Antibody negative PA

[Roses46]

Hi. I read the above referred to by an administrator on a previous post and just asking for further info please (post comments were turned off). I've had a test for intrinsic factor that came back negative (yet was told in 2006 that I'd be on injections for life as I can't absorb tablets). Is this the same thing?

[Nackapan]

I wad told the same.I think thrn assumed ad not dietary present IFA test failed as no antibodies present so not failed as such but no definitive test.

IFA neg. PA assumed snd injections fir life

I think it was foggyme who explained this term some time ago

[fbirder]

Here is the source - onlinelibrary.wiley.com/doi...

The finding of a low total serum cobalamin level may be further evaluated by

testing for anti-IFAB. If positive, the test has a high positive predictive value (95%) for the presence of pernicious anaemia (Toh et al, 1997), with a concurrent low false positive rate (1–2%) i.e. a high specificity. It identifies those patients with a need for lifelong cobalamin replacement therapy. IFAB is positive in 40–60% of cases (Ungar et al, 1967), i.e., low sensitivity, and the finding of a negative IFAB assay does not therefore rule out pernicious anaemia (hereafter referred to as AbNegPA)

If your deficiency isn't dietary then it's almost certainly an absorption problem. And the most common absorption problem is PA.

If you have an acknowledged B12 deficiency that is not dietary (you eat plenty of meat/fish) yet a negative IFAB test, then your doctor needs to explain -

a) What is the cause of the deficiency?

b) Why is it not AbNegPA , as described by the BCSH?

[Nackapan in reply to fbirder]

I know I get muddled with abbreviations. Odd as an ex NHS employee that uses tgrm all of the time. ABNegPA

So is that just antybodynegative Pernicious aneamia

Rather than intrinsic factor negative PA ?

I thought I'd seen

IFAnegPA ?

Must get the term right as I'm assuming thats what I have

Not having had an intrinsic antybody test done at the right time or at all

But a parietal cell antybody one before loading doses.

New takeover of surgery imminent .

I know you had this too

Nurses gone .

Gps remain at present

May I ask if amitriptyline good for nerve pain?

[fbirder in reply to Nackapan]

My neuropathy (not caused by B12d) seems to have two sorts of pain.

There is a continuous pain that makes it feel as if I'm walking on broken glass (even when my feet are up). This is helped to some extent by alpha lipoic acid (3 x 600 mg per day) and to a much better extent by amitriptyline (20 mg each evening).

Then there are random stabbing pains (the evil gnome with the red-hot needle) that happen most in my big toes, but can be anywhere in my feet. It's much worse in the evening/night. That is helped a lot by gabapentin (300 mg morning and lunch, 600 mg in the evening).

Nothing helps with the continuous tingling in hands and feet, nor with the numbness (so bad I cannot tell if I'm standing on a thick carpet, or bare floorboards - in bare feet).

[Nackapan in reply to fbirder]

Glad you are getting relief for much of the pain. Sounds horrid .

You do well with walking your hounds.

Hope they appreciate it!!

Amitriptyline seems to have many uses .

Also gabapentin seems to serve you well too T C

[Skimmingstone226 in reply to fbirder]

Since my more rapid physical decline from March I have been experiencing severe pain down my spine into my back pelvis area and down legs. As I won the lottery with the hospital consultant and am currently on EOD for four weeks,I thought this pain would go. However it is more of an issue now than previously and I am maxing out paracetamol and ibuprofen every day just to be able to function. Is this pain typical of late diagnosis and will my pain go once my B12 is replete sufficiently? Or should I be asking for better pain relief?

[fbirder in reply to Skimmingstone226]

That really doesn't sound like it's being caused by a B12 deficiency. Have you seen a neurologist? Have you been offered other medication for pain relief. Paracetamol and NSAIDs like ibuprofen can be totally ineffective against some nerve pain (like mine).

[mountainice in reply to fbirder]

What do you think your numbness and neuropathy is from? Mine is getting worse in feet and legs

[fbirder in reply to mountainice]

I had a really good neurologist who admitted he had no real idea what the cause was. So he referred me to an expert at the National Hospital for for Neurology and Neurosurgery.

That guy gave me a thorough examination, tested for almost everything in my blood, sent me upstairs for a nerve conduction examination and told me that it was Idiopathic Axonal Neuropathy. And that it was common in very tall men in their 60s. At the time I was 59 years old at 195 cm.

Nobody knows what causes it. But the prof predicted how it would progress (no improvement, no real degradation) over the next six months. And he was totally correct.

That was over 4 years ago and his prediction was spot-on. The pain is getting very slowly worse but I've still got a bit of leeway to go for increasing the doses of my meds (although taking more gabapentin does get me stoned, so I'm resisting).

The accompanying ataxia, which means I find it difficult to keep my balance when standing still, doesn't seem to be getting any worse. That was my big worry - that I would find it more and more difficult to walk.

Have you seen a neurologist?

[mountainice in reply to fbirder]

Hi, yes, it is worrying if our balance and walking go off. I have seen a neurologist more than once. First when I was diagnosed with B12D in 2008 and again this year saw a neurologist. I had nerve conduction tests the first and second time round. They said they look the same, but I know it is worse. Got a follow-up appointment in July. I had a frightening experience driving on the motorway recently. Lost position sense in my left foot when trying to use the clutch. Got really scared. Husband was with me. Managed to exit and eventually pull off after driving through a coned roadworks area. I was crying as was scared we would crash. I've got a call from gp today about it but I expect she will say wait for neuro appt . Don't have much faith in the neuro as in a phone call she told me my B12 is 'replaced' and I am wasting my money self-injecting.

[Foggyme Administrator in reply to Nackapan]

AbNegPA is the term used for antibody negative Pernicious Anaemia in the BSH diagnostic and treatment guidelines, so that term is used to remain consistent with those guidelines.

Here's a link to the BSH diagnostic flowchart that shows use of the term:

stichtingb12tekort.nl/engli...

IFANegPA is another way of expressing the same thing, but rather it refers to intrinsic factor antibody negative Pernicious Aneamia. 👍

[Roses46 in reply to Foggyme]

Sorry, I'm totally baffled. Doesn't help having a demanding 6yr old so may re-try reading later. Am I understanding correctly that even with negative intrinsic factor test I could have PA? When I asked the Dr couldn't explain why I was given the diagnosis of lifelong injections (is that Colbamin?) as it wasn't in my notes. I've had to rely on verbal recollection of my Dr saying I couldn't absorb tablets, which is awkward as he decided to leave the practice and go private

[Foggyme Administrator in reply to Roses46]

Roses46, I've left a more detailed explanation for you in a reply below that might help clarify (our posting crossed, I think).

In short, yes you’re right - it is possible to have a negative intrinsic factor test but still have pernicious anaemia.

Cobalamin is the name for B12, of which there are several 'types' or forms (cyanocobalamin, hydroxocobalamin, methylcobalamin and adenosylcobalamin). Hydroxocobalamin is the form prescribed in the U.K.

Take a peek at the reply below, have a trawl through the guidelines, and post again if you have any more questions.

Good luck with the demanding six year old - what a lovely age 🙂x

[Roses46 in reply to Foggyme]

Thanks, I'll have a peruse. Can I just query something else... I has my appendix out when I was 7 and during that they found out I had worms....I know operations and parasites can cause B12 deficiency (I was in my 20s when diagnosed) - if they caused my malabsorbtion deficiency (have no way of knowing, I'm just curious), does this mean it wouldn't be due to PA? If that's already explained in the detail I've not yet read, pls ignore this (getting the 6yr old to bed is hard 🙃)!

[Foggyme Administrator in reply to Roses46]

Worms and parasites - good question. Yes, they can cause B12 deficiency. But once the infestation has been treated, then B12 absorption reverts to normal and treatment for B12 deficiency is no longer required (that is, once B12 stores in the liver have been replenished).

Appendicectomy - another good question. During appendicectomy, it’s possible that the terminal ilium (where B12 absorption happens) can be either damaged or removed - it all depends on the extent of the surgery required - and the only way of knowing this may be to obtain your medical records and look at a copy of the surgical report to see what surgery was performed. It the terminal ilium was damaged or removed, then your body would no longer be able to absorb vitamin B12. In this case, once liver stores of B12 have been depleted, then the body would become B12 deficient. This can take a number of years but again there’s no way of knowing exactly how long because we're all different 🤷‍♀️.

If you did have B12 deficiency due to removal or damage to the terminal ileum, then your B12 deficiency would be caused by that (an absorption issue) rather than PA (an absorption issue with a different cause). However, the treatment would be the same - life long treatment with B12 injections.

Hope the six year old is safely tucked up and that you're having some rare moment of peace (in between eating and dashing around tacking jobs 🤣).

[Roses46 in reply to Foggyme]

Thanks, that's all really helpful! Alas no re child though, sat in bed with her still tossing about!! Can't wait to get my own back during the teenage years....

[Foggyme Administrator in reply to Roses46]

Oh those teenage years come all too soon - revenge is sweet, but I so missed that snuggling in bed with lovely little people. But then, I have grandchildren now, and that’s just lovely, all over again 🙃

[Roses46 in reply to Foggyme]

💗 yes, she's tiny still but getting all legs and arms 😍

[waveylines in reply to Foggyme]

Thanks foggyme for the great explanations. Really interesting. Does gluten intolerance play a part too? I had to go gluten free at Christmas was really poorly....miles better now. GP thinks I have Gluten Ataxia has referred me through but doubt will get an appointment for months maybe years given the pandemic!! Still have to inject b12 twice daily and cannot understand why but if I dont numbness, tremors, blurred vision etc hit with a vengeance. And was interested to read about your big toe stabbing pain as I have a stabbing pain in my big toe which started a month ago. I have Vitiligo Universal which has a link to PA.....but tested negative for intrinsic factor .....all very confusing!!

[fbirder in reply to waveylines]

Are you sure it's gluten that is causing your problem? It's more likely to be FODMAPs - newscientist.com/article/21...

[waveylines in reply to fbirder]

Thanks but we have had this conversation before and I have looked at FODMAPS -they are not the problem and I eat them happily in my diet with no issues. Its gluten. To be specific I frequently eat the fructose mentioned in the article of your link that are in the grains too that are also present in foods like onions, garlic and chickpeas with no gut issues at all. Over the years I have looked at this many times. I dont have irritable bowel syndrome.

[Hidden in reply to waveylines]

I am exactly the same as you. Have tried the tests and the eliminations and it’s definitely gluten for me. Amazing the difference abstinence has made!

[waveylines in reply to Hidden]

Absolutely agree Martin. Glad you feel better without the gluten. 😊

[Foggyme Administrator in reply to waveylines]

Yes, gluten intolerance can cause B12 deficiency, as can many inflammatory conditions that affect the bowel.

Here's something that you might find interesting:

healthandscience.eu/index.p...

I'm assuming you’ve been tested for coeliac disease? Woild hope,so and it sounds like it? If not, you need to have been including gluten in your diet six week prior to the test, since the test 'works' by measuring the body’s reaction to gluten - and if you haven’t been eating it, there’s nothing to measure.

Here's another interesting paper:

pubmed.ncbi.nlm.nih.gov/112...

Unfortunately there isn’t a 'gold standard' test for PA - 40%-60% of those with PA return a negative IF test, so you can test negative on the IF test and still have PA - that’s called antibody negative PA (AbNegPA). Most GP's have never heard of it.

Vitiligo is also linked to other autoimmune conditions - if your ill health is proving to be a bit of a mystery, might be a good idea to ask your GP to do an auto antibody test (if they haven’t already). The symptoms of B12 deficiency overlap with many other medical conditions and these can exist simultaneously with B12 deficiency (I had B12 deficiency first and was then diagnosed with Lupus when symptoms returned - I originally though it was the re-emergence of B12 deficient symptoms, and it wasn’t). Certainly not suggesting you have any other conditions - autoimmune or otherwise - just putting it out there for consideration in case you hit a diagnostic wall.

Oh and… stabbing pain in both my big toes turned out to be psoriatic arthritis - I appear to be collecting autoimmune conditions 🤣. Not suggesting you have that either 🙂.

Good luck.

[waveylines in reply to Foggyme]

Thanks Foggyme very interesting. I couldnt get the first link to work so not read that one. I have been tested a couple of times in the past but negative IGA IGE. The gp thinks that the clinic can test in other ways. I know I have to reintroduce the gluten but am dreading it and am not sure Imprepared to do so tbh. The gluten ataxia clinic should be able to see if there is any permenant damage to my brain.....I still have tremors though much milder and mt toes are pretty numb.

[Foggyme Administrator in reply to waveylines]

Sorry about the broken link, I didn’t spot it. I've fixed it so it works now.

Understand perfectly about not wanting to reintroduce gluten. Let’s hope the ataxia clinic have a solution to that.

About the numb toes - I know that these can be caused by gluten ataxia but in view of the negative tests (so far), wondering if other cause have been ruled out? Always a good idea because two conditions can run simultaneously (i.e. I have lupus and B12 deficiency, both of which can cause neuropathy - mine is due to lupus and autoimmune neuropathy and not B12 deficiency, as I originally thought). It’s sometimes so difficult to isolate and identify what symptoms are due to which condition. Symptoms overlap can be a nightmare.

With so much going on symptoms wise, hope your GP has screened you for autoantibodies (ANA etc.) - just to rule out the possibility of underlying autoimmune conditions, other than coeliacs (there are so many with overlapping symptoms that again, it’s often difficult to isolate and identify one from one from another).

Good luck with the ataxia clinic - would love to hear how you get on x

[waveylines in reply to Foggyme]

Thanks Foggyme. Thats interesting. I really dont know if they have screened me for other autoimmune conditions. I do have a couple! Autoimmune conditions are big in my family -RA, Vitiligo, Psoriosis, Sjogrens Hypothyroidism, hayfever and both my cousin and I have food sensitivities -mine has been around grains for years but never medically specifically identified. My cousins says hers is yeast and shes fine if she avoids yeasts, can eat cereal, flat breads. My sisters is dairy medically identified. So yes it wouldn't suprise me! I just dont think the NHS is geared up to identifying them.....and GPs dont have time (knowledge?)to look beyond a presenting symptom.

[jointpain in reply to Foggyme]

Thank you for mentioning the damage or removal of the ileum during an appendectomy as a cause for PA. This is something that I feel may have happened to me, but unable to prove. I actually think that it began with undiagnosed celiac disease which possibly damaged the villi within the ilium and the damage extended to the appendix. Which, when removed along with at least some of the ilium brought on my B12 deficiency/incorrectly undiagnosed PA. Since becoming a gluten avoider, what was left of my ilium has repaired and after over a year of avoiding gluten I am now able to, and have been for two years enjoy eating dairy products without the bloating and chronic gut pains. I still have to inject every four days and am unable to extend this period without getting some PA symptoms returning.

[Foggyme Administrator in reply to jointpain]

Yes, coeliac disease can cause B12 deficiency, as can many inflammatory conditions that affect the the GI tract.

Here's something that you might find interesting (but may have already seen).

healthandscience.eu/index.p...

The symptoms of PA are symptoms of the B12 deficiency it causes - so not surprised that your 'PA' symptoms re-occur when you don’t inject enough B12. And you have a potential 'double whammy' - the appendicectomy and the Coeliac's 😬.

Surprised you can tolerate gluten with the Coeliac's - most can’t. No idea how that works, or why 🤷‍♀️.

Thank goodness for injectable B12… 🙂.

[jointpain in reply to Foggyme]

Thanks for the reply, my wording may be a little confusing, but I assure you I cannot tolerate gluten at all. If I do ever accidentally have gluten I get terrible bloating, joint pain, malaise, mouth blisters and bloody stools. To name but a few.

[Foggyme Administrator in reply to jointpain]

Ah ha - sorry about that. Though it was odd. I think my brain must have 'hung' on 'enjoy eating' …and made the rest up as it went along. Cognitive failures are my speciality subject at the moment 😬. Pleased that you're able to now tolerate diary foods, at least 🙂.

[Nackapan in reply to Foggyme]

Thank you for the clear explanation.

[Foggyme Administrator in reply to Nackapan]

Most welcome Nackapan x

[fbirder in reply to Foggyme]

Just a quick correction - It's the BCSH - British Committee on Standards in Haematology, not BSH - British Society of Haematologists. Makes it easier to search for it later.

The flowchart is from the paper I linked to above.

[Foggyme Administrator in reply to fbirder]

Thanks fbirder. Update on your correction.

They changed the name of the British Committee for Standards in Haematology to the British Society for Haematology about 18 months ago. Hence BSH.

b-s-h.org.uk

No problems searching for the B12 treatment guidelines under the new name (BSH) - returned as first item.

Searching using the previous name (BCSH) automatically directs to the newly named BSH.

I have managed to also find a website called ‘ British Committee for Standards in Haematology' - it’s an American website selling BCSH guidelines. Nothing now registered in the U.K. under BCSH.

Wikipedia search for BCSH returns as 'page does not exist' (but guidelines written under this old name do appear). A page does exist if searched for under the newly named BSH.

Seems it’s off with the old and on with the new.

[fbirder in reply to Foggyme]

Ah! Didn't know that. Thanks.

[Foggyme Administrator]

Roses46, here's a copy of the BSH diagnostic flowchart that shows medics the diagnostic steps to take to determine the cause of B12 deficiency - of which there are many, with PA being only one of those causes. Here comes the link:

stichtingb12tekort.nl/engli... (BSH diagnostic and treatment guidelines B12 deficiencies).

PA is the most common cause of B12 deficiency and many GP'S do not realise that not everyone with PA has intrinsic factor antibodies (approximately 50% of those with PA never produce antibodies, so it’s possible to have PA and be antibody negative (AbNegPA).

So, in your case, according to the BSH guidelines, if all other causes for your deficiency have been ruled out, then your diagnosis should be antibody negative PA (AbNegPA). Many never get this diagnosis because GP's are not aware that it exists. Sadly. However…

It’s also the case that any form of B12 deficiency caused by an absorption problem needs treatment for life - that includes PA and other forms of B12 deficiency too. The main thing here is that treatment is continued when an absorption issue is present - some never get a formal diagnosis or a reason for their deficiency, but the prime imperative is to continue treatment.

Here's a link to the full copy of the BSH diagnostic and treatment guidelines for B12 and folate deficiencies:

onlinelibrary.wiley.com/doi... in Haematology (BSH) Guidelines: Treatment of B12 Deficiency and Folate Disorders)

They give useful information about different forms of B12 deficiency, together with the steps a medic should take to diagnosis the different causes of B12 deficiency. Well worth a read.

It's worth noting that many GP's work to what are called 'local guidelines'. These are most often many years out of date and do not confirm to the recognised BSH guidelines for the diagnosis and treatment of B12 deficiency. Some are so inaccurate as to be downright dangerous. For anyone reading who is having trouble getting a diagnosis and / or treatment for B12 deficiency, it’s worth printing the full guidelines (in the second posted link above) - then highlight the bit relevant to your case and send the full guidelines to your GP with a letter, asking to be treated according to these guidelines. A letter often works best because it’s a formal record of your request and has to be entered in your medical records. And I'd also like to think that the GP will take the time to read the guidelines! So, educating your GP to help others too

Hope the information helps.

[Roses46 in reply to Foggyme]

Thanks very much, your explanation really helps and I'll print off the links tomorrow x

[Hidden]

I have microscopic colitis which is why I can't absorb B12, my Doctor didn't bother testing IF and just said that whatever the reason (already ruled out diet) I'd be on injections for life. My father had pernicious anaemia though so I suspect I have too. I hope you get the help you need.

[Roses46 in reply to Hidden]

My mum died about 6 months after a colitis diagnosis (we suspect she also had cancer) & she was being treated for severe B12 deficiency as a result. She had mental heth issues all my life - since this diagnosis I've wondered if B12 deficiency always lingered for her

[Hidden in reply to Roses46]

Ah I'm so sorry to hear that, how heartbreaking for you 😥 I had a CT scan last week. I was diagnosed with the colitis five years ago in India and my GP hasn't been interested in monitoring it. I'm in a terrible mess now and so scared it's cancer. My mum also died of cancer and like you, I've often wondered if her ME diagnosis was actually B12 deficiency 😭 Sending a hug to you. You never get over seeing your Mum suffer like that do you? ❤️

[Roses46 in reply to Hidden]

Thank you. I hope I haven't worried you though - the reason I mentioned cancer is that they'd found a mass in her stomach but she was too unwell at the end to have it investigated. She didn't really help herself with her diet and wouldn't let anyone help so was too far gone in the end to get better. It's hard but try not to let your GP fob you off, ask to speak to someone else if they won't help x

[Hidden in reply to Roses46]

No need to apologise.... I've gone private through my husband's work healthcare so hopefully will get the results quickly. I wish you well and don't be fobbed off either 😊❤️