Started Rituximab at OMI/Center for Complex Diseases

pogoman

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Yes, I have you im my list of patients who have taken rituximab. Have you seen any improvements in ME/CFS symptoms?

Do you satisfy the Canadian consensus criteria for ME/CFS by the way?
Ritux has helped with lessening of symptoms overall, I can tell during the last month before each treatment that its worn off.
It also seems to have slowed or stopped the muscle necrosis in my leg where the myopathy is, doing it every 6 months.

On the Canadian criteria, I have met all the requirements at one time or another in the past.
The ritux and taking mito supplements has helped tremendously the past few years along with meds to control neuro issues and muscle hypertonia.

They've become much milder to the point where my spinal pain has become more prominent during sleep and in the morning when I wake up.
Thats why I pushed my endo to start TRT after MRI's found I have scoliosis and spinal arthritis, the bone density x-rays she ordered show I have osteopenia so I'm taking more calcium and have vit K on order.
 

Hip

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Ritux has helped with lessening of symptoms overall, I can tell during the last month before each treatment that its worn off.
Can you quantify that improvement in symptoms in terms of where you were on the ME/CFS scale of: very severe, severe, moderate, mild, remission before rituximab treatment, and where you are on that scale after treatment?

Have you moved up by one level on that scale (eg, moving from severe to moderate, or moderate to mild)? Or perhaps moved up by a half level?
 

pogoman

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Can you quantify that improvement in symptoms in terms of where you were on the ME/CFS scale of: very severe, severe, moderate, mild, remission before rituximab treatment, and where you are on that scale after treatment?

Have you moved up by one level on that scale (eg, moving from severe to moderate, or moderate to mild)? Or perhaps moved up by a half level?
Some of the criteria is very subjective but let me try to quantify it, some of them overlap.

1. fatigue- very severe and its improved to severe/moderate. I've learned to know how much I can do before I hit the wall but sometimes I miss.

2. PEM- very severe during the start of hot weather during summer, now its moderate.

3. Sleep- severe and now moderate. I still get muscle hypertonia but the morning muscle pain is whats really gotten better.

4. Pain- omg yes it was very severe to where I was on opiate meds.
Mito supplements have helped but the muscle pain has improved to where its controlled by otc and non-opiate meds to moderate.

5. Neuro- kind of a wash, I take oxcarbazepine for what I call nerve jolts mainly at night, with the spine issues now predominating. Probably was at and still at severe to moderate.
Short term memory seems to have improved tho and I can concentrate to where I read more like I used to do before this all started.

6. Of the three categories, the main ones I suffered were heat intolerance, night sweats, uncontrolled sweating during the day especially in the morning, light headedness standing up, IBS for a long time.
Ritux helped with the IBS and lightheadedness, but not heat or sweating. The three weeks I've been on testosterone no more night sweats and uncontrolled sweating tho.
 

pogoman

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So when you say your fatigue and PEM were very severe before rituximab, you are saying that you were bedbound 24 hours a day, except for a few minutes each day to go to the toilet?

Very severe ME/CFS means bedbound 24/7.
Not quite that bad except maybe the first couple times I had PEM in hot weather, had to stay inside the house to recuperate for a couple of days just sleeping and not moving.
Put it this way, I barely had enough energy to put stuff away and go inside and I felt like I could collapse at any minute.
That was several years ago before I learned I had to ration energy expenditure and before the rituximab.
 

Hip

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Not quite that bad except maybe the first couple times I had PEM in hot weather, had to stay inside the house to recuperate for a couple of days just sleeping and not moving.
So maybe you had severe ME/CFS, rather than very severe? Severe is where you are in bed most of the day and night, but up for a severals hours a day, probably mostly on the sofa, maybe watching TV or using a laptop. Would that better describe you before rituximab?

And after rituximab, would you say you are now at the moderate level of ME/CFS? Moderate means you are out out bed all day (except perhaps for a nap for an hour or two during the day), but still fairly housebound, and don't leave the house much.
 

jaybee00

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Why have you been on rituximab for 2 years? Why is your physician giving you a medication that is not indicated for ME/CFS?
 
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pogoman

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So maybe you had severe ME/CFS, rather than very severe? Severe is where you are in bed most of the day and night, but up for a severals hours a day, probably mostly on the sofa, maybe watching TV or using a laptop. Would that better describe you before rituximab?

And after rituximab, would you say you are now at the moderate level of ME/CFS? Moderate means you are out out bed all day (except perhaps for a nap for an hour or two during the day), but still fairly housebound, and don't leave the house much.
Ok I didn't notice you had a link to descriptions of each level until now.
Basically without writing a book it would veer from moderate to severe with maybe a day or two of very severe when it got very hot.
Much of the time was having a various mixture of moderate and severe symptoms, a lot depended on how hard I pushed myself and the amount of prescription pain meds I felt I needed.
Thinking about back then, without those pain meds the symptoms would have been worse and I would have been unable to work.
Now, after ritux, various meds and supplements, its mainly mild. The test is helping with energy and sleep quality to the point I noticed I'm not having to do midday naps.
 

pogoman

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Why have you been on rituximab for 2 years? Why is your physician giving you a medication that is not indicated for ME/CFS?
I don't have ME/CFS, its not a diagnosis in the US and especially for Kaiser Permanente HMO that I'm a member of.

What I have is an unknown non-inflammatory myopathy in my right leg found by muscle biopsy in 2014, the year I joined this forum.
The working diagnosis is necrotizing autoimmune myopathy and ritux is one of the main drugs of choice for NAM.
I've already done ivig and methotrexate the past few years, ritux has helped the most.
NAM was almost unknown when I was diagnosed, Dr Christopher-Stine at John Hopkins led research into it when statin users started getting muscle damage after stopping statin drugs.

This also reminds me of my Invitae myopathy and nuero panel lab tests I had done in 2017 and 2018 by Kaiser.

I had several variants of unknown significance, for one of them the FBXO38 gene my test results made it into the NCBI Clinvar database.
With the muscle loss and now spinal issues starting to appear I am wondering if this is the actual disease.
Unfortunately until there is further research into this gene I won't know, thats why its a VUS.

https://www.ncbi.nlm.nih.gov/clinvar/RCV000651190/

Distal hereditary motor neuronopathy 2D (HMN2D)
Synonyms:HMN IID; NEUROPATHY, DISTAL HEREDITARY MOTOR, TYPE IID; SPINAL MUSCULAR ATROPHY, DISTAL, AUTOSOMAL DOMINANT, CALF-PREDOMINANT

If you click on the evidence tab this is what my test results state.


Description
This sequence change affects a donor splice site in intron 9 of the FBXO38 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FBXO38-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in FBXO38 cause disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
 
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So you are saying you think you are probably not an ME/CFS patient?
I interpreted what @pogoman said was this could be a coexisting illness with ME/CFS but Kaiser in the US does NOT recognize ME/CFS as a treatable disease. Kaiser is one of the largest medical groups in the US and it has NO physicians for ME/CFS, and rarely allows patients to see doctors outside of their group. So in effect Kaiser does not recognize ME/CFS.

My experience in the US has been that doctors don't generally believe in CFS as an illness. In Kaiser that is a fact as described by many patients.
 
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pattismith

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I don't have ME/CFS, its not a diagnosis in the US and especially for Kaiser Permanente HMO that I'm a member of.

What I have is an unknown non-inflammatory myopathy in my right leg found by muscle biopsy in 2014, the year I joined this forum.
The working diagnosis is necrotizing autoimmune myopathy and ritux is one of the main drugs of choice for NAM.
I've already done ivig and methotrexate the past few years, ritux has helped the most.
NAM was almost unknown when I was diagnosed, Dr Christopher-Stine at John Hopkins led research into it when statin users started getting muscle damage after stopping statin drugs.

This also reminds me of my Invitae myopathy and nuero panel lab tests I had done in 2017 and 2018 by Kaiser.

I had several variants of unknown significance, for one of them the FBXO38 gene my test results made it into the NCBI Clinvar database.
With the muscle loss and now spinal issues starting to appear I am wondering if this is the actual disease.
Unfortunately until there is further research into this gene I won't know, thats why its a VUS.

https://www.ncbi.nlm.nih.gov/clinvar/RCV000651190/




If you click on the evidence tab this is what my test results state.

@pogoman, your illness seems quite serious and complexe, involving both neuropathy and myopathy.

Sometimes, I feel it may be better if docs doesn't care about the ME/CFS diagnosis, it may provide more opportunities for investigations ...
FBX038 gene mutation can produce Distal Hereditary Motor Neuropathy. It's a peripheral large fibers neuropathy.

Do you know if you had nerve conduction velocity testing showing any defect?
 

pogoman

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So you are saying you think you are probably not an ME/CFS patient?
At the time in 2014, I thought it ME/CFS a possibility but I was looking more for interpretation of my 23andme results.
PR was one of the few sites talking about that.
wigglethemouse hit the nail on the head about Kaiser.

I interpreted what @pogoman said was this could be a coexisting illness with ME/CFS but Kaiser in the US does NOT recognize ME/CFS as a treatable disease. Kaiser is one of the largest medical groups in the US and it has NO physicians for ME/CFS, and rarely allows patients to see doctors outside of their group. So in effect Kaiser does not recognize ME/CFS.

My experience in the US has been that doctors don't generally believe in CFS as an illness. In Kaiser that is a fact as described by many patients.
Exactly! I had been pushing my doctors the last 15 years something was wrong and not until 2013 when they found I had high cpk did they start seriously looking to see what I had.
I had mentioned ME and lyme and he scoffed.
At my Kaiser the older neurologists have retired and younger ones with knowledge of the newer diseases are coming in.
The new neuro I had for a year until he left Kaiser was very knowledgeable, he did the tests that found spinal issues like scoliosis, radiculopathy and degenerative arthritis.
I told my earlier neuro's about the same issues and they never would try to find out what caused them, they just lumped it under the myopathy.

@pogoman, your illness seems quite serious and complexe, involving both neuropathy and myopathy.

Sometimes, I feel it may be better if docs doesn't care about the ME/CFS diagnosis, it may provide more opportunities for investigations ...
FBX038 gene mutation can produce Distal Hereditary Motor Neuropathy. It's a peripheral large fibers neuropathy.

Do you know if you had nerve conduction velocity testing showing any defect?
Yes its turned very complex the past year.
I've had several emg/needle conduction tests since 2014, a couple in 2019 I think.
That is when the spinal issues started to be recognized.


@pogoman The gnomAD database (genome aggregation database from the Broad Institute) shows 1 person with this variation in the European, non Finnish population cohort database .
https://gnomad.broadinstitute.org/variant/5-147790330-T-A?dataset=gnomad_r2_1

There is a high confidence prediction that the variant leads to loss of function (pLoF)
View attachment 38410
Thank you for the link, will have go thru them and figure out what they mean lol
I see it links to my Clinvar results page but its incorrect about lineage and sex.
On my fathers side its generally northern European and on my mothers side its Japanese and I'm male.
I had found out Invitae submits positive test results to Clinvar so I waited to see if my FBXO38 results would be listed, they did show up last year.

This is what I received from my Invitae myopathy and neuro panels in 2018 about the gene splice.
It was potentially eligible for their VUS resolution program but as my parents are dead and nobody in the immediate family have the same issues I didn't pursue it.

Invitae1.jpg
 
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I see it links to my Clinvar results page but its incorrect about lineage and sex.
On my fathers side its generally northern European and on my mothers side its Japanese and I'm male.
They were right about Northern European ancestry!

1595797120649.png


Regarding sex there is an FAQ HERE where they described sex is a calculation
How is sex determined for gnomAD samples?
We used a combination of X-chromosome homozygosity (F-stat, impute_sex function in Hail) and X and Y chromosomes normalized coverage to assign sex for each gnomAD sample. Note that we used different combination of metrics (mostly due to their availability) for the different gnomAD datasets (see below for details). The F-stat was computed for each sample using high-confidence QC SNVs (bi-allelic SNVs, LD-pruned to r2 < 0.1, with allele frequency > 0.1% and call rate > 99%) on non-pseudoautosomal regions (non-PAR) of the X chromosome. The normalized coverage was computed as the mean coverage on sex chromosomes / mean coverage on chromosome 20. The exact metrics and threshold used for sex assignment were as follows:
  • Genomes (gnomAD v3):
    • Males: chromosome X (non-PAR) F-stat > 0.2 & 0.5 < normalized X coverage > 1.4 & 1.2 < normalized Y coverage > 0.15
    • Females: chromosome X (non-PAR) F-stat < -0.2 & 1.4 < normalized X coverage > 2.25 & normalized X coverage < 0.1
  • Exomes (gnomAD v2):
    • Males: chromosome X (non-PAR) F-stat > 0.6 & normalized Y chromosome coverage ≥ 0.1
    • Females: chromosome X (non-PAR) F-stat < 0.5 & normalized Y chromosome coverage < 0.1
  • Genomes (gnomAD v2):
    • Males: chromosome X (non-PAR) F-stat > 0.8
    • Females: chromosome X (non-PAR) F-stat < 0.5