EBV in bone marrow of rheumatoid arthritis patients predicts response to Rituximab

[SOC]

Sorry Tristen, i dont know how to interpret these, but i am close to getting the same tests done myself. Thing is, i am thinking the same thing as you - are the tests reliable? Well, they are reliable if the problem is in your blood i guess, but if they are intracelular or in the bone marrow, or hiden elsewhere then i guess the tests arent going to pick up on it.
That being the case, i am thinking about going straight to antivirals instead. Difficult.

IMO, current standard tests for herpesviruses don't mean much for PWME. To get a feel for the problems with herpesvirus tests, read this chart about HHV-6 tests: http://www.hhv-6foundation.org/patients/hhv-6-testing-for-patients. Tests for other herpesviruses can have similar problems. These tests were not designed to detect reactivated infections, particularly in people with immune abnormalities.

As I understand it, the main reason EBV was dismissed years ago was that some patients' tests indicated that they had never been infected with EBV (negative IgG) and therefore EBV could not be the cause of ME. It was not considered that 1) those patients could be not producing enough antibodies to be detectable because of an immune deficiency, or 2)one of several herpesviruses might cause ME, not only EBV. HHV-6, for example is looking like a likely candidate.

IMO, herpesvirus tests are close to worthless for PWME. And it's extremely difficult to get a doc to prescribe a potentially dangerous antiviral like Valcyte without some evidence of an infection. Valtrex is pretty safe, though, so you might convince a doc to prescribe it, but not for the length of time usually needed for PWME.

 

[heapsreal]

I have tested positive to ebv with IgG antibodies which are suppose to be life long and then several years later before i used any antivirals i tested neg to ebv IgG, i believe this happen in some cfs people in lake tahoe which is documented in oslers web. I wonder if our immune systems are sometimes not capable of making antibodies if to depressed??

cheers!!!

 

[snowathlete]

OK, if the problem (lets suppose its a herpes virus for the moment) is in the bone marrow and the bone marrow doesnt allow blood flow into the bone marrow, then that explains why anti-virals make some improvement with a number of people, but doesnt cure them - because the virus is locked away in the bone marrow. Maybe even causing changes in the blood cells being generated...

Could you get an anti-viral injection directly into your bone marrow? Do they do this for any other illnesses?

 

[heapsreal]

OK, if the problem (lets suppose its a herpes virus for the moment) is in the bone marrow and the bone marrow doesnt allow blood flow into the bone marrow, then that explains why anti-virals make some improvement with a number of people, but doesnt cure them - because the virus is locked away in the bone marrow. Maybe even causing changes in the blood cells being generated...

Could you get an anti-viral injection directly into your bone marrow? Do they do this for any other illnesses?

Also possibly in nervous system as well as intracellular. I think from memeory for them to replicate they have to come back into the normal circulation etc, this is when the antivirals can get at them, but antivirals dont kill these viruses, just stop them replicating. I think this is why dr lerner has his patients on antivirals for a few years as it takes awhile for these viruses to 'burn' out. SO antiviral basically help lower the viral load to a level that the immune system can now handle it or like already mentioned, burn out.

This might be a strange comparison or example but i think of antivirals as like desexing every male on the planet, after 100 years or so there would be no humans left. Antivirals are doing something similar to herpes viruses, so we stop them making more viruses and wait for them to die out. Also why people refer to viral load, as the amount of virus circulating is slowly coming down, after 3 months on av's your viral load should be lower??? As your viral load comes down there should be less strain on your immune system and it should be able to fight other pathogens etc??

cheers!!!

 

[snowathlete]

I think from memeory for them to replicate they have to come back into the normal circulation etc, this is when the antivirals can get at them, but antivirals dont kill these viruses, just stop them replicating.

What if they can replicate in the bone marrow also though? Why not, its nutrient and blood rich. Just an idea - what do you think?

Has anyone looked at deceased ME patients and looked at what is in the organs etc, including the BM?

 

[heapsreal]

What if they can replicate in the bone marrow also though? Why not, its nutrient and blood rich. Just an idea - what do you think?

Has anyone looked at deceased ME patients and looked at what is in the organs etc, including the BM?

it wouldnt suprise me if it did rrplicate else where, theres alot they still dont know about. I just recall reading that they only rrplicate in blood, but our immunity could also throw a spanner in thr works too. Might be why chemo treatments help cfs too???

 

[user9876]

i dont know how safe it is, but from what i read bone marrow transplants are quite easy compared to how they used to be. As i understand it they suck out some bone marrow from the doner, then transfuse it with the patients blood (presumably after having sucked out some of their bad bone marrow) and then it goes into the patients veins and the blood carries it to the bones itself.

im super interested in this, it could be a major component of treatment in the future.

Its a little more complex than that assuming you are getting someone elses bone marrow rather than your own healthy cells replanted. For a leukemia patient there is a first stage of chemo to kill the leukemia and this should allow normal bone marrow to regrow. The second stage is to have more conditioning chemo and radio theropy that kills of the bone marrow that is there. Both these are quite severe things and they don't do the full chemo on people who are not healthy as it might kill them. They are doing a less intense conditioning chemo for people who are not fit enough to go through the full process. I believe that this less intense version is still quite an experimental thing.

After that they do the bone marrow infusion. There is a very long recovery period and various risks including infections, graft vs host disease and rejection. If the chemo didn't work well enough then there is a risk that the host bone marrow regrows not the donor (not a problem if you have donated your own cells). My experiance is that this last stage is done in an iscolation ward until the blood counts start to rise as infection control is absolutly key. For some time afterwards people are also given anti virals, anti fungals and an immune suppressant to help manage graft vs host disease. Then you have a lifetime on antibiotics.

Infections are be a real problem some can be fought with anti virals and anti biotics they can also look for granucyte donors what is some of the white blood cells that fight new disease.

I've no idea what the survival rates are my guess is it depends on how healthy you are.

There is quite a large database of donors now.

I know someone with FM/ME who has just had a transplant those symptoms seem better but hard to tell (too early). Someone posted on this thread that someone they new had a transplant and that made the sympoms go but they came back later. If ME/FM are auto immune diseases (perhaps as the rituximab trial suggest) a bone marrow transplant should be a cure but if you are transplanted back with your own bone marrow then it may reoccur. I've seen a couple of papers from the late 90s talking of using bone marrow transplants for RA but I think they concluded that they were too dangerous. I think it is interesting that auto immune diseases are inherited and tend to effect women more than men which seems to corrospond to some of the ME literature.

I think it would be interesting to create a database of people who have had various forms of treatment (such as BMT and chemo) and look at how there ME/FM symptoms were affected. This might provide a clue to researchers. I believe with the Rituximab trial they were oncologists who noticed that they also affected the ME symptoms. perhaps a wider collection of what worked and what had no effect would help in deducing some form of causal relationships or ruling out others factors.

 

[Nielk]

I was just diagnoses with Rheumatoid Arthritis this past week. I have been suffering from painful swollen hands for a long time. I finally went to a rheumatologist who found high antibodies load in my blood. A sonogram of my hands confirmed widespread inflammation.

I was put on Methylprednisolone as well as Plaquenil. I wonder though now after reading this thread if i should not have asked for Rituximab with the hope that it would relieve my ME/CFS symptoms as well?

 

[Kati]

Hi Nielk,
so sorry for your new diagnosis. As far as I understand, Rituxan is not a first line of treatment for RA. I have been on Plaquenil for about 12 years, (stopping to be tested at Dr Klimas' office) and it's done wonders for me when it kicked in-know that it takes a few months before it works optimally.

i remember that the brand name drug was easier on my stomach than the generic brand, and I took my 400 mg in the evening/ bedtime with food.

RA has dedicated medical specialty and millions in research, so hopefully competent health care won't be a problem for you.

And back to the topic of the bone marrow finding predicting response for Rituxan, I shared it with my ME specialist and he was very interested.

 

[Nielk]

Thanks @Kati -

I too was prescribed 400mg a day but, my drugstore gave me the generic - hydroxychloroquine.
This is only the third day that I have been taking it and feel somewhat nauseous. I am not sure if it's from this or the steroid that I started at the same time. Either way, I am probably better off taking it at night as you said.

It's good to hear that it has helped you. My doctor said not to expect quick relief. he said it will probably take at least a month for it to start working.

Yes, I have experience healthcare as it should be with this problem. If only I could say the same for my ME/CFS!

 

[Kati]

Both drugs are hard on the stomach, so do make sure you take food to 'coat' your stomach. Usually steroids are taken in the morning due to the fact that it stimulates and may cause insomnia.

The plaquenil I got read plaquenil on the tablets, and my insurance company ( Canada)did not cover it, but covered the generic.Wen they switched me to the generic it made a big difference for me. there was something about how well coated Plaquenil is that made the differencefor me. And the difference was 60$ per refill, (can't remember how long was the refill for) , but well worth it in my case. If this continues to be a problem, I would not hesitate to ask your pharmacist for a better alternative. It is a very good drug and non steroid, which is better for you in the long run.

 

[Nielk]

I really appreciate all this advice @Kati , as I am so new at this. My doctor said that he would not like to keep me on the steroids for longer than two months but it sounds like the Paquil will be long term.

 

[Kati]

It is imperative you get yearly eye exam while on Plaquenil and that you report vision changes. I cross my fingers it works well for you. I had small joints pain, fingers and toes,and was started on Plaquenil and high dose NSAIDS, and when they tried to take off the Plaquenil, the pain came back. (I have never been diagnosed with a rheum condition, just very high ANA)

i have now been off it for nearly 4 years, sick with ME for 5+

 

[Nielk]

I have positive ANA as well as high anti CCP which is a distinct marker for RA. The doctor did tell me about potential eye problem. Thank you for the heads up.

Are you still having symptoms since you have been off the med?

 

[Kati]

Fingers and toes are fine, bigger joints have been sore on and off. The bigger issue is ME in case you missed it somewhere else, Rituximab has not proven helpful in my case.

 

[snowathlete]

I was just diagnoses with Rheumatoid Arthritis this past week. I have been suffering from painful swollen hands for a long time. I finally went to a rheumatologist who found high antibodies load in my blood. A sonogram of my hands confirmed widespread inflammation.

I was put on Methylprednisolone as well as Plaquenil. I wonder though now after reading this thread if i should not have asked for Rituximab with the hope that it would relieve my ME/CFS symptoms as well?

Sorry to hear your news Gabby. I hope the treatment works wonders for you though. I am taking steriods at the moment for my UC - not been as horrible as some people say, so hopefully it'll be alright for you too. One thing I would say though is don't forget to take the darn things, which is what I have just realised I forgot to do today. I was about to got to bed, and just spotted my error, so I have just taken my dose. Unfortunatley this probably means that I wont have much luck getting sleep tonight!

Rituximab is well worth considering I'd have thought. If I were you I would read up on its use in RA and then consider asking about it if the steriods and plaquenil don't make things a lot better?

 

[Nielk]

Thank you @snowathlete - I appreciate it. I hope that the steroids are helping you as well. I used to be on it for years when I had active Crohn's. I know that it's very dangerous to skip dosages. It's good advice though not to take it too late in the day. I hope you sleep well!

 

[Firestormm]

I was just diagnoses with Rheumatoid Arthritis this past week. I have been suffering from painful swollen hands for a long time. I finally went to a rheumatologist who found high antibodies load in my blood. A sonogram of my hands confirmed widespread inflammation.

I was put on Methylprednisolone as well as Plaquenil. I wonder though now after reading this thread if i should not have asked for Rituximab with the hope that it would relieve my ME/CFS symptoms as well?

Thanks @Kati -

I too was prescribed 400mg a day but, my drugstore gave me the generic - hydroxychloroquine.
This is only the third day that I have been taking it and feel somewhat nauseous. I am not sure if it's from this or the steroid that I started at the same time. Either way, I am probably better off taking it at night as you said.

It's good to hear that it has helped you. My doctor said not to expect quick relief. he said it will probably take at least a month for it to start working.

Yes, I have experience healthcare as it should be with this problem. If only I could say the same for my ME/CFS!

Damn! I did not know the details - you never said! So sorry to hear this Gabby - on top of everything else I really hope that with the right treatment and once it has settled you find some relief from the symptoms.

Mum has RA too. Are you in a lot of pain? You know Mum has often said that she feels she has ME because many of our symptoms and our level of functioning seem very similar. I do hope the diagnosis and treatment might relieve some of the other symptoms you have had to endure.

It would be interesting for me to learn if they do and I can then let Mum know as well. Perhaps it's worth having an RA thread somewhere? Makes me wonder how many others there are with a diagnosis of ME who also have RA.

Maybe Ritux might be an option under the circumstances - I have a friend here in the UK with ME who was treated with Ritux by Kogelnik though it didn't work for him. But perhaps with the RA as well it might work for you, if the currents medications don't?

You did that massive article as well. How the heck did you do that with swollen hands?! Amazing.

 

[Nielk]

Damn! I did not know the details - you never said! So sorry to hear this Gabby - on top of everything else I really hope that with the right treatment and once it has settled you find some relief from the symptoms.

Mum has RA too. Are you in a lot of pain? You know Mum has often said that she feels she has ME because many of our symptoms and our level of functioning seem very similar. I do hope the diagnosis and treatment might relieve some of the other symptoms you have had to endure.

It would be interesting for me to learn if they do and I can then let Mum know as well. Perhaps it's worth having an RA thread somewhere? Makes me wonder how many others there are with a diagnosis of ME who also have RA.

Maybe Ritux might be an option under the circumstances - I have a friend here in the UK with ME who was treated with Ritux by Kogelnik though it didn't work for him. But perhaps with the RA as well it might work for you, if the currents medications don't?

You did that massive article as well. How the heck did you do that with swollen hands?! Amazing.

Thank you @Firestormm -

I have a lot of pain in my hands and am restricted with what I can do with them now. I can't grab anything nor make a fist. I can't hold a pen nor a paintbrush which is really disturbing for me because I have not been able to do my artwork now for months. I am able to somewhat type on the computer though.

My hope is that, now that I have a firm diagnosis and have started on aggressive treatments, that it will start to slowly resolve itself. I didn't know anything about RA before and I thought at first that it might be Lupus since my mother suffered from Lupus. After more detailed lab work and the sonogram on my hands, they were able to give me a definite RA diagnosis.

I have been reading some about RA and it does seem that many symptoms overlap. The past few months I have been feeling weaker than my regular weak state and very exhausted.

To be honest, i am not sure what is happening with me because besides this diagnosis, I have suddenly signs of diabetes too and am being evaluated for that as well. My latest bloodwork also showed high liver enzymes so I'm going for a sonogram of the liver as well. It seems like I am falling apart at the seams.

I'll tell you something funny though; I am certainly enjoying seeing clinicians taking me seriously! If only they would treat me the same way when I come in with my ME/CFS issues!

 

[Kati]

Hang in there Nielk. We'll walk the walk with you.