Etiology of sicca syndrome in a consecutive series of 199 patients with chronic fatigue syndrome

Dear Sir,

Chronic fatigue syndrome (CFS) is a heterogeneous and multisystemic disorder of unknown pathogenesis and etiology. It is characterized by prolonged generalized and abnormal fatigue post-exercise (98%), recurrent headache (90%) and problems of concentration and memory (85%) that have lasted for at least 6 months. It is accompanied by such other symptoms as tender lymph nodes (80%), musculoskeletal pain (75%) and psychiatric problems (65%).1,2 The prevalence of CFS is estimated to be between 0.5 and 2.5%, predominantly in women (4:1).1,2 Many patients with CFS also complain of sicca symptoms in up to 30–87%, and are more likely to have thyroid disorder and sleep disruption;2,3 that may suggest an underlying role of the immune system in these patients. Primary Sjögren’ syndrome (PSS) is a systemic autoimmune disease, that presents chronic exocrine glands hypofunction leading to xerostomia and/or xerophthalmia, and extraglandular involvement, of which autoimmune hypothyroidism (AIHT) is the most common autoimmune disease developed4. Patients with PSS, also experience CFS-like musculoskeletal and neurocognitive symptoms more than 50%, and the two disorders share some similar immunologic defects.4 The purpose of this study was to determine the causality of sicca symptoms in 199 consecutive patients diagnosed as having CFS, and the possible association with PSS, although few studies that have examined this association (between 2010 and 2012 in our chronic fatigue unit of Joan XXIII University Hospital) according to the Fukuda’ criteria of 1994.

You can read the rest of this article here: http://www.reumatologiaclinica.org/en/etiology-sicca-syndrome-in-consecutive/articulo/S2173574314001075/

 

Source: Qanneta R, Fontova R, Pàmies A. Etiology of sicca syndrome in a consecutive series of 199 patients with chronic fatigue syndrome. Reumatol Clin. 2014 Jul-Aug;10(4):269-70. doi: 10.1016/j.reuma.2013.11.002. Epub 2013 Dec 17. http://www.reumatologiaclinica.org/en/etiology-sicca-syndrome-in-consecutive/articulo/S2173574314001075/ (Full article)

 

‘Sometimes it feels as if the world goes on without me’: adolescents’ experiences of living with chronic fatigue syndrome

Abstract:

AIMS AND OBJECTIVES: To explore the experience of being an adolescent with chronic fatigue syndrome.

BACKGROUND: Despite ample research, chronic fatigue syndrome is still poorly understood, and there are still controversies related to the illness. Adolescents with chronic fatigue syndrome are often unable to attend school and lose social relations with friends. The challenges they face will affect their quality of life.

DESIGN: A qualitative, phenomenological hermeneutical design.

METHOD: Six boys and twelve girls, aged 12-18, were interviewed, emphasising their own experiences living with chronic fatigue syndrome. Analyses were performed using a phenomenological hermeneutical method.

RESULTS: The core theme, ‘Sometimes it feels as if the world goes on without me’, encompasses the feelings an adolescent living with chronic fatigue syndrome might have about life. The core theme was supported by four subthemes: ‘On the side of life–locked in and shut out’; ‘the body, the illness and me’; ‘if the illness is not visible to others, does it exist?’; and ‘handling life while hoping for a better future’. The subthemes reflect the experience of social isolation, their own and others’ understanding of the illness and hope for the future.

CONCLUSIONS: Not being able to be with friends, or attend school, made the adolescents feel different and forgotten. They felt alienated in their own bodies and were struggling to be visible to themselves and to their surroundings. Spending less time with friends and more time with their parents constituted a threat to independence and development. Yet they managed to envision a better future despite all the difficulties.

RELEVANCE FOR CLINICAL PRACTICE: To provide effective support and constructive relations to adolescents with chronic fatigue syndrome, all health professions involved need insight from the persons who are themselves ill. Health centres could function as resource centres for patients and healthcare professionals.

© 2013 John Wiley & Sons Ltd.

 

Source: Winger A, Ekstedt M, Wyller VB, Helseth S. ‘Sometimes it feels as if the world goes on without me’: adolescents’ experiences of living with chronic fatigue syndrome. J Clin Nurs. 2014 Sep;23(17-18):2649-57. doi: 10.1111/jocn.12522. Epub 2013 Dec 20. https://www.ncbi.nlm.nih.gov/pubmed/24354631

 

Chronic fatigue syndrome: a patient’s perspective

In 1999 I contracted a throat infection that receded after many weeks, but I was still unbelievably exhausted with the most intense flu-like malaise. Two years later I was diagnosed with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and joined the 240 000-plus people in the UK with this illness. I assumed that a diagnosis would lead to effective treatment, but I was in for a shock.

Initially my GP suggested I see a psychotherapist. It seemed a strange recommendation, but I trusted his judgement and decided to see if this would help. Unfortunately it had no impact at all on the illness. My GP then referred me to an endocrinologist who boldly announced that, as the test results were all normal, everything was fine and offered to prescribe antidepressants. I was deeply frustrated by the suggestion that clear test panels meant I should be treated as a depressed patient. I was not inclined to agree that antidepressants were the best treatment when my experience of the symptoms was closer to that of an infection than a mood disorder. In fact, I have been told a number of times that I’m simply depressed, or that I am de-conditioned and just need to exercise. I wouldn’t mind if either diagnosis were true, as there are effective treatments available, but they are inadequate explanations.

CFS/ME waxes and wanes but also causes post-exertional malaise: when patients go beyond their usual (restricted) activity level they suffer a worsening of symptoms which can be severe. Patients often refer to this as a crash. For me this can mean being bedridden for weeks with muscle weakness, dizziness, loss of appetite, and indescribable physical and mental exhaustion. It’s worth noting that my GP has only ever seen me when the symptoms are at the lesser end of the scale. During a crash I am too ill to leave my bed, let alone travel to the surgery.

When I first got sick, CFS/ME seemed to be largely treated as a mysterious psychological condition, with doctors encouraged to limit the number of tests done, and with patients left to self-manage. Since then things have improved a little in that there are fatigue clinics in some areas, but the overall treatment situation remains poor, with most patients receiving little or no effective treatment through the NHS.

The PACE trial is the largest study performed into CFS/ME treatments, primarily cognitive behavioural therapy (CBT) and graded exercise therapy (GET). I think the £5 million cost would have been better spent on immunological studies, exercise physiology testing, and understanding the disease mechanisms. A recently published PACE trial paper reported on ‘recovery’ rates.1 However, the letters published in response to the paper show that the study’s post-hoc definition of ‘recovery’ was seriously flawed, and so much looser than the recovery criteria outlined in the trial’s protocol that the ‘recovery’ outcomes bear no relation to what an average person, or clinician, would define as recovery of health. PACE was an un-blinded study and the primary outcomes were all subjective self-report measures at risk of response bias. Changes from the trial protocol2 also meant that it was easier for patients to be classed as improved, yet even then the addition of CBT and GET to specialist medical care led to only an extra 11–15% of patients reporting improvement.3 This simply underscores the need for more research across all areas to find effective treatments.

CFS/ME presents difficulties for both patients and doctors, reinforcing the need for them to work together in partnership. A recent BMJ editorial4 entitled Let the Patient Revolution Begin could not have said it better:

‘ … health care won’t get better until patients play a leading role in fixing it.’

You can read the full comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839372/

 

Source: Cornes O. Chronic fatigue syndrome: a patient’s perspective. Br J Gen Pract. 2013 Dec;63(617):648. doi: 10.3399/bjgp13X675458. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839372/ (Full article)

 

Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

Perturbations in immune processes are a hallmark of a number of autoimmune and inflammatory disorders. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is an inflammatory disorder with possible autoimmune correlates, characterized by reduced NK cell activity, elevations in regulatory T cells (Tregs) and dysregulation in cytokine levels. The purpose of this article is to examine innate and adaptive immune cell phenotypes and functional characteristics that have not been previously examined in CFS/ME patients.

Thirty patients with CFS/ME and 25 non-fatigued controls were recruited for this study. Whole blood samples were collected from all participants for the assessment of cell phenotypes, functional properties, receptors, adhesion molecules, antigens and intracellular proteins using flow cytometric protocols. The cells investigated included NK cells, dendritic cells, neutrophils, B cells, T cells, γδT cells and Tregs.

Significant changes were observed in B-cell subsets, Tregs, CD4(+)CD73(+)CD39(+) T cells, cytotoxic activity, granzyme B, neutrophil antigens, TNF-α and IFN-γ in the CFS/ME patients in comparison with the non-fatigued controls. Alterations in B cells, Tregs, NK cells and neutrophils suggest significant impairments in immune regulation in CFS/ME and these may have similarities to a number of autoimmune disorders.

 

Source: Brenu EW, Huth TK, Hardcastle SL, Fuller K, Kaur M, Johnston S, Ramos SB, Staines DR, Marshall-Gradisnik SM. Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis. Int Immunol. 2014 Apr;26(4):233-42. doi: 10.1093/intimm/dxt068. Epub 2013 Dec 16. http://intimm.oxfordjournals.org/content/26/4/233.long (Full article)

 

Recovery of upper limb muscle function in chronic fatigue syndrome with and without fibromyalgia

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) patients frequently complain of muscle fatigue and abnormally slow recovery, especially of the upper limb muscles during and after activities of daily living. Furthermore, disease heterogeneity has not yet been studied in relation to recovery of muscle function in CFS. Here, we examine recovery of upper limb muscle function from a fatiguing exercise in CFS patients with (CFS+FM) and without (CFS-only) comorbid fibromyalgia and compare their results with a matched inactive control group.

DESIGN: In this case-control study, 18 CFS-only patients, 30 CFS+FM patients and 30 healthy inactive controls performed a fatiguing upper limb exercise test with subsequent recovery measures.

RESULTS: There was no significant difference among the three groups for maximal handgrip strength of the non-dominant hand. A significant worse recovery of upper limb muscle function was found in the CFS+FM, but not in de CFS-only group compared with the controls (P < 0·05).

CONCLUSIONS: This study reveals, for the first time, delayed recovery of upper limb muscle function in CFS+FM, but not in CFS-only patients. The results underline that CFS is a heterogeneous disorder suggesting that reducing the heterogeneity of the disorder in future research is important to make progress towards a better understanding and uncovering of mechanisms regarding the nature of divers impairments in these patients.

© 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

 

Source: Ickmans K, Meeus M, De Kooning M, Lambrecht L, Nijs J. Recovery of upper limb muscle function in chronic fatigue syndrome with and without fibromyalgia. Eur J Clin Invest. 2014 Feb;44(2):153-9. doi: 10.1111/eci.12201. Epub 2013 Dec 9. https://www.ncbi.nlm.nih.gov/pubmed/24313704

 

Conditions, controversies and contradictions between Central Sensitivity Syndrome and Depressive Disorders

Abstract:

We present a description of the Central Sensitivity Syndrome (CSS) and some of its main components such as Multiple Chemical Sensitivity Syndrome, Chronic Fatigue Syndrome and Fibromyalgia. We review the changes in pain perception, describing the physiology and pathophysiology of the painful experience from the medulla horn to the CNS. We explain the theory of central sensitization as the basis to the syndrome. We refer to the differences between fibromyalgia and depressive disorders, is spite of their frequent presentation in comorbidity.

We state the main clinical and neurobiological differences. We point out the main psychoneuroimmunoendocrinologic differences such as adrenal activity (hypoactivity vs. hyperactivity, DST hypersuppressive response vs. DST non suppression, hypersensitivity of central glucocorticoid receptors vs. desensitization of these, among others), thyroid (probable reverse T3 vs. flat stimuli TSH response curve) and growth hormone secretion (probable increase vs. disruption of normal circadian rhythm) that makes CSS resemble PTSD. We describe differential changes in sleep patterns (alpha-delta intrusion vs. altered sleep time, REM latency, and stage 3/4) and immunological disturbances almost opposite in each pathological entity. We finally argue which medical specialty should treat these complex syndromes.

 

Source: Maresca T, Covini E, Mato AM. Conditions, controversies and contradictions between Central Sensitivity Syndrome and Depressive Disorders.Vertex. 2013 Sep-Oct;24(111):373-91. [Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/24312923

 

Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis

Abstract:

Myalgic encephalomyelitis (ME, also called Chronic Fatigue Syndrome), a common disease with chronic fatigability, cognitive dysfunction and myalgia of unknown etiology, often starts with an infection. The chaperonin human heat shock protein 60 (HSP60) occurs in mitochondria and in bacteria, is highly conserved, antigenic and a major autoantigen.

The anti-HSP60 humoral (IgG and IgM) immune response was studied in 69 ME patients and 76 blood donors (BD) (the Training set) with recombinant human and E coli HSP60, and 136 30-mer overlapping and targeted peptides from HSP60 of humans, Chlamydia, Mycoplasma and 26 other species in a multiplex suspension array. Peptides from HSP60 helix I had a chaperonin-like activity, but these and other HSP60 peptides also bound IgG and IgM with an ME preference, theoretically indicating a competition between HSP60 function and antibody binding. A HSP60-based panel of 25 antigens was selected.

When evaluated with 61 other ME and 399 non-ME samples (331 BD, 20 Multiple Sclerosis and 48 Systemic Lupus Erythematosus patients), a peptide from Chlamydia pneumoniae HSP60 detected IgM in 15 of 61 (24%) of ME, and in 1 of 399 non-ME at a high cutoff (p<0.0001). IgM to specific cross-reactive epitopes of human and microbial HSP60 occurs in a subset of ME, compatible with infection-induced autoimmunity.

 

Source: Elfaitouri A, Herrmann B, Bölin-Wiener A, Wang Y, Gottfries CG, Zachrisson O, Pipkorn R, Rönnblom L, Blomberg J. Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis. PLoS One. 2013 Nov 28;8(11):e81155. doi: 10.1371/journal.pone.0081155. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842916/ (Full article)

 

The feasibility and acceptability of conducting a trial of specialist medical care and the Lightning Process in children with chronic fatigue syndrome: feasibility randomized controlled trial (SMILE study)

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is relatively common in children with limited evidence for treatment. The Phil Parker Lightning Process (LP) is a trademarked intervention, which >250 children use annually. There are no reported studies investigating the effectiveness or possible side effects of LP.

METHODS: The trial population was drawn from the Bath and Bristol NHS specialist paediatric CFS or ME service. The study was designed as a pilot randomized trial with children (aged 12 to 18 years) comparing specialist medical care with specialist medical care plus the Lightning Process. Integrated qualitative methodology was used to explore the feasibility and acceptability of the recruitment, randomization and interventions.

RESULTS: A total of 56 children were recruited from 156 eligible children (1 October 2010 to 16 June 2012). Recruitment, randomization and both interventions were feasible and acceptable. Participants suggested changes to improve feasibility and acceptability and we incorporated the following in the trial protocol: stopped collecting 6-week outcomes; introduced a second reminder letter; used phone calls to collect primary outcomes from nonresponders; informed participants about different approaches of each intervention and changed our recommendation for the primary outcome for the full study from school attendance to disability (SF-36 physical function subscale) and fatigue (Chalder Fatigue Scale).

CONCLUSIONS:Conducting randomized controlled trials (RCTs) to investigate an alternative treatment such as LP is feasible and acceptable for children with CFS or ME. Feasibility studies that incorporate qualitative methodology enable changes to be made to trial protocols to improve acceptability to participants. This is likely to improve recruitment rate and trial retention.

TRIAL REGISTRATION: Feasibility study first randomization: 29 September 2010. Trial registration: Current Controlled Trials ISRCTN81456207 (31 July 2012). Full trial first randomization: 19 September 2012.

 

Source: Crawley E, Mills N, Beasant L, Johnson D, Collin SM, Deans Z, White K, Montgomery A. The feasibility and acceptability of conducting a trial of specialist medical care and the Lightning Process in children with chronic fatigue syndrome: feasibility randomized controlled trial (SMILE study). Trials. 2013 Dec 5;14:415. doi: 10.1186/1745-6215-14-415. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235039/ (Full article)

 

News from the CDC: chronic fatigue syndrome (CFS) and standardized patient videos - a novel approach to educating medical students about CFS

The Centers for Disease Control and Prevention (CDC), Division of High-Consequence Pathogens and Pathology, Chronic Viral Diseases Branch houses CDC’s chronic fatigue syndrome (CFS) research and education program. The program’s provider education and outreach initiative has conducted research and implemented activities to educate healthcare professionals about CFS diagnosis and management, including evaluating knowledge, attitudes, and beliefs among US providers [1], assessing best methods for CFS continuing medical education (CME) [2], and developing a train-the-trainer program [3]. In 2012, meetings with stakeholders and evaluations of existing outreach efforts informed the program’s decision to target medical students and residents as a way to influence CFS education at the beginning of the medical education process. This report describes the background and process for developing a CFS education curriculum using standardized patients and plans to disseminate the curriculum using MedEd Portal.

You can read the rest of this article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830016/

 

Source: Brimmer DJ, Campbell C, Bonner K, Lin JM. News from the CDC: chronic fatigue syndrome (CFS) and standardized patient videos - a novel approach to educating medical students about CFS. Transl Behav Med. 2013 Dec;3(4):338-9. doi: 10.1007/s13142-013-0229-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830016/ (Full article)

 

Natural killer cells in patients with severe chronic fatigue syndrome

Abstract:

Maintenance of health and physiological homeostasis is a synergistic process involving tight regulation of proteins, transcription factors and other molecular processes. The immune system consists of innate and adaptive immune cells that are required to sustain immunity. The presence of pathogens and tumour cells activates innate immune cells, in particular Natural Killer (NK) cells.

Stochastic expression of NK receptors activates either inhibitory or activating signals and results in cytokine production and activation of pathways that result in apoptosis of target cells. Thus, NK cells are a necessary component of the immunological process and aberrations in their functional processes, including equivocal levels of NK cells and cytotoxic activity pre-empts recurrent viral infections, autoimmune diseases and altered inflammatory responses. NK cells are implicated in a number of diseases including chronic fatigue syndrome (CFS). The purpose of this review is to highlight the different profiles of NK cells reported in CFS patients and to determine the extent of NK immune dysfunction in subtypes of CFS patients based on severity in symptoms.

 

Source: Brenu EW, Hardcastle SL, Atkinson GM, van Driel ML, Kreijkamp-Kaspers S, Ashton KJ, Staines DR, Marshall-Gradisnik SM. Natural killer cells in patients with severe chronic fatigue syndrome. Auto Immun Highlights. 2013 Apr 16;4(3):69-80. doi: 10.1007/s13317-013-0051-x. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389023/ (Full article)