Autism and the gut
Ben Goldacre's dissection of the woeful Observer autism article
(defended by the Observer's readers' editor, and oh so unconnected
with the same journalist's interview with Wakefield before his GMC
hearing) has finally been published in the Guardian and the BMJ.
I don't need to bang on any more on that topic, but something that has
baffled me is the continuing support for Wakefield from so many
parents. What is it that the MMR 'link' with autism does for them? I
suppose it gives them someone to blame (or sue), and perhaps lets them
off the hook if they have the misguided worry that it is somehow their
fault (say from upbringing or genetics), although I'm not too sure how
it is anymore palatable than that they gave their child autism by
giving them the MMR.
Of course there are always cranks and crackpots, and the anti-vaccine
movement has a long and not so illustrious history preceding the MMR
controversy, but looking at the comments from these parents in many of
the above discussions it struck me that something many of them
mentioned was the gut symptoms that their autistic children showed.
This has been something of a focus of Wakefield, who originally set
out to blame Crohn's disease on measles infection. So how many people
would we expect to show this association?
MMR is given in two injections at ages 1-5yrs, on a back of the
envelope calculation (assuming no connection, which may well not be
valid), if we just look at proper inflammatory bowel disease rather
than just vague gut symptoms we find that taking annual incidence of
6/100k for IBD, and 8/10k for autism spectrum, and estimating around 4
million of the little blighters in the UK, that we'd only expect about
one child to show both over that period.
However, if we broaden our coverage to gut symptoms in general we get
a rather different story, it turns out that GI symptoms are rather
common, with some 16% of 10-11yr olds (you find the data for the under
5s!) fulfilling criteria for recurrent abdominal pain, and 2% showing
lymphonodular hyperplasia on endoscopy, suggesting several hundred
autistic spectrum children with lymphoid changes in the 1-5yr old age
range. Funnily enough it is ileal lymphonodular hyperplasia that
Wakefield reports as being associated with autism (with gut symptoms),
rather than true IBD, and it looks like he will have a steady supply
of patients with the right symptoms and timing to keep supporting him.
An interesting review appeared recently in Histopathology:
Aims: To review the literature on the histopathological diagnosis
of the condition termed `autistic enterocolitis'.
Methods and results: We have reviewed all published works where
mucosal biopsy specimens from autistic children have been examined
histopathologically. Abstracts were excluded. Our review of the
published works, nearly all from a single centre, identifies major
inconsistencies between studies, lack of appropriate controls and
misinterpretation of normal findings as pathology. Ileal lymphoid
hyperplasia may be more prevalent in children with regressive
autism but is also seen in children with food allergies and severe
constipation, the latter being an extremely common finding in
autistic children.
Conclusion: The histopathological diagnosis of autistic
enterocolitis should be treated with caution until a proper study
with appropriate methodology and controls is undertaken.
And concluded:
There is no doubt that autistic children suffer considerable gut
symptoms and these have a significant effect on their quality of
life. But is the claim that these children have an underlying IBD
justified? We can only speculate why severe constipation was not
acknowledged as a significant gut symptom in the original paper1
and was revealed only in correspondence.8 Having accepted, however,
that this was a major problem in these children, subsequent studies
from this group should have explicitly included developmentally
normal children with severe constipation as the appropriate control
group. The conclusions of the 1998 and 2000 papers from the Royal
Free must therefore be regarded as unreliable because of the use of
inappropriate controls. By the time this group did include a
control group with ILNH and constipation and indeed reported the
lack of significant difference in mucosal pathology between
autistic children and controls,3 media and public opinion were
already entrenched.
Significant bias was introduced to the studies from the Royal Free
by the interpretation of histological changes seen in normal
lymphoid follicles as pathology...It is also disturbing that the
investigators have not attempted to re-inforce the
histopathological diagnosis of enterocolitis by having the slides
examined in an open forum by independent pathologists, especially
since another small series has found no abnormalities...
There is no evidence from the papers discussed above that a
significant number of autistic children have `enteritis', i.e.
inflammation of the small intestine. The only consistent
abnormality seen in these children may be ILNH, but we have
explained why this finding is not unexpected in constipated
individuals...
Evidence has been presented to suggest that autistic children have
a `colitis'. In their efforts to present convincing findings,
however, the authors have failed to use appropriate controls and
rigorous methodology, leading to serious flaws and unreliable
conclusions...As to the aetiology of the colitis in autistic
children, there is no convincing evidence that the changes are due
to the autism per se. Indeed, as pointed out in the Royal Free
papers, many autistic children have severe constipation and/or food
allergy, either of which could be responsible for the pathological
abnormalities seen. Other possible causes of inflammation in these
children include parasitic infestation and swallowing foreign
bodies.
...
In conclusion, we are highly sceptical that `autistic
enterocolitis' is a genuine histopathological entity in children
with regressive autism. Further studies with rigorous methodology
and appropriate control groups could be carried out, but if these
are not possible, the histology slides from the autistic children
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