Chronic Fatigue Syndrome - Myalgic Encephalomyelitis - Systemic Exertion Intolerance Disease - Chronic Fatigue Immune DeficiencySyndrome

Fatigue is one of the most common reasons people seek consultation with health care providers. 

Recently the Institute of Medicine released a report suggesting that Chronic Fatigue Syndrome (CFS)  and Myalgic Encephalomyelitis (ME) be reclassified as Systemic Exertion Intolerance Disease (SEID).  This has raised many questions and concerns about the new classification being too broad, as pointed out here. There is no known single etiology for ME/CFS, but current research coming out of the Stanford ME/CFS Initiative is pointing towards immune system disruption. Because of this I actually prefer the term Chronic Fatigue Immune Deficiency Syndrome (CFIDS). Honestly, at this point, I don't really care what they call it, as long as it is recognized by the Medical/Scientific Community and we start looking for a cure.

Currently, there are between 800,000 and 2.5 million adults in the United States suffering from Chronic Fatigue Syndrome (CFS). The CDC now estimates that 85% of ME/CFS cases may be undiagnosed and the actual number could be 6 to 10 times higher. It is estimated that over 130 Million Americans are currently diagnosed with a Chronic Illness and another 50 million suffering from autoimmune disease. How many of them also suffer from ME &/or CFS?

The fact is, there is no known single cause for ME or CFS, but the most widely accepted theory is that a viral or bacterial illness triggers something similar to an autoimmune response. I'm not going to go into etiology until later, but I will tell you, there is a ton of evidence suggesting the presence of immune dysfunction in connection with ME and CFS.  In my daughters case, Parvo B-19, Ehrlichia Chaffeensis plus Lyme and co-infections caused ME/CFS and she is still dealing with it 3 years later.

*See My Personal/Professional Backstory on CFS Below

The CDC Definition of Chronic Fatigue Syndrome (CFS):

The primary symptom of CFS is unexplained, severe fatigue lasting at least 6 months that is not improved by bed rest and that can get worse after physical activity or mental exertion. Individuals with CFS experience a fatigue so strong that their activity levels and stamina decline dramatically. However, fatigue is not the only symptom, and for some patients may not be the symptom that bothers them the most.

As stated in the 1994 Fukuta case definition, the fatigue of CFS is accompanied by at least 4 of 8 characteristic symptoms lasting at least 6 months. These symptoms include:

• Post-exertion malaise 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

International Consensus Criteria for Myalgic Encephalomyelitis (ME):

Resent research has strongly pointed towards widespread inflammation and multi-systemic neuropathology as the cause of ME. There are a broad spectrum of symptoms as follows: 

• Postexertional neuroimmune exhaustion (PENE) The cardinal feature here is a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions. 
• Neurological impairments (at least 1 of the following 3 symptoms)
• Neurocognitive impairment: difficulty processing info or memory loss.
• Pain: Headache or musculoskeletal pain.
• Sleep disturbance: disturbed sleep pattern or unrefresing sleep.
• Neurosensory, perceptual and motor disturbances: 
• Hypersensitivity to light, sound, vibration, taste, touch. 
• Muscle twitching, poor coordination, ataxia.
• Immune, gastro-instestinal and genitourinary Impairments (1 of the following 5)
• Flu-Like symptoms (may include sore tender lymph nodes)
• Susteptibility to viral infections with prolonged recovery
• Gastro-intestinal symptoms: Nausea, Irritable Bowel
• Multiple sensitivities to food, medications, ordors or chemicals
• Energy production/transportational impairments: (at least 1 of 4)
• Cardiovascular: orthostatic intolerance, POTS, palpitations, dizziness
• Respiratory: air hunger, labored breathing
• Loss of thermostatic stability: subnormal body temp, feeling feverish without a fever.
• Intolerance of Heat/Cold
• Pediatric Considerations:
• The headaches are often severe or debilitating. Migraine may accompany a rapid drop in body temperature, shaking, vomiting, diarrhea and weakness.
• Neurocognitive impairment: difficulty focusing eyes, reading, dyslexia, slow processing and difficulty following verbal instructions are common. 
• Pain may seem erratic and migrate quickly. 

Unfortunately, in their Wichita clinical Study, the CDC is not making a distinction between patients with Chronic Fatigue who do or do not also have symptoms of Myalgic Encephalomyelitis. I have met patients who have either ME or CFS separately, and many more who have both ME & CFS together. To me, the hallmark of CFS is the profound, lasting fatigue, and the hallmark of ME is the measurable neurologic dysfunction. From a patients perspective, see the definition of Spoon Therory.

Although ME and CFS are frequently used interchangeably, the case criteria for ME and CFS are clinically two distinctively different entities. The following figure delineates the partial overlapping patient populations by definition.

The IOM's Diagnostic Criteria for Systemic Exertion Intolerance Disease: SEID

For a positive Diagnosis the patient must have all of the following three symptoms: 

1. A substantial reduction or impairment in the ability to engage in pre-illess levels of occupation, educational, social, or personal activities, that persists for more than 6 months and is accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is to the result of ongoing excessive exertion, and is not substantially alleviated by rest, and
2. Post-exertional malaise, and
3. Unrefreshing sleep

And At least one of the following two symptoms: 

1. Cognitive impairment, or
2. Orthostatic intollerance 

* What I don't like about this new SEID criteria is that someone who is clinically depressed will be thrown into the same ICD-10 diagnosis as someone with a post-viral encephalomyelitis. 

I didn't really understand the significant differences between the diagnoses until I chatted with Kit a blogger at arainbowatnight.com who has suffered a decade with M.E. She feels lumping the diagnoses together does a great disservice to patients with Myalgic Encephalomyelitis as pointed out here

So What is Causing ME and CFS? 

My gut says it is a combination of genetic predisposition, and either a latent viral or bacterial infection that is triggered by a new, acute infection. There are a number of infections that through antigenic variation are able to avoid immune clearance. "Pathogens with antigenic variation systems are able to evade the immune response, thus gaining a selective advantage…"  These pathogens lend themselves to chronic infections, lingering, hiding, invading and causing immune deficiency. 

These are Examples of Infections that Avoid Immune Clearance through Antigenic Variation: 

• Anaplasma marginale (bovine Rickettsiales)
• Borrelia burgdorferi (Lyme)
• Borrelia hermsii (tick-borne relapsing fever)
• Camplyobacter jejuni (causes gastroenteritis)
• Candida species (yeast infection)
• HIV(causes AIDS)
• Influenza Virus (the Flu)
• Mycoplasma synoviae (infectious synovitis in poultry)
• Mycoplasma pulmonis (mice/rats host, can transfer to humans)
• Neisseria gonorrhoeae (gonorrhea)
• Neisseria Meningigitidis (causes meningitis)
• Plasmodium falciparum (Malaria)
• Treponema pallidum (Syphilis)
• Trypanosoma brucei (sleeping sickness)

I believe science is on the verge of proving ME and CFS are caused by an infectious disease. Because the infection can be viral or bacterial or both, I do not think there will be a one-size-fits-all approach to a cure. I do believe the treatment will need to include antibiotics and/or anti-viral therapy as well as restoring the immune system. How exactly we do this I don't know, but As Professor Rolf M. Zinkernagel, Nobel Prize Winner for Medicine in 1996 said,

"To combat an infection, one first needs to understand the host immune system."

I'll talk more about this later… 

*My Backstory on Chronic Fatigue Syndrome and Fibromyalgia
When I was going to college to become a Physical Therapist, I worked for a large group of Neurologists in their pain management clinic. Most of our patients had a clear-cut diagnosis, like a bulging disc or were status-post discectomy or spinal fusion surgery. We had standardized protocols for these patients and treating them became second nature for me. There was however, another subset of patients that absolutely confounded me. They were the "fibromyalgia" and "chronic fatigue" patients. I was always stumped on how to make them better. Deep tissue massage made them worse. Graded exercise made them worse. Heat sometimes made them dizzy and nauseous. So little was known about this syndrome back then. There was no know etiology and no standardized treatment protocol. It was very frustrating and I'll admit these patients became my least favorite to work on.

After I graduated from PT school there was one thing I knew I did not want to do--work in a pain management clinic. I first worked for a large Rehabilitation facility in Los Angeles on the spinal cord injury unit. After I left L.A. I landed my dream job working for a Hospital where I specialized in Emergency and Acute Care. That means most of my working experience has been with burns, head injuries, motor vehicle injuries (spinal injuries, broken bones), strokes, acute cardiac rehab and orthopedic post-ops (like total knee and total hip replacements).

When my daughter became ill in 2012 (her story here), I was in a situation I hadn't been in for years. I was faced with a patient suffering from chronic pain and chronic fatigue, except this time the patient was my own child. Thankfully, my training and experience came back to me. Because I had to quit work to take care of her I was able to spend a good deal of time researching how to treat ME and CFS. Finding a cure for my daughter and others like her has become my passion in life.

Additional Considerations: 

Ehlers-Danlos Syndrome, a genetic condition which affects connective tissue, and should be considered in all patients with hyper mobility.

References:
Evidence for the Presence of Immune Dysfunction in Chronic Fatigue Syndrome | NCBI
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC120010/

Evidence for a heritable predisposition to Chronic Fatigue Syndrome | BioMed Central 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128000/

B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome | PLOSone
http://www.ncbi.nlm.nih.gov/pubmed/26132314

Altered functional B cell subset populations in patients with Chronic Fatigue Syndrome compared to healthy controls. | Journal of Translational Immunology
http://www.ncbi.nlm.nih.gov/pubmed/23480187

Role of adaptive and innate immune cells in Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis |
http://www.ncbi.nlm.nih.gov/pubmed/23480187

Autoimmune Basis for Postural Tachycardia Syndrome | Journal of the American Heart Association
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959717/

Health Care Costs, Utilization and Patterns of Care following Lyme Disease | Johns Hopkins Study
(63% of patients with Lyme Disease have lingering symptoms after antibiotic treatment PTLDS)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317177/

Postural tachycardia syndrome is associated with significant symptoms and functional impairment…
(POTS is detected in approximately 15% of ME/CFS patients)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317177/

Chronic Fatigue: NIH Literature Review Faulted | Medscape
http://www.medscape.com/viewarticle/833428

Stanford Study Finds Brain Abnormalities in Chronic Fatigue Patients | Stanford Medicine
http://med.stanford.edu/news/all-news/2014/10/study-finds-brain-abnormalities-in-chronic-fatigue-patients.html

Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome | Radiology
http://pubs.rsna.org/doi/abs/10.1148/radiol.14141079

Immune system disruption: The search for answers | Stanford Medicine
http://stanmed.stanford.edu/2014fall/immune-system-disruption.html

Evidence in Chronic Fatigue Syndrome for severity-dependent up regulation of prefrontal myelination that is independent of anxiety and depression. | NCBI
http://www.ncbi.nlm.nih.gov/pubmed/?term=Evidence+in+chronic+fatigue+syndrome+for+severity-dependent+upregulation%C2%A0of

Accurate diagnosis of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome based upon objective  test methods for characteristic symptoms.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482824/

Detailed Analysis of Sequence Changes Occuring during vIsE Antigenic Variation in the Mouse Model of Borrelia burgdorferi |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632889/

Epigenic Regulation of Immune Cell Functions During Post-septic Immune Suppression
http://www.ncbi.nlm.nih.gov/pubmed/21048427

Diagnostic Criteria:
CDC Case Definition for Chronic Fatigue (1994 Fukuta Criteria)
http://www.cdc.gov/cfs/case-definition/1994.html

Chronic Fatigue Syndrome: A working case definition | NCBI (Holmes Criteria 1998)
http://www.ncbi.nlm.nih.gov/pubmed/2829679

Chronic Fatigue Syndrome--A clinically empirical approach to its definition and study | BioMed Central (Reeves Criteria 2005)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1334212/

Contrasting Case Definitions for Chronic Fatigue Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Myalgic Encephalomyelitis
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658447/

Note: I am a licensed Health Professional, but I AM NOT A DOCTOR. I cannot diagnose nor can I prescribe treatment. While I will attempt to provide citations the basic information contained in this blog is simply my opinion. 

Editied: 7/26/15