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…
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.
- 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.
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.
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.
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.
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.
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.
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.