Category: Fibromyalgia

Prevalence of fibromyalgia 10 years after infection with Giardia lamblia: a controlled prospective cohort study

Abstract:

Objectives: To investigate whether acute infection with Giardia lamblia is associated with fibromyalgia 10 years after infection and whether fibromyalgia is associated with irritable bowel syndrome (IBS) and chronic fatigue (CF) in this setting.

Methods: A cohort study was established after an outbreak of G. lamblia in Bergen, Norway, 2004. Laboratory-confirmed cases and a matched control group were followed for 10 years. The main outcome was fibromyalgia 10 years after giardiasis, defined by the 2016 revisions of the fibromyalgia diagnostic criteria using the Fibromyalgia Survey Questionnaire (FSQ).

Results: The prevalence of fibromyalgia was 8.6% (49/572) among Giardia exposed compared to 3.1% (21/673) in controls (p<0.001). Unadjusted odds for having fibromyalgia was higher for Giardia exposed compared to controls (odds ratio (OR): 2.91, 95% confidence interval (CI): 1.72, 4.91), but adjusted for IBS and CF it was not (OR: 1.05, 95% CI: 0.57, 1.95). Among participants without CF the odds for fibromyalgia was 6.27 times higher for participants with IBS than those without (95% CI: 3.31, 11.91) regardless of exposure. Among participants without IBS the odds for fibromyalgia was 4.80 times higher for those with CF than those without (95% CI: 2.75, 8.37).

Conclusions: We found a higher prevalence of fibromyalgia among Giardia exposed compared to controls 10 years after the acute infection. Fibromyalgia was strongly associated with IBS and CF, and the difference between the exposed and controls can be attributed to the high prevalence of IBS and CF among the Giardia exposed. Notably, this study was not designed to establish causality between Giardia exposure and the outcomes.

Source: Hunskar GS, Rortveit G, Litleskare S, Eide GE, Hanevik K, Langeland N, Wensaas KA. Prevalence of fibromyalgia 10 years after infection with Giardia lamblia: a controlled prospective cohort study. Scand J Pain. 2021 Oct 21;22(2):348-355. doi: 10.1515/sjpain-2021-0122. PMID: 34679267. https://www.degruyter.com/document/doi/10.1515/sjpain-2021-0122/html (Full text)

Clinical overlap between fibromyalgia and myalgic encephalomyelitis. A systematic review and meta-analysis

Abstract:

Myalgic encephalomyelitis is an illness characterized by profound malaise after mental or physical effort occurring in patients already suffering from constant fatigue. On the other hand, widespread pain and widespread allodynia are the core fibromyalgia clinical features. There is controversy on these two syndromes alikeness. Through the years, different diagnostic and/or classification criteria have been put forward to appraise both fibromyalgia and myalgic encephalomyelitis. The epidemiology of these two illnesses, and their overlap, may vary accordingly to the used definition. The most recent Wolfe et al. 2016 fibromyalgia diagnostic criteria incorporates three myalgic encephalomyelitis features including fatigue, waking unrefreshed and dyscognition. The objective of this meta-analysis was to define the clinical overlap between fibromyalgia and myalgic encephalomyelitis based on a systematic literature review.

Methods: PubMed, Embase, Lilacs, and Cochrane data bases were searched on January 25, 2021 linking the medical subject heading “Fibromyalgia” to the following terms “chronic fatigue syndrome”, “myalgic encephalomyelitis” and “systemic exertion intolerance disease”. Our review included all original articles in which the clinical overlap between fibromyalgia and myalgic encephalomyelitis could be quantified based on recognized diagnostic or classification criteria. Articles scrutiny and selection followed the PRISMA guidelines. Each study quality was assessed according to GRADE recommendations. The global clinical overlap was calculated using a fixed effect model with inverse variance-weighted average method.

Results: Twenty one publications were included in the meta-analysis. Reviewed studies were highly dissimilar in their design, objectives, sample size, diagnostic criteria, and/or outcomes yielding a 98% heterogeneity index. Nevertheless, the clinical overlap between fibromyalgia and myalgic encephalomyelitis was a well defined outcome that could be reliably calculated despite the high heterogeneity value. All reviewed publications had moderate GRADE evidence level. Most evaluated articles used the old 1990 Wolfe et al. fibromyalgia diagnostic criteria. Myalgic encephalomyelitis and fibromyalgia diagnoses overlapped in 47.3% (95% CI: 45.97-48.63) of the reported cases.

Conclusion: This meta-analysis found prominent clinical overlap between fibromyalgia and myalgic encephalomyelitis. It seems likely that this concordance would be even higher when using the most recent Wolfe et al. 2016 fibromyalgia diagnostic criteria.

Source: Ramírez-Morales R, Bermúdez-Benítez E, Martínez-Martínez LA, Martínez-Lavín M. Clinical overlap between fibromyalgia and myalgic encephalomyelitis. A systematic review and meta-analysis. Autoimmun Rev. 2022 Jun 8:103129. doi: 10.1016/j.autrev.2022.103129. Epub ahead of print. PMID: 35690247. https://pubmed.ncbi.nlm.nih.gov/35690247/

Mechanistic factors contributing to pain and fatigue in fibromyalgia and ME/CFS: autonomic and inflammatory insights from an experimental medicine study

Abstract:

Background: Fibromyalgia and ME/CFS are multifaceted conditions with overlapping symptoms(1); the pathoaetiological mechanisms are complex and debated(2), however there is a strong association with features of hereditary disorders of connective tissue (hypermobility) and autonomic and inflammatory abnormalities (1,2).

Objectives: To determine potential autonomic and inflammatory mechanisms of pain and fatigue in fibromyalgia and ME/CFS

Methods: After excluding participants with WCC higher than 10 (suggesting acute infection) baseline markers of inflammation (CRP and ESR) were available for 60 patients with confirmed diagnoses of Fibromyalgia and/ or ME/CFS and 23 matched controls. Participants then underwent full research diagnostic evaluation including a hypermobility assessment(1) and autonomic challenge (60 degree head up tilt, ISRCTN78820481). Subjective pain and fatigue were assessed before and after challenge (VAS). Linear regression models were used to explore predictors, with adjustment for confounders as appropriate. Mediation analyses (looking for mechanistic effects) were conducted according to the method of Hayes (3) and mediation considered significant if bootstrapped confidence intervals of the estimated indirect effect did not cross zero. In these mediation analyses predictor variable was group membership (patient or control), outcome variable was change in 1)pain and 2)fatigue induced by challenge and mediatiors 1)no of connective tissue features in hypermobility diagnostic criteria endorsed by participant; 2)baseline inflammatory markers.

Results: ESR and CRP were significantly higher in patients rather than controls, even after correcting for BMI, age and sex (B=5.15, t=2.05, p=0.044; B=1.77, t=2.15, p=0.044 respectively). Adjusted ESR and CRP correlated with both subjective fatigue (B=0.44, t=2.09, p=0.04; B=1.63, t=2.60, p=0.011) and pain severity (B=0.13, t=2.51, p=0.014; B=0.45, t=3.01, p=0.004) at baseline. Autonomic challenge amplified pain (B=14.20, t=2.87, p=0.005) and fatigue (B=31.48, t=5.95, p=<0.001) in patients to a significantly greater degree than controls, controlling for baseline levels. Baseline ESR and CRP also predicted challenge-induced increase in fatigue (B=0.78, t=370, p=<0.001; B=1.91, t=3.36, p=<0.001) and ESR challenge-induced increases in pain (B=0.46, t=2.35, p=0.021).

Mediation analysis demonstrated that number of connective tissue features expressed in hypermobility criteria mediated the degree to which subjective pain was increased by the autonomic challenge (Bootstraped 95% CI of indirect effect do not cross zero, 0.1572 – 6.8171). ESR mediated the degree to which subjective fatigue was increased by the autonomic challenge (Bootstraped 95% CI of indirect effect do not cross zero,0.7541 – 7.3888).

Conclusion: To our knowledge this is the first study to directly explore autonomic and inflammatory mechanisms of pain and fatigue in a combined population of Fibromyalgia and ME/CFS. This study this adds to the evidence-base of baseline inflammatory abnormalities in fibromyalgia and ME/CFS. It highlights their potential role in predicting symptom severity and their potential mechanistic role in autonomic induced pain and fatigue, suggesting future treatment strategies.

Source: Eccles J, Thompson C, Thompson B, et al. AB1209 MECHANISTIC FACTORS CONTRIBUTING TO PAIN AND FATIGUE IN FIBROMYALGIA AND ME/CFS: AUTONOMIC AND INFLAMMATORY INSIGHTS FROM AN EXPERIMENTAL MEDICINE STUDY. Annals of the Rheumatic Diseases 2022;81:1719 https://ard.bmj.com/content/annrheumdis/81/Suppl_1/1719.2.full.pdf (Full text available as PDF file)

Carnitine Palmitoyl Transferase Deficiency in a University Immunology Practice

Abstract:

Purpose: This report describes the clinical manifestations of 35 patients sent to a University Immunology clinic with a diagnosis of fatigue and exercise intolerance who were identified to have low carnitine palmitoyl transferase activity on muscle biopsies.

Recent findings: All of the patients presented with fatigue and exercise intolerance and many had been diagnosed with fibromyalgia. Their symptoms responded to treatment of the metabolic disease. Associated symptoms included bloating, diarrhea, constipation, gastrointestinal reflux symptoms, recurrent infections, arthritis, dyspnea, dry eye, visual loss, and hearing loss. Associated medical conditions included Hashimoto thyroiditis, Sjogren’s syndrome, seronegative arthritis, food hypersensitivities, asthma, sleep apnea, and vasculitis. This study identifies clinical features that should alert physicians to the possibility of an underlying metabolic disease. Treatment of the metabolic disease leads to symptomatic improvement.

Source: Bax K, Isackson PJ, Moore M, Ambrus JL Jr. Carnitine Palmitoyl Transferase Deficiency in a University Immunology Practice. Curr Rheumatol Rep. 2020 Feb 14;22(3):8. doi: 10.1007/s11926-020-0879-9. PMID: 32067119. https://pubmed.ncbi.nlm.nih.gov/32067119/

Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia

Abstract:

The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of peripheral blood mononuclear cells and identified a natural killer (NK) cell decrease in patients with FMS. Circulating NK cells in FMS were exhausted yet activated, evidenced by lower surface expression of CD16, CD96, and CD226 and more CD107a and TIGIT. These NK cells were hyperresponsive, with increased CCL4 production and expression of CD107a when co-cultured with human leukocyte antigen null target cells. Genetic and transcriptomic pathway analyses identified significant enrichment of cell activation pathways in FMS driven by NK cells. Skin biopsies showed increased expression of NK activation ligand, unique long 16-binding protein, on subepidermal nerves of patients FMS and the presence of NK cells near peripheral nerves. Collectively, our results suggest that chronic activation and redistribution of circulating NK cells to the peripheral nerves contribute to the immunopathology associated with FMS.

Source: Verma V, Drury GL, Parisien M, Özdağ Acarli AN, Al-Aubodah TA, Nijnik A, Wen X, Tugarinov N, Verner M, Klares R 3rd, Linton A, Krock E, Morado Urbina CE, Winsvold B, Fritsche LG, Fors EA, Piccirillo C, Khoutorsky A, Svensson CI, Fitzcharles MA, Ingelmo PM, Bernard NF, Dupuy FP, Üçeyler N, Sommer C, King IL, Meloto CB, Diatchenko L; HUNT-All In Pain. Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia. Pain. 2021 Sep 24:10.1097/j.pain.0000000000002498. doi: 10.1097/j.pain.0000000000002498. Epub ahead of print. PMID: 34913882; PMCID: PMC8942876. https://pubmed.ncbi.nlm.nih.gov/34913882/

Gastric herpes simplex virus type 1 infection is associated with functional gastrointestinal disorders in the presence and absence of comorbid fibromyalgia: a pilot case-control study

Abstract:

Purpose: Animal studies have linked gastric herpesvirus infections to symptoms associated with functional gastrointestinal disorders (FGIDs). Herpesviruses have also been hypothesized to contribute to fibromyalgia (FM), a chronic pain syndrome frequently comorbid with FGIDs. The purpose of this study was to compare the prevalence of gastric herpesvirus infection in patients with FGIDs, with and without comorbid FM, to that of controls.

Methods: For this pilot case-control study, we enrolled 30 patients who met both the Rome IV diagnostic criteria for one or more FGIDs and the American College of Rheumatology 2010 criteria for FM, 15 patients with one or more FGIDs without comorbid FM, and 15 control patients. Following endoscopic examination, gastric biopsies were analyzed for herpesvirus DNA and protein, Helicobacter pylori infection, and histological evidence of gastritis. Importantly, the viral nonstructural protein ICP8 was used as a marker to differentiate cell-associated actively replicating virus from latent infection and/or free virus passing through the GI tract.

Results: Gastric herpes simplex virus type 1 (HSV-1) infection, as indicated by ICP8 presence, was significantly associated with FGIDs in the presence (OR 70.00, 95% CI 7.42-660.50; P < .001) and absence (OR 38.50, 95% CI 3.75-395.40; P < .001) of comorbid FM. Neither histological gastritis nor H. pylori infection were found to be associated with FGIDs or FM.

Conclusions: HSV-1 infection was identified in gastric mucosal biopsies from patients with diverse FGIDs, with and without comorbid FM. Larger, multi-center studies investigating the prevalence of this association are warranted.

Source: Duffy C, Pridgen WL, Whitley RJ. Gastric herpes simplex virus type 1 infection is associated with functional gastrointestinal disorders in the presence and absence of comorbid fibromyalgia: a pilot case-control study. Infection. 2022 Apr 21. doi: 10.1007/s15010-022-01823-w. Epub ahead of print. PMID: 35445970.  https://link.springer.com/article/10.1007/s15010-022-01823-w (Full text)

Altered Pain in the Brainstem and Spinal Cord of Fibromyalgia Patients During the Anticipation and Experience of Experimental Pain

Abstract:

Chronic pain associated with fibromyalgia (FM) affects a large portion of the population but the underlying mechanisms leading to this altered pain are still poorly understood. Evidence suggests that FM involves altered neural processes in the central nervous system and neuroimaging methods such as functional magnetic resonance imaging (fMRI) are used to reveal these underlying alterations. While many fMRI studies of FM have been conducted in the brain, recent evidence shows that the changes in pain processing in FM may be linked to autonomic and homeostatic dysregulation, thus requiring further investigation in the brainstem and spinal cord.

Functional magnetic resonance imaging data from 15 women with FM and 15 healthy controls were obtained in the cervical spinal cord and brainstem at 3 tesla using previously established methods. In order to investigate differences in pain processing in these groups, participants underwent trials in which they anticipated and received a predictable painful stimulus, randomly interleaved with trials with no stimulus. Differences in functional connectivity between the groups were investigated by means of structural equation modeling.

The results demonstrate significant differences in brainstem/spinal cord network connectivity between the FM and control groups which also correlated with individual differences in pain responses. The regions involved in these differences in connectivity included the LC, hypothalamus, PAG, and PBN, which are known to be associated with autonomic homeostatic regulation, including fight or flight responses. This study extends our understanding of altered neural processes associated with FM and the important link between sensory and autonomic regulation systems in this disorder.

Source: Ioachim G, Warren HJM, Powers JM, Staud R, Pukall CF, Stroman PW. Altered Pain in the Brainstem and Spinal Cord of Fibromyalgia Patients During the Anticipation and Experience of Experimental Pain. Front Neurol. 2022 May 6;13:862976. doi: 10.3389/fneur.2022.862976. PMID: 35599729; PMCID: PMC9120571. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120571/ (Full text)

The impact of Micro RNA-320a serum level on severity of symptoms and cerebral processing of pain in patients with fibromyalgia

Abstract:

Objectives: The aim of this work was to explore the expression of miR-320a level in fibromyalgia patients in comparison to healthy controls, and to clarify its impact on the severity of symptoms and the cerebral processing of pain assessed by middle latency somatosensory evoked potentials (SSEPs).

Design: Case-control study.

Setting: Rheumatology and Neurology outpatient clinics.

Subjects: Seventy-four fibromyalgia patients and seventy-four normal healthy controls.

Methods: The included patients were subjected to detailed history taking, assessment of severity of fibromyalgia symptoms using the Fibromyalgia Impact Questionnaire Revised (FIQR), assessment of pain intensity using the Neuropathic Pain Symptom Inventory (NPSI), measurement of the serum level of miR-320a in addition to of measurement peak latencies and amplitudes of middle latency SSEPs.

Results: Fibromyalgia patients had significantly higher micro-RNA-320a levels (0.907 ± 0.022) in comparison to controls (0.874 ± 0.015) (P-value < 0.001). The mean values of micro-RNA-320a levels were significantly higher in fibromyalgia patients with insomnia, chronic fatigue syndrome, persistent depressive disorder, and primary headache disorder than those without (P-value = 0.024, <0.001, 0.006, 0.036 respectively). There were statistically significant positive correlations between micro-RNA-320a levels, and disease duration, FIQR and NPSI total scores (P-value <0.001, 0.003, 0.002 respectively). There were no statistically significant correlations between micro-RNA-320a levels and middle latency SSEPs.

Discussion: Micro-RNA-320a level is significantly upregulated in fibromyalgia patient. It has a crucial impact on the severity of symptoms but not related to the cerebral processing of pain.

Source: Hussein M, Fathy W, Abdelaleem EA, Nasser M, Yehia A, Elanwar R. The impact of Micro RNA-320a serum level on severity of symptoms and cerebral processing of pain in patients with fibromyalgia. Pain Med. 2022 May 19:pnac076. doi: 10.1093/pm/pnac076. Epub ahead of print. PMID: 35587745. https://pubmed.ncbi.nlm.nih.gov/35587745/

Intimate partner violence and women living with episodic disabilities: a scoping review protocol

Abstract:

Background: Violence towards women with disabilities is most commonly perpetrated by current or former intimate partners and more than half of disabled women experience intimate partner violence in their lifetime. Disabilities differ by presence, type, and complexity, yet are commonly researched collectively. A more nuanced understanding of the relationship between intimate partner violence and episodic disability is required to better support women living with these concurrent challenges. The objective of this scoping review is to investigate and synthesize the literature reporting on intimate partner violence for women living with an episodic disability to identify key concepts and knowledge gaps on this topic. Ultimately, this review aims to improve health services for this stigmatized group of women with episodic disabilities.

Methods: This scoping review will consider all studies that focus on women (18 years of age or older) who have experienced intimate partner violence and have an episodic disability. Episodic disabilities will include multiple sclerosis, chronic fatigue syndrome, fibromyalgia, lupus, or rheumatoid arthritis. The broad review question is what is known about intimate partner violence within the context of women living with an episodic disability? Databases to be searched include MEDLINE (OVID), CINAHL, Embase, PsychInfo, and Scopus with no limits on language or time frame. Joanna Briggs Institute methodology will guide this scoping review to address the review questions outlined in the protocol. For papers that meet the inclusion criteria, data will be extracted, and findings will be presented in tables and narrative form. A PRISMA table will be included to enhance the transparency of the process. A descriptive qualitative approach to analysis will be conducted following Braun and Clarke’s reflexive thematic analysis. The findings of the scoping review will be presented through a thematic narrative.

Discussion: Findings from this review will be used to identify important priorities for future research based on knowledge gaps and inform both health care practices and health and social interventions for women living with intimate partner violence and episodic disabilities.

Source: Campbell KA, Ford-Gilboe M, Stanley M, MacKinnon K. Intimate partner violence and women living with episodic disabilities: a scoping review protocol. Syst Rev. 2022 May 18;11(1):97. doi: 10.1186/s13643-022-01972-x. PMID: 35585642. https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-022-01972-x  (Full text)

Pain Burden in Post-COVID-19 Syndrome following Mild COVID-19 Infection

Abstract:

The global pandemic of SARS-CoV-2 has affected several hundred million people, and many infected people have suffered from a milder initial infection but have never fully recovered. This observational study investigates the pain burden in sufferers of post-COVID-19 syndrome after a milder initial infection.

One hundred post-COVID-19 patients filled out questionnaires regarding sociodemographic data, previous comorbidities, present pharmacological treatment, pain intensity and pain localisation. Health-related quality of life, fatigue, emotional status, and insomnia were measured by validated questionnaires. Multiple post-COVID-19 symptoms, including post-exertional malaise, were evaluated by a symptom questionnaire. Among the 100 participants (mean age 44.5 years), 82% were women, 61% had higher education, and 56% were working full or part time. Nine participants reported previous pain or inflammatory conditions. Among the most painful sites were the head/face, chest, lower extremities, and migrating sites. Generalised pain was self-reported by 75 participants and was estimated in 50 participants. Diagnosis of fibromyalgia according to the 2016 criteria was suspected in 40 participants. Subgroup analyses indicated that comorbidities might play a role in the development of pain.

In conclusion, a major part of sufferers from post-COVID-19 syndrome develop pain, and in addition to its many disabling symptoms, there is an urgent need for pain management in post-COVID-19 syndrome.

Source: Bileviciute-Ljungar I, Norrefalk JR, Borg K. Pain Burden in Post-COVID-19 Syndrome following Mild COVID-19 Infection. J Clin Med. 2022 Jan 31;11(3):771. doi: 10.3390/jcm11030771. PMID: 35160223; PMCID: PMC8836662. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836662/ (Full text)