Tag: fibromyalgia

Co-occurrence of immune-mediated conditions and endometriosis among adolescents and adult women

Abstract:

Problem: Associations between immune dysfunction conditions (eg, systemic lupus erythematous, rheumatoid arthritis) and endometriosis have been observed in adult women, but not assessed among a younger population. We investigated the association between immune-mediated conditions and endometriosis among young women.

Method of study: This cross-sectional analysis in the Women’s Health Study: From Adolescence to Adulthood included 551 participants with surgically diagnosed endometriosis (median age=19) and 652 controls without endometriosis (median age=24). Participants completed an expanded Endometriosis Phenome and Biobanking Harmonization Project questionnaire. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to investigate the associations between autoimmune/inflammatory, atopic, chronic pain/fatigue, and endocrine disorders with endometriosis, adjusting for confounders.

Results: Participants with any autoimmune and/or inflammatory condition had an increased odds of co-occurring endometriosis (OR: 1.87; CI: 0.92-3.80), as did participants with allergies (OR: 1.76; CI: 1.32-2.36), asthma (OR: 1.35; CI: 0.97-1.88), chronic fatigue syndrome and/or fibromyalgia (OR: 5.81; CI: 1.89-17.9), or previous mononucleosis (OR: 1.75; CI: 1.14-2.68). Odds of endometriosis were lower among participants with eczema (OR: 0.68; CI: 0.44-1.04). We observed a positive trend between the number of immune-mediated conditions and the odds of endometriosis (p-trend=0.0002). Endocrine disorders were not associated with endometriosis.

Conclusions: Among this population of adolescents and adult women, endometriosis was more likely among participants with autoimmune and/or inflammatory diseases, allergies, asthma, previous mononucleosis infection, and chronic fatigue and/or fibromyalgia. We observed that an increasing number of immune-mediated conditions were positively associated with endometriosis risk. It is important for clinicians who care for adolescents and women with these conditions to consider endometriosis as a comorbidity.

Source: Shafrir AL, Palmor MC, Fourquet J, DiVasta AD, Farland LV, Vitonis AF, Harris HR, Laufer MR, Cramer DW, Terry KL, Missmer SA. Co-occurrence of immune-mediated conditions and endometriosis among adolescents and adult women. Am J Reprod Immunol. 2021 Feb 14:e13404. doi: 10.1111/aji.13404. Epub ahead of print. PMID: 33583078. https://pubmed.ncbi.nlm.nih.gov/33583078/

Numeric Rating Scales Show Prolonged Post-exertional Symptoms After Orthostatic Testing of Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Introduction: Muscle pain, fatigue, and concentration problems are common among individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These symptoms are commonly increased as part of the phenomenon of postexertional malaise (PEM). An increase in the severity of these symptoms is described following physical or mental exercise in ME/CFS patients. Another important symptom of ME/CFS is orthostatic intolerance, which can be detected by head-up tilt testing (HUT). The effect of HUT on PEM has not been studied extensively. For this purpose, we assessed numeric rating scales (NRS) for pain, fatigue, and concentration pre- and post-HUT. As pain is a core symptom in fibromyalgia (FM), we subgrouped ME/CFS patients by the presence or absence of FM.

Methods and Results: In eligible ME/CFS patients who underwent HUT, NRS of pain, fatigue, and concentration were obtained pre-HUT, immediately after HUT, at 24 and 48 h, and at 7 days posttest. We studied 174 ME/CFS patients with FM, 104 without FM, and 30 healthy controls (HC). Values for all symptoms were unchanged for HC pre- and post-HUT. Compared with pre-HUT, the three NRS post-HUT were significantly elevated in both ME/CFS patient groups even after 7 days. NRS pain was significantly higher at all time points measured in the ME/CFS patients with FM compared with those without FM. In ME/CFS patients, the maximum fatigue and concentration scores occurred directly post-HUT, whereas pain perception reached the maximum 24 h post-HUT.

Conclusion: NRS scores of pain, fatigue, and concentration were significantly increased even at 7 days post-HUT compared with pre-HUT in ME/CFS patients with and without FM, suggesting that orthostatic stress is an important determinant of PEM.

Source: C (Linda) M. C. van Campen, Peter C. Rowe, Freek W. A. Verheugt and Frans C. Visser. Numeric Rating Scales Show Prolonged Post-exertional Symptoms After Orthostatic Testing of Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front. Med., 27 January 2021 | https://doi.org/10.3389/fmed.2020.602894 https://www.frontiersin.org/articles/10.3389/fmed.2020.602894/full  (Full text)

Food Implications in Central Sensitization Syndromes

Abstract:

Fibromyalgia (FM), chronic fatigue syndrome (CFS) and multiple chemical sensitivity (MCS) are some of the central sensitization syndromes (CSSs). The complexity of their diagnosis, the high interindividual heterogeneity and the existence of multi-syndromic patients requires a multifaceted treatment. The scientific literature is contradictory regarding the role of food in CSS, and evidence on the role of nutrition in MCS is particularly scarce. This review consists in gathering information about the current status of dietary recommendations (i.e., special dietary interventions, the role of additives, presence of micronutrient deficiencies, nutritional supplements and elimination of other nutrients and substances) and discussing the scientific evidence in depth to shed light on appropriate nutritional treatment managements for CSS patients. Current indications show that dietary modifications may vastly improve the patients’ quality of life at a low cost. We suggest personalized treatment, taking into consideration the severity of the disease symptoms, quality of life, coexistence with other diseases, pharmacological treatment, changing clinical characteristics, nutritional status, energy requirements and food tolerances, among others, as the best ways to tailor specific dietary interventions. These approaches will partially overcome the lack of scientific and clinical research on MSC. Patients should also be advised on the serious consequences of following dietary guidelines without a dietitian’s and clinician’s supervision.

Source: Aguilar-Aguilar E, Marcos-Pasero H, Ikonomopoulou MP, Loria-Kohen V. Food Implications in Central Sensitization Syndromes. J Clin Med. 2020 Dec 19;9(12):E4106. doi: 10.3390/jcm9124106. PMID: 33352747. https://pubmed.ncbi.nlm.nih.gov/33352747/

High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome

Abstract:

Objective: Pain in fibromyalgia (FM) and chronic fatigue syndrome (CFS) is assumed to originate from central sensitization. Perineural cysts or Tarlov cysts (TCs) are nerve root dilations resulting from pathologically increased cerebrospinal fluid pressure. These cysts initially affect sensory neurons and axons in dorsal root ganglia and produce sensory symptoms (pain and paresthesia). Symptomatic TC (STC) patients often complain about widespread pain and fatigue. Consequently, STC patients may initially be diagnosed with FM, CFS, or both. The objective of this study was to document the prevalence of TCs in patients diagnosed with FM or CFS.

Design: A retrospective study.

Setting: An outpatient clinic for musculoskeletal disorders.

Subjects: Patients diagnosed with FM according to the 1990 American College of Rheumatology criteria or with CFS according to the 1994 Centers for Disease Control criteria were selected.

Methods: Review of lumbar and sacral magnetic resonance imaging scans including TCs ≥5 mm in size.

Results: In total, 197 patients with FM, CFS, or both underwent magnetic resonance imaging. Ninety-one percent were women. The mean age was 48.1 (±11.9) years. TCs were observed in 39% of patients, with a mean size of 11.8 (±5.2) mm. In males, the prevalence was 12%, vs. 42% in females.

Conclusions: In patients diagnosed with FM or CFS, the prevalence of TCs was three times higher than that in the general population. This observation supports the hypothesis that STCs, FM, and CFS may share the same pathophysiological mechanism, i.e., moderately increased cerebrospinal fluid pressure, causing irritation of neurons and axons in dorsal root ganglia.

Source: Hulens M, Bruyninckx F, Dankaerts W, Rasschaert R, De Mulder P, Stalmans I, Vansant G, Bervoets C. High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome. Pain Med. 2020 Dec 1:pnaa410. doi: 10.1093/pm/pnaa410. Epub ahead of print. PMID: 33260218. https://pubmed.ncbi.nlm.nih.gov/33260218/

The Interplay between Oxidative Stress, Exercise, and Pain in Health and Disease: Potential Role of Autonomic Regulation and Epigenetic Mechanisms

Abstract:

Oxidative stress can be induced by various stimuli and altered in certain conditions, including exercise and pain. Although many studies have investigated oxidative stress in relation to either exercise or pain, the literature presents conflicting results. Therefore, this review critically discusses existing literature about this topic, aiming to provide a clear overview of known interactions between oxidative stress, exercise, and pain in healthy people as well as in people with chronic pain, and to highlight possible confounding factors to keep in mind when reflecting on these interactions. In addition, autonomic regulation and epigenetic mechanisms are proposed as potential mechanisms of action underlying the interplay between oxidative stress, exercise, and pain.

This review highlights that the relation between oxidative stress, exercise, and pain is poorly understood and not straightforward, as it is dependent on the characteristics of exercise, but also on which population is investigated. To be able to compare studies on this topic, strict guidelines should be developed to limit the effect of several confounding factors. This way, the true interplay between oxidative stress, exercise, and pain, and the underlying mechanisms of action can be revealed and validated via independent studies.

Source: Hendrix J, Nijs J, Ickmans K, Godderis L, Ghosh M, Polli A. The Interplay between Oxidative Stress, Exercise, and Pain in Health and Disease: Potential Role of Autonomic Regulation and Epigenetic Mechanisms. Antioxidants (Basel). 2020 Nov 23;9(11):1166. doi: 10.3390/antiox9111166. PMID: 33238564; PMCID: PMC7700330. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700330/  (Full text)

Fibromyalgia and Chronic Fatigue Syndrome in the Age of COVID-19

Excerpt:

It has been demonstrated that clinical outcomes of COVID-19 are significantly worse in persons with advanced age and those with “traditional” medical comorbidities (cardiovascular disease, pulmonary disease, diabetes, malignancy, and immunosuppression). But what about the ever-increasing group of people in our society, many of whom do not have “traditional” medical comorbidities, who suffer chronically from pain, fatigue, and functional decline? We are referring to patients with fibromyalgia (FM) and chronic fatigue syndrome (CFS): 2 conditions that, although medically distinct, share a common pathophysiological etiology: central sensitization (CS)., , , 

Source: Mohabbat AB, Mohabbat NML, Wight EC. Fibromyalgia and Chronic Fatigue Syndrome in the Age of COVID-19. Mayo Clin Proc Innov Qual Outcomes. 2020 Nov 13. doi: 10.1016/j.mayocpiqo.2020.08.002. Epub ahead of print. PMID: 33204998; PMCID: PMC7661943. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661943/ (Full text)

The antinuclear antibody dense fine speckled pattern and possible clinical associations: An indication of a proinflammatory microenvironment

Abstract:

Background: Indirect immunofluorescence (IIF) is the most prevalent screening antinuclear antibody test for systemic autoimmune rheumatic disease (SARD). Certain IIF patterns have known antibody and disease associations, but the dense fine speckled (ANA-DFS) pattern has no confirmed clinical associations. Our objective was to determine the prevalence of SARD among a group of ANA-DFS positive individuals and to identify final diagnoses among non-SARD individuals in order to determine possible clinical associations with the ANA-DFS pattern.

Methods: A retrospective study of 425 patients from a university health care system with a positive ANA-DFS pattern consecutively between August 2017 and September 2018. Sera samples underwent ANA testing by IIF on HEp-2 cell substrates (Euroimmun, Germany). Clinical information was retrieved from electronic health records and stored in a de-identified database.

Results: The prevalence of SARD was 24%. Undetermined diagnosis (17%), skin disorders (12.1%), and fibromyalgia/chronic pain syndrome/chronic fatigue syndrome (11.8%) were the most common non-SARD diagnoses. Taking into account past medical history, the most common non-SARD were atopic disorders (21.2%), fibromyalgia/chronic pain syndrome/chronic fatigue syndrome (17.6%), and skin disorders (16.7%).

Conclusions: The ANA-DFS pattern may be indicative of an underlying antigen-antibody interaction that plays a role in either the initiation or propagation of immunologic reactions. DFS70/LEDGF is a transcription factor involved in cell survival and stress protection, and autoantibodies may inhibit its function. It is likely that there are other antibodies producing the ANA-DFS pattern besides anti-DFS70/LEDGF, and more research is necessary to identify additional antibody specificities. The ANA-DFS pattern may be an indicator of a proinflammatory microenvironment given the high frequency of symptomatic patients and disease processes with an immunologic basis (including SARD).

Source: Lundgren MC, Sapkota S, Peterson DJ, Crosson JT. The antinuclear antibody dense fine speckled pattern and possible clinical associations: An indication of a proinflammatory microenvironment. J Immunol Methods. 2020 Oct 26:112904. doi: 10.1016/j.jim.2020.112904. Epub ahead of print. PMID: 33121975. https://pubmed.ncbi.nlm.nih.gov/33121975/

Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract:

Introduction: In a large study with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients, we showed that 86% had symptoms of orthostatic intolerance in daily life and that 90% had an abnormal reduction in cerebral blood flow (CBF) during a standard tilt test. A standard head-up tilt test might not be tolerated by the most severely affected bed-ridden ME/CFS patients. Sitting upright is a milder orthostatic stress. The present study examined whether a sitting test, measuring cerebral blood flow by extracranial Doppler, would be sufficient to provoke abnormal reductions in cerebral blood flow in severe ME/CFS patients.

Methods and results: 100 severe ME/CFS patients were studied, (88 females) and were compared with 15 healthy controls (HC) (13 females). CBF was measured first while seated for at least one hour, followed by a CBF measurement in the supine position. Fibromyalgia was present in 37 patients. Demographic data as well as supine heart rate and blood pressures were not different between ME/CFS patients and HC. Heart rate and blood pressure did not change significantly between supine and sitting both in patients and HC. Supine CBF was not different between patients and HC. In contrast, absolute CBF during sitting was lower in patients compared to HC: 474 (96) mL/min in patients and 627 (89) mL/min in HC; p < 0.0001. As a result, percent CBF reduction while seated was −24.5 (9.4)% in severe ME/CFS patients and −0.4 (1.2)% in HC (p < 0.0001). In the ten patients who had no orthostatic intolerance complaints in daily life, the CBF reduction was −2.7 (2.1)%, which was not significantly different from HC (p = 0.58). The remaining 90 patients with orthostatic intolerance complaints had a −26.9 (6.2)% CBF reduction. No difference in CBF parameters was found in patients with and without fibromyalgia. Patients with a previous diagnosis of postural orthostatic tachycardia syndrome (POTS) had a significantly larger CBF reduction compared with those without POTS: 28.8 (7.2)% vs. 22.3 (9.7)% (p = 0.0008).

Conclusions: A sitting test in severe ME/CFS patients was sufficient to provoke a clinically and statistically significant mean CBF decline of 24.5%. Patients with a previous diagnosis of POTS had a larger CBF reduction while seated, compared to patients without POTS. The magnitude of these CBF reductions is similar to the results in less severely affected ME/CFS patients during head-up tilt, suggesting that a sitting test is adequate for the diagnosis of orthostatic intolerance in severely affected patients.

Source: C (Linda) MC van Campen, Peter C. Rowe, and Frans C Visser. Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Healthcare 2020, 8(4), 394; https://doi.org/10.3390/healthcare8040394 https://www.mdpi.com/2227-9032/8/4/394/htm (Full text)

Predictors of New Onsets of Irritable Bowel Syndrome, Chronic Fatigue Syndrome and Fibromyalgia: The Lifelines Study

Abstract:

Background: It has been claimed that functional somatic syndromes share a common etiology. This prospective population-based study assessed whether the same variables predict new onsets of irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS) and fibromyalgia (FM).

Methods: The study included 152 180 adults in the Dutch Lifelines study who reported the presence/absence of relevant syndromes at baseline and follow-up. They were screened at baseline for physical and psychological disorders, socio-demographic, psycho-social and behavioral variables. At follow-up (mean 2.4 years) new onsets of each syndrome were identified by self-report. We performed separate analyses for the three syndromes including participants free of the relevant syndrome or its key symptom at baseline. LASSO logistic regressions were applied to identify which of the 102 baseline variables predicted new onsets of each syndrome.

Results: There were 1595 (1.2%), 296 (0.2%) and 692 (0.5%) new onsets of IBS, CFS, and FM, respectively. LASSO logistic regression selected 26, 7 and 19 predictors for IBS, CFS and FM, respectively. Four predictors were shared by all three syndromes, four predicted IBS and FM and two predicted IBS and CFS but 28 predictors were specific to a single syndrome. CFS was more distinct from IBS and FM, which predicted each other.

Conclusions: Syndrome-specific predictors were more common than shared ones and these predictors might form a better starting point to unravel the heterogeneous etiologies of these syndromes than the current approach based on symptom patterns. The close relationship between IBS and FM is striking and requires further research.

Source: Monden R, Rosmalen JGM, Wardenaar KJ, Creed F. Predictors of new onsets of irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia: the lifelines study [published online ahead of print, 2020 Jun 17]. Psychol Med. 2020;1-9. doi:10.1017/S0033291720001774 https://pubmed.ncbi.nlm.nih.gov/32546287/

DNA Methylation and BDNF Expression Account for Symptoms and Widespread Hyperalgesia in Patients With Chronic Fatigue Syndrome and Fibromyalgia

Abstract:

Background: Epigenetics of neurotrophic factors holds the potential to unravel the mechanisms underlying the pathophysiology of complex conditions such as chronic fatigue syndrome (CFS). This study explored the role of brain-derived neurotrophic factor (BDNF) genetics, epigenetics, and protein expression in patients with both CFS and comorbid fibromyalgia (CFS/FM).

Methods: A repeated-measures study in 54 participants (28 patients with CFS/FM and 26 matched healthy controls) was conducted. Participants underwent a comprehensive assessment, including questionnaires, sensory testing, and blood withdrawal. BDNF protein level was measured in serum (sBDNF) using ELISA, while polymorphism and DNA methylation were measured in blood, using pyrosequencing technology. To assess temporal stability of the measures, participants underwent the same assessment twice within four days.

Results: Repeated-measures mixed linear models were performed for between-group analysis. sBNDF was higher in patients with CFS/FM (F=15.703; mean difference: 3.31 ng/ml, 95% C.I. 1.65 to 4.96; p=.001), whereas BDNF DNA methylation was lower in Exon IX (F=9.312; mean difference -2.38%, C.I. -3.93 to -0.83; p=.003). BDNF DNA methylation was mediated by the Val66Met (rs6265) polymorphism. Lower methylation in the same region predicted higher sBDNF (F=4.910, t= -2.216, p=.029, 95% C.I. = -.712 to -.039) which in turn predicted participants’ symptoms (F=14.410, t= 3.796, 95% C.I.= 1.79 to 5.71, p=.001) and widespread hyperalgesia (F=4.147, t= 2.036, 95% C.I.= .01 to .08, p=.044).

Discussion: sBDNF is higher in patients with CFS/FM and BDNF methylation in exon IX accounts for regulating protein expression. Altered BDNF might represent a key mechanism explaining CFS/FM pathophysiology.

Source: Polli A, Ghosh M, Bakusic J, et al. DNA methylation and BDNF expression account for symptoms and widespread hyperalgesia in patients with Chronic Fatigue Syndrome and Fibromyalgia [published online ahead of print, 2020 Jun 20]. Arthritis Rheumatol. 2020;10.1002/art.41405. doi:10.1002/art.41405 https://pubmed.ncbi.nlm.nih.gov/32562379/