What test to confirm or rule out PANDAS?

[Mayzoo]

Kiddo is going to a pediatrician tomorrow. If I can get the pedi to run tests, what blood tests should I request to confirm or rule out PANDAS besides the Strep antibody test? I am going to get a throat culture for her too.

 

Thanks for any help.

[Mayzoo]

I found this in FAQ.....anything else I should have tested?

 

Tests: Streptococcal Exotoxin antibody tests (ASO and AntiDNAseB)

 

Q: My child has a positive throat culture. Should I also have tests for ASO or Anti-DNAseB?

A: We'd recommend against it. The unfortunate reason is that some doctors think that if your ASO comes back negative you can't have PANDAS. That is not true. ASO has a 46% false-negative rate. That's almost the same as a coin flip. If you have a positive throat culture, treat it. If it is associated with significant exacerbation, PANDAS is probable.

 

Q: My child was negative for a strep culture. Should I have get ASO or AntiDNAse B tests?

A: Yes, ASO and Anti-DNAse together are better than either test individually; however, you still need to determine when you likely were exposed to strep. ASO rises approximately 1-4 weeks from colonization and Anti-DNAseB rises between 6-8 weeks from colonization. Even then ASO and Anti-DNAse B together fail to show a rise in 31% of children with strep colonization.

 

Q: Is a single measurement of ASO or Anti-DNAse B enough?

A: Actually no. titers have to be measured at two points (typically a week apart). ASO is typically measured at 3 and 4 weeks from the date of suspected infection and Anti-DNAseB measured at 6 weeks and 8 weeks from the suspected event. The two data points are needed to look for a rise. Absolute values are not as important as the rise/fall of the titer. For this reason it is important that both samples are done by the same lab. In the absence of having two titers, many labs use a measure known as the "upper-limit-of-normal". This value is helpful if the measured value is significantly higher than the upper limit. If it is lower than the ULN, then typically two samples are needed to look at the slope/trend.

 

Q: We had low ASO titers, does that rule out PANDAS?

A: No. Anti-Streptolycin O is a measure of an exotoxin of Group A Beta-Hemolytic streptococcus. Although most strains of GABHS do produce Streptolycin-O, cholesterol (particularly in the skin) can absorb this exotoxin. In one study, ASO did not rise in 46% of patients despite positive throat cultures and perfect timing for taking the ASO titer. So ASO can confirm a previous strep infection but cannot rule out strep or PANDAS.

 

Q: We had low Anti-DNAseB and ASO titers, does that rule out PANDAS?

A: Unfortunately, No. First, the tests have to be taken during the rising titer period. ASO tends to rise 1-4 weeks post infection and Anti-DNAseB tends to reach a peak at around 6-8 weeks. Even with perfect timing of titer draws, 31% of children with confirmed colonized strep did not have a rise in either ASO or Anti-DNAse B. So anti-DNaseB and ASO can confirm a previous strep infection, but cannot rule one out.

[Dean1065]

Our daughter had an ASO of 691 and a DNase Antibody of 1000. Does that say anything about the timing of the infection?

[Dean1065]

Kiddo is going to a pediatrician tomorrow. If I can get the pedi to run tests, what blood tests should I request to confirm or rule out PANDAS besides the Strep antibody test? I am going to get a throat culture for her too.

 

Thanks for any help.

 

Mayzoo,

 

We are very new to this and obviously still learning every day, but many have told us that a mycoplasma test is imprtant too.

[Mayzoo]

[/color]

Our daughter had an ASO of 691 and a DNase Antibody of 1000. Does that say anything about the timing of the infection?

 

I hope this answers your question, I have not read it all yet but am about to. I highlighted in red what is close to your question. I found this on helpful threads.

 

 

 

 

In reading through multiple posts, it seems there is a lot of confusion about titers and carriage of streptococcal infection. As a parent struggling to understand the medical information, I wanted to post what I've learned thus far and I hope it will be of use to you.

 

1) Titers need to be compared to a baseline. Direction is much more important than absolute value.

Some people produce very significant antibody responses, some don't. Some have high baselines, some don't. Since most often there isn't a test result from the prior month to compare against, most doctors (and labs) use a measure known as the "upper limit of normal" [uLN] as defining the baseline for ASO tests. Then if your single sample is > 130%-150% (depends on lab) of this baseline, they consider the test positive.

 

2) So this begs the question of what is the ULN for ASO? There are lots of studies here but what is important is that the studies have a very large range. For example in one study, kids not suspected of GABHS strep in the 5-10 year range, had

 

48% had titers below 100

6.8% had titers of 100

10.6% between 101-125

7.6% between 126-156,

22.1% between 157-195

and 4.5% in 196-244

 

 

Unfortunately, even in this study, there didn't seem to be a second measurement taken within 1-2 weeks to look for rise/decline.

 

3) This begs the question of "what level of response consistitutes a positive?." Could a result of <100 still be an indication of a recent strep infection?

The answer appears to be yes, but only if you have a prior value done by the same lab, using the same technique. Most studies show that subjects will have a response 2-4x their baseline, this statistically could still fall within this "normal" range depending on the individual. So again, the importance is to look at trends and not absolute values.

 

4) What about falling titers? Does a high number indicate a current strep infection?

The answer seems to be no. There is just no good study about how fast ASO titers fall and what drives the rate of fall. Thus a single sample really gives no good indication of direction. Most studies agree that the rise is within a week of infection with a peak at 4 weeks, but there isn't a study of whether this peak remains if the initial infection goes untreated. So could someone with an untreated strep infection have a declining ASO titer? -- the answer appears to be yes.

 

For example, the most recent study by Kurlan [June 2008 - Pediatrics] has one subject that has positive throat cultures for 23 of 25 months but the ASO titers are falling within this entire time. What does this mean? No one knows.

 

5) Do all strains of strep produce an ASO reponse?

 

The best study I've found on this is Kaplan's 2003 paper "Immune Response to Group A streptococcal C5a Peptidase in Children: Implications for Vaccine Development." What this paper shows is that despite positive strep cultures on day 1, at a subsequent visit 4 weeks later,

 

46% of subjects presented no ASO rise,

55% presented no Anti-DNAseB rise,

and 37% presented no rise of either ASO nor Anti-DNAseB

 

 

There also seems to be good research indicating that skin GABHS infections does not produce ASO response despite producing Streptolysin O.

 

What does this mean?

Does this mean that the test was bad? That some strains don't produce the streptolysin O protein? That some people don't mount a high immune response? That the individual is a strep carrier? That the strep was going on for some time and the ASO titers have already fallen? That skin GABHS infection differs from pharangytis GABHS? The answer is that the scientific community doesn't know. There has been no careful study of the decline rate of ASO titers and the entire field of "strep carriers" is not at all clear.

 

So summarizing,

 

a rising ASO titer (regardless of absolute value) is an indication of GABHS strep; however, you need a baseline to be sure it is rising.

A falling ASO titer indicates that there was strep, but no one knows when.

A high ASO titer could be anything including that the titer is falling, rising, or just a high baseline. Statistically it is likely to be a falling titer.

Most will treat a titer of > 400 IU's as a falling titer (i.e., that there was once a strep infection sometime in the past). But the exact time of the infection is not known.

The interpretation of a low ASO titer is unclear. There could have been an infection and the titer has already fallen, the baseline for the person could be low, the individual may not respond with a strong immune response, the strain may not produce significant amounts of streptolysin O.

 

 

One final comment, Swedo does not require high ASO titers or even rising ASO titers to diagnose PANDAS. The titers are checked only when a positive strep culture is not available and you are retroactively looking for an indication of past infection. The flaw with using titers as an indication of prior strep infection is (as I stated above) that "low" values can still be associated with prior strep infections since the rate of ASO titer decline is not known, most people only have a single sample, and the ASO response is variable across individual and strep type.

 

Regards,

 

Buster

Edited January 4, 2012 by Mayzoo

[Mayzoo]

Kiddo is going to a pediatrician tomorrow. If I can get the pedi to run tests, what blood tests should I request to confirm or rule out PANDAS besides the Strep antibody test? I am going to get a throat culture for her too.

 

Thanks for any help.

 

Mayzoo,

 

We are very new to this and obviously still learning every day, but many have told us that a mycoplasma test is imprtant too.

 

Thanks

[Dedee]

You should add Mycoplasma Pneumonia IgG and IgM titers. Even if your child does not have signs of a respiratory infection, get them anyway. Also, get an immune panel. Your doctor should know what that includes. If possible get strep titers and myco p titers for everyone in the house. Good Luck.

 

Dedee