Extremely high B cells (CD19) - what's going on? Help understanding results

[Eeyore]

@Antares in NYC - That makes sense to give Fe in that case. What you describe sounds like iron deficiency anemia.

 

[Antares in NYC]

@Antares in NYC - That makes sense to give Fe in that case. What you describe sounds like iron deficiency anemia.

Thanks, @Eeyore. Now that you guys mention it, I recently took my genome data from 23andMe, and ran it through an online diagnostic tool. It did say I carried both genes for hemochromatosis. Of course, I did find this out recently, a full month after the ferritin infusions, so now I wonder if it was the right thing to do. Bad timing.

That said, in addition to extremely low levels of ferritin (and hemoglobin), in recent years I have developed major deficiencies, including B12, D, and magnesium. Iron anemia has been the last weird addition to my collection of bizarre symptoms since my CFS worsened steadily in the last 5 years.

 

[Eeyore]

@Antares in NYC - Well, I'd definitely mention the hemochromatosis going forward. Especially if you are not just a carrier but have 2 variant alleles. I only have the milder of the 2 - H63D - which is fairly common - and my other allele is wild type - but if you have one of each, you are at very real risk of serious issues from hemochromatosis and should have this followed up aggressively. The key to good outcomes in hemochromatosis is early diagnosis and management.

Normally hemochromatosis does present with high ferritin. Alex has mentioned cases where this is not the case, but I haven't heard of it. It may be the case - but it's not the norm, so your low ferritin makes it less likely you are currently affected. Most people with hemochromatosis are not affected when young, only as they get older.

B12 is important in making RBC's, and deficiency is reflected in the CBC as elevated MCV (megaloblastic anemia).

You should probably see a hematologist to have this sorted out in the background of 2 mutated HFE alleles.

 

[xks201]

Did your cfs start with a vaccine?

 

[Jonathan Edwards]

Do any of our medical scientists here understand what is the point of having a reference range if being outside the reference range isn't important? Shouldn't reference ranges be set so that being outside them is likely to mean something other than "It's probably not of any significance"? What's even the point of testing if having abnormal values on the test isn't significant?

I understand the point that some apparently healthy people might have out of range values, but that should be considered an oddity, not a reason to dismiss out-of-range values in unhealthy people. There has be be more reason than that to consider reference ranges of no particular importance in evaluating test results.

Yes, I understand, SOC.
There are two ways to define a reference range. One is to define it by what is statistically likely to be healthy. That would be useful if it were not for the fact that what is healthy varies enormously with the clinical problem. The level of urate that is likely to indicate gout in a middle aged man is quite different from the level of urate that is likely to indicate pre-eclampsia in a pregnant woman. Different people have different calibration of their CRP response by a factor of up to something like 5 - so healthy ranges for two people can be quite different. If labs used healthy ranges there would have to be a manual attached to every item on the print out. There are times when a few comments might help but the labs have generally opted for a centile- based range.

If you use a centile based range (taken from healthy people) you can choose something like 5th to 95th centile or first to 99th centile. If you take the former then about one result in ten will fall outside the reference range in a normal population. If you use the latter you will miss a lot of unhealthy results because there is usually at least a few percent overlap between unhealthy and healthy people's results. Setting ranges to around 99 per cent so that you can be SURE it is abnormal will produce precisely the problem we want to avoid - missing results in the tail end of the normal range that are actually an important sign of disease. Most labs I think go for about 5th to 95th centile, or maybe 2.5 and 97.5. That means that if you get a batch of tests with forty numbers you should expect at least two of those numbers to be outside range if you are healthy - every time.

There is more reason in considering out of range lymphocyte subsets as unimportant because (a) the numbers of these cells in the circulation is of pretty little biological significance anyway - so is not tightly regulated and varies over a wide range and (b) cell sorting is notoriously prone to technical errors.

Antares said nothing about the physician dismissing the result. So I presume the reference is to me 'dismissing the result', which I think is a bit tactless and uncalled for, to be honest. As a doctor I have to take into account the fact that people will tend to take seriously what I say about results. If I were to say that a result is very likely a sign of lymphoma I might cause a huge amount of distress. In this case I do not think the test is a sign of lymphoma but nobody is sure and a recommendation to check things has been made. I read a lot of posts on this site that look to me as if they will terrify the wits out of other members and I try to avoid that, while making sure nobody forgets to follow up on things that are uncertainties. I am very well aware that doctors do dismiss significant results, like the one who dismissed my prostate cancer result, but that is not happening here and it seems to me a hare has been raised that has nothing to do with the original question.

 

[Eeyore]

@Jonathan Edwards - I did make a reference to docs dismissing results, and I think I clarified it on the original thread to make it clear it was not by docs on this forum (which mostly means you in terms of activity). I don't think it was targeted at me but wanted to make that absolutely clear that I do not see you as doing that and would never make such an accusation.

I think your approach is very measured and thoughtful. One problem I find frequently on the boards that patients experience with their treating physicians is that results are dismissed, often with good justification, but without explanation, which can be frustrating for patients. Patients do not understand the origin of reference ranges, and docs don't explain it, although they are used lots of values falling a bit outside the reference range and meaning nothing, especially if they don't fit any known pattern of disease.

I believe the major labs in the US generally use 2 standard deviations, or 5-95.

Although I am not a doctor, sometimes I do know an answer to a question, and I think you're an excellent model of how to answer these questions. Results that may be significant shouldn't be dismissed; patients should not be overly alarmed about results that, while potentially serious, are not likely to be; followup with the treating physician should be encouraged if there is doubt. You're also good at explaining why some results can be safely dismissed - an area physicians really should be better at communicating to patients.

I can't speak for everyone, but I do believe based on reading posts in the time I've been here (and before when I only lurked) that your presence is very much appreciated on these forums. Many patients want more than anything to have a medical professional actually listen. I wish I had not gotten sick just as I was about to enter med school - I could have been a physician who listened to patients and helped them through tough times. I had an amazing infectious disease specialist when I first became sick, and while he never could really solve the problem, his thoughtful approach, excellent communication, and personal support were invaluable in a difficult medical time. Docs have something to offer all their patients, even those who cannot respond to known medical treatments.

You are a scientific skeptic - which, I suppose, is the same thing as a scientist - and that is a good thing. I want answers to ME, and if I'm barking up the wrong tree, or my theory is full of holes, I want to know that. I don't want AN answer, I want the RIGHT answer. I've gotten far too many answers over the years which were wrong - they don't help anything.

Anyways - just in case that was partially or completely based on my post above, it wasn't directed at you.

I wonder if your prostate cancer diagnosis has had some effect on you in the way ME has on most of us - lack of trust in doctors who quickly dismiss. Docs are trained to trusted specialists just as patients are expected to trust their docs. Most of us on this forum do not believe we can totally trust our docs, and instead that we have to be actively involved in our own medical care. My sister has a well understood very serious medical condition (or conditions), and we have both been actively involved in digging deeper - and we've found things that her specialists missed, and ultimately improved outcome (albeit modestly). My guess is that you had a PSA that was elevated and dismissed (which is common - as PSA's give lots of false positives and false negatives). I'm still young for that, but my dad is about your age I think and, while he doesn't have prostate cancer, has had high PSA's (but they were followed by biopsy).

Anyways, thank you for your continued presence on this board, your scientific skepticism combined with open-mindedness, and your desire to help an under served patient population. I'm pretty sure most of the board feels that way.

 

[Eeyore]

@SOC - I think Dr. Edwards already gave a good explanation, and I'd agree with everything he said.

I'll add a bit.

Doctors are not just looking at reference ranges. They are looking for evidence that supports a diagnosis. Often a panel of tests is run, looking for information that suggests a particular diagnosis. Say you're worried about disease X based on clinical presentation, and it causes an elevation in lab marker Y. If you get back the report and Y is reduced and just below normal range, that doesn't support your potential diagnosis of disease X, so you'll likely dismiss it unless, in isolation, it suggests another disease that fits clinically with what you are observing.

Lab tests - or any medical tests - usually cannot be interpreted in isolation, which is why docs generally should be involved in the interpretation. Various studies must be correlated clinically with signs, symptoms, and history, as well as with other studies.

Many ME patients will get extensive lab work and have a number of results that, just by chance, fall outside the normal reference range. Sometimes, these results are replicable and it is something the patient frequently sees. I have some results like this. This becomes interesting to me if other patients are frequently reporting this result, or even more so if published papers document this abnormality or tendency in ME patients. However, if it is totally isolated, then I do not worry too much about it in general, although I will keep it in the back of my mind, as it may be something that later gives me a clue.

Some patients are genetically programmed to have certain results be abnormal, although not pathogenically. I have very low triglycerides. I am often outside the normal reference range (it can be 20 or 30 sometimes), no matter what I eat, what I weigh, or how bad my cholesterol is. I never knew why, but it's not rare in my family (on one side). Recently I found out I have a very rare mutation in the APOC3 gene which is involved in lipid transport. It's essentially a knockout in one allele, leaving only one functional copy. This was studied in the NEJM recently in a cohort of over 75,000 people, and found to have an allele frequency of about 1 in 720 - and to reduce rates of heart disease and stroke pretty dramatically, and it's being studied in the development of new drugs. The point is, I could have spent years worrying about why my triglycerides were out of the normal range. There is a reason - but I didn't know if for 20 yrs or so. Now I know it, and it's not something to be worried about. Docs didn't worry either because they couldn't think of a disease it would indicate (high would be another story).

We're all different genetically, and may have abnormal results for that reason (as Dr. Edwards mentions, CRP baseline values vary by a factor of up to 5 - this is probably genetically determined). You have to interpret a CRP vs a baseline. Other results just tend to fluctuate a lot, such as lymphocyte populations, and this occurs in healthy people too. Sometimes, it's an indication of a problem, but more often, it's nothing. If the doc isn't sure, or is a bit worried, follow up or repeat testing is warranted. Labs make errors too, which can sometimes give a flukey result.

I think the real problem is that treating physicians, when they are treating populations of patients with ME or other illnesses where patients have no choice but to take an active role if they want good treatment, do not explain why results are dismissed. I urge you to question them and just ask for an explanation of why the result is not concerning. The physician has probably thought about it and has a reason for dismissing it. Also, if you are concerned, they will often offer a repeat test to make sure things are ok.

 

[Antares in NYC]

Did your CFS start with a vaccine?

No, not that I'm aware of. It started 16 years ago with a massive flu-like crash that left me bed-ridden for months, and then intermittently bed-ridden for two more years after that.

Turns out 2 months before that initial virulent episode I had a strange bulls-eye rash in my chest that no doctor in Massachusetts could explain. I found out much later that it was a WB positive infection for borreliosis that went untreated for way too long. I think that was the beginning of my problems to this day, and the very likely origin of my current immune dysfunctions and ME/CFS.

There was a very clear before and after that flu-like episode.

 

[duncan]

Regarding the earlier remarks about hemochromatosis: My paternal aunt has hemochromatosis. I tested negative. If I remember correctly, treatment for this is bloodletting. How's that for high-tech?

 

[Antares in NYC]

I wish I had not gotten sick just as I was about to enter med school - I could have been a physician who listened to patients and helped them through tough times.

It's really heartbreaking to read stories like yours, and in a way it makes me feel a little bit less alone, albeit angry that so many of us had our dreams and careers cut short by this awful plague.

My story is a case of terrible luck and terrible timing: I moved to the Boston area as I was applying to study at the MIT Media Lab (the place to be in high tech media experimentation in the late 90s), and was also applying to Harvard at night, so I could continue my postgraduate studies at either one of those prestigious institutions while working full time at a local new media agency....

And just within months of settling in Boston I felt extremely ill, bed-ridden, and had to postpone everything. Everything changed, nothing was ever the same. My once proud photographic memory was replaced by a foggy and scattered mess of a brain. My contributions to society, community and family were cut short forever. Yet I'm not alone. We are a legion of people left broken by this thing. Jen Brea's story (Canary in a Coalmine) is also very similar to ours.

I wonder about the true economic impact of ME/CFS, Lyme and other severely debilitating illnesses that authorities have ignored, allowed to fester, and grow exponentially over the last three decades.

Ok, rant over! Sorry for that.

 

[Daffodil]

i had all that after decades of CFS...extremely low iron (i figured this was "anemia of inflammation"), low 25-D, low Mg, etc. but now i am getting better with Lyme treatment....

 

[Eeyore]

@duncan - have you done 23andme? You might have tested negative biochemically, but not genetically, or you might be a carrier for hemochromatosis.

 

[Eeyore]

@Daffodil - Anemia of chronic disease is associated with high ferritin - the sequestration of iron in ferritin prevents erythropoiesis. It looks different from iron deficiency anemia in that the latter is associated with low ferritin - there just isn't enough iron anywhere.

 

[Jonathan Edwards]

I did make a reference to docs dismissing results, and I think I clarified it on the original thread to make it clear it was not by docs on this forum (which mostly means you in terms of activity). I don't think it was targeted at me but ...

It wasn't. Your approach is very measured and thoughtful too, Eeyore.

I wonder if your prostate cancer diagnosis has had some effect on you in the way ME has on most of us - lack of trust in doctors who quickly dismiss.

My lack of trust has more to do with my coming to terms with my own arrogance and ignorance as a young doctor. I recognise that some of my colleagues never grow out of that. And the failure to diagnose or treat my wife's insanity brought it home - quite a bit before the prostate business!

 

[Eeyore]

@Jonathan Edwards - Humility is a great trait in anyone, and especially in doctors. The older and wiser we get, the more we know just how much we don't know.

I think it was Socrates who said something along the lines of the first step towards wisdom being recognition of our own ignorance.

 

[Daffodil]

@Daffodil - Anemia of chronic disease is associated with high ferritin - the sequestration of iron in ferritin prevents erythropoiesis. It looks different from iron deficiency anemia in that the latter is associated with low ferritin - there just isn't enough iron anywhere.

@Daffodil - Anemia of chronic disease is associated with high ferritin - the sequestration of iron in ferritin prevents erythropoiesis. It looks different from iron deficiency anemia in that the latter is associated with low ferritin - there just isn't enough iron anywhere.

ohhh, i never was sure what the difference between iron deficiency and anemia was......thanks!!!

 

[SOC]

There are times when a few comments might help but the labs have generally opted for a centile- based range.

If you use a centile based range (taken from healthy people) you can choose something like 5th to 95th centile or first to 99th centile. If you take the former then about one result in ten will fall outside the reference range in a normal population. If you use the latter you will miss a lot of unhealthy results because there is usually at least a few percent overlap between unhealthy and healthy people's results. Setting ranges to around 99 per cent so that you can be SURE it is abnormal will produce precisely the problem we want to avoid - missing results in the tail end of the normal range that are actually an important sign of disease. Most labs I think go for about 5th to 95th centile, or maybe 2.5 and 97.5. That means that if you get a batch of tests with forty numbers you should expect at least two of those numbers to be outside range if you are healthy - every time.

Thanks, Jonathan, I think that helps to some extent. So the reference ranges are centiles which don't have a direct correlation to healthy or unhealthy conditions? That means doctors need to use judgement based on clinical presentation and other test results to evaluate the importance of out-of-range results rather than simply making major health decisions based on whether a single result is just inside or just outside a reference range, right?

I'm still a little puzzled why <5%, >95% results aren't treated with more concern (such as further testing) given that we don't know if the results are abnormal or just unusual. I can see that assuming an out-of-range result is automatically bad is unwarranted, but assuming it's normal without checking doesn't seem like the wisest path, either.

So I presume the reference is to me 'dismissing the result', which I think is a bit tactless and uncalled for, to be honest.

Actually, no. I didn't realize you had dismissed the result. I don't read everything you post anymore than you read everything I post.

The issue of doctors dismissing out-of-range results has arisen in other threads recently, which it why it was on my mind. There were also some comments in this thread about doctors dismissing, or at least not being concerned about, out-of-range results.

As a doctor I have to take into account the fact that people will tend to take seriously what I say about results. If I were to say that a result is very likely a sign of lymphoma I might cause a huge amount of distress.

I certainly wouldn't expect you to suggest anything of the sort. It would be inappropriate for you to make that kind of evaluation about a member's reported lab results as well as against forum rules, which I know as a board member you are very well aware of. I also wouldn't expect you to tell people that their out-of-range lab results are unimportant since that would also be providing a medical decision I know you know better than to post at PR.

I read a lot of posts on this site that look to me as if they will terrify the wits out of other members, and I try to avoid that...

I think perhaps you don't give the membership enough credit here. We are adults, not children. We don't get terrified over every little thing. We don't need to be protected from reality. We are mature enough to make our own evaluations about the information we're given and how we are going to react to it. Many things about this illness are upsetting and possibly frightening. We can't pretend that's not true, but fortunately we've got plenty of experience coping with disturbing news about our health and future.

... while making sure nobody forgets to follow up on things that are uncertainties.

That's an important contribution and something that all of us try to do for each other. I thank you (and all other members) for that.

I am very well aware that doctors do dismiss significant results, like the one who dismissed my prostate cancer result, but that is not happening here and it seems to me a hare has been raised that has nothing to do with the original question.

So basically your concern here is that I was OT. Maybe I was. If so, I apologize.

 

[5150]

No, not that I'm aware of. It started 16 years ago with a massive flu-like crash that left me bed-ridden for months, and then intermittently bed-ridden for two more years after that.

Turns out 2 months before that initial virulent episode I had a strange bulls-eye rash in my chest that no doctor in Massachusetts could explain. I found out much later that it was a WB positive infection for borreliosis that went untreated for way too long. I think that was the beginning of my problems to this day, and the very likely origin of my current immune dysfunctions and ME/CFS.

There was a very clear before and after that flu-like episode.

-------------------------------
My case started like yours, but subsided, then came back & stayed with a vengeance.
Big Question: if this turns out to be Lyme (I am not yet convinced), is Lyme contagious in a general, non-sexual way? More than one person that I know has said it was acquired from a kiss from an infected person. (me too)
Can this be true if we are going to treat Lyme? If not sexually transmitted, then it must be via saliva if kissing is involved? Can Lyme do that?

Any facts here that somebody may help with? Thanks.

 

[Valentijn]

I think perhaps you don't give the membership enough credit here. We are adults, not children. We don't get terrified over every little thing.

I think this is true for the longer term forum members, but we do get a few dropping in from time to time who get overly excited about every little thing. At the very least, it's a good idea to use a lot of caution when discussing risks with people whose temperament isn't known yet. And we also need to take into account that excitable people could be reading the threads where more even-keeled forum members are discussing risks and abnormalities.

 

[Eeyore]

I agree with @Valentijn and Dr. Edwards - unless you really do see major cause for concern (forum member posts that their last creatinine was 12.6 when it was always normal, and wants to know if that is something to worry about) - then you do need to be cautious. Many of the tests we see have many interpretations. When a clear answer can be offered, there is no reason not to do so, but when the actual interpretation remains unclear, as is commonly the case with ME patients, it's appropriate to mention possible risks, but also to explain that in many cases, the result is normal or insignificant.

I don't think anyone is suggesting we hide the truth from members. It's rather about whether a result that has multiple interpretations should cause you to leap to the worst one or not and hit the panic button. In this thread, I did mention the possibility of monoclonal lymphocyte expansion (this would be either a form of cancer or pre-cancer) - but there are other abnormalities that are missing that would be typical of that disorder. Just because something remains possible doesn't mean it is probable, and not only are we not doctors (with rare exceptions like Dr. Edwards), but we are not the doctors treating these people, and we may not have all the information.

I'm the first one to challenge a doctor who is acting unprofessionally or is obviously wrong (it happens, a lot). However, I've spent a lot of time thinking about the nature of the doctor patient relationship and how it should be built. Because ME patients have been generally neglected by the medical community, there is anger. The anger is often justified - but it may not be justified towards each doctor you encounter. As patients we need to try to understand the pressures doctors are under. As Dr. Edwards points out, he has to be particularly careful what he says in interpreting tests because of how much weight his words as a doctor carry. He doesn't mention it, but I think part of it is that being a doctor does not mean one is in a doctor-patient relationship, and one has to be cautious in dispensing medical advice outside of such a relationship, where one does not have all of the information, and out of deference to the treating physician who actually is examining and treating the patient. We also must try to understand the pressure on doctors brought by insurance, govt regulators, potential lawsuits, and the medical community as a whole. Doctors aren't too happy in their professions right now in the US - and maybe elsewhere too - where they are overworked and underpaid, and forced to spend more time doing paperwork than helping patients. The whole system is broken, and ME patients seem to be among its worst victims, but each doctor is not personally responsible for every failure of the system. Sure, some are just awful - I had such an experience last year. Worst doctor I've ever dealt with - abusive, dismissive, not very bright, and generally just nasty. Many are just "ok." A few are extraordinarily good.

As poorly as I've been treated by some docs I still encourage people to seek out good ones and form a good relationship with them, and to work with them as partners in improving their health. I definitely do not encourage patients to ignore doctors and come to this forum as a substitute, and I suspect that any doctors on this forum would agree. It's always great to come here and get advice and information that you can then go back to your doctor with. Medical information gathered here should complement and enhance, rather than replace, a good doctor-patient relationship. Often, for us especially, the relationship with the PCP may be the most important of all.