Need help, may have 2nd disease

Hi Lori,

I just did some research on CD4 and PID. Many things can affect the CD4 count so until you know more and they do this test a couple times, keep the faith. I know it is hard to see your baby ill. What I can get from my reading is that CD4 levels can change dependent on the time of day they are taken and can go down when other infections are present. They are a measure of total viral count in our system. I would assume PID would be one of these. It also lists pneumonia, HIV, and other things that can lower the count so I would be asking my dr. some questions about this. Could this be the result of an underlying and undiagnosed infection? Keep pushing for answers.

I was also able to find info stating IVIG is the treatment of choice for PID so your little boy is already getting the treatment he would require if it is infact PID.

Please keep us posted and I hope you can find comfort in talking to people on this forum until you are able to get answers. If I can do more research for you, say the word.

Take care.
Janet

I wonder, would a year of iv solumedrol cause such a low drop in t-cells? Steriods are systemic, affecting both T & B cells. Ritux would affect b-cells directly, but could there be a negative feedback to the t’s as a result?

Lori,

can you think back, and remember what immunizations Dell has had? Wondering if titres can be measured – might give a timeline when immune responded (or didn’t) in an appropriate manner.

Lori,
I agree the diaper rash has some connection. I remember reading something about fungus (diaper rash in this case) and cidp.
Try to ask about that 3g/kg dose for children, I will look for the abstract. Also, if they do decide it is pid, gammaguard s/d(powder) is supposed to be better. I would be very surprised if it is pid, I cannot understand how the immune system could be over active with cidp and also underactive with pid. You would think one would balance out the other.

I noticed in my readings that pid people get sub-Q injections of ivig, I wonder if he could get both? (Assuming he does have pid) There has to be some connection between the rituxin and the blood work. The doctors will find it out! We are praying for your family.
Dawn

Lori,

T-cell deficiency does not seem linked to autoimmunity – hope this calms your fears til more is known.

quotes: (emphasis mine)

Autoimmunity is uncommon in patients with pure T-cell
immunodeficiency (Rosen, 1987). Children with X-linked
severe combined immunodeficiency exhibit T-cell maturation
arrest within the thymus (Sleasman et al, 1994). B-cell
numbers are normal, and immunoglobulin secretion can
occur in the presence of normal T-cell help. Although this is
the most common form of human SCID, autoimmunity has
not been reported in these patients,…..

While opportunistic infections are a
prominant feature of both adults and children with idiopathic
or congenital CD4+ T lymphocytopenia, [COLOR=”Blue”]autoimmune disease
has not been associated with this newly described
immunodeficiency of CD4+ T lymphocytes [/COLOR](Sleasman et al,
1990; Duncan et al, 1993; Ho et al, 1993; Smith et al,
1993; Spira et al, 1993).

In contrast to purely T-cell deficiencies, defects in immunoregulatory peptides involved
in cell-to-cell interactions are commonly associated with
autoimmune disease.

[COLOR=”Blue”]Unlike T-cell defects, humoral immunodeficiencies carry
a high risk of autoimmunity.[/COLOR] Children with X-linked
agammaglobulinemia have little detectable immunoglobulin
production due to a maturation defect in B-cell development
(Conley, 1985). Children with this disorder have a high
incidence of polyarticular arthritis and inflammatory bowel
disease (Barnett et al, 1970). X-linked hyper-IgM syndrome
results from a mutation within the gene encoding the ligand
for CD40 (Aruffo et al, 1993). This defect results in
ineffective immunoglobulin isotype class-switching from
IgM to IgG or IgA. In addition to antibody deficiency and
recurrent infections, affected boys have a high incidence of
autoimmune thrombocytopenia and autoimmune hemolytic
anemia (Cairns and Rosen, 1986).

lori,
What about thymic hyperplasia. The thymus is where the t-cells are seperated into good and bad, our kids do not do this, hence the cidp. This process is related to cd4. CD4 is a positive t-receptor cell, and our kids does not work. Apparently ther is a drug called septrin that is relative to this, I have not looked it up for Kevin yet. Additionally, I think there is some connection between cd95, fas ligand.

I read that thymic hyperplasia is defined as an enlargement of the thymus that occurs when stress has occurred via chemotherapy, steroid therapy, irradiation. This causes the thymus to become atrophic. Once the stressors are subsided, the thymus shrinks in most but not in all. there is also a phenomenon called rebound hyperplasia where the thymus increases even with cesation of chemo or steroids. Has Dells thymus been checked?

Sorry for bouncing all over, so many thoughts! Good luck tonight!
Dawn

The diaper rash is one of the few things that “fit” into the 10 signs of pid – chronic skin infection (and failure to grow). You had mentioned that Dell has been healthy – no colds, sinus, ear infections. That is supposed to be one of the hallmark indicators of pid when combined with low immune cell counts. Dell has always had cell counts at the low end of normal until just recently when they started dipping below acceptable levels. That makes me wonder if his latest low counts are a result of all the different treatments to suppress in the past year as opposed to an inherited deficiency.

Warning signs of primary immunodeficiency:
[url]http://www.aafp.org/afp/20031115/2011ph.html[/url]

Hi, I would like to offer a few comments.
First and foremost, people consider not only the absolute CD4 count, but also the relative numbers and function when thinking about immunodeficiency. The absolute numbers can go down if the number of white blood cells are reduced. This definitely happens after rituxan and can happen after IV IgG. I have seen a lowered white blood cell count after almost every cycle of rituxan given in children in our clinic including given for autoimmune diseases. Please let us know what his WBC count is. He could have an appropriate CD4 percentage, but a low WBC and the absolute number of CD4 cells will be low. For example, if someone has a WBC of 5000, the calculated number for absolute CD4 might be very different than if the WBC was 1000, but the percentage could be appropriate.
T cells are the generals or directors of the immune response and help make sure than B cells act appropriately. As compactdisc states, often people look at T cell dependent immune responses to see if the rest of the immune system “works” specifically against challenges in order to figure out if the problem is just with T cells, just with B cells, or with both. Often people look at specific antibody titers to tetanus and pneumococcus–which is why he asked about immunizations.
The fact that Dell is almost 4 years old and has not had lots of significant infections is a very strong argument that he does not have a severe combined immunodeficiency with both B and T cells not working.
The most important point of this point is that people have to look at the whole immune system to figure out what is wrong and that a low CD4 count does not always mean that the problem is with the T cell system.

2. Whatever the reason for a lowered CD4 count, it is definitely worth being safe to take bactrim (as I think you meant) or septra (as Dawn meant). this is the same medicine, but two different brand names. It helps prevent “opportunistic infections” particularly a kind of pneumonia for which T cells are important fighters. At our institution, we often put children who are getting high doses of steroids on bactrim (septra) as a precaution.

3. My third point is that it is REALLY unusual for a tiny baby like Dell to get an autoimmune disease. It happens, but people should always think about if the immune system is able to regulate and balance itself correctly when this happens meaning if there is a primary immunodeficiency problem that leads to dysregulation. Your immunologist is good to think about it. It does not mean that it is there, but you want to know because if it is…
a. All of you can know other ways to help keep Dell safe in life.
b. It might give some insights into other ways to treat the CIDP.
The biggest point of this is that knowledge is not always bad and that if he has a primary immunodeficiency, it does not mean it is a completely separate disease–they are likely related and knowing this might be a good thing because it might help change the approach to them and might even result in better control of the CIDP, but definitely in better safety with treatment.

4. If the WBC number and the absolute B cell number were okay before the rituxan, it might be a good thing to have the whole picture looked over by someone that specializes in primary immunodeficiencies in children. Many major medical centers with children’s hospitals (typically associated with medical schools) have such departments. We have a really good immunodeficiency clinic here at this very large children’s hospital in Indiana, but I know there are also good ones in New Orleans (through LSU or Tulane) and University of Alabama in Birmingham. I cannot at this late hour think of people in Mississippi, but I could ask around if you would like. I do not know where you live in Mississippi. If you live in northwest Mississippi, St Jude’s probably has primary immunodeficiency experts.

WithHope for cure of these diseases.

Lori,

I am so sorry to hear there are more problems for Dell. I hope with all of my heart you find out what’s really going on and can get it treated.

you’re in my prayers,

Stacey

Hi Lori,

I am so glad to hear you were able to get some sleep. There are so many intelligent and knowledgeable people on this site. I am constantly learning from them. I hope they help you find the path to answers….In the meantime, always remember to take care of yourself. A strong and healthy caregiver is so important to those of us who struggle with this disease. You all mean the world to us and it is hard to remember that some days when the going gets tough. I know I often got caught up in how this affected me but forgot to consider the impact it has had on my husband and family. God bless…

Janet

Lori,
I’m so sorry you have to go through all this. I wished I could be of more help to you. Perhaps a chart would let us see visually what’s going on with the numbers. You did not mention when he was getting Solumetrol and how often the Copaxone. I still think Solumetrol might have an effect on all cell counts. It seems clear from looking at the chart that the Rituxan did have an effect on the white blood count which is to be expected for the B-cell component. As I told you in another post in my case the effect was not very great. But then children often react much stronger than us adults.
I would be happy to update the chart with more information if you feel it is helpful.
Take care
[IMG]http://www.ourbluemarble.us/forum/Dell.jpg[/IMG]

One more thing: CD4 is also found on monocytes and macrophages. I am still researching Copaxone. It shifts from Th1 (inflammatory) to Th2 (anti-inflammatory). I’m trying to find out if CD4 appears on either one.

Lori,

The good news is that Dell is not sick – just his numbers are not what was expected.

Here, another explanation for possible causes of low t-cells:

(in case it becomes relevant to future developements)

Rituxan:
a transient decrease in t-cells occurs that is “likely to be associated with the use of corticosteriods”. This decrease is recovered in about 4 weeks.

[url]http://www.emea.europa.eu/humandocs/PDFs/EPAR/Mabthera/Mabthera-H-259-II-39.pdf[/url]

There was no clinically relevant difference between treatment groups in mean changes from baseline
in total T-cell (CD3+) counts, helper T-cell (CD4+), and cytotoxic T-cell (CD8+) counts.
[COLOR=”Blue”]The observed transient decrease in mean counts after each infusion (recovered again to baseline levels by Week 4) is likely to be associated with the use of corticosteroids during the initial phase of the study.[/COLOR] The [COLOR=”Blue”]latter seemed to be confirmed [/COLOR]by the impact of the corticosteroid regimen on T cell counts observed in the phase IIb study.

Additional info from Copaxone Label:

Adverse Reactions

Hemic and Lymphatic:
◆ Infrequent: Leukopenia, anemia, cyanosis, eosinophilia, hematemesis, lymphedema, pancytopenia,
and splenomegaly.

WithHope:

You have such valuable knowledge from your experiences – would you have any info/experiences with

lymphocyte transformation test (LTT) or DTH Test? The suggestion of looking for titres against vaccinations indicate a state of functionality of th-2 cells, and now I am looking for specific tests that would reveal function of th-1 and th-17 cells.

Three subclasses of CD4 “effector” T-cells:

Th1 intra-cellular pathogens
Th2 extra-cellular pathogens – signals b-cells
Th17 inflammatory response

If I find something significant, I will post for all (along w/references).

cd

compactdisc already answered my question about CD4. I did not know about Th17.

Here a chart showing the interrelationship between the two subtypes of T helper cells. It also shows which one produces what cytokine, IL-2 versus IL-4 etc.

[IMG]http://www.ourbluemarble.us/forum/Thelper.jpg[/IMG]

On the subject of the white blood count: looking at the distribution of different cell types, I don’t think that the Rituxan would have caused the dramatic drop. I still suspect the Solumetrol especially since you are saying that he’s getting it every week. Here’s the breakdown:

[U]White blood cells percentages[/U]:
Neutrophils 50 to 70%
eosinophils 1 to 3%
basophils <1%
lymphocytes 28 to 39%
monocytes 3 to 7%
NK cells 10 to 19%

I could not find the breakdown of lymphocytes into T cells, B cells and macrophages. NK cells are also lymphocytes but shown separately in the table above.

Take care

Does anyone think the thymus gland has anything to do with this? Since the T-Cells are separated in the thymus gland, and all of a sudden there are these new problems, could thymic hyperplasia be responsible for the new problems?

CD, is what you mention regarding steroid treatment the same as thymic hyperplasia?

Could the thymus be enlarged?

I hope you find some answers soon from the doctors, we are thinking about you and will pray for you in church tonight!
Dawn

Lets hope its the Solumedrol. I updated Dell’s chart (see below). In February 2007 his CD4 count was normal. The following month he started getting weekly treatments of Solumedrol and the CD4 count kept going down ever since. It could be coincidental but in my opinion it looks rather suspicious.

Regarding the antibiotic, check a post by Norb, immunosuppressants explained or something like that. He mentions in an article he refered to that cyclosporin specifically works with t-cells. Maybe you could copy the info he posted and ask the doc if it has any relavence to Dell.

We just returned from the living stations for Good Friday service, I prayed for Dell, Kevie, Emily, Abby, all the children, and all of the adults. I asked God if he could cut the time short that everyone has to bear this cross of cidp and help the scientists find a cure quickly. I didn’t get an answer, but I am not giving up hope!!!

Praying that tommorow brings a brighter day!
Dawn Kevies mom

So I was up thinking about Dell too last night. When were the blood draws taken? Were they shortly after getting Solumedrol? If the Solumedrol can affect C4’s then maybe you should wait until the day before the next Solumedrol infusion to do a draw. Just to see if that makes any kind of difference. The dr might order a series. I would think that he would want to get the levels before, a few days after & then right before the next dose to see if there is any change.

Kelly

Lori,

This sounds promising, it makes sense. Enjoy your lunch date, no jello.

Love,
Cindy