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View Full Version : Is there a connection between RTX and lung infections ?



Alysia
04-17-2014, 04:00 PM
Hi,
we really enjoy our rtx, if I can say so :unsure:
but yesterday at the hospital, during my IV, I was told by another woman who also got it (for Scleroderma) that she got 3 lungs infections this year and that the docs told her that it was caused by rtx :w00t::w00t: STILL she is getting it, but only 500mg and no more 1000mg.
so I though to ask you, who knows anything about it, and also search the web.
here is a link that I found:
http://www.ersj.org.uk/content/35/3/681.full
I copy the conclusions:
In conclusion, the present study confirms the pulmonary toxicity of rituximab. Our data should prove helpful to clinicians in assessing causality in patients with respiratory symptoms following rituximab therapy. Three distinct clinical presentations were identified according to time to onset, suggesting different underlying mechanisms. For each, we suggest specific recommendations. Pulmonologists must ensure the early diagnosis and treatment of rituximab-induced lung disease and inform other specialists of this complication and of the need for close monitoring of respiratory status.
:crying:
there are more articles suggesting it, like this:
http://www.nejm.org/doi/full/10.1056/NEJM200306263482619
it seems that overall it increases infections (as I can tell from my experience), like in the following links :
Does rituximab increase the incidence of infectious complications? A narrative review (http://www.sciencedirect.com/science/article/pii/S120197121002504X)
http://www.iwmf.com/docs/rituximab-associated_infections-seminars_in_hematology.pdf
please, do not read it before going to sleep :w00t:
the consolation is that it is written that complcations are rare.
and we can't do without it... (sigh)

Pete
04-17-2014, 10:36 PM
Intuitively, we should expect to be more susceptible to infection while immunosuppressed, no matter what drug we use. Certainly good hygiene and staying away from people with colds, flu, etc., should reduce our chances of getting sick.

Debbie C
04-18-2014, 01:47 AM
Alysia, I personally think all these drugs prescribed for not only this but other diseases surely have other effects on the body. If you were too look at all the possible side effects ( which I usually do ) you wouldn't take them ( which I usually don't ) I can't understand the need for rtx infusions ( when it is such a powerful drug ) if one is in remission or there are no huge signs of the illness. Like the saying goes " if it's not broke don't fix it ". Maybe you should ask your dr. about it,maybe that's why you keep getting uti's ...it gotta come out somewhere !!! Hope you are better soon....Hugs

annekat
04-18-2014, 02:06 AM
Thanks for finding the links, Alysia, and sharing a conclusion. It is true that we are all taking risks with any of the drugs we take. I understand your concern, and we can only hope that you and others on here who are taking RTX will be in the majority who do not have these problems. I'm sorry you have to worry about this while trying to get better... :hug2:

Geoff
04-18-2014, 04:38 AM
Gosh this has made me sit up with a jolt. I was DX 6 years ago and have been amazed that apaft from ONE cold, i have enjoyed a relatively germ free life.
In feb this year i finished my 2 year cycle of RTX. There were a few questions raised beford the last IV and Dr Jayne did ponder the opinion that perhaps i had had too much rtx in the time. Given my size, 6'4" and 18 stone, i was infussed every 4 months.
Be that as it may, i now find 2 months later i am struggling to shake off the worst chest infection i have ever had, and the 2nd to boot! I have finished another round of antibiotics and got the all clear from my GP on tuesday who confirmed my lungs were 'clear'.
Thing is do i now flag this up to Addenbrookes or carry on with my recovery and wait till June for my next appt? I thought i knew the answer but this latest info from Alysia has raised concerns.

Debbie C
04-18-2014, 09:15 AM
Before my first and only infusion, I read a pamplet on all that can happen within just minutes of getting this so surely repeated infusions can reak haffeck on you. I know it is the " wonder drug " but now it make you "wonder " in different ways.
Geoff, I would ask if the infection could possibly be from the infusion. That could be an answer to alot of peoples problems...too much of a good thing !!!!:w00t:

pberggren1
04-18-2014, 10:56 AM
I just had an infusion of RTX last month and came down with a lung infection shortly after.

me2
04-18-2014, 03:54 PM
At my doc visit a few days ago he expressed very vocal concern about me dying from infection based on the all the imunosuppresants I am on. Prednisone, methotrexate, and Rituxan.
The only infection I have had was persistant Staph in my sinuses. I had surgery to help with this. So far I seem better.
I lead a fairly isolated life from people and take reasonable precautions when in public- like hand washing during and after being out. I know not everyone can live this way.

pberggren1
04-18-2014, 04:44 PM
What specialty is your doc Kirk? Do you have damage to your lungs? Was he referring to a specific area like the lungs?

me2
04-18-2014, 05:02 PM
Hi Phil, this doc is my Rheumy who oversees my general care for several years now. I do not have significant damage to my lungs (although they are not exactly normal). He did not mention a specific area that I might be prone to infection but if I had to guess it would be lungs- even for me.

This is where we take in bugs and they can get a foothold easily in that nice warm, moist incubator. Its just my thoughts on this, I don't really know.
I would also suspect that we would be prone to infection wherever we have the most damage. I recently had surgery on my very bad sinuses and they were filled with Staph.
My Rheumy said this was not surprising for a WG patient.

pberggren1
04-18-2014, 05:05 PM
Ya, the lungs even for a healthy person can be the most perfect area for infections. The entire airway system is a breeding ground for Staph. I have had a few staph infections in the lungs.

Alysia
04-18-2014, 06:17 PM
Thanks everyone for your thoughts.
thanks for the good words, Anne and Deb :thumbup:
I think that there are 2 issues here:
1. getting infections easly because we are "immuno-supressive".
2. getting lung infection AS A RESULT of the rtx, like what happened to the woman I saw at the hospital.
for this, I also found this link:
http://erj.ersjournals.com/content/early/2009/07/16/09031936.00080209.full.pdf
I copy to here something which seems related to what Geoff wrote above:
Given the potential severity of rituximab-induced lung disease and the strong suspicion
of underlying hypersensitivity, we suggest a number of recommendations. First,
patients should be told that respiratory disease may develop, with the risk being greatest about 15 days after the last infusion and around the fourth cycle. Second, respiratory symptoms should be looked for routinely after each infusion. Third, any clinical manifestation, however mild, should prompt a chest radiograph. Finally, when the findings support a diagnosis of rituximab-induced lung disease, steroid therapy should be started immediately, as it seems to improve the outcome. Furthermore, instead of the currently recommended methylprednisolone infusion at each rituximab administration, a longer period of steroid therapy with tapering of the dose to avoid a rebound reaction may be appropriate.
Late-onset organizing pneumonia (which may occur up to several months after the last
rituximab infusion) may be related either to toxicity of the drug, whose biological half-life is poorly known but probably long, or to immune system restoration.

Alysia
04-18-2014, 06:22 PM
In feb this year i finished my 2 year cycle of RTX. There were a few questions raised beford the last IV and Dr Jayne did ponder the opinion that perhaps i had had too much rtx in the time. Given my size, 6'4" and 18 stone, i was infussed every 4 months.
Be that as it may, i now find 2 months later i am struggling to shake off the worst chest infection i have ever had, and the 2nd to boot! I have finished another round of antibiotics and got the all clear from my GP on tuesday who confirmed my lungs were 'clear'.
.

I am sorry Geoff :crying: I hope that you are already feeling better ? :hug2:
anyway, the woman I met at the hospital told me that the docs continue to give her rtx but only half dose. not 1000mg every 6 months but 500mg.
maybe you should get less :unsure:

Alysia
04-18-2014, 06:25 PM
I recently had surgery on my very bad sinuses and they were filled with Staph.

are you feeling better now ? :hug2:

Alysia
04-18-2014, 06:27 PM
I just had an infusion of RTX last month and came down with a lung infection shortly after.
:crying: isn't it time for some peace for you ? :hug1:

Geoff
04-18-2014, 07:21 PM
Hi Alysia and many thanks for this thread and your love and support. I do feel better, especially the past 2 days, (must have been all the birthday cake!)
However I will contact the crew at Adds for a referral and above all "peace of mind".
Despite the overall tone of this thread, I believe it is best to know the cause and effect that fills our Weggie lives, hence my original post on this forum, "Glad to be diagnosed".

me2
04-19-2014, 01:12 AM
Wow, you found some really relevant info Alysia. Thanks. It is always better to know more. I was not aware of much of this. Honestly, I was kind of taking a break from years of always looking for answers
and keeping up on the latest. -- Now, you , and others, are doing it for me . ha Thanks again.
And yes, my sinus are doing better. Unfortunately I went into a flare right after they were starting to heal well but even in the midst of that I could tell I was better off than before.

My recent arguements with my doc will lead me to my next question. How much infection do we carry around in our sinuses as WG patients and how aggressive should we be in treating this? I dunno
Is it possible there is more going on than is being generally diagnosed and treated and leads to a fair amount of our difficulties? I dunno

Thanks again for the Rituxan info- relevant to so many of us. And the hug blah blah blah, mushy stuff, blah blah:rolleyes1:

Alysia
04-19-2014, 01:28 AM
:lol: me2. lots of questions remained open....
Geoff, maybe your docs will be able to say more about it. please update us.
I hope we can find some answers....
anyway, we don't have much choice :sad:
at least we are together in this....
thanks for being here. I love you all :love: :hug1:

MaxD
04-22-2014, 01:40 AM
Just adding my 2c here. First, we have to be aware of the possible side-effects of any drug we take. Yes, Rituxan does compromise our immune system - that's exactly what it is supposed to do! Before starting Rituxan treatment, my doc had me checked out for a variety of infections, including TB, Hepatitis B and HIV, among others. She also started me on Bactrim 2 weeks before treatments (to ward off pneumocystis pneumonia), and I'm already on steroids which are being tapered as per the RAVE study from 3 years back. Note that steroids are used to fight off any lung infections - so between the Bactrim and the steroids I feel well covered (fingers crossed!).

Second, I went over the references Alysia posted (thank you for that!). These are older than the RAVE study. Also, if you read carefully, the papers address a different population - patients being treated primarily for Lymphoma, with Rituxan and chemotherapy, and do not differentiate between patients with/without prior lung infections. The conclusions apply "under specific circumstances," as one of the papers states upfront in the abstract.

So, we shouldn't jump to the conclusion that Rituxan is a "very strong" drug that causes lung infections. Yes, it may result in lung infections if one is already compromised and one must always be watchful. And, no it is NOT a very strong drug, especially in comparison with Cytoxan (which provably increases the risks of bladder cancer and lymphoma several fold). It is a LESS toxic, biologic drug that targets B-cells, and not everything in its way like chemotherapy does. The risk of PML is extremely low (as my doc put it, infinitesimal).

I am grateful that my docs are treating me with Rituxan, even as I am aware of possible complications of a compromised immune system. But I agree with my docs, and the RAVE study, that it is the best available option for me.

Alysia
04-22-2014, 02:23 AM
WOW, Thank you so much Max for the info and the thinking :thumbsup:
can you tell more about the RAVE study ?

Geoff
04-22-2014, 03:19 AM
Great to get feed back from Dr Jayne who wants me straight into Clinic for a check up and CT scan. His response was that i had a persistent chest infection and wouldnt comment within the framework of an email as to any connection with my 2 year RTX IV. I will however take the opportunity at Clinic to discuss, altho Dr J is away on holiday.
For myself, I am sleeping better and feeling as tho i have good energy levels. Still persistent cough and sore chest, still onwards and upwards!

DEE
04-22-2014, 05:03 AM
Hope you get all the right answers from your clinic visit. I've just slept for 24hrs straight don't know why but feel better than when I went to sleep:rolleyes1: x

MaxD
04-22-2014, 05:26 AM
Hi Alysia,

Here is the paper describing the results of the RAVE study:

http://www.immunetolerance.org/sites/files/2010_NEJM_Stone.pdf

It's very clearly written, and the study included most of the preeminent vasculitis centers in the US. By the way, it was on the basis of this study that the FDA approved Rituxan for GPA in 2011. I haven't looked at ongoing studies, but it sure would be nice to see results of longer-term investigations. One problem may be that there are relatively few GPA patients, and while some of our symptoms are common to all of us, many are not, we're spread out age-wise, etc. So by the time our population is carved up according to different criteria, each category has small sample size that it's hard to draw conclusions with high degree of statistical confidence.



WOW, Thank you so much Max for the info and the thinking :thumbsup:
can you tell more about the RAVE study ?

Alysia
04-23-2014, 02:33 AM
Thanks Max :thumbsup: comforting info.
Geoff, I hope you will continue to feel better :hug1:you are so blessed to have your doc. please let us know what he will say.

Alysia
05-03-2014, 10:36 PM
I just saw this one on the vasculitis group:
Late Infections Seen With Rituxan in Vasculitis (http://www.medpagetoday.com/MeetingCoverage/BSR/45528)
2 important points in it:
1. The serious infections were more common among patients with these subnormal IgG levels.
2. None of the patients have died, and there were no opportunistic infections suggesting loss of T-cell function.

kelly anne
05-03-2014, 10:52 PM
I thought this was common knowledge and the reason I was prescribed Bactrim for the 6-month life of the rituxan...to avoid lung infection.

annekat
05-04-2014, 12:03 AM
A lot of us take Bactrim for that reason, to prevent a certain opportunistic lung infection while on any immunosuppressant. That part is common knowledge. The discussion about lung infections after RTX seems to be a little different.... since I'm not on RTX and never have been, haven't looked into it that deeply, but it seems to be a more unexpected development, different infections, maybe, or coming about for different reasons? This thread has been going for awhile and maybe looking at the beginning of it will shed some light on what is being said other than just what we take Bactrim for. In any case, I feel good taking Bactrim for whatever it might prevent or control.

me2
05-04-2014, 01:00 AM
Bactrim was in use for us long before Rituxan was invented. The initial reason was to prevent Staph infection which is unique in its ability to cause WG relapse. The bactrim is prophalactic for Staph infection.
Well, it WAS. I think the reasoning might now be expanded with the use of Rituxan and the risks it poses for infection- although I don't know that.

annekat
05-04-2014, 11:11 AM
I have always read on here that Bactrim is prophylactic for pneumocystiis carnii, as described in this article:
Pneumocystis carnii Pneumonia: A Clinical Review - American Family Physician (http://www.aafp.org/afp/1999/1015/p1699.html), and that that's why it is primarily used for us. That doesn't mean that it could not also be used as prophylactic for staph or other things. Maybe, as you say, Kirk, it was used for us to prevent staph early on, before the advent of AIDS, when that particular form of pneumonia could have become more recognized as something to use Bactrim as a prophylactic for. Although it would already be known about in relation to immunosuppressed patients, I'd think, before AIDs. I sort of skimmed the article. I'll try looking up Bactrim for staph next. And of course, if it helps with whatever people might get after using RTX, or anything else, great.

annekat
05-04-2014, 11:43 AM
The type of pneumonia mentioned above has always been referred to as PCP, and now the more common name for it, and considered more correct, is P. jirovecii pneumonia, but it is still going by the same abbreviation, PCP. I'm sure this is the one most often mentioned on here for why we use Bactrim.

Have found a lot on using Bactrim to treat different forms of staphylococcus aureus, including MRSA, but not so much on prophylactic use for that, although I think there was some.... no more time to investigate this right now.

me2
05-04-2014, 02:22 PM
Bactrim was at one time, and I assume it still is, used prophylacticly for pheumocystiis carinii as described in the article you gave for aids patients. As I remember it they were finding that this infection was becoming the highest cause of death for people with acquired immune deficiency from this virus and Bactrim was used for that.

I don' think that our immune deficiency is actually what we are using Bactrim for. Not for pcp.

At one of the WG conferences in Kansas City I got to attend a small seminar and talk directly with the doctor who discovered that Bactrim had unique use in WG patients. His discovery was that Bactrim alone in some rare cases could induce remission of Wg . This was unheard of. But as one of the citations states --
In Wegener's Granulomatosis (WG) chronic carriage of Staphylococcus aureus (S. aureus) is associated with a strongly increased risk for relapsing disease.

I couldn't find the definitive article I was looking for by Dr DeRemee so I have to use the shot gun approach and just give the literature I could find- it consistently says pretty much the same thing:

http://www.ncbi.nlm.nih.gov/pubmed/8880118

JAMA Network | JAMA Internal Medicine | Treatment of Wegener's Granulomatosis With Sulfamethoxazole-Trimethoprim (http://archinte.jamanetwork.com/article.aspx?articleid=615420)

Co-trimoxazole and prevention of relapses of P... [Eur J Med Res. 2009] - PubMed - NCBI (http://www.ncbi.nlm.nih.gov/pubmed/20156769)

Vasculitis and infections: contribution to the... [Autoimmun Rev. 2008] - PubMed - NCBI (http://www.ncbi.nlm.nih.gov/pubmed/18703171)

[Wegener's granulomatosi... [Rev Med Inst Mex Seguro Soc. 2006 May-Jun] - PubMed - NCBI (http://www.ncbi.nlm.nih.gov/pubmed/16870120)

The relation between Staphylococcus aureus and We... [Intern Med. 2003] - PubMed - NCBI (http://www.ncbi.nlm.nih.gov/pubmed/14518661)

Infections and Wegener's granulomatosis--a cause and eff... [QJM. 1997] - PubMed - NCBI (http://www.ncbi.nlm.nih.gov/pubmed/9205673)

Staphylococcus aureus, tri... [Sarcoidosis Vasc Diffuse Lung Dis. 1996] - PubMed - NCBI (http://www.ncbi.nlm.nih.gov/pubmed/8946595)

What is the evidence for prophylactic an... [Curr Opin Rheumatol. 2011] - PubMed - NCBI (http://www.ncbi.nlm.nih.gov/pubmed/21346576)

Chronic crusting, nasal carriage of Stap... [J Physiol Pharmacol. 2008] - PubMed - NCBI (http://www.ncbi.nlm.nih.gov/pubmed/19218710)

Staphylococcus aureus and Wegener's granulomat... [Arthritis Res. 2002] - PubMed - NCBI (http://www.ncbi.nlm.nih.gov/pubmed/11879541)

As a side note , I met with Dr Deremee after the seminar and told him I was allergic to Bactrim. He told me that (at that time) it was not known which of the two agents in Bactrim were responsible for the beneficial result or whether both trimethaprime and sulfamethoxazole were necessary. He suggested I try the trimethaprime if I could not use Bactrim and see what happened. Most likely the sulfamethoxazole is the component that people have an allergy to.

Well, I came home and started doing my own research on Bactrim use (the internet had just been invented) and found it was being used largely for aids patients with pcp. It was then that I discovered there was a desensitization protocol for Bactrim with a very high success rate. I printed out the article I found and took it took to my doctor. He had outlined some treatment using other drugs until I showed him what I had found . When I showed him the info he said "Lets do that" .
I was able to desensitize to Bactrim and can still take it now. What is striking to me , even now , is that at that time, even Dr DeRemee was not aware of the desensitization protocol or he would have told me. It is common knowledge now in the treatment of wg and use of Bactrim.
Sorry to be so long winded but you see way back then I had to work very hard to get information to stay alive.

me2
05-04-2014, 02:32 PM
Well, I didn't drone on long enough I wanted to add one more thing (LOL). On the Rituxan issue and Bactrim.

I know that with Rituxan use we are now at increased risk of infection. We already were with Cytoxan and prednisone so I'm not sure what the current thinking is regarding Bactrim use and Rituxan. I have not seen any articles on it. But then I don't work that hard at staying informed anymore either.

I would guess they would say something like "Well, they already take Bactrim for staph, it can't be anything but helpful for any other opportunistic infection caused by Rituxan"
Just a guess. Drone finished.

Alysia
05-04-2014, 02:36 PM
WOW kirk, such an impressing research :thumbsup:
it will take me some time to look at all the links, but meantime, thank you so much !
I wanted to say that bactrim IS NOT effective to all infections. for example, I have many UTI's, and in all cases, bactrim didn't fit to cure it.

me2
05-04-2014, 03:10 PM
Too bad Bactrim doesn't help your UTI's Alysia. That would have been a good co-incidence.

I will add one little drone addendum. I recently had sinus surgery to correct severe structural damage to my sinuses from years of having WG. I was having infections that would not go away and was on antibiotics for a long time (Cipro, not bactrim) The ENT fella took a culture of what was causing me so much trouble.

When I saw my Rhuemy I said "Guess what the surgeon found growing in my sinus"
He played along with me and said " Staph aureous"

I said "Bingo, score one for the Rheumy"

He said "It wasn't that hard of a guess, many WG patient have staph growing their sinus"

Reading the above citations you get the picture why.

Alysia
05-04-2014, 03:14 PM
I forget to mention that I can't use bactrim anymore because it elevated my liver functions beyond normal.
I am glad, Kirk, that you are recovering. take care :hug1:

me2
05-04-2014, 03:17 PM
Thanks Alysia. I can't take Bactrim right now either because it is contra-indicated with methotrexate. You take care too. Its good to see you here.

annekat
05-04-2014, 11:33 PM
Kirk, I take Bactrim with MTX and I think a few of us do here. I know there are contraindications and can't explain them but know that the doc thinks it's OK as long as certain things are checked for in the blood on a regular basis. I'll never have the time and energy to do the kind of research you have done in the past to be able to explain things precisely, so am thankful that the info is more out in the open now via the forum or the greater knowledge of the medical community, or whatever. As long as I don't have any problems with the Bactrim/MTX combo, then I will keep taking it.

Thanks for all those links and the work you went to to put them into your post. I had read about Bactrim being used to keep people in remission and also about the s. aureus issue, that many of us are or could be carrying it. I'm sure it is true that Bactrim is used against that but don't see why it wouldn't also be used to prevent PCP, after all, we don't have AIDS, but our immune systems are compromised for a different reason, and we would still be susceptible to an opportunistic lung infection such as that. Quite possibly Bactrim helps us in many ways but that is just the one that gets repeated because it is easy for them rather than going into all the details.

My pharmacist assumed I was taking Bactrim against UTI's and said that many people take it for that. But I guess it doesn't work for all of them, all the time.

I'll take a look at some of those links when I get the chance.

gunnyl
05-09-2014, 11:47 PM
When I was first diagnosed I, it presented in my lungs and I was coughing up significant amounts of blood. I have gone through Citoxan, Methotrexate and Imuran mixed with Prednisone. I tend to flare about every two months though and the end of last month started to relapse but was able to catch it quickly because this disease has made me so much more in tune with my body.
I start Retuxan infusions on the 21st and am hoping that it will help me get into remission for a longer basis. I have a friend who did Retuxan infusions and was symptom free for two years afterwards.
Problem with this disease is that there really is no standard of treatment for it. They try a very small handful of different drug combinations and hope that they work for our particular situation. Unfortunately all of the drugs have side effects and we have to be careful and cognizant of what's going on with our bodies so that we can make changes when required. Retuxan is not a wonder drug and it's not going to be the right drug for every situation. If you are prone to lung infections you might want to steer towards another treatment option.

Alysia
05-10-2014, 08:41 PM
I start Retuxan infusions on the 21st and am hoping that it will help me get into remission for a longer basis.
.
If you are prone to lung infections you might want to steer towards another treatment option.

good luck with your RTX. I hope it will bring you to long lasting remission.
btw, we are all prone to lung infections... :sad: