‘Flowers’ in the blood – abnormally shaped red blood cells in CFS

CASE REPORT Abstract

 

Introduction:

Chronic fatigue syndrome is a debilitating condition characterized by persistent fatigue, post-exertional malaise, myalgia, arthralgia, lymph node tenderness, impaired memory and concentration, autonomic irregularities, and other specific symptoms affecting multiple body systems.

Diverse hypotheses have been investigated to ascertain the disease etiology. Some of these include metabolic and mitochondrial deficiencies, exposure to environmental toxins, dysautonomia associated with orthostatic intolerance, autoimmune reactions, neuroendocrine aberrations, and chronic viral infections.

However, a consistently observed biomarker for chronic fatigue has not been identified. A comprehensive, standardized strategy for accurate diagnosis and successful treatment remains elusive.

 

Case Report:

A 28-year-old Caucasian female presented with chronic fatigue persisting for nine months following infectious mononucleosis.

Laboratory evaluation excluded classic causes of fatigue. Peripheral blood smear examination revealed numerous pairs of unusual nondiscocytic C-shaped erythrocytes [red blood cells], coupled in perpendicular crosses resembling four-petalled flowers.

The presence of the erythrocyte pairs abated with the patient’s recovery from chronic fatigue syndrome over a 24-month period. This erythrocyte arrangement has not been reported elsewhere in medical literature.

Conclusion:

A novel erythrocyte “flower” formation was identified in a patient with chronic fatigue syndrome. The presence of this arrangement paralleled the course of the illness and was no longer observed upon recovery.

The physiological relevance of the structure remains a subject for future research. Several hypotheses are suggested, including enhanced membrane deformability resulting from elevated catecholamine levels, and immunemediated agglutination, possibly stemming from viral infection.

 

“Flowers” in the blood: A novel paired erythrocyte arrangement in a patient with chronic fatigue syndrome following infectious mononucleosis by Carrie E Burdzinski, in Int J Case Rep Images 2014 [provisional article]

NB Dr Les Simpson from New Zealand reported in the 1980s about his discovery of abnormally shaped blood cells in people with ME.

Nondiscocytic erythrocytes in myalgic encephalomyelitis

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Sleep disturbance in POTS

Many patients with Postural Tachycardia Syndrome (PoTS) suffer from fatigue, daytime sleepiness and sleeping disturbances. The objective of this study was to compare subjective and objective sleep quality of PoTS patients with a group of healthy controls.

All Patients completed a Pittsburgh Sleep Quality Index questionnaire and the Epworth Sleepiness Scale. The patients sleep architecture, heart rate and heart rate variability measurements were taken during one night at the sleep laboratorium. All Data was collected at the Sleep Unit, at Helios Klinikum Wuppertal. 38 patients diagnosed with PoTS were compared to 31 healthy controls, matched in age and gender.

Patients with PoTS reached significantly higher scores in sleep questionnaires, which means that they were more sleepy and had a lower sleep quality.

Polysomnography showed a significantly higher proportion of stage 2 sleep. The results of heart rate variability analysis in different sleep stages confirmed changes in autonomic activity in both groups.

PoTS patients, however, showed a diminished variability of the LF band, HF band and LF/HF ratio in different sleep stages. It can therefore be gathererd that PoTS could be considered as potential differential diagnosis for sleep disturbances since PoTS patients had a subjective diminished sleep quality, reached higher levels of daytime sleepiness and showed a higher proportion of stage 2 sleep.

PoTS patients showed furthermore a reduction of LF/HF ratio variability in different sleep stages.

Sleep disturbances and autonomic dysfunction in patients with postural orthostatic tachycardia syndrome  by Julia Mallien et al in Front. Neurol.

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Altered immune response to exercise in CFS/ME

Abstract

An increasing number of studies have examined how the immune system of patients with Chronic Fatigue Syndrome (CFS), or myalgic encephalomyelitis, responds to exercise.

 

The objective of the present study was to systematically review the scientific literature addressing exercise-induced immunological changes in CFS patients compared to healthy control subjects.

 

A systematic literature search was conducted in the PubMed and Web of science databases using different keyword combinations. We included 23 case control studies that examined whether CFS patients, compared to healthy sedentary controls, have a different immune response to exercise. The included articles were evaluated on their methodological quality.

 

Compared to the normal response of the immune system to exercise as seen in healthy subjects, patients with CFS have a more pronounced response in the complement system (i.e. C4a split product levels), oxidative stress system (i.e. enhanced oxidative stress combined with a delayed and reduced anti-oxidant response), and an alteration in the immune cells’ gene expression profile (increases in post-exercise interleukin-10 and toll-like receptor 4 gene expression), but not in circulating pro- or anti-inflammatory cytokines.

 

Many of these immune changes relate to post-exertional malaise in CFS, a major characteristic of the illness. The literature review provides level B evidence for an altered immune response to exercise in patients with CFS.

 

Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review by J Nijs et al in Exerc Immunol Rev. 2014; 20:94-116

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Altered lymphocytes and immune system in CFS

Research Announcement

Objective:

The goal of our research is to define immunologic deficiencies of patients with chronic fatigue syndrome (CFS) and ultimately to improve the health of these patients by increasing their immunity.

Setting:

CFS is a debilitating disease of unknown cause(s) defined by the Centers for Disease Control and Prevention (CDC) in Atlanta, GA. Our patient population is the well-known Reno-Lake Tahoe CFS cohort.

Methods:

Peripheral blood is the site of traffic of lymphocytes with varying roles in immunity. Lymphocytes are circulating so as to be available to fight infections anywhere in the body or trafficking into secondary lymphoid organs where the lymphocytes will proliferate and differentiate.There are different types of lymphocytes in the blood [including helper T cells, cytotoxic T cells, T cells, B cells, natural killer (NK), and NK-T cells]. Alterations in these populations from healthy individuals are a hallmark of immune stress. To profile these populations, we used flow cytometry with fluorescent antibodies to identify the different populations of lymphocytes in the peripheral blood of CFS patients.

Results:

We found unusual increases in a ‘hybrid’ population of lymphocytes in CFS patients. This population has features of both T cells and NK cells and is normally 1-5% of all lymphocytes but can be as high as 30% in the CFS patients.

Interpretation:

The results are consistent with altered immunity in CFS patients, particularly altered immune responses to chronic viral infections. Further characterization, including repeated tests of the same patients, is needed to determine if this unusual population is persistent and to determine if it can mediate cytotoxicity towards virally infected cells.

Altered Distribution of Lymphocyte Populations in Chronic Fatigue Syndrome Patients, by Isabel Barao, Ph.D., Daniel Peterson, M.D., Dorothy Hudig, abstract on CTRIN website June 2014

An ongoing study into lymphocytes is taking place at Leeds University.

The main aim of the investigation is to shed light on any major common immunological mechanisms that might be responsible for the catalogue of symptoms shared by people with cancer or ME/CFS.

Lymphocyte phenotype and cytokine production in ME/CFS patients and patients treated with chemotherapy for breast cancer

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46% think CFS or ME legitimate reason to miss work

A quarter of UK residents don’t believe chronic illness is a legitimate reason to miss work. Many chronic and often invisible health conditions are not regarded by the British public as legitimate reasons for long term absence from work, survey findings show. The survey of 2,000 people found that while the majority (77%) of Britons agreed that chronic illness could be a legitimate cause of long term absence, perceptions of individual conditions differed widely. Migraine, repetitive strain injury and chronic skin complaints were perceived by most as not legitimate causes of absence, while only 7.6% were sympathetic to allergy-related absence. In contrast more than half (51.8%) felt that someone suffering from chronic joint problems such as rheumatoid arthritis, psoriatic arthritis, RSI and fibromyalgia would be justified in taking a long term sickness absence from work. Likewise more than two out of every five people questioned believed it was legitimate for people with inflammatory bowel disease and digestive conditions such as IBS and Crohn’s disease (45%) and chronic fatigue syndrome or ME (46%) to have time off sick. More than half (56%) were also sympathetic to people with chronic back pain to be signed off work sick, even though the symptoms are invisible to everyone apart from the sufferer. Interestingly, attitudes varied across the UK. London residents were least sympathetic to long term work absence due to chronic illness, with 29% saying none of the above mentioned conditions were sufficient reason to miss work. Yorkshire residents also took a firm stance against absenteeism, with 28% disagreeing with long term absence due to chronic illness. Northern Ireland were more tolerant however, with just 11% of residents against long term absence. Chronic illness ‘not an excuse’ for missing work  in Practice business 25/6/14

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Misdiagnosis of Femoral Arteriovenous Fistula as CFS

Case study abstract

Percutaneous arterial catheterisation is commonly undertaken for a range of diagnostic and interventional procedures.

Iatrogenic femoral arteriovenous fistulas are an uncommon complication of these procedures. Most are asymptomatic and close spontaneously, but can rarely increase in size leading to the development of symptoms.

We report a case of an iatrogenic femoral arteriovenous fistula, causing worsening congestive cardiac failure, in a 34-year-old marathon runner. This was originally diagnosed as chronic fatigue syndrome.

Following clinical examination, duplex ultrasound, and CT angiography a significant arteriovenous fistula was confirmed. Elective open surgery was performed, leading to a dramatic and rapid improvement in symptoms. Femoral arteriovenous fistulas have the potential to cause significant haemodynamic effects and can present many years after the initial procedure. Conservative, endovascular, and open surgical management strategies are available.

A Case of Femoral Arteriovenous Fistula Causing High-Output Cardiac Failure, Originally Misdiagnosed as Chronic Fatigue Syndrome by J Porter, Q Al-Jarrah and S Richardson in  Case Reports in Vascular Medicine Vol 2014 (2014), Article ID 510429

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Why people with CFS think they feel better or worse

Abstract

The purpose of this mixed methods study was to identify participants’ attributions for their global impression of change ratings in a behavioral intervention for unexplained chronic fatigue and chronic fatigue syndrome.

 

At 3-month follow-up, participants (N = 67) were asked “Why do you think you are (improved, unchanged, worse)?” Improved patients pointed to specific behavioral changes, unchanged patients referred to a lack of change in lifestyle, and worsened patients invoked stress and/or specific life events.

 

Identifying patient perceptions of behaviors associated with patient global impression of change-rated improvement and non-improvement may assist in developing more effective management strategies in clinical care.

 

Participant attributions for global change ratings in unexplained chronic fatigue and chronic fatigue syndrome by F Friedberg et al in J Health Psychol. 2014 Jun 8 [Epub ahead of print]

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A definition of recovery in ME & CFS should be based on objective measures

Abstract

 

INTRODUCTION:

Adamowicz and colleagues recently proposed to use “a consistent definition of recovery that captures a broad-based return to health with assessments of both fatigue and function as well as the patients’ perceptions of his/her recovery status” for patients with chronic fatigue syndrome (CFS).

 

METHODS:

A qualitative analysis of case definitions for Myalgic encephalomyelitis (ME) and CFS and methods to assess the symptoms and clinical status of ME and CFS patients objectively.

 

RESULTS:

The criteria of CFS define a heterogeneous disorder. ME, often used interchangeably with CFS, is principally defined by muscle weakness, cognitive impairment etc., but above all post-exertional “malaise”: a long-lasting increase in symptoms, e.g. muscle pain and cognitive deficits, after a minor exertion. The principle symptom of CFS however is “chronic fatigue”. Since post-exertional “malaise” is not obligatory for CFS, only part of the CFS patients meet the diagnostic criteria for ME, while not all ME patients qualify as CFS patients. There are several accepted methods to assess characteristic symptoms and the clinical status of ME and CFS patients using objective measures, e.g. (repeated) cardiopulmonary exercise tests.

 

CONCLUSION:

To resolve the debate about the clinical status, proposed effectiveness of therapies and recovery in ME and CFS, it is crucial to accurately diagnose patients using well-defined criteria for ME and CFS and an objective assessment of various typical symptoms, since subjective measures such as “fatigue” will perpetuate the debate.

 

A definition of recovery in myalgic encephalomyelitis and chronic fatigue syndrome  should be based upon objective measures, by FN Twisk in Qual Life Res Jun 17 2014  [Epub ahead of print]

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Macrophagic myofasciitis, vaccinations and CFS

Abstract

Macrophagic myofasciitis (MMF) characterized by specific muscle lesions assessing long-term persistence of aluminium hydroxide within macrophages at the site of previous immunization has been reported with increasing frequency in the past 10 years. We describe clinical and laboratory findings in patients with MMF.

We did a retrospective analysis of 16 cases observed in our Neuropathology Laboratory, between January 2000 and July 2013. The mean age of the 16 patients was 48.8 ± 18.0 years; 80.0 % were female. Chronic fatigue syndrome was found in 8 of 16 patients. Half of the patients had elevated creatinine kinase levels, and 25.0 % had a myopathic electromyogram.

Thirteen patients received intramuscular administration of aluminum-containing vaccine prior to the onset of symptoms.

MMF may mirror a distinctive pattern of an inflammatory myopathy. The vaccines containing this adjuvant may trigger MMF in some patients.

Macrophagic myofasciitis and vaccination: Consequence or coincidence? by T Santiago, O Rebelo, L Negrão,  A Matos in Rheumatol Int. 2014 Jun 13. [Epub ahead of print]

 

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Is CFS a meme (dysfunctional culturally-transmitted idea-infection)?

Response to 2004 article by Peter White: What causes Chronic Fatigue Syndrome?

Is Chronic Fatigue Syndrome a meme?, by Anthony D Collings, David Newton in BMJ 18 June 2014

In his 1976 book ‘The Selfish Gene’ (1) Richard Dawkins coined the term ‘meme’. Dawkins used the term particularly in relation to religious beliefs and defined it as an idea or group of ideas which propagate between individuals and which share many of the characteristics of life, including the abilities of propagation and self defence, and the capacity to evolve.

The concept of culturally-driven disease-disorders is not new (2) and memes have been suggested as a means of cultural transmission in various disorders including, in a general sense, in CFS (3).

Meme-mediated syndromes, it may be argued, are common in the history of medicine, from railway brain which dogged early travellers on railways in the mid-1800s, manifesting itself as neurological agitation and psychosis, attributed by some at the time to invisible damage to the brain caused by the unaccustomed jolting which necessarily accompanied railway travel in that era, via neurasthenia, a term used in the 19th century to describe ‘nerve weakness’ to (perhaps) whiplash and fibromyalgia. They arise and fall or in the case, arguably, of neurasthenia, evolve, to suit the culture that they live within.

Aaron Lynch (2) described general patterns of meme transmission:

Transmission within families – Transmission of memes vertically from parent to child.

Cultural separatism – Separatism creates a barrier to exposure of competing ideas

Proselytic-transmission Horizontal transmission: beyond the family.

Preservational Ideas that influence their hosts to hold them for a long time.

Adversative Ideas that influence those that hold them to attack or sabotage competing ideas and/or those that hold them.

Motivational Ideas that people adopt because they perceive some self–interest in adopting them.

How well does Chronic Fatigue Syndrome fit this model?

CFS has no known organic cause. It is diagnosed on the basis of exclusion of other morbidities which otherwise might explain the presenting symptoms. To use Lynch’s general patterns of meme transmission, with some examples:

Family: CFS clusters do occur in families, for no known cause.

Adversative. Preservational. There is a large group of sufferers who vociferously deny the possibility of a psychosocial cause for their symptoms, and discount accordingly the value of psychosocial treatments, though the only evidence based treatment addresses such causes. These sufferers tend to regard their condition as beyond cure

Cultural Separatism. Proselytive: It is generally accepted that membership of a CFS peer group is a predictor of poor outcome of treatment, and it has been argued that this may be due to negativity within the groups as to diagnosis, treatment and prognosis. CFS groups often make extensive use of information technology to promote their ideas and activities. Conversely, it has been suggested that being Asian (groups, arguably, whose distinctive cultural identities might well form barriers to memes) is a protective factor against CFS (4)

Motivational: A medical diagnosis can help to secure benefits and insurance recognition/validation.

It seems unlikely that memes alone account for the aetiology of CFS: quite likely many factors combine to bring about the condition. CFS might perhaps be most usefully thought of an emergent phenomenon, an ordered entity arising from a disordered combination of psychological, memeological, social and behavioural factors, much as a wave emerges from the complex, chaotic interplay of wind on water. It does however seem reasonable to conclude that the transmission, retention and evolution of the defining characteristics of CFS, particularly perhaps in the group one might term ‘Psychosocial Deniers’ might usefully be viewed through the meme model lens.

What is the practical use of viewing CFS as a meme?

Harmful memes can be displaced by benign memes, or influenced to evolve towards benignity. The mechanisms of bringing this about, as applied for instance in the ‘deprogramming’ of cultists may have useful applications in ‘dememeing’ CFS sufferers. Of course, GET and CBT, the sole treatments with significant evidence for the efficacy in CFS treatment, could be viewed as processes of dememeing.

Following this model, avoiding reinforcing of the meme would be advisable: avoidance of CFS (ME) peer groups; discouragement from indiscriminate reading around the subject (particularly on the Internet, a notoriously efficient spreader of memes); avoidance wherever possible of labelling sufferers with a diagnosis of CFS. Involvement of family therapists in treatment would be beneficial, to explore and combat vertical transmission.

Some or all of the above measures, as workers in the field would recognise, are followed to a lesser or greater extent by CFS services: reference to the meme model offers additional back-up for clinical practice.

CFS, then, might be usefully viewed as a meme, a dysfunctional culturally-transmitted idea-infection. Characteristics of transmission and retention of CFS fit well the characteristics of meme transmission and retention described in the literature. Present mainstream treatments for CFS make sense when viewed as a process of dememeing. Lessons may be learned for refinement of existing therapies or creation of new ones when viewing CFS from a meme perspective.

1. Dawkins, Richard (1989), The Selfish Gene (2 ed.), Oxford University Press, p. 192, ISBN 0-19-286092-5,

2. Lynch, Aaron (1996), Thought contagion: how belief spreads through society, New York: BasicBooks, p. 208, ISBN 0-465-08467-2

3. Ross SE. (1999), “Memes” as infectious agents in psychosomatic illness. Ann Intern Med; 131: 867-871.

4. Sokratis Dinos,1* Bernadette Khoshaba,1 Deborah Ashby,2 Peter D White,1 James Nazroo,3Simon Wessely4 and Kamaldeep S Bhui1: A systematic review of chronic fatigue, its syndromes and ethnicity: prevalence, severity, co-morbidity and coping. International Journal of Epidemiology 2009;38:1554–1570

Rapid response re: What causes chronic fatigue syndrome? 19 June 2014

Almost all of my patients with CFS/ME are self-diaqnosed, so when they say ‘I think have “ME”, I immediately agree.

Wherever I go, there is “ME”?

Presumably those cases transmitted by Anthony Collings “MeMe” constitute the homozygous form ?

L Sam Lewis, GP Trainer  NHS, Surgery, Newport, Pembrokeshire, SA420TJ

Other responses: EM Goudsmit  Stephen E Ralph  Ellen CG Grant  Nasim Marie Jafry  Neil C Abbot  Suzy Chapman  JK Anand

 

 

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