History Of Chronic Fatigue Syndrome

Evidence Of Abnormalities In Me/cfs And Loss Of Normal Homeostasis

Concepts that are relevant here are those of homeostasis and allostasis. While homeostasis refers to the âstability of physiological systems,â allostasis has been defined as âthe adaptive processes aimed to maintain homeostasis following acute stress, and which contribute to wear and tear on the body and the brain, or allostatic overloadâ . A central characteristic of individuals with ME/CFS points to a state of homeostatic failure , aggravated by the incidence of, or increase in, levels of new stressors or by the increase in allostatic load . Typical stressors include infection , physical exertion and cognitive effort triggering post-exertional malaise , comorbid conditions and a range of environmental and individual factors .

There is a growing body of evidence on biological abnormalities in ME/CFS that has been reviewed elsewhere , and summarized by Komaroff . Of note, many of the abnormalities shown in severe injury have also been identified in ME/CFS such as: immune dysfunction, including pro-inflammatory response autonomic nervous system HPA axis dysfunction hypovolemia nitrosamine and oxidative stress endothelial dysfunction metabolic dysfunction dysfunction of membrane transport and, tissue hypoxia .

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In December of 2012, I came down with what at first looked like a bad case of mononucleosis. I felt tired and had a sore throat, a cough, and a slight fever. At the time, I was twenty-six and working as an adjunct English professor at a small college in Westchester, New York. It was Christmas break, so I thought that I would sleep it off and feel better by the New Year. But over the next few months my symptoms grew to include muscle pain, migraines, and occasional vertigo. The cough went away but the tiredness got worse, and by the summer I was spending half my time resting in bed. I was used to playing pickup basketball several times a week after work, but now a few pushups left me exhausted. I couldnt figure out what was happening. One afternoon, as an experiment, I went for a run near my apartment, in uptown Hoboken. I clipped my iPod Shuffle to my mesh shorts and jogged past Italian delis with dry-cured sausages in their windows and along a pier that hugged the Hudson. It felt amazing. But the next day, while grading papers with a few other teachers, suddenly, I became dizzy and weak. I left the office without explanation, and, for the next several days, I barely left my bedroom.

A previous version of this story incorrectly described cytokines and misstated the location of a clinic dispensing Ampligen.

A Hypothetical Association Between Ebv And Me/cfs

As mentioned above, EBV infection has been identified as a risk factor in a subgroup of ME/CFS patients . There are studies showing a statistically significant elevation of anti-EBV-dUTPase antibodies , a defective EBV-specific B and T cell response , a high rate of active EBV infection , serologic evidence of EBV reactivation with elevated IgM antibodies against late VCA antigen , and a positive up-regulation of EBV-induced gene 2 mRNA in peripheral blood mononuclear cells from a subgroup of patients with ME/CFS. However, serological observations related to EBV were not always confirmed and, accordingly, the association between EBV infection and ME/CFS is not established . Furthermore, the presence of an active EBV infection in a subgroup of ME/CFS patients has been actively debated, because most studies revealed no increase in EBV viral load in ME/CFS patients. If a third state of virus, defined as abortive/lytic/leaky replication could explain the presence of certain EBV proteins with the potential capacity to contribute to the symptomatology of ME/CFS , is an hypothesis that remains unconfirmed.

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Is There A Cure For Chronic Fatigue Syndrome

Unfortunately, no. But there are methods for managing symptoms. As an article in The Atlantic eloquently explained in an interview with David Kaufman, the medical director of the Open Medicine Institute in Mountain View, California:

Simple diseases work like a chain of dominoes, with a clear cause setting off a series of possible symptoms, which hint at a diagnosis, and, usually, a standard treatment. Click, click, click, youre cured. Chronic fatigue is more like a pile of pick-up sticks: a giant mess in which no one can see a beginning or end. Most patients begin their history by saying something like, I was totally fine, and I got mono at 19 and Ive never been the same since, said Kaufman, who later treated Vastag .I want to find a single, neat, nice packaged cause. Every day I think Im less and less likely to find that.’

Some people who suffer from CFS are housebound or bedridden, long-term or for short periods of time. The majority of patients, however, are able to remain functional with a regime of different medications, therapies, exercise plans, or other interventions.

To learn more about what treatment options are available to you, click the link below. There, youll find a doctor who can review your chronic fatigue syndrome symptoms and provide options for finding relief.

Disease Severity And Reversibility

It is unknown how the initial host response to a stressor or insult compares in individuals who do or do not develop typical symptoms of ME/CFS. However, the return to good health, which happens to most people following exposure to mild or moderate levels of insult, seems to be impeded in ME/CFS when symptoms persist for longer than 3â6 months the time interval that is featured in some of the currently used diagnostic criteria . This suggests that subsequent mechanisms involved in the host response will differ at some point in those who develop ME/CFS from those who regain full health. Therefore, a key question is what determines full recovery? Or alternatively, what determines the perpetuation and transformation of symptoms?

While the abnormalities observed in acute disease are general and mostly reversible once the challenge from the stressor ceases, some degree of dysfunction may persist for longer periods. The degree of reversibility of various physiological abnormalities is likely to decrease with time, and some permanent functional, and even structural, damage may occur consequently. This is likely caused by either the persistence or frequent reactivation of the initial stressor , an accumulation of insults, a continuing dysfunctional host-response, or the effects of the numerous psychosocial risk factors that influence disease development and progression , or a combination of all of these.

Figure 2. Hypothetical stages of disease in ME/CFS.

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Do I Have Chronic Fatigue Syndrome

Unfortunately, reaching a diagnosis can be a complicated and long process for many patients. Because it shares so many symptoms with other conditions, its diagnosed by ruling out similar diseases. However, there is a path to diagnosis.

As HealthLine notes, to be diagnosed with chronic fatigue syndrome, you must have at least four major symptoms. In addition: You also must have severe, unexplained fatigue that cant be cured with bed rest. The fatigue and other symptoms must last for six months or longer.

You may have chronic fatigue syndrome if:

• You have severe, unexplained fatigue that is severely impacting your quality of life
• Youre suffering from a combination of post-exertional malaise, unrefreshing sleep, cognitive impairments, or symptoms that worsen when you stand upright
• Your symptoms rule out another similar condition, like fibromyalgia or Lyme disease
• These symptoms have lasted for six months or more

You may also be more likely to have CFS if youre a middle-aged woman. According to some sources, chronic fatigue syndrome is diagnosed four times more often in women than men.

However, many believe that chronic fatigue syndrome is seriously under-reported and under-diagnosed. You should always talk to your doctor or a pain specialist if you believe that youre suffering from this condition.

Key Points About Chronic Fatigue Syndrome

• Chronic fatigue syndrome is characterized by profound tiredness.
• Symptoms often worsen with physical or mental activity.
• In addition to severe fatigue, symptoms include light sensitivity, headache, muscle and joint pain, difficulty concentrating, mood swings, and depression.
• Treatments may include medicines, exercise, supplements, and counseling.

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Diagnosis Of Chronic Fatigue Syndrome

• Clinical criteria

• Laboratory evaluation to exclude non-CFS disorders

The diagnosis of CFS is made by the characteristic history combined with a normal physical examination and normal laboratory test results. Any abnormal physical findings or laboratory tests must be evaluated and alternative diagnoses that cause those findings and/or the patient’s symptoms excluded before the diagnosis of CFS can be made. The case definition is often useful but should be considered an epidemiologic and research tool and in some circumstances should not be strictly applied to individual patients.

In February 2015, the Institute of Medicine published an extensive review of this disease called Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. In this review, they proposed a new name, systemic exertion intolerance disease , and new diagnostic criteria that simplified the diagnosis and emphasized the most consistent features. In addition, the review clearly emphasized the validity of this debilitating disease.

Prevalence And Clinical Features

It is difficult to establish the prevalence of CFS, since it depends on the diagnostic criteria used and the study population. Initial research suggested a prevalence between 0.002% and 0.04%. . However, latest epidemiological studies in the USA and in the United Kingdom show prevalence rates ranging from 0.007% to 2.5% of the general population. These rates increase up to 0.5-2.5% when the population assessed includes individuals seen in primary care facilities instead of the global population. In the United Kingdom, according the Oxford criteria , the prevalence in the global population has been estimated in 0.6%. In Japan the prevalence has been found to be 1.5% in the general population. Thus, the prevalence in the general population appears to be much higher than previously indicated. Even with strict criteria for CFS, it is estimated that approximately 1% of the adult population experiences this condition. Interestingly, a large part of this group remains unrecognized by the general practitioner. A striking similarity in lifestyle pattern between SF, CF and CFS calls for further research.

CFS mainly affects young adults from 20 to 40 years, although the symptoms also exist in childhood, adolescence and in the elderly . It has a 2-3 times higher prevalence in women than in men. No evidence exists showing that any socio-economic group is more affected than others .

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Impact And Prognosis Of Me/cfs

• Nacul L.
• Lacerda E.M.

Pharmacoecon Open.

• Campion P.
• et al.

BMC Public Health.J Chronic Fatigue Syndr.

• Cox D.L.
• Findley L.J.

Br J Occup Ther.

• Mild: mobile and self-caring may continue working but will have reduced other activities
• Moderate: reduced mobility, restricted in instrumental activities of daily living, needs frequent periods of rest usually not working
• Severe: mostly housebound limited to minimal activities of daily living severe cognitive difficulties may be wheelchair dependent
• Very severe: mostly bedridden unable to independently carry out most activities of daily living often experience extreme sensitivity to light, sound, and other sensory input

• Tian H.
• et al.

Am J Epidemiol.Chronic Illn.

Qual Life Res.Disabil Rehabil.Occup Med .

Rehabil Psychol.Front Pediatr.Fatigue.

Predisposition And Triggering Of Disease

Individuals with a combination of genetic predispositions and exposures to environmental factors may first manifest symptoms of ME/CFS following their encounter with a specific trigger, of which acute infections of various etiologies are the most commonly reported other patients report a more insidious onset with no obvious initiating factor . While it remains unclear exactly which individuals are predisposed to develop ME/CFS and why, some patterns have emerged. For example, gender- and age-specific factors are thought to contribute to the risk of ME/CFS , with epidemiological studies consistently reporting higher rates of the disease in females . Although most cases are endemic, there have been reports of epidemic cases, suggesting an infectious or other environmental cause play a role although discrepancies in onset patterns and case definitions make these epidemics difficult to compare . Many studies have reported an association between acute viral infection and the development of ME/CFS . Cases are predominantly reported in North America, Europe, and Oceania however, the occurrence of ME/CFS is thought to be global with evidence of cases in other parts of the world .

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What Are The Symptoms Of Chronic Fatigue Syndrome

Symptoms of CFS often mimic the flu. The following are the most common symptoms of CFS. However, each person may experience symptoms differently. Symptoms may include:

• Sensitivity to light
• Low-grade fever
• Depression

The symptoms of CFS may look like other medical conditions. Always talk with your healthcare provider for a diagnosis.

How Is Chronic Fatigue Syndrome Diagnosed

CFS diagnosis depends on two criteria:

A specific treatment for CFS has yet to be proven effective. Vitamin supplements and medicines have some benefit. Many treatments just relieve the symptoms of CFS.

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Health Care Costs And Utilization

Patients with ME/CFS spend considerably more on health care than thegeneral medical patient population . They also see morephysicians and visit their health care providers more often relative tothe general medical patient population . Manypatients report barriers to accessing health care as well, including thenature of their illness and financial considerations .

Common Comorbidities In Me/cfs

There are a number of comorbid conditions associated with ME/CFS and, as such, these comorbidities can complicate diagnosis, treatment and research of the disease. Comorbidities have been found in up to 97% of people with ME/CFS with some developing before, with, or after ME/CFS onset . The complexity of ME/CFS is in part due to the number of different systems affected that contribute to the many and varied symptoms experienced. ME/CFS and FM share a number of overlapping core symptoms that mean the two are commonly experienced together FM has been reported to co-occur in 12â91% of PWME . However, there is evidence to suggest the two conditions differ in their hormone dynamics, genetic/molecular biology, and autonomic function . This is reiterated by the absence of post-exertional malaise in FM , which is one of the key features of ME/CFS .

Also highly prevalent in those with ME/CFS is orthostatic intolerance , a common multifactorial disorder commonly accompanying neurodegenerative, cardiovascular, metabolic, and renal disorders . Disruptions to ANS and reduced blood volume contribute to OI and the same systemic dysfunctions have been reported in those with ME/CFS however, not all people with OI disorders have ME/CFS .

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Diagnosis And Treatment For Me/cfs

Currently, there is no single test to diagnose ME/CFS. Doctors make a diagnosis by excluding all other illnesses that might be causing symptoms and following accepted diagnostic criteria. The persons results from routine medical tests will often be normal, but additional tests may show abnormalities.

Tips For Exercising Safely With Me/cfs

If you feel you can tolerate some exercise, be guided by your doctor or specialist, but general suggestions include:

• Experiment to find the type of exercise that works best for you. Choose from a range of gentle activities such as stretching, yoga, tai chi, walking and light weight training. Often, people find exercises lying down use less energy.
• Keep an activity diary so you have a long-term picture of your performance levels and factors that might impact on your symptoms. Some people with ME/CFS find they feel good straight after exercise, but then crash later on, so make sure you monitor how you feel, hours to days after exercise.
• Stop the physical activity well before you feel any symptom flare. Pacing yourself is very important.
• Remember that the amount of exercise you can do will change from one day to the next.
• Listen to your body if you dont feel up to exercising on a particular day, dont.
• Find out as much as you can about your ME/CFS. Make sure you consult with health professionals who fully understand ME/CFS as a biomedical disease

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Treatment Of Chronic Fatigue Syndrome

• Acknowledgment of patient’s symptoms

• Sometimes graded exercise, limited to avoid a setback

• Drugs for depression, sleep, or pain if indicated

To provide effective care to patients with CFS, physicians must acknowledge and accept the validity of patients’ symptoms. Whatever the underlying cause, these patients are not malingerers but are suffering and strongly desire a return to their previous state of health. For successful management patients need to accept and accommodate their disability, focusing on what they can still do instead of lamenting what they cannot do.

If these measures are ineffective, hypnotic drugs and/or referral to a sleep specialist may be necessary. Patients with pain widespread tenderness of muscles, areas around… read more ) can be treated using a number of drugs such as pregabalin, duloxetine, amitriptyline, or gabapentin. Physical therapy is also often helpful. Treatment for orthostatic hypotension Treatment Orthostatic hypotension is an excessive fall in blood pressure when an upright position is assumed. The consensus definition is a drop of > 20 mm Hg systolic, > 10 mm Hg diastolic… read more may also be helpful.

Unproven or disproven treatments, such as antivirals, immunosuppressants, elimination diets, and amalgam extractions, should be avoided.

Summary Of Key Features Of The Case Definitions For Chronic Fatigue Syndrome/myalgic Encephalomyelitis

Overview of Inclusions

• Fatigue + 4 out of 8 case-defining symptoms:
• PEM lasting more than 24 hours
• Unrefreshing sleep
• Significant impairment of short-term memory or concentration
• Muscle pain
• Pain in the joints without swelling or redness
• Headaches of a new type, pattern, or severity
• Tender lymph nodes in the neck or armpit
• A sore throat that is frequent or recurring

Duration

• 6 months

Fatigue

• 6 months new onset severe persistent or relapsing fatigue
• Unexplained after clinical evaluation
• Not explained by ongoing exertion
• Not substantially relieved by rest
• Results in substantial reduction in occupational, educational, social, or personal activities

Post-exertional malaise

• Not required but one of the 8 case defining symptoms

Minimum number of symptoms5

Exclusions

• Active medical condition that explains chronic fatigue untreated hypothyroidism, sleep apnea, narcolepsy, medication side effects
• Previous diagnosis not unequivocally resolved chronic hepatitis, malignancy
• Past or current major depressive disorder with psychotic or melancholic features, bipolar disorder, schizophrenia, delusional disorders, dementias, anorexia nervosa, bulimia nervosa
• Alcohol or substance abuse within 2 years of illness onset or anytime after
• Severe obesity

Accepted co-morbidities

ReferenceFukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: A comprehensive approach to its definition and study. Ann Intern Med 121:953-959, 1994.

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