Came across a great article on the relationship between inflammation, allergies and a poor immunity in CLL. ncbi.nlm.nih.gov/pmc/articl...
Every now and then I hear about people with CLL on the forums saying that they never really get properly sick. So for example a cold comes along and it just doesn't really descend on them like it used to.
We might assume that was a good thing, until we realise that many of the symptoms of a cold are actually the effect of our immune system responding to the infection. So in fact sometimes we may be sicker than we think we are. So it is very possible for us to be harbouring a low grade infection without really realising we are. And of course low grade infections are well known to produce fatigue, so I do wonder sometimes how much of our fatigue might evaporate if we were able to get rid of any low grade infections floating around.
In my own case, this business of our immune system not responding properly caused some confusion to a local hospital when I first presented with pneumonia (and during that illness became diagnosed with CLL). Why weren't my neutrophils raised if I had a significant pneumonia? Why wasn't my temperature raised until several weeks in when I suddenly began to go into sepsis whereupon it hit almost 40C? Why weren't my inflammatory markers raised at the beginning of the illness till eventually they turned on like a switch? The answer once we were clear I had CLL seemed to be that my immune system really wasn't that bothered initially that bacteria were gnawing away at my lung tissue.
Practically this is why for some of us a raised temperature even before treatment might be a much more concerning symptom than it would be in someone with a normal immune system. If we are not successfully mounting an immune response to an infection (of which a temperature is) in the early stages, but then do mount one when it has become much more advanced, then the advice to go to an ER if we have a temperature over 38/100.4 seems very reasonable.
Since my diagnosis like many others I have also had a significant worsening in my allergy symptoms so that I am now constantly in need of high dose antihistamines to stop myself scratching my skin off and that coupled with steroid nose spray and a saline rinse just about keeps my sinuses at bay...although lately I am starting to realise that perhaps they haven't been kept quite as much at bay as I thought they were. A few weeks back I developed a severe sinus headache simultaneously to a chest infection, and am currently into my third week of treatment with an antibiotic on top of my regular prophylactics to try and sort all this out.
This over-activity of some of our immune systems against allergens and yet under activity against infectious agents is quite common in people with CLL. And of course our immune systems sometimes also turn against our own bodies leading to various autoimmune problems too.
The article I found had a lovely way of explaining the cause of all this:
"A paradoxical deregulation of the immune system that produces an exaggerated inflammatory response to minor insult or to self-antigens coupled with an inadequate response to infectious stimuli is typically found in patients with CLL"
To translate that into regular English
The immune system becomes confused and disorganised. It both over-reacts to non threatening things it comes into contact with (such as pollen, dust, and mosquito bites), can even attack the body itself, but also under reacts to infections.
The article then goes on to review what information was available in 2013 about all this, it would be interesting to find out how much more research has been done since then, though I rather get the idea there may not be that much more.
The paper describes a study that showed that certain inflammatory cytokines were higher in patients with CLL than healthy controls. It was a relatively small study.
In patients with ME/CFS and Fibromyalgia it has been shown that certain patterns of altered cytokine concentrations are associated with patients having worse symptoms. Despite careful searching of pubmed I have not been able to find any study to identify if certain patterns of dysregulation of cytokines are associated with more fatigue in patients with CLL. It would be fascinating to take a group of patients with severe, moderate, mild, or no fatigue and compare their cytokine profiles. Perhaps we could even have a blood test that proved there was a reason for how crap we were feeling...it would be great to be able to prove it is not just in our minds!
I wonder if any of you have had your cytokine profile measured? It doesn't seem to be done routinely.
Another test that could be of interest is looking at the number of T cells and natural killer (NK) cells. The paper explains these are often INCREASED at the time of diagnosis as the body tries to fight off the CLL, and one wonders why we don't measure them routinely as apparently if this increase is present it suggests there will be a longer time to first treatment, presumably because this increase is initially helpful.
Conversely it seems the real problem with CLL is when those cells give up and are no longer fighting CLL properly. CD8+ (cytotoxic) T cells will often increase more than the CD4+ Helper T cells, and apparently this ratio can also have important prognostic implications. But again I don't think we are often tested for the amounts of these subtypes, except perhaps the CD4 levels where I understand some doctors use that as a marker for whether or not you should be on some prophylactic medications.
Now of course the argument against testing for all these things would be, but is there anything we can actually DO about it? Perhaps there isn't just yet, but wouldn't it be interesting to begin to look at firstly how the derangement of the immune system is correlated with symptoms, but also to look in more detail at how predictive it is of our future health, and perhaps start to look at how it could be influenced.
The paper also explains that certain pro-inflammatory genetic mutations are also seen in patients with CLL.
How the inflammatory state could be influenced is where this paper gets really interesting. Advocates of certain diets sometime claim their diets are anti-inflammatory and that therefore they can reduce the rate of development of the disease. This paper might even support that hypothesis (if that is it could be proved that the diet itself genuinely was anti-inflammatory even if someone isn't actually allergic to the food they cut out). Since the idea seems to be that anything that switches off inflammation may help CLL. Of course most evidence for such diets is largely anecdotal and the paper doesn't mention diet as a possible intervention.
The paper does review evidence for the efficacy of a range of anti-inflammatory drugs including the ultimate anti-inflammatory steroids, non steroidal anti-inflammatory drugs including aspirin, statins, and even points out that Ibrutinib is actually working by counteracting certain inflammatory pathways.
So should we all be taking an aspirin a day and even if our cholesterol isn't up a statin? Sadly the studies haven't been conclusive (perhaps not large enough?), and I suspect the effect if real may be small, but if even 100 of us had to take an aspirin a day to delay a relapse in one patient by one year perhaps that would be worthwhile?
With all the excitement about new drugs I doubt that much interest will go into trying to further confirm the old data this paper reviews. Perhaps some younger haematologists may even forget that steroids can actually help our disease!
Speaking of steroids, on the occasions I have had to take a week of steroids (eg after my tonsil operations) I have felt an instant and dramatic improvement in my fatigue levels which is much more than just the fact they also stop you from sleeping. So much so I have often mused about begging a doctor to put me on a low dose steroid to as an old respiratory doctor actually suggested "just settle down any residual inflammation that may be there". There are serious side effects of steroids that mean that perhaps that is not as good an idea as it immediately sounds. But if I could just pop a single tablet on a day I wanted to achieve more.....
Anyway this has gone on long enough, and if you would like to learn more, the paper this article is based on can be found here:
ncbi.nlm.nih.gov/pmc/articl...
This is an unlocked post as it is about clinical data. Please do not share personal experiences you would not want to find on google below.
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