Autistic enterocolitis
Encyclopedia
"Autistic enterocolitis" is a controversial term first used by discredited British
gastroenterologist Andrew Wakefield
to describe a number of common clinical symptoms and signs which he contends are distinctive to autism
. The existence of such an enterocolitis has been dismissed by experts as having "not been established", and Wakefield's fraudulent studies used inadequate controls and suppressed negative findings in the now-retracted reports. Multiple attempts to replicate his results have been unsuccessful.
Reviews in the medical literature have found no link between the MMR vaccine and autism or with bowel disease.
Most of Wakefield's coauthors later retracted the conclusions of the original paper proposing the hypothesis, and Wakefield has been found guilty of manipulating patient data and misreporting results in the paper by the General Medical Council. His work was later identified to be falsified and described as an "elaborate fraud".
was rarely accepted to be a distinctive diagnosis, but, following changes to the Diagnostic and Statistical Manual of the American Psychiatric Association
it is diagnosed much more often. How much of this increase is due to greater diagnostic vigilance by doctors, changes in diagnostic categories, or an actual increase in prevalence
, remains unclear. Late-onset autism cases are estimated at 25% and reported by sources including the British Medical Journal
as not having changed in recent years.
Despite others describing common bowel features, there have been no peer review
ed studies yet published, as of 2006, corroborating the existence of autistic enterocolitis; other studies have explicitly refuted its existence. Thus, it is not generally accepted that the types of colitis diagnosed in autistic individuals are either unique to autism, or more common in autistic people than in the general population.
s in the Lancet
, they evaluated a dozen children with pervasive developmental disorder
s, apparent developmental regression, and intestinal symptoms, referred to the Royal Free Hospital
.
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. A variety of colonic and rectal mucosal features were reported in eight cases. Biopsies of the ileum were reported to have shown reactive lymphoid follicular hyperplasia in seven. Biopsies of the colon
were reported to have shown a diffuse mononuclear cell infiltrate in six.
Wakefield and his colleagues said they described features of regressive autism 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:
In an April 2010 investigation into the origins of claims for "autistic enterocolitis", reporter Brian Deer
revealed in the BMJ
that the original pathology results on the children in the study (obtained from the Royal Free hospital) had been subjected to wholesale changes, from normal to abnormal, in the medical school. On 2 January 2011, Deer provided two tables comparing the data on the twelve children, showing the original hospital data and the data with the wholesale changes as used in the 1998 Lancet article.
A 2011 article in the British Medical Journal
described how the data in the study had been falsified by Wakefield so it would arrive at a predetermined conclusion. An accompanying editorial in the same journal described Wakefield's work as an "elaborate fraud" which led to lower vaccination rates, putting hundreds of thousands of children at risk and diverting energy and money away from research into the true cause of autism.
that follows from exposure to the vaccination
s given to children during a period when their immune systems are rapidly developing. Other research, however, rejects this hypothesis, and other groups have not reproduced Wakefield's findings. Researchers have identified a high incidence of bowel symptoms in autistic children before the MMR vaccine was licensed. 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.
where he raised concerns regarding administration of the MMR vaccine. In the Lancet paper, Wakefield and his co-authors said on the issue:
In 2004, 10 of the 13 authors issued a statement in the Lancet 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:
In the retraction, issued in March 2004, they said:
The authors also said:
Just before the retraction, criticism arose over the fact that the Royal Free Hospital
had received £55,000 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. However, it was subsequently revealed by The Sunday Times
of London that Wakefield had personally been paid more than £400,000.
Wakefield, who did not sign the retraction, currently faces disciplinary charges before the General Medical Council
over the conduct of this research. In February 2009 The Sunday Times reported that Wakefield had manipulated patient data and misreported results in his 1998 paper, creating the appearance of a link with autism.
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 disorder
s. 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".
rendered three opinions in three "test cases" that were proceeding in that court, each of which addressed causation issues relating to MMR vaccine and autism spectrum disorders (ASDs). The opinions were critical of Arthur Krigsman
and his testimony about autistic enterocolitis, which the court said that he described as a "new form of gastrointestinal [GI] disorder." Typical of their criticism was the following passage found at page 199 of the opinion in the Snyder case: "Doctor Krigsman was qualified to testify about gastroenterology [but his] qualifications to establish the validity of a new form of gastrointestinal disorder, unrecognized by other authorities in the field, were ... sadly lacking." The court noted that the "medical textbooks" do not recognize autistic enterocolitis. At page 27, the same opinion stated that "Dr. Krigsman’s testimony about autistic enterocolitis as a diagnostic entity was speculative."
In his judgment in Cedillo v Secretary for Health and Human Services, February 12 2009, Special Master George Hastings said:
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
gastroenterologist Andrew Wakefield
Andrew Wakefield
Andrew Wakefield is a British former surgeon and medical researcher, known as an advocate for the discredited claim that there is a link between the measles, mumps and rubella vaccine, autism and bowel disease, and for his fraudulent 1998 research paper in support of that claim.Four years after...
to describe a number of common clinical symptoms and signs which he contends are distinctive to autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
. The existence of such an enterocolitis has been dismissed by experts as having "not been established", and Wakefield's fraudulent studies used inadequate controls and suppressed negative findings in the now-retracted reports. Multiple attempts to replicate his results have been unsuccessful.
Reviews in the medical literature have found no link between the MMR vaccine and autism or with bowel disease.
Most of Wakefield's coauthors later retracted the conclusions of the original paper proposing the hypothesis, and Wakefield has been found guilty of manipulating patient data and misreporting results in the paper by the General Medical Council. His work was later identified to be falsified and described as an "elaborate fraud".
Background
Until the 1970s, autismAutism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
was rarely accepted to be a distinctive diagnosis, but, following changes to the Diagnostic and Statistical Manual of the American Psychiatric Association
American Psychiatric Association
The American Psychiatric Association is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the most influential worldwide. Its some 38,000 members are mainly American but some are international...
it is diagnosed much more often. How much of this increase is due to greater diagnostic vigilance by doctors, changes in diagnostic categories, or an actual increase in prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
, remains unclear. Late-onset autism cases are estimated at 25% and reported by sources including the British Medical Journal
British Medical Journal
BMJ is a partially open-access peer-reviewed medical journal. Originally called the British Medical Journal, the title was officially shortened to BMJ in 1988. The journal is published by the BMJ Group, a wholly owned subsidiary of the British Medical Association...
as not having changed in recent years.
Despite others describing common bowel features, there have been no peer review
Peer review
Peer review is a process of self-regulation by a profession or a process of evaluation involving qualified individuals within the relevant field. Peer review methods are employed to maintain standards, improve performance and provide credibility...
ed studies yet published, as of 2006, corroborating the existence of autistic enterocolitis; other studies have explicitly refuted its existence. Thus, it is not generally accepted that the types of colitis diagnosed in autistic individuals are either unique to autism, or more common in autistic people than in the general population.
Lancet study
When Wakefield and his colleagues first reported in 1998 a possible association between autistic regression, IBD, and MMR vaccineMMR vaccine
The MMR vaccine is an immunization shot against measles, mumps, and rubella . It was first developed by Maurice Hilleman while at Merck in the late 1960s....
s in the Lancet
The Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...
, they evaluated a dozen children with pervasive developmental disorder
Pervasive developmental disorder
Pervasive developmental disorders is a diagnostic category refers to a group of disorders characterized by delays or impairments in communication, social behaviors, and cognitive development.Pervasive developmental disorders include Autism, Asperger's syndrome, Rett's syndrome, Childhood...
s, apparent developmental regression, and intestinal symptoms, referred to the Royal Free Hospital
Royal Free Hospital
The Royal Free Hospital is a major teaching hospital in Hampstead, London, England and part of the Royal Free Hampstead NHS Trust....
.
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
Ileum
The ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
in nine of the children. This feature has also been reported to be very common in non-autistic children. A variety of colonic and rectal mucosal features were reported in eight cases. Biopsies of the ileum were reported to have shown reactive lymphoid follicular hyperplasia in seven. Biopsies of the colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
were reported to have shown a diffuse mononuclear cell infiltrate in six.
Wakefield and his colleagues said they described features of regressive autism 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:
- Most of the children were reported to have swelling of the lymphLymphLymph is considered a part of the interstitial fluid, the fluid which lies in the interstices of all body tissues. Interstitial fluid becomes lymph when it enters a lymph capillary...
oid tissue lining the intestineIntestineIn human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
s, particularly near where the small and large intestineLarge intestineThe large intestine is the third-to-last part of the digestive system — — in vertebrate animals. Its function is to absorb water from the remaining indigestible food matter, and then to pass useless waste material from the body...
s meet, and inflammation of the large intestine, associated with constipationConstipationConstipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
, diarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
and, in some cases, pain. - In some affected children, impaired cellular immunity to common recall antigenAntigenAn antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s, with low numbers of circulating white blood cellWhite blood cellWhite blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s were reported. - A specific measlesMeaslesMeasles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
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.
- AllergiesAllergyAn Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
, food intoleranceFood intoleranceFood intolerance or non-allergic food hypersensitivity is a term used widely for varied physiological responses associated with a particular food, or compound found in a range of foods....
s are also reported in some children.
In an April 2010 investigation into the origins of claims for "autistic enterocolitis", reporter Brian Deer
Brian Deer
Brian Deer is a British investigative reporter, best known for inquiries into the drug industry, medicine and social issues for the Sunday Times of London.- Career :...
revealed in the BMJ
BMJ
BMJ is a partially open-access peer-reviewed medical journal. Originally called the British Medical Journal, the title was officially shortened to BMJ in 1988. The journal is published by the BMJ Group, a wholly owned subsidiary of the British Medical Association...
that the original pathology results on the children in the study (obtained from the Royal Free hospital) had been subjected to wholesale changes, from normal to abnormal, in the medical school. On 2 January 2011, Deer provided two tables comparing the data on the twelve children, showing the original hospital data and the data with the wholesale changes as used in the 1998 Lancet article.
A 2011 article in the British Medical Journal
British Medical Journal
BMJ is a partially open-access peer-reviewed medical journal. Originally called the British Medical Journal, the title was officially shortened to BMJ in 1988. The journal is published by the BMJ Group, a wholly owned subsidiary of the British Medical Association...
described how the data in the study had been falsified by Wakefield so it would arrive at a predetermined conclusion. An accompanying editorial in the same journal described Wakefield's work as an "elaborate fraud" which led to lower vaccination rates, putting hundreds of thousands of children at risk and diverting energy and money away from research into the true cause of autism.
Discredited link to MMR vaccinations
Wakefield has hypothesized that autistic enterocolitis is an emergent IBD phenotypePhenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
that follows from exposure to the vaccination
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
s given to children during a period when their immune systems are rapidly developing. Other research, however, rejects this hypothesis, and other groups have not reproduced Wakefield's findings. Researchers have identified a high incidence of bowel symptoms in autistic children before the MMR vaccine was licensed. 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
Conflict of interest
A conflict of interest occurs when an individual or organization is involved in multiple interests, one of which could possibly corrupt the motivation for an act in the other....
, which Wakefield denies, has led many to criticize Wakefield and his results. The British General Medical Council
General Medical Council
The General Medical Council registers and regulates doctors practising in the United Kingdom. It has the power to revoke or restrict a doctor's registration if it deems them unfit to practise...
has launched an inquiry into possible dishonesty by Wakefield regarding his research.
"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 Minutes60 Minutes
60 Minutes is an American television news magazine, which has run on CBS since 1968. The program was created by producer Don Hewitt who set it apart by using a unique style of reporter-centered investigation....
where he raised concerns regarding administration of the MMR vaccine. In the Lancet paper, Wakefield and his co-authors said on the issue:
- "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, 10 of the 13 authors issued a statement in the Lancet 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:
- "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
Royal Free Hospital
The Royal Free Hospital is a major teaching hospital in Hampstead, London, England and part of the Royal Free Hampstead NHS Trust....
had received £55,000 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. However, it was subsequently revealed by The Sunday Times
The Sunday Times
The Sunday Times is a British Sunday newspaper.The Sunday Times may also refer to:*The Sunday Times *The Sunday Times *The Sunday Times *The Sunday Times...
of London that Wakefield had personally been paid more than £400,000.
Wakefield, who did not sign the retraction, currently faces disciplinary charges before the General Medical Council
General Medical Council
The General Medical Council registers and regulates doctors practising in the United Kingdom. It has the power to revoke or restrict a doctor's registration if it deems them unfit to practise...
over the conduct of this research. In February 2009 The Sunday Times reported that Wakefield had manipulated patient data and misreported results in his 1998 paper, creating the appearance of a link with autism.
In October 2005, the Cochrane Library
Cochrane Library
The Cochrane Library is a collection of databases in medicine and other healthcare specialties provided by the Cochrane Collaboration and other organisations. At its core is the collection of Cochrane Reviews, a database of systematic reviews and meta-analyses which summarize and interpret the...
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 disorder
Pervasive developmental disorder
Pervasive developmental disorders is a diagnostic category refers to a group of disorders characterized by delays or impairments in communication, social behaviors, and cognitive development.Pervasive developmental disorders include Autism, Asperger's syndrome, Rett's syndrome, Childhood...
s. 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".
U.S. Court of Federal Claims
On February 12, 2009, three Special Masters of the United States Court of Federal ClaimsUnited States Court of Federal Claims
The United States Court of Federal Claims is a United States federal court that hears monetary claims against the U.S. government. The court is established pursuant to Congress's authority under Article One of the United States Constitution...
rendered three opinions in three "test cases" that were proceeding in that court, each of which addressed causation issues relating to MMR vaccine and autism spectrum disorders (ASDs). The opinions were critical of Arthur Krigsman
Arthur Krigsman
Arthur Krigsman, MD, is a pediatrician and gastroenterologist best known for his controversial and widely-criticized research in which he attempted to prove that the MMR vaccine caused diseases, especially autism...
and his testimony about autistic enterocolitis, which the court said that he described as a "new form of gastrointestinal [GI] disorder." Typical of their criticism was the following passage found at page 199 of the opinion in the Snyder case: "Doctor Krigsman was qualified to testify about gastroenterology [but his] qualifications to establish the validity of a new form of gastrointestinal disorder, unrecognized by other authorities in the field, were ... sadly lacking." The court noted that the "medical textbooks" do not recognize autistic enterocolitis. At page 27, the same opinion stated that "Dr. Krigsman’s testimony about autistic enterocolitis as a diagnostic entity was speculative."
In his judgment in Cedillo v Secretary for Health and Human Services, February 12 2009, Special Master George Hastings said:
- "To be sure, the petitioners in this case have stressed that they rely upon Dr Krigsman as their expert concerning the causation of GI symptoms, not Dr Wakefield. Thus, they argue that criticisms of the personal integrity of Dr Wakefield are not relevant here. However, because Dr Krigsman’s general causation approach clearly was strongly influenced by Dr Wakefield’s theory, criticisms of Dr Wakefield’s “autistic enterocolitis” theory are relevant, and criticisms relating to Dr Wakefield’s credibility in developing that theory are of relevance as well. Therefore, it is a noteworthy point that not only has that “autistic enterocolitis” theory not been accepted into gastroenterology textbooks, but that theory, and Dr Wakefield’s role in its development, have been strongly criticized as constituting defective or fraudulent science."
External links
- Measles Vaccine and Inflammatory Bowel Disease (IBD) - Archived link to 'FAQs about measles vaccine and inflammatory bowel disease', Centers for Disease Control
- http://www2.cochrane.org/reviews/en/ab004407.html - 'The Cochrane Library publishes the most thorough survey of MMR vaccination data which strongly supports its use', Cochrane LibraryCochrane LibraryThe Cochrane Library is a collection of databases in medicine and other healthcare specialties provided by the Cochrane Collaboration and other organisations. At its core is the collection of Cochrane Reviews, a database of systematic reviews and meta-analyses which summarize and interpret the...
(October 19, 2005)