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

 

Comorbidity of postural orthostatic tachycardia syndrome and chronic fatigue syndrome in an Australian cohort

Abstract:

OBJECTIVE: Patients with chronic fatigue syndrome (CFS) are frequently diagnosed with comorbid postural orthostatic tachycardia syndrome (POTS), suggesting a shared pathogenesis. The aim of this study was to examine the relationship between demographic characteristics, autonomic functioning and fatigue levels amongst CFS patients with and without comorbid POTS.

DESIGN AND SETTING: All patients presenting to the CFS Discovery Clinic between 2009 and 2012 completed a 20-min standing task as part of their initial assessment. Heart rate and pulse pressure were recorded at baseline, at 2-min intervals poststanding, at the end of the task and following a recovery period. Average heart rate and pulse pressure variability were calculated from this data. Age, gender, length of illness and self-reported fatigue scores were also recorded. POTS patients were diagnosed by an orthostatic increase in heart rate >30 beats per min, concomitant symptoms of orthostatic intolerance and no orthostatic hypotension. Differences in autonomic functioning between POTS and CFS patients were compared using independent samples t-tests, whilst logistic and linear regressions were performed to examine the contribution of autonomic functioning to task completion and perceived fatigue, respectively.

RESULTS:Comorbidity of CFS and POTS (CFS-POTS) was observed in 11% (33/306) of patients. CFS-POTS patients were significantly younger (P < 0.001), had a shorter length of illness (P = 0.034), experienced greater task difficulty (P = 0.002) and were able to stand for significantly shorter periods compared to the CFS-only patients (P < 0.001). CFS-POTS patients experienced significantly lower baseline diastolic blood pressure (P = 0.002), significantly higher heart rate and lower pulse pressures at each standing measurement. Early heart rate changes (P = 0.002) and overall heart rate change (P < 0.001) were significant predictors of completion status, whereas heart rate variability (P < 0.001) and female gender (P < 0.001) were significant predictors of increased perceived task difficulty.

CONCLUSIONS:Haemodynamic and demographic differences between CFS-POTS and CFS-only patients suggest that the former group reflects a distinct subgroup of the CFS population. The findings highlight the utility of screening younger patients with fatigue for POTS, and identified heart rate variability as an important marker of fatigue for CFS patients in general.

© 2013 The Association for the Publication of the Journal of Internal Medicine.

 

Source: Reynolds GK, Lewis DP, Richardson AM, Lidbury BA. Comorbidity of postural orthostatic tachycardia syndrome and chronic fatigue syndrome in an Australian cohort. J Intern Med. 2014 Apr;275(4):409-17. doi: 10.1111/joim.12161. Epub 2013 Nov 29. http://onlinelibrary.wiley.com/doi/10.1111/joim.12161/full (Full article)

 

Undiagnosed and comorbid disorders in patients with presumed chronic fatigue syndrome

Abstract:

OBJECTIVE: To assess undiagnosed and comorbid disorders in patients referred to a tertiary care center with a presumed diagnosis of chronic fatigue syndrome (CFS).

METHODS: Patients referred for chronic unexplained fatigue entered an integrated diagnostic pathway, including internal medicine assessment, psychodiagnostic screening, physiotherapeutic assessment and polysomnography+multiple sleep latency testing. Final diagnosis resulted from a multidisciplinary team discussion. Fukuda criteria were used for the diagnosis of CFS, DSM-IV-TR criteria for psychiatric disorders, ICSD-2 criteria for sleep disorders.

RESULTS: Out of 377 patients referred, 279 (74.0%) were included in the study [84.9% female; mean age 38.8years (SD 10.3)]. A diagnosis of unequivocal CFS was made in 23.3%. In 21.1%, CFS was associated with a sleep disorder and/or psychiatric disorder, not invalidating the diagnosis of CFS. A predominant sleep disorder was found in 9.7%, 19.0% had a psychiatric disorder and 20.8% a combination of both. Only 2.2% was diagnosed with a classical internal disease. In the total sample, a sleep disorder was found in 49.8%, especially obstructive sleep apnea syndrome, followed by psychophysiologic insomnia and periodic limb movement disorder. A psychiatric disorder was diagnosed in 45.2%; mostly mood and anxiety disorder.

CONCLUSIONS: A multidisciplinary approach to presumed CFS yields unequivocal CFS in only a minority of patients, and reveals a broad spectrum of exclusionary or comorbid conditions within the domains of sleep medicine and psychiatry. These findings favor a systematic diagnostic approach to CFS, suitable to identify a wide range of diagnostic categories that may be subject to dedicated care.

© 2013. Published by Elsevier Inc. All rights reserved.

 

Source: Mariman A, Delesie L, Tobback E, Hanoulle I, Sermijn E, Vermeir P, Pevernagie D, Vogelaers D. Undiagnosed and comorbid disorders in patients with presumed chronic fatigue syndrome. J Psychosom Res. 2013 Nov;75(5):491-6. doi: 10.1016/j.jpsychores.2013.07.010. Epub 2013 Aug 20. https://www.ncbi.nlm.nih.gov/pubmed/24182640

 

Examining the impact of obesity on individuals with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a complex disorder affecting multiple body systems. The most commonly used definition of CFS is 6 or more months of fatigue and the presence of at least four of eight minor symptoms. In addition, many health and psychological conditions, including severe obesity-body mass index (BMI) of 40 kg/m(2) or greater-exclude individuals from a diagnosis of CFS. Obesity has been correlated with fatigue, sleep problems, and less satisfaction with general health, functioning, and vitality.

The current study investigated weight trends over time in a community-based sample of individuals with CFS and healthy controls. The study further investigated the impact of comorbid weight issues on several health and disability outcomes in a subset of overweight individuals.

Overweight and obese individuals with CFS demonstrated poorer functioning than controls who were similarly weighted. One participant was excluded because she had gained weight at a monitoring visit and her BMI was greater than 40 kg/m(2). The implications of these findings for health care workers are discussed.

Copyright 2013, SLACK Incorporated.

 

Source: Flores S, Brown A, Adeoye S, Jason LA, Evans M. Examining the impact of obesity on individuals with chronic fatigue syndrome.Workplace Health Saf. 2013 Jul;61(7):299-307. doi: 10.3928/21650799-20130617-12. Epub 2013 Jun 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899694/ (Full article)

 

Prognostic factors for recent-onset interstitial cystitis/painful bladder syndrome

Abstract:

Study Type – Prognosis (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Interstitial cystitis/painful bladder syndrome (IC/PBS) comprises pain perceived to be from the bladder, urinary urgency and frequency, and nocturia. As diagnosed at present, it is primarily identified in adult women. It is a chronic disease yet its natural history has not been well studied. In a prospective study of 304 incident female IC/PBS cases followed for a median of 33 months after onset, women with baseline chronic fatigue syndrome had a worse prognosis for IC/PBS. Mild IC/PBS at baseline was the only variable that was directly associated with a good prognosis.

OBJECTIVE: To identify baseline variables that predict the prognosis of interstitial cystitis/painful bladder syndrome (IC/PBS) in women seeking medical care for recent onset of this syndrome.

SUBJECTS AND METHODS: In a prospective study of women with incident IC/PBS (≤12 months of symptoms), we contacted patients at intervals and asked standardized questions about IC/PBS symptoms in the previous week. Logistic regression analyses assessed baseline variables as predictors of mild vs more severe IC/PBS at the last follow-up.

RESULTS: Median length of follow-up was 33 months after onset of IC/PBS; 304 (97%) patients had at least one follow-up assessment. Mild IC/PBS at baseline was the only variable that was directly associated with a mild IC/PBS endpoint. Conversely, a history of chronic fatigue syndrome (CFS) was inversely associated with a mild endpoint of IC/PBS (i.e. individuals with CFS had a worse prognosis for their IC/PBS symptoms).

CONCLUSIONS: At a median of nearly 3 years after onset, baseline mild IC/PBS was directly associated with a milder disease severity. Baseline co-morbid CFS was associated with more severe disease. Whether CFS was uniquely associated or represented several co-morbid non-bladder syndromes (NBSs) could not be determined.

© 2012 BJU INTERNATIONAL.

Comment in: Re: prognostic factors for recent-onset interstitial cystitis/painful bladder syndrome. [J Urol. 2013]

 

Source: Warren JW, Clauw DJ, Langenberg P. Prognostic factors for recent-onset interstitial cystitis/painful bladder syndrome. BJU Int. 2013 Mar;111(3 Pt B):E92-7. doi: 10.1111/j.1464-410X.2012.11422.x. Epub 2012 Aug 9. http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2012.11422.x/full (Full article)

Psychophysical distress and alexithymic traits in chronic fatigue syndrome with and without comorbid depression

Abstract:

Patients with chronic fatigue syndrome (CFS) often report a comorbid depressive disorder. Comorbid depression may negatively influence the long-term outcome of CFS therefore it must be correctly diagnosed and treated. The aim of the present study is to provide a clinical and psychometric assessment of CFS patients with and without depressive features.

A comparative analysis between 57 CFS subjects (CDC, 1994), 17 of whom with a comorbid depression, and 55 matched healthy volunteers was assessed to evaluate the presence of any psychophysical distress and alexithymic traits, by means of Symptom Checklist-90-R (SCL-90R) and Toronto Alexithymia Scale (TAS-20). The severity of fatigue was also assessed in all CFS patients using the Fatigue Impact Scale (FIS). With regard to psychiatric comorbidity, the SCL-90R scores showed higher levels of somatic complaints in CFS patients than in healthy subjects, whereas augmented depressive and obsessive-compulsive symptoms were observed only in the depressed CFS subgroup.

When comparing the TAS-20 scores, we observed a selective impairment in the capacity to identify feelings and emotions, as measured by the Difficulty in Identifying Feelings subscale (DIF), non-depressed CFS patients showing an intermediate score between depressed CFS and healthy controls. Finally, in terms of FIS scores, a statistical trend versus a higher fatigue severity in depressed CFS patients, with respect to non-depressed ones, was observed. In conclusion, comorbid depression in CFS significantly increased the level of psychophysical distress and the severity of alexithymic traits. These findings suggest an urgent need to address and treat depressive disorders in the clinical care of CFS cases, to improve social functioning and quality of life in such patients.

 

Source: Sepede G, Racciatti D, Gorgoretti V, Nacci M, Pizzigallo E, Onofrj M, Di Giannantonio M, Niolu C, Salerno RM, Gambi F. Psychophysical distress and alexithymic traits in chronic fatigue syndrome with and without comorbid depression. Int J Immunopathol Pharmacol. 2011 Oct-Dec;24(4):1017-25. https://www.ncbi.nlm.nih.gov/pubmed/22230407

 

Conditions comorbid with chronic fatigue in a population-based sample

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) has been found to be comorbid with various medical conditions in clinical samples, but little research has investigated CFS comorbidity in population-based samples.

OBJECTIVE: This study investigated conditions concurrent with a CFS-like illness among twins in the population-based Mid-Atlantic Twin Registry (MATR), including chronic widespread pain (CWP), irritable bowel syndrome (IBS), and major depressive disorder (MDD).

METHOD: A survey was mailed to participants in the MATR in 1999. Generalized estimating equations were used to estimate odds ratios to assess associations between CFS-like illness and each comorbid condition.

RESULTS: A total of 4590 completed surveys were collected. Most participants were female (86.3%); mean age was 44.7 years. Among participants with a CFS-like illness, lifetime prevalences of CWP, IBS, and MDD were 41%, 16%, and 57% respectively. Participants reporting at least one of the three comorbid conditions were about 14 times more likely to have CFS-like illness than those without CWP, IBS, or MDD (95% confidence interval 8.1%-21.3%). Only MDD showed a temporal pattern of presentation during the same year as diagnosis of CFS-like illness. Age, gender, body mass index, age at illness onset, exercise level, self-reported health status, fatigue symptoms, and personality measures did not differ between those reporting CFS-like illness with and without comorbidity.

CONCLUSION: These results support findings in clinically based samples that CFS-like illness is frequently cormorbid with CWP, IBS, and/or MDD. We found no evidence that CFS-like illnesses with comorbidities are clinically distinct from those without comorbidities.

Copyright © 2012 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Source: Dansie EJ, Furberg H, Afari N, Buchwald D, Edwards K, Goldberg J, Schur E, Sullivan PF. Conditions comorbid with chronic fatigue in a population-based sample. Psychosomatics. 2012 Jan-Feb;53(1):44-50. doi: 10.1016/j.psym.2011.04.001. Epub 2011 Sep 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3254018/ (Full article)

 

Responses to exercise differ for chronic fatigue syndrome patients with fibromyalgia

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are chronic multisymptom illnesses with substantial clinical and diagnostic overlap. We have previously shown that, when controlling for aerobic fitness and accounting for comorbid FM, CFS patients do not exhibit abnormal cardiorespiratory responses during maximal aerobic exercise compared with healthy controls, despite differences in pain and exertion.

PURPOSE: The purpose of the present study was to examine cardiac and perceptual responses to steady-state submaximal exercise in CFS patients and healthy controls.

METHODS: Twenty-one CFS patients (13 CFS with comorbid FM (CFS + FM)) and 14 controls completed 20 min of submaximal cycling exercise. Impedance cardiography was used to determine cardiac responses during exercise. Systolic blood pressure (SBP), RPE, and leg muscle pain were also measured. Data were analyzed using a doubly multivariate, repeated-measures MANOVA to model the exercise response.

RESULTS: There was a significant multivariate time-by-group interaction (P < 0.05). The CFS + FM group exhibited an exercise response characterized by higher stroke index, ventilatory equivalents for oxygen and carbon dioxide and RPE, lower SBP, and similar HR responses compared to controls.

CONCLUSIONS: The present results extend on our previous work with maximal exercise and show that CFS and CFS + FM differ in their responses to steady-state exercise. These results highlight the importance of accounting for comorbid conditions when conducting CFS research, particularly when examining psychophysiological responses to exercise.

 

Source: Cook DB, Stegner AJ, Nagelkirk PR, Meyer JD, Togo F, Natelson BH. Responses to exercise differ for chronic fatigue syndrome patients with fibromyalgia. Med Sci Sports Exerc. 2012 Jun;44(6):1186-93. doi: 10.1249/MSS.0b013e3182417b9a. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319493/ (Full article)

 

Psychiatric comorbidity and chronic fatigue syndrome

Prins et al (2005) assessed psychiatric comorbidity in chronic fatigue syndrome (CFS) using the Structured Clinical Interview for DSM–III–R. Comorbidity was remarkably low compared with similar investigations, and in particular the apparent absence of current post-traumatic stress disorder (PTSD) was striking. The authors speculated that the low comorbidity rates might result mainly from a lack of ‘psychiatric bias’ of the examiners. They also found that psychiatric comorbidity did not predict the outcome of cognitive–behavioural therapy.

You can read the rest of this comment here: http://bjp.rcpsych.org/content/188/4/395.2.long

 

Source: Van Houdenhove B. Psychiatric comorbidity and chronic fatigue syndrome. Br J Psychiatry. 2006 Apr;188:395; author reply 396. http://bjp.rcpsych.org/content/188/4/395.2.long (Full article)

 

 

Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms

Abstract:

Previously we and others found that a majority of chronic fatigue syndrome (CFS) patients showed evidence of systemic mycoplasmal infections, and their blood tested positive using a polymerase chain reaction assay for at least one of the four following Mycoplasma species: M. fermentans, M. hominis, M. pneumoniae or M. penetrans.

Consistent with previous results, patients in the current study (n=200) showed a high prevalence (overall 52%) of mycoplasmal infections. Using forensic polymerase chain reaction we also examined whether these same patients showed evidence of infections with Chlamydia pneumoniae (overall 7.5% positive) and/or active human herpes virus-6 (HHV-6, overall 30.5% positive).

Since the presence of one or more infections may predispose patients to other infections, we examined the prevalence of C. pneumoniae and HHV-6 active infections in mycoplasma-positive and -negative patients. Unexpectedly, we found that the incidence of C. pneumoniae or HHV-6 was similar in Mycoplasma-positive and -negative patients, and the converse was also found in active HHV-6-positive and -negative patients. Control subjects (n=100) had low rates of mycoplasmal (6%), active HHV-6 (9%) or chlamydial (1%) infections, and there were no co-infections in control subjects. Differences in bacterial and/or viral infections in CFS patients compared to control subjects were significant.

Severity and incidence of patients’ signs and symptoms were compared within the above groups. Although there was a tendency for patients with multiple infections to have more severe signs and symptoms (p<0.01), the only significant differences found were in the incidence and severity of certain signs and symptoms in patients with multiple co-infections of any type compared to the other groups (p<0.01). There was no correlation between the type of co-infection and severity of signs and symptoms. The results indicate that a large subset of CFS patients show evidence of bacterial and/or viral infection(s), and these infections may contribute to the severity of signs and symptoms found in these patients.

 

Source: Nicolson GL, Gan R, Haier J. Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. APMIS. 2003 May;111(5):557-66. http://www.ncbi.nlm.nih.gov/pubmed/12887507