COMMITTEE ON GOVERNMENT REFORM
2157 RAYBURN HOUSE OFFICE BUILDING
WASHINGTON, DC 20515
(202) 225-5074

June 19, 2002

Arthur Krigsman MD

http://www.house.gov/reform/krigsman.htm

Mr. Chairman and members of the committee:

This testimony represents the scientific findings of data accumulated over the past year and a half from autistic children during the course of standard evaluations of their gastrointestinal symptoms. This testimony should in no way be taken as anti-vaccine. Children in my pediatric practice continue to receive all vaccinations in accordance with the guidelines set forth by the American Academy of Pediatrics. The observations expressed herein are my own, and do not represent the opinions of any institution, organization, clinic, or medical practice with which I may be associated.

My involvement with autistic children began approximately one and a half years ago. At that time, I was approached by a colleague who was caring for a large number of autistic patients. He observed that a large proportion of these patients suffered from chronic, unexplained gastrointestinal symptoms and that these symptoms were a source of great anxiety to the parents. I agreed to evaluate them, and my findings are detailed below. The evaluations undertaken were standard “textbook” evaluations of children with chronic diarrhea, constipation, and abdominal pain, uninfluenced by the fact that these children were autistic.

Patient Population

Our experience consists of a total of 43 consecutive children aged 2-10 years of age. Most were referred by private practitioners but many were self referred after much frustration with their children’s ongoing discomfort. 42 patients had received a diagnosis of either autistic disorder or autistic spectrum disorder by a pediatric neurologist or developmental pediatrician. Many children had received independent confirmation from a second or even a third pediatric specialist. In no instance was the diagnosis disputed by a second specialist. The remaining patient carried a diagnosis of Aspergers syndrome.

The majority of patients had a clear history of developmental regression. Specifically, these children developed in an entirely normal fashion for the first 12-18 months. They typically had a vocabulary of 15-25 words, maintained normal eye contact, were playful and interactive, and were not overly irritable. At some point during this age interval of 12-18 months, they had either a precipitous or gradual decline in all the above mentioned developmental markers, and this was accompanied by the appearance of typical autistic behaviors, “stimming”, and bouts of unexplained irritability. In some patients, verbal stagnation, but not regression occurred. However, in these patients, clear regression was seen in the interactive and social skills of the children.

The majority of patients are from the northeastern United States. The ratio of males to females was 7:1.

Symptomatology

The most common gastrointestinal symptom noted by the parents was diarrhea. In some children, the diarrhea took the form of a soupy liquid that occurred 4 to 7 times per day and would frequently leak from the child’s diaper. However, the majority of parents reported a stool frequency of 1-3 per day with a consistency of mashed potatoes. The stool is particularly malodorous, and usually contains pieces of undigested foods. Irritability is often noted just prior to the bowel movement.

Constipation is another frequent complaint, consisting of bowel movements every 3-6 days and typically accompanied by great irritability upon passage of the stool. The consistency of the passed stool was not overly hard, suggesting that these children are actually withholding stool and not truly constipated in the strict sense of the term. This constipation is often accompanied by abdominal distension and flatulence. Most patients experienced periods of diarrhea alternating with periods of constipation.

Abdominal pain is another frequent complaint. Most of these children are poorly communicative, and parents often rely on body language cues in determining that their child is experiencing abdominal pain. Children often drop unexpectedly to the floor howling and screaming. This often lasts for up to half an hour. Many children clutch their abdomen and bend over. Some assume a fetal position on the bed or floor, and others take the parents hand and rub their abdomen.

Finally, we have noticed that most regressive autistic children show poor growth, with the majority falling in the lower 10th %tile weight for age. Interestingly, there does not seem to be a concomitant percentile deficit in height for age.

Evaluation

All children underwent initial evaluation of their gastrointestinal symptoms. This included a thorough history and physical exam, complete blood count with platelets, erythrocyte sedimentation rate, serum chemistries, celiac antibody panel with serum IgA, inflammatory bowel disease serology, and stool examination for ova and parasites, culture, and occult blood. The patients diet was thoroughly reviewed to assure that it did not contain excessive nonabsorbed carbohydrates or fruit juices. Therapeutic alterations in the diet were undertaken, including the removal of all gluten and casein containing foods. Medications and supplements were reviewed to assure that they did not contribute to the symptoms.

The evaluation above invariably did not lead to a diagnosis and patients then underwent colonoscopy. Upper endoscopy was performed only if pain was a predominant complaint or if celiac disease was strongly suspected.

Findings

The above images depict the terminal ileum in two patients. They are representative of the gross endoscopic findings of 90% of these patients in whom the lymphoid nodules of the terminal ileum were found to be markedly enlarged. This is in agreement with the previously published findings of Dr. Wakefield in which a similar proportion of patients were found to have abnormal lymphonodular hyperplasia of the terminal ileum.

The second significant finding in our series was on histologic evaluation of the biopsy specimens. The results are summarized below.

% patients with colitis
28/43
65%

% patients with active colitis
22/43
51%

% patients with chronic colitis
17/43
40%

% patients with eosinophilic colitis
3/43
7%

% LNH (macro) of terminal ileum
36/40
90%

% neither active, chronic, nor eosinophilic
15/43
35%

Colitis was determined as per the report of the institutional pathologist. The interpretation of whether the degree of inflammation represented true pathologic inflammation versus a normal variant was subject to the personal experience of the individual pathologist and was not subjected to a uniform rating system.

The patterns of inflammation were patchy and unpredictable in any given patient, but overall were noted in all parts of the colon and terminal ileum. Although the table above lists chronic and active colitis separately, most patients with colitis had both chronic and active inflammation. Most patients had at least 3-4 distinct areas of histologic inflammation, with an equal number of biopsies that were histologically normal. The intensity of the inflammatory lesions varied as well, with many being subtle and somewhat focal, and others being more marked and diffuse. The latter included areas of cryptitis, crypt abscess, ulcerations, and dense inflammatory infiltration. One patient was found to have an inflammatory polyp. Most significantly, these findings were consistent and seen repeatedly amongst the majority of patients.

In regards to the last group of patients in the table above, it should be noted that although the histology did not reveal pathologic colonic inflammation, the majority of these patients were found to have a heavy and diffuse lymphoid hyperplasia of the colon (macroscopic and microscopic), signifying an activation of the colon’s internal immune system.

Conclusion

In a series of 43 autistic children, mostly regressive, with chronic gastrointestinal symptoms, the majority were found to have pathologic inflammation of the colon and terminal ileum. 90% had pathologic lymphonodular hyperplasia of the terminal ileum. Moreover, the findings were similar and consistent from patient to patient within the affected group.

Questions

1) Does autistic colitis occur equally in regressive vs. non-regressive autism?

2) Do differences in growth exist between the colitis and non-colitis group?

3) Do differences in growth exist between the regressive vs. non-regressive group?

4) In a retrospective analysis of growth, will onset of growth failure coincide with the onset of regressive behaviors?

US experts back MMR doctor's findings

Filed: 23/06/2002

From News.telegraph.co.uk

http://portal.telegraph.co.uk/news/main.jhtml?xml=/news/2002/06/23/ixnewstop.html

The man whose research first raised concern over the vaccine's safety is winning support. Lorraine Fraser reports from an influential Congressional hearing.

Scientists in America have reported the first independent corroboration of the research findings of Dr Andrew Wakefield, the specialist who has questioned the safety of the childhood MMR vaccine.

Dr Arthur Krigsman, from New York University School of Medicine, has observed serious intestinal inflammation in autistic children identical to that described by the controversial British doctor and his colleagues in a research paper four years ago.

Dr Krigsman's discovery is significant because it independently supports Dr Wakefield's conclusion that a previously unidentified and devastating combination of bowel and brain disease is afflicting young children - a claim that the Department of Health has dismissed as "bad science".

Dr Wakefield has seen nearly 200 previously normal youngsters who apparently developed the combined behaviour and digestive problems after receiving the three-in-one measles, mumps and rubella jab - a vaccination given routinely to babies and pre-school children in Britain and the United States.

Pathologists at Trinity College, Dublin, have since identified measles virus in bowel tissue samples from 75 of these children and, as reported in The Telegraph last week, now claim to have evidence that the virus comes from MMR.

The Department of Health refuses to accept that such results cast doubt on MMR's safety. A principal criticism levelled at Dr Wakefield and his colleagues is that no part of their research has been replicated by scientists elsewhere.

Last Wednesday, however, Dr Krigsman reported that he had seen the same pattern of illness in 43 American children.

At a hearing of the Government Reform Committee of the United States Congress on the safety of MMR and other vaccines, he said that - like the British children - his patients had all inexplicably deteriorated, losing language and other skills, at around 12 to 18 months of age.

All the children had a definite diagnosis of autism and had come to him because they had symptoms of serious digestive problems, such as pain, constipation and diarrhoea, for which no explanation could be found.

"Our findings, which are independent of Dr Wakefield's findings, completely support his explanation and his observations of the abnormalities in the bowels of these children," he said.

The intestines of the children were "not normal", he added. One 13-year-old autistic boy, who had become so violent that his parents had wanted to institutionalise him, had the "worst case" of inflammation of the colon the doctor had ever seen through a fibre-optic scope.

Dr Krigsman, an experienced consultant paediatric gastroenterologist and an assistant professor at the university, told the committee that he did not know whether his patients' illnesses were linked to MMR. However, he now plans to have the biopsies he took during the examinations tested independently to check for evidence of measles virus infection.

The results will be awaited anxiously by parents and public health officials in Britain, where the debate over the safety of MMR began with the report from Dr Wakefield and other doctors at the Royal Free Hospital in north London in 1998.

Dr Krigsman's research was among presentations described as "significant findings" by Dan Burton, an Indiana congressman chairing the Congressional committee.

Doctors in Britain and America are recognising more autistic children than ever. The US National Institute of Health estimates that one American child in 250 is affected, compared with one in 10,000 a decade ago. A recent survey by the National Autistic Society in England suggested that one in 86 primary school pupils may have the condition.

Health officials in both countries insist, however, that there is no evidence to link this apparent increase with the use of MMR or any other vaccine, and say there is no reason for parents to worry. In Britain, the Department of Health has rejected calls to allow single measles vaccines on the NHS as an alternative, claiming that numerous statistical studies have concluded that MMR is safe.

The Congressional committee heard evidence from other specialists suggesting that MMR and the mercury-based preservative, Thimerosal, may both harm susceptible children, possibly by altering their immune system. Thimerosal is not used in MMR, but is contained in other childhood jabs such as DTP - the diphtheria, tetanus and whooping-cough vaccine.

Dr Jeff Bradstreet, the medical director of the International Child Development Resource Centre in Florida, disclosed that tests on his eight-year-old autistic son Matthew - who received vaccines containing mercury and the MMR jab - have found particles of measles virus in the fluid that bathes his brain and spine as well as in his intestines.

Two other boys with autism who, like Matthew, have recently started to suffer seizures, also have measles virus in their cerebrospinal fluid.

While the significance of this is not yet clear, Dr Bradstreet said he was broadening his research in this area.