Fibromyalgia and chronic fatigue: the underlying biology and related theoretical issues

Abstract:

There is an increasing interest in understanding the biological mechanism underpinning fibromyalgia (FM) and chronic fatigue syndrome (CFS). Despite the presence of mixed findings in this area, a few biological systems have been consistently involved, and the increasing number of studies in the field is encouraging. This chapter will focus on inflammatory and oxidative stress pathways and on the neuroendocrine system, which have been more commonly examined.

Chronic inflammation, together with raised levels of oxidative stress and mitochondrial dysfunction, has been increasingly associated with the manifestation of symptoms such as pain, fatigue, impaired memory, and depression, which largely characterise at least some patients suffering from CFS and FM.

Furthermore, the presence of blunted hypothalamic-pituitary-adrenal axis activity, with reduced cortisol secretion both at baseline and in response to stimulation tests, suggests a role for the hypothalamic-pituitary-adrenal axis and cortisol in the pathogenesis of these syndromes. However, to what extent these systems’ abnormalities could be considered as primary or secondary factors causing FM and CFS has yet to be clarified.

© 2015 S. Karger AG, Basel.

 

Source: Romano GF, Tomassi S, Russell A, Mondelli V, Pariante CM. Fibromyalgia and chronic fatigue: the underlying biology and related theoretical issues. Adv Psychosom Med. 2015;34:61-77. doi: 10.1159/000369085. Epub 2015 Mar 30. https://www.ncbi.nlm.nih.gov/pubmed/25832514

 

Chronic fatigue syndrome and fibromyalgia in Canada: prevalence and associations with six health status indicators

Abstract:

INTRODUCTION: Few studies have considered the factors independently associated with chronic fatigue syndrome (CFS) and/or fibromyalgia (FM) or considered the impact of these conditions on health status using population-based data.

METHODS: We used data from the nationally representative 2010 Canadian Community Health Survey (n = 59 101) to describe self-reported health professional-diagnosed CFS and/or FM, and their associations with 6 health status indicators.

RESULTS: In 2010, diagnosed CFS and FM are reported by 1.4% (95% confidence interval [CI]: 1.3%-1.6%) and 1.5% (1.4%-1.7%), respectively, of the Canadian household population aged 12 years and over, with comorbid CFS and FM affecting 0.3% (0.3%-0.4%) of that population. Prevalent CFS and/or FM were more common among women, adults aged 40 years and over, those with lowest income, and those with certain risk factors for chronic disease (i.e. obesity, physical inactivity and smoking). After controlling for differences between the groups, people with CFS and/or FM reported poorer health status than those with neither condition on 5 indicators of health status, but not on the measure of fair/poor mental health. Having both CFS and FM and having multiple comorbid conditions was associated with poorer health status.

CONCLUSION: Co-occurrence of CFS and FM and having other chronic conditions were strongly related to poorer health status and accounted for much of the differences in health status. Understanding factors contributing to improved quality of life in people with CFS and/or FM, particularly in those with both conditions and other comorbidities, may be an important area for future research.

 

Source: Rusu C, Gee ME, Lagacé C, Parlor M. Chronic fatigue syndrome and fibromyalgia in Canada: prevalence and associations with six health status indicators. Health Promot Chronic Dis Prev Can. 2015 Mar;35(1):3-11. [Article in English, French; Abstract available in French from the publisher] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939456/ (Full article)

 

Metals as a common trigger of inflammation resulting in non-specific symptoms: diagnosis and treatment

Abstract:

BACKGROUND: The multiple symptoms of chronic fatigue syndrome (CFS) and fibromyalgia resemble those described in patients suffering from autoimmune/inflammatory syndrome induced by adjuvants (ASIA). It has been suggested that chronic metal-induced inflammation might play a role both in CFS and fibromyalgia as well as in ASIA. Humans are exposed to metals mainly through the release of metal ions from corroding dental restorations and orthopedic implants, food, vaccines and jewelry. Metals readily bind to sulphur and other groups in the mitochondria, enzymes and cell proteins. Metal-bound proteins are recognized by the immune system of susceptible subjects and might trigger an abnormal immune response, including allergy and autoimmunity.

OBJECTIVES: To study three subjects with CFS and two with fibromyalgia, all of whom suspected metal exposure as a trigger for their ill health.

METHODS: We measured delayed-type hypersensitivity to metals (metal allergy) using a validated lymphocyte transformation test, LTT-MELISA. All patients except one were sensitized to metals present in their dental restorations. The remaining patient reacted to metals in his skull implant. The removal of sensitizing metals resulted in long-term health improvement. Nine healthy controls matched for gender and age showed only marginal reactivity to the metals tested.

CONCLUSIONS: Patients with CFS and fibromyalgia are frequently sensitized to metals found in the environment or used in dentistry and surgery. This allergy to metals might initiate or aggravate non-specific symptoms in metal-sensitized patients.

 

Source: Stejskal V. Metals as a common trigger of inflammation resulting in non-specific symptoms: diagnosis and treatment. Isr Med Assoc J. 2014 Dec;16(12):753-8. https://www.ima.org.il/FilesUpload/IMAJ/0/100/50323.pdf (Full article as PDF)

 

Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the ‘autoimmune (auto-inflammatory) syndrome induced by adjuvants’ (ASIA)

Abstract:

The objectives of this study were to gather information regarding demographic and clinical characteristics of patients diagnosed with either fibromyalgia (FM) or chronic fatigue (CFS) following hepatitis B vaccination (HBVv) and furthermore to apply the recently suggested criteria of autoimmune (auto-inflammatory) syndromes induced by adjuvants (ASIA), in the aim of identifying common characteristics that may suggest an association between fibromyalgia, chronic fatigue and HBV vaccination.

Medical records of 19 patients with CFS and/or fibromyalgia following HBVv immunization were analyzed. All of which were immunized during 1990-2008 in different centers in the USA. All medical records were evaluated for demographics, medical history, the number of vaccine doses, as well as immediate and long term post-immunization adverse events and clinical manifestations. In addition, available blood tests, imaging results, treatments and outcomes were analyzed. ASIA criteria were applied to all patients.

The mean age of patients was 28.6 ± 11 years, of which 68.4 % were females. 21.05 % had either personal or familial background of autoimmune disease. The mean latency period from the last dose of HBVv to onset of symptoms was 38.6 ± 79.4 days, ranging from days to a year. Eight (42.1 %) patients continued with the immunization program despite experiencing adverse events. Manifestations that were commonly reported included neurological manifestations (84.2 %), musculoskeletal (78.9 %), psychiatric (63.1 %), fatigue (63.1 %), gastrointestinal complains (58 %) and mucocutaneous manifestations (36.8 %). Autoantibodies were detected in 71 % of patients tested. All patients fulfilled the ASIA criteria.

This study suggests that in some cases CFS and FM can be temporally related to immunization, as part of ASIA syndrome. The appearance of adverse event during immunization, the presence of autoimmune susceptibility and higher titers of autoantibodies all can be suggested as risk factors. ASIA criteria were fulfilled in all patients eluding the plausible link between ASIA and CFS/FM.

 

Source: Agmon-Levin N, Zafrir Y, Kivity S, Balofsky A, Amital H, Shoenfeld Y. Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the ‘autoimmune (auto-inflammatory) syndrome induced by adjuvants’ (ASIA). Immunol Res. 2014 Dec;60(2-3):376-83. doi: 10.1007/s12026-014-8604-2. https://www.ncbi.nlm.nih.gov/pubmed/25427994

 

What is in a name? Comparing diagnostic criteria for chronic fatigue syndrome with or without fibromyalgia

Abstract:

The current study had two objectives. (1) to compare objective and self-report measures in patients with chronic fatigue syndrome (CFS) according to the 1994 Center for Disease Control (CDC) criteria, patients with multiple sclerosis (MS), and healthy controls, and (2) to contrast CFS patients who only fulfill CDC criteria to those who also fulfill the criteria for myalgic encephalomyelitis (ME), the 2003 Canadian criteria for ME/CFS, or the comorbid diagnosis of fibromyalgia (FM).

One hundred six participants (48 CFS patients diagnosed following the 1994 CDC criteria, 19 MS patients, and 39 healthy controls) completed questionnaires assessing symptom severity, quality of life, daily functioning, and psychological factors. Objective measures consisted of activity monitoring, evaluation of maximal voluntary contraction and muscle recovery, and cognitive performance. CFS patients were screened whether they also fulfilled ME criteria, the Canadian criteria, and the diagnosis of FM.

CFS patients scored higher on symptom severity, lower on quality of life, and higher on depression and kinesiophobia and worse on MVC, muscle recovery, and cognitive performance compared to the MS patients and the healthy subjects. Daily activity levels were also lower compared to healthy subjects. Only one difference was found between those fulfilling the ME criteria and those who did not regarding the degree of kinesiophobia (lower in ME), while comorbidity for FM significantly increased the symptom burden.

CFS patients report more severe symptoms and are more disabled compared to MS patients and healthy controls. Based on the present study, fulfillment of the ME or Canadian criteria did not seem to give a clinically different picture, whereas a diagnosis of comorbid FM selected symptomatically worse and more disabled patients.

 

Source: Meeus M, Ickmans K, Struyf F, Kos D, Lambrecht L, Willekens B, Cras P, Nijs J. What is in a name? Comparing diagnostic criteria for chronic fatigue syndrome with or without fibromyalgia. Clin Rheumatol. 2016 Jan;35(1):191-203. doi: 10.1007/s10067-014-2793-x. Epub 2014 Oct 14. https://www.ncbi.nlm.nih.gov/pubmed/25308475

 

The effect of relaxation therapy on autonomic functioning, symptoms and daily functioning, in patients with chronic fatigue syndrome or fibromyalgia: a systematic review

Abstract:

OBJECTIVE: To establish the effects of relaxation therapy on autonomic function, pain, fatigue and daily functioning in patients with chronic fatigue syndrome or fibromyalgia.

METHOD: A systematic literature study was performed. Using specific keywords related to fibromyalgia or chronic fatigue syndrome and relaxation therapy, the electronic databases PubMed and Web of Science were searched. Included articles were assessed for their risk of bias and relevant information regarding relaxation was extracted. The review was conducted and reported according to the PRISMA-statement.

RESULTS: Thirteen randomized clinical trials of sufficient quality were included, resulting in a total of 650 fibromyalgia patients (11 studies) and 88 chronic fatigue syndrome patients (3 studies). None of the studies reported effects on autonomic function. Six studies reported the effect of guided imagery on pain and daily functioning in fibromyalgia. The acute effect of a single session of guided imagery was studied in two studies and seems beneficial for pain relief. For other relaxation techniques (eg. muscle relaxation, autogenic training) no conclusive evidence was found for the effect on pain and functioning in fibromyalgia patients comparison to multimodal treatment programs. For fatigue a multimodal approach seemed better than relaxation, as shown in the sole three studies on chronic fatigue syndrome patients.

CONCLUSION: There is moderate evidence for the acute effect of guided imagery on pain, although the content of the visualization is a matter of debate. Other relaxation formats and the effects on functionality and autonomic function require further study.

© The Author(s) 2014.

 

Source: Meeus M, Nijs J, Vanderheiden T, Baert I, Descheemaeker F, Struyf F. The effect of relaxation therapy on autonomic functioning, symptoms and daily functioning, in patients with chronic fatigue syndrome or fibromyalgia: a systematic review. Clin Rehabil. 2015 Mar;29(3):221-33. doi: 10.1177/0269215514542635. Epub 2014 Sep 8. https://www.ncbi.nlm.nih.gov/pubmed/25200878

 

Fibromyalgia and chronic fatigue syndrome caused by non-celiac gluten sensitivity

Dear Editor:

Sensitivity to gluten with negative celiac disease testing or non-celiac sensitivity to gluten is a recently recognized problem with clinical manifestations that are superimposed with those of fibromyalgia, chronic fatigue and irritable bowel syndrome.

We present the case of a 40-year-old woman who came to the clinic with a 7-year history of generalized pain and chronic fatigue. She had been diagnosed with fibromyalgia by several rheumatologists and complied with the 1990 American College or Rheumatology criteria. She also presented chronic fatigue syndrome criteria. She had concentration and memory problems, «foggy mind», and intermittent diarrhea. The severity of the affection led to limitation in her daily activities which limited her to bed rest in spite of several visits to specialists in rheumatology, gastroenterology and alternative medicine/homeopathy. In addition to the typical symptoms of fibromyalgia, chronic fatigue and intermittent diarrhea, she had oral ulcers, autoimmune hypothyroidism and a history of iron deficiency. She had undergone multiple studies with normal findings, including anti-transglutaminase IgA antibodies to rule out celiac disease.

We suspected sensitivity to gluten and more studies were performed. Laboratory studies showed iron deficiency and low vitamin D levels. On a screening test for anti-transglutaminase and anti-deaminated gliadin peptide antibodies, both IgG and IgA were negative. HLA typing showed the presence of DQ2 (DQA1*05 DQB1*02). Gastroscopy showed small erythematous lesions on the duodenal bulb. Duodenal biopsies showed normal villi structure and lymphocytic duodenitis with apical redistribution, 28 CD3 lymphocytes for every 100 enterocytes (stage I Marsh lesions). Urease testing for Helicobacter pylori was positive. Celiac disease was ruled out due to the absence of specific antibodies or intestinal villi atrophy, though we still suspected sensitivity to gluten. A gluten-free diet was recommended without treating the infection by Helicobacter pylori.

You can read the rest of this letter here: http://www.reumatologiaclinica.org/en/fibromyalgia-chronic-fatigue-syndrome-caused/articulo/S2173574314001403/

Comment in

 

Source: Isasi C, Tejerina E, Fernandez-Puga N, Serrano-Vela JI. Fibromyalgia and chronic fatigue syndrome caused by non-celiac gluten sensitivity. Reumatol Clin. 2015 Jan-Feb;11(1):56-7. doi: 10.1016/j.reuma.2014.06.005. Epub 2014 Jul 19. [Article in English, Spanish] http://www.reumatologiaclinica.org/es/linkresolver/fibromialgia-fatiga-cronica-causada-por/S1699258X14001326/ (Full article)

Endogenous pain modulation in response to exercise in patients with rheumatoid arthritis, patients with chronic fatigue syndrome and comorbid fibromyalgia, and healthy controls: a double-blind randomized controlled trial

Abstract:

OBJECTIVE: Temporal summation (TS) of pain, conditioned pain modulation (CPM), and exercise-induced analgesia (EIA) are often investigated in chronic pain populations as an indicator for enhanced pain facilitation and impaired endogenous pain inhibition, respectively, but interactions are not yet clear both in healthy controls and in chronic pain patients. Therefore, the present double-blind randomized placebo-controlled study evaluates pains cores, TS, and CPM in response to exercise in healthy controls, patients with chronic fatigue syndrome and comorbid fibromyalgia (CFS/FM), and patients with rheumatoid arthritis (RA), both under placebo and paracetamol condition.

METHODS: Fifty-three female volunteers – of which 19 patients with CFS/FM, 16 patients with RA, and 18 healthy controls – underwent a submaximal exercise test on a bicycle ergometer on 2 different occasions (paracetamol vs. placebo), with an interval of 7 days. Before and after exercise, participants rated pain intensity during TS and CPM.

RESULTS: Patients with rheumatoid arthritis showed decreased TS after exercise, both after paracetamol and placebo (P < 0.05). In patients with CFS/FM, results were less univocal. A nonsignificant decrease in TS was only observed after taking paracetamol. CPM responses to exercise are inconclusive, but seem to worsen after exercise. No adverse effects were seen.

CONCLUSION: This study evaluates pain scores, TS, and CPM in response to submaximal exercise in 2 different chronic pain populations and healthy controls. In patients with RA, exercise had positive effects on TS, suggesting normal EIA. In patients with CFS/FM, these positive effects were only observed after paracetamol and results were inconsistent.

TRIAL REGISTRATION: ClinicalTrials.gov NCT01154647.

 

Source: Meeus M, Hermans L, Ickmans K, Struyf F, Van Cauwenbergh D, Bronckaerts L, De Clerck LS, Moorken G, Hans G, Grosemans S, Nijs J. Endogenous pain modulation in response to exercise in patients with rheumatoid arthritis, patients with chronic fatigue syndrome and comorbid fibromyalgia, and healthy controls: a double-blind randomized controlled trial. Pain Pract. 2015 Feb;15(2):98-106. doi: 10.1111/papr.12181. Epub 2014 Feb 17. https://www.ncbi.nlm.nih.gov/pubmed/24528544

 

Living with the unexplained: coping, distress, and depression among women with chronic fatigue syndrome and/or fibromyalgia compared to an autoimmune disorder

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia are disabling conditions without objective diagnostic tests, clear-cut treatments, or established etiologies. Those with the disorders are viewed suspiciously, and claims of malingering are common, thus promoting further distress. It was hypothesized in the current study that levels of unsupportive social interactions and the coping styles used among those with CFS/fibromyalgia would be associated with perceived distress and depressive symptoms.

Women with CFS/fibromyalgia (n=39), in fact, reported higher depression scores, greater perceived distress and more frequent unsupportive relationships than healthy women (n=55), whereas those with a chronic, but medically accepted illness comprising an autoimmune disorder (lupus erythematosus, multiple sclerosis, rheumatoid arthritis; n=28), displayed intermediate scores. High problem-focused coping was associated with low levels of depression and perceived distress in those with an autoimmune condition.

In contrast, although CFS/fibromyalgia was also accompanied by higher depression scores and higher perceived distress, this occurred irrespective of problem-focused coping. It is suggested that because the veracity of ambiguous illnesses is often questioned, this might represent a potent stressor in women with such illnesses, and even coping methods typically thought to be useful in other conditions, are not associated with diminished distress among those with CFS/fibromyalgia.

 

Source: McInnis OA, Matheson K, Anisman H. Living with the unexplained: coping, distress, and depression among women with chronic fatigue syndrome and/or fibromyalgia compared to an autoimmune disorder. Anxiety Stress Coping. 2014;27(6):601-18. doi: 10.1080/10615806.2014.888060. Epub 2014 Mar 3. https://www.ncbi.nlm.nih.gov/pubmed/24479644

 

Impact of the fibromyalgia in the chronic fatigue syndrome

Abstract:

BACKGROUND AND OBJECTIVE: Different studies have showed association of the chronic fatigue syndrome (CFS) with other pathologies, including fibromyalgia (FM). The objective of this study is to analyze whether there are differences in the clinic and in the assessment of fatigue in CFS patients associated or not with FM.

PATIENTS AND METHODS: A cross-sectional, single-site observational study was undertaken on a consecutive cases of a register of CFS patients at CFS Unit in Vall d’Hebron Hospital, Barcelona, from January 2008 until March 2011. The variables analyzed were FM comorbidity, sleep and fatigue characteristics and cognitive, neurological and autonomic symptoms. Questionnaires of fatigue impact scale, fatigue strength and impact on quality of life SF-36 were evaluated.

RESULTS: We included 980 CFS patients (mean age: 48±9 years; 91% women). Fibromyalgia was present in 528 patients (54%). The level of fatigue (P=.001) and pain (P<.001) was higher in FM patients. Patients with CFS and FM had more prevalence of sleep-related phenomena. The percentage of patients and the degree of severity of cognitive symptoms, neurological and autonomic dysfunction was higher in FM patients (P<.001). FM patients scored higher on the fatigue impact scale (P<.001) and showed worse results in the quality of life questionnaire (P<.001).

CONCLUSIONS: FM co-morbidity worse clinical parameters, fatigue and the perception of quality of life in CFS patients.

Copyright © 2013 Elsevier España, S.L. All rights reserved.

 

Source: Faro M, Sáez-Francàs N, Castro-Marrero J, Aliste L, Collado A, Alegre J. Impact of the fibromyalgia in the chronic fatigue syndrome. Med Clin (Barc). 2014 Jun 16;142(12):519-25. doi: 10.1016/j.medcli.2013.06.030. Epub 2014 Jan 2. [Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/24387955