Causes and Treatments of ME/CFS
Once you have ruled out common diseases with similar symptoms, and have settled on a diagnosis of ME/CFS, then next stage is to try to identify the underlying infections and other factors that may be causing or contributing to your ME/CFS. This is best performed with the help of a doctor specializing in chronic fatigue syndrome laboratory testing and treatment.
There are many laboratory tests that people with ME/CFS might choose to take. In this roadmap to ME/CFS testing and treatment, the tests suggested are grouped into various rounds, with the most important tests placed in the earlier rounds. After each round of testing, depending on the test results, advice on an appropriate course of action for treatment is given.
Tests for causal factors that have a corresponding treatment or cure are prioritized, since the main goal of this roadmap is to guide people with ME/CFS to treatments that may improve or cure their condition. Tests that provide insight into your circumstances of health, but having done so, do not lead to corresponding treatments, are deferred to later.
The suggested treatment plans are those generally employed by leading chronic fatigue syndrome doctors and researchers in the field. There are no hard and fast rules for chronic fatigue syndrome treatment, and you may wish to follow different courses of action to those given here. These guidelines are an ongoing project which aims to be reasonably comprehensive; but they are not an exhaustive chart of ME/CFS treatments.
Research indicates that treatment-resistant ME/CFS of unproven etiology generally appears to be associated with viruses from the enterovirus genus (specifically: coxsackievirus B and echovirus) and/or to viruses from the herpes family (specifically: human herpes six virus, cytomegalovirus, Epstein-Barr virus). More treatable or curable forms of ME/CFS may be caused by parvovirus B19, Chlamydia pneumoniae, as well as other microbes. Non-microbial causes or contributory factors to ME/CFS include: mold toxin exposure and pesticide exposure. The first round of testing detailed below suggests you consider or get tested for all these microbes and causal factors.
Notes on Pathogen Testing
Most ME/CFS-associated microbes are very commonly found in the general population: Epstein-Barr virus, for example, is found in 95% of adults. Microbes found in the body are generally acquired from infections earlier in life, but once the immune system has them under control, these infections become largely inactive and dormant; so microbes from past infections normally exist in the body in a latent state (though these pathogens can reactivate and become more active if there is weakness in the immune system).
When a test is performed for a microbe, we want to know not only whether you have it in your body, but more importantly, whether it is active or not. In chronic infections, the level of activity of a microbe can be determined to an extent by the amount of IgG antibodies your body produces in response to that microbe. High levels of IgG antibodies suggests an active chronic infection.
Antibody testing. Antibody testing is a common way of measuring the activity of a microbial infection in the body. An overview of antibody testing is as follows. The immune system manufactures antibodies specific for each microbe you catch. Antibodies are made to target and bind to a particular microbe, facilitating its destruction. At the onset of a microbial infection (such as when you first catch a cold), the immune system initially responds by making IgM type antibodies to target the microbe. As this acute infection is slowly brought under control (when your cold is finally going), IgM has done its job, and the levels of IgM gradually go down to zero. At the same time, the immune system now starts making IgG type antibodies, which are designed to take over the job of IgM. IgG antibodies remain in the body for your whole life, trying to prevent the same infection from flaring up again.
In an antibody blood test, it is therefore clear that finding high levels of IgM and no IgG indicates you have an infection in its initial acute stage. Conversely, finding IgG, but little or no IgM, indicates you have a past infection (which is where a microbial infection from an earlier point in your life has now been brought under control by the immune system, and so this infection is in a dormant state). However, finding slightly higher levels of IgG and little or no IgM indicates the infection has not been fully brought under control, and that you have an active chronic ongoing infection. One or more active chronic ongoing infections are often found in ME/CFS patients.
Antibody levels are measured by what is known as a titer. The higher the titer, the more antibodies you have, and the higher the microbial activity in your body.
Note that the activity of some microbes, notably enteroviruses, cannot be so accurately determined by antibody tests, due to the fact that these microbes can also live inside human cells, as an intracellular infection. The immune system does not readily make antibodies to microbes living inside human cells, so you may have a significant intracellular enterovirus infection, but show relatively low antibody levels when you take a test. Other means of pathogen testing may be employed in these situations. Alternative methods of testing for the presence of pathogens in the body include: PCR (polymerase chain reaction) and viral culture. Viral culture is usually the "gold standard" by which other viral detection methods are judged.
Empirical testing. While it is always better to test for pathogens or health conditions before using treatments, because some tests are expensive, not available in all countries, or might not always be reliable or sensitive enough to detect certain pathogens, you may choose to bypass the test and go straight to treatment. This is known as empirical testing: using a treatment itself as a test for a pathogen or health condition. Empirical testing makes the assumption that if you get better on the treatment, you may well have the pathogen or the health condition that the treatment targets. (However, most drugs and herbs have multiple actions, so for example if an antibacterial drug helps, it may be for reasons other than its antibacterial properties).
1st Round Tests
The first set of ME/CFS causal factors to consider and/or test for is shown in the table below. The various microbial (and other) causal factors are listed in the left hand column, and recommended tests for these causal factors (plus some basic guidance on interpreting the test result) are given in the right hand column of the table.
FIRST ROUND TESTS
Causal Factor
Tests and Results Interpretation
Epstein-Barr virus (EBV)
There is a high 95% prevalence of Epstein-Barr virus in the adult population, so most people will have this virus in their system, but usually in a latent inactive state. However, if you have an active EBV infection, it is possible this may be contributing to or causing your ME/CFS symptoms. New evidence indicates that some subtypes of ME/CFS may be due to partial reactivation of Epstein-Barr virus.1 2
Epstein-Barr virus antibodies. A blood test showing an EBV VCA IgG antibody titer of 1:1280 or more suggests an active infection.1
Dr A Martin Lerner says that a positive diagnosis of Epstein-Barr virus infection requires a positive EBV early antigen (EA) diffuse test, and/or a positive EBV IgM viral capsid antibodies (VCA) test.1
Epstein-Barr virus PCR.
Lymphocyte subset panel. If this test shows elevated CD8 T-cells, this can indicate an ongoing viral infection with EBV or cytomegalovirus, which both raise CD8.1
Human herpes virus six (HHV-6)
HHV-6 is found in over 90% of adults, usually in a latent inactive state. If you have an active HHV-6 infection, this may be contributing to or causing your symptoms, as active HHV-6 is linked to ME/CFS.1 2 There are two main variants of HHV-6: variant A and variant B, often denoted as HHV-6A and HHV-6B. Tests for HHV-6 do not usually distinguish between the two variants.
Most individuals that test positive for HHV-6 will have the more benign HHV-6B variant; but just under 3% will have the more nasty HHV-6A variant. It is this HHV-6A variant which is more strongly linked to ME/CFS.1 So a positive test for HHV-6A may be quite significant if this virus is active.
Dr Kazuhiro Kondo has a theory that partial reactivation of HHV-6 may cause ME/CFS, as well as depression and bipolar disorder.1
HHV-6 antibodies. A blood test showing an HHV-6 IgG antibody titer of 1:320 or more suggests an active infection. Dr Jose Montoya believes that IgG antibody levels are a better guide to the HHV-6 activity in the central nervous system than viral culture from the blood.1
Nested PCR for HHV-6A. Regular tests do not distinguish between the these two variants of HHV-6, so if you tested positive for HHV-6, you could have either (or both). However, nested PCR tests can specifically determine if you have HHV-6A.
HHV-6 PCR.
Further info:
HHV-6 Foundation: Viral Testing
HHV-6 Foundation: Research Papers
Cytomegalovirus (CMV)
Cytomegalovirus is found in 50% of adults, usually in a latent inactive state. If you have an active CMV infection, this may be contributing to or causing your ME/CFS symptoms.
Cytomegalovirus IgG antibodies. Dr A Martin Lerner says that a diagnosis of cytomegalovirus infection is made by examining the CMV IgG antibody titer. (Lerner says the IgM titer for CMV is inaccurate and insensitive.) The higher the CMV IgG titer, the greater the viral load.1
Cytomegalovirus PCR.
Coxsackievirus B and echovirus
There are six coxsackievirus B types and thirty-two different echoviruses. All are part of the enterovirus genus. Coxsackievirus B is found in 55% of adults, according to a study in Scotland.1
If you have an active coxsackievirus B or echovirus infection, this may be contributing to or causing your ME/CFS symptoms.1 2 3 4
Part of the difficulty in treating a chronic enterovirus infection is that this virus can exist in two distinct forms in the body: the regular enterovirus, and the non-cytopathic enterovirus. The infection begins with a regular enterovirus, but then some regular enteroviruses convert into non-cytopathic enteroviruses within the body. Unlike regular enteroviruses, these non-cytopathic enteroviruses reside within human cells, and so are hard to detect, but may be contributing to or causing your ME/CFS symptoms.1 2 3
Coxsackievirus B and echovirus antibodies. Only one testing lab has an enterovirus antibody test sufficiently sensitive to detect the low-level "smoldering" chronic enterovirus infections of ME/CFS: ARUP Lab, in Utah. These test are: Coxsackievirus B Antibodies, Echovirus antibodies. Titers of 1:320 and higher are good indicators of an active infection. ARUP tests can be ordered directly, or ordered through Labcorp.
Stomach biopsy (immunohistochemistry). This test, which requires a sample of stomach tissue obtained by an endoscope, is the most reliable for detecting a chronic enteroviral infection. Dr Chia's lab can process the stomach tissue sample.
PCR testing is not sensitive for chronic enteroviral infections, as these viruses disappear from the blood after the acute phase of the infection is over (the acute phase of an enterovirus infection is a short window that starts just after initial exposure, and last for around 10 days).
Complement fixation test (CFT) is useless for testing enteroviral activity in chronic infections. The CFT is only of value within the acute phase (first 10 days) of an enterovirus infection.
Non-cytopathic enterovirus testing. There are no commercially available tests for non-cytopathic enteroviruses, which reside within human cells.
Further info:
Enterovirus Foundation: Testing for chronic enteroviral infections
Parvovirus B19
Parvovirus B19 is found in 50% of adults, usually in a latent inactive state. If you have an active parvovirus B19 infection, this may be contributing to or causing your symptoms.1 2
Parvovirus B19 antibodies. A blood test showing a parvovirus IgG antibody titer of 1:?? or more suggests an active infection.
Chlamydia pneumoniae
Chlamydia pneumoniae is an intracellular bacterium (one that lives inside human cells) which is found in a latent state in 74% of the adult population, according to a study conducted in Israel. About 10% of this population had a persistent active infection with this bacterium.1
Further info:
Cpnhelp.org
Stanford University: Chlamydia Pneumoniae
Chlamydia pneumoniae
Mold toxin exposure
Mold can synthesize toxic substances (mycotoxins) that can damage the central nervous system, intestines, kidneys. These toxins have been linked to the triggering of ME/CFS.1
Mold growth can be visible, or it may be hidden behind walls and domestic appliances. People can become ill from hidden mold growths without knowing the cause (though a moldy, musty smell in the environment provides a warning to the possible presence of mold). Usually several species of mold can be found in a mold infestation. Mold species that have very potent mycotoxins include: Stachybotrys, Memnoniella and Acremonium. These three species depend on damp cellulose material (wood, paper, cotton) for nutrition, and thus typically thrive in water damaged-buildings that contain plenty of wood, wallpaper, etc.
Pesticide exposure
Chronic exposure to significant amounts of organophosphate or pyrethroid pesticides can cause ME/CFS-like illnesses, or act as a co-factor in precipitating ME/CFS.
Further info: PAN
Sources of pesticide exposure include garden sprays used by you or your neighbor, which can be tracked into the house on shoes. Agricultural exposure may occur in rural areas through crop spraying. Pyrethroids are found in pet flea control products. Pesticide residues on foodstuffs are generally very minimal, and are not of concern.1 Organophosphate pesticides are detoxified from the body by an enzyme called paraoxonase; differences in the paraoxonase gene can increase an individual's susceptibility to organophosphates.1 2