Autism, inflammatory bowel disease, and MMR vaccine
1998; Elsevier BV; Volume: 351; Issue: 9112 Linguagem: Inglês
10.1016/s0140-6736(05)79084-x
ISSN1474-547X
Autores Tópico(s)Viral gastroenteritis research and epidemiology
ResumoLetters in The Lancet and the letter of March 27, 1998 (PL/CMO/98/2) to all doctors by Sir Kenneth Calman, Chief Medical Oficer, Department of Health, on measles, mumps, and rubella (MMR) vaccine, Crohn's disease, and autism are in danger of completely obscuring the observation we made of an association between ileal lymphoid nodular hyperplasia, non-specific colitis, and autism in childhood. As the senior clinician on the study I would like to make several points.We did not describe any increase in Crohn's disease or ulcerative colitis in children with autism so the observations of Eric Fombonne (March 28, p 255)1Fombonne E Inflammatory bowel disease and autism.Lancet. 1998; 351: 955Summary Full Text Full Text PDF PubMed Scopus (24) Google Scholar are not surprising. What we did describe was non-specific colitis with ileal lymphoid nodular hyperplasia. The colitis we described was ignored in Robert Chen and Frank De Stefano's commentary accompanying our Lancet paper. Calman seeks to dismiss our findings concerning lymphoid hyperplasia and also makes no mention of colitis. Indeed, he selectively quotes from my own publications on this topic since 1983 but makes a number of false assumptions. Because our Lancet paper was a preliminary report we did not expand on the diagnostic term “ileal lymphoid nodular hyperplasia”. This is a term often used inexactly by radiologists and endoscopists to describe both a normal finding in children and a pathological finding which may be accompanied by abdominal pain and diarrhoea requiring therapy.The 1983 Walker-Smith, Hamilton, and Walker reference cited by Calman does indeed state that ileal lymphoid nodular hyperplasia “has been termed benign” but we went on to say that recurrent abdominal pain and diarrhoea often prompt a diagnostic barium study to permit this radiological diagnosis. We also stated that symptoms could be so severe that steroids may be used and even that surgery might be contemplated (although is this not recommended owing to uncertain knowledge concerning outcome). Calman also cites a 1990 radiological study3Lipson A Bartram CI Williams CB Slavin G Walker-Smith JA Barium studies and ileoscopy compared in children with suspected Crohn's disease.Clin Radiol. 1990; 41: 5-8Summary Full Text PDF PubMed Scopus (64) Google Scholar which indicated that 24% of children referred for investigation of inflammatory bowel disease had a form of lymphoid nodular hyperplasia with a disorganised mucosal fold pattern. What was new was that this report distinguished two patterns of lymphoid hyperplasia. Lymphoid hyperplasia causing small nodular defects about 2 mm in diameter is considered a normal variant but there is a more exaggerated change, probably reflecting enlargement of Peyer's patches. This latter pattern can occur in yersiniosis and it could represent an early lesion of Crohn's disease. That paper referred back to our 1987 endoscopic study describing lymphoid follicles in the ileum of 23 children of whom only seven children had identifiable disease. Three cases were described as lymphoid nodular hyperplasia with recurrent abdominal pain and diarrhoea. This proportion (13%) accords with the 12% found in the endoscopic study of Lindley and Milla.4Lindley KJ Milla PJ Autism, inflammatory bowel disease, and MMR vaccine.Lancet. 1998; 351: 907Summary Full Text Full Text PDF PubMed Google Scholar In their endoscopic study Williams and Nicholls5Williams CB Nicholls S Endoscopic features of chronic inflammatory bowel disease in childhood.Baillières Clin Gastroenterol. 1994; 8: 121-131Summary Full Text PDF PubMed Scopus (30) Google Scholar referred to the radiological diagnostic confusion.3Lipson A Bartram CI Williams CB Slavin G Walker-Smith JA Barium studies and ileoscopy compared in children with suspected Crohn's disease.Clin Radiol. 1990; 41: 5-8Summary Full Text PDF PubMed Scopus (64) Google Scholar They describe “1–5 mm nodules, usually pink and shiny… dotted singly or in coalescing masses. Localised conglomerations around 10–15 mm diameter are described as Peyer's patches”. They published a photograph identical with the findings in our Lancet paper. Williams and Nicholls did indeed warn “against misdiagnosis of ileal Crohn's disease” but, incredibly, Calman left out the phrase “of ileal Crohn's disease” so that his subsequent phrase “inappropriate medication”, which applies only to Crohn's disease, has a wholly different meaning.I must also further address the issue of why we published this preliminary study. Our observation had been presented at the First International Symposium on Pediatric Neurogastroenterology (1997) and an expanded series of 30 children, with two scientific studies of the mucosal lesion, was presented to the British Society of Gastroenterology in March, 1998. (J Pediatr Gastroenterol Nutr 1997; 25 [suppl 1]: S47, S48 and Gut 1998; 42 [suppl 1]: A24, A85, F93). We would not have published this preliminary report without knowledge of all these further studies.It is one thing for the Chief Medical Officer to defend MMR vaccination but quite another to criticise so severely and be so dismissive of gastrointestinal findings that have been published after peer review in The Lancet and selected for presentation, also by peer review, at an international and a national meeting. Letters in The Lancet and the letter of March 27, 1998 (PL/CMO/98/2) to all doctors by Sir Kenneth Calman, Chief Medical Oficer, Department of Health, on measles, mumps, and rubella (MMR) vaccine, Crohn's disease, and autism are in danger of completely obscuring the observation we made of an association between ileal lymphoid nodular hyperplasia, non-specific colitis, and autism in childhood. As the senior clinician on the study I would like to make several points. We did not describe any increase in Crohn's disease or ulcerative colitis in children with autism so the observations of Eric Fombonne (March 28, p 255)1Fombonne E Inflammatory bowel disease and autism.Lancet. 1998; 351: 955Summary Full Text Full Text PDF PubMed Scopus (24) Google Scholar are not surprising. What we did describe was non-specific colitis with ileal lymphoid nodular hyperplasia. The colitis we described was ignored in Robert Chen and Frank De Stefano's commentary accompanying our Lancet paper. Calman seeks to dismiss our findings concerning lymphoid hyperplasia and also makes no mention of colitis. Indeed, he selectively quotes from my own publications on this topic since 1983 but makes a number of false assumptions. Because our Lancet paper was a preliminary report we did not expand on the diagnostic term “ileal lymphoid nodular hyperplasia”. This is a term often used inexactly by radiologists and endoscopists to describe both a normal finding in children and a pathological finding which may be accompanied by abdominal pain and diarrhoea requiring therapy. The 1983 Walker-Smith, Hamilton, and Walker reference cited by Calman does indeed state that ileal lymphoid nodular hyperplasia “has been termed benign” but we went on to say that recurrent abdominal pain and diarrhoea often prompt a diagnostic barium study to permit this radiological diagnosis. We also stated that symptoms could be so severe that steroids may be used and even that surgery might be contemplated (although is this not recommended owing to uncertain knowledge concerning outcome). Calman also cites a 1990 radiological study3Lipson A Bartram CI Williams CB Slavin G Walker-Smith JA Barium studies and ileoscopy compared in children with suspected Crohn's disease.Clin Radiol. 1990; 41: 5-8Summary Full Text PDF PubMed Scopus (64) Google Scholar which indicated that 24% of children referred for investigation of inflammatory bowel disease had a form of lymphoid nodular hyperplasia with a disorganised mucosal fold pattern. What was new was that this report distinguished two patterns of lymphoid hyperplasia. Lymphoid hyperplasia causing small nodular defects about 2 mm in diameter is considered a normal variant but there is a more exaggerated change, probably reflecting enlargement of Peyer's patches. This latter pattern can occur in yersiniosis and it could represent an early lesion of Crohn's disease. That paper referred back to our 1987 endoscopic study describing lymphoid follicles in the ileum of 23 children of whom only seven children had identifiable disease. Three cases were described as lymphoid nodular hyperplasia with recurrent abdominal pain and diarrhoea. This proportion (13%) accords with the 12% found in the endoscopic study of Lindley and Milla.4Lindley KJ Milla PJ Autism, inflammatory bowel disease, and MMR vaccine.Lancet. 1998; 351: 907Summary Full Text Full Text PDF PubMed Google Scholar In their endoscopic study Williams and Nicholls5Williams CB Nicholls S Endoscopic features of chronic inflammatory bowel disease in childhood.Baillières Clin Gastroenterol. 1994; 8: 121-131Summary Full Text PDF PubMed Scopus (30) Google Scholar referred to the radiological diagnostic confusion.3Lipson A Bartram CI Williams CB Slavin G Walker-Smith JA Barium studies and ileoscopy compared in children with suspected Crohn's disease.Clin Radiol. 1990; 41: 5-8Summary Full Text PDF PubMed Scopus (64) Google Scholar They describe “1–5 mm nodules, usually pink and shiny… dotted singly or in coalescing masses. Localised conglomerations around 10–15 mm diameter are described as Peyer's patches”. They published a photograph identical with the findings in our Lancet paper. Williams and Nicholls did indeed warn “against misdiagnosis of ileal Crohn's disease” but, incredibly, Calman left out the phrase “of ileal Crohn's disease” so that his subsequent phrase “inappropriate medication”, which applies only to Crohn's disease, has a wholly different meaning. I must also further address the issue of why we published this preliminary study. Our observation had been presented at the First International Symposium on Pediatric Neurogastroenterology (1997) and an expanded series of 30 children, with two scientific studies of the mucosal lesion, was presented to the British Society of Gastroenterology in March, 1998. (J Pediatr Gastroenterol Nutr 1997; 25 [suppl 1]: S47, S48 and Gut 1998; 42 [suppl 1]: A24, A85, F93). We would not have published this preliminary report without knowledge of all these further studies. It is one thing for the Chief Medical Officer to defend MMR vaccination but quite another to criticise so severely and be so dismissive of gastrointestinal findings that have been published after peer review in The Lancet and selected for presentation, also by peer review, at an international and a national meeting. Autism, inflammatory bowel disease, and MMR vaccineAuthor's reply Full-Text PDF Autism, inflammatory bowel disease, and MMR vaccineAuthor's reply Full-Text PDF
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