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Feature Autism Research

Wakefield’s “autistic enterocolitis” under the microscope

BMJ 2010; 340 doi: (Published 15 April 2010) Cite this as: BMJ 2010;340:c1127

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Caution in assessing histopathological opinions.

As one of the pathologists in question, I wish to respond to some of
the issues raised in the recent article by Brian Deer(1), and accompanying
editorial by Nick Wright(2), on the histopathological aspects of autistic
enterocolitis. There is some misrepresentation of my involvement and lack
of understanding of the process in studies involving histopathology.

Firstly, at the time in question I was working solely for the NHS and
acted as the key pathologist for the clinical gastroenterology paediatric
team. I was not the lead pathologist for this, or any other Wakefield

Secondly, I was not responsible for reporting the majority of the
biopsy specimens from the twelve children, initially written up in the
Lancet paper(3). This period predated the advent of subspecialty reporting
and a number of consultants, each with varying levels of expertise and
gastroenterology interest, were responsible for reporting these cases. It
is erroneous to consider these reports to be more accurate than any
subsequent review. Nick Wright writes that there is nothing intrinsically
wrong with such a review of the histopathology. I would state more
strongly that ANY study of histopathology has more credence, with reduced
inter- and intra-observer variation, when a systematic review, using
defined structured criteria over a short time-frame, is performed.

As to the severity of any pathology, there was a gradual awareness by
those attending the regular clinicopathological conferences that we were
identifying subtle changes in some of the mucosal biopsies from autistic
children. Subtle does not always indicate insignificant: the focal
features of cow’s milk protein enteropathy may be misinterpreted as
normal; the hidden pathogen in immunodeficient syndromes is identified
only by close scrutiny; the presence of Helicobacter pylori in gastric
biopsies was previously not recorded, as they were considered

The significance of any minor changes cannot be determined at the
outset; the natural history evolves and/or may be altered by any therapy,
but the changes must first be recognised. It may not be widely appreciated
that the separation of the upper limit of normal from the lower spectrum
of abnormal in histopathology is not always clear cut (and not only in the
gastrointestinal tract).

Without going into extensive detailed histopathological description,
there does appear to be some confusion within the discussion of these
cases. It should be appreciated that the term ‘colitis’ covers a range of
changes from minimal, self-limiting and non-specific, to extensive, severe
and characteristic; as such it is difficult to select a point from within
a spectrum for a single definition. Reference was made to focal active
colitis(4), although later it is stated that minor changes are not to be
called colitis. In personal practice, as evidenced at the GMC hearing, I
had a different threshold from the other co-authors who performed the
review and translated those findings into words.

While a clinical gastroenterologist might consider caecal active
inflammation with incipient crypt abscess formation to be normal in
children(1), this is a significant finding to be recorded by pathologists.

The dismissal of ‘a bit of architectural distortion’ as insignificant
underscores the problem of histopathological complexity as this, in fact,
is a key feature in the assessment of colonic biopsies(5).

Time may indeed bring greater clarity to our understanding of what,
if any histopathological changes may be associated with autism.


1. Deer B. Wakefield’s ‘autistic colitis’ under the microscope. BMJ 2010;
340: 838-41.

2. Wright N. Does autistic enterocolitis exist? BMJ 2010; 340: 819-821.

3. Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, et
al. Ileal-lymphoid-nodular hyperplasia, nonspecific colitis, and pervasive
developmental disorders in children. Lancet 1998; 351: 637-41.

4. Greenson JK, Stern RA, Carpenter SL, Barnett JL. The clinical
significance of focal active colitis. Hum Pathol 1997;28:729-33.[

5. Jenkins D, Balsitis M, Gallivan S et al. Guidelines for the initial
biopsy diagnosis of suspected chronic idiopathic inflammatory bowel
disease. The British Society of Gastroenterology Initiative. J. Clin.
Pathol. 1997; 50; 93–105.

Susan E Davies

Competing interests:
None declared

Competing interests: No competing interests

30 April 2010
Susan E Davies
Consultant Histopathologist
Addenbrooke's Hospital, Cambridge CB2 0QQ