Chronic Fatigue Syndrome

A Roadmap for Testing and Treatment





Introduction
Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME) and usually abbreviated to ME/CFS, is a neurological condition characterized by cognitive dysfunction, mood disorders, fatigue, post-exertional malaise, and an array of other symptoms.

The following guidelines will help you determine: (1) whether you have chronic fatigue syndrome, and if so: (2) which laboratory tests can be performed to identify the infections and other possible factors that underpin your ME/CFS, and: (3) what treatments you can follow to address these infections and factors, and treat the symptoms that arise from them.



Chronic Fatigue Syndrome Diagnosis
There are currently no laboratory tests or biomarkers that can be singularly used to diagnose ME/CFS, so diagnosis is performed on symptoms alone. ME/CFS manifests a whole array of clinical symptoms, both physical and mental/cognitive, which typically include the following:

SYMPTOMS OF CHRONIC FATIGUE SYNDROME
Persistent fatigue not due to ongoing exertion, and not really relieved by rest. The fatigue is of a new onset, and greatly reduces activity levels, compared to before the onset. Unrefreshing sleep, often with a disturbed circadian rhythm. Cognitive dysfunction (also known as brain fog) which consists of: short-term memory deficits, difficulty processing information, problems recalling words or names, loss of focus and awareness, confusion and disorientation. Neuropsychological changes: including: emotional sensitivity, flat emotions, emotional lability (where emotions are unstable or exaggerated). Anxiety, panic attacks and depression can appear in ME/CFS. Post-exertional malaise (PEM): physical or mental exertion triggers a state of profoundly worse symptom severity. PEM appears right after the exertion, or hours or days later. This PEM state then lasts for days or even weeks.
Abdominal: gut pain, irritable bowel, diarrhea. Headaches of a new type. Chest pain. Tinnitus, dizziness, balance problems, fainting. Irregular heartbeat. Chronic sore throat or a recurring sore throat. Chronic cough. Sensitivities to sounds, light, chaotic or busy environments, heat or cold. Intolerances to foods, alcohol, odors, chemicals, pollen or medications may appear. Dry mouth, dry eyes, blurred vision. Muscles: aches, pain, weakness or tingling sensations in muscles. Lymph nodes: enlarged or painful in the neck and armpits. Joint pain: moving from one joint to another, but without swelling or redness. Orthostatic intolerance: an upright posture (standing up) creates symptoms such as fatigue, dizziness, nausea, greatly increased heart rate, sweating, lightheadedness, blood pressure drop, and sometimes passing out.

For the complete set of symptoms formally used for ME/CFS diagnosis, see the CDC 1994 CFS Criteria, the Canadian Consensus ME/CFS Criteria or the International Consensus ME/CFS Criteria.



Ruling Out Other Conditions With Similar Symptoms to ME/CFS
The inherent problem with diagnosing ME/CFS by its symptoms is that many of the same symptoms manifest in other diseases and conditions such as: Lyme disease, hypothyroidism, celiac disease, lupus, anemia, hepatitis B or C, and many others. Thus if you have symptoms resembling chronic fatigue syndrome, you and your doctor first need to rule out diseases and conditions with very similar symptoms before a diagnosis of ME/CFS can be given with reasonable certainty.

RULING OUT CONDITIONS SIMILAR TO ME/CFS
Condition
Tests and Results Interpretation
Lyme disease
Lyme disease is believed to be caused by a chronic infection with certain species of Borrelia bacteria. These bacteria are contracted through the bite of infected Ixodes ticks. When Borrelia is first contracted through the bite of an infected tick, it often (but not always) causes a characteristic erythema migrans rash. Early symptoms of Lyme disease include: fever, headache, fatigue and depression.
Borrelia ELISA + western Blot: Dr A Martin Lerner uses western blot and ELISA to test for Borrelia burgdorferi IgM and IgG antibodies.1

This combination of ELISA followed by a western blot (also called immunoblot) has been shown to be nearly 100% reliable in diagnosing Lyme disease.1 Results are considered positive only when both the ELISA and western blot are positive.1

Lyme and ME/CFS differences in symptoms: in Lyme there is often pain and swelling in the large joints, most often the knees; by contrast in ME/CFS there can sometimes be pain in the joints, but this occurs without swelling. Facial palsy can occur in Lyme, but this does not occur in ME/CFS. These differences in symptoms can act as a differential diagnosis, to help distinguish Lyme disease from ME/CFS. Living or working in a Lyme risk area increases the likelihood you may have Lyme. This chart shows the incidence (and thus the risk) of Lyme across US states.

Note: although here we are trying to differentiate Lyme disease from ME/CFS, some doctors view Lyme as just a particular form of ME/CFS.
Hypothyroidism
Hypothyroidism occurs when your thyroid gland does not produce enough of the thyroid hormone thyroxine.
The symptoms of hypothyroidism are quite similar to those of ME/CFS. Hypothyroidism is diagnosed by a blood test which measures the levels of various thyroid hormones.
Celiac disease
Celiac disease is an autoimmune reaction triggered by gluten, causing damage to the small intestine and nutrient malabsorption. Celiac disease symptoms vary widely between patients, but can resemble those of ME/CFS.

Info: Celiac Disease Symptoms.
Transglutaminase antibody blood test and an upper endoscopy with biopsy of the duodenum are used to diagnose celiac disease.

Since celiac symptoms greatly improve after removing ALL gluten from the diet, if you feel much better going gluten-free, it hints you might have celiac disease (though gluten sensitive people without celiac disease will also feel better going gluten-free).
Systemic lupus erythematosus (SLE)
SLE is an autoimmune diseases that can cause various symptoms such as joint pains, muscle pains, skin rashes, fatigue and brain fog.
Antinuclear antibody test (ANA). Nearly all patients with systemic lupus erythematosus (SLE) will have a positive ANA result, but in ME/CFS patients a positive ANA is no more common than in the general population (around 3% to 15% of the general population have a positive ANA).1 Though note that ME/CFS patients who also have autoimmune conditions such as Sjögren's syndrome or Hashimoto’s thyroiditis are more likely to have a positive ANA. So while not perfect, the ANA test can be a useful tool to help distinguish SLE from ME/CFS.

Up to 50% of SLE patients exhibit a red butterfly rash on the face, which is not found in ME/CFS.
Anemia
Anemia is a decrease in the number of red blood cells, or a decrease in the amount of hemoglobin in those cells, either of which results in a reduced ability of the blood to carry oxygen.
The symptoms of anemia are similar to those of ME/CFS. Anemia can be diagnosed by a full blood count.

More info on testing for anemia: How Anemia Is Diagnosed and Treated.
Hepatitis B or C virus infection
Chronic hepatitis B and hepatitis C viral infections can produce symptoms that resemble those of ME/CFS.
Hepatitis B virus can be caught from unprotected sex, including anal and oral sex, and also from sharing needles to inject street drugs. Hepatitis C virus is most commonly caught by sharing of needles to inject street drugs, and is sometimes caught from unprotected sex. Your doctor or a sexual health clinic can provide testing for hepatitis B and hepatitis C virus infections.

For more info on diseases that have similar symptoms to ME/CFS, see: AAFP ME/CFS Differential Diagnosis, Dr Myhill's ME/CFS Differential Diagnosis and Diseases similar to ME/CFS.



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 factors (infections, toxic exposures, etc) that may be causing or contributing to your ME/CFS. ME/CFS patients may have several factors contributing to their symptoms, and in order best treat ME/CFS, these factors need to be identified and addressed. This is ideally 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 suggested tests 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.

The suggested treatment plans are those generally employed by leading chronic fatigue syndrome doctors and researchers in the field, and those which are backed up by published studies. 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 all ME/CFS treatments.

Most cases of ME/CFS appear to be triggered by viral infection, and ME/CFS is associated with ongoing active infections of certain viruses from the enterovirus genus (specifically: coxsackievirus B and echovirus) and of certain viruses from the herpes family (specifically: Epstein-Barr virus, human herpes six virus and cytomegalovirus). ME/CFS can also be caused by parvovirus B19, Chlamydia pneumoniae, as well as other microbes. Non-microbial causes or contributory factors to ME/CFS include: mold toxin (mycotoxin) exposure and pesticide exposure. The first round of testing detailed below suggests you consider or get tested for all these microbes and contributory factors.



Notes on Pathogen Testing
Most ME/CFS-associated microbes are 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, and are then classified as past infections, or latent infections (though these pathogens can reactivate if there is weakness in the immune system).

However, in ME/CFS patients it is often found that one or more past infections have reactivated, and have become chronically active. If you have such a chronic active infection with a virus or bacterium that is known to be linked to ME/CFS, then this infection may be the cause or a contributory factor to your ME/CFS. Whereas if the infection is in a dormant and latent state, then it likely is not playing a causal role.

So when we test 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, because the level of activity indicates whether or not it may be playing an causal role in your ME/CFS. The level of activity of a pathogen can be gauged by the amount of IgG and IgM antibodies your body produces in response to that microbe, so this is why antibody tests for microbes are used.

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 (if the treatment well tolerated and safe). 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.



1st Round Tests: Common Microbial Infections in ME/CFS
The first set of ME/CFS possible 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
Possible Causal Factor
Tests and Results Interpretation
Coxsackievirus B and echovirus (CVB & EV)
These viruses have been strongly linked to ME/CFS in numerous studies spanning decades.1 There are 6 coxsackievirus B serotypes and 32 different echovirus serotypes. All are part of the enterovirus genus. If you have an active infection with coxsackievirus B or echovirus, this may be causing your ME/CFS.1 2 3 4

Intracellular infections: enteroviruses can exist in two distinct forms within the body in chronic infections: the normal lytic virus form, which lives in the blood and tissues; and the non-cytolytic virus form, which actually lives inside human cells, as an intracellular infection. Because non-cytolytic enteroviruses live inside human cells, they are hard to detect. Dr John Chia and other researchers think non-cytolytic enteroviruses may be a major causal factor in ME/CFS.1 2

The prevalence of coxsackievirus B ranges from around 7% to 22% of the general population, according to a study in Greece.1
Coxsackievirus B and echovirus antibody neutralization test. Dr John Chia found that the only blood test sensitive enough to reliably detect the chronic enterovirus infections in ME/CFS patients is the neutralization antibody test (plaque reduction neutralization test or the similar microneutralization assay). ARUP Lab in Utah, USA offers such microneutralization antibody tests for coxsackievirus B and echovirus which cost around $440 each.

Antibody titers of 1:320 and higher in the ARUP tests are good indicators of an active infection. If you have such an active infection, that could be the cause of your ME/CFS, and you may want to treat it with the appropriate antivirals (see the 1st Round Treatments section).

As well as the ARUP tests, Dr Chia also uses the echovirus neutralizing antibody test offered by Cambridge Biomedical which costs around $390, and is similar to the ARUP echovirus test.

Stomach biopsy (immunohistochemistry). This test, which requires a sample of stomach tissue obtained by an endoscope, is the most sensitive for detecting a chronic enteroviral infection, although it will not indicate which particular CVB and EV serotypes you have. You send your stomach tissue sample to Dr Chia's lab which then tests it for enterovirus. The cost is $250 (excluding the endoscopy fees).

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.

Further info:
Enterovirus Foundation: Testing for chronic enteroviral infections
Enterovirus-Associated ME/CFS Etiology
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.

After mononucleosis (glandular fever), which is mostly caused by EBV, ME/CFS was found as a sequelae in 9% of cases.1 Another study found that at 6, 12 and 24 months after mononucleosis, 13%, 7% and 4% of patients respectively met the criteria for CFS, indicating that post-mononucleosis CFS can clear up over time, to an extent.1

Evidence indicates that some subtypes of ME/CFS may be due to partial reactivation of Epstein-Barr virus.1 2
Epstein-Barr virus antibodies. Dr A Martin Lerner says ME/CFS patients have an active EBV infection when there are elevated ELISA antibodies in the EBV IgM VCA test and/or the EBV EA diffuse test.1 2

Similarly, Professor Jose Montoya considers that when the Quest EBV IgG VCA test result is 1:640 or higher and/or the Quest EBV IgG EA test result is 1:160 or higher, this is indicative of an active EBV infection.1

Note that:
EA = early antigen
VCA = virus capsid antigen (also denoted by CA)
EBNA = Epstein-Barr nuclear antigen

If you have an active EBV infection, that could be the cause of your ME/CFS, and you may want to treat it with the appropriate antivirals (see the 1st Round Treatments section).


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 T-cells.1
Human herpes virus six (HHV-6)
HHV-6 is found in nearly 100% 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 3 4 There are two variants of HHV-6: variant A and variant B, often denoted as HHV-6A and HHV-6B. The A variant is more neurotropic (attacks the nervous system). In healthy blood donors seropositive by PCR for HHV-6B, 62% were also seropositive for HHV-6A.1 So both are common. Tests for HHV-6 do not usually distinguish between the two variants. 

Dr Daniel Peterson found that 15% of ME/CFS patients have a HHV-6A infection in their cerebrospinal-fluid.1

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. Dr A Martin Lerner says that when tested using the LabCorp HHV-6 IgM test and the LabCorp HHV-6 IgG test, antibody titers of 1:160 or higher are indicative of an active HHV-6 infection.1 2

Alternatively, Professor Jose Montoya considers that when tested using the Quest HHV-6 IgG IFA test, an HHV-6 IgG antibody titer of 1:320 or higher is indicative of an active HHV-6 infection.1

If you have an active HHV-6 infection, that could be the cause of your ME/CFS, and you may want to treat it with the appropriate antivirals (see the 1st Round Treatments section).

Further info:
HHV-6 Foundation: Viral Testing


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.1

Parvovirus B19 (PB19)
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 3
Parvovirus B19 antibodies.

Note that ME/CFS may arise after an acute parvovirus B19 infection; however, attributing a particular case of ME/CFS to parvovirus may be extremely difficult without a positive parvovirus blood test taken at the onset of fatigue, when the parvovirus infection was still in its acute phase.1
Chlamydia pneumoniae
Chlamydia pneumoniae, an intracellular bacterium (that lives inside human cells), is a known cause of ME/CFS. 1 This bacterium is found in a latent state in 74% of the adult population, and about 10% of the population have a persistent active infection with this bacterium, according to a study conducted in Israel.1 Dr Chia has found that Chlamydia pneumoniae is the cause of ME/CFS as much as 10% of his ME/CFS patients.1

Further info:
Cpnhelp.org
Accurate Chlamydia pneumoniae testing poses significant difficulties and uncertainties. As a result, if you have a negative blood test for Chlamydia pneumoniae, this does not preclude you from having a Chlamydia pneumoniae infection.

More info on Chlamydia pneumoniae testing:
Diagnosis Issues | Cpnhelp.org
Mold toxin exposure
Molds synthesize toxic substances called mycotoxins, and some mycotoxins can damage the central nervous system, intestines and kidneys. Molds, which are a type of fungus, can grow on many surfaces provided moisture and oxygen are present.

In the home, molds may typically grow where there is high humidity, such as in a bathroom, kitchen or basement. Molds may also grow where there is moisture from slow water leaks, such as from a leaky roof or leaky dishwasher; or where there is condensation, such as around windows. Previously water damaged areas of buildings are also common places to find mold.

Mycotoxins from mold have been linked to the triggering of ME/CFS. A study by Dr Joseph Brewer found the following mycotoxins in ME/CFS patients: ochratoxin A in 83% of patients, macrocyclic trichothecenes in 44%, and aflatoxins in 12% of patients. None of these mycotoxins were found in healthy controls.1


Visual contrast sensitivity test (VCS) can be used to diagnose mold illness. This visual test utilizes your eye's ability to detect shades of contrast as a means to gauge exposure to mold toxins.

A free online version of the VCS test, developed by Dr Ritchie Shoemaker and Dr H. Kenneth Hudnell, which takes just a few minutes to complete, can be found here. If your VCS test comes out positive, it suggests you may be exposed to mold toxins (or other biotoxins or neurotoxins such as ciguatoxin), and have a mold-induced illness.

Note that a positive VCS test result may also occur in Lyme disease, Babesia, diabetes, Parkinson's and Alzheimer's. Furthermore, the VCS test may sometimes come out negative even when there is mold exposure.

Examine your home or workplace for mold. Mycotoxins released from mold growths in the home or workplace float in the air, and may be inhaled, leading to ill health or mold-induced illness. Mold growths can be visible, or may be hidden behind walls and domestic appliances. People can become ill from concealed mold growths without knowing the cause (though a moldy, musty smell warns of the presence of mold). Mold growths are often found in water damaged-buildings containing lots of cellulose material like wood, wallpaper, etc.

Dr Joseph Brewer has hypothesized that a mold infection may also be harbored within the body, continually releasing mycotoxins into the body which contribute to ongoing chronic illness. Brewer suggests that the nasal cavities and sinuses are the most likely sites for harboring mold infections,1 and Dr Brewer has had good success in treating patients with antifungal nasal sprays to kill the sinus and nasal mold.1

Chronic inflammatory response syndrome (CIRS) testing. CIRS is the name given by Dr Shoemaker to the chronic illness induced by mycotoxins and other biotoxins, an illness for which he has developed a treatment protocol. Shoemaker has found that 24% of the population have a genotype that make them susceptible to developing CIRS after exposure to biotoxins, because they cannot properly detoxify biotoxins from their body. The HLA DR blood test can determine if you are one of the susceptible 24% who cannot detoxify biotoxins; having such a genetic susceptibility is one of the criteria required for a CIRS diagnosis, with the other required criteria for CIRS detailed on page 4 of this document.
Pesticide exposure
Chronic exposure to significant amounts of organophosphate pesticides such as malathion have been linked to triggering ME/CFS.1 In one study, farmers using organophosphate-based "sheep dip" in Scotland were found to have rates of ME/CFS four times higher than the national average.1 So this study suggests major exposure to organophosphates increases the risk developing ME/CFS by 4 times.

Pyrethroid pesticides have been linked to ME/CFS as well.1 2

Organochlorine pesticides such as DDT and dieldrin have also been linked to ME/CFS,1 2 3 but most organochlorines have been banned for several decades now, with some exceptions such as dicofol which is banned in Europe but still used on cotton and fruit crops in the US, and DDT which is still used for malaria control in Africa and parts of Asia.
Pesticides can enter the body through the mouth, skin, eyes or lungs. Sources of pesticide exposure include garden pesticide 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. Pesticide exposure can also occur through treating wood with preservatives, and treating livestock with anti-parastitic preparations, such as sheep dip.

In most countries, pesticide residues on foodstuffs are generally very minimal, and are not of concern.

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

Further info: Pesticide Routes of Exposure – PAN UK



1st Round Treatments
In the light of the results of the first round of tests:

Coxsackievirus B and echovirus infection. If your tests indicate you have an active infection with one or more enteroviruses of the coxsackievirus B or echovirus species, then Dr John Chia has found (via his informal study) that around 30% of people will make major improvements with an immunomodulator called oxymatrine.1 Though Dr Chia suggests that patients with autoimmune tendencies should not take oxymatrine, as there is a risk oxymatrine may trigger rheumatoid arthritis — more info here.

Dr Chia has formulated his own brand of oxymatrine called Equilibrant, but there is also White Tiger oxymatrine, and Alternative Medicine Solutions oxymatrine, which work with similar efficacy. Once the benefits of oxymatrine have manifested, Dr Chia says men can stop taking it after 3 to 6 months, but women usually have to continue taking oxymatrine, otherwise they relapse and get worse again.1 Dr Chia sometimes adds rifampin (also called rifampicin) to boost the effects of oxymatrine.1

More info on oxymatrine: Dr Chia: Oxymatrine, Oxymatrine, Autoimmunity, ME/CFS and FM, Quixotic: Equilibrant, Invest in ME 2010 conference transcript, oxymatrine effects, immunomodulators info.

Dr Chia often adds the antiviral lamivudine (Epivir) 150 mg twice daily to patients' medications.1 Dr Chia says this well-tolerated drug has anti-enterovirus effects (but note that Epivir has no effect against echoviruses EV6 and EV7). Dr Chia says 1 in 3 ME/CFS patients respond well to Epivir.1

Dr Chia has also used intravenous interferon therapy for ME/CFS patients with enterovirus infections (cost $15,000); many patients went into full remission after this therapy, but unfortunately tended to relapse after around 4 to 14 months, so this is not a permanent cure, but perhaps an encouraging result.1 More info: Chia's Interferon Therapy. Note that Dr Chia found interferon does not work for ME/CFS linked to coxsackievirus B4.1
Epstein-Barr virus infection. If your tests indicate you have an active infection with EBV, this may be causing or contributing to your ME/CFS symptoms. Dr A. Martin Lerner has shown that the antiviral drug valacyclovir (Valtrex) at a dose of 1,000 mg four times daily often improves ME/CFS symptoms, though usually the benefits only begin to become noticeable after around 3.5 months of treatment.1 The full improvements from this drug appear after 2 years of treatment.1 Valacyclovir can cause decreased kidney function or kidney failure, so it is advisable to test kidney function while on this drug. Those who experience side effects from valacyclovir can substitute with famciclovir (Famvir) at the same dosage; Famvir is usually much better tolerated.

In Dr Lerner's study on 142 ME/CFS patients with herpes virus infections, 75% of patients responded to the appropriate antiviral treatment (Valtrex/Famvir for EBV, and/or Valcyte for HHV-6 and cytomegalovirus); the average improvement in ME/CFS symptoms was a 2-point increase on the Energy Index Point Score scale (for example, as a result of antiviral treatment, an average patient may go from level 4 to level 6 on this scale).1

Professor Jose Montoya has found valganciclovir (Valcyte) effective when there is an active EBV infection. This drug needs to be taken for 6 month in order to see improvements.1 Valcyte can have serious side effects and thus patients taking it must be medically monitored.

More info on Lerner and Montoya's antiviral treatment for ME/CFS given in this post.

Dr Jay Goldstein used the H2 antihistamine cimetidine (Tagamet) 300 mg three times daily as an off-label treatment for mononucleosis.1 2 The H2 antihistamine ranitidine (Zantac), which is available over the counter without prescription, can be used in place of cimetidine.

The antiviral Nexavir (formerly Kutapressin) may have some activity against Epstein-Barr virus.1
Human herpesvirus 6 infection. If your tests indicate you have an active infection with HHV-6, Dr A. Martin Lerner has shown that the antiviral valganciclovir (Valcyte) 450 mg three times daily is often beneficial.1

In Dr Lerner's study on 142 ME/CFS patients with herpes virus infections, 75% of patients responded to the appropriate antiviral treatment (Valtrex/Famvir for EBV, and/or Valcyte for HHV-6 and cytomegalovirus); the average improvement in ME/CFS symptoms was a 2-point increase on the Energy Index Point Score scale (for example, as a result of antiviral treatment, an average patient may go from level 4 to level 6 on this scale).1

Professor Jose Montoya also found valganciclovir (Valcyte) 450 mg twice daily effective when there is an active HHV-6 infection.1 It takes around 6 months before the benefits of Valcyte manifest. Note that Valcyte is potent antiviral drug with potentially serious side effects, and should only be taken under medical supervision. More info: Valcyte for CFS. Valcyte is expensive: the cheapest price is around $7 for one 450 mg tablet. Professor Montoya also prescribes the anti-inflammatory colchicine and hydroxychloroquine which treats autoimmunity.

More info on Lerner and Montoya's antiviral treatment for ME/CFS given in this post.

The antiviral Nexavir (formerly Kutapressin) displays potent in vitro activity against HHV-6,1 and this well-tolerated drug is used to treat ME/CFS.

The antimalarial drug artesunate may have efficacy against HHV-6.1

Dr Dan Peterson has had success using the antiviral cidofovir (Vistide) for ME/CFS patients with infections from the herpes family viruses HHV-6 and cytomegalovirus. Cidofovir is potent antiviral drug with potentially serious side effects, and should only be taken under medical supervision. More Info: Peterson Reports Cidofovir Effective in Treating Herpesvirus Infected ME/CFS Patients.

The HIV antiretroviral drug raltegravir (Isentress) is effective against cytomegalovirus, herpes simplex I virus,1 and may have efficacy against the whole family of herpesviruses.1
Cytomegalovirus infection. If your tests indicate you have an active infection with cytomegalovirus, Dr A. Martin Lerner has shown that the antiviral valganciclovir (Valcyte) 450 mg three times daily is often beneficial.1 More info in this post.

Cidofovir (Vistide) is a potent antiviral for cytomegalovirus, and Dr Dan Peterson uses cidofovir for patients with cytomegalovirus or HHV-6 infections.1 The antimalarial drug artesunate may have efficacy against cytomegalovirus.1
Parvovirus B19 infection. If your tests indicate your ME/CFS is likely caused by parvovirus B19 and nothing else, then intravenous immunoglobulin (IVIG) treatment may fully cure you, since parvovirus B19 infection is one of the few curable forms of ME/CFS.1 2 More info: IVIG (Immunoglobulins).
Chlamydia pneumoniae infection. If you have Chlamydia pneumoniae and no other infections, then antibiotic treatment with azithromycin or rifampin may clear this bacterium, and may cure fully your ME/CFS. Chlamydia pneumoniae infection is an uncommon but treatable cause of chronic fatigue.1 More info: Dr Stratton's CFS protocol, Chlamydia pneumoniae Treatment Protocols.
Toxic mold exposure. If you have been exposed to high amounts of toxic mold in your home or other building, ensure you prevent further exposure. If the mold growth area in your home is less than around 10 square feet, the EPA suggest that in most case you can perform the cleanup yourself, using the guidelines given in this document: Mold Cleanup in Your Home. However, if the mold growth is greater than 10 square feet, and/or there has been a lot of water damage, you may need to employ a mold remediation contractor.

An air purifier can be employed to remove mold spores and mycotoxins from the indoor air (a purifier with a HEPA filter will remove the mold spores; a purifier with an activated carbon filter is required to remove the mycotoxins).

Dr Ritchie C. Shoemaker is an expert in treating mold-induced illness. The illness precipitated by mold from water-damaged buildings Dr Shoemaker calls chronic inflammatory response syndrome (CIRS), and he has developed an 11 step protocol to treat CIRS (see also here). The first step removes the source of toxic mold, the next step involves using cholestyramine to detoxify mycotoxins from the body, and the third step uses a BEG nasal spray to eliminate MARCoNS from the nasal and sinus mucous membranes (if tests show MARCoNS are present). In later steps, a no amylose diet may be employed in patients with elevated MMP-9. A clear and easy to read overview of CIRS and its treatment is found here.

CIRS induced by mold can be considered a distinct disease from ME/CFS, and although the symptoms of these two diseases are similar, CIRS has its own treatment. Thus it is important for you and your doctor to consider whether you may have CIRS rather than ME/CFS, otherwise you may receive the wrong treatment. Some patients may have a combination of CIRS and ME/CFS: CIRS usually involves mold (or other biotoxin) triggers, whereas ME/CFS usually involves viral triggers, but some patients may be exposed to both mold and viruses.

Dr Joseph Brewer hypothesizes that ME/CFS patients may harbor chronic mold infections in their sinus cavities, constantly creating mycotoxins. Dr Brewer has developed some anti-fungal nasal spray protocols to treat these sinus mold infections. One nasal spray he uses contains amphotericin B, and another equally effective nasal spray he uses contains itraconazole. Dr Brewer's 2015 paper showed that approximately 60% of his patients with chronic illnesses make a substantial improvement on this nasal spray protocol.1 More info here.

The BEG nasal spray used in the Shoemaker mold protocol, and the anti-fungal nasal spray used by the Brewer mold protocol, can be purchased at Woodland Hills Pharmacy.
Organophosphate, pyrethroid or organochlorine pesticide exposure. If you have been exposed to organophosphate, pyrethroid or organochlorine pesticides, ensure you prevent any further exposure. Some ME/CFS patients with high blood levels of organochlorines achieved remission from their symptoms after a detoxification regimen comprising choline and ascorbic acid.1 2

Note: some cases of ME/CFS may be due to a combination of the above pathogenic infections (as well as other causal factors). In which case, conceivably, it may be possible to combine the above treatments in order to tackle the various individual infections.

Before undertaking any treatment, however, you should first become familiar with any risks of taking that treatment, and if unsure, you should run it by a good ME/CFS doctor first.

More info: Antivirals and Antibiotics for ME/CFS.



Antiviral Drugs Summary
The following table summarizes the antiviral and immunomodulator drugs detailed above, and the particular viruses that each drug has useful efficacy against in ME/CFS patients:

Antiviral
Viruses Targeted
Valtrex (valacyclovir) EBV VZV HSV-1 HSV-2
Famvir (famciclovir) EBV VZV HSV-1 HSV-2
Valcyte (valganciclovir) EBV HHV-6 CMV VZV HSV-1 HSV-2
Vistide (cidofovir) EBV HHV-6 CMV VZV HSV-1 HSV-2
Falcigo (artesunate) EBV HHV-6 CMV HSV-1
Nexavir EBV HHV-6
Foscavir (foscarnet) HHV-6 CMV HSV-1 HSV-2
IVIG PB19
Oxymatrine CVB EV

For treating ME/CFS associated with herpes family viruses, Valcyte is stronger, has a broader antiviral spectrum, and is generally much more efficacious than Valtrex or Famvir. Valcyte (valganciclovir), cidofovir and foscarnet can sometimes cause serious side effects, so their use must always be monitored by a medical professional.

Herpes family viruses include: Epstein-Barr virus (EBV), human herpes 6 virus (HHV-6), cytomegalovirus (CMV), varicella zoster virus (VZV) and herpes simplex virus (HSV-1 and HSV-2). Enteroviruses include: coxsackievirus B (CVB) and echovirus (EV). Valtrex (valacyclovir) is the prodrug of Zovirax (acyclovir); Famvir (famciclovir) is the prodrug of penciclovir; Valcyte (valganciclovir) is the prodrug of Cytovene (ganciclovir). References: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10.



General Therapies for ME/CFS
As well as specific pathogen-targeted therapies, there are many additional therapies that can be helpful in chronic fatigue syndrome. These include:

Antiviral immunomodulators. These are drugs and supplements that modulate (modify) the functioning of immune system so as increase antiviral and intracellular immunity. Some antiviral immunomodulators used in ME/CFS shift the immune response away from the Th2 mode and into the desired Th1 mode. There is evidence that ME/CFS patients may be stuck in the Th2 mode, whereas they should be in the Th1 mode, because it is the Th1 immune response that fights the viruses and intracellular bacteria linked to ME/CFS.1 Th2-to-Th1 shifting immunomodulators include oxymatrine and inosine.

Oxymatrine is a Th2-to-Th1 immunomodulator used to treat enterovirus-associated ME/CFS, and is detailed in the above "Coxsackievirus B and echovirus infection" section.          

Inosine is another Th2-to-Th1 immunomodulator (there is also a drug version of inosine called Imunovir, but ME/CFS doctors say Imunovir is no more effective than the supplement inosine, which is much cheaper and available without prescription).1

Note that Th2-to-Th1 shifting immunomodulators can make you feel worse for the first few months, as the body begins to fight off viral infections; but benefits begin to appear after that initial period. Dr Paul Cheney believes that the immunomodulator inosine will lose it's effect if you do not "pulse" it. Pulsing means taking regular breaks inosine, using an on/off regimen such as taking inosine for 5 days, then stopping for 2 days. Oxymatrine however should not be pulsed.

Low-intensity exercise like walking, tai chi and yoga help shift towards the desirable Th1 mode, whereas higher intensity exercise and longer workout durations shift towards the undesirable Th2 mode.1 ME/CFS patients however must be very careful with exercise, as going past your limit will trigger an episode of post-exertional malaise (PEM).

Rintatolimod (Ampligen) is an immunomodulator drug that anecdotally has produced near full remission in a very small subset of ME/CFS patients, though for most patients, this drug only appears to yield minor improvements. The drug has been shown efficacious in phase III clinical trials, and is licensed as an ME/CFS treatment in Argentina.1 Ampligen is an interferon inducer which works by stimulating the intracellular immune response to fight viral infections existing inside human cells. Ampligen is administered by intravenous infusion twice a week. Ampligen is expensive, costing around $15,000 a year (excluding the medical costs of the infusions). More info: Ampligen - MEpedia.

Intravenous immunoglobulin (IVIG) has had mixed results, but can bring benefits (cost is around $25,000 for a course of treatment). More info: IVIG - MEpedia, IVIG and ME/CFS.

Azithromycin is an antibiotic that acts as an immunomodulator and can lessen ME/CFS symptoms.1 Macrolide antibiotics like azithromycin have immunomodulatory effects on the Th1 and Th2 immune responses.

More info about the immunomodulators used in ME/CFS is found here.
Rituximab (Rituxan) is an anti-autoimmunity drug which depletes B-cells in the blood, thereby reducing the autoantibodies that are made by B-cells and which can attack crucial structures in the body. A phase II clinical trial of rituximab for ME/CFS showed that around two-thirds of patients derived benefit, sometimes very major benefits.1 A phase III clinical trial is now underway.1

The fact that rituximab has major efficacy for ME/CFS suggest that ME/CFS may be an autoimmune disease (at least in part, or at least in a subset of patients).

Rituximab is expensive, costing around $15,000 to $50,000 a year. Rituximab treatment for ME/CFS patients is available at the Open Medicine Institute, California ($50,000) and Kolibri Medical, Stavanger, Norway ($15,000). More info about Kolibri here. Kolibri find that rituximab treatment cures ⅓ of ME/CFS patients, makes an improvement in another ⅓ of patients, and has no effect in the final ⅓ of patients.1

More info: Rituximab - MEpedia.
Low-dose naltrexone (LDN). The drug naltrexone at a low dose of 3 to 4.5 mg daily, taken before bed, can have positive effects for ME/CFS as well as various autoimmune and neurodegenerative diseases. Dr Chia finds LDN helps only a small percentage of ME/CFS patients, but for those it helps, he says it does so very significantly.1 LDN seems to help most fibromyalgia patients.1 LDN is cheap, costing $6 per month.

LDN has mutiple effects in the body: it blocks the mu-, delta- and kappa-opioid receptors briefly (which is thought to up-regulate endorphins), it increases levels of met-enkephalin and its receptor, blocks TLR-4 on microglia, and LDN is believed to increase natural killer cell function (NK function is often low in ME/CFS patients). Note: it is possible that vitamin D3 may be essential for LDN to work properly, so it may be good idea to take vitamin D3 5,000 to 10,000 IU with LDN — see here.

More info on LDN: LDN for ME/CFS, LDN Overview, Low dose naltrexone - MEpedia.
Vitamin B12 injections or B12 sublingual tablets. Many ME/CFS patients find that high dose vitamin B12 substantially reduces their cognitive dysfunction (brain fog) symptoms. The recommended forms of vitamin B12 are: methylcobalamin or hydroxocobalamin. One study found that ME/CFS patients taking methylcobalamin responded better than those taking hydroxocobalamin.1 Injectable vitamin B12 doses are around 1000 mcg three times a week; if taken sublingually instead, the dose is 5000 mcg daily. Improvements in symptoms usually appear after a few weeks of taking B12. Further reading: Rationale for using vitamin B12 in CFS, Methylation, B12, Glutathione, Chelation.
Methylation protocol. Dr Rich Van Konynenburg believed that insufficient methylation is a factor behind ME/CFS, and recommends boosting methylation using a supplement regimen based on the treatment program developed by Dr Amy Yasko for autism.

The methylation protocol involves taking the following supplements daily: vitamin B12 hydroxocobalamin 2000 mcg sublingual, L-5-MTHF 200 mcg, folinic acid 200 mcg, lecithin 1200 mg, and a multivitamin/multimineral tablet. Full details here: Revised Simplified Methylation Protocol (this is the last revision Rich made to his protocol before his untimely death in 2012).

Rich's study on 30 ME/CFS patients found that 27% of them achieved major improvements from methylation after three months.1 Patients found it took an average of 5 to 6 weeks before the protocol started to work. Some patients find this protocol does not work until they switch to the methylcobalamin form of vitamin B12 rather than using the hydroxocobalamin form.

Prof Carl-Gerhard Gottfries of the Gottfries Clinic in Sweden observed that vitamin B12 plus folate helps around 20 to 50% of ME/CFS or fibromyalgia patients with the MTHFR mutation. ME/CFS practitioners in the US observe similar results. To properly validate this observation, the Open Medicine Institute are currently running a three-year placebo-controlled, double-blinded study on the efficacy of vitamin B12 plus folate for treating ME/CFS.1

The Health Diagnostics and Research Institute in New Jersey provide a test for methylation status, as do the European Laboratory of Nutrients (see their "amino acids analysis"). More info about methylation: Glutathione and the Methylation Cycle, Methylation cycle hypothesis - MEpedia.
Nexavir injections. The injectable drug Nexavir (formerly Kutapressin) is an antiviral, an anti-inflammatory, and an immunomodulator that has demonstrated overall benefits for ME/CFS, and this drug is often employed by ME/CFS doctors, including Dr Cheney, Dr Enlander and Dr De Meirleir. Nexavir treatment protocols vary, but in one study, ME/CFS patients were given one subcutaneous 2 ml injection of Nexavir daily for the first 25 days of treatment; thereafter one injection every two days, for the next 50 days; and thereafter one injection three times a week for the next 105 days. This study reported a 42% remission rate in these patients at the end of this course of Nexavir treatment.1 Each injection costs around $10. A low preservative version of Nexavir called 4ME is used by Dr Kenny De Meirleir. 4ME is available here.

Dr De Meirleir reports that around 70% of his ME/CFS patients experience at least a 20 point increase on the Karnofsky scale as a consequence of taking Nexavir.1 Dr Enlander says that Nexavir helps about 30% of his ME/CFS patients, and when combined with other compounds including vitamin B12 and glutathione injections, Dr Enlander reports Nexavir helps 67% of his ME/CFS patients.1
Supplements beneficial for ME/CFS. Acetyl-L-carnitine improves mental fatigue in ME/CFS.1 L-carnitine helps ME/CFS.1 Omega 3 with omega 6 fatty acids (fish oil plus evening primrose oil) improve ME/CFS symptoms.1 VegEPA (EPA-rich essential fatty acids) produces ME/CFS symptom remission and structural brain changes.1 2 Magnesium (either applied transdermally on the skin, or given by injection) can be of benefit in ME/CFS.1 DHEA improves pain, fatigue, anxiety, memory and sexual problems in ME/CFS patients.1 NADH helps ME/CFS.1 Co-enzyme Q10 may increase energy in ME/CFS,1 and 150 mg of Q10 daily has been shown in a clinical trial to improve cognitive function and autonomic dysfunction in ME/CFS.1 Undenatured whey protein may help ME/CFS by boosting intracellular glutathione.1

Malic acid taken with magnesium can increase energy in ME/CFS and reduce pain in fibromyalgia.1 2 Pharmaton capsules (which comprise Panax ginseng and B vitamins) significantly improve fatigue in ME/CFS.1 Multi-vitamin and multi-mineral supplements may improve fatigue, sleep disorders, autonomic nervous system symptoms and headaches in ME/CFS.1 Vitamin D supplementation can result in a marked reduction in pain in fibromyalgia.1 Probiotics improve ME/CFS symptoms,1 and reduce anxiety symptoms in ME/CFS.1 D-ribose can significantly improve ME/CFS and fibromyalgia symptoms.1 Melatonin before bed improves fatigue, concentration and motivation in ME/CFS.1 Folinic acid reduces fatigue and pain in ME/CFS.1
Pharmaceuticals beneficial for ME/CFS. Hydrocortisone reduces fatigue.1 Moclobemide improves brain fog.1 Very low dose amisulpride 50 mg daily reduces fatigue and somatic symptoms, and is well tolerated.1 Methylphenidate (Ritalin) 10 mg twice daily reduces fatigue and improves concetration.1 Several ME/CFS doctors say clonazepam (Klonopin) helps reduce the unpleasant sensory overload problems of ME/CFS, improves sleep and treats anxiety;1 however 32% of patients had severe side effects when trying to stop this drug, although 36% experienced no negative effects when stopping.1

Several ME/CFS doctors find the anticonvulsant drug gabapentin (Neurontin), which is a GABA analog, helps reduce pain, reduces oversensitivity to stimuli, and enhances deep sleep; but on discontinuation this drug can cause significant withdrawal symptoms that can last for months.1 Dr David Bell found amantadine 25 mg to 50 mg twice daily helps ME/CFS, but says higher doses can exacerbate symptoms.1 Several ME/CFS doctors find the stimulant drug modafinil helpful for some ME/CFS patients.1 The drug piracetam (which can also be bought without prescription as a supplement) can treat brain fog symptoms and also improves blood microcirculation and mitochondrial functioning; doses are 800 mg daily or higher.1

More info on various ME/CFS therapies: Dr Jay Goldstein's ME/CFS drug treatments, ME/CFS Immune System Treatments at Phoenix Rising, Dr Jacob Teitelbaum's 30 Top Tips for Treating CFS, ME/CFS Medications Database, Maija Haavisto's free abridged ebook "Reviving the Broken Marionette" which lists ME/CFS drugs (full version here), Erica Verrillo and Lauren Gellman's book "CFS Treatment Guide" (1st edition available for free online), Chronic Fatigue Syndrome Treatment – Wikipedia, MEpedia.

Lists of ME/CFS treatments user-rated for effectiveness can be found here, here and here (see page 9).



2nd Round Tests: Common Comorbid Diseases of ME/CFS
This second round of tests and possible causal factors focuses on a few of the comorbid diseases and conditions that are frequently found in ME/CFS patients —€” in many cases, prior to the triggering factor that precipitated the ME/CFS condition (triggering factors such as an enteroviruses, herpesviruses, mold exposure, etc).

Comorbid conditions that are statistically more prevalent in ME/CFS or fibromyalgia patients (either prior to ME/CFS onset, or subsequent to onset) include: irritable bowel syndrome, interstitial cystitis and overactive bladder (irritable bladder), chronic pelvic pain syndrome, endometriosis, Raynaud’s disease, atopy (predisposition to allergies), increased allergies, multiple chemical sensitivity, temporomandibular joint disorder, myofascial pain syndrome, attention deficit hyperactivity disorder, depression, generalized anxiety disorder, eating disorders, Hashimoto’s thyroiditis, prolapsed mitral valve, Sjögren's syndrome (sicca syndrome), postural orthostatic tachycardia syndrome (POTS), and neurally mediated hypotension.1 2 3 4

Some of these common comorbid conditions likely play a causal role in the development of ME/CFS (though there is no direct proof of this; all we know at present is that these comorbid conditions are statistically more prevalent in ME/CFS patients).

SECOND ROUND TESTS

Possible Causal Factor
Tests and Results Interpretation
Intestinal dysbiosis
Intestinal dysbiosis is where the populations of harmful bacteria or fungi in the large intestine outweigh the populations of beneficial bacteria. People with ME/CFS often have intestinal dysbiosis, and their bowels may harbor some pathogenic microbial species.1 These conditions may be contributing to your ME/CFS symptoms.
Full digestive stool analysis. A stool analysis test will determine whether you have bacterial or fungal overgrowth in your intestines, and will determine whether there are any pathogenic or potentially pathogenic microbes present (potentially pathogenic microbes are those that only cause problems if their populations in the gut become too large).


More info on gut dysbiosis: Fermentation in the gut and CFS
Leaky gut (intestinal permeability)
Leaky gut is an intestinal dysfunction that can allow toxic contents of the small intestine to enter the bloodstream. Leaky gut arises from a dysfunction of the tight junctions in the intestinal wall. Tight junctions are an intelligent barrier that normally precisely controls which substances can pass through the intestinal wall.

Fixing leaky gut improves ME/CFS, and sometimes achieves full remission from ME/CFS. 1 2

Note: 39% of those with diarrhea predominant IBS were found to have leaky gut.1
The lactulose/mannitol test can detect if you have a leaky gut (intestinal permeability), but this focuses only on the small intestine, and does not test the colon for leakiness.

The polyethylene glycol (PEG) test for leaky gut checks your intestines as a whole for leakiness (the small intestine and the colon).

Irritable bowel syndrome (IBS)
IBS symptoms may include: abdominal pain and bloating; bouts of diarrhoea and/or constipation.

Irritable bowel syndrome is a very common comorbid condition in ME/CFS and fibromyalgia.1 2 One study found 92% of ME/CFS patients, and 77% of fibromyalgia patients had IBS in their lifetime (compared to 18% for healthy controls).1

Note: 39% of those with diarrhea-predominant IBS were found to have leaky gut.1
IBS is generally diagnosed by its symptoms; there are no specific tests for IBS. The diagnosis of IBS is performed using either a set of rules called the Manning criteria, or a set of rules called the Rome criteria.

More info: The Manning and Rome Criteria for Irritable Bowel Syndrome.
Small intestine bacterial overgrowth (SIBO)

SIBO is a condition in which abnormally large numbers of bacteria grow in the small intestine. SIBO symptoms are very similar to those of IBS, and include nausea, bloating, vomiting, diarrhea, nutrient malabsorption (thus consequently malnutrition), and weight loss. SIBO is found in 84% of IBS patients, and some hypothesize that SIBO may be the cause of IBS in these cases.1

Eradication of SIBO (if present) has been shown to improve the symptoms of ME/CFS.1
Hydrogen breath test. SIBO can be detected using a hydrogen breath test, which involves drinking some lactulose sugar, and measuring the hydrogen or methane gas produced by bacteria in the small intestine as they metabolize this sugar. (These gases enter the bloodstream and are expelled by the lungs, where they are detected in the breath).

A hydrogen breath test can be used as a differential diagnosis to determine whether a patient with IBS-like symptoms actually has IBS or SIBO; these two conditions cannot be distinguished by symptoms alone. 1

D-xylose test. Malabsorption due to SIBO can be detected by the D-xylose test, which involves drinking D-xylose, and measuring levels in the urine and blood; if no D-xylose is found in the urine and blood, it suggests that the small bowel is not absorbing properly.

More info:
Testing for SIBO (a very informative website by Dr Allison Siebecker).
Labs that offer hydrogen breath tests.
Interstitial cystitis (bladder pain syndrome) and overactive bladder
These two conditions involve an excessive urgency to urinate, and increased frequency of urination. Bladder pain is involved in interstitial cystitis.1 Interstitial cystitis and overactive bladder are common comorbid conditions in fibromyalgia and ME/CFS.1 2 3 Research on cats with interstitial cystitis shows that they may have mild primary adrenal insufficiency.1
Interstitial cystitis (IC) cannot be diagnosed with a simple test. IC is initially diagnosed by exclusion, by ruling out other conditions with similar symptoms, such as infection, bladder stones, bladder cancer, kidney disease, multiple sclerosis, endometriosis, and sexually transmitted diseases. To confirm the initial diagnosis of IC, a fiber-optic tube and camera (cystoscope) is inserted through the urethra and into the bladder (under general anesthetic), to examine the bladder lining. A common sign of IC is numerous red pinpoint spots of blood (glomerulations) on the bladder wall lining.

More info on testing for IC:
Diagnosing and treating interstitial cystitis

Overactive bladder is also initially diagnosed by exclusion, by ruling out other conditions with similar symptoms, such as infection. The diagnosis is confirmed by a procedure called flow cystometry, which involves the insertion of a catheter into the urethra in order to measure the fluid pressure pulses generated by bladder contractions.
Allergies or food intolerances
Allergies and/or food intolerances are commonly found in ME/CFS.1 2 Allergies or food intolerances, especially to gluten or dairy products, may exacerbate ME/CFS symptoms.
Postural orthostatic tachycardia syndrome
There is a high prevalence postural orthostatic tachycardia syndrome (POTS) in ME/CFS.1 The symptoms of POTS include: postural tachycardia (increased heart rate on standing), headache, abdominal discomfort, dizziness, feeling faint, nausea, fatigue, lightheadedness, sweating, tremor, anxiety, palpitations, exercise intolerance.

POTS is a type of orthostatic intolerance, where an upright posture (standing up) will trigger symptoms.

Note that as well as being a common condition in ME/CFS patients, POTS can also occur on its own without ME/CFS, and in these cases, POTS can sometimes be misdiagnosed as ME/CFS, since POTS symptoms are similar to those of ME/CFS.

POTS is a treatable condition to an extent, so everyone with ME/CFS should investigate whether they have POTS, as POTS could be contributing to your symptoms.
POTS is diagnosed using the tilt table test, or the active standing test, and these have been shown to be comparable in accuracy.1

The active standing test is sometimes called the "poor man's tilt table test", and can easily be performed at home. The active standing test involves measuring the increase in your heart rate that occurs when you stand up from a relaxed lying down position. To perform the active standing test, you simply lie down horizontally and relax for 10 minutes, and at the end of this 10 minute period, measure your heart rate. Then stand up, and after two minutes standing, measure you heart rate again. After 5 minutes standing, measure your heart rate a third time, and after 10 minutes standing, measure it a fourth and final time. If any of your heart rate measurements taken on standing are faster by 27 beats per minute or more than your heart rate while lying down, then you have POTS.

Note that when using a tilt table, the threshold for diagnosis of POTS is an increase in heart rate of 30 beats per minute or more; but Streeten says that for the active standing test, the threshold for diagnosis is best set at 27 beats per minute or more.

Dr Raj suggests that for maximum sensitivity, testing for POTS should be performed in the morning, because POTS symptoms are worse in the morning.1 Note that those aged 12 to 19 years old must have an increase of at least 40 beats per minute in order to be diagnosed with POTS.

Further info on POTS:
Orthostatic Intolerance in CFS II
dinet.org – POTS Symptoms
dinet.org – POTS Diagnosis
dinet.org – POTS Treatment
www.potsuk.org
www.potsuk.org – Diagnosis
POTSgrrl
POTSgrrl – Treatments
Orthostatic hypotension (OH), and
Neurally mediated hypotension (NMH)

OH and NMH are conditions in which your blood pressure drops upon standing. In OH the pressure drop is immediate; in NMH the drop occurs after a long period of time standing, or also sometimes after having an unpleasant or upsetting experience.

Symptoms of OH or NMH include: dizziness or light-headedness, feeling that you are going to faint, blurred vision, confusion, weakness, fatigue, nausea. These symptoms appear within a few seconds or minutes of standing up after you've been sitting or lying down, and will disappear if you sit or lie down for a few minutes.1

OH and NMH are types of orthostatic intolerance, where an upright posture (standing up) will trigger symptoms.

Patients with ME/CFS have a high prevalence of neurally mediated hypotension (NMH),1 which is due to a dysfunction of the autonomic nervous system. In some cases ME/CFS patients can experience almost complete resolution of their ME/CFS symptoms once their NMH is treated.1

OH is also called:
Postural hypotension

NMH is also called:
Neurally mediated syncope
Neurocardiogenic syncope
Orthostatic hypotension is diagnosed when, on standing from a sitting or lying position, there is a fall in systolic blood pressure of 20 mm Hg or more, and/or a fall in diastolic blood pressure of 10 mm Hg or more within 5 minutes from standing.1 In some people with OH, the drop in blood pressure can take up to 10 minutes to appear. If the occurrence of the blood pressure drop is delayed for more than 3 minutes after standing, this is called delayed orthostatic hypotension. In ME/CFS it is the delayed variety of orthostatic hypotension that usually occurs.

These blood pressure measurements can be made with an ordinary home blood pressure meter. Note that a blood pressure reading is expressed as systolic / diastolic, for example: 120 / 80.


Neurally mediated hypotension is diagnosed using a tilt table test that keeps the patient in the upright position for 30 to 45 minutes, to observe whether syncope occurs (syncope is a temporary lost of consciousness due to a drop in blood pressure). More info on the diagnostic technique used for NMH is given here.


More info:
Orthostatic Hypotension
Neurally Mediated Hypotension and its Treatment




2nd Round Treatments
In the light of the results of the second round of tests:

Intestinal dysbiosis. If your digestive stool analysis test indicates bacterial overgrowth and/or the substantial presence of potentially pathogenic gut bacteria such as Aeromonas, Bacillus cereus, Campylobacter jejuni, Citrobacter, Clostridium difficile, pathogenic strains of Escherichia coli, Klebsiella, Morganella morganii, Proteus, Pseudomonas, Salmonella, Shigella, Staphylococcus aureus, Vibrio and Yersinia, then a course of antibiotics, and/or probiotics may help reduce these bacterial populations. Note that some people ME/CFS, typically those who have had this disease for a decade or more, may find their gut is too sensitive to take probiotics.
Irritable bowel syndrome. If you have been diagnosed with irritable bowel syndrome (IBS), note that IBS can be caused by the intestinal protozoan parasites Giardia lamblia and Blastocystis hominis, all of which are treatable. There is also evidence of bacterial infection in IBS (in that the antibiotic rifaximin can put IBS into remission for three months).

For Giardia lamblia, a single dose of the antiprotozoal drug tinidazole is an effective treatment.1 For Blastocystis hominis, a triple drug protocol comprising secnidazole 400 mg x 3 daily, furazolidone 100 mg x 3 daily and nitazoxanide 500 mg x 2 daily, all taken for 10 days, achieves an 82% eradication rate.1 More Blastocystis hominis eradication protocols are detailed here. A two week course of rifaximin, a unique antibiotic which is not absorbed in the intestines (and so remains in the bowels), improves IBS symptoms, and this improvement then lasts for three months.1

Fecal transplant (bacteriotherapy) may be worth considering: it has a good response rate for treating ME/CFS patients with IBS. According to a study by Dr Thomas Borody in Australia, 58% of ME/CFS patients with IBS given a fecal transplant achieved resolution from their ME/CFS symptoms (of sleep deprivation, lethargy/fatigue). And this resolution in symptoms has been sustained for two decades to date, according to the study. Cost of a fecal transplant is up to $10,000.1 2 3

A new product called Openbiome FMT Capsules G3, which is bacteriotherapy in a convenient and cheap pill form, has been made available (costs just $635). More info here.
Small intestine bacterial overgrowth. If you have been diagnosed with small intestine bacterial overgrowth (SIBO), there are a number of treatment options, including: the antibiotics rifaximin, neomycin and metronidazole; an elemental diet (to starve the bacteria); and dietary treatments that reduce food sources for the bacteria. See: Treatments Strategy for SIBO. Once the bacterial overgrowth in the small intestine is brought under control by these treatments, it is then necessary to adopt a prevention strategy (such as an ongoing dietary treatment) to stop SIBO from reappearing. Without adopting a prevention strategy, recurrence of SIBO is common.
Leaky gut. If you find you have a leaky gut (intestinal hyperpermeability), this means that potent endotoxins such as lipopolysaccharide (LPS) made by bacteria in your gut may theoretically be escaping into your bloodstream, which may increase inflammation in the body. LPS also reduces the antiviral Th1 immune response, potentially making it harder for your body to fight off viruses.1

Dr Michael Maes demonstrated that anti-inflammatory and antioxidant supplements such as glutamine, N-acetyl-cysteine and zinc, along with a leaky gut diet, can help fix intestinal hyperpermeability, which in turn can lead to clinical improvements in ME/CFS symptoms (though these improvements may take many months to appear).1 Sometimes, complete remission from ME/CFS can be obtained by normalizing a leaky gut.1 A comprehensive list of supplements which studies have shown can reduce intestinal permeability are given here.
Postural orthostatic tachycardia syndrome (POTS). If you are diagnosed with POTS, drugs for treating POTS include: beta blockers such as propranolol (most useful in those with elevated norepinephrine); clonidine (Catepres), desmopressin (DDAVP); erythropoietin; fludrocortisone (Florinef); ivabradine (Procoralan); labetalol (Trandate); methyldopa (Aldomet); pyridostigmine (Mestinon); ibuprofen; intravenous saline; SSRI drugs such as escitalopram (Lexapro); SNRI drugs such as venlafaxine (Efexor); bupropion (Wellbutrin); vasoconstrictors such as ergotamine, midodrine, octreotide, ephedrine, pseudoephedrine, yohimbine, theophylline and methylphenidate (Ritalin).

Non-pharmaceutical approaches to treating POTS include: increasing salt or sodium intake (different doctors have recommended anything between 3 and 15 grams of salt daily), along with drinking more water (at least 2 liters a day). Licorice root can be helpful for POTS.

More info on POTS treatments: POTS - What Helps
Neurally mediated hypotension (NMH). If you are diagnosed with NMH, it can be treated by increased salt intake along with increased water intake (at least 2 liters each day) — but note that the salt treatment will not be effective unless it is accompanied by the increased water intake,1 vasoconstrictors (see POTS section above), beta blockers, fludrocortisone (Florinef), and licorice root.



3rd Round Tests: Less Common Microbial Infections in ME/CFS
This third round of tests focuses on rarer microbial causes and contributory factors of ME/CFS.

THIRD ROUND TESTS
Possible Causal Factor
Tests and Results Interpretation
Giardia lamblia
Giardia lamblia (also called Giardia intestinalis) is a protozoan parasite that colonizes and replicates in the small intestine, causing giardiasis. One study found that after giardiasis, at least 5% of patients developed ME/CFS symptoms.1

Another study found that giardiasis can trigger ME/CFS which can then last as long as five years; the study also noted that improvements in these ME/CFS symptoms often appear after three years.1

Giardia lamblia also predisposes you to acquiring IBS.1
Giardia lamblia antigen test.
Mycoplasma species bacteria
60% of ME/CFS patients are found to have blood infections with one or more of the following: Mycoplasma pneumoniae, Mycoplasma fermentans, Mycoplasma hominis and Mycoplasma penetrans. By contrast, such infections are detected in the blood of only 10% of healthy adults. ME/CFS patients infected with more than one mycoplasmal species generally had a longer history of illness, suggesting that they may have contracted additional mycoplasmal infections with time.1 2

It has been speculated that Mycoplasma species may contribute to ME/CFS symptoms.
Mycoplasma pneumoniae IgM and IgG antibodies. Dr A Martin Lerner only considers a ME/CFS patient to have a persistent Mycoplasma pneumoniae infection if their titer is 1:600 or more (Lerner uses LabCorp for testing).1

Mycoplasma PCR.
Coxiella burnetii
Coxiella burnetii bacteria cause Q fever, a disease which may be acute or chronic. Most people with acute Q fever recover, but an ME/CFS-like post-Q fever fatigue syndrome occurs in 10% to 25% of acute cases. Note: post-Q fever fatigue syndrome is not the same as chronic Q fever; the latter involves ongoing infection, typically endocarditis heart infection.1

Coxiella burnetii can be treated with antibiotics. The incubation period of Coxiella burnetii is 2 to 3 weeks.1 2 3
PCR. During the acute phase of Q fever, PCR can determine if a patient has Q fever (PCR is most sensitive in the first week of illness). However a negative PCR result does not rule out the possibility of having Q fever.

Indirect immunofluorescence assay (IFA) is the gold standard test for acute Q fever.

More about Coxiella burnetii testing here.
Brucella
Brucella bacteria can cause ME/CFS-like symptoms. This bacterium can be treated with antibiotics. Brucella’s incubation period is 1 to 3 weeks.
Brucella antibodies.
Human T-lymphotropic virus I & II (HTLV)
Infection with HTLV I or II is a remote possibility to explain a chronic fatiguing condition, though the symptoms of these viruses take decades to appear, as HTLV has a very long incubation period (however these viruses can be contracted early in life as an infant from breastfeeding).

Note though that the vast majority of people (99%) who have these viruses in their body remain healthy, and never manifest any of the diseases HTLV can cause.
HTLV I and II antibody test.

Note that HTLV is a rare infection in the US and Europe. In the UK for example, only 1 person in 3000 carries HTLV I, and the prevalence of HTLV II is even lower.

However, HTLV I is endemic in areas such as Florida USA, Japan, the Caribbean and South America, where the prevalence can be as high as 1 person in 100. In the US and Europe, HTLV II infection is highest among injecting drug users.

More info: What is HTLV-I, What is HTLV-II.
Ross River virus
This mosquito-borne virus is only found in parts of Australia, Papua New Guinea, and some South Pacific islands. This virus has been associated with ME/CFS, though most infections of Ross River virus do not produce clinical symptoms and go unnoticed.1 2
Ross River virus antibodies.
Herpes simplex virus 1 & 2 (HSV)
HSV 1 is found in 58% and HSV 2 is found in 16% of the adult population. It has been suggested that HSV 1 & 2 may play a role in ME/CFS.1
HSV 1 & 2 antibodies.
Varicella zoster virus (VZV)
VZV is the virus which causes chickenpox. Having VZV has been linked to ME/CFS.1 It has been hypothesized that some cases of ME/CFS may be caused by the reactivation of VZV in peripheral nerve ganglia.1 Enterovirus infections in their first two months have been shown to cause immunosuppression due to CD8 depletion which can reactivate VZV.1
VZV antibodies.



3rd Round Treatments
In the light of the results of the third round of tests:

Giardia lamblia infection . If you tested positive for an Giardia lamblia infection (giardiasis), then either a week course of metronidazole, or a single dose of tinidazole or ornidazole, was found to cure the infection in 90% of cases.1 In those with Giardia lamblia infection and ME/CFS or chronic fatigue as their main symptom, treatment of this giardiasis resulted in a complete cure of fatigue in 27% of patients, and a marked improvement in 44% of patients.1
Mycoplasma infection. If you have a Mycoplasma infection, macrolide and tetracycline classes of antibiotics (such as azithromycin and doxycycline) are effective treatments. For healthy people, two or three weeks treatment is required; longer treatment is usually needed in chronic illness like ME/CFS.1

Dr A Martin Lerner treats Mycoplasma pneumoniae infection in his ME/CFS patients with intravenous doxycycline 150 mg for six weeks, followed by oral doxycycline 100 to 150 mg twice daily or moxifloxacin 400 mg once daily for three months.1
Coxiella burnetii infection. If you have a Coxiella burnetii infection, doxycycline 100 mg daily for 3 months can lead to significant improvements in symptoms.1
Varicella zoster virus infection. If you have an active infection with varicella zoster virus, then treatment with one of the antiviral drugs acyclovir, valacyclovir or famciclovir may be beneficial.1 The H2 antihistamine cimetidine 200 mg three times daily daily plus 400 mg just before bed can be an effective off-label treatment for varicella zoster virus.1 2
Herpes simplex virus infection. If you have an active infection with herpes simplex virus I or II, then treatment with one of the antiviral drugs acyclovir, valacyclovir or famciclovir may be beneficial.1 The supplement L-lysine (1000 mg twice daily) is also beneficial.1 2 The H2 antihistamine cimetidine may be an effective off-label treatment for herpes simplex virus.1 2

Dr William Pridgen's potent antiviral protocol for herpes simplex infection combines famciclovir with COX-2 inhibitor drug celecoxib, and in clinical trials this combination has proved effective in treating fibromyalgia.1 2 More info here.



4th Round Tests: Rarer Causes and Contributory Factors of ME/CFS
This fourth set includes rarer causes or contributory factors of ME/CFS.

FOURTH ROUND TESTS
Possible Causal Factor
Tests and Results Interpretation
Blood transfusion
A study found that 4.5% of ME/CFS patients received a blood transfusion just days before developing a flu-like illness that appeared to trigger their ME/CFS.1

This development of ME/CFS immediately after a blood transfusion may well be caused by the patient acquiring an infection from the transfusion, as blood products may contain viruses such as enteroviruses which are linked to triggering ME/CFS.

Major surgery is also known to sometimes trigger ME/CFS, and since surgery often involves blood transfusion, this may explain why ME/CFS can appear after such major operations.1

Physical trauma (eg: car accident)
Physical trauma such as a road accident or a fall can precipitate fibromyalgia and ME/CFS,1 particularly if a head or neck injury is sustained (such as whiplash or concussion).

Fibromyalgia or ME/CFS can appear immediately after an accident, or begin to develop over the subsequent months.1 2 One study found fibromyalgia was 13 times more likely to occur following neck injury compared to lower extremity injury.1 However, another study of 264 whiplash patients found no evidence of a greater incidence of fibromyalgia.1

A concussion can precipitate a condition similar to ME/CFS called post-concussion syndrome (PCS). A concussion is a mild traumatic brain injury typically caused by a blow to the head, resulting in short-lived initial symptoms such as loss of consciousness or disturbances in vision (such as "seeing stars"). Most cases of PCS will resolve within six months, but 1 in 10 cases will persist for more than a year.
Note that hypopituitarism will occur in up to 30% of people who sustain a moderate or severe traumatic brain injury (TBI), and can sometimes occur even in mild TBI cases. Hypopituitarism can have symptoms very close to those of ME/CFS.1 Thus there is a real danger of misdiagnosing such symptoms ME/CFS when the true cause is hypopituitarism.

If a traumatic brain injury is involved, and ME/CFS-like symptoms ensue, testing for hypopituitarism would be advised. The short synacthen test (also called the ACTH stimulation test) is a standard test for hypopituitarism, but this test is not very accurate, and in fact misses 40% of hypopituitarism cases. A more accurate but more complex and risky test for hypopituitarism is the insulin tolerance test.

A trauma to the spine can sometimes cause a syringomyelia to later form in the spinal cord, which may result in ME/CFS-like symptoms. Syringomyelia can be treated surgically.
Temporomandibular joint dysfunction (jaw misalignment)
Temporomandibular joint dysfunction (TMJD) is an inflammation and misalignment of the temporomandibular joint (which connects the jaw bone to the skull). TMJD can cause symptoms similar to fibromyalgia and ME/CFS.

More info:
Recovery from CFS using oral orthotics
Hannah's Story
Temporomandibular joint dysfunction can be diagnosed by dental professionals. If you have temporomandibular joint dysfunction (jaw misalignment), or have noticed changes in the shape or alignment of your jaw bone or face, this could be contributing to or underpinning ME/CFS-like or fibromyalgia-like symptoms.

One UK dentist who specializes in diagnosing and treating jaw misalignment causing ME/CFS-like symptoms is Dr M. Amir. Dr Amir says that when jaw misalignment is present, the lateral pterygoid muscle (the muscle on your cheek just in front of your ear) is very painful if you press it.1

One speculative theory of how jaw misalignment might create ME/CFS symptoms centers on the fact that inflammation around the trigeminal or vagus nerves can trigger what is known as the sickness behavior response, and this response has symptoms very similar to those of ME/CFS. Thus possibly, a squeezed trigeminal nerve due to jaw misalignment could conceivably create inflammation in the nerve, thereby triggering ME/CFS-like symptoms.

Another speculative theory of how jaw misalignment might play a role in precipitating fibromyalgia-like symptoms relates to a compound called substance P. Substance P is raised in fibromyalgia patients (but not in ME/CFS patients), and some researchers believe it may play a role in fibromyalgia. Now, raised levels of substance P are also found in TMJD patients, with substance P being released into the cerebrospinal fluid when the trigeminal nerve (which runs through the face and jaw) is stimulated. Thus substance P originating from TMJD offers a possible explanation of how jaw misalignment might trigger or worsen fibromyalgia symptoms, and may explain how treating TMJD can lead to improvements in fibromyalgia.
Jaw bone cavitation infection
Cases of ME/CFS have occasionally been caused or worsened by infections located within the jaw bone (osteomyelitis). Such infections develop inside hollow pockets within the jaw bone called cavitations. Cavitations can be left in the jaw bone after a tooth extraction; and cavitations can be created as a result of osteonecrosis (the death of bone tissue due to poor blood flow to the bone).1

When these jaw bone cavitations also induce facial pain, they are called NICO lesions.

Jaw bone cavitations induce the inflammatory chemokine RANTES, as well as FGF-2, which are both linked to systemic disease.1 2 Increased RANTES has been found in jawbone samples and in the serum of ME/CFS patients, suggesting that RANTES from jaw bone cavitations may play a role in the pathogenesis of ME/CFS.1 More info here.

Here are some stories of ME/CFS improving after treatment of jaw bone cavitations:
My recovery story
Cavitations and root canals
Ian's CFS Website
Jaw bone infections can be hard to detect, as they often cause only very minimal local symptoms. Yet a local infection within the jaw bone can cause a condition symptomatically identical to ME/CFS.

Sometimes a jaw bone cavitation infection may cause chronic facial pain, but such facial pain is not always present. A simple test for a jaw bone infection is applying pressure with a finger on the gums to the jaw bone beneath; if any area feels painful, this indicates a possible bone infection. Jaw bone infections may cause a sour, bitter taste in the mouth causing bad breath or even gagging.

Panoramic dental X-rays can detect jaw bone cavitations, but are not very reliable, and they also require skilled interpretation by dentists experienced with detecting cavitations (very few dentists have this experience). Ordinary MRI scans or CT scans are not good at detecting jaw bone cavitations, but the MRI STIR scan is accurate and effective in detection. A handheld ultrasound device called the Cavitat scanner is the best and most effective way to detect jaw bone cavitations.

More info on the diagnosis and treatment of jaw bone cavitation infections is given here:
Symptoms and Location of Cavitations
The Appearance of NICO Lesions
Diagnosis and Treatment of Cavitational Lesions
Cavitations of the Jawbone  

Jaw bone cavitation infections come under the category of focal infections, which are defined as infections localized in a small region of the body. Focal infections within the tonsils may also lead to fatigue symptoms.

UK dental clinics which specialize in diagnosing and treating jaw bone cavitation infections include: Munro-Hall Clinic (Bedford), Tooth Fairy Holistic (Kent).
Sinusitis (sinus infection)
Sinusitis can cause chronic fatigue, and so conceivably sinus infections may worsen ME/CFS.1

Patients suffering chronic fatigue (but not proper ME/CFS) due to obstructive sinusitis have reported significant improvements in fatigue after undergoing sinus surgery. The improvements are likely to derive from the easing of sinus inflammation after surgery.

Further info:
Sinus surgery can improve chronic fatigue
Sinusitis is usually diagnosed from its symptoms (blocked nose or runny nose, and facial pain).

In his studies, Dr Joseph Brewer discovered mycotoxins in ME/CFS patients, and he hypothesizes that these mycotoxins may come from chronic mold infections in this sinuses of ME/CFS patients. See the mold toxin exposure section earlier in this document for more information.

Vaccination
In some cases, ME/CFS appears after vaccination. Dr John Chia has found that around 1.5% of his ME/CFS patients appeared to have their disease triggered by vaccination.1 Dr Charles Shepherd says that the vaccine most commonly linked to triggering ME/CFS is hepatitis B. To a much lesser extent, influenza, BCG, tetanus, meningitis, MMR, polio, hepatitis A and typhoid vaccines have also been anecdotally linked to triggering ME/CFS.1 2

The causal factor in vaccine-triggered disease may be the adjuvant in the vaccine, which Dr Yehuda Shoenfeld says can instigate a condition he has dubbed autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA).1 Adjuvants that can precipitate ASIA include: aluminum hydroxide, squalene and silicone.1 One study examining how ME/CFS or fibromyalgia can arise after hepatitis B vaccination indicated that these diseases can both arise as specific manifestations of ASIA.1

In 2013 the Federal US Court ruled that hepatitis B vaccine caused ME/CFS in one patient, and awarded the patient $1.1 million plus lifetime medical expenses.1

Silicone breast implant leakage
Silicone used for breast and other implants, as well as silicone injections, can in rare cases cause an ME/CFS like illness, as well as autoimmune conditions, if it leaks into the body.1 Silicone is known to affect the immune system (silicone is used as an immune stimulating adjuvant in vaccines for this reason).

More info on silicone illness here.
Silicone breast implant leakage symptoms can include: pain, swelling, redness and sometimes tingling of the breasts.
Ciguatoxin
Ciguatoxin exposure causes the disease of ciguatera, which can later sometimes lead to ME/CFS,1 2 although Dr Shoemaker says ciguatoxin causes CIRS rather than ME/CFS. CIRS is detailed in the mold section.

Ciguatoxin is found in some predatory fish which eat smaller fish that feed on ciguatoxin-producing algae. This toxin cannot be destroyed by cooking.

Ciguatoxin poisoning from fish occurs in tropical and subtropical areas, particularly in the Pacific Ocean, the Indian Ocean, and the Caribbean. All reef fish are capable of causing ciguatera poisoning, but in particular, the species: barracuda, grouper, red snapper, moray eel, amberjack, parrotfish, hogfish, sturgeon, kingfish, coral trout, and sea bass present a risk.
Visual contrast sensitivity test (VCS). This visual test utilizes your eye's ability to detect shades of contrast as a means to gauge your exposure to neurotoxins, including ciguatoxin and mold toxins. A free version of the VCS test, which takes just a few minutes to complete, can be found online here.

Note that a positive VCS test result may also occur in Lyme disease, Babesia, diabetes, Parkinson's and Alzheimer's. Furthermore, the VCS test may sometimes come out negative even when there is exposure.
Radiotherapy or chemotherapy
When undertaken as a cancer treatment, either can lead to ME/CFS soon afterwards.1
Ionizing radiation
This can cause ME/CFS-like symptoms (chronic radiation syndrome).1
More info: National CFIDS Foundation — Ionizing Radiation and CFIDS/ME
Corticosteroids
If corticosteroids (immunosuppressants) are given during the acute phase of a significant respiratory infection, this has been found to sometimes precipitate ME/CFS a few weeks or months later. ME/CFS specialist Dr John Chia discovered this acute infection + corticosteroids = ME/CFS etiology by taking detailed medical histories of all his ME/CFS patients.1
Tung oil
Dr Jay Goldstein has noted that many of his ME/CFS patients developed their illness after exposure to tung oil, a solvent used as a wood preservative.1 Dr Carol Jessop has also noted the association between tung oil exposure and ME/CFS.1 Tung oil, also known as China wood oil, is extracted from the seed of the tung tree (Vernicia fordii).

Tung oil is known to potently reactivate Epstein-Barr virus.1 The phorbol ester HHPA in tung oil reactivates EBV.
Meningitis
An episode of meningitis can afterwards lead to ME/CFS.1

Viral and bacterial meningitis was found to cause pituitary dysfunction leading to growth hormone deficiency in 29% of cases.1 Low levels of growth hormone can cause symptoms very similar to those of ME/CFS.
It may be a good idea for ME/CFS patients who have had an episode of meningitis or encephalomeningitis to have their growth hormone levels checked. The symptoms of adult growth hormone deficiency are listed here.
Food poisoning
Very occasionally, there have been reports of food poisoning precipitating ME/CFS.
Lymph fluid obstruction/stagnation
Osteopath Raymond Perrin has found that ME/CFS patients have improved, and some have even been cured, by a massage technique that he developed for treating ME/CFS, which is designed to circulate lymph fluid. Perrin theorizes that lymph stagnation prevents proper cerebrospinal fluid drainage, thus creating a toxic build-up in the central nervous system that underpins or contributes to ME/CFS.

Further info:
Perrin Technique
Testing for lymph flow obstruction. Raymond Perrin found that his ME/CFS patients have a sore and tender spot just under the third rib on their left side. To Perrin, the presence of this soreness indicates a lymph flow stagnation. To test this spot in yourself, press your fingers into a point around 2 cm above and 2 cm to the left of your left nipple; if there is soreness or tenderness at this point, this indicates to Perrin that there is a lymph flow blockage.




4th Round Treatments
In the light of the results of the fourth round of tests:

Physical trauma. If you think your ME/CFS or fibromyalgia may be due to a physical trauma, such as a car accident that involved a head or neck injury, a physical therapy spinal manipulation such as cranial osteopathy or chiropractic may perhaps yield benefits. If the physical trauma led to hypopituitarism, then replacement pituitary hormones may need to be taken.
Temporomandibular joint dysfunction. If you have ME/CFS-like symptoms and you have been diagnosed with temporomandibular joint dysfunction (jaw misalignment), or have noticed changes in the shape or alignment of your jaw or face, consider treating this, because it may help improve your symptoms. Dr M. Amir is a UK Dentist who specializes in diagnosing and treating ME/CFS-like symptoms that may be caused by jaw misalignment or facial asymmetries.
Jaw bone infection. If you suspect you may have a jaw bone cavitation infection, you may want to seek help from a dentist or maxillofacial surgeon who specializes in diagnosis and treatment of jaw bone cavitations.
Sinusitis. Antibiotics may help for bacterial sinusitis, otherwise corticosteroid nasal sprays can help reduce the sinus and nasal inflammation. Avoiding dairy products can improve sinusitis. Surgery to enlarge the sinus openings can be considered when all else fails.
Silicone breast implant leakage. Symptoms caused by leakage of silicone from breast implants usually improve on removal of the breast implants.1
Ciguatoxin poisoning. The anti-inflammatory effects of herb Vitex trifolia are useful for treating ciguatera poisoning.1
Lymph flow obstruction. If you think you may have a lymph flow obstruction, you may wish to try the Perrin Technique, which improves lymphatic and cerebrospinal fluid drainage using osteopathic massage and manipulation. Patients also follow a massage and exercise routine at home, involving spinal twists (Perrin twists) which manually activate the thoracic duct (the body's main pump for lymph fluid).



Testing Laboratories
Testing laboratories (pathology labs) where the tests recommended in this document can be obtained are listed below. To search for a test at the labs listed below, click here.

TESTING LABORATORIES
USA
UK / Europe
Canada
ARUP Laboratories
Viracor
Focus Diagnostics (owned by Quest)
Quest Diagnostics
Medical Diagnostic Laboratories
Genova Diagnostics
LabCorp
Life Extension Tests (via LabCorp)
NeuroScience, Inc
Great Plains Laboratory
Advanced Laboratory Services
DirectLabs
IGeneX
Genova Diagnostics
Biolab Medical Unit
Neuro Lab
Nutrition Geeks
The Doctors Laboratory (TDL)
TDL Manchester
YorkTest Laboratories
MELISA Diagnostics Ltd
Dr MyHill's Test Portfolio
Pure Health Clinic
Medichecks (sends samples to TDL)
Blue Horizon Medicals (sends to TDL)
Home Blood Testing (sends to Biolab)
Home Blood Test (finger prick tests)
Blood Tests London (uses TDL service)
Harley Street Blood Tests (uses HCA Laboratories)
Privatebloodtests.com (Nuffield hospitals)
Privatebloodtests.co.uk (Spire hospitals)

ArminLabs
Red Labs (Belgium)
European Laboratory of Nutrients (Netherlands)
Blood Tests Canada
Australia
New Zealand
Ireland
Centre for Digestive Diseases
MedLab Pathology
Private Blood Tests Ireland



ME/CFS Doctors and Clinics
Some of the world's leading ME/CFS doctors and clinics are listed in the table below. More info on ME/CFS doctors and clinics: Co-Cure ME/CFS & fibromyalgia Good Doctor List (good for finding local doctors), Chronic Fatigue Syndrome Doctors and Clinics (good for finding local doctors), Phoenix Rising Forum ME/CFS Doctors.

ME/CFS DOCTORS AND CLINICS
USA
Dr John Chia (Torrance, California)Article on Dr ChiaVideo InterviewMEpedia
Dr Chia is an infectious disease specialist with special interest in enteroviruses (which include coxsackievirus B and echoviruses), and is the leading researcher in enterovirus-associated ME/CFS, which he uses the immunomodulator oxymatrine to treat.

Dr A Martin Lerner (Oakland, Michigan)Article on Dr LernerMEpedia
Dr Lerner is a leading researcher in ME/CFS associated with herpesvirus and uses antivirals (Valtrex and Valcyte) to treat these infections. He also has particular interest in the cardiac problems and cardiac insufficiency often found in ME/CFS. Update: Dr Lerner died in Oct 2015, after decades of work helping ME/CFS patients.

Professor Jose Montoya (Stanford University, California)Article on Prof MontoyaVideo InterviewMEpedia
Dr Montoya is a leading researcher in ME/CFS associated with herpesvirus such as HHV-6, EBV, cytomegalovirus, and uses the powerful antiviral drug Valcyte to treat these herpesviruses where appropriate.

Dr Daniel Peterson (Sierra Internal Medicine, Nevada)Article on Dr Peterson Video InterviewMEpedia
Dr Peterson is a very experienced ME/CFS doctor and researcher, and has a special interest in natural killer cell functioning in ME/CFS. Dr Peterson uses the antiviral Vistide (cidofovir) in patients with HHV6 and cytomegalovirus infections.

Dr Paul Cheney (Asheville, North Carolina)Article on Dr CheneyMEpedia
Dr Cheney is an innovative doctor and researcher using leading edge medicine to treat ME/CFS. Dr Cheney is now semi-retired; he will still do some email and phone consultations.

Dr Nancy Klimas (Miami, Florida)Article on Dr KlimasMEpedia
Dr Klimas is a ME/CFS doctor and researcher who runs a ME/CFS clinic. She has significant experience in using immune modulators for treating ME/CFS.

Dr Charles W. Lapp (Charlotte, North Carolina)Article on Dr LappMEpedia
Dr Lapp runs clinical trials for drugs for ME/CFS and fibromyalgia, and has been using the immunomodulator drug Ampligen for ME/CFS.

Dr Lucinda Bateman (Salt Lake City, Utah)Article on Dr BatemanMEpedia
Dr Bateman is an internist specializing in the treatment of ME/CFS.

Dr Derek Enlander (New York)Video InterviewMEpedia
Dr Enlander uses immune modulators for treating ME/CFS, and the antiviral drug Valcyte.

Dr Garth Nicolson (Huntington Beach, California)MEpedia
Dr Nicolson works with ME/CFS, autoimmune diseases, Gulf War illness, and the infectious causes of autism and neurodegenerative diseases.

Dr Andreas M. Kogelnik (Open Medicine Institute, Mountain View, California)Video InterviewMEpedia
Dr Kogelnik is an infectious disease doctor, and an ME/CFS specialist and researcher. He is the founder and director of the Open Medicine Institute. He uses Valcyte or a subset of ME/CFS patients.

Dr David Kaufman (Open Medicine Institute, Mountain View, California)MEpedia
Dr Kaufman is a HIV/AIDS researcher with clinical experience in HIV and Lyme disease. He is principal director at the Open Medicine Institute.

Dr Daniel Dantini (Ormond Beach, Florida)Article on Dr Dantini
Dr Dantini uses the antiviral drugs Valtrex (valacyclovir) and Famvir (famciclovir) for herpesviruses in his treatment of ME/CFS where appropriate.

Dr Kent Holtorf (Hortof Medical Group: Los Angeles; Foster City CA; Atlanta; Philadelphia)
Dr Holtorf focuses on the endocrine system, testing hormones (thyroid, growth hormone, testosterone) and prescribing hormone replacement therapy where necessary. He also addresses mitochondrial and infectious issues.

Dr Alan Weiss (Annapolis, Maryland)
Dr Weiss is an internist who focuses on treatment with supplements, hormone replacement, diet.

Dr Jacob Teitelbaum (Kona, Hawaii)MEpedia
Dr Teitelbaum is an internist whose uses his SHINE protocol (Sleep, Hormones, Immunity, Nutrition and Exercise) to treat ME/CFS.

Dr Joseph Garabedian (King of Prussia, Pennsylvania)
Dr Garabedian runs the Garabedian Medical Center, and in his ME/CFS treatment focuses on the HPA axis, mitochondria, infections, neurotoxins, hormone replacement, neutraceuticals.

Dr Ritchie Shoemaker (Pocomoke City, Maryland)MEpedia
Dr Shoemaker specializes in mold- and biotoxin-triggered illnesses. He has retired from seeing patients, but is still available for phone consultations. There also many Shoemaker certified doctors who follow his protocol.

Dr Joseph H. Brewer (Kansas City, Missouri)MEpedia
Dr Brewer is an infectious disease doctor who specializes in ME/CFS, Lyme disease and AIDS. His researches and treats mold infections harbored in the sinuses of ME/CFS patients.

Dr Susan Levine (New, York, New York)MEpedia
Dr Levine employs various treatments including low-dose naltrexone, intravenous immunoglobulin and antivirals.

Some other ME/CFS doctors: Dr Ginerva Liptan (Lake Oswego, Oregon), Dr Benjamin Natelson (New York), Dr Alan Pocinki (Washinton DC), Dr Irma Rey (Miami, Florida), Dr Peter Rowe (Baltimore, Maryland), Dr Mark Sivieri (Columbia, Maryland).
UK / Europe
Dr Kenny De Meirleir (Himmunitas, near Brussels, Belgium)Article on Dr MeirleirVideo InterviewMEpedia
Dr Meirleir is a leading ME/CFS doctor and researcher who runs a ME/CFS clinic in Brussels. Dr De Meirleir has a particular interest in the intestinal dysfunction and intestinal dysbiosis of ME/CFS.

Dr Nigel Speight (Durham, UK)MEpedia
Dr Speight is paediatric medical adviser to the ME Association. He treats ME/CFS using drugs like amitriptyline for sleep and pain, melatonin for sleep, methylphenidate (Ritalin) for brain fog.

Dr Sarah Myhill (Powys, Wales, UK)MEpedia
Dr Myhill is a GP with significant experience of ME/CFS, has pioneered and published research on mitochondrial dysfunction in ME/CFS, and has a website from which various lab tests can be ordered and interpreted by Dr Myhill.

Dr William Weir (10 Harley Street, London)MEpedia
Dr Weir is a a retired consultant physician with a special interest in ME/CFS.

Dr Vinod Patel (Nuneaton, Warwickshire, UK)
Dr Patel uses amitriptyline, gabapentin, melatonin, duloextine and testosterone replacement to treat ME/CFS.

Breakspear Medical Group (Hertfordshire, UK)MEpedia
Breakspear focuses on allergy and environmental illness. For ME/CFS treatment they use antivirals, gammaglobulins for parvovirus, and test and treat rickettsial and bacterial co-infections.

Professor Carmen Scheibenbogen (Charité University Hospital, Berlin, Germany)MEpedia
Professor Scheibenbogen specializes in the role of Epstein-Barr virus in ME/CFS.

Professor Carl-Gerhard Gottfries (Gottfries Clinic, Mölndal, Sweden)Video InterviewMEpedia
Professor Gottfries pioneered the use of the vaccine Staphypan to treat ME/CFS, which showed major benefits in two clinical trials (unfortunately the manufacturer withdrew Staphypan). The Gottfries Clinic uses vitamin B12 and folate to treat ME/CFS.
Canada
Dr Byron Hyde (Nightingale Research Foundation, Ottawa)MEpedia
Dr Hyde uses SPECT scans to demonstrate dysfunction in the brain in ME/CFS patients.

Dr Alison Bested (Toronto, Ontario)MEpedia
Dr Bested is a hematological pathologist specializing in ME/CFS.
Australia
Australian ME/CFS Good Doctor List

New Zealand
Dr Rosamund Vallings (Howick, Auckland)Article on Dr Vallings
Dr Vallings is one of New Zealand’s leading authorities on ME/CFS and has over three decades' experience in treating this disease. Dr Vallings uses the immunomodulator and antiviral Imunovir as one of her treatments for ME/CFS.



Sourcing Pharmaceutical Drugs
Good ME/CFS doctors who provide the appropriate drugs for ME/CFS patients are few and far between, and the average primary care doctor is often reluctant to prescribe drugs for off-label or experimental use in ME/CFS. Thus it may be necessary to buy the drugs you need directly from a reliable online pharmacy.

The law in many counties allows 3 months worth of prescription drugs for personal use to be imported from abroad (though these drugs of course cannot be controlled substances). Courtesy of this law, it is possible to easily and legally obtain drugs from online overseas pharmacies, usually without needing to provide a prescription. There are many online overseas pharmacies to choose from, but it is important to find a good one that is trustworthy and reliable. Some reliable prescription-free online pharmacies are listed here.



Sourcing Cheap Supplements
ME/CFS patients often take a range of supplements to help combat the myriad symptoms of this problematic disease. To save on costs, note that there are supplement suppliers like iHerb, Vitacost in the US, and HealthMonthly in the UK, who are well-known for their very low prices. eBay also usually has excellent supplement prices.

Vitamin, herbal and amino acid supplements can be also obtained at very substantial discounts —€” around 5 times cheaper than the regular price —€” if you buy these in bulk powder form, rather than tablet or capsule form. Supplements in powder form can be taken in a smoothie-type drink, or take by swallowing a dose of powder with a little water. A digital weighing scales can be useful for measuring the power dosage (these can be bought for as little as $10).

Some bulk powder supplement suppliers include:

BULK POWDER SUPPLEMENT SUPPLIERS
USA
UK
Australia
purebulk.com www.bulksupplements.com www.nutraplanet.com www.myprotein.com www.bulkpowders.co.uk www.bulkpowders.com.au