Patients with Fibromyalgia Scored Worse in Memory, Attention, Cognitive Function

Press release:

A cross-sectional study demonstrated significant impairments in attention, memory, and higher cognitive functions among a cohort of patients with fibromyalgia and rheumatoid arthritis (RA), according to a study published in Psychology Research and Behavior Management.1

Investigators believe deficits in the fibromyalgia cohort could be explained by secondary symptoms coupled with more severe pain. A cognitive screening could help curate personalized treatment plans to improve the quality of life among patients with RA and fibromyalgia.

“Research directly comparing cognitive performance between patients with fibromyalgia and RA is still scarce. Some studies suggested deficits of similar magnitude in both patient groups,” wrote a group of investigators led by Carmen María Galvez Sánchez, PhD, associated with the Department of Personality, Evaluation and Psychological Treatment at the University of Murcia, Spain. “In response to this exigency, there is a requisite for the evaluation of cognitive impairments in individuals with chronic pain, aiming to formulate and implement interventions rooted in neuropsychological training. This approach is intended to ameliorate cognitive performance and mitigate its consequential impact on health-related quality of life.”

In certain patients with fibromyalgia, cognitive impairment was linked to clinical pain severity, depression, fatigue, insomnia, and anxiety. Similarly, these were also reported in patients with RA, although pain and emotional symptoms within the fibromyalgia cohort.2 Symptoms of fibromyalgia and RA often include depression, fatigue, insomnia, and cognitive issues.

Investigators analyzed the performance in cognitive domains between patients with RA and fibromyalgia using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Questionnaire scores were combined to determine the symptom severity factor, which was used as a control variable within the group comparisons.

A total of 64 patients with fibromyalgia, 34 patients with RA, and 32 healthy controls were included in the study. All patients were female.

Without controlling for the severity of symptoms, patients with either fibromyalgia or RA performed worse when compared with controls in terms of cognitive domains including verbal memory, visual memory, and strategic planning.

Additionally, over deficits were observed in the fibromyalgia cohort compared with RA. Patients with fibromyalgia reported more severe symptoms, such as pain intensity, total pain, anxiety, depression, insomnia, and fatigue, compared with patients with RA. After controlling for symptom severity a significant proportion of cognitive test, a large proportion of cognitive test parameters were not different between rheumatologic cohorts.

Limitations included the lack of information regarding the influence of psychotropic and pain medication on cognitive performance among rheumatic patients. Although the limitation could have been determined using subgroup analysis, the current sample size was too small to form these subgroups.

Further, no data on treatment and disease activity were collected in the RA subgroup and the analysis of the effects of clinical symptoms on cognitive performance was limited. Additionally, not all psychological factors that may impact cognition were assessed in the analysis. The generalizability of findings may be hindered as only women were included in the analysis and the recruitment of subjects was not randomly performed. Lastly, the RA and fibromyalgia diagnoses were performed by different rheumatologists, which may have introduced selection bias.

“Based on the present results, it is recommended that screening for cognitive deficits be part of routine diagnostics for fibromyalgia and RA, which may help to guide the design of personalized interventions to optimize cognitive performance of patients with fibromyalgia and RA,” investigators concluded.

Source: Lana Pine. HCP Live.

Incident autoimmune diseases in association with a SARS-CoV-2 infection: A matched cohort study

Abstract:

Objectives To investigate whether the risk of developing an incident autoimmune disease is increased in patients with previous COVID-19 disease compared to people without COVID-19.

Method A cohort was selected from German routine health care data covering 38.9 million individuals. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020. Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19.

Results In total, 641,704 patients with COVID-19 were included. Comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69-15.42) and matched control groups (IR=10.55, 95% CI: 10.25-10.86), we found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune disease of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune diseases.

Conclusions SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection.

Source: Falko Tesch, Franz Ehm, Annika Vivirito, Danny Wende, Manuel Batram, Friedrich Loser, Simone Menzer, Josephine Jacob, Martin Roessler, Martin Seifert, Barbara Kind, Christina König, Claudia Schulte, Tilo Buschmann, Dagmar Hertle, Pedro Ballesteros, Stefan Baßler, Barbara Bertele, Thomas Bitterer, Cordula Riederer, Franziska Sobik, Lukas Reitzle, Christa Scheidt-Nave, Jochen Schmitt. Incident autoimmune diseases in association with a SARS-CoV-2 infection: A matched cohort study. medRxiv 2023.01.25.23285014; doi:

The autoimmune aetiology of unexplained chronic pain

Abstract:

Chronic pain is the leading cause of life years lived with disability worldwide. The aetiology of most chronic pain conditions has remained poorly understood and there is a dearth of effective therapies. The WHO ICD-11 has categorised unexplained chronic pain states as ‘chronic primary pains’ (CPP), which are further defined by their association with significant distress and/or dysfunction. The new mechanistic term, ‘nociplasticic pain’ has been developed to illustrate their presumed generation by a structurally intact, but abnormally functioning nociceptive system.

Recently, researchers have unravelled the surprising, ubiquitous presence of pain-sensitising autoantibodies in four investigated CPP indicating autoimmune causation. In persistent complex regional pain syndrome, fibromyalgia syndrome, chronic post-traumatic limb pain, and non-inflammatory joint pain associated with rheumatoid arthritis, passive transfer experiments have shown that either IgG or IgM antibodies from patient-donors cause symptoms upon injection to rodents that closely resemble those of the clinical disorders. Targets of antibody-binding and downstream effects vary between conditions, and more research is needed to elucidate the molecular and cellular details.

The central nervous system appears largely unaffected by antibody binding, suggesting that the clinically evident CNS symptoms associated with CPP might arise downstream of peripheral processes. In this narrative review pertinent findings are described, and it is suggested that additional symptom-based disorders might be examined for the contribution of antibody-mediated autoimmune mechanisms.

Source: Goebel A, Andersson D, Helyes Z, Clark JD, Dulake D, Svensson C. The autoimmune aetiology of unexplained chronic pain. Autoimmun Rev. 2022 Mar;21(3):103015. doi: 10.1016/j.autrev.2021.103015. Epub 2021 Dec 10. PMID: 34902604. https://www.sciencedirect.com/science/article/abs/pii/S1568997221002974 (Full text)

Influence of morphine and naloxone on pain modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia and controls: a double blind randomized placebo-controlled cross-over study

Abstract:

BACKGROUND: Impaired pain inhibitory and enhanced pain facilitatory mechanisms are repeatedly reported in patients with central sensitization pain. However, the exact effects of frequently prescribed opioids on central pain modulation are still unknown.

METHODS: A randomized, double-blind, placebo-controlled cross-over trial was carried out. Ten CFS/FM patients, 11 RA patients and 20 controls were randomly allocated to the experimental (10 mg morphine or 0.2 mg/ml Naloxone) and placebo (2 ml Aqua) group. Pressure Pain Thresholds (PPTs) and temporal summation at the Trapezius and Quadriceps were assessed by algometry. Conditioned Pain Modulation (CPM) efficacy and Deep Tissue Pain pressure were assessed by adding ischemic occlusion at the opposite upper arm.

RESULTS: Deep Tissue Pain pressure was lower and temporal summation higher in CFS/FM (p=0.002 respectively p=0.010) and RA patients (p=0.011 respectively p=0.047) compared to controls at baseline. Morphine had only a positive effect on PPTs in both patient groups (p time =0.034). Accordingly, PPTs increased after placebo, and no effects on the other pain parameters were objectified. There were no significant effects of naloxone nor nocebo on PPT, Deep Tissue Pain, temporal summation or CPM in the control group.

CONCLUSIONS: This study revealed anti-hyperalgesia effects of morphine in CFS/FM and RA patients. Nevertheless, these effects were comparable to placebo. Besides, neither morphine nor naloxone influenced Deep Tissue Pain, temporal summation or CPM. Therefore, these results suggest that the opioid system is not dominant in (enhanced) bottom-up sensitization (temporal summation) or (impaired) endogenous pain inhibition (CPM) in patients with CFS/FM or RA.

This article is protected by copyright. All rights reserved.

Source: Hermans L, Nijs J, Calders P, De Clerck L, Moorkens G, Hans G, Grosemans S, Roman De Mettelinge T, Tuynman J, Meeus M. Influence of morphine and naloxone on pain modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia and controls: a double blind randomized placebo-controlled cross-over study. Pain Pract. 2017 Jul 19. doi: 10.1111/papr.12613. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28722815

Does acetaminophen activate endogenous pain inhibition in chronic fatigue syndrome/fibromyalgia and rheumatoid arthritis? A double-blind randomized controlled cross-over trial

Abstract:

BACKGROUND: Although enhanced temporal summation (TS) and conditioned pain modulation (CPM), as characteristic for central sensitization, has been proved to be impaired in different chronic pain populations, the exact nature is still unknown.

OBJECTIVES: We examined differences in TS and CPM in 2 chronic pain populations, patients with both chronic fatigue syndrome (CFS) and comorbid fibromyalgia (FM) and patients with rheumatoid arthritis (RA), and in sedentary, healthy controls, and evaluated whether activation of serotonergic descending pathways by acetaminophen improves central pain processing.

STUDY DESIGN: Double-blind randomized controlled trial with cross-over design.

METHODS: Fifty-three women (19 CFS/FM patients, 16 RA patients, and 18 healthy women) were randomly allocated to the experimental group (1 g acetaminophen) or the placebo group (1 g dextrose). Participants underwent an assessment of endogenous pain inhibition, consisting of an evaluation of temporal summation with and without conditioned pain modulation (CPM). Seven days later groups were crossed-over. Patients and assessors were blinded for the allocation.

RESULTS: After intake of acetaminophen, pain thresholds increased slightly in CFS/FM patients, and decreased in the RA and the control group. Temporal summation was reduced in the 3 groups and CPM at the shoulder was better overall, however only statistically significant for the RA group. Healthy controls showed improved CPM for both finger and shoulder after acetaminophen, although not significant.

LIMITATIONS: The influence of acetaminophen on pain processing is inconsistent, especially in the patient groups examined.

CONCLUSION: This is the first study comparing the influence of acetaminophen on central pain processing in healthy controls and patients with CFS/FM and RA. It seems that CFS/FM patients present more central pain processing abnormalities than RA patients, and that acetaminophen may have a limited positive effect on central pain inhibition, but other contributors have to be identified and evaluated.

 

Source: Meeus M, Ickmans K, Struyf F, Hermans L, Van Noesel K, Oderkerk J, Declerck LS, Moorkens G, Hans G, Grosemans S, Nijs J. Does acetaminophen activate endogenous pain inhibition in chronic fatigue syndrome/fibromyalgia and rheumatoid arthritis? A double-blind randomized controlled cross-over trial. Pain Physician. 2013 Mar-Apr;16(2):E61-70. http://www.painphysicianjournal.com/linkout?issn=1533-3159&vol=16&page=E61 (Full article available as PDF file)

 

Free radicals in chronic fatigue syndrome: cause or effect?

Abstract:

We have demonstrated that certain morphological and biochemical changes occur in chronic fatigue syndrome (CFS) and in rheumatoid arthritis (RA). These changes in RA can be explained by the well-established inappropriate increase in free radical generation. The similar changes in CFS suggest a similar explanation and a possible role for free radicals in the aetiology of this condition.

 

Source: Richards RS, Roberts TK, Dunstan RH, McGregor NR, Butt HL. Free radicals in chronic fatigue syndrome: cause or effect? Redox Rep. 2000;5(2-3):146-7. http://www.ncbi.nlm.nih.gov/pubmed/10939298

 

Personality and social attitudes in chronic fatigue syndrome

Abstract:

One hundred one chronic fatigue syndrome (CFS) patients attending a specialist CFS clinic were compared with 45 rheumatoid arthritis (RA) patients on a range of standardized questionnaire measures, to investigate whether CFS patients are characterized by particular personality traits or social attitudes.

No differences were found between CFS and RA patients in measures of perfectionism, attitudes toward mental illness, defensiveness, social desirability, or sensitivity to punishment (a concept related to neuroticism), on either crude or adjusted analyses. Alexithymia scores were greater in the RA patient group (p<0.05). Social adjustment, based on subjective assessment of overall restriction in activities and relationship difficulties, was substantially poorer in the CFS group (p<0.001). This was highly associated with depressive symptoms, but remained significant even after adjusting for depressive symptomatology.

There was no evidence from this study of major differences between the personalities of CFS patients and RA patients. The stereotype of CFS sufferers as perfectionists with negative attitudes toward psychiatry was not supported.

 

Source: Wood B, Wessely S. Personality and social attitudes in chronic fatigue syndrome. J Psychosom Res. 1999 Oct;47(4):385-97. http://www.ncbi.nlm.nih.gov/pubmed/10616232

 

Psychological symptoms in chronic fatigue and juvenile rheumatoid arthritis

Abstract:

OBJECTIVE: To determine if psychological morbidity in youth with chronic fatigue is caused by the stress of coping with a chronic illness.

STUDY DESIGN: Case-control study comparing pediatric patients with debilitating chronic fatigue and matched subjects with juvenile rheumatoid arthritis, a chronic medical illness with similar functional sequelae.

SETTING: Pediatric Infectious Diseases Clinic and Juvenile Rheumatoid Arthritis Clinic of Kosair Children’s Hospital.

PARTICIPANTS: Nineteen children and adolescents with debilitating chronic fatigue and 19 age- and sex-matched peers with juvenile rheumatoid arthritis. Outcome. Structured Interview, Kaufman Brief Intelligence Test, Child Behavior Checklist, and Youth Self-Report.

RESULTS: Intellectual functioning on the Kaufman Brief Intelligence Test Composite was average (103, standard score) for both groups. Pediatric patients with chronic fatigue had higher levels of internalizing psychological distress than patients suffering from juvenile rheumatoid arthritis, despite the fact that both groups had a similar pattern of decline in social and physical activities. Duration of illness did not explain the difference in psychological symptoms.

CONCLUSIONS: Psychological factors may play a more active role in debilitating chronic fatigue in pediatric patients than can be explained by the stress of coping with a similar chronic, non-life-threatening illness.

 

Source: Carter BD, Kronenberger WG, Edwards JF, Marshall GS, Schikler KN, Causey DL. Psychological symptoms in chronic fatigue and juvenile rheumatoid arthritis. Pediatrics. 1999 May;103(5 Pt 1):975-9. http://www.ncbi.nlm.nih.gov/pubmed/10224175

 

Mild adrenocortical deficiency, chronic allergies, autoimmune disorders and the chronic fatigue syndrome: a continuation of the cortisone story

Abstract:

The possibility that patients with disorders that improve with administration of large, pharmacologic dosages of glucocorticoids, such as chronic allergies and autoimmune disorders, might have mild deficiency of cortisol production or utilization has received little attention.

Yet evidence that patients with rheumatoid arthritis improved with small, physiologic dosages of cortisol or cortisone acetate was reported over 25 years ago, and that patients with chronic allergic disorders or unexplained chronic fatigue also improved with administration of such small dosages was reported over 15 years ago, suggesting that these disorders might be associated with mild adrenocortical deficiency.

The apparent reasons for the failure of these reports to be confirmed or mentioned in medical textbooks and the facts needed to restore perspective are reviewed, and the need for further studies of the possible relationship of a mild deficiency of the production or utilization of cortisol and possibly other normal adrenocortical hormones to the development of these disorders is discussed.

 

Source: Jefferies WM. Mild adrenocortical deficiency, chronic allergies, autoimmune disorders and the chronic fatigue syndrome: a continuation of the cortisone story. Med Hypotheses. 1994 Mar;42(3):183-9. http://www.ncbi.nlm.nih.gov/pubmed/8057974

 

Psychiatric illness in patients with chronic fatigue and those with rheumatoid arthritis

Abstract

OBJECTIVES: To identify psychiatric differences between patients with chronic fatigue and those with rheumatoid arthritis and to investigate whether patients meeting Centers for Disease Control (CDC) criteria for chronic fatigue syndrome (CFS) can be differentiated from patients with chronic fatigue on measures of disability and psychosocial distress.

DESIGN: Cross-sectional study comparing 98 patients with chronic fatigue with 31 patients with rheumatoid arthritis on structured psychiatric interviews and patient questionnaires. Nineteen patients meeting CDC criteria for CFS were compared with 79 patients with chronic fatigue not meeting CDC criteria on questionnaires measuring disability and psychosocial distress.

SETTING: Consecutive patients with chronic fatigue were selected from a chronic fatigue clinic at the University of Washington, and 31 consecutive patients with rheumatoid arthritis were sampled from a private rheumatology practice.

MAIN RESULTS: Patients with chronic fatigue had a significantly higher prevalence of lifetime major depression and somatization disorder than did patients with rheumatoid arthritis. Patients with chronic fatigue also had a significantly higher prevalence of current and lifetime psychiatric diagnoses. Only 19 of 98 patients with chronic fatigue met CDC criteria for CFS. Patients meeting CDC criteria for CFS could not be differentiated from the larger group of patients with chronic fatigue on any study variable.

CONCLUSIONS: Patients with chronic fatigue have a significantly higher burden of psychiatric illness than do patients with rheumatoid arthritis. The psychiatric illness preceded the development of chronic fatigue in over half the patients. Centers for Disease Control criteria for CFS did not select a subset of chronic fatigue patients who could be differentiated on disability or psychosocial parameters from patients with chronic fatigue who did not meet CDC criteria.

Comment in The trouble with chronic fatigue. [J Gen Intern Med. 1991]

 

Source: Katon WJ, Buchwald DS, Simon GE, Russo JE, Mease PJ. Psychiatric illness in patients with chronic fatigue and those with rheumatoid arthritis. J Gen Intern Med. 1991 Jul-Aug;6(4):277-85. http://www.ncbi.nlm.nih.gov/pubmed/1890495