Autistic enterocolitis is a controversial term first used by British gastroenterologist Andrew Wakefield to describe a number of common clinical symptoms and signs which he contends are distinctive to autism. The existence of autistic enterocolitis is controversial, as the methodology of Wakefield's studies has been criticized and his results have not been replicated by other groups.^[1] Gastroenterology or Gastrology might be better described as the field of digestive diseases, which are traditionally separated by anatomic or functional category. ... Andrew Wakefield (born 1956 in the United Kingdom) is a Canadian trained surgeon, best known as the lead author of a controversial 1998 research study, published in The Lancet, which reported bowel symptoms in a selected sample of twelve children with autistic spectrum disorders and other disabilities, and alleged a... Autism is a brain development disorder characterized by impairments in social interaction and communication, and restricted and repetitive behavior, all exhibited before a child is three years old. ...

Background

Until the 1970s, autism was considered a very rare condition, but it is diagnosed much more often nowadays, whether due to increased diagnostic vigilance by doctors, changes of diagnostic categories, or an actual increase in incidence. Estimates of the percentage of late-onset autism cases range from 20% to 80%,^{[citation needed]} with the lower percentage reported by sources including the British Medical Journal as not having changed in recent years.[1] Wakefield, however, contends that a regressive syndrome "may reflect a subset of children with developmental disorders with distinct etiological and clinical features." The 1970s decade refers to the years from 1970 to 1979, also called The Seventies. ... Autism is a brain development disorder characterized by impairments in social interaction and communication, and restricted and repetitive behavior, all exhibited before a child is three years old. ... The British Medical Journal (BMJ) is a medical journal published weekly in the United Kingdom by the British Medical Association (BMA)which published its first issue in 1845. ...

Despite others describing common bowel features, there have been no peer reviewed studies yet published, as of 2006, corroborating the existence of autistic enterocolitis; other studies have explicitly denied its existence.[2] [3]. Thus, it is not generally accepted that the types of colitis found in autism are unique to autism.[4]To date, no adequately controlled study has been published comparing the gut pathology of autistic and non-autistic children.^{[citation needed]} Peer review (known as refereeing in some academic fields) is a scholarly process used in the publication of manuscripts and in the awarding of funding for research. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ...

The Lancet study

When Wakefield and his colleagues first reported in 1998 a possible association between autistic regression, IBD, and MMR vaccines in the Lancet, they evaluated a dozen children with pervasive developmental disorders, apparent developmental regression, and intestinal symptoms, referred to the Royal Free Hospital. The MMR vaccine is a mixture of live attenuated viruses, administered via injection for immunization against measles, mumps and rubella. ... Lancet may refer to: A lancet is a medical instrument, similar to a scalpel but with a double-edged blade. ... The Royal Free Hospital is a large and modern London teaching hospital, United Kingdom. ...

According to parents, onset of behavioral symptoms was linked to recent (within two weeks) immunization with MMR vaccine in eight of the children diagnosed with developmental disorders. The most consistent report was lymphoid nodular hyperplasia of the terminal ileum in nine of the children. This feature has also been reported to be very common in non-autistic children.[5] A variety of colonic and rectal mucosal features was reported in eight cases. Biopsies of the ileum was reported to have shown reactive lymphoid follicular hyperplasia in seven. Biopsies of the colon was reported to have shown a diffuse mononuclear cell infiltrate in six. Grays Fig. ... It has been suggested that this article or section be merged with Large intestine. ...

Wakefield and his colleagues say they have described features of regressive autistism with bowel disorders, or what Wakefield would later call autistic enterocolitis, although these findings have been questioned, with claims that the association of features is substantially an artifact of preselection of vaccinated children with both developmental disorders and bowel symptoms for a UK lawsuit [6]:

• Most of the children were reported to have swelling of the lymphoid tissue lining the intestines, particularly near where the small and large intestines meet, and inflammation of the large intestine, associated with constipation, diarrhea and, in some cases, pain.
• In some affected children, impaired cellular immunity to common recall antigens, with low numbers of circulating white blood cells were reported.
• A specific measles protein signal is claimed to have been detected in inflamed lymphoid tissue.
• In some cases, loss of speech and language, bowel disturbances, self-injury, and a self-limited diet, associated with cravings for particular foods.
• Allergies, food intolerances are also reported in some children.

In mammals including humans, the lymphatic vessels (or lymphatics) are a network of thin tubes that branch, like blood vessels, into tissues throughout the body. ... In anatomy, the intestine is the segment of the alimentary canal extending from the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine. ... The large intestine, an organ which is now more commonly referred to by its Greek name, the colon, is the last part of the digestive system: the final stage of the alimentary canal in vertebrate animals. ... Constipation or irregularity, is a condition of the digestive system where a person (or animal) experiences hard feces that are difficult to egest; it may be extremely painful, and in severe cases (fecal impaction) lead to symptoms of bowel obstruction. ... Types 5-7 on the Bristol Stool Chart are often associated with diarrhea Diarrhea (in American English) or diarrhoea (in British English) is a condition in which the sufferer has frequent watery, loose bowel movements (from the Greek word διάρροια; literally meaning through-flowing). Acute infectious diarrhea is a common cause... For the server security software, see Microsoft Forefront. ... “White Blood Cells” redirects here. ... Allergy is an abnormal reaction to a substance foreign to the body that is acquired, predictable and rapid. ... // Food intolerance or food sensitivity is a negative reaction to a food that may or may not be related to the immune system or to food poisoning. ...

IBD and regressive autism

Although also characterized by intestinal lymphoid tissue disease activity, the primary symptoms and diagnostic criteria of the syndrome are claimed to be behavioral and developmental. Age, dose of infection and the interaction of two or more viruses are claimed to be factors leading to regressive autism. According to Wakefield, "it is possible that the emergence of this new type of autism is related to a different pattern of exposure to environmental triggers." In mammals including humans, the lymphatic vessels (or lymphatics) are a network of thin tubes that branch, like blood vessels, into tissues throughout the body. ... This article does not cite any references or sources. ...

Abnormal metabolites of macro-nutriments are claimed to have been found in the urine of some autistic children, suggesting an incomplete or insufficient intra-intestinal digestion.[7]

Supposed link to MMR vaccinations

Central to one of the most acrimonious controversies in autism, Wakefield has hypothesized that autistic enterocolitis is an emergent IBD phenotype that follows from exposure ro the vaccinations given to children during a period when their immune systems are rapidly developing. Specifically, Wakefield asserts the autistic enterocolitis syndrome involves increased permeation of neurotoxic substances across the blood-brain barrier during a vulnerable part of brain development, leading to regressive autism. There is considerable disagreement over the exact nature of autism, however it is generally considered to be a neurodevelopmental condition which manifests itself in markedly abnormal social interaction, communication ability, patterns of interests, and patterns of behavior. ... Individuals in the mollusk species Donax variabilis show diverse coloration and patterning in their phenotypes. ... A vial of the vaccine against influenza. ... The blood-brain barrier (BBB) is a membranic structure that acts primarily to protect the brain from chemicals in the blood, while still allowing essential metabolic function. ... Regressive autism is a manner of the neurological development of an autistic child in which they first develop some non-autistic skills, such as speech, and then start to lose those skills at about the age of 18 months, thereafter following the standard pattern of autistic neurological development. ...

Other research, however, rejects this hypothesis, and other groups have not reproduced Wakefield's findings.[8] Researchers have identified a high incidence of bowel symptoms in autistic children before the MMR vaccine was licensed [9] It was also revealed that, prior to the publication of Wakefield's studies alleging a connection between the MMR vaccine and autistic enterocolitis, he had received over £400,000 from lawyers attempting to sue vaccine manufacturers. This conflict of interest, which Wakefield denies, has led many to criticize Wakefield and his results. The British General Medical Council has launched an inquiry into possible dishonesty by Wakefield regarding his research.^[2] A conflict of interest is a situation in which someone in a position of trust, such as a lawyer, a politician, or an executive or director of a corporation, has competing professional or personal interests. ... The General Medical Council (the GMC) is the regulator of the medical profession in the United Kingdom. ...

"Retraction of an interpretation"

The Lancet paper has been widely cited as an impetus for concerns regarding the MMR vaccine being a cause of Autism. Wakefield gave interviews after the publication of the paper, including on 60 minutes where he raised concerns regarding administraiton of the MMR vaccine. In the Lancet paper, Wakefield and his co-authors said on the issue: This article is about the CBS news magazine. ...

"We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described. Virological studies are underway that may help to resolve this issue"

In 2004, ten of the 13 authors issued a statement in the Lancet (2004;363:750) entitled "Retraction of an interpretation". In this, the authors retracted the conclusion section of the paper, formally known in the Lancet and in many biomedical journals, as the "interpretation". The section of the paper retracted said: Year 2004 (MMIV) was a leap year starting on Thursday of the Gregorian calendar. ...

"Interpretation. We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers."

In the retraction, issued in March 2004, they said:

"We wish to make it clear that in this paper no causal link was established between MMR vaccine and autism as the data were insufficient. However, the possibility of such a link was raised and consequent events have had major implications for public health. In view of this, we consider now is the appropriate time that we should together formally retract the interpretation placed upon these findings in the paper, according to precedent."

The authors also said:

"The main thrust of this paper was the first description of an unexpected intestinal lesion in the children reported. Further evidence has been forthcoming in studies from the Royal Free Centre for Paediatric Gastroenterology and other groups to support and extend these findings. While much uncertainty remains about the nature of these changes, we believe it important that such work continues, as autistic children can potentially be helped by recognition and treatment of gastrointestinal problems."

Just before the retraction, criticism arose over the fact that the Royal Free Hospital had received £55 000,00 in August 1996 from lawyers preparing to sue MMR manufacturers for support of Dr. Wakefield's research. Wakefield asserted that the donation was to fund a second clinical study; some of the children involved were subjects in both studies.[10]. However, it was subsequently revealed by The Sunday Times of London that Wakefield had personally been paid more than £400,000 [11]. The Royal Free Hospital is a large and modern London teaching hospital, United Kingdom. ... The Sunday Times is a Sunday broadsheet newspaper distributed in the United Kingdom and Republic of Ireland, published by Times Newspapers Ltd, a subsidiary of News International which is in turn owned by News Corporation. ...

Wakefield, who did not sign the retraction, currently face disciplinary charges before the General Medical Council over the conduct of this research.[12] The General Medical Council (the GMC) is the regulator of the medical profession in the United Kingdom. ...

In October 2005, the Cochrane Library published its analysis of 31 "high quality" medical studies which concluded no link could be found between the MMR vaccine and bowel disease, autism or other pervasive developmental disorders. To increase the rigor of the meta-analysis, the criteria of the meta-analysis excluded smaller studies and studies that had the potential for bias. Wakefield's work was specifically excluded in the meta-analysis due to small sample size. With regard to the vaccine, Cochrane said that its survey of research "strongly supports its use."[13] Year 2005 (MMV) was a common year starting on Saturday (link displays full calendar) of the Gregorian calendar. ... The Cochrane Library is a collection of databases in medicine and other healthcare specialties provided by the Cochrane Collaboration. ...

References

• Black C, Kaye J, Jick H (Aug 24 2002). "Relation of childhood gastrointestinal disorders to autism: nested case-control study using data from the UK General Practice Research Database.". BMJ 325 (7361): 419-21. PMID 12193358. 
• Fombonne E, Chakrabarti S (Oct 2001). "No evidence for a new variant of measles-mumps-rubella-induced autism.". Pediatrics 108 (4): E58. PMID 11581466. 
• Thjodleifsson B, Davídsdóttir K, Agnarsson U, Sigthórsson G, Kjeld M, Bjarnason I (Dec 2002). "Inflammation and Inflammatory Bowel Disease: Effect of Pentavac and measles-mumps-rubella (MMR) vaccination on the intestine.". Gut 51 (6): 816-7. PMID 12427783. 
• Wakefield A, Murch S, Anthony A et al. (1998). "Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children". Lancet 351 (9103): 637–41. doi:10.1016/S0140-6736(97)11096-0. PMID 9500320. Retrieved on 2007-09-05. 
• Wakefield A, Anthony A, Murch S, Thomson M, Montgomery S, Davies S, O'Leary J, Berelowitz M, Walker-Smith J (Sep 2000). "Enterocolitis in children with developmental disorders.". Am J Gastroenterol 95 (9): 2285-95. PMID 11007230. 

A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Brian Deer is an award-winning British investigative reporter, best known for inquiries into the drug industry, medicine and social issues for the Sunday Times of London. ... is the 365th day of the year (366th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... is the 109th day of the year (110th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... The British Medical Journal (BMJ) is a medical journal published weekly in the United Kingdom by the British Medical Association (BMA)which published its first issue in 1845. ... Eric Fombonne, MD, FRCP, (b. ... Andrew Wakefield (born 1956 in the United Kingdom) is a Canadian trained surgeon, best known as the lead author of a controversial 1998 research study, published in The Lancet, which reported bowel symptoms in a selected sample of twelve children with autistic spectrum disorders and other disabilities, and alleged a... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 248th day of the year (249th in leap years) in the Gregorian calendar. ... Sworn enemy of the American Gastroenterological Association (AGA), The American College of Gastroenterology (ACG), founded in 1932, serves to advance the scientific study and medical practice of diseases of the gastrointestinal tract. ...

External links

• Autism-BioMed.org - 'MMR vaccine and autism, revisited' (commentary)', Ronald J. Kallen, MD, Autism Biomedical Information Network (May 31, 2000)
• MelaniePhillips.com - 'MMR: the unanswered questions', Melanie Phillips, Daily Mail, (October 31, 2005)
• "The MMR skeptic who just doesn't understand science", Ben Goldacre, The Guardian (November 2, 2005)
• MelaniePhillips.com - 'Evidence-based' ignorance over MMR, Melanie Phillips, Daily Mail, (November 08, 2005)
• BrianDeer.com - 'The MMR-autism scare - Summary of a Scandal', Brian Deer (2005)
• CDC.gov - 'FAQs about measles vaccine and inflammatory bowel disease', Centers for Disease Control
• Cochrane.org - 'The Cochrane Library publishes the most thorough survey of MMR vaccination data which strongly supports its use', Cochrane Library (October 19, 2005)
• MedAdNews.com - 'Impact of Gastrointestinal Dysfunction in Autistic Children'. PRNewswire (January 11, 2006)
• NeuroDiversity.com - 'Autism & Gastrointestinal Concerns'
• RxPGNews.com - 'MMR vaccine - An End to the Controversy' (October 19, 2005)
• Tripod.com - 'Autism, Viral Infection and the Gut-Brain Axis', Andrew J. Wakefield, Scott M. Montgomery, Journal of Pediatric Gastroenterology and Nutrition. vol 34 p S14-S17 (May/June 2002)