Proposal for a working definition and classification of PITANDS

[Dr_Rosario_Trifiletti]

Proposal for a working definition and classification of PITANDS

 

 

Working definition of PITANDS

 

1. First onset of symptoms in Pediatric age group 0-18 years

 

2. Acute or persistent onset of neuropsychiatric symptoms, characteristically, but not limited to tics or OCD

 

3. Usually, but not always, in association with an acute or persistent identified infectious triggers (GABHS, mycoplasma, others)

 

4. Rapid improvement of symptoms with anti-infective agents, usually antibiotics

 

 

Notice these criteria are much broader than the Swedo PANDAS criteria, still verifiable, but still including most children discussed in this forum.

 

Notice that the hardest to verify part, the "autoimmune" part, is left out of the criteria (though it always behind the scenes)

 

 

 

 

 

SUBGROUPS

 

Type 1 PITANDS - PITANDS in an apparently immunocompetent host

 

A. PANDAS (exclusively streptococcal trigger) - more common in younger children

Swedo-type (classical PANDAS)

PANDAS variants OR atypical PANDAS(see PAVONE ET AL, 2006)

 

B. PANDAM (exclusively mycoplasma trigger)

 

C. PANDAF (exclusively flagellated bacteria trigger) - covers Lyme and Lyme-like cases - maybe be the most common non-PANDAX group

 

D. PANDAX (multiple infectious triggers) - many of our children fall into this category - more common in older children

 

E. Idiopathic anti-INFECTIVE-responsive neuropsychiatric disorder, not otherwise specified (PITANDS-NOS) - the wastebasket group

 

 

Type 2 PITANDS - PITANDS in an congenitally immunocompromised host

 

This group typically shows:

 

1. Lack of serological response to known triggers despite independent documentation of infection (includes culture (+) strep but antibody negative group)

2. Often, but not always, unusual response to vaccines including lack of serological response to vaccines

3. Often, but not always, a history of very frequent infections, including strep, before age 2

 

A. With humoral (B-cell) immunodeficiency - includes CVID, subclass deficiency, HyperIgE/Job and HyperIgM (including female type)

 

B. With cell-mediated (T-cell) immunodeficiency

 

 

Note:

 

1. Children may start off as PANDAS, PANDAM or PANDAF but as they get older and persistent infections pile up, most end up as PANDAX

 

2. Children with Type 1 PITANDS may start off immunocompetent but then become progressively (and usually selectively) immunocompromised. This is different that the Type 2 group where the children are immunocompromised very early on.

[Allison]

Thank you Dr. T. This is very good.

 

I wonder about your #4 in that Im not sure we see rapid improvement. Can you qualify that?

 

I like the Pandax subgroup as I do think it fits my dd16.

 

A

[momto2pandas]

I like it VERY much (as you know my vote has been to broaden the criteria for a long time), but why not include an autoimmune component? Especially given that the "A" is still in the name, shouldn't there be something about "A" somewhere in the criteria? Could be as general as something like "generally associated with evidence of autoimmunity e.g. comorbid diagnoses, autoantibodies, etc." Otherwise, aren't there infections that could directly cause neuro symptoms and that you would want to distinguish from PITAND (Hep C, syphilis, maybe even meningitis, other febrile conditions, etc.) - especially since you're being very broad with the possible range of neuropsych symptoms and not requiring acute onset?

 

Might also want to say something about "appropriate" antibiotics, since obviously most will not improve with the wrong antibiotic.

 

Also, are you saying that for Type 2 PITANDS, you don't specify the agent, i.e. S, M, or F, as you do for Type 1 PITANDS, presumably because you might not easily figure it out given failure to produce a serological response? If that's true, then it might be difficult to meet the general criteria #3 since it might be difficult to actually "identify" the specific infectious agent, even though you can see that an infection is happening.

 

Can you really diagnose this down to age 0? How do you identify neuropsychiatric symptoms in a young infant?

 

How does Note #2 at bottom work into the classification? I'm thinking, for example, about my 3 and 6 year olds, who were just immunologically tested for the first time. How would I know if they were the Type 1 group and had become immunocompromised over time vs. the Type 2 group? They did have a bunch of early infections, but so do a lot of babies. Is this meaningful for treatment? My guess is that most cases don't get immune testing until after PANDAS has been diagnosed already and then how do you know if you were Type 1 with immunolopathological sequelae vs. Type 2?

 

 

Proposal for a working definition and classification of PITANDS

 

 

Working definition of PITANDS

 

1. First onset of symptoms in Pediatric age group 0-18 years

 

2. Acute or persistent onset of neuropsychiatric symptoms, characteristically, but not limited to tics or OCD

 

3. Usually, but not always, in association with an acute or persistent identified infectious triggers (GABHS, mycoplasma, others)

 

4. Rapid improvement of symptoms with anti-infective agents, usually antibiotics

 

 

Notice these criteria are much broader than the Swedo PANDAS criteria, still verifiable, but still including most children discussed in this forum.

 

Notice that the hardest to verify part, the "autoimmune" part, is left out of the criteria (though it always behind the scenes)

 

 

 

 

 

SUBGROUPS

 

Type 1 PITANDS - PITANDS in an apparently immunocompetent host

 

A. PANDAS (exclusively streptococcal trigger) - more common in younger children

Swedo-type (classical PANDAS)

PANDAS variants OR atypical PANDAS(see PAVONE ET AL, 2006)

 

B. PANDAM (exclusively mycoplasma trigger)

 

C. PANDAF (exclusively flagellated bacteria trigger) - covers Lyme and Lyme-like cases - maybe be the most common non-PANDAX group

 

D. PANDAX (multiple infectious triggers) - many of our children fall into this category - more common in older children

 

E. Idiopathic anti-INFECTIVE-responsive neuropsychiatric disorder, not otherwise specified (PITANDS-NOS) - the wastebasket group

 

 

Type 2 PITANDS - PITANDS in an congenitally immunocompromised host

 

This group typically shows:

 

1. Lack of serological response to known triggers despite independent documentation of infection (includes culture (+) strep but antibody negative group)

2. Often, but not always, unusual response to vaccines including lack of serological response to vaccines

3. Often, but not always, a history of very frequent infections, including strep, before age 2

 

A. With humoral (B-cell) immunodeficiency - includes CVID, subclass deficiency, HyperIgE/Job and HyperIgM (including female type)

 

B. With cell-mediated (T-cell) immunodeficiency

 

 

Note:

 

1. Children may start off as PANDAS, PANDAM or PANDAF but as they get older and persistent infections pile up, most end up as PANDAX

 

2. Children with Type 1 PITANDS may start off immunocompetent but then become progressively (and usually selectively) immunocompromised. This is different that the Type 2 group where the children are immunocompromised very early on.

[momto2pandas]

Forgot to mention that you may also want to add anorexia nervosa to the list of "characteristic" or "possible" neuropsychiatric symptoms. I'm betting that PANDAS is at least as frequently overlooked as a cause of anorexia nervosa - probably more so - than it is as a cause of OCD or tics. And given the morbidity and mortality (and healthcare expense!) caused by anorexia, this is particularly tragic. Adding it as an example of a possible manifestation might help to bring to mind that PITANDS should be ruled out for cases of abrupt onset anorexia, particularly in the younger set and in the absence of obvious psychological risk factors.

 

Proposal for a working definition and classification of PITANDS

 

 

Working definition of PITANDS

 

1. First onset of symptoms in Pediatric age group 0-18 years

 

2. Acute or persistent onset of neuropsychiatric symptoms, characteristically, but not limited to tics or OCD

 

3. Usually, but not always, in association with an acute or persistent identified infectious triggers (GABHS, mycoplasma, others)

 

4. Rapid improvement of symptoms with anti-infective agents, usually antibiotics

 

 

Notice these criteria are much broader than the Swedo PANDAS criteria, still verifiable, but still including most children discussed in this forum.

 

Notice that the hardest to verify part, the "autoimmune" part, is left out of the criteria (though it always behind the scenes)

 

 

 

 

 

SUBGROUPS

 

Type 1 PITANDS - PITANDS in an apparently immunocompetent host

 

A. PANDAS (exclusively streptococcal trigger) - more common in younger children

Swedo-type (classical PANDAS)

PANDAS variants OR atypical PANDAS(see PAVONE ET AL, 2006)

 

B. PANDAM (exclusively mycoplasma trigger)

 

C. PANDAF (exclusively flagellated bacteria trigger) - covers Lyme and Lyme-like cases - maybe be the most common non-PANDAX group

 

D. PANDAX (multiple infectious triggers) - many of our children fall into this category - more common in older children

 

E. Idiopathic anti-INFECTIVE-responsive neuropsychiatric disorder, not otherwise specified (PITANDS-NOS) - the wastebasket group

 

 

Type 2 PITANDS - PITANDS in an congenitally immunocompromised host

 

This group typically shows:

 

1. Lack of serological response to known triggers despite independent documentation of infection (includes culture (+) strep but antibody negative group)

2. Often, but not always, unusual response to vaccines including lack of serological response to vaccines

3. Often, but not always, a history of very frequent infections, including strep, before age 2

 

A. With humoral (B-cell) immunodeficiency - includes CVID, subclass deficiency, HyperIgE/Job and HyperIgM (including female type)

 

B. With cell-mediated (T-cell) immunodeficiency

 

 

Note:

 

1. Children may start off as PANDAS, PANDAM or PANDAF but as they get older and persistent infections pile up, most end up as PANDAX

 

2. Children with Type 1 PITANDS may start off immunocompetent but then become progressively (and usually selectively) immunocompromised. This is different that the Type 2 group where the children are immunocompromised very early on.

[LNN]

Proposal for a working definition and classification of PITANDS

Notice that the hardest to verify part, the "autoimmune" part, is left out of the criteria (though it always behind the scenes)

 

SUBGROUPS

 

Type 1 PITANDS - PITANDS in an apparently immunocompetent host

 

 

E. Idiopathic anti-INFECTIVE-responsive neuropsychiatric disorder, not otherwise specified (PITANDS-NOS) - the wastebasket group

 

I think it's good to widen the net and move away from the strep aspect of the disease. This seems to be the big source of controversy, so I applaud the focus on infectious agent, but I'm trying to look at this from the perspective of a naysayer...

 

It seems like classic childhood OCD and chronic tic cases would fall into Type 1 subgroup E "wastebasket" and yet this is presumably the largest class of kids in the general population. And if I'm reading correctly, a kid gets put into this group if they develop OCD or tics and doesn't respond to antibiotics. Am I mis-reading? Would this definition suggest that all kids who develop OCD or tics first be treated with abx and non-responders would be diagnosed with classic OCD/tics? This would draw tremendous attack from naysayers and would doom a number of kids if they were given the wrong abx, an insufficient dosage or for too short of a time. Can you clarify this for me?

 

I'll go back to my soapbox and say that my wish for the upcoming think tanks is that a uniform series of diagnostic tests be agreed upon so that we can start to look at all patients with the same data - a full immuno workup (whatever that might entail), tests for mycoplasma and lyme (from the correct lab), ANA levels, CAM K II levels, an illness history questionnaire, and a neuro exam to check for choreiform movements including piano playing. I think until we start gathering consistent data prior to treatments, we won't be able to say why something works for some and not others - the naysayers will have a field day with "bad research." Somehow the autoimmunity piece has to be captured in order to distinguish this disease type and justify the current family of treatments (especially from an insurance perspective)

 

Likewise, without long term follow up tracking the same data, we're not capturing the full story of what works, what doesn't and why. Parents are left playing roulette with our kids futures.

 

I think you're on the right track with sub-groups, each having a different trigger (and possibly a different course of treatments) - and away from strep and the only trigger. I'd lust love to see some uniform data points gathered along this track.

[thereishope]

So, if the child's sudden onset is triggered by strep but then the child has subsequent exacerbations from other triggers, would that be PANDAS or PANDAX?

 

For my son, first sudden onset brought on by first known strep infection. During recovery, viral triggers would increase PANDAS symptoms. the futher on in recovery, the viral trigers weakened. Strep remained the "big gun".

 

Prior to the strep triggered sudden onset, the only problem was a reaction to the chicken pox vaccine.

 

So, I guess my son would be...started as PANDAS, graduated to PANDAX, but is in a kind of limbo right now.

 

So, the child may always flip back and forth on the diagnosis or is it based on the initial cause that started it all?

[kimballot]

I like the focus on PITAND with PANDAS as a subgroup. I like the general list (1-4) under PITAND.

 

I am wondering if other neuropsychiatric symptoms should be included in the acute or persistent onset - specifically ADHD symptoms. My son initially presented as a toddler with hyperactivity, including chronic biting, hitting, headbutting, climbing, etc, that became unmanageable with sinus infections and then dropped off significantly with antibiotic. This cycle persisted for several years. He later told me he bit because he felt that if he did not bite he "couldn't breathe". Was this an OCD behavior that we did not recognize because he did not have the language to communicate it? He did not have his firs true "OCD" symptom or tic until age 5. If we expand the age of PITAND to 0-18, how would we know if a pre-linguistic child is having OCD issues? Perhaps my son is an exception, but I would hate to think that we would have missed 5 years of treatment even though the behaviors were so closely tied to infection and antibiotics. Also, today he continues to have attention problems as his initial symptom, though the tics and OCD follow if left untreated. Anyone else have ADHD as a primary issue?

 

Also - point of clarification- would all kids with this disorder be labeled "PITAND" and then the subgroup be identified with the current case? So my son would have "PITAND" and if he his strep throat triggered a reaction last year he would have had PITAND - PANDAS last year, but if mycoplasma triggered one yesterday I would say he currently has PITAND-PANDAM ?

 

Also - regarding PITAND -NOS - would things like allergy triggers, or H1N1 triggers fall into this category?

 

 

Thank you, again, for everything. I cannot tell you how helpful and exciting it is to be in touch with people who can make sense of all of my experiences for the last 13 years!

[dcmom]

I agree with most of the replies.

 

If this working definition is to be published, I would agree that somewhere needs to be an exhaustive list of possible neuropsychiatric symptoms. Many doctors are not well versed on the ways ocd manifests.

 

My major concern is the quick response to antibiotics. Unfortunately, I really don't think this should be used as a criteria. My younger- classic Swedo-type pandas, only responded to antibiotics after 30 days of daily zithromax (which followed about 30 days of amoxicillin). I don't think anyone would consider this rapid. After this initial episode, she had another episode which did not respond to antibiotics, but did respond to steriods and finally plasma pheresis.

 

My second daughter had a milder onset at the same time, she went untreated for much longer. She did not respond to antibiotics, however did respond to steroids.

 

I would hate to see a bunch of these kids turned away as pandas, if they don't respond quickly to antibiotics. If most of our kids did, this forum would not be so busy!

 

Thanks Dr T!

[Worried_Dad]

As others have stated, I really like the broadening to include multiple infectious triggers / subgroups. I agree that this has provided plenty of fuel for the skeptics' fires: presentation can vary considerably, and no single treatment regimen works for every child. With different underlying causes that manifest similarly, that makes sense. But - of course - critics can always use that as ammo to complain that the disorder is too "fuzzy," too ill-defined to be a distinct clinical entity. Don't know how to counteract that, since this bloody illness does seem pretty fuzzy!

 

I'd echo momto2pandas's point about anorexia. This was perhaps the most terrifying symptom our son exhibited - he lost 20 pounds in a couple of months, and getting him to eat anything during that time was sheer torture. Buster's / EAmom's daughter had to be hospitalized because of anorexia.

 

I also loved LLM's point about developing a uniform series of diagnostic tests. Our son's ASO did rise during exacerbations, so we're pretty sure strep was the trigger... but he's older (13) and - as you point out, Dr. T - seems like the older kids usually wind up with PANDAX / multiple triggers. Our original DAN doc did test for Lyme initially, but I don't think he did the "top-tier" Lyme testing with Igenex or another gold-standard Lyme lab. And we never had a test for myco p. or any full-blown immuno workup. Even though our son's doing great on the high-dose augmentin XR, I get paranoid when I read various forum posts about possible co-infections that we haven't tested for!

 

This is great stuff, Dr. T. And broadening the triggers from just strep does seem like it might satisfy some of the prominent naysayers who say "maybe PAND exists, but not PANDAS."

 

BTW - the "PITANDS" acronym (vs.PITAND)? Does that final S stand for "Syndrome"? "Spectrum"? Just curious. Definitely seems like this is a spectrum disorder (and frankly - as our son was originally diagnosed ARF/SC - PANDAS itself seems to be part of a spectrum that could include ARF and SC as well).

[7upMom]

BTW - the "PITANDS" acronym (vs.PITAND)? Does that final S stand for "Syndrome"? "Spectrum"? Just curious. Definitely seems like this is a spectrum disorder (and frankly - as our son was originally diagnosed ARF/SC - PANDAS itself seems to be part of a spectrum that could include ARF and SC as well).

 

True, we were also diagnosed RF as have been a lot of other PANDAS parents. The immune doc here told us "that is a completely separate issue- one has nothing to do with the other and we are not even going to discuss the R/F" So clarification wise- is it a misdiagnosis but actually was pandas they just weren't as aware of Pandas before? or is it completely its own separate thing or included ?

[dut]

Hello.

 

Good stuff....

 

Could no. 4 use a word different from "rapid" or leave it out all together.

 

Could the auto-immune angle be used on no. 4 too? Such as anti-infective or immune -modulating agents?

 

I know that not every single case can be covered by a diagnostic criteria but I imagine that we are like many other cases in that initial triggering episodes responded well to abx (strep or myco) but later episodes don't and that is when steroids/IVIG/PEX (or time) does the trick.

 

I like the 0-18 years. With hindsight and the benefit of an older child with PANDAS (if you can say that), we have pinpointed our ds' probable earliest symptoms to 7 months old. I really believe this disorder starts way younger with these children than is acknowledged and welcome the opportunity for that to be recognised, despite the difficulties surrounding recognising the symptoms in very young children.

 

Thanks for being so very proactive

[momto2pandas]

One other thing that just occurred to me in the shower: what about neuro symptoms that aren't considered psychiatric? Are sensory issues/symptoms ubiquitous enough to fit in there somewhere? What about other things, like speech issues/changes, handwriting changes, etc.?

 

My kids express sensory issues and speech changes (starting words/sentences multiple times) much more than they do "psychiatric" symptoms, I would say, and the sensory/neuro issues started much earlier.

 

Speaking of which, my ds3's speech pathologist said that she's had other PANDAS patients and that his particular "dysfluencies" are characteristic of PANDAS in her experience. Has anyone else seen this or has this been noted anywhere?

 

 

 

Proposal for a working definition and classification of PITANDS

 

 

Working definition of PITANDS

 

1. First onset of symptoms in Pediatric age group 0-18 years

 

2. Acute or persistent onset of neuropsychiatric symptoms, characteristically, but not limited to tics or OCD

 

3. Usually, but not always, in association with an acute or persistent identified infectious triggers (GABHS, mycoplasma, others)

 

4. Rapid improvement of symptoms with anti-infective agents, usually antibiotics

 

 

Notice these criteria are much broader than the Swedo PANDAS criteria, still verifiable, but still including most children discussed in this forum.

 

Notice that the hardest to verify part, the "autoimmune" part, is left out of the criteria (though it always behind the scenes)

 

 

 

 

 

SUBGROUPS

 

Type 1 PITANDS - PITANDS in an apparently immunocompetent host

 

A. PANDAS (exclusively streptococcal trigger) - more common in younger children

Swedo-type (classical PANDAS)

PANDAS variants OR atypical PANDAS(see PAVONE ET AL, 2006)

 

B. PANDAM (exclusively mycoplasma trigger)

 

C. PANDAF (exclusively flagellated bacteria trigger) - covers Lyme and Lyme-like cases - maybe be the most common non-PANDAX group

 

D. PANDAX (multiple infectious triggers) - many of our children fall into this category - more common in older children

 

E. Idiopathic anti-INFECTIVE-responsive neuropsychiatric disorder, not otherwise specified (PITANDS-NOS) - the wastebasket group

 

 

Type 2 PITANDS - PITANDS in an congenitally immunocompromised host

 

This group typically shows:

 

1. Lack of serological response to known triggers despite independent documentation of infection (includes culture (+) strep but antibody negative group)

2. Often, but not always, unusual response to vaccines including lack of serological response to vaccines

3. Often, but not always, a history of very frequent infections, including strep, before age 2

 

A. With humoral (B-cell) immunodeficiency - includes CVID, subclass deficiency, HyperIgE/Job and HyperIgM (including female type)

 

B. With cell-mediated (T-cell) immunodeficiency

 

 

Note:

 

1. Children may start off as PANDAS, PANDAM or PANDAF but as they get older and persistent infections pile up, most end up as PANDAX

 

2. Children with Type 1 PITANDS may start off immunocompetent but then become progressively (and usually selectively) immunocompromised. This is different that the Type 2 group where the children are immunocompromised very early on.

[simplygina]

I definitely like the idea of expanding the definition to include multiple triggers. Not sure if strep is what started it all for us, but I know it has definitely been a trigger. I suspect we are PANDAX now because colds and allergies now cause a downward spiral as well. Do we think that catching classic PANDAS early on would prevent a move to the PANDAX group over time?

 

And I do think changing the age requirement is a good thing. Looking back over my son's medical history, he began to show aggressive tendencies and severe sensory issues at about 2 following a year where he had something like 8 ear infections. I think THAT is really when his issues started, but strep at age 5 is when the stuff hit the fan. By lowering the age, maybe we can catch things for some kids sooner.

 

I hope by changing the criteria pediatricians would be aware to watch for psycho-nuerological changes in their patients that do have a lot of infections. A list of possible manifestations would be critical in my opinion. For me I didn't know if we'd just hit the terrible twos or what, but looking back, the sensory issues and change from being very good natured to very aggressive should have been a red flag. I'd hate to subject kids to a million tests when but when a kid is having soooo many ear infections and is unable to clear them, shouldn't we be wondering what is going on. Especially when the constant ear infections clear but then the constant strep starts. That is my biggest complaint with most doctors these days, they don't look for "why", they just treat the 7th ear infection and schedule tubes assuming "why" doesn't matter as long as we fix it. Then later treat the 7th strep infection and schedule the T & A assuming that will fix the strep problem. But I now realize the "why" can still affect them in other ways because it hasn't been addressed. And if that same kid is the one the mom starts bringing in saying, something is wrong, does he have ADHD? Something is wrong, i think he has OCD. Something is wrong, he gets so many stomachaches and headaches. Something is wrong I think he has Tourettes. Something is wrong, does he have a learning disorder because his schoolwork is deteriorating and his handwriting is awful. Shouldn't a doctor be able to connect the dots here? Why is this one kid having so many problems!!! Changing the criteria would help, but I guess the big question is how we get pediatricians on board with this. How do we find a way to get the word out so it is common knowledge, not something they think they read something about once but it is so rare it can't possibly be your kid.

[Fixit]

One other thing that just occurred to me in the shower: what about neuro symptoms that aren't considered psychiatric? Are sensory issues/symptoms ubiquitous enough to fit in there somewhere? What about other things, like speech issues/changes, handwriting changes, etc.?

 

My kids express sensory issues and speech changes (starting words/sentences multiple times) much more than they do "psychiatric" symptoms, I would say, and the sensory/neuro issues started much earlier.

 

Speaking of which, my ds3's speech pathologist said that she's had other PANDAS patients and that his particular "dysfluencies" are characteristic of PANDAS in her experience. Has anyone else seen this or has this been noted anywhere?

 

 

I almost wonder if these would be a precurser to tendency of gettings pit/pans as the body is growing.....then if these children catch something...it explodes with the more obvious symptoms

 

my ds

sensory/tactile issues *******

oppostional

hand writing

[JAG10]

Momto2pandas,

 

I am a SLP and have always been keenly aware of my dd10's changes in fluency and linguistic output. Before we were recently made aware of the PANDAS connection, we were on the psychiatric med merry-go-round for 4 years. She usually had a positive response to SSRIs that would quickly fade as well as result in behavioral activation. One thing I would always notice on the initial positive side would be her improvement in linguistic fluency, word retrieval and vocabulary usage (which duh, helps socially). Similarly, so went the handwriting, so went dd10. You can look at her assignment copybook and see the patterns of fluxuation in her handwriting that matched how she was functioning at that time. Since on to PANDAS and abx, we have seen similar improvements and ups & downs in her language and handwriting. I viewed these changes as her manifestation of cognitive static, but isn't it interesting that these symptoms (albeit temporarily) improved with SSRIs (not stimulants or mood stabilizers) and abx. similarly to OCD.

 

The psychiatrists would always look at me funny when I would describe these types of improvements with SSRIs or indicators of decline when they stopped working.

 

Jill