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Blood Tests: Why Test the Blood? Dr Charles Shepherd

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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…

Human 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.

If 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.

Screening 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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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, ... ?
 
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.
 
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.
 
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.
 
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.
 
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.
 
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.
 
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.
 
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?
 
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.
 
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.
 
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.

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.
 
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