out in order to discover whether the worsened symptomatology continues because of their hypersensitised state.

Cost analysis of chronic pain due to musculoskeletal disorders in Chile.

The magnitude of the cost of chronic pain has been a matter of concern in many countries worldwide. The high prevalence, the cost it implies for the health system, productivity, and absenteeism need to be addressed urgently. Studies have begun describing this problem in Chile, but there is still a debt in highlighting its importance and urgency on contributing to chronic pain financial coverage. This study objective is to estimate the expected cost of chronic pain and its related musculoskeletal diseases in the Chilean adult population. We conducted a mathematical decision model exercise, Markov Model, to estimate costs and consequences. Patients were classified into severe, moderate, and mild pain groups, restricted to five diseases: knee osteoarthritis, hip osteoarthritis, lower back pain, shoulder pain, and fibromyalgia. Data analysis considered a set of transition probabilities to estimate the total cost, sick leave payment, and productivity losses. Results show that the total annual cost for chronic pain in Chile is USD 943,413,490, corresponding an 80% to the five diseases studied. The highest costs are related to therapeutic management, followed by productivity losses and sick leave days. Low back pain and fibromyalgia are both the costlier chronic pain-related musculoskeletal diseases. We can conclude that the magnitude of the cost in our country's approach to chronic pain is related to increased productivity losses and sick leave payments. Incorporating actions to ensure access and financial coverage and new care strategies that reorganize care delivery to more integrated and comprehensive care could potentially impact costs in both patients and the health system. Finally, the impact of the COVID-19 pandemic will probably deepen even more this problem.

Prevalence of post-COVID-19 in patients with fibromyalgia: a comparative study with other inflammatory and autoimmune rheumatic diseases.

OBJECTIVES: To determine the prevalence and characteristics of post-COVID-19 (PC) in fibromyalgia (FM) patients. METHODS: Retrospective, multi-centric, observational study, comparing a group of FM patients (FM group) with another group of patients with other rheumatic diseases (RD group). COVID-19 diagnosis was established by positive polymerase chain reaction or antigen during acute infection or by positive antibodies thereafter. We considered PC diagnosis when symptoms remain after COVID-19. We collected the principal characteristics of COVID-19, the severity of fatigue, waking unrefreshed and cognitive impairment, and persistent symptoms. The American College of Rheumatology (ACR) criteria and the Combined Index of Severity in Fibromyalgia (ICAF) were collected in the FM group. RESULTS: RD group (n = 56) had more pneumonia (p = 0.001) and hospital admissions (p = 0.002), but the FM group (n = 78) had a higher number of symptoms (p = 0.002). The percentage of patients with PC was similar between groups (FM group 79.5%; RD group 66.1%, p = 0.081). FM group had more PC symptoms (p = 0.001), more impairment after COVID-19 (p = 0.002) and higher severity of fatigue, waking unrefreshed and cognitive impairment (p <  0.0001). Only loss of smell was more frequent in the FM group (p = 0.005). The FM group with PC (n = 29) showed more severity of the Combined Index of Severity in Fibromyalgia (ICAF) total score and physical factor after COVID-19, while emotional, coping factors and the ACR criteria did not change. CONCLUSIONS: The prevalence of PC in FM patients is similar to RD patients. In FM patients, the presence of PC does not appear to impact the severity of FM.

The relationship between COVID-19 and fibromyalgia syndrome: prevalence, pandemic effects, symptom mechanisms, and COVID-19 vaccines.

On March 11, 2020, the World Health Organization, realizing the level of spread worldwide and the severity of the condition, accepted coronavirus disease 19 (COVID-19) as a pandemic. Subsequently, quarantine conditions were implemented around the world, and these triggered particular results. Like all other individuals, fibromyalgia syndrome (FMS) patients were affected by these conditions. The stress load in pandemic conditions, difficulties in accessing healthcare services, changes in exercise compliance, variations in physiotherapy programs, and remote work conditions all had an impact on FMS patients. Although general expectations were negative, some FMS patients were able to manage the pandemic conditions and even turn them in their favor. This is thought to be due to this patient group having established strategies to cope with stress in the pre-pandemic period, and they had sufficient ability to adapt to changing situations. FMS-related symptoms occur in a subset of individuals following COVID-19. One of the factors is the increased psychological burden after COVID-19. There is evidence that neuroinflammatory pathways affect neuroplasticity in the central nervous system and trigger the onset of FMS-related symptoms. Among the probable mechanisms are alterations in inflammatory and anti-inflammatory pathways. Changes in the autonomic nervous system with the effect of SARS-CoV-2 may induce the emergence of FMS-related symptoms. FMS and COVID-19 can coexist, and FMS may create a tendency to vaccine hesitancy. Future studies should focus on elucidating FMS-related symptoms occurring post-COVID-19. There is a need to determine distinctions between the FMS clinical status that emerged following COVID-19 and the regular patient group in terms of diagnosis, treatment, and follow-up.

The impact of COVID-19 pandemic on mental and physical wellbeing in women with fibromyalgia: a longitudinal mixed-methods study.

OBJECTIVE: The COVID-19 pandemic has strongly influenced psychological and physical health worldwide. The aim of this study was to examine the impact of the pandemic on women with fibromyalgia. METHODS: This mixed methods pilot study explored measures of pain severity and interference, as well as pain catastrophizing and level of fibromyalgia impact among women with fibromyalgia before and during the COVID-19 pandemic in the USA. Fibromyalgia patients completed demographic, pain-related, and other validated psychosocial questionnaires prior to the onset of the COVID-19 pandemic, and then were re-assessed with those questionnaires, as well as a pandemic-related questionnaire assessing the impact of the pandemic on the patients' life, during the pandemic. RESULTS: When comparing data reported before the pandemic to data collected 3-6 months into the pandemic, women with fibromyalgia reported a general worsening of their pain and pain-related symptoms. During the pandemic, pain catastrophizing (p ≤ 0.05) and fibromyalgia impact (p ≤ 0.05) increased significantly compared to before the pandemic. The increase in pain catastrophizing scores was highly correlated with the impact of the pandemic on the participants' ability to cope with pain and on their mental health. Qualitative analysis corroborated the significant impact of the pandemic on patients' mental health, with the vast majority reporting a worsening of their mood. Other impacted domains included anxiety, level of activity and sleep. CONCLUSIONS: Collectively, the pandemic appears to have produced a substantive worsening of pain-related symptomatology among women with fibromyalgia, which should be addressed by targeted interventions.

Physical and mental impact of COVID-19 outbreak on fibromyalgia patients.

OBJECTIVES: Acute or chronic stress may trigger or aggravate symptoms of fibromyalgia (FM). We aimed to evaluate the physical and mental health of fibromyalgia patients during the COVID 19 outbreak and identify protective/risk factors. METHODS: An online survey was published in May 2020, following two months of lockdown due to the COVID 19 outbreak, including questionnaires regarding demographic characteristics, access to medical services, anxiety, depression, life approach, coping strategies, perception of social support, widespread pain index (WPI) and symptoms severity scale (SSS), insomnia severity index (ISI) and patient global assessment. RESULTS: Of the 233 patients included in the study, 98% were forced to discontinue complementary or alternative treatments during lockdown. Up to 30% of responders who had been treated with medical cannabis had to stop due to logistic difficulties and this was associated with significantly higher scores of WPI/SSS (p=0.024). Higher levels of anxiety and depression were significantly correlated with higher levels of pain, sleep disorders and subjective perception of deterioration (p=0.00). Higher scores of social support and positive life approach were correlated with less anxiety and depression (p<0.01), lower levels of pain (p<0.05) and less sleep disturbances (p<0.01). Avoidant coping style was strongly associated to higher levels of pain, sleep disturbances, anxiety, depression, and subjective perception of worsening (p<0.01). CONCLUSIONS: Fibromyalgia patients reported adverse mental and physical outcomes during the COVID-19 outbreak. Factors such as stopping current treatments may play a central role. Social support and a positive life approach appear to be protective.

A better but persistently low health status in women with fibromyalgia during the COVID-19 pandemic: a repeated cross-sectional data analysis.

Multiple overlapping and complementary theoretical arguments suggest that the COVID-19 pandemic could worsen health in fibromyalgia. The aim of this study was to determine mental and physical health in women with fibromyalgia before and during the pandemic. In a 3-sample, repeated cross-sectional design, we analyzed questionnaire data from Dutch women with fibromyalgia, collected in three independent samples: before the COVID-19 pandemic (2018; n = 142) and during the first acute (2020; n = 304) and prolonged (2021; n = 95) phases of the pandemic. Eight dimensions of mental and physical health were assessed using The RAND 36-Item Short Form Health Survey (RAND SF-36). Compared to norm group data, both before and during the pandemic, women with fibromyalgia showed high levels of fatigue and pain and low levels of general health, social functioning, physical functioning, role physical functioning (d > 1.2, very large effect sizes), role emotional functioning, and mental health (0.71 < d < 1.2, medium to large effect sizes). Contrary to theoretical expectation, levels at five health variables before vs. during the pandemic did not differ (p > 0.05), and levels of pain (p < 0.001), role physical functioning (p < 0.001), and physical functioning (p = 0.03) (0.014 ≤ pη2 ≤ 0.042, small effect sizes) reflected a healthier status during than before the pandemic. These findings indicate a somewhat better but persistently low health status in women with fibromyalgia during the pandemic. This suggests that the pandemic may include changed circumstances that are favorable for some women with fibromyalgia.

Telemedicine in the Management of Patients with Rheumatic Disease during COVID-19 Pandemic: Incidence of Psychiatric Disorders and Fibromyalgia in Patients with Rheumatoid Arthritis and Psoriatic Arthritis.

The management of patients with immuno-rheumatological diseases has profoundly changed during the COVID-19 pandemic and telemedicine has played an important role in the disease follow-up. In addition to monitoring disease activity and any adverse events, especially infectious events, assessing the psychological situation of the patient can be fundamental. Furthermore, COVID-19 has a serious impact on mental health and, since the beginning of the pandemic, a significantly higher incidence of anxiety disorders and depressive symptoms especially in younger people was observed. In this study, we evaluated the incidence of depressive disorders, anxiety, and fibromyalgia (FM) in our patients with rheumatoid arthritis and psoriatic arthritis during the lockdown period due to the COVID-19 pandemic and we validate the use of telemedicine in the clinical management of these patients. Mental and physical stress during the COVID-19 pandemic can greatly worsen FM symptoms and intensify patients' suffering without a clinical flare of the inflammatory disease for patients affected by rheumatoid arthritis. Telemedicine has allowed us to identify patients who needed a face-to-face approach for therapeutic reevaluation even if not related to a flare of the inflammatory disease. Even if our data does not allow us to draw definitive conclusions regarding the effectiveness of telemedicine as greater than or equal to the standard face-to-face approach, we continue to work by modifying our approach to try to ensure the necessary care in compliance with safety and, optimistically, this tool will become an important part of rheumatic disease management.

COVID-19 associated hospitalization in 571 patients with fibromyalgia-A population-based study.

OBJECTIVE: To identify predicators of patients with fibromyalgia (FM) that are associated with a severe COVID-19 disease course. METHODS: We utilized the data base of the Clalit Health Services (CHS); the largest public organization in Israel, and extracted data concerning patients with FM. We matched two subjects without FM to each subject with FM by sex and age and geographic location. Baseline characteristics were evaluated by t-test for continuous variables and chi-square for categorical variables. Predictors of COVID-19 associated hospitalization were identified using univariable logistic regression model, significant variables were selected and analyzed by a multivariable logistic regression model. RESULTS: The initial cohort comprised 18,598 patients with FM and 36,985 matched controls. The mean age was 57.5± 14.5(SD), with a female dominance of 91%. Out of this cohort we extracted the study population, which included all patients contracted with COVID-19, and consisted of 571 patients with FM and 1008 controls. By multivariable analysis, the following variables were found to predict COVID-19 associated hospitalization in patients with FM: older age (OR, 1.25; CI, 1.13-1.39; p<0.001), male sex (OR, 2.63; CI, 1.18-5.88; p<0.05) and hypertension (OR, 1.75; CI, 1.04-2.95; p<0.05). CONCLUSION: The current population-based study revealed that FM per se was not directly associated with COVID-19 hospitalization or related mortality. Yet classical risk factors endangering the general population were also relevant among patients with FM.

COVID-19 pandemic and exercising: a cross-sectional study with 1156 patients with fibromyalgia.

OBJECTIVE: The aim of this study was to analyze the effects of pandemic in the exercising practice and impact of the disease in patients with Fibromyalgia. METHODS: This is a cross-sectional, Internet-based survey answered by 1156 individuals with Fibromyalgia diagnosis. Questions were on epidemiology, social distancing habits, and exercise practice before and after COVID-19 pandemic, including subtypes of exercises (for resistance, flexibility, balance, and strength). The Fibromyalgia Impact Questionnaire was applied. RESULTS: In the whole sample, 57.7% of individuals practiced exercises before pandemic; during pandemic, only 34.8% practiced and 39.6% left this practice. Among those taking quarantine (n=440), 52.9% used to do exercises prior to pandemic; in the pandemic, 28.1% (reduction of 53.2%). The median Fibromyalgia Impact Questionnaire among those who practiced exercises in the pandemic was 73.6 (61.1-83.2) and that among those who did not was 80.4 (71.9-86.9), with p<0.0001. The Fibromyalgia Impact Questionnaire did not change according to the type of physical exercise (p=0.27). CONCLUSION: A high proportion of patients with Fibromyalgia stopped exercising during COVID-19 pandemic; as a result, the impact of the disease during this period was worse among those not practicing exercises.

Efficacy of the FIBROWALK Multicomponent Program Moved to a Virtual Setting for Patients with Fibromyalgia during the COVID-19 Pandemic: A Proof-of-Concept RCT Performed Alongside the State of Alarm in Spain.

FIBROWALK is a multicomponent program including pain neuroscience education, therapeutic exercise, cognitive behavioral therapy and mindfulness training that has recently been found to be effective in patients with fibromyalgia (FM). This RCT started before the COVID-19 pandemic and was moved to a virtual format (i.e., online videos) when the lockdown was declared in Spain. This study is aimed to evaluate the efficacy of a virtual FIBROWALK compared to Treatment-As-Usual (TAU) in patients with FM during the first state of alarm in Spain. A total of 151 patients with FM were randomized into two study arms: FIBROWALK plus TAU vs. TAU alone. The primary outcome was functional impairment. Secondary outcomes were kinesiophobia, anxiety and depressive symptomatology, and physical functioning. Differences between groups at post-treatment assessment were analyzed using Intention-To-Treat (ITT) and completer approaches. Baseline differences between clinical responders and non-responders were also explored. Statistically significant improvements with small-to-moderate effect sizes were observed in FIBROWALK+TAU vs. TAU regarding functional impairment and most secondary outcomes. In our study, the NNT was 5, which was, albeit modestly, indicative of an efficacious intervention. The results of this proof-of-concept RCT preliminarily support the efficacy of virtual FIBROWALK in patients with FM during the Spanish COVID-19 lockdown.

Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey.

OBJECTIVE: Postacute COVID-19 syndrome (PACS) is an emerging entity characterised by a large array of manifestations, including musculoskeletal complaints, fatigue and cognitive or sleep disturbances. Since similar symptoms are present also in patients with fibromyalgia (FM), we decided to perform a web-based cross-sectional survey aimed at investigating the prevalence and predictors of FM in patients who recovered from COVID-19. METHODS: Data were anonymously collected between 5 and 18 April 2021. The collection form consisted of 28 questions gathering demographic information, features and duration of acute COVID-19, comorbid diseases, and other individual's attributes such as height and weight. The American College of Rheumatology (ACR) Survey Criteria and the Italian version of the Fibromyalgia Impact Questionnaire completed the survey. RESULTS: A final sample of 616 individuals (77.4% women) filled the form 6±3 months after the COVID-19 diagnosis. Of these, 189 (30.7%) satisfied the ACR survey criteria for FM (56.6% women). A multivariate logistic regression model including demographic and clinical factors showed that male gender (OR: 9.95, 95% CI 6.02 to 16.43, p<0.0001) and obesity (OR: 41.20, 95% CI 18.00 to 98.88, p<0.0001) were the strongest predictors of being classified as having post-COVID-19 FM. Hospital admission rate was significantly higher in men (15.8% vs 9.2%, p=0.001) and obese (19.2 vs 10.8%, p=0.016) respondents. CONCLUSION: Our data suggest that clinical features of FM are common in patients who recovered from COVID-19 and that obesity and male gender affect the risk of developing post-COVID-19 FM.