Pernicious Anaemia or ME - misdiagnosis concerns

Sly Saint

Sly Saint

Senior Member (Voting Rights)
Martyn Hooper Chair of Pernicious Anaemia Society on new NICE guidelines for ME:

"Last week I was at a NICE consultation which was looking at the problems with the diagnosis of Myalgic Encephalopathy (or encephalomyelitis). Because there are so many contentious issues concerning the disease NICE are going to take a good look at the subject and issue a new Guideline for doctors.

Similar Symptoms
The symptoms of the disease are incredibly similar to those of Pernicious Anaemia – extreme and constant tiredness, difficulty thinking straight, mood swings etc. etc. And I know that a great many members of the Pernicious Anaemia were suspected of having ME and diagnosed with the condition before finally being told that they had Pernicious Anaemia.
I suspect that a great many people who have been diagnosed as having ME/CFS actually have Pernicious Anaemia; and the reason I say this is because the current NICE Guideline states that no investigation for any B12 Deficiency should take place unless there was signs of macrocytosis from the full blood count taken. Now, we know that only around 50-60% of patients with low B12 will have enlarged red blood cells and so if a patient’s blood shows no macrocytosis no investigation takes place as to whether low B12 could be the cause of the patient’s symptoms."

https://www.martynhooper.com/2018/02/10/chronic-fatigue-syndrome/
 
Sly Saint said:
I suspect that a great many people who have been diagnosed as having ME/CFS actually have Pernicious Anaemia; and the reason I say this is because the current NICE Guideline states that no investigation for any B12 Deficiency should take place unless there was signs of macrocytosis from the full blood count taken.
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NICE's "do not do" guidelines need to take a long walk off a short pier, along with whoever contributed to or approved them :expressionless:
 
Considering they regard diagnosis of ME as one of exclusion, the NICE guidelines are pretty poor with regards to all the conditions that should be excluded before the diagnosis is made.
The 2004 guidelines for children and young adults (RCPTH) although still not complete, are much more thorough
see this post https://www.s4me.info/threads/esther-crawley-what-drives-her-plus-quotes.1139/page-2#post-29076
Another one that is deemed not necessary is homocysteine levels.

I can understand them being reluctant to do all possible tests for everyone in say the first year of illness but would have thought that they would be made available/tried when someone has been ill for several years.
 
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I had to fight exceedingly hard for a blood test for pernicious anaemia... GP didn't want 'to go on a fishing expedition' - despite the fact my grandfather had died from suspected complications from pernicious anaemia back in the fifties. Took quite a lot of arguing that it's not a fishing expedition if you have a second-degree relative with the condition. I still don't know if they actually did the right test or just looked for enlarged red blood cells as described above.
 
The MEA has commented on this here:

Pernicious Anaemia: symptoms, diagnosis, Vitamin B12, ME/CFS and the NICE guideline review | 16 February 2018

Summary of the key points:
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  • Although some people with M.E. report that vitamin B12 injections have been helpful, there is no robust scientific evidence to currently demonstrate that vitamin B12 deficiency occurs in M.E.
  • There are no results from clinical trials to indicate that vitamin B12 injections are a safe and effective form of treatment in M.E.
  • If people are going to take vitamin B12 it is very important to make sure that Pernicious Anaemia (PA) has first been excluded. PA is an autoimmune condition that results in decreased absorption of B12 from the gut – hence the need for injections.
  • Excluding PA is important because it can cause very serious neurological complications (i.e. sub-acute combined degeneration of the spinal cord
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The rest of the MEA article is here:

http://www.meassociation.org.uk/201...d-the-nice-guideline-review-16-february-2018/
 
Trish said:
The rest of the MEA article
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"If people are going to take vitamin B12 it is very important to make sure that Pernicious Anaemia (PA) has first been excluded".

This is what Martyn Hooper is saying...........but the NHS don't test for it routinely(as part of ME diagnosis) and if they do, the test they use is not reliable.

It goes on to say:
"Finally, it is worth noting that vitamin supplements are not recommended in the current NICE guideline for ME/CFS. Therefore, most doctors are going to be reluctant to prescribe injections to people with M.E. – unless there are sound reasons for doing so. What NICE currently regard as inappropriate prescribing of vitamin B12 can also lead to a GMC investigation and ban."

So what are the sound reasons? A positive test for pernicious anaemia perhaps? But then they don't test for it.
Repeat ad nauseum.
 
Sly Saint said:
"If people are going to take vitamin B12 it is very important to make sure that Pernicious Anaemia (PA) has first been excluded".

This is what Martyn Hooper is saying...........but the NHS don't test for it routinely(as part of ME diagnosis) and if they do, the test they use is not reliable.
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I think it is a bit more subtle than that. The MEA site indicates that people should not take oral B12 if it is not known whether PA is present - because then injections are needed. There is no evidence for B12 being useful in ME so the suggestion is that people should only be taking B12 of any form if they are actually deficient - in which case the reason for deficiency should be sorted out.

The Pernicious Anaemia Society point out that tests are not always easy to interpret. I am sure that is true but I worry there may be confusion about what the sensible approach is.

As far as I am aware the symptoms of PA relate either to anaemia (fatigue, breathlessness) or neuropathy/myelopathy (unsteadiness, numbness, tingling etc.). Anaemia sufficient to cause symptoms is easily picked up on a blood count and even if deficiency is borderline a blood count is likely to show large red cells (bigger than 100 femtolitres). The PA society point out that B12 levels may be low without large red cells but then I think the logical conclusion is most likely to be that the low B12 is not actually a problem. Presumably there is considerable variation in how much B12 is carried in blood in healthy people.

Neurological changes are potentially progressive and irreversible but peripheral neuropathy is usually pretty easy to diagnose if one has had a proper neurology training (I appreciate that many doctors have not). At a reversible stage physical examination should show clear cut signs.

So someone with tingling hands and feet or unsteadiness should have a proper examination but in someone with fatigue without a convincing neurological history I do not think testing for B12 is likely to be needed.

I personally think it is pretty unlikely that someone presenting with features of ME will turn out to have pernicious anaemia if the blood count is normal and there are no neurological signs of PA and so I think not doing a B12 level is reasonable. As the PA society point out B12 levels and other more complicated tests are not actually reliable enough to help much further. Antibodies to intrinsic factor or parietal cells are not diagnostic of PA. Quite a lot of normal people have autoantibodies of this sort.

If it were the case that PA caused fatigue or PEM even without anaemia then things might be different but I am not aware that this is the case.
 
Thyroid UK also cite the importance of checking for PA:
"Ask your doctor to check your B12, folate, ferritin and Vitamin D levels as deficiencies of any one of these could be a reason for your ill health. The symptoms for Pernicious Anaemia are very similar to those of hypothyroidism. The range for B12 is quite wide and some patients feel much better at the upper end of the range. The BBC produced a programme regarding this - “Inside Out 30 Oct 2006 - Vitamin B12 Deficiency” - which you may be able to watch online.

You can find more information on the website of the Pernicious Anaemia Society -
www.pernicious-anaemia-society.org/ "

As far as I am aware none of the potential deficiencies listed are routinely tested for before making a diagnosis of ME/CFS (?)

eta:
http://www.thyroiduk.org.uk/tuk/diagnosis/getting_diagnosis.html
 
Sly Saint said:
As far as I am aware none of the potential deficiencies listed are routinely tested for before making a diagnosis of ME/CFS (?)
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I was tested as part of the screening but when the IF test result came back negative the GP ignored the rest of the blood results which had low haemoglobin, low RBC count, lowish B12 (200's) and low folate. They were low, but not ultra low. There is debate about whether the cut off for B12 is right ...it's a lot higher in other places in the world.

I think it's as you describe, the GPs are not very proficient at interpreting and joining up,the dots or understanding the test results other than what the lab tell them (I also had borderline TSH). Certainly presentation of brain fog and peripheral neuropathy for someone who is on long term carbamazepine prescription should have rung a few bells for further routine testing.

Further follow up with the GP just led to him saying ...you can go back to the CFS clinic or buy the B12 yourself.

I chose to treat myself and feel better for it. there is no help from the NHS even if you have PA judging by the comments on the PA forums so it's a little unhelpful for the MEA to pretend otherwise.
 
Sly Saint said:
Ask your doctor to check your B12, folate, ferritin and Vitamin D levels as deficiencies of any one of these could be a reason for your ill health. The symptoms for Pernicious Anaemia are very similar to those of hypothyroidism.
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I think this is the sort of vague advice that NICE rightly tries to steer away from. In my experience the clinical presentation of hypothyroidism is not like ME or PA or vitamin D deficiency. I also suspect that the idea that some patients feel much better on the upper end of the range for B12 is not backed up by any blinded studies.

If NICE is bombarded with stuff that is not based on any hard evidence the psych lobby will have an easy time of winning the argument.
 
After being diagnosed ME in 2008 I was sick and had many crashes, many blood tests, investigations, scans etc. Not sure if B12 was ever checked. In 2015 I was very dizzy and sick and hospitalized 3 a.m. Next day blood tests revealed slight anemia but very low B12. More tests done to established PA and I was told I didn't have PA. I was put on B12 injections and they helped but I never had normal B12 in my blood until very recently. Well only in my last test in December it was normal without injections. So I stopped the injections. But I'm not any better in health wise in general.
 
Jonathan Edwards said:
The PA society point out that B12 levels may be low without large red cells but then I think the logical conclusion is most likely to be that the low B12 is not actually a problem.
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B12 deficiencies can have a lot of impact aside from altering the size of red blood cells and/or causing pernicious anemia, from what I understand. It looks like the effect of a deficiency on the nervous system happens via a separate mechanism, primarily due to the reduction of myelin formation resulting from accumulations of MMA.

The impression I'm getting is that large blood cells are primarily a symptom of the problem, rather than being the sole problem, or even the more important problem. And they result from reduced formation of blood cells, hence the amount of red blood cells may still be low even if there are not megaloblasts. Folate supplementation can be problematic precisely because it will fix the megaloblasts while the actual B12 deficiency remains, thus masking a B12 deficiency.

So it sounds like a deficiency is definitely a problem, even if red blood cells are not large. And at least one common cause of normal blood cell size in the presence of a B12 deficiency is known. Everything I've seen says that a B12 deficiency is a serious and even urgent problem, which can cause permanent damage to the nervous system, and some symptoms start when levels are only slightly below the normal range.

Maybe @alicec can explain it better, or correct any mistakes I've made :p
 
Valentijn said:
So it sounds like a deficiency is definitely a problem, even if red blood cells are not large. And at least one common cause of normal blood cell size in the presence of a B12 deficiency is known. Everything I've seen says that a B12 deficiency is a serious and even urgent problem, which can cause permanent damage to the nervous system, and some symptoms start when levels are only slightly below the normal range.
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That is what the support groups would have us believe. However, if missed cases leading to serious neurological problems occurred with any frequency I think I would have heard about it. Such cases would have provided ideal material for Thursday afternoon case reports in my department, where something like 3,000 people were followed up over periods of twenty years or more. Not a single case was mentioned. And if not on Thursdays other teams would have brought them to Grand Rounds on Wednesdays to provide a cautionary tale for everyone else (the main purpose of Wednesdays). But none were reported in the thirty years I worked there as far as I know. And the hospital probably served ~200,000 people directly and more as a tertiary centre.

When it comes to folate deficiency, which is common enough as a secondary problem in rheumatology, red cells get big even before the haemoglobin goes down noticeably. It seems that the system compensates with big cells pretty well.

My understanding is that pernicious anaemia is reasonably common in older people (~1%) but in the younger age groups that present with ME it is much less common (~0.1%). If all my colleagues and I were missing PA we would known about it because we went on looking after the patients for another ten years on average. I have missed scleroderma and hypothyroidism for a while but I think it unlikely that I missed a progressive neurological disorder.

I remain to be convinced. I am sure GPs are missing PA, but I suspect largely because they are not doing an FBC.
 
GPs don' t really interpret blood tests at all if everything is in " normal" range.
They also are not at all interested at how things change if everything is in normal range. We have had huge changes in phosphate, borderline ferritin, blood glucose rising, low vit D ( tested after hassling and then looked sheepish) and TSH that keeps heading in one direction but has not hit " above normal" . What is normal if you have HPA axis problems?
Standard B12 also tests how much you have swilling about- not how much is in the active form -there can be a huge difference. MMA would give a better indication. Sadly GPs ( or maybe just ours) don' t appreciate this.
 
Jonathan Edwards said:
That is what the support groups would have us believe.
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That information came from Wikipedia, not support groups. Their source for the statements about the dangers of masking a B12 deficiency are a fact sheet from the NIH:
The neurological symptoms of vitamin B12 deficiency can occur without anemia, so early diagnosis and intervention is important to avoid irreversible damage.
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Large amounts of folic acid can mask the damaging effects of vitamin B12 deficiency by correcting the megaloblastic anemia caused by vitamin B12 deficiency without correcting the neurological damage that also occurs. Moreover, preliminary evidence suggests that high serum folate levels might not only mask vitamin B12 deficiency, but could also exacerbate the anemia and worsen the cognitive symptoms associated with vitamin B12 deficiency. Permanent nerve damage can occur if vitamin B12 deficiency is not treated.
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The Department of Health in England has asked NICE to develop a clinical guideline on thyroid disease.
This is due to be published in 2019, so they are about a year ahead of the one for ME/CFS.
Might be interesting to follow it to see how the process for it compares.

This is the draft scope for consultation with registered stakeholders
https://www.nice.org.uk/guidance/gid-ng10074/documents/draft-scope

other docs here:
https://www.nice.org.uk/guidance/indevelopment/gid-ng10074/documents

sigh; at least they don't appear to have the psychs to contend with (yet).
 
I did have low B12 and taking it did help the low B12 symptoms, and gave me a bit more energy (maybe 5%)...
That said its worth testing for and even a trial of B12 won't hurt anyone (injections are not needed, oral takes longer to raise levels but it does so just fine, as long as its methylcobalamin). I suspect the percentage of cured for misdiagnosed ME/CFS will be a few percent at best.
 
Just thought I would post the following from guidance issued in the British Journal of Haematology:

https://www.ncbi.nlm.nih.gov/pubmed/24942828

I think its important to note that PA is one form of B12 deficiency and that the current blood tests offered are not particularly useful to identify deficiencies.

This is how NHS Salisbury gives guidance for B12 deficiency

http://www.icid.salisbury.nhs.uk/Cl...anagementofVitaminB12andFolateDeficiency.aspx

This section is relevent I think:

"2.2.1 Macrocytic anaemia
Macrocytosis in itself may or may not be present with anaemia but those patients who have macrocytosis with anaemia should have vitamin B12 and folate measurements performed.

2.2.2 Macrocytosis
The level of macrocytosis can predict the probability of vitamin B12 and folate deficiency being present. As the MCV increases above 100 fl, so the probability of vitamin B12 and folate deficiency increases. This is particularly true of patients with an MCV above 130 fl, except for those receiving hydroxycarbamide.

The probability of B12 or folate deficiency is less with MCVs between 100 and 110 fl, which is more likely to be related to other causes of macrocytosis, such as alcohol abuse, liver disease, anti-neoplastic drugs, human immunodeficiency virus infection, and also haematological disorders, such as myelodysplastic syndromes or haemolytic conditions.

Blood film comments may help to point to a diagnosis: hypersegmented neutrophils and macro-ovalocytes are associated with vitamin B12 and folate deficiency, a uniform macrocytosis with alcohol abuse, target cells with liver disease, and polychromasia with haemolysis.

2.2.3 Neuropsychiatric abnormalities (check vitamin B12 only unless co-existant macrocytosis or anaemia)
Several neuropsychiatric abnormalities have been described in association with vitamin B12 deficiency (including paraesthesia, ataxia, peripheral neuropathy, and memory loss). These may occur in the absence of either anaemia or macrocytosis. Objective signs associated with vitamin B12 deficiency include impaired vibration, touch, pain, and position sense, together with an abnormal gait.

Folate levels should not be requested in patients with neuropsychiatric abnormailities unless there is a;so macrocytosis or anaemia.

2.2.4 Severe oral ulceration
B12/folate deficiency can occasionally present with glossitis or severe oropharyngeal ulceration without changes in the blood count and respond to vitamin B12 or folate treatment.

2.2.5 Coexisting conditions
Coexisting conditions such as iron deficiency or thalassaemia trait may mask the development of macrocytosis and, therefore, in patients who have anaemia without a raised MCV, dual conditions should be considered as a possible diagnosis, and vitamin B12 and folate should be measured if the origin of the anaemia cannot be established by initial tests."
 
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