Buster

Hi, It really is a battle. I'm sorry for all you are going through. One slight comment is that rising titers are not a sign of an active strep infection, but rather that there was an active strep infection 1-4 weeks ago (in the case of ASO) and 4-6 weeks ago (in the case of Anti-DNAseB). ASO and AntiDNAseB are responses to exotoxins of GABHS. Usually people go to the titers only if they really think there was strep but there's no positive culture or they missed it. Has your PANDAS son done well when inbetween episodes? Buster

Yes, the chart was meant to summarize research. I debated putting footnotes in each box with the papers associated with the finding. When I did it the first time it was pretty messy. I also wondered about putting a column "improves with Advil" but there are no research studies on that outside of alzheimers or studies on Cox-2 inhibitors - yet many parents would report improvement. I agree about the siblings. This highlights a strong genetic link - however, no study that I've found on the topic. I could add the column though. On remits with time, there are arguments in the research papers that Sydenham Chorea is monophasic and self-resolving at 6 months from onset. Digging in that literature about 60% of cases are monophasic and the rest have a second episode within 2 years. On self-resolving, there is data that the chorea does remit at about 6 months in 60-70% of cases. The remaining 30-40% of cases the chorea is sustained without some type of intervention (e.g., drugs or PEX or ...). Finally there is a high OCD association with Sydenham Chorea (estimated at 70%). There is inconsistent data on whether the OCD with SC remits or not without intervention. Buster

Remission means a reduction or cessation of symptoms for a period of time. This is not "cure" because we don't know if it will come back.

Hi Eljomom, I think the key is the closing of the BBB in either case. Once the BBB closes it probably doesn't matter if there are anti-neuronal antibodies in the blood stream, they don't have a target and so just circulate until they die off (typically 21 days later). Antibiotics don't "kill" bacteria but rather slow down bacterial growth. The current theory is that there are 3 things going on: There's an abnormal reponse to an infection that creates an anti-host antibody There's then a failure of the Tregs in suppressing the anti-host antibody -- normally they suppress these things Then there's a breach of the BBB that allows the antibody to reach neuronal tissue Antibiotics can help to reduce the number of antigens causing #1. Some antibiotics are anti-inflammatory and can help #3. Predinsone and IVIG are both highly anti-inflammatory and would help close the BBB (as well as suppress the antibody creation). Sort of. Most are taking antibiotics to prevent new infections and the antibody production. This is why it is called prophylactic antibiotics. You are right about the anti-inflammatory nature of a number of the antibiotics. I actually think this is why azith and advil both seem to help. Yes. Yup. Yes, prednisone is highly anti-inflammatory and is shown in MS to help close the BBB. That's a really personal decision that is best discussed with your doctor. Dr. K tends to use the steroid burst as a confirmatory test (i.e., it reminds parents what their kids were once like. It basically helps to confirm an auto-imune diseases. Very hard to say. IVIG is a blood product and while generally thought to be quite safe there are complications that could occur. Plasmapheresis has good safety record and is quite effective for acute treatment of auto-immune issues; however, you are putting in a central line that has it's own issues too. Personally we wouldn't have gone to IVIG if the very scary anorexia hadn't returned. IVIG does seem to work for kids who have strong confirmation of auto-immune disease (i.e., symptoms remit on a prednisone burst, or onset was extremely rapid and severe). IVIG was uneffective for patients with chronic tics (i.e., were not having episodic course). The decision to use ivig is a very tough time. I can tell you it helped our daughter, but we too lay awake nights thinking about the pro/cons. Wishing you the best, Buster

Hi P.Mom, The fine piano playing movements in stressed stance are referred to as a choreiform movement. Although the term sounds like chorea, it actually has nothing to do with chorea. It's really unfortunate that the two terms sound so similar as this has probably caused a lot of confusion. Dr. Latimer commented at the IOCD conference how often pediaticians get confused there. You can absolutely trust her comments as she is extraordinarily knowledgable about choreiform movements and separating from chorea. Bottom line, chorea is exclusionary for PANDAS (meaning if you have Sydenham Chorea, then you don't have PANDAS). Much like if you have ADEM, then you don't have Tourettes syndrome (because by definition). Buster

Hi Fixit, It's a definitional item. Swedo said that existance of chorea is exclusionary for PANDAS. It's possible they are related but you have to have chorea for SC and you can't have chorea for PANDAS. Buster

I was realizing there was a lot of questions recently on comparing different syndromes. I thought the attached table might be helpful. Let me know what you think is missing: Please consider this a working draft. I could add reference papers for each cell but it got a bit complicated. Buster

I think I should have explained the diagram better. I'm showing where a person shows up. A person can have OCD and have Tics. What I'm trying to do is size where someone fits. Take my daughter (for example), she could have been in SC (with sudden onset OCD) if we considered her movement disorder to be chorea. Or she'd be in the PANDAS + sudden onset OCD group and then we'd have to decide whether her vocal grunt is a tic or not to know if this would be in the very intersection of PANDAS + sudden onset OCD + episodic tics. Tourettes is in the picture (I just didn't label it). It would be a subset of Tics with overlap of OCD -- but seems not the sudden onset OCD group. I'll keep tweaking it and thanks for the comments. Buster

Round 2: I revised the picture based on the feedback. It turns out to be much harder to draw than I thought. Size is particularly difficult to represent while also covering set union/intersection. Here's what I'm trying to show: 1. ARF usually has mitral valve involvement 2. SC can be a sole identifying trait in ARF and SC appears in about 30% of ARF cases 3. in about 70% of SC cases, there is onset of OCD 4. There's an interesting paper from Brazil that says OCD doesn't happen in ARF without SC (this could be a sampling issue, but interesting) 5. Not all tics are episodic 6. Not all OCD is sudden onset/episodic 7. Some PANDAS and PITAND could be outside the sudden onset (this was Pavone's paper on chronic PANDAS) The incidence of ARF is tricky. About 4% of people are genetically susceptible, but incidence looks like more .3% in US and 1-2% world wide. OCD incidence is quoted several places as about 2-3% in the 5-12 age group Tic incidence is quoted several places as about 4% Co-occurance of OCD and Tics is listed as about 1% Buster

Kimballot, what great questions! It does appear that 24.3.1 is primarily associated with GABHS; however, other superantigens can cause recruitment and activation of T-cells without having the specificity. exotoxins to GABHS are superantigens and can activate many differnet T-cells and B-cells. What's in the papers is high correlation with GABHS, but it might be high correlation with exotoxins of GABHS. The epitype of the antibody had signature very similar to GlcNAC carbohydrate on the exterior of the GABHS cell wall, so that gives some bias that this is more GABHS activated -- but it could be something else. GlcNAC is a very common carbohydrate. Yes, very possible. While Cunningham isolated 24.3.1, she also isolated 31.1.1 and 37.2.1. There are likely a whole bunch of others. She was looking for markers but not strictly causal activation. It's really possible given the way the tests are done where they don't filter first, that another antibody (i.e., not one of the 4 she typically tests) is doing the activation. Doing antibody isolation is pretty expensive. So right now she's using a combination of inhibitory ELISAs on things like lysogangliosides, D1, D2 and Tubulin to see if the combination of CaM Kinase and these 4 inbibitory tests isolate the antibody. Hope that helps, Buster

Hi folks, Thanks for the feedback. I'll incorporate the modifications into the picture. It'll take me a bit to revise the document appropriately. What I got was that: * I need to figure out size of bubble rather than just rough intersections (y'all are good analytics :-) ) * I need to calculate what % of carditis is associated with ARF * Need to calculate size of OCD bubble (and sudden onset OCD within that) * Need to adjust the tics/OCD balance (i.e., where are the PANDAS cases -- how many are pure tic) * Need to add the comorbid/co-occuring symptoms of Sep Anxiety/Anorexia/... from the survey results. I'll try a revision and repost. Buster

It sure looks like at least 24.3.1 is causing Cam Kinase II activation. There may be a couple other antibodies that are doing it too, but 24.3.1 seemed to be both an anti-lysoganglioside (discussed in a moment) and a CaM Kinase II activator. Yikes. Well, let me try an explanation here and we'll see if it help. CaM Kinase II activation is generally tested by assay or microplate. A sample of blood serum (which contains antibodies) is incubated with neuronal tissues (typically those from neuroblastoma cells) to generate a potential CaM Kinase II sample. The sample is then incubated with a microplate substrate in the presence of a radioactively tagged ATP. Consider this a radioactive flag that signals that a particular type of activation is occuring. There's a bunch of steps next that wash the substrate, but the end result is that the microplate will have a radio-signature that indicates a quantity of CaM Kinase II activation. While in the Nature paper, Kirvan isolated and cloned the 24.3.1 antibody. These days I think they test without isolating the individual antibody, but rather taking a diluted sample of blood serum and seeing if any of the ATP changes state (i.. raises the flag). If it does then they assume the likely cause is the 24.3.1 antibody. It's a pretty good bet. Now CaM Kinase II regulates Calcium channels and potentiation (meaning keeping channels open). This has effect on cell signalling (particularly fo neurons). So lots of CaM Kinase II activation likely means a lot of neurons would be firing. It appears it is elevated from a specific antibody (which is an autoimmune response). Absolutely. Here's the way to think about it. When you get an infection, your body produces antibodies to help find bacteria and flag it. Quite literally antibodies are little Y shaped structures that attach to specific carbohydrates or proteins on a cell surface. They flag for destruction. There's these other cells known as macrophages that come along and see the flag and "eat" the bacteria. The macrophages then send a signal saying "found some" or "make more antibodies" (this is a short hand, there's a lot going on here). Anyway, the body makes more antibodies and more macrophages until the infection is resolved. Now when the infection is gone, the anti-bodies will still be around for a while (typically 21-28 days). This is actually a half-life. This means every 21 days about half the antibodies have been used up. Now this assumes you don't get another infection that ramps everything back up. In auto-immune diseases, a portion of the host can act as a recipient of the Y antibody. This is a mistake (i.e., the immune system is supposed to not make antibodies that will bind with host cells. For whatever reason the check of "is it going to attack the host" is broken or ineffective so the feedback cycle starts. The target of the auto-immune disease (think neuron cells) now acts as if it were the bacteria. The immune system sees these monoclonal antibodies and tries to engulf the cell. Do we know that this is what is really going on.... not really, but it sure seems plausible. You could therefore ask how do you break the cycle? Well if the stuff is across the blood brain barrier, closing the BBB helps break the cycle. If the stuff is heart muscle or joints or ... then prednisone can help break an autoimmne cycle. It is not known whether the antibiotics are having an immunomodulating effect, an antiinflammatory effect and closing the BBB, or some other effect. Please post again if above isn't clear. Buster

Would love some thoughts about this picture and whether it matches the literature. About 4% of people have a genetic susceptibility to acute rheumatic fever About 50% of people with ARF have carditis About 30% of people with ARF have Sydenham Chorea About 70% of people with Sydenham Chorea get dramatic acute onset OCD PANDAS represents a group that doesn't have SC (i.e., doesn't have ARF or Carditis), that could have episodic tics or acute onset and dramatic episodic OCD. Episodic meaning has distinct starts/stops or dramatic exacerbations and falls (sawtooth pattern). Thoughts? Buster

Hi Eljomom, I absolutely get your question. The reason all the studies were on strep is that Swedo was looking at sudden onset OCD in kids who developed sydenham chorea. Sydenham Chorea is generally accepted as a sequela to untreated GABHS infection. She noticed that sometimes the OCD came before the chorea and sometimes after. She then got some kids with sudden onset OCD but didn't get chorea. That's weird (she thought). Is the sudden onset OCD something else? About 21% of patients who get Acute Rheumatic Fever gets sudden onset OCD. About 30% of patients with Acute Rheumatic Fever get Sydenham Chorea, but only 70% of those who get SC get OCD and apparently a few kids (i.e., the 50 she was looking at) get OCD but no SC. So now she's thinking -- I wonder if the SC and OCD are triggered by the same antibody or is it two different antibodies. She found in a really small study that two kids with sudden OCD but no SC had strep and another two kids with sudden OC but no SC had a virus. So now she's stuck. It could be that it's caused by strep or caused by a virus. She tried immunomodulating therapy and all the kids got better. Now that's weird (she thought again). Others tried treating the OCD in SC kids with IVIG and they got better too. Wow! Another group tried treating OCD in non-SC kids and they didn't get better at all. Hmmm, somethings going on here. Maybe this sudden onset is the thing. She's got a bunch of people around her who know tons about streptococcus so she focuses there first. Here's the key -- it's possible sydenham chorea might also be streptococcus and viruses too... Everyone sort of thinks it only comes from untreated strep -- but maybe not. So the team starts looking at just untreated streptococcus -- she thought this would be easy to prove, then they could come back to those pesky viruses. But now here's the key problem she ran into.... In her original definition, she said that PANDAS was sudden and dramatic onset of OCD and/or tics. Kurlan flipped out and said "all tics are dramatic and sudden". So Swedo's stuck -- how does she look for these auto-antibodies if she doesn't have a good way to separate out the kids who have them from the kids who don't. Swedo landed on these comorbid or coincident psychological manifestations. The kids who seeemed to fit this PANDAS profile had separation anxiety and daytime urinary frequency and other such symptoms. So Kirvan and Cunninham used serum from a group of kids who had OCD and these other symptoms and started looking for the preverbial needle in haystack and found antibody 24.3.1. Now the question is whether the kids with just tics caused by auto-immune have this 24.3.1. We frankly don't know. Kurlan sort of refused to pursue any kids with the dramatic onset of OCD (i.e., he stuck to kids with long term tics) and kept not finding the anti-basal ganglia antibodies. Most likely because he didn't actually have any kids who fit the expanded PANDAS profile (i.e., the ones with seperation anxiety or daytime urinary frequency or dilated pupils, ...). So I totally get what you are saying that "what happened to all the folks who are affected primarily by non-strep" -- right now Swedo still doesn't have everyone agreeing that 24.3.1 (cunningham's tests) are meaningful. So she's still working that one and until she can prove that, there's not a lot of money/research being spent on other harder to find viruses and bacteria. Buster

It certainly sounds like you are somewhere in the first 3 groups. Were the OCD/Sep anxiety sudden onset or a slow and gradual course? Did antibiotics or pred have any effect on the symptoms? What does your doctor say? The CamK is certainly consistent with other kids in the PANDAS group. Buster

The estimated half-life for the antibodies is around 21-27 days. This of course is in the absence of an antigen that is causing the B-cell to regenerate more antibodies. Yes, it does seem that once "primed" the antibodies do come back. One theory is that the neuronal tissue itself (with which the antibodies cross-react) acts as an a trigger. The explanation would be that the BBB opens and the T-cells/B-cells are able to be activated. The actual mechanism isn't exactly known. Not sure what to say. We might be seeing the antibiotic effect. We might be seeing an anti-inflammatory effect. We might be seeing an immunomodulating effect. What's interesting is that the antibiotics usually talked about on this forum (azith and augmentin) both have other properties beyond their straight antibiotic effect. It's a valid concern and worth running liver panels every so often. Well, there's a lot that could be going on. I don't know a ton about Lyme, but from what I've read it sure seems that the co-infections play havoc with the immune system and tend to recruit a lot of the T-cells to attack decoys creating over-recruitment of the immune system. Buster

Hi P.Mom, I agree with you. Absolutely kids with only tics can have PANDAS or PITAND. If we look through the literature, the kids basically split into five categories: those with sudden onset OCD and simultaneous separation anxiety/urinary frequency or other symptoms those with sudden onset OCD and a tic disorder those with sudden onset separation anxiety/urinary frequency with or without a tic disorder those with a tic disorder and no other symptoms (who improve on antibiotics or other immuno-modulating therapies) those with a tic disorder who don't fit the other categories There is significant misunderstanding by doctors about all 5 categories, but if we look at who is stirring up controversy, it is a specific set of neurologists who are studying #5 -- those with a long-term tic disorder. Unfortunately their inability to repeat experiments on patients in #4 or #5 is clouding all the other categories. If we look at the studies done by Kurlan and Singer, they are on patients in #5. The patients were drawn from the Tourette's study group with older children who had consistent tics for > 3 years with no remission > 3 consecutive months. In their 2 year longitudinal study in 2008, none of the greater than 80 subjects had any variance in OCD symptoms. While the sudden onset OCD or OC behavior seems to separate the first 3 categories, I don't think the "controversy" will end until the research community comes to agreement on how to separate category #4 and category #5. Best regards, Buster As always, thanks Buster for all the information. I would like to respond to this quote because I feel it is necessary for parents to know that the kids do not, in order to be considered PANDAS/PITANDS, need to have OCD, etc. I understand there is much debate with the docs over this. However, there is much debate about the existance of PANDAS and we all know it exists. (regardless of what some docs may say)

Well, I guess both a typo and too much simplification.... I meant to say more Th2 is produced than Th1. Sigh. Azithromycin suppresses IL-12: http://www.biolsci.org/v05p0667.htm Th1 basically matures into more things that "eat" or "kill" cells. It also tends to have more "inflammation". Th2 matures into activating B-cells that produce antibodies that help signal what needs to be killed (like little flags on the "bad" cells). So technically neither is really intracellular or extracellular. The macrophages, Eosinophils and NK cells will take out either extracellular pathogens or flagged internal cells. I mixed up my Th1 and Th2 in the prior post. It should have said that more Th2 is produced than Th1. Oops. Thank kimballot. Buster Hi Buster - first off - thanks for the great picture. I am confused,though, and either I don't understand the picture or you made a typo when posting. From the picture (and my knowledge of zith), Th1 is focused on intracellular and Th2 is focused on B-cells, which produce humoral extracellular antibodies... I do understand that " What Azithromycin does is bias the balance point so more Th1 is produced than Th2."... but I believe that means that it shifts from extracellular to intracellular, which is why azith is so good for mycoplasma and intracellular strep. Is that correct?

It is very likely that PANDAS, SC and Acute Rheumatic Fever are all related. My best guess is that there are four or more distinct antibodies that are very similar. One targets heart muscle and produces carditis. One targets joints and produces arthritis, one targets tubulin and affects motor function, one targets D1/D2 receptors and affects neuronal signalling. Maybe it's not that simple. The good news is that MRIs don't seem to indicate any grey or white matter lesions or any demylination (unlike ADEM). I've been trying to find prognosis reports on patients with Sydenham Chorea and look at their long term outlook. Certainly the motor abnormalities go away (with some recurrence during pregnancy). It is unclear about the OCD manifestations. I also see that OCD symptoms sometimes precede motor abnormalities in SC and sometimes follow (by as much as 2 months). In both cases only after untreated GABHS infection. This makes me wonder if the antibodies are distinct between the OCD manifestation and the SC motor abnormality. My guess is this is why Cunningham is checking for multiple cross-reactivities. Well, little is really known here. There was a small study looking at permeability and found that motrin does seem to cross the BBB. The actual mechanism is unknown. http://www.scipharm.at/download.asp?id=452 With respect to antibiotics, antibiotics won't do anything to the antibodies (per se). So one of the effects may either be to help control reinfection (i.e., minimize response of inflammatory cytokines by getting rid of the bacteria sooner) or shifting the immune response to a less inflammatory response (i.e., what macrolides are thought to do). Well, here's the most recent paper I've found: http://www.jneurovirol.com/pdf/5(6)/570-578.pdf It looks like B cells can cross the BBB under certain circumstances. I thought they'd be too big to get across but it does look possible. I asked Cunningham and she thought antibody crossing far more likely than a B cell getting across and running into a APC on the other side. My bias about the B cell was that it might explain the burst of symptoms. Still not sure what to make of the science here, but it does look like B-cells cross. Mine too. What we've observed is that we have to retrain some skills that were lost/not learned during the exacerbation. As far as I can tell from the literature in SC or PANDAS/PITAND cases, the kids recover. I'm ever watchful for the papers here though. I found CBT extremely helpful for me as a parent because it helped at least me learn coping skills. In an extreme exacerbation, it was useless. In mild ones it was helpful. CBT really requires insight before it can be effective. Best regards, Buster

I strongly support kimballot's comments here. Exactly right. There is little disagreement that there is a group of kids who have sudden onset debilitating OCD accompanied with concurrent separation anxiety and regressive behavior. These clincal symptoms are pronounced and distinct. There is considerable debate from certain neurologists at Johns Hopkins (and somewhat at Yale) whether kids with tics must also have sudden onset and debilitating OCD to be considered part of the "syndrome". The real debate is then once you've isolated the symptoms, how do you treat the symptoms. If the sydrome has a different cause then treating it the same as traditional OCD doesn't make sense. It's sort of someone complaining of heart pains and in one case is having a heart attack and in another they have a sword impaled through their chest. You probably want to treat these differently. It took over 100 years for people to recognize that Sydenham Chorea was likely caused by antibodies to an untreated streptococcal infection. It would be practically impossible to "discover" this today because any clincial trial would have to treat any strep infection found (and therefore there would be no untreated strep infection and thus no 1st time event SC). At this point, the best evidence we've got is that PANDAS is caused by 3 things for this specific group of kids with sudden onset OCD: an untreated GABHS infection that triggers the creation of an anti-host antibody that cross-reacts with neuronal tissue a failure of the immune system to suppress the anti-host antibody a breech of the blood brain barrier that allows the antibody to reach neuronal tissue After the first infection, it looks like other infections can trigger the antibody response. It is not clear whether this is just superantigen T-cell recruitment or that the B-cell is easily triggered once activated. The breech of the blood brain barrier seems to be the key item that defines the effectiveness of treatment. The half-life of the antibodies seems to be around 21 days. Rapid relief is typically explained by assuming the BBB is closed. This is a plausible explanation for why IVIG and Pred both have been seen as effective. Antibiotics can affect the antibody creation and can break the cycle of antibody response -- but in and of themselves, the antibiotics don't tend to close the BBB -- this means that it is often 3 weeks before symptoms improve. I realize folks want to see quick responses (like overnight) and frankly that's very unlikely without the BBB closing. Long response, but hope it helps. Buster

Hi Christo, Take a deep breath. Okay, you haven't done any harm with giving azith. Azith is used in long term prophylaxis for a number of diseases (most notably cystic fibrosis). The reason doctors don't want you to arbitrarily just give azith for every flu/cold/infection is that azith is really only useful for gram positive bacteria. In addition, macrolides (such as azith) tend to lose effectiveness over time on certain bacteria that mutate in how they replicate. These are called resistant strains. Most bacteria are kept in check by other bacteria using up all the building blocks. So when you use an antibiotics, you tend to allow stuff not affected by the antibiotic to grow (because you've stopped the gram-positive stuff from replicating). The probability that your child has developed a resistant strain of a bacteria is very very small, but it is there. If you have enough kids (say 42 million in the US) and each one is getting antibiotics for every cold/... then there is a good chance that a resistant strain is created. This is why prophylaxis is basically only recommended when you've got a good reason to think that colonization or infection will cause a more severe reaction (as is the case in Acute Rheumatic Fever or Sydenham Chorea). I don't know enough about your case to give you advice one way or the other, but if your child has sudden onset OCD associated with infections and these remit on antibiotics, then I think the evidence is that the antibiotics are way less dangerous than the known side effects of the atypical anti-psychotics or SSRIs often prescribed for OCD and worth a try. Regards, Buster

Sigh, this is a complicated topic. You might write to Dr. Leckman and ask him the rationale or perhaps a paper reference supporting his position. Currently PANDAS is thought to be caused by three things: the activation of an abnormal antibody response to an antigen (often GABHS) that targets neuronal tissue a failure to suppress the "self" antibody response (sometimes referred to as Treg) a breach of the blood brain barrier that allows the antibody to reach neuronal tissue Prednisone affects all three parts by reducing antibody production (1) and (2) and being highly anti-inflammatory and potentially closing the Blood-brain barrier. Antibiotics can help the immune system overcome antigens by slowing the progress of the antigen. Antibiotics do not "kill" bacteria (in the tradtional sense), they just slow down the bacterial growth so that the immune system can kill the bacteria. This means that you basically need a working immune system to kill a bacterial infection. Okay, so when you use Prednisone, it is immuno suppressive. It dramatically reduces the feedback loop that causes activation of T-cells and release of antibodies by B-cells. If you have already been on antibiotics for an extended period of time, it is unlikely that pred would cause increased activation of the bacteria. Most of the time bacteria is kept in check by other bacteria competing for the same building blocks. People on predinsone shouldn't be around people with colds/flu/bacterial infections because yes they have weaker immune responses. Dr. K tends to refer to the prednisone burst as confirmatory because if you do see a dramatic improvement when on pred you are likely seeing either the anti-inflammatory effect or the immuno suppressive effect therefore highlighting a likely auto-immune issue. Hope that helps, Buster

If you look at the picture, there are two types of immune responses being shown. Th1 is focused on macrophages (that target extracellular antigens or invaders) and Th2 focuses on B-cell and anti-body production (really for intracellular antigens). The choice of whether to produce Th1 or Th2 is a balancing act influenced by specific combinations of chemicals. What Azithromycin does is bias the balance point so more Th2 is produced than Th1. Curiously progesterone and several other hormones have similar effects. All I was trying to say was that immunomodulating means that a dampening effect is introduced by antibiotics (like azithromycin). These are "suppressive" in a sense in that they lower the number of eosinophils and inflammatory cytokines. This tends to also cause an anti-inflammatory effect too. In terms of T cells there's another form of Thelper cell called Th17 and some antibiotics seem to affect Th17 production as well. I think kimballot posted a nice summary of Th17 in one of her posts. Bottom line, immunomodulating is often a good think in auto-immune disorders -- it means you are breaking a cycle of immune system activation. Let me know if you want more here. I know I posted something about this some time ago and can try to find the old thread. Buster EDITED to fix Th1 to Th2 typo

What medication is she on now? What meds have you used with her in last 4 months? Buster