Letters Response

Amar Dhillon replies to “Pathology reports solve ‘new bowel disease’ riddle”

BMJ 2011; 343 doi: http://dx.doi.org/10.1136/bmj.d7907 (Published 07 December 2011) Cite this as: BMJ 2011;343:d7907
  1. Amar Dhillon, pathologist1
  1. 1Department of Cellular Pathology, UCL Medical School, Royal Free Campus, London NW3 2PF, UK
  1. a.dhillon{at}ucl.ac.uk

The reappearance of some of my histology grading sheets for the Wakefield study is interesting.1 2 I have not seen them since 1997-8, when I gave them to Andy Wakefield. The BMJ’s articles on these grading sheets in the issue of 12 November show several misunderstandings.3 Many are a result of a lack of understanding of the difference between, on the one hand, the systematic documentation of specific microscopical features in a grading sheet by a “blinded” pathologist and, on the other, conclusion of an overall clinicopathological diagnosis by integrating clinical information with diverse lines of investigation. The difference between the two activities should be understood better.

Routine diagnostic histopathology is done with knowledge of an individual patient’s clinical details at the time of diagnostic reporting, so rendering a diagnostic histopathological opinion is usual and appropriate (in direct contrast to a blinded research review). The perceived clinical significance of microscopic observations may change as further clinical and other information becomes available, and the histological diagnostic interpretation might have to be corrected subsequently. Bowel disease is not diagnosed by gut mucosal histopathology alone: “A final diagnosis can only be made with the full clinical information and a biopsy specimen should be reported as diagnostic only if full supportive clinical information is available.”4

The online grading sheets are an incomplete record of my observations of the slides of gut mucosal biopsy specimens from patients included in the Lancet 1998 study, and there were also “normal control” biopsy samples. Which slides were of study cases and which were controls was unknown to me. Neither the clinical details of each case nor the original diagnostic histopathology reports were available to me.

The boxes with assigned patient “case numbers” on the online grading sheets have been put on to the grading sheets by someone else: this information was not available to me at the time of my review of the slides.

Of those grading sheets attributed to me, not all are mine. Grading sheets on pp 38-47 and pp 55-64 inclusive belong to someone else.1 By themselves, my grading sheet observations cannot conclude a final diagnostic assignment of colitis (which has to be made in the light of full clinical/endoscopic/radiologic/laboratory data and response to treatment). On my grading sheets “nonspecific” means “this microscopical appearance doesn’t remind me of any particular disease entity.”

In 1998 there was no paediatric gastrointestinal pathology literature to refer to for guidance about ileal and colonic mucosal biopsy microscopical appearances and their interpretation or significance in autistic children. In 1998 the series of cases in the Lancet paper was unusual, if not unique, and it was one of the aims of the study to explore the significance or otherwise of the subtle histological changes in autistic children with gastrointestinal symptoms. Prejudgment of the significance or otherwise of the histological changes in isolation in the 1998 study cases would have been inappropriate previously, and remains so now. Several expert gastrointestinal pathologists and gastroenterologists commenting on the grading sheets stated in the BMJ that the findings cannot be colitis. However:

  • To apply uncritically adult gastrointestinal biopsy histopathological thresholds of normality v abnormality to children is a mistake

  • To try to assess the diagnostic implications of data represented in histopathological grading sheets in isolation is a mistake

  • The current opinions of the experts on the significance of the histology grading sheet observations are subject to retrospective bias through knowledge of events since 1998.

At the time of submission of the Lancet 1998 publication I had the clinical, laboratory, endoscopic, and histology information presented to me in summary tabular form and as aggregated descriptive text. My grading sheets were with Andy Wakefield, and my general recollection of my impression of my slide review was that some biopsy specimens were a bit inflamed and others were not. So far as I recall, the changes were not severe in any of the slides, but it is not unusual for gut mucosal biopsies to show little abnormality even in clinically well defined cases of gastrointestinal disease, particularly in children. My clinical colleagues had collated all of the available information, including my microscopical grading sheet observations in the context of their knowledge of each patient’s condition and concluded a final diagnosis of colitis when this was considered by them to be appropriate. Thus, at the time of submission of the Lancet 1998 publication, with the limited supplementary information available to me and in the context of a comprehensive clinicopathological review by trusted clinical colleagues, the designated diagnosis of colitis seemed to me to be plausible.

Notes

Cite this as: BMJ 2011;343:d7907

Footnotes

  • This statement is not a formal representation of UCL’s position.

  • Competing interests: AD is a co-author of the Wakefield paper.2

References