By far the
most read post in this blog is one about histamine and allergies, which means
many people are searching on Google for “histamine, allergy and autism”.
Our reader Kei recently commented that his daughter, without allergy, was again showing signs of summertime raging and that his neurologist confirmed that summertime raging does indeed happen and nobody knows why.
I did figure
out how to deal with our version of “summertime raging” and the post-bumetanide
“dumber in the summer” phenomena. There
were several posts on this subject. The lasting
solution was to treat the raging as if it was caused by inflammation driven by
pollen allergy and to note that inflammation will further worsen the KCC2/NKCC1
imbalance in Bumetanide-responsive autism, making those people appear “dumber
in the summer”. This also accounts for
the “Bumetanide has stopped working” phenomenon, reported by some parents. You need to minimize inflammation from
allergy and increase Bumetanide (or add Azosemide). My discovery was that Verapamil was actually
more effective than anti-histamines and actual mast cell stabilizers. Mast
cells degranulate via a process dependent of the L-type calcium channels that
Verapamil blocks. Mast cells release
histamine and inflammatory cytokines like IL-6.
This spring
when Monty’s brother asked why Monty was acting dumber, it was time to
implement the “dumber in the summer” therapies.
Add a morning tablet of cetirizine (Zyrtec) and a nasal spray of Dymista
(Azelastine + Fluticasone).
Dymista is
inexpensive and OTC where we live, but I see in the US it is quite an expensive
prescription drug. It is a favourite of
Monty’s pediatrician and his ENT doctor.
Summertime
Regression in the Research Literature
I recently
came across two very relevant papers on this subject by a proactive American
immunologist called Dr Marvin Boris. If
you live in New York, he looks like a useful person to know.
In his first
study he investigated whether the onset of the allergy season caused a
deterioration in behavior of children with autism or ADHD; in more than half of
the trial subjects, it did.
In his
second study he went on to make a double‐blind crossover study with nasal
inhalation of a pollen extract or placebo on alternate weeks during the
winter. This was his way to recreate the
pollen season during winter.
Sixteen
of 29 (55%) children with ASD and 12 of 18 (67%) children with ADHD or a total
of 28 of 47 (60%) children regressed significantly from their baseline. Nasal
pollen challenge produced significant neurobehavioral regression in these
children. This regression occurred in both allergic and non‐allergic children
and was not associated with respiratory symptoms.
In other
words, half of children with autism regress when exposed to pollen, even though
they may not show any symptoms of allergy, or test positive for allergy. This should be of interest to Kei and his
neurologist.
Purpose: To determine
whether children with autistic spectrum disorders (ASD) or attention deficit
hyperactive disorder (ADHD) exhibit neurobehavioral regressive changes during
pollen seasons.
Design: A behavioral
questionnaire‐based survey, with results matched to pollen counts; an
uncontrolled, open non‐intervention study.
Materials and Methods: Twenty‐nine children identified with ASD and 18 children
with ADHD comprised the study population. The parents of the study children
completed the Allergic Symptom Screen for 2 weeks during the winter prior to
the pollen allergy season under investigation. The parents of the ASD children
also completed the Aberrant Behavior Checklist and the parents of the ADHD
children completed Conners' Revised Parent Short Form for the same periods. The
parents completed the respective forms weekly from 1 March to 31 October 2002.
Pollen counts from the geographical area of study were recorded on a daily
basis during this period.
Results: During natural
pollen exposure, 15 of 29 (52%) children with ASD and 10 of 18 (56%) children with
ADHD demonstrated neurobehavioral regression. There was no correlation with the
child's allergic status (IgE, skin tests and RAST) or allergy symptoms.
Conclusions: Pollen
exposure can produce neurobehavioral regression in the majority of children
with ASD or ADHD on a non‐IgE‐mediated mechanism. Psychological dysfunction can
be potentiated by environmental exposures.
Pollen Exposure as a Cause for the Deterioration of Neurobehavioral Function in Children with Autism and Attention Deficit Hyperactive Disorder: Nasal Pollen Challenge
Purpose: In a previous study
it was established that children with attention deficit hyperactive disorder
(ADHD) and autistic spectrum disorders (ASD) had regressed during pollen
seasons. The purpose of this study was to determine if these children regressed
on direct nasal pollen challenge.
Design: A double‐blind crossover
placebo‐controlled nasal challenge study. Materials and Methods: Twenty‐nine
children with ASD and 18 with ADHD comprised the population. The study was a
double‐blind crossover with nasal instillation of a pollen extract or placebo
on alternate weeks during the winter. The pollens used were oak tree, timothy
grass and ragweed. The dose insufflated into each nostril was 25 mg (±15%) of
each pollen.
Results: Sixteen of 29 (55%) children with ASD and 12 of 18 (67%) children
with ADHD or a total of 28 of 47 (60%) children regressed significantly from their baseline.
Nasal pollen challenge produced significant
neurobehavioral regression in these children. This regression occurred in both
allergic and non‐allergic children and was not associated with respiratory
symptoms. There was no correlation to the child's IgE level, positive RAST
pollen tests, or skin tests.
Conclusion
When I was figuring out Monty’s
summertime raging and cognitive decline, several years ago, there were no
significant signs of allergy present.
Nowadays there are far more visible signs of allergy.
Dr Boris does not suggest any therapy
for summertime raging, but he did show that it can be driven by pollen in half of
those with autism, even children who have no signs of having any allergy.
His studies were published more than a
decade ago and seem to have been forgotten.
This seems a pity, but it says a lot.
I only stumbled upon his papers
because I was reading another of his decade old papers. That paper is based on his early use of
Pioglitazone in autism, which resulted in several hundred children being
successfully prescribed this drug. Pioglitazone selectively stimulates the
peroxisome proliferator-activated receptor gamma (PPAR-γ) and to a
lesser extent PPAR-α.
There was a bladder cancer scare, lots
of hungry lawyers and I suppose people stopped prescribing Pioglitazone for
autism a decade ago. The numerous subsequent safety
studies and meta-analysis show either a small increased risk, or no increased
risk, very much dependent on who financed the research. Pioglitazone is given to people with type 2
diabetes, and they are already at an increased risk of bladder cancer. In those people, that risk increases between
0 and about 20%, depending on the study.
We are talking about 0.07% to 0.1% of people with T2 diabetes taking
Pioglitazone later developing bladder cancer.
A decade later and Pioglitazone is
again back in fashion with trials in humans with autism and studies in mouse
models of autism. The current autism research does not see cancer risk as
reason not to use Pioglitazone. I agree
with them.
It looks like a minority of people
taking Pioglitazone are more likely to suffer upper respiratory tract
infections. That is the risk that I
consider relevant. I also note that in
trials even the placebo can appear to cause upper respiratory tract infections.
Pioglitazone was covered in earlier posts,
but there will soon be a new post. For most people I think histamine, allergy and summertime raging will continue to be of more interest.