Blood Tests: Why Test the Blood? Dr Charles Shepherd

February 6, 2014

The Medical Advisor to the ME Association, Dr Charles Shepherd, writes about the importance of blood testing prior to receiving a diagnosis, explains what each test means including for children, and considers when new tests might be necessary…

Blood Tests - NHSHuman blood contains red cells, white cells, platelets and plasma. Red blood cells carry oxygen around the body – so a deficiency or abnormality will probably cause anaemia.

White blood cells help to fight off infections and respond to allergies. They are sub-divided into cells called basophils, eosinophils, lymphocytes and neutrophils – each with a slightly different function.

A rise in the overall number of white cells usually indicates the presence of infection or inflammation somewhere in the body. A decrease in the white cell count may mean that your body isn’t so good at fighting infections. Causes of a low white cell count include drug side-effects and diseases involving the bone marrow, where white blood cells are made.

Platelets help to form blood clots and prevent bleeding. So a platelet deficiency can cause a problem with excessive or prolonged bleeding from a wound site.

Human blood also contains a wide variety of immune system products (e.g. antibodies), enzymes, hormones and proteins that are made or excreted by various organs and tissues in the body.

Laboratory analysis of a small sample of blood can, therefore, reveal a great deal of basic information about your state of health and the function of various organ systems.

Is there a diagnostic test for ME/CFS?

The simple answer is no. An ‘ME blood test’ seems unlikely to be developed in the foreseeable future.

Minor blood abnormalities can occur in ME/CFS but none of them are sufficiently consistent or robust to turn them into diagnostic markers.

When we understand more about the basic underlying pathology of ME/CFS, possibly as a result of new research taking place at the ME Biobank, it is possible that a diagnostic test will then emerge.

Blood tests and ME/CFS

Everyone should have a number of routine blood tests before a diagnosis of ME/CFS is confirmed. This is to help rule out conditions that can also produce fatigue and other ME/CFS-like symptoms. The routine tests that make up this list are:

  • Full blood count: red cells, white cells, platelets etc
  • ESR and CRP (C-reactive protein)
  • Biochemistry screen – including electrolytes, calcium and urea
  • Blood glucose – for diabetes
  • Coeliac disease screening – IgA anti-tissue transglutaminase antibodies
  • Creatine kinase – for muscle disease
  • Creatinine – for kidney function
  • Liver function tests
  • Thyroid function tests
  • Adrenal function – 9am cortisol

Depending on the results and/or the type of symptoms that are occurring, a number of other tests may be also necessary. These include tests that check for:

  • Infections such as HIV, hepatitis B or C, Lyme disease
  • Rheumatic conditions such as lupus/SLE
  • Vitamin D deficiency – which can occur in people with ME/CFS who lack exposure to sunlight

There are also a number of private (i.e .non-NHS) tests that are promoted to people with ME/CFS. These can be quite expensive and current medical consensus is that most of these tests are unproven or unnecessary as they are not helpful in either the diagnosis or management of ME/CFS.

Two tests that fall into this group are the RNAse-L test (for antiviral activity) and CFS urinary markers (CFSUMs) – both of which have been assessed in research studies funded by the ME Association.

Blood tests and children

Doctors are more reluctant to carry out extensive testing on children. Even so, it is also important to rule out other possible explanations before the diagnosis is confirmed in a child. There are also some other blood tests that may be recommended in the case of children and adolescents.

These include:

  • Viral studies that could help to confirm a recent or current infection with Epstein-Barr virus (glandular fever).
  • Tests for other types of infection which can sometimes cause an ME/CFS-like illness in children. Examples include Lyme disease and toxoplasmosis.
  • Serum ferritin level – a measure of iron status in the body.
  • Tests for some of the rare disorders of childhood that can produce fatigue.

The results – what do they mean?

After a blood sample is taken by your GP, it is sent to the hospital laboratory for analysis in a machine. The results should be back within a few days.

Each test will have a numerical result giving the level in the blood. If this measurement falls within what is called the normal range, there is usually nothing to worry about.

In some cases, an abnormality occurs when the result is higher than normal. If it’s just outside the normal range, this may be acceptable and all that needs to be done is for the test to be repeated after an interval.

Results that are significantly higher than normal usually indicate the need for further assessment and/or investigation. Results that are significantly lower than normal are also important – an example being a low level of thyroid hormone or haemoglobin.

Detailed information on the use of all of these blood tests and their role in ME/CFS can be found in the Investigations section of ‘ME/CFS An Exploration of the Key Clinical Issues‘, written by Dr Charles Shepherd and Consultant Neurologist, Dr Abhijit Chaudhuri, and available from the ME Association.

pruple-booklet-front-cover-213x300If you are resident in the UK you might also like to be aware of the campaign that has allowed thousands of free copies of this valued resource to be sent to UK doctors and medical libraries, and to know that patients are still able to nominate recipients.

To read more about the campaign, and to learn how to nominate a doctor, please click the image for more information. The booklet (and also this article – which is now available in leaflet form) – can be ordered by completing the order form: HERE.

 

When should blood tests be repeated?

Once a diagnosis of ME/CFS has been confirmed, further investigation isn’t usually necessary. But it’s worth noting that new symptoms shouldn’t just be automatically linked to ME/CFS as they may need to be investigated.

If ME/CFS persists, especially if you are over 40, there is a strong case for repeating some of the routine tests, such as thyroid function, every few years. This is because conditions such as diabetes and hypothyroidism often appear very gradually – so they can be easily missed when you already have ME/CFS.

Specific tests

Full blood count and differential

Checks the level of haemoglobin, white blood cells and platelets as well as providing information on the size of the red blood cells and a breakdown of the white count into its components.

Anaemia is not part of ME/CFS and if present must be investigated further – as it always has a cause. One of the commonest situations is iron deficiency due to bleeding (sometimes menstrual) but a number of conditions with ME/CFS-like symptoms can also cause anaemia. These include coeliac disease and low thyroid function (hypothyroidism).

Anaemia can also be caused by dietary deficiencies and is sometimes found in teenage girls with ME/CFS who do not eat enough iron-containing foods.

Minor abnormalities in the white cell count – such as what are called atypical lymphocytes – are sometimes found in ME/CFS, especially in the very early stages when the illness follows a viral infection such as glandular fever. More persistent or significant abnormalities in the white cell count will need to be investigated, especially when accompanied by physical signs such as enlarged glands.

The platelet count should be normal in ME/CFS.

Biochemistry screen

Checks the level of salts/electrolytes in the blood (ie sodium, potassium), calcium and urea.

An increase or decrease in the level of calcium suggests that there may be another cause for symptoms. One condition that can cause a raised level of calcium is sarcoidosis – this would need to be considered if you also have chest symptoms. Thyroid disease can also raise the level of calcium in the blood.

The levels of sodium and potassium provide vital clues as to how your body is dealing with fluid load and how your kidneys are functioning. An increased level of sodium could indicate lack of water intake (dehydration) or an unusual hormonal condition called diabetes insipidus.

A decreased level of sodium could indicate an excessive water intake or Addison’s disease, where there is a serious fall in the output of the hormone cortisol. A decrease in the level of potassium could be caused by drugs (including diuretics, liquorice and carbenoxalone), diabetes, kidney problems or malabsorption of potassium in the gut.

The level of blood urea gives a rough guide to kidney function.

Blood glucose

A raised level of blood glucose indicates that you may have diabetes – an illness that can come gradually with increasing fatigue and urinary symptoms. If so, more specific tests will probably need to be arranged.

Creatine kinase (CK)

This is an enzyme that passes into the blood from damaged or inflamed muscle. Although CK is usually within normal limits in ME/CFS, there are occasional reports where it is raised. Any significant increase in the level of CK will need to be investigated,possibly with a muscle biopsy (where a small sample of muscle is removed for examination under the microscope) to exclude a primary muscle disease.

ESR and/or CRP (C-reactive protein)

These are two tests that simply pick up whether there is inflammation or infection somewhere in the body. Results of these tests should be normal in people with ME/CFS. If raised, further investigations are likely to be necessary.

Hormone function tests

The only hormone levels that need to be routinely checked in people with ME/CFS are thyroid and adrenal gland function – where cortisol is produced. If symptoms, or electrolyte results, are suggestive of Addison’s disease – a very rare condition where the adrenal glands produce dangerously low levels of cortisol – this will require further hospital-based tests.

In some circumstances, other hormones may need investigation. One possible example is serum oestradiol and FSH levels in women who have a significant exacerbation of symptoms at period time. This is because they may benefit from treatment with hormonal supplementation if levels are low (reference: Studd J and Panay M. Chronic fatigue syndrome. Lancet, 1996, 348, 1384).

Immune function tests

The white blood count gives a rough idea of how your immune system is functioning. There are also specialised tests of immune system function that show how the various different components are functioning. Although abnormalities do quite often occur in ME/CFS involving different components – eg autoantibodies, cytokines, immunoglobulin levels, natural killer cells – the changes are not sufficiently consistent to be helpful in diagnosis. And, in most situations, the results are not going to affect the management of your illness. So a more comprehensive investigation of the immune system is not normally required.

Liver function tests

These measure the level of various chemicals, proteins and enzymes produced in the liver.

Minor abnormalities can occur in ME/CFS for a number of reasons. These include the type of infection that triggered the illness and drugs (eg antidepressants) or herbal remedies that affect liver function. A benign condition of the liver called Gilbert’s syndrome is more common in ME/CFS and this can cause an intermittent rise in the level of bilirubin – a pigment that causes jaundice. And a condition called primary biliary cirrhosis, which can cause debilitating fatigue, should be considered when liver function is abnormal – especially where someone also complains of skin itching.

blood-20745_1280Screening for coeliac disease

Anyone with irritable bowel-type symptoms – ie abdominal pain, bloating, changes in bowel habit – must be properly checked for coeliac disease as this is a fairly common disorder that has a number of symptoms in common with ME/CFS. An antibody screening test (ie IgA antitissue transglutaminase) is commonly used.

If the result suggests coeliac disease you may then be asked to have a biopsy of the gut lining. Coeliac disease symptoms, including the fatigue, often respond very well to a gluten-free diet.

Screening for infection

Antibodies, which are part of the body’s immune system response to infection, often remain in the blood fo a period of time after the acute infection. So looking for antibodies to specific infections can provide clues as to what triggered your ME/CFS.

Unfortunately, this sort of information isn’t usually of any help in diagnosing or managing ME/CFS – so most doctors believe that looking for antibodies to past infections isn’t normally of any practical value. And these type of antibodies can be present in perfectly healthy people.

Even so, there are a number of specific and treatable infections that do sometimes need to be checked for if your clinical history suggests that one of them could be involved. Examples include hepatitis B and C, HIV, Lyme disease and Q fever.

Autoantibodies are antibodies that the body sometimes produces against its own tissues and this type of abnormal immune system response can sometimes follow an infection. This may explain why low levels of autoantibodies are sometimes found in people with ME/CFS.

Screening for rheumatic conditions

ME/CFS can produce pain in the joints. If this is more pronounced, or accompanied by inflammation, swelling or deformity, you will probably need to be investigated for some of the rheumatic diseases that can produce fatigue. This will involve immunological tests that are positive in conditions like lupus/SLE.

Thyroid function tests

As both underactivity (hypothyroidism) and overactivity (hyperthyroidism) can produce an ME/CFS-like illness, testing thyroid function is essential before a diagnosis of ME/CFS is confirmed.

The most sensitive test of thyroid function involves measuring TSH – thyroid stimulating hormone. As the name suggests, this is a hormone (produced in the brain) whose function is to stimulate thyroid hormone (thyroxine) production.

If thyroxine output is low then the TSH level rises. If too much thyroxine is being produced, then the TSH level falls. Thyroid hormones that are measured in the blood are T3 (occasionally) and T4.

Some private doctors prescribe thyroid hormones to patients with ME/CFS who have normal thyroid function test results. However, this is inappropriate and potentially dangerous because even small extra amounts of thyroxine can trigger serious heart rhythm disturbances.

Disclaimer:

Medical information contained in this article is not intended to be a substitute for medical advice or treatment from your own doctor.

The ME Association recommends that you always consult with your own doctor or healthcare professional about any specific problem.

They further recommend that any medical information provided by the MEA is, where appropriate, shown to and discussed with your doctor.

The narrative for this article first appeared in the current edition of ‘ME Essential’ (Winter 2013-14), and has been reproduced here with kind permission of The ME Association.

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59 comments

{ 59 comments… read them below or add one }

justy February 6, 2014 at 4:02 am

Do I have to be the first to say this?

Not good enough Dr Shepard, by a long shot.

Simon February 6, 2014 at 6:44 am

Big thanks to Charles Shepherd for some solid, no-nonsense advice.

Eliza February 6, 2014 at 8:13 am

Tell me,
How Will you find out whether someone has Lyme instead of ME if looking closer at the immune system shouln't be part of the tests?
Everybody knows traces of borellia dissapear from the blood as soon as 48 hours after infection. NK cells and their function , cd57 counts together with some other immune markers lead the way to possible lyme. Spinal taps can add to this diagnosis as do symptoms of course.

How Will you diagnose people with lupus if antibody screening shouln't be done?

How Will you find out about Adisson's disease if à 24 hour urine collection isn't even mentioned? 24 hour, not just one bloodsample is necessary, non invasive, we'll recognized as a testmethod, … Yet even this shouln't be done?!

Totally agree with Justin: this article doesn't even scratch the surface of what tests contribute to avoiding misdiagnosing or correctly diagnosing ME patients.
There are tests that can and should be done. Test that have been repeatedly been mentioned in ME research.

What about tilt table testing for OI, CPET testing to get an idea of physical impairment, neurocognitive testing, SPECT scans to look at brain bloodflow, … ?

heapsreal February 6, 2014 at 8:22 am

This is how i would make sense of this, if something shows up in a blood test its not cfs/me. Anything showing the immune system is involved is a recent infection and will go away unless something overt such as some type of lymphoma or immune defiency that is chronic. Otherwise if nothing shows on the test than u have cfs/me. We wont worry about nk function rnaseL because we cant do anything about it. So treatment is to give them something to shut them up and maybe make them feel better about feeling like shit, mmm prozac. If they respond poorly its the patients fault and they didnt follow instructions and there just depressed hypochondriacs.

This is what i call a flick pass, sorry cant help you but here is a referral to a great psychologist who will have u up and exercising in no time.

Its this sort of info that sets cfs/me back decades, which i think where the research came from??

definately no non-sense, absolutely no sense at all.

heapsreal February 6, 2014 at 8:28 am

im cured i dont have cfs/me anymore because i now have moderate chronic neutropenia:confused::confused:

Esther12 February 6, 2014 at 8:44 am
Eliza

Tell me,
Everybody knows traces of borellia dissapear from the blood as soon as 48 hours after infection. NK cells and their function , cd57 counts together with some other immune markers lead the way to possible lyme. Spinal taps can add to this diagnosis as do symptoms of course.

I don't think that this is right.

I've tended to assume that blood test are, at the moment, only valuable for identifying alternative diagnoses or research. I've not seen any good evidence to the contrary yet.

justy February 6, 2014 at 9:14 am

There are also a number of private (i.e .non-NHS) tests that are promoted to people with ME/CFS. These can be quite expensive and current medical consensus is that most of these tests are unproven or unnecessary as they are not helpful in either the diagnosis or management of ME/CFS.

Tell that to all the Americans on here who have access to the top M.E doctors in the states, who have been helped with managing symptoms by the results of these 'unproven' tests.

Tell that to the patients of KDM in Belgium who is finding and treating co infections in huge numbers of his patients, and for many this may result in either a resolution or lessening of symptoms.

Dr Myhills test may not have told me I speciaifcally had M.E, but it certainly proved, for the frist time in 15 years that my illness wasn't in my head – the results of this test also where defiantely useful in 'managing' my M.E.

I am disgusted by his comments, they mirror exactly those of NICE. Do a few basic tests and if nothing shows up then do no more. M.E can really only be diagnosed if other diseases have been excluded, such as M.S, Lupus, other autoimmune and connective tissue diseases. I have never had these illnesses ruled out despite having symptoms of them at one time or another. The misdiagnosis rate is way too high in this disease – exactly because further testing isn't carried out.

Don't even get me started on this bit:

Some private doctors prescribe thyroid hormones to patients with ME/CFS who have normal thyroid function test results. However, this is inappropriate and potentially dangerous because even small extra amounts of thyroxine can trigger serious heart rhythm disturbances.

I have read the testimony of many patients, treated by Dr Skinner (who sadly passed away recently) who have been given back their lives by this man listening to their symptoms alongside test results and treating them when the NHS had turend their backs on them. Unfortunately I was not one of them, but I am hopeful that his advice will still help me in the future.

Justy.

justy February 6, 2014 at 9:14 am

Sorry still having problems with getting the quotes button to wrap the text – don't know why – is it just me? perhaps i'm doing it wrong?

Esther12 February 6, 2014 at 9:43 am

The sad fact is that testing which is not of clinical value may well be of political and social value because of the prejudices which surround ME/CFS. I saw Shepherd's article as only being about what the medical value of blood testing, rather than the more complicated political side of things.

Considering validity of the 'testing' of the DWP and ATOS (and the Chalder Fatigue Scale) it certainly seem like those with power are able to get away with claiming the testing that tells them what they want is accurate regardless of the evidence.

Esther12 February 6, 2014 at 9:44 am
justy

Sorry still having problems with getting the quotes button to wrap the text – don't know why – is it just me? perhaps i'm doing it wrong?

Just showing off!

Seems to work fine for me.

Legendrew February 6, 2014 at 1:57 pm

It seems a few people have taken this article a little offensively which I don't feel it is whatsoever. As I see it, this article sets out to simply list the blood tests that are required before a diagnosis of ME/CFS should be made. By the current definitions, ME/CFS is a diagnosis of exclusion – it is therefore very important to exclude everything possible before the diagnosis is made. This however doesn't occur very often and I know many (myself included) have been diagnosed with ME/CFS before everything has been ruled out. This often means that some people are diagnosed with ME/CFS only to later be found to have other diseases, whether that be thyroid problems, autoimmune diseases such as lupus and a plethora of other conditions. It seems people are taking this article as a 'these are the blood tests people with ME need' whereas in truth this is more a list of blood tests needed to be done before a diagnosis of ME is made – assuming all of the tests draw a blank.

The trouble is that a premature diagnosis of ME not only hinders the further investigation of the single patient into their particular health problem, but it also increases the number of patients under the ME/CFS group. As most agree, ME/CFS is not a single disease entity which hinders greatly any effort to find consistent biological markers of each – if patients are prematurely diagnosed with ME only to later find they are in-fact suffering a known disease this problem is further intensified. For both of these reasons it is very important that going forwards doctors run thorough testing before a diagnosis of ME/CFS is made. Whichever tests are done post diagnosis are then in the hands of a patients doctor and that patient – it is however true that, as Dr. Shepherd states, many of these ME/CFS tests are often quite expensive and their value is not yet known.

SOC February 6, 2014 at 2:46 pm
justy

Sorry still having problems with getting the quotes button to wrap the text – don't know why – is it just me? perhaps i'm doing it wrong?

I fixed it for you.

For future reference, the text you want to quote needs to go between the bracket quote bracket and the bracket /quote bracket. When you click the quotes button both parts come up. You need to insert the text between them. Or type the text, then highlight and click the quotes button.

justy February 6, 2014 at 3:49 pm

Thanks @SOC think I've got it now – Doh!

vamah February 6, 2014 at 5:51 pm
Legendrew

It seems a few people have taken this article a little offensively which I don't feel it is whatsoever. As I see it, this article sets out to simply list the blood tests that are required before a diagnosis of ME/CFS should be made. By the current definitions, ME/CFS is a diagnosis of exclusion – it is therefore very important to exclude everything possible before the diagnosis is made. This however doesn't occur very often and I know many (myself included) have been diagnosed with ME/CFS before everything has been ruled out. This often means that some people are diagnosed with ME/CFS only to later be found to have other diseases, whether that be thyroid problems, autoimmune diseases such as lupus and a plethora of other conditions. It seems people are taking this article as a 'these are the blood tests people with ME need' whereas in truth this is more a list of blood tests needed to be done before a diagnosis of ME is made – assuming all of the tests draw a blank.

The trouble is that a premature diagnosis of ME not only hinders the further investigation of the single patient into their particular health problem, but it also increases the number of patients under the ME/CFS group. As most agree, ME/CFS is not a single disease entity which hinders greatly any effort to find consistent biological markers of each – if patients are prematurely diagnosed with ME only to later find they are in-fact suffering a known disease this problem is further intensified. For both of these reasons it is very important that going forwards doctors run thorough testing before a diagnosis of ME/CFS is made. Whichever tests are done post diagnosis are then in the hands of a patients doctor and that patient – it is however true that, as Dr. Shepherd states, many of these ME/CFS tests are often quite expensive and their value is not yet known.

I have to agree, although I think the list of tests could be longer. I think so often a person is labeled with cfs and then can't get tests or treatment because so many doctors treat it as a psychological illness. Also, since it probably has different triggers for different people, it is important to try and find that underlying trigger. That is the point where you start traeting the illness instead of just symptoms.

SOC February 6, 2014 at 5:55 pm
vamah

I have to agree, although I think the list of tests could be longer. I think so often a person is labeled with cfs and then can't get tests or treatment because so many doctors treat it as a psychological illness. Also, since it probably has different triggers for different people, it is important to try and find that underlying trigger. That is the point where you start traeting the illness instead of just symptoms.

Do we even have any sense for what that treatable "underlying trigger" might be? Aren't we stuck, at the moment, with just treating the symptoms until someone figures out the cause of the illness?

SOC February 6, 2014 at 6:00 pm
Legendrew

It seems a few people have taken this article a little offensively which I don't feel it is whatsoever. As I see it, this article sets out to simply list the blood tests that are required before a diagnosis of ME/CFS should be made.

I might agree with you if it weren't for statements like this:

There are also a number of private (i.e .non-NHS) tests that are promoted to people with ME/CFS. These can be quite expensive and current medical consensus is that most of these tests are unproven or unnecessary as they are not helpful in either the diagnosis or management of ME/CFS.

[my bolding and underlining]

Clearly he's not just talking about diagnosis, but claiming further tests are not useful in the management of ME/CFS.

heapsreal February 6, 2014 at 6:53 pm

I think the other tests can help guide docs in diagnosing cfs. I know there not in the outdated criteria's but there is enough research to show our immune system is dysfunctional. My testing showed elevated total lymphocytes that we tracked for awhile before treating with antivirals, the lymphocyte subsets to this day are still dysfunctional but improved with antivirals. Most tests show i had some type of neutropenia mostly mild but the last few months classed as moderate, this has helped my doc together with some other tests to understand why i have ongoing sinusitis for the last 2 years and justifies using antibiotics.

Gradually many of my hormones have dropped below the referance range, dhea, free testosterone levels, other hormones barely in range.

So there are tests out there that have helped me and my doctor in the way im treated. Does having these abnormal test results not put me in the cfs/me diagnosis.

NK cells, theres nothing we can do about it so dont worry, they just kill cancer infected cells and viral infected cells, nothing to worry about testing this??

I think the above article is very simplified explanation that doesnt help anyone. A forward thinking doctor would use more tests and can interpret them in a way to help him confirm a cfs/me diagnosis and can help guide certain treatments. If every doctor followed the above than there wouldnt be any research into cfs and no treatments at all for cfs/me, most would balk at symptomatic treatment as well. A good forward thinking doc is hard to find also.

Sushi February 6, 2014 at 7:21 pm

Those "other tests that have been promoted to people with ME/CFS " have been important in monitoring and managing my treatment. But of course it is also important to have a doctor who knows how to use these tests and put them together to get a good clinical picture.

Sushi

Legendrew February 6, 2014 at 8:35 pm
SOC

I might agree with you if it weren't for statements like this:

[my bolding and underlining]

Clearly he's not just talking about diagnosis, but claiming further tests are not useful in the management of ME/CFS.

Well, as odd as it sounds, tests themselves are of little use in the management of a disease if you're not completely sure of what you're looking for. There are examples to the contrary of this such as measuring antibodies and TSH (among the other thyroid hormones) which do help in the management through allowing for the right dosage of treatment, however many of the tests used by some physicians for ME/CFS patients do nothing to aid disease management other than informing of the ongoing problem which, while very helpful to researchers in understanding the disease mechanisms at play, are very hard to transfer into use disease management.

I realise many will be quick to point out testing for viruses and antivirals that lie therein but I don't prescribe to the notion that ME/CFS is of infectious origins, perhaps triggered but certainly in my opinion not perpetuated. My analogy that I feel I refer too far too often is that of a wildfire in a forest; a virus or other infectious agent serves as a spark which sets ablaze the forest but after this event there is little point in trying to track down the spark given that it is more than likely an impossible task as the spark has long since been absent, besides which the blaze is of much greater concern!

I fear I may have lost my point somewhat but my takeaway message I suppose it that we simply know too little at this point for the any testing to be of great use in clinical practice given that we don't even know what to look for, that's not to say however that none should be done at all – that of course comes down to the decision of the patient and doctor in question.

vamah

I have to agree, although I think the list of tests could be longer. I think so often a person is labeled with cfs and then can't get tests or treatment because so many doctors treat it as a psychological illness. Also, since it probably has different triggers for different people, it is important to try and find that underlying trigger. That is the point where you start treating the illness instead of just symptoms.

I agree with your first point regarding the stigma a diagnosis of ME brings and the problems that arise therein with further testing when often it is warranted but I think all too often we get wrapped up in finding what triggers illness. This is an important question for researchers trying to understand disease mechanisms however for a patient and doctor the cause is of little help. If someone catches a virus or breaks a leg there is little point in trying to find out the circumstances under which such events happened, what's important is the steps you take in the present. I think with chronic diseases we all have a tendency, myself included, to mull over the "what ifs" when really we should be looking at the present a little more.

I do however think certain diseases and the testing necessary to rule them out was missed from this list.

lansbergen February 6, 2014 at 8:57 pm

there is little point in trying to track down the spark given that it is more than likely an impossible task as the spark has long since been absent

I disagree. The pathogen I suspect does not go away but sadly there is no test for it.

Esther12 February 6, 2014 at 9:02 pm

PS: For some reason I'm surprised to have Shepherd contribute an article here. I thought we were a weird backwater.

Welcome to PR!

SOC February 6, 2014 at 9:42 pm
Legendrew

I realise many will be quick to point out testing for viruses and antivirals that lie therein but I don't prescribe to the notion that ME/CFS is of infectious origins, …

You can believe what you want and not get tests on yourself as a consequence. The fact is that multiple highly respected researchers are finding multiple ongoing known infections in PWME. Of course you'll never find them if you don't test for them.

Immune testing (considered unnecessary by Shepard) is also indicating ongoing currently unidentified pathogens (as @Iansbergen mentioned) in some patients. Immune testing has shown immune dysfunction that can benefit from immune modulators/treatments. Of course we'd never know that if we did "unnecessary" immune testing, either.

So fine, don't get pathogen or immune testing if you don't want to believe ME/CFS is of infectious origin, but do the rest of us a favor and don't suggest that testing isn't beneficial for PWME.

heapsreal February 7, 2014 at 1:19 am
Legendrew

Well, as odd as it sounds, tests themselves are of little use in the management of a disease if you're not completely sure of what you're looking for. There are examples to the contrary of this such as measuring antibodies and TSH (among the other thyroid hormones) which do help in the management through allowing for the right dosage of treatment, however many of the tests used by some physicians for ME/CFS patients do nothing to aid disease management other than informing of the ongoing problem which, while very helpful to researchers in understanding the disease mechanisms at play, are very hard to transfer into use disease management.

I realise many will be quick to point out testing for viruses and antivirals that lie therein but I don't prescribe to the notion that ME/CFS is of infectious origins, perhaps triggered but certainly in my opinion not perpetuated. My analogy that I feel I refer too far too often is that of a wildfire in a forest; a virus or other infectious agent serves as a spark which sets ablaze the forest but after this event there is little point in trying to track down the spark given that it is more than likely an impossible task as the spark has long since been absent, besides which the blaze is of much greater concern!

I fear I may have lost my point somewhat but my takeaway message I suppose it that we simply know too little at this point for the any testing to be of great use in clinical practice given that we don't even know what to look for, that's not to say however that none should be done at all – that of course comes down to the decision of the patient and doctor in question.

I agree with your first point regarding the stigma a diagnosis of ME brings and the problems that arise therein with further testing when often it is warranted but I think all too often we get wrapped up in finding what triggers illness. This is an important question for researchers trying to understand disease mechanisms however for a patient and doctor the cause is of little help. If someone catches a virus or breaks a leg there is little point in trying to find out the circumstances under which such events happened, what's important is the steps you take in the present. I think with chronic diseases we all have a tendency, myself included, to mull over the "what ifs" when really we should be looking at the present a little more.

I do however think certain diseases and the testing necessary to rule them out was missed from this list.

So your theory of not treating Infections because we dont know the real cause is like saying hiv they shouldn't treat coinfections as they arent the main issue. U would have alot of hiv people die of cmv, mycoplasma etc.

Eliza February 7, 2014 at 5:00 am
Esther12
Eliza

Tell me,
Everybody knows traces of borellia dissapear from the blood as soon as 48 hours after infection. NK cells and their function , cd57 counts together with some other immune markers lead the way to possible lyme. Spinal taps can add to this diagnosis as do symptoms of course.

I don't think that this is right.

I've tended to assume that blood test are, at the moment, only valuable for identifying alternative diagnoses or research. I've not seen any good evidence to the contrary yet.

Esther12,

"blood tests are only valuable for identifying altnerative diagnoses and research"

Ok, so when you don't do any additional testing, how will you know your diagnosis is correct?

And yes, testing is valuable for research, but also for the clinician treating you.
If he or she doesn't look into your immune problems, endocrine problems, viral load, bacterial load, gut dysbiosis, exercise capacity, … any further than what is suggested in this article, how will he or she be able to handle you and your disease properly?

An active viral infection doesn't mean you don't have ME. It's typical for ME.
But … this viral infection could explain your immune problem or vice versa.
Should you put such patients on a treadmill and let them exhaust themselves knowing they have an ongoing infection with high cytokin loads or should you be very very cautious?

I would have thought any MD would want to know this kind of impartant info in order to help his patient and not send him or her totally off the cliff and into bed for many years to come.

MeSci February 7, 2014 at 7:08 am
heapsreal

If every doctor followed the above than there wouldnt be any research into cfs and no treatments at all for cfs/me, most would balk at symptomatic treatment as well. A good forward thinking doc is hard to find also.

I agree with a lot of what you say, but I don't think that what doctors do (or don't do) has much influence on what researchers do (or don't do). More sadly perhaps (although clinical data are potentially invaluable research info), research findings take a very long time to be translated into clinical practice. They are two very different lines of work.

heapsreal February 7, 2014 at 8:08 am
MeSci

I agree with a lot of what you say, but I don't think that what doctors do (or don't do) has much influence on what researchers do (or don't do). More sadly perhaps (although clinical data are potentially invaluable research info), research findings take a very long time to be translated into clinical practice. They are two very different lines of work.

I see where your coming from but the research we have going on now is mostly done by gp's with an interest in cfs/me and then go into research, probably due to the lack of efforts from other research avenues. Dr k, Dr P, klimas, kdm etc
i guess its a 2 way street, its gp's generally in contact with patients and where it all begins, generally researcher dont see patients first up but stimulated to research by doctors trying to treat these patients??

Its a can of worms?? but the dr/researchers above are using tests to help them diagnose and treat cfs/me. We are only just beginning to see there efforts to stimulate more researchers.

charles shepherd February 7, 2014 at 8:43 am

Before anyone else misinterprets or misunderstands what this MEA information on blood testing is for:

It was produced as a very basic MEA magazine item to cover ALL the routine blood tests that EVERYONE should normally have here in the UK before a diagnosis of ME/CFS is considered or made.

It is NOT designed to be a comprehensive list of all the blood tests that may need to be arranged – eg Lyme disease testing; neuroendocrine testing for Addison’s disease, pituitary disorders; further investigation of liver function if minor abnormalities are found; serum hydroxyvitamin D in those at risk of vitamin D deficiency; comprehensive autoimmune disease screen. This list is long and will depend on the history given by the patient and the examination findings obtained during a proper clinical assessment. There just wasn’t the space to include all of these tests, along with when they could/should be used, in ME Essential.

However, all of these additional tests are all covered in considerable detail in the sections (7 pages of A4) covering differential diagnosis, clinical assessment and investigations in the MEA purple booklet:

http://www.meassociation.org.uk/2013/06/available-now-–-latest-edition-of-the-me-association-clinical-practice-booklet/

Regarding the use of thyroxine: this has to prescribed with great caution in people who have/may have adrenal insufficiency/hypocortisolaemia (as may be the case in ME/CFS) and should NOT be prescribed in such circumstances in people who have normal thyroid function tests.

Regarding tests for Lyme disease: almost a whole page of the MEA purple booklet is given over to Lyme disease, including NHS and private laboratory testing. Some of the commercial tests are not reliable and I would suggest that people have a look at a recent BBC documentary when it appears on BBC iplayer:

http://www.bbc.co.uk/programmes/b03sqyp2

……where a perfectly healthy BBC reporter I know was tested ? positive using a private sector laboratory.

heapsreal February 7, 2014 at 8:47 am

Thanks for clarifying. A hot topic here;)

Legendrew February 7, 2014 at 9:53 am
SOC

You can believe what you want and not get tests on yourself as a consequence. The fact is that multiple highly respected researchers are finding multiple ongoing known infections in PWME. Of course you'll never find them if you don't test for them.

Immune testing (considered unnecessary by Shepard) is also indicating ongoing currently unidentified pathogens (as @Iansbergen mentioned) in some patients. Immune testing has shown immune dysfunction that can benefit from immune modulators/treatments. Of course we'd never know that if we did "unnecessary" immune testing, either.

So fine, don't get pathogen or immune testing if you don't want to believe ME/CFS is of infectious origin, but do the rest of us a favor and don't suggest that testing isn't beneficial for PWME.

I disagree that immune testing implies ongoing unidentified pathogens. I fear I'm fighting against a lot of years of belief of ME/CFS as being of infectious origin but I believe the immune activation in the absence of any consistent pathogen findings over a 20+ year period means we should perhaps be looking more towards a disease of autoimmune pathology rather than of infectious. Immune testing is I believe helpful in showing that there is something not working as it should but it's a silly jump in my opinion to automatically assuming that something is a pathogen that has evaded detection for so long. I believe unfortunately that people "want" there to be a virus at the heart of the conditions purely because it is a simple explanation but that's not to say it's the right one. Perhaps the hunt for viruses will be looked back upon as holding back the advancement of our understanding of the condition. I also think our current understanding of the inner workings and interconnections of the immune system make it very difficult to treat immune dysfunction – I'd go as far as to say that "immune-modulators" are very unlikely to get at the heart of the condition purely because we don't yet know what in particular needs targeting, with something as complex as the immune system a shotgun approach isn't going to get you very far and could indeed make things worse. With regards to the findings of known infections, these are very often found at similar levels in the normal population, the question is why these known infections begin to cause a problem and that is likely the immune dysfunction we know appears in ME – this is very common in most diseases that cause a dysfunctional immune system and does nothing to support the notion of ME/CFS as of infectious origins.

I want to make it clear that I'm not putting down these tests and treatment, I am however saying that the clinical evidence simply isn't there to support their use hence it comes down to the opinion of the patient and doctor. Co-infectious are something frequently discussed and I do believe they play a part in some people but only as a later result of the observable immune dysfunction, which incidentally I only feel is unnecessary purely because we don't yet know how to interpret the results in, a think a similar example would be testing thyroid hormone levels without having a reference range – the results are simply of no use for treatment other than giving a very broad "somethings not right". Treating these co-infections may help symptoms a little but it's not going to solve the bigger issues at the heart of the condition – just as treating co-infections in HIV/AIDS does not cure the condition overall.

heapsreal February 7, 2014 at 10:08 am

treating co-infections in hiv reduces mortality.

Low nk function is a common finding in cfs/me, if u look at the role of nk cells they kill viral infected cells as well as cancer infected cells. Its just common sense that if apart of your immune system isnt working then infections are going to play a big part.

Also i dont think we are saying herpes viruses are the cause of cfs but occur due to the immune dysfunction. If it had no bearing then why do we see improvement of some cfsers with antivirals treatments which are backed up by improved immune/infection labs. Herpes virus reactivation is common in other illness with immune dysfunction supression. Maybe for some its a hit and run but for others many of these infections are ongoing. This brings us back to sub groups again.

bertiedog February 7, 2014 at 1:32 pm
justy

Tell that to all the Americans on here who have access to the top M.E doctors in the states, who have been helped with managing symptoms by the results of these 'unproven' tests.

Don't even get me started on this bit:

I have read the testimony of many patients, treated by Dr Skinner (who sadly passed away recently) who have been given back their lives by this man listening to their symptoms alongside test results and treating them when the NHS had turend their backs on them. Unfortunately I was not one of them, but I am hopeful that his advice will still help me in the future.

Justy.

Hi Justy

I am one of those patients who got their lives back way back in 2002 because I found a knowledgeable private Endo who after getting these so called waste of time tests done for me showed I had a severe adrenal and thyroid problem and started on hydrocortisone and dessicated thyroid.

It soon felt like I had my life back, not a cure but I continue being able to do so much more than the majority of people with ME/CFS. Only today I brought a friend round to my house who has Fibromyalgia plus ME/CFS and no treatment. She seriously cannot go on like this but I recognise that she has severe adrenal issues and probably thyroid involvement too so I am going to get a saliva test done for her and once we get the results she will probably self treat. That is how desperate we can be here in the UK because the NHS has let her down. She feels she has no quality of life whatsover, she has lost everything and doesn't want to continue living like this.

I would like Dr Shepherd to see just what I can do in a day. Very shortly tonight I will be doing my jigsaw but as I put on dance music to help my concentration I know I will just have to get up and dance, I cannot stop myself and everytime I do this I feel such delight and joy.

This is on top of me already doing 5371 steps today (according to my FITBIT monitor) which included a good walk with my dog, shopping and having the visit from my friend.

Treating the thyroid and adrenals if indicated can literally give you back a life worth living.

Pam

MeSci February 7, 2014 at 1:58 pm
bertiedog

Hi Justy

I am one of those patients who got their lives back way back in 2002 because I found a knowledgeable private Endo who after getting these so called waste of time tests done for me showed I had a severe adrenal and thyroid problem and started on hydrocortisone and dessicated thyroid.

It soon felt like I had my life back, not a cure but I continue being able to do so much more than the majority of people with ME/CFS. Only today I brought a friend round to my house who has Fibromyalgia plus ME/CFS and no treatment. She seriously cannot go on like this but I recognise that she has severe adrenal issues and probably thyroid involvement too so I am going to get a saliva test done for her and once we get the results she will probably self treat. That is how desperate we can be here in the UK because the NHS has let her down. She feels she has no quality of life whatsover, she has lost everything and doesn't want to continue living like this.

I would like Dr Shepherd to see just what I can do in a day. Very shortly tonight I will be doing my jigsaw but as I put on dance music to help my concentration I know I will just have to get up and dance, I cannot stop myself and everytime I do this I feel such delight and joy.

This is on top of me already doing 5371 steps today (according to my FITBIT monitor) which included a good walk with my dog, shopping and having the visit from my friend.

Treating the thyroid and adrenals if indicated can literally give you back a life worth living.

Pam

But Dr Shepherd does recommend adrenal and thyroid tests – repeated ones in fact. A frequent problem is that UK doctors are not doing them, hence the MEA's offer to send them the booklets. The booklets may not be perfect, but I think they have the potential to improve GPs' woefully-limited understanding and treatment. I have requested one to be sent to my GP.

charles shepherd February 7, 2014 at 2:45 pm

Here is just one example (=Sjogren's syndrome) from the Differential Diagnosis section of our MEA booklet for doctors of how I go into considerable detail about the need for proper and detailed investigation for a long list of conditions that are misdiagnosed as ME/CFS.

Sjögren’s syndrome (SS): A number of viruses, including Epstein-Barr virus and endogenous retroviruses have been implicated in the causation of SS, as well as an uprated cytokine profile. The commonest presenting features are dry eyes (causing a gritty sensation) and a dry mouth. Vaginal dryness (causing painful intercourse) and respiratory tract dryness (causing a dry cough) may also be present. Debilitating fatigue and/or arthralgia is present in a significant proportion. Anti-Ro and/or anti-La antibodies are found in approximately 75% of SS patients. Hypergamma- globulinaemia with raised immunoglobulin G (IgG) and/or IgM is common. A Schirmer test assesses occular dryness.

charles shepherd February 7, 2014 at 2:46 pm
charles shepherd

Here is just one example (=Sjogren's syndrome) from the Differential Diagnosis section of our MEA booklet for doctors of how I go into considerable detail about the need for proper and detailed investigation for a long list of conditions that are misdiagnosed as ME/CFS.

Sjögren’s syndrome (SS): A number of viruses, including Epstein-Barr virus and endogenous retroviruses have been implicated in the causation of SS, as well as an uprated cytokine profile. The commonest presenting features are dry eyes (causing a gritty sensation) and a dry mouth. Vaginal dryness (causing painful intercourse) and respiratory tract dryness (causing a dry cough) may also be present. Debilitating fatigue and/or arthralgia is present in a significant proportion. Anti-Ro and/or anti-La antibodies are found in approximately 75% of SS patients. Hypergamma- globulinaemia with raised immunoglobulin G (IgG) and/or IgM is common. A Schirmer test assesses occular dryness.

Which other clinical guideline on ME/CFS goes into this sort of detail?

lansbergen February 7, 2014 at 4:03 pm

I'd go as far as to say that "immune-modulators" are very unlikely to get at the heart of the condition purely because we don't yet know what in particular needs targeting, with something as complex as the immune system a shotgun approach isn't going to get you very far and could indeed make things worse.

Well an immunemodulator saved my live and very slowly but steadily improves my health. It was a calculated gamble and I still do not regret it.

As for autoimmunity, the pathogen I suspect does not induce an adaptive response. So how can it be autoimmunity????

I do not know what you have but if you have what I have you are just at the beginning of your journey.

SOC February 7, 2014 at 4:56 pm
Legendrew

I disagree that immune testing implies ongoing unidentified pathogens.

I doubt you know more about it than my immunologist who says my immune dysfunction pattern is clearly indicative of an ongoing infection, even when we've (temporarily) cleared all the known, testable infections. She says it looks like I have an ongoing infection with something we can't yet detect. In my mind, her training and experience in patterns of immune dysfunction and what they might mean trump your belief.

Naturally, I have no interest in changing your belief. You're entitled to believe what you want. I'm a researcher by inclination and training and prefer scientific data to belief, so I'm going with established data for myself.

I fear I'm fighting against a lot of years of belief of ME/CFS as being of infectious origin but I believe the immune activation in the absence of any consistent pathogen findings over a 20+ year period means we should perhaps be looking more towards a disease of autoimmune pathology rather than of infectious.

I think we are experiencing several layers of confusion here. The first is in interpreting the results of pathogen testing in ME/CFS. Research has not (yet) found a single pathogen in all ME/CFS patients. It is NOT true that NO pathogens have been found in ME/CFS patients. In fact, there are quite a few known pathogens found frequently in ME/CFS patients. It's just not the same single pathogen in everyone. So it's not that NO pathogens are found, it's that a unique universal pathogen has not been found. Big difference.

A second layer of confusion lies, I think, in confusing cause and effect. Most of us would agree that no single pathogen has been found to be the cause of ME/CFS. Nevertheless, having ME/CFS (whatever the cause) and the resulting immune dysfunction results in multiple pathogens in PWME.

Those pathogens need to be identified and treated. Just because they are not the primary cause of the illness doesn't mean they shouldn't be treated. In fact, they may be the cause of the majority of our symptoms.

Which is where a third layer of confusion comes in. The primary cause of the illness does not need to be the infection or condition that causes the majority of, or the most serious, symptoms. Treating symptoms and secondary conditions can make a vast improvement in the patient's condition even when the primary cause cannot be addressed.

We have HIV/AIDS as a model here. Patients were first identified because they were suffering from reactivations of common infections in the herpesvirus family, among other known infections. Sound familiar? It was determined that none of those infections was the cause of AIDS in part because all patients did not have the same infections. Sound familiar? Nevertheless, those infections were causing the vast majority of the symptoms in AIDS. Patients were not dying from the immediate effect of the HIV virus, they were dying from the secondary infections that their bodies could not control because HIV was destroying their immune systems' ability to fight those infections.

What did they do in the early days of AIDS treatment before HIV was identified? They treated the secondary infections which were causing most of the symptoms. This was long before they knew why these peoples' immune systems were misbehaving. It was long before they had any clue what the unknown infection was. While they couldn't stop the damage to the immune system, not knowing the cause, they could vastly improve quality of life and reduce damage to the body done by the secondary infections.

We don't have to know the primary cause of the illness to know that patients have many secondary infections and that those infections need to be treated to prevent further damage to the body and to reduce symptoms. But if we refuse to test for and treat those secondary infections simply because they are not the primary cause of the illness, we are fools. Infections are infections. The damage is done whether or not the infection is primary or secondary.

There is no concrete evidence that ME/CFS is not infectious in origin. It appears not to be caused by a single currently known pathogen, but there's even some question about that. We don't know everything about the interaction of infections with genetic and environmental factors. In fact, there's much we don't know about the infections we are already aware of. And of course, there's still the possibility of infections that have not yet been identified.

ME/CFS could be the result of hit-and-run damage by multiple pathogens. That might be the root of an autoimmune situation. It could be the result of an ongoing infection that we are currently unable to detect, as in the HIV situation not that long ago. It could be caused by something else entirely. We simply don't know at this time.

Immune testing is I believe helpful in showing that there is something not working as it should but it's a silly jump in my opinion to automatically assuming that something is a pathogen that has evaded detection for so long.

I'm certainly not jumping to the conclusion that the primary cause of ME/CFS is an infection. I'm just not jumping to the silly conclusion that it's definitely not. Nor am I jumping to the silly conclusion that medical science has already detected every pathogen that exists. Now that IS silly.

The cause is unknown. It could be any number of things. There are quite a few possibilities currently being researched. What's silly at this point is jumping to conclusions about what is or is not the cause at this point in the research.

I believe unfortunately that people "want" there to be a virus at the heart of the conditions purely because it is a simple explanation but that's not to say it's the right one.

I doubt anyone "wants" a virus to be at the heart of the condition simply because that's a simple explanation. First of all, it is far from a simple explanation. If it IS an infection (which is far from certain) it's probably a difficult and complex infection probably in a difficult to find location like the nervous system or the gut. (Ian Lipkin is no fool)

What most of us "want" is not a simple explanation, but broad and open-minded research which includes investigation into the possibility of a pathogen at the root. What we do NOT want is the dismissal of a likely avenue of research because of ridiculous assumptions and poor interpretation of current knowledge.

I also think our current understanding of the inner workings and interconnections of the immune system make it very difficult to treat immune dysfunction – I'd go as far as to say that "immune-modulators" are very unlikely to get at the heart of the condition purely because we don't yet know what in particular needs targeting, with something as complex as the immune system a shotgun approach isn't going to get you very far and could indeed make things worse.

And there you've given a good explanation for why extensive immune testing is valuable for PWME. A shotgun approach to treating immune dysfunction is certainly problematic. Much better to have some knowledge — through individual testing — of what's malfunctioning in your own individual immune system and treating accordingly when possible.

For example, my daughter and I do not have identical immune dysfunctions, therefore we don't use the same immune treatments. How would we know what to do if we didn't have the test data to work from? Without testing, the choices are to do nothing or risk doing the wrong thing. Why should we not test when tests are available to guide treatment?

Treating these co-infections may help symptoms a little but it's not going to solve the bigger issues at the heart of the condition – just as treating co-infections in HIV/AIDS does not cure the condition overall.

Quite a few people who have treated these co-infections will argue that they help symptoms only "a little". In my family alone, my uncle went from mild/moderate to full remission with antiviral treatment. My daughter was so sick she would have had to drop out of college during her first year when she got antiviral treatment. Now she's in remission and in graduate school in engineering. I went from bedbound and unable to read to up all day and tutoring 15-20 hours a week. While I'm not in remission, I don't consider going from bedbound with no life worth speaking of to being a functioning adult earning some income a "little" improvement. I can't do everything I want, but I don't feel like I constantly have the flu. I can read. I can put together lucid sentences. I'm not in constant pain. I don't call that a "little" improvement in symptoms. I call it getting some of my life back.

We are not the only people who have had more than "a little" improvement from treating co-infections. Dr Petersen would not be treating patients with antibiotics and antivirals if he was only seeing "a little" improvement from them. Nor would Dr Klimas, or Dr Montoya, or Dr Kogelnik, or Dr DeMeirleir. They are using them because they see significant improvements.

No one is suggesting, especially those doctors, that pathogen treatments cure ME/CFS. We don't have a cure yet. But to avoid (or worse, deny patients access to) treatments that can provide significant improvement simply because they are not a cure for the primary cause is beyond stupid.

Testing for pathogens and immune dysfunction is NOT unnecessary. It is critical for guiding appropriate treatment to give significant quality of life improvements in PWME.

SOC February 7, 2014 at 5:01 pm
charles shepherd

Which other clinical guideline on ME/CFS goes into this sort of detail?

How about the ME/CFS Primer for Clinical Practioners?

Not that I'm suggesting there's any excellent clinical guideline. ;) That's something we're sorely lacking.

charles shepherd February 7, 2014 at 6:05 pm

Both cover fairly similar ground but the MEA purple booklet (52 pages with around 300 referenced papers) goes into far more detail on differential diagnosis/misdiagnosis and investigations.

SOC February 7, 2014 at 6:56 pm
charles shepherd

Both cover fairly similar ground but the MEA purple booklet (52 pages with around 300 referenced papers) goes into far more detail on differential diagnosis/misdiagnosis and investigations.

Yes, both are useful documents with different focuses. Differential diagnosis is critical, as is treatment.

Hopefully someday we'll have a single document that does a superb job of both. That's a very big challenge, though, and maybe not possible.

charles shepherd February 8, 2014 at 4:15 am

The MEA (evidence based) guidance in our purple booklet covering clinical assessment, differential diagnosis and management of ME/CFS is clearly aimed at health professionals (HPs) here in the UK – where the vast majority of HPs work within the National Health Service and consequently have to work to restrictions in relation to the way in which patients can be investigated and managed. I am not defending the situation and the MEA has made it very clear that we do not regard the NICE guideline on ME/CFS, with its emphasis on CBT and GET, as being fit for purpose. So I think there are real difficulties in producing guidelines on ME/CFS that are going to be acceptable on an international basis. And this is one of the reasons why guidelines produced by doctors outside the UK (e.g. Canadian Criteria) are not being endorsed for use in the UK NHS.

charles shepherd February 8, 2014 at 6:47 am
justy

Do I have to be the first to say this?

Not good enough Dr Shepard, by a long shot.

Justy – I have only just joined this forum in order to respond to some of the comments.

So please will you have a careful look at the more detailed responses I have made to people who appear to have misunderstood the purpose of this item on blood testing.

This is a short review of all the blood tests that EVERYONE should have before a diagnosis of ME/CFS is considered or made.

It is not intended to be a review of all the different tests relating to virology, immunology, endocrinology etc that would/might need to be arranged in view of the history given by the patient and any examination findings during the clinical assessment phase.

These tests are all covered in considerable detail, along with differential diagnosis/misdiagnosis of ME/CFS, in the MEA purple booklet – a 52 page document that is evidence based and referenced to key research papers and clinical trials (over 300 key references). The section on differential diagnosis and investigation of someone who may have a diagnosis of ME/CFS covers 8 pages of A4.

heapsreal February 8, 2014 at 6:51 am

@charles shepherd as a doctor treating ME patients in the UK do u find it frustrating being limited in testing and treatments available to you? I think it must be a hard job for you and would place u under the microscope alot from the policy makers above. Again thanks for clarifying the article, we always appreciate hearing from cfs/me doctors.

cheers!!!

charles shepherd February 8, 2014 at 7:42 am

The simple answer is that while our National Health Service can be really excellent (and I've just been with someone this morning with a tumour who is having the most exceptional terminal care from everyone involved) the restrictions imposed by NICE and our other regulatory bodies mean that many doctors are becoming reluctant to use what is termed 'clinal judgement' when it comes to how you assess and manage patients and this is being replaced by a tick box approach to medicine that obeys all the rules but may not always be in the best interest of the patient.

Eliza February 8, 2014 at 9:59 am
SOC
Legendrew

I disagree that immune testing implies ongoing unidentified pathogens.

I doubt you know more about it than my immunologist who says my immune dysfunction pattern is clearly indicative of an ongoing infection, even when we've (temporarily) cleared all the known, testable infections. She says it looks like I have an ongoing infection with something we can't yet detect. In my mind, her training and experience in patterns of immune dysfunction and what they might mean trump your belief.

Naturally, I have no interest in changing your belief. You're entitled to believe what you want. I'm a researcher by inclination and training and prefer scientific data to belief, so I'm going with established data for myself.

I fear I'm fighting against a lot of years of belief of ME/CFS as being of infectious origin but I believe the immune activation in the absence of any consistent pathogen findings over a 20+ year period means we should perhaps be looking more towards a disease of autoimmune pathology rather than of infectious.

I think we are experiencing several layers of confusion here. The first is in interpreting the results of pathogen testing in ME/CFS. Research has not (yet) found a single pathogen in all ME/CFS patients. It is NOT true that NO pathogens have been found in ME/CFS patients. In fact, there are quite a few known pathogens found frequently in ME/CFS patients. It's just not the same single pathogen in everyone. So it's not that NO pathogens are found, it's that a unique universal pathogen has not been found. Big difference.

A second layer of confusion lies, I think, in confusing cause and effect. Most of us would agree that no single pathogen has been found to be the cause of ME/CFS. Nevertheless, having ME/CFS (whatever the cause) and the resulting immune dysfunction results in multiple pathogens in PWME.

Those pathogens need to be identified and treated. Just because they are not the primary cause of the illness doesn't mean they shouldn't be treated. In fact, they may be the cause of the majority of our symptoms.

Which is where a third layer of confusion comes in. The primary cause of the illness does not need to be the infection or condition that causes the majority of, or the most serious, symptoms. Treating symptoms and secondary conditions can make a vast improvement in the patient's condition even when the primary cause cannot be addressed.

We have HIV/AIDS as a model here. Patients were first identified because they were suffering from reactivations of common infections in the herpesvirus family, among other known infections. Sound familiar? It was determined that none of those infections was the cause of AIDS in part because all patients did not have the same infections. Sound familiar? Nevertheless, those infections were causing the vast majority of the symptoms in AIDS. Patients were not dying from the immediate effect of the HIV virus, they were dying from the secondary infections that their bodies could not control because HIV was destroying their immune systems' ability to fight those infections.

What did they do in the early days of AIDS treatment before HIV was identified? They treated the secondary infections which were causing most of the symptoms. This was long before they knew why these peoples' immune systems were misbehaving. It was long before they had any clue what the unknown infection was. While they couldn't stop the damage to the immune system, not knowing the cause, they could vastly improve quality of life and reduce damage to the body done by the secondary infections.

We don't have to know the primary cause of the illness to know that patients have many secondary infections and that those infections need to be treated to prevent further damage to the body and to reduce symptoms. But if we refuse to test for and treat those secondary infections simply because they are not the primary cause of the illness, we are fools. Infections are infections. The damage is done whether or not the infection is primary or secondary.

There is no concrete evidence that ME/CFS is not infectious in origin. It appears not to be caused by a single currently known pathogen, but there's even some question about that. We don't know everything about the interaction of infections with genetic and environmental factors. In fact, there's much we don't know about the infections we are already aware of. And of course, there's still the possibility of infections that have not yet been identified.

ME/CFS could be the result of hit-and-run damage by multiple pathogens. That might be the root of an autoimmune situation. It could be the result of an ongoing infection that we are currently unable to detect, as in the HIV situation not that long ago. It could be caused by something else entirely. We simply don't know at this time.

Immune testing is I believe helpful in showing that there is something not working as it should but it's a silly jump in my opinion to automatically assuming that something is a pathogen that has evaded detection for so long.

I'm certainly not jumping to the conclusion that the primary cause of ME/CFS is an infection. I'm just not jumping to the silly conclusion that it's definitely not. Nor am I jumping to the silly conclusion that medical science has already detected every pathogen that exists. Now that IS silly.

The cause is unknown. It could be any number of things. There are quite a few possibilities currently being researched. What's silly at this point is jumping to conclusions about what is or is not the cause at this point in the research.

I believe unfortunately that people "want" there to be a virus at the heart of the conditions purely because it is a simple explanation but that's not to say it's the right one.

I doubt anyone "wants" a virus to be at the heart of the condition simply because that's a simple explanation. First of all, it is far from a simple explanation. If it IS an infection (which is far from certain) it's probably a difficult and complex infection probably in a difficult to find location like the nervous system or the gut. (Ian Lipkin is no fool)

What most of us "want" is not a simple explanation, but broad and open-minded research which includes investigation into the possibility of a pathogen at the root. What we do NOT want is the dismissal of a likely avenue of research because of ridiculous assumptions and poor interpretation of current knowledge.

I also think our current understanding of the inner workings and interconnections of the immune system make it very difficult to treat immune dysfunction – I'd go as far as to say that "immune-modulators" are very unlikely to get at the heart of the condition purely because we don't yet know what in particular needs targeting, with something as complex as the immune system a shotgun approach isn't going to get you very far and could indeed make things worse.

And there you've given a good explanation for why extensive immune testing is valuable for PWME. A shotgun approach to treating immune dysfunction is certainly problematic. Much better to have some knowledge — through individual testing — of what's malfunctioning in your own individual immune system and treating accordingly when possible.

For example, my daughter and I do not have identical immune dysfunctions, therefore we don't use the same immune treatments. How would we know what to do if we didn't have the test data to work from? Without testing, the choices are to do nothing or risk doing the wrong thing. Why should we not test when tests are available to guide treatment?

Treating these co-infections may help symptoms a little but it's not going to solve the bigger issues at the heart of the condition – just as treating co-infections in HIV/AIDS does not cure the condition overall.

Quite a few people who have treated these co-infections will argue that they help symptoms "a little". In my family alone, my uncle went from mild/moderate to full remission with antiviral treatment. My daughter was so sick she would have had to drop out of college during her first year when she got antiviral treatment. Now she's in remission and in graduate school in engineering. I went from bedbound and unable to read to up all day and tutoring 15-20 hours a week. While I'm not in remission, I don't consider going from bedbound with no life worth speaking of to being a functioning adult earning some income a "little" improvement. I can't do everything I want, but I don't feel like I constantly have the flu. I can read. I can put together lucid sentences. I'm not in constant pain. I don't call that a "little" improvement in symptoms. I call it getting some of my life back.

We are not the only people who have had more than "a little" improvement from treating co-infections. Dr Petersen would not be treating patients with antibiotics and antivirals if he was only seeing "a little" improvement from them. Nor would Dr Klimas, or Dr Montoya, or Dr Kogelnik, or Dr DeMeirleir. They are using them because they see significant improvements.

No one is suggesting, especially those doctors, that pathogen treatments cure ME/CFS. We don't have a cure yet. But to avoid (or worse, deny patients access to) treatments that can provide significant improvement simply because they are not a cure for the primary cause is beyond stupid.

Testing for pathogens and immune dysfunction is NOT unnecessary. It is critical for guiding appropriate treatment to give significant quality of life improvements in PWME.

well said SOC!
I totally agree with everything.

Everything in my immune tests screams "chronic intracellular infection".
And I mean EVERYTHING.

Targeted immune and gut treatment has made me go from the first 8 years of being sick (not fatigued but truly SICK as in hangover+marathon+severy flu) to remaining housebound but not sick anymore (except from a few episodes).

This doesn't sound like "huge improvement" but to me it is. My quality of life, although still having to live in my tiny little bubble, has improved a lot. I can sit up again, I don't feel the tears dripping anymore every time I open my eyes (tears of pure physical agony). I've got my pain under control and immune modulators etc. keep that sick awful feeling away.

I'm far from cured. Far from …
My CPET tests haven't improved. Neither have my neuro-cognitive tests.
But as I said, if I keep within my boundaries, I am a human being again instead of that heap of misery I used to be. How I survived those first 8 yrs is now a riddle to me. Honest.
Everytime I get a sick episode again, I wonder how I did it.

Without the help of my ME/CFS MD I wouldn't be this human being again.
Standard testing, CBT/GET, … didn't help me one bit. On the contrary.

Knowing about my consistent (not a one time off) immune-endocrine-gut- … abnormalities makes me understand more about what's going on. It doesn't tell me what the "cause" is, but it does tell me in which research subgroup I don't belong and in which I do belong.
I can keep up with research better that way and my ME/CFS MD knows what things I shouldn't do and which are worth trying.

I paid almost everything myself and I don't regret a penny of it.
The sad part is not everybody has the money to have this kind of elaborate testing done.

Esther12 February 8, 2014 at 10:26 am
charles shepherd

The simple answer is that while our National Health Service can be really excellent (and I've just been with someone this morning with a tumour who is having the most exceptional terminal care from everyone involved) the restrictions imposed by NICE and our other regulatory bodies mean that many doctors are becoming reluctant to use what is termed 'clinal judgement' when it comes to how you assess and manage patients and this is being replaced by a tick box approach to medicine that obeys all the rules but may not always be in the best interest of the patient.

It's not as if there's been a great history with CFS and 'clinical judgement' though.

edit – actually, this is moving things OT in an already complicated thread. Ignore!

Legendrew February 8, 2014 at 12:02 pm
SOC

I doubt you know more about it than my immunologist who says my immune dysfunction pattern is clearly indicative of an ongoing infection, even when we've (temporarily) cleared all the known, testable infections. She says it looks like I have an ongoing infection with something we can't yet detect. In my mind, her training and experience in patterns of immune dysfunction and what they might mean trump your belief.

Naturally, I have no interest in changing your belief. You're entitled to believe what you want. I'm a researcher by inclination and training and prefer scientific data to belief, so I'm going with established data for myself.

I think we are experiencing several layers of confusion here. The first is in interpreting the results of pathogen testing in ME/CFS. Research has not (yet) found a single pathogen in all ME/CFS patients. It is NOT true that NO pathogens have been found in ME/CFS patients. In fact, there are quite a few known pathogens found frequently in ME/CFS patients. It's just not the same single pathogen in everyone. So it's not that NO pathogens are found, it's that a unique universal pathogen has not been found. Big difference.

A second layer of confusion lies, I think, in confusing cause and effect. Most of us would agree that no single pathogen has been found to be the cause of ME/CFS. Nevertheless, having ME/CFS (whatever the cause) and the resulting immune dysfunction results in multiple pathogens in PWME.

Those pathogens need to be identified and treated. Just because they are not the primary cause of the illness doesn't mean they shouldn't be treated. In fact, they may be the cause of the majority of our symptoms.

Which is where a third layer of confusion comes in. The primary cause of the illness does not need to be the infection or condition that causes the majority of, or the most serious, symptoms. Treating symptoms and secondary conditions can make a vast improvement in the patient's condition even when the primary cause cannot be addressed.

We have HIV/AIDS as a model here. Patients were first identified because they were suffering from reactivations of common infections in the herpesvirus family, among other known infections. Sound familiar? It was determined that none of those infections was the cause of AIDS in part because all patients did not have the same infections. Sound familiar? Nevertheless, those infections were causing the vast majority of the symptoms in AIDS. Patients were not dying from the immediate effect of the HIV virus, they were dying from the secondary infections that their bodies could not control because HIV was destroying their immune systems' ability to fight those infections.

What did they do in the early days of AIDS treatment before HIV was identified? They treated the secondary infections which were causing most of the symptoms. This was long before they knew why these peoples' immune systems were misbehaving. It was long before they had any clue what the unknown infection was. While they couldn't stop the damage to the immune system, not knowing the cause, they could vastly improve quality of life and reduce damage to the body done by the secondary infections.

We don't have to know the primary cause of the illness to know that patients have many secondary infections and that those infections need to be treated to prevent further damage to the body and to reduce symptoms. But if we refuse to test for and treat those secondary infections simply because they are not the primary cause of the illness, we are fools. Infections are infections. The damage is done whether or not the infection is primary or secondary.

Sorry, I believe we've got a lot of confusion going on here which appears to be leaning towards a degree of confrontation so i'll do my best to explain my position and opinions and why I hold them. Firstly I realise there are a lot of findings of viruses in ME patients and I do not dispute this as it is clearly an important finding, but as you point out we are missing that crucial, consistent pathogen that would confirm ME/CFS as of purely infectious origins. There have been many quite rigorous studies in search of this yet they always seem to draw a blank, what I'm proposing is that perhaps we're trying to square the circle in this endeavor. It's very hard to judge at which point to move onto another hypothesis without the advantage of hindsight but I think personally we've moved beyond that point already. For me the big Lipkin study is something of a last throw of the die for hunting out such a pathogen, although I fear still that if that study still fails to find such a pathogen people will simply put it down to a super reclusive ninja of a pathogen. I think the XMRV affair does clearly show what a popular hypotheis the pathogen is for ME/CFS but we should not believe it just because lots of other people do.

As I've been going through the literature it's interesting to read these studies wherein they conclude they found no causative agent yet they always remark upon the significant degree of immune dysregulation they've observed. This is often interpreted as being proof that they've not been rigorous enough in their pathogen hunt, I personally believe that this immune dysregulation is in fact much more indicative – in the absence of that magic pathogen – of an autoimmune process. If we take a step back and look at the evidence we see a disease affecting a higher proportion of women than men, onset is often very sudden (being triggered by a plethora of viruses, stress and even vaccinations) and the disease has a waxing and waning outlook but with very low recovery numbers. To me I think the immunological findings are the most important part of any of these studies as they give many more avenues for further exploration than the finding of many seemingly unconnected viruses which as I mentioned are often similar to those found in the healthy population, a point which cannot be understated.

I think we should steer clear of the HIV model simply because it's easy to draw comparisons that seem logical but mean very little. My example would be if I were to compare a snail and a tortoise; both have outer shells, move slowly and enjoy green leaves so it makes sense that they're closely related, you could likely tell a young child this and they'd believe you given the evidence you have but this is clearly not true. There are similarities between ME/CFS and HIV/AIDS as you point out with co-infectious being problems for both but what we are doing by drawing these comparisons is not in fact telling us anything whatsoever but simply serves to further complicate matters. I read a recent paper comparing ME/CFS and MS, while it made lots of good points it did the same as you've done by putting two diseases next to one another and pointing out the similarities and likely convinced a lot of people ME/CFS and MS were closely related but didn't gain any credence from academics because it is not truly telling us anything we do not know about ME/CFS. We are much better studying diseases in isolation, we can look over our shoulders to another condition for pointers but putting them side by side when we know little about one means it's all too easy to believe they are closely related when in all actuality they couldn't be much more separate as with the snail and tortoise.

I understand your argument of the possibility of multiple hit and run viruses building up over time to create such an illness, I do however fail to believe this sufficiently explains the sudden onset in healthy people although it is of note that this could well represent a proportion of people diagnosed with ME/CFS. It is definitely however, as you state, worth testing for these and treating them wherever you find sufficient evidence of ongoing infections since the depressed immune system likely struggles with certain viruses which may come on following the onset of ME.

There is no concrete evidence that ME/CFS is not infectious in origin. It appears not to be caused by a single currently known pathogen, but there's even some question about that. We don't know everything about the interaction of infections with genetic and environmental factors. In fact, there's much we don't know about the infections we are already aware of. And of course, there's still the possibility of infections that have not yet been identified.

I just wanted to say that I'm a firm believer in the idea that we should not believe anything until it is proven, for that reason I strongly disagree with your point that there is no evidence to the contrary as being a good enough reason to believe a pathogen may be at the heart of the disease. Infections and the agents which cause them are very complicated things as you say, i'd go as far as to say very interesting – just a shame they target us!

I'm certainly not jumping to the conclusion that the primary cause of ME/CFS is an infection. I'm just not jumping to the silly conclusion that it's definitely not. Nor am I jumping to the silly conclusion that medical science has already detected every pathogen that exists. Now that IS silly.

I think this underlines why it is so important that we have such rigorous studies trying to find any pathogens in patients, we do hoever have had quite a few of these done now and as i've mentioned previously they seem to draw a blank. My main point is that perhaps more time should be done investigating the immune dysfunction found in patients than hunting for pathogens – wherever this leads I think it is a better avenue going forwards than continuing as we are. Both can co-exist as avenues, I just believe we should take a step back and explore a few new hypotheses.

The cause is unknown. It could be any number of things. There are quite a few possibilities currently being researched. What's silly at this point is jumping to conclusions about what is or is not the cause at this point in the research.

I doubt anyone "wants" a virus to be at the heart of the condition simply because that's a simple explanation. First of all, it is far from a simple explanation. If it IS an infection (which is far from certain) it's probably a difficult and complex infection probably in a difficult to find location like the nervous system or the gut. (Ian Lipkin is no fool)

What most of us "want" is not a simple explanation, but broad and open-minded research which includes investigation into the possibility of a pathogen at the root. What we do NOT want is the dismissal of a likely avenue of research because of ridiculous assumptions and poor interpretation of current knowledge.

I think you've hit the nail on the head there with not tying thing down to what is or isn't the cause. It is for this reason it frustrates me so much to see people in general talking of nothing but pathogens as a potential cause of ME/CFS. This has been the leading hypothesis for too long in my opinion and i'd love to see a wider spectrum of research taking place aside from pathogens, which I think deserves to continue being researched, just not exclusively!

Reading back my comment about people wanting it to be a virus I believe I've worded my meaning wrongly. What i mean to say is that people understand why a virus could explain their symptoms. Everyone is familiar with viruses to some degree whether it be through having flu or learning about it in biology class. That experience makes the virus a well known cause of disease which is why when discussed as a cause of a chronic condition, many people will believe it because "they've never felt as bad since they had the flu". I'm not sure my wording here is much better but my point I attempted to make is that while people don't want to be ill or have a disease it's easy to understand that a virus can cause you to be very ill and in a chronic condition people are often looking to find out why. If doctors cannot provide the answers then people often look to other diseases they've experienced and the internet – both of can lead to people believing a virus is the cause given that most people will have experienced a virus and the leading hypothesis is without a doubt a virus.

For example, my daughter and I do not have identical immune dysfunctions, therefore we don't use the same immune treatments. How would we know what to do if we didn't have the test data to work from? Without testing, the choices are to do nothing or risk doing the wrong thing. Why should we not test when tests are available to guide treatment?

Quite a few people who have treated these co-infections will argue that they help symptoms only "a little". In my family alone, my uncle went from mild/moderate to full remission with antiviral treatment. My daughter was so sick she would have had to drop out of college during her first year when she got antiviral treatment. Now she's in remission and in graduate school in engineering. I went from bedbound and unable to read to up all day and tutoring 15-20 hours a week. While I'm not in remission, I don't consider going from bedbound with no life worth speaking of to being a functioning adult earning some income a "little" improvement. I can't do everything I want, but I don't feel like I constantly have the flu. I can read. I can put together lucid sentences. I'm not in constant pain. I don't call that a "little" improvement in symptoms. I call it getting some of my life back.

We are not the only people who have had more than "a little" improvement from treating co-infections. Dr Petersen would not be treating patients with antibiotics and antivirals if he was only seeing "a little" improvement from them. Nor would Dr Klimas, or Dr Montoya, or Dr Kogelnik, or Dr DeMeirleir. They are using them because they see significant improvements.

No one is suggesting, especially those doctors, that pathogen treatments cure ME/CFS. We don't have a cure yet. But to avoid (or worse, deny patients access to) treatments that can provide significant improvement simply because they are not a cure for the primary cause is beyond stupid.

Testing for pathogens and immune dysfunction is NOT unnecessary. It is critical for guiding appropriate treatment to give significant quality of life improvements in PWME.

It's interesting to hear just how many of your family have been effected by ME/CFS, it's clear why you have strong opinions regarding the condition! It does make me wonder about the genetic component of the disease. From my own view this could imply your family has a predisposition towards the immune dysfunction involved in ME. I think this pattern is seen a lot in diseases of autoimmune origin, although I have heard of families also having greater susceptibility to certain viruses – things are never easy to interpret unfortunately. I hope I've managed to sort out a few points there anyway. I think we can both agree to disagree on certain points but the thing I believe we can agree on I think is the importance of rigorous immunological testing aside from pathogen testing in further clinical trials to try to gleam a better understanding of why things have gone so awry.

tatt February 10, 2014 at 5:54 am

@charles shepherd

I wonder if Dr Shepherd has any advice for a UK patient who has found it extremely difficult to get these tests before diagnosis (and yes I have seen a so-called ME specialist, I managed to get a few more then) and when results are slightly abnormal does not have any further investigation because "that wouldn't explain your symptoms" or "that's to be expected at your age". Obviously by the nature of ME you aren't normally feeling well enough to argue the toss.

I'd also like to ask your view on the reliability of these tests since eg liver function tests are, I understand, only about 60% reliable. Shouldn't ME patients all be getting a fibroscan given the similarity of ME symptoms and those of liver disease?

Would you care to say more about low calcium levels? I had lowish calcium and vitamin D but as usual my doctors dont consider it necessary to investigate further. If you once get a diagnosis of ME in the UK it's a recipe for poor medical care thereafter.

tatt February 10, 2014 at 5:56 am

@charles shepherd

sorry – forgot can you comment specifically on the effect of low vitamin D on liver function tests? Many people with ME are vitamin D deficient.

Esther12 February 10, 2014 at 8:50 am

PS: Thanks to PR and Shepherd for the article.

I do often worry that some of the blood tests people mention on here seem potentially dodgy, and it would be good if there was a bit more easy to access information on which tests had good evidence of their value, which were experimental (with it being important that patients be made aware of this) but potentially of some value, and which had evidence indicating that they were not of value.

I guess that there are always new things emerging, both of possible value and stuff that's almost certainly quackery, so it would be hard to keep anything up to date.

Marilyn60 February 14, 2014 at 10:06 am
charles shepherd

Before anyone else misinterprets or misunderstands what this MEA information on blood testing is for:

It was produced as a very basic MEA magazine item to cover ALL the routine blood tests that EVERYONE should normally have here in the UK before a diagnosis of ME/CFS is considered or made.

It is NOT designed to be a comprehensive list of all the blood tests that may need to be arranged – eg Lyme disease testing; neuroendocrine testing for Addison’s disease, pituitary disorders; further investigation of liver function if minor abnormalities are found; serum hydroxyvitamin D in those at risk of vitamin D deficiency; comprehensive autoimmune disease screen. This list is long and will depend on the history given by the patient and the examination findings obtained during a proper clinical assessment. There just wasn’t the space to include all of these tests, along with when they could/should be used, in ME Essential.

However, all of these additional tests are all covered in considerable detail in the sections (7 pages of A4) covering differential diagnosis, clinical assessment and investigations in the MEA purple booklet:

http://www.meassociation.org.uk/2013/06/available-now-–-latest-edition-of-the-me-association-clinical-practice-booklet/

Regarding the use of thyroxine: this has to prescribed with great caution in people who have/may have adrenal insufficiency/hypocortisolaemia (as may be the case in ME/CFS) and should NOT be prescribed in such circumstances in people who have normal thyroid function tests.

Regarding tests for Lyme disease: almost a whole page of the MEA purple booklet is given over to Lyme disease, including NHS and private laboratory testing. Some of the commercial tests are not reliable and I would suggest that people have a look at a recent BBC documentary when it appears on BBC iplayer:

http://www.bbc.co.uk/programmes/b03sqyp2

……where a perfectly healthy BBC reporter I know was tested ? positive using a private sector laboratory.

Dr Shepherd the program you refer to was not very well researched and yes it is quite possible as you must know, for a person to test positive for Lyme Disease and be without symptoms, as it is with other illnesses that can remain in our bodies without causing symptoms.

In order to conduct proper trials of test performance it would need many more samples to be looked at under proper laboratory conditions which maybe the direction Public Health England decide to go as they have been in talks with IgeneX.

Currently as the program did highlight there is no test available that can show a current active Borrelia (Lyme Disease) infection. The tests that NHS currently use miss many cases they are antibody tests and there are many reasons why we can or do not produce the antibodies that are being tested for. Most doctors should realise that as in other health areas antibody testing is often problematic. Porton Down who are currently the testing centre in UK say that we need better testing and are looking at other options.

Public Health England and Dept of Health were involved with the James Lind Alliance Research which found many uncertainties in diagnosis and treatment of Lyme Disease now documented on NHS DUETS database http://www.library.nhs.uk/duets/SearchResults.aspx?catID=15587&tabID=296 this will eventually result in current guidance on PHE website being updated, which could be a two year process according to PHE. Meanwhile the best available information for patients and clinicians and the results of James Lind Alliance research can be found on http://www.lymediseaseaction.org.uk/

My ME/CFS turned out to be Lyme Disease it was a chance course of antibiotics that improved my health significantly and led my GP to suspect Lyme Disease my history and clinical picture supported that and my response to antibiotics meant that over a long period taking oral antibiotics I recovered my health.

roxie60 February 19, 2014 at 1:16 am
charles shepherd

The simple answer is that while our National Health Service can be really excellent (and I've just been with someone this morning with a tumour who is having the most exceptional terminal care from everyone involved) the restrictions imposed by NICE and our other regulatory bodies mean that many doctors are becoming reluctant to use what is termed 'clinal judgement' when it comes to how you assess and manage patients and this is being replaced by a tick box approach to medicine that obeys all the rules but may not always be in the best interest of the patient.

That is why we go to doctors, we expect not only are they going to evaluate history, tests but will offer 'clinical judgement'. If doctors are forced to follow insurance company and government restrictive guidelines to arrive at cookie cutter diagnoses then why do we need doctors anymore. Maybe that is the goal. In the USA clinical judgement by doctors for those with chronic illness has gone the way of the dodo bird, nearly extinct and any doctor trying to be a doctor gets beat up by the corporations (medical and insurance corporations).

If they are are measured by disappointment and aggravation then the USA medical paradigm will pass with flying colors. If they are measured by successful recovery of their patients the US medical field gets a big fat 'F'. I know the operating environments in other countries are just as difficult but when did it become ok for doctors to be told how to test/treat their patients, when did it become ok to not figure out what is wrong and pass a patient around til they give up and die.

It is criminal what is happening to hundreds of thousands of people suffering, trying to get answers and being misdiagnosed, mislead, drained of financial resources and even in some cases out right abused. If we could measure the loses of the individuals (financial, relationships, health, quality of life, careers) it would reach to the heavens not to mention the loss of productivity to society because we can not function.

I wish I had the answers but it is an indictment of those in power (governments, medical organizations and insurance companies) who care not about getting to the truth of what is making people sick, rather toss them to the gutter if they cost too much to treat. After 10 years of trying to find answers to my own multisystem illness (now it looks likely it is Lyme but still not good test) I feel I am living in the dark ages not the 21st century.

Even now I am overwhelmed because it has become my responsibility to try and educate myself and figure out what tests I should have done to try and have empirical evidence of Lyme infection so I can keep disability (that is another back hole of tasks). We have to expend energy just trying to generally move forward, trying not to lose hope for an answer and cure.

charles shepherd February 20, 2014 at 12:42 pm
tatt

@charles shepherd

I wonder if Dr Shepherd has any advice for a UK patient who has found it extremely difficult to get these tests before diagnosis (and yes I have seen a so-called ME specialist, I managed to get a few more then) and when results are slightly abnormal does not have any further investigation because "that wouldn't explain your symptoms" or "that's to be expected at your age". Obviously by the nature of ME you aren't normally feeling well enough to argue the toss.

I'd also like to ask your view on the reliability of these tests since eg liver function tests are, I understand, only about 60% reliable. Shouldn't ME patients all be getting a fibroscan given the similarity of ME symptoms and those of liver disease?

Would you care to say more about low calcium levels? I had lowish calcium and vitamin D but as usual my doctors dont consider it necessary to investigate further. If you once get a diagnosis of ME in the UK it's a recipe for poor medical care thereafter.

To answer your questions:

1: there should not be any difficulty in getting ALL the routine blood tests mentioned in the MEA leaflet done in primary care/by a GP. This is an essential part of the clinical assessment and diagnosis of someone who may have ME/CFS.

2: minor abnormalities can occur in blood tests and are often nothing to worry about. A patient can often be reassured if the abnormality is no longer present if the test is repeated – a very simple thing to do.

3: if a minor abnormality is present, or persists, this should also be viewed as a warning sign to say that another explanation may be possible. This may need to be followed up by taking a more detailed clinical history and/or arranging further tests,

4: liver function tests should be both sensitive and accurate. Again, if minor abnormalities are present, this could be a clue that an underlying liver disease – e.g. hepatitis C, primary biliary cirrhosis, 'fatty liver' – is causing an ME/CFS like illness. The same logic applies to abnormalities in calcium levels.

5: there is no reason why ALL people with a possible diagnosis of ME/CFS should have a liver scan.

6: some people with ME/CFS have vitamin D deficiency and there is a good case for people at increased risk (especially those who are housebound and do not have exposure to sunlight) to take vitamin D supplementation under medical supervision. We have an MEA information sheet covering vitamin D deficiency in relation to ME/CFS.

charles shepherd February 20, 2014 at 12:48 pm
Marilyn60
charles shepherd

Before anyone else misinterprets or misunderstands what this MEA information on blood testing is for:

It was produced as a very basic MEA magazine item to cover ALL the routine blood tests that EVERYONE should normally have here in the UK before a diagnosis of ME/CFS is considered or made.

It is NOT designed to be a comprehensive list of all the blood tests that may need to be arranged – eg Lyme disease testing; neuroendocrine testing for Addison’s disease, pituitary disorders; further investigation of liver function if minor abnormalities are found; serum hydroxyvitamin D in those at risk of vitamin D deficiency; comprehensive autoimmune disease screen. This list is long and will depend on the history given by the patient and the examination findings obtained during a proper clinical assessment. There just wasn’t the space to include all of these tests, along with when they could/should be used, in ME Essential.

However, all of these additional tests are all covered in considerable detail in the sections (7 pages of A4) covering differential diagnosis, clinical assessment and investigations in the MEA purple booklet:

http://www.meassociation.org.uk/2013/06/available-now-–-latest-edition-of-the-me-association-clinical-practice-booklet/

Regarding the use of thyroxine: this has to prescribed with great caution in people who have/may have adrenal insufficiency/hypocortisolaemia (as may be the case in ME/CFS) and should NOT be prescribed in such circumstances in people who have normal thyroid function tests.

Regarding tests for Lyme disease: almost a whole page of the MEA purple booklet is given over to Lyme disease, including NHS and private laboratory testing. Some of the commercial tests are not reliable and I would suggest that people have a look at a recent BBC documentary when it appears on BBC iplayer:

http://www.bbc.co.uk/programmes/b03sqyp2

……where a perfectly healthy BBC reporter I know was tested ? positive using a private sector laboratory.

Dr Shepherd the program you refer to was not very well researched and yes it is quite possible as you must know, for a person to test positive for Lyme Disease and be without symptoms, as it is with other illnesses that can remain in our bodies without causing symptoms.

In order to conduct proper trials of test performance it would need many more samples to be looked at under proper laboratory conditions which maybe the direction Public Health England decide to go as they have been in talks with IgeneX.

Currently as the program did highlight there is no test available that can show a current active Borrelia (Lyme Disease) infection. The tests that NHS currently use miss many cases they are antibody tests and there are many reasons why we can or do not produce the antibodies that are being tested for. Most doctors should realise that as in other health areas antibody testing is often problematic. Porton Down who are currently the testing centre in UK say that we need better testing and are looking at other options.

Public Health England and Dept of Health were involved with the James Lind Alliance Research which found many uncertainties in diagnosis and treatment of Lyme Disease now documented on NHS DUETS database http://www.library.nhs.uk/duets/SearchResults.aspx?catID=15587&tabID=296 this will eventually result in current guidance on PHE website being updated, which could be a two year process according to PHE. Meanwhile the best available information for patients and clinicians and the results of James Lind Alliance research can be found on http://www.lymediseaseaction.org.uk/

My ME/CFS turned out to be Lyme Disease it was a chance course of antibiotics that improved my health significantly and led my GP to suspect Lyme Disease my history and clinical picture supported that and my response to antibiotics meant that over a long period taking oral antibiotics I recovered my health.

Information on Lyme disease testing from MEA purple booklet:

Lyme disease
Doctors have recently been warned by the Medical Defence Union about the growing incidence of Lyme disease – an infection caused by Borrelia burgdorferi that is transmitted to humans by tick bites, although some people do not recall a bite taking place.

Infected ticks are more common in woodland, heathland and moorland in areas such as Exmoor, Lake District, New Forest, Yorkshire moors and Scottish Highlands.

The earliest symptom can be a slowly expanding localised erythematous rash (erythema migrans), which spreads out from the bite, usually after about 5-15 days. Other early symptoms can include lymphadenopathy and a flu-like illness. Laboratory evidence should always be sought if the diagnosis seems possible. Diagnosed early, treatment with antibiotics is often successful. Left untreated, Lyme disease can cause serious heart, joint and neuro-logical complications.

Analysis of cerebrospinal fluid from cases of early disseminated Lyme disease and ME/CFS has identified a range of proteins that appear to separate the two conditions (Angel et al 2012).

Misdiagnosis of Lyme disease: There are also well documented concerns about over-diagnosis and inappropriate management of Lyme disease. A retrospective case note study of 115 adults with suspected Lyme disease who were referred to a UK infectious diseases clinic found that only a minority had Lyme disease; one third had ME/CFS; and no specific diagnosis was made in a further third (Cottle et al 2012). At least 53 unnecessary courses of antibiotics had been prescribed.

Lyme disease diagnostic services
The Autumn 2009 issue of the Chief Medical Officer’s Update contained a warning about the accuracy of some of the private (i.e. non-NHS) tests for Lyme Disease and consequent dangers of misdiagnosis. The full statement can be found on the MEA website: http://www.meassociation.org.uk/ ?p=697

As of 1st June 2012, the Health Protection Agency’s Lyme diagnostic service is provided by the Rare and Imported Pathogens Laboratory (RIPL), HPA Porton Down.

Lyme disease is usually diagnosed by serology. RIPL uses a two-tier testing methodology. The screening test is a C6 antigen-based ELISA (combined IgG and IgM), followed by a confirmatory Western blot (separate IgG and IgM). PCR is also available and may be useful in testing joint fluid and biopsies of rashes. It has poor sensitivity on CSF and antibody detection is the preferred first line test on CSF. PCR is not usually performed on blood as the duration of bacteraemia is short.

RIPL also has capacity to perform further testing and tests for diseases related to Lyme. Contact RIPL to discuss if required.

RIPL clinical staff are available to discuss cases with medical professionals during working hours on 01980 612348 or by email referral to Lyme.RIPL@hpa.org.uk. There is no clinic at HPA Porton and they are unable to see patients or to give telephone advice directly to members of the public.

RIPL website:
http://www.hpa.org.uk/Topics/InfectiousDiseases/ InfectionsAZ/LymeDisease/
This gives details of where patients can be tested for Lyme disease on the NHS.

The ME Association has a patient information on Lyme Disease written by consultant microbiologist Dr Darrel Ho-Yen

tatt February 22, 2014 at 2:04 pm
charles shepherd

To answer your questions:

1: there should not be any difficulty in getting ALL the routine blood tests mentioned in the MEA leaflet done in primary care/by a GP. This is an essential part of the clinical assessment and diagnosis of someone who may have ME/CFS.

2: minor abnormalities can occur in blood tests and are often nothing to worry about. A patient can often be reassured if the abnormality is no longer present if the test is repeated – a very simple thing to do.

3: if a minor abnormality is present, or persists, this should also be viewed as a warning sign to say that another explanation may be possible. This may need to be followed up by taking a more detailed clinical history and/or arranging further tests,

4: liver function tests should be both sensitive and accurate. Again, if minor abnormalities are present, this could be a clue that an underlying liver disease – e.g. hepatitis C, primary biliary cirrhosis, 'fatty liver' – is causing an ME/CFS like illness. The same logic applies to abnormalities in calcium levels.

5: there is no reason why ALL people with a possible diagnosis of ME/CFS should have a liver scan.

6: some people with ME/CFS have vitamin D deficiency and there is a good case for people at increased risk (especially those who are housebound and do not have exposure to sunlight) to take vitamin D supplementation under medical supervision. We have an MEA information sheet covering vitamin D deficiency in relation to ME/CFS.

1. Shouldn't be a problem but was – short of making a formal complaint and/or changing gp any suggestions? Another gp in the practice misdiagnosed an allergic reaction as a viral rash (despite me saying it was an allergic reaction, confirmed eventually by a dermatologist) so a different gp in the practice not likely to be any better.

2. No repeat testing offered.

3. my blood tests were fine, fibroscan suggest a problem. I think I'll disagree with you on the need for fibroscan. Btw I drink about 3 units of alcohol a week on average.

Guidance is only any use if gps follow it

barbc56 February 22, 2014 at 8:48 pm

Dr. Shepard, I have been following this thread but for a myriad of reasons, I haven't been able to post much on PR as of late. I want to thank you for writing this article. I have found it to be very helpful.

I do have a question. Did you include a test for ferritin? As I understand it, my cbc count is fine and low ferritin has many of the same symptoms as anemia.. I might have missed this in the article, as I only have access to my crummy tablet atm and can't always zoom.

The reason I ask this is because I have had very low ferritin levels in the past. My sleep doctor sent me to a hematologist and I had an all day infusion of iron. He always gets a level for ferritin, especially for his patients with RLS as the level needs to be higher. While this procedure helped with my RLS, it only brought a small improvement in my ME/CFS/FM symptoms but at least I have the assurance that my ferritin level is now normal.

Would this test be considered only if you have symptoms of anemia but a normal cbc? I would think this would also apply for a sleep study?

My personal choice is to get the tests that have scientific backup and it's sometimes difficult to sort out these tests. While these tests may prove to eventually be valid, we simply don't know with our current state of medical knowledge. I want tests that are medically valid. If they aren't, IMPO, it only muddies the waters and makes it more difficult in the long run to sort out what is medically warranted to improve our health. I also want tests that are of good quality (unlike the PACE trial) and based on prior plausibility.

I kind of veered off topic towards the last but I am strongly committed to the above principle.

Again, thank you.
Barb.

Leopardtail March 26, 2014 at 6:05 pm
Legendrew
SOC

I might agree with you if it weren't for statements like this:

[my bolding and underlining]

Clearly he's not just talking about diagnosis, but claiming further tests are not useful in the management of ME/CFS.

Well, as odd as it sounds, tests themselves are of little use in the management of a disease if you're not completely sure of what you're looking for. There are examples to the contrary of this such as measuring antibodies and TSH (among the other thyroid hormones) which do help in the management through allowing for the right dosage of treatment, however many of the tests used by some physicians for ME/CFS patients do nothing to aid disease management other than informing of the ongoing problem which, while very helpful to researchers in understanding the disease mechanisms at play, are very hard to transfer into use disease management.

I realise many will be quick to point out testing for viruses and antivirals that lie therein but I don't prescribe to the notion that ME/CFS is of infectious origins, perhaps triggered but certainly in my opinion not perpetuated. My analogy that I feel I refer too far too often is that of a wildfire in a forest; a virus or other infectious agent serves as a spark which sets ablaze the forest but after this event there is little point in trying to track down the spark given that it is more than likely an impossible task as the spark has long since been absent, besides which the blaze is of much greater concern!

I fear I may have lost my point somewhat but my takeaway message I suppose it that we simply know too little at this point for the any testing to be of great use in clinical practice given that we don't even know what to look for, that's not to say however that none should be done at all – that of course comes down to the decision of the patient and doctor in question.

vamah

I have to agree, although I think the list of tests could be longer. I think so often a person is labeled with cfs and then can't get tests or treatment because so many doctors treat it as a psychological illness. Also, since it probably has different triggers for different people, it is important to try and find that underlying trigger. That is the point where you start treating the illness instead of just symptoms.

I agree with your first point regarding the stigma a diagnosis of ME brings and the problems that arise therein with further testing when often it is warranted but I think all too often we get wrapped up in finding what triggers illness. This is an important question for researchers trying to understand disease mechanisms however for a patient and doctor the cause is of little help. If someone catches a virus or breaks a leg there is little point in trying to find out the circumstances under which such events happened, what's important is the steps you take in the present. I think with chronic diseases we all have a tendency, myself included, to mull over the "what ifs" when really we should be looking at the present a little more.

I do however think certain diseases and the testing necessary to rule them out was missed from this list.

L.

several points however remain. Firstly there are tests such as MTHFR polymorphisms that can produce stunning improvements in severe fatiguing illness. Test showing defects in B-Vitamin metabolism in general can show similar use. The problem is that medics dismiss what they do not understand and much of B vitamin metabolism is beyond their expertise. While I would not say that every test is money well spent for every person with CFS (including Thyroid tests) they should be given adequate consideration, not dismissed out of hand.

Further with respect to 'infective agents'. Infection when persisting can elevate Thyroid and Glucocorticoid hormones and make a patient feel truly awful. In combination with other treatment anti-viral, anti-biotic treatments can be vital especially when compromised immunity is present.

Dr Sheppard is far too 'all or nothing' and also belittle's many treatments that are highly effective for many of us.

tatt March 27, 2014 at 2:04 am

Well I agree with him to some extent – no point in tests that don't improve management of the condition. We need more research on the treatments that seem promising then tests to see who would benefit from them. However I disagree that the current range of tests is enough. Personally I'd like a cortisol test, a test for POTS and a B12 test included with thryoid antibody tests and mitocondrial antibody tests put through clinical trials. Everyone with ME should have vitamin D levels tested. If you can afford it get a fibroscan – and if it shows a problem treat yourself with NAC. Most liver problems they advise diet changes and exercise and anyone with ME who hasn't changed heir diet and excluded alcohol should try it for at least 6 weeks.

People with even slightly abnormal results should have further testing because the "reassurance" is rubbish. If you don't know what is causing ME how can you say even small abnormalities don't matter? I treat my "small abnormalities" and my health has improved.

MeSci March 27, 2014 at 3:51 am

Could people please ensure that they have read all Dr Shepherd's messages in this thread before criticising him, as it seems that he is still being misinterpreted. Message #28 on this page answers several recent criticisms.

Firestormm March 27, 2014 at 4:46 am
MeSci

Could people please ensure that they have read all Dr Shepherd's messages in this thread before criticising him, as it seems that he is still being misinterpreted. Message #28 on this page answers several recent criticisms.

Direct link: http://forums.phoenixrising.me/inde…-dr-charles-shepherd.28065/page-2#post-428009

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