Vaccine injury & GI tract - Autism and the Gastrointestinal Tract

[Guest guest]

this can apply to any GI involvement after

vaccines, not just the extreme of autism

" Autism and the Gastrointestinal Tract "

http://www-east.elsevier.com/ajg/issues/9509/ajg3247edi.htm

Editorial

September 2000

Volume 95, Number 9

Pages 2154-2156

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Autism and the Gastrointestinal Tract

Eamonn M. M. Quigley, M.D., F.A.C.G.,a and Hurley, M.B.a

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Autism is a behavioral disorder characterized by

impairment of social contact and communication

and by restricted and repetitive interests and

behaviors (1). Of these cardinal features,

deficits in social contact and interaction are

usually the most prominent; typically, at least

one of these features is apparent by the age of 3

yr. Children often seem normal at birth, only to

develop regression to autistic behavior between

the first or second years of life: a most

distressing scenario for the parents and

caregivers (2). The manifestations of this

disorder may vary in severity and may be

associated with a wide range of levels of

intelligence from normal to impaired. Related

disorders include Asperger's syndrome, pervasive

development disorder, not otherwise specified

(PDD-NOS), childhood disintegrative disorder, and Rett syndrome.

The etiology of autism remains unknown. Recent

studies have suggested a possible genetic

contribution (3), and there is also evidence for

a developmental abnormality in the brainstem (4).

Others have emphasized the possible impact of a

number of postnatal factors ranging from

environmental toxins to dietary factors, and a

variety of infectious agents. Of these, the

possible relationship to casein and gluten

intolerance (5), on one hand, and measles and MMR

vaccination (6), on the other, have generated

particular interest. As a consequence of the

former, many of these children, who often already

have a very limited diet because of highly

selective eating patterns, are placed on casein

and gluten-free diets, rendering an already

precarious dietary intake even more so. The

association between autism and measles virus and

measles vaccination has generated considerable

controversy (7) reaching the lay press and even a Congressional hearing (8).

Autistic children frequently develop

gastrointestinal symptoms including constipation,

diarrhea, abdominal discomfort, gaseousness, and

distension. Horvath et al. reported a 69%

prevalence of histological esophagitis and a 58%

prevalence of intestinal disaccheridase

deficiency in a group of 36 autistic children

studied by upper gastrointestinal endoscopy and

biopsy (9). Pancreatic insufficiency has also

been suggested (10). However, it is the possible

association of autism with ileocolonic disease

that has attracted the most attention. Wakefield

et al. first reported prominent ileal lymphoid

nodular hyperplasia (LNH) and ileocolitis in an

uncontrolled study of 12 autistic children and

went on to speculate a link to MMR vaccination

(6). The same group had previously postulated a

similar link between measles, MMR, and

inflammatory bowel disease in adults (11, 12). In

this issue of the Journal, Wakefield et al.

report on a total 60 children with developmental

disorders (primarily autism) and compare their

ileocolonoscopic findings (both macroscopic and

histological) with those of 22 " control " children

and 20 with ulcerative colitis. In all, 93% of

affected children had LNH in comparison to 29% of

" controls " and chronic colitis was identified in

88% of affected children in comparison to 5% of

" controls " (13). The authors conclude that

children with developmental disorders frequently

exhibit a new variant of inflammatory bowel disease: " autistic enterocolitis. "

The gut-brain connection is now recognized as a

basic tenet of physiology and medicine, and

examples of gastrointestinal involvement in a

variety of neurological diseases are extensive

(14). The pathophysiology of these

gastrointestinal expressions of a central nervous

system is often unclear, but may variably reflect

the parallel involvement of the gut and brain by

the same disease process or the consequences of a

primary disease of the brain or gut on the gut or

brain, respectively. The description of

gastrointestinal dysfunction in autism should

come as no surprise, therefore. Indeed, some of

the symptoms manifested by these children are

quite similar to those reported by adults with

degenerative central nervous system disorders,

such as Parkinson's disease, for example (15).

What is of particular interest is the suggestion

that a developmental disorder may be associated

with inflammatory bowel disease. How firm is this

association? Certain features of the study limit

our ability to adequately address this question.

With regard to the association with LNH, it

remains unclear whether this finding reflects a

true abnormality, given the differences in median

age between patients and " controls " . This group

was also confronted with a ubiquitous issue in

pediatric research: that of obtaining a true

control population. Their " controls " were, in

fact a group of symptomatic children in whom the

diagnosis of inflammatory bowel disease had been

excluded: hardly a perfect comparator. LNH could

also be a secondary phenomenon, related to

infections or infestations, immunodeficiency, or

even constipation (16). The histological

appearances of the ileal biopsies, reviewed

blindly by three pathologists, commonly included

reactive follicular hyperplasia, marked expansion

of lymphoid tissue, and acute cryptitis; ileitis,

eosinophil infiltration, and an increase in

intraepithelial lymphocytes (IELs) were unusual.

In the colon, biopsies showed appearances that

were similar to, but less severe than, those seen

in the children with established ulcerative

colitis, being perhaps more reminiscent of the

features of lymphocytic colitis, as seen in

adults (17). It is of interest, given the

proposed association of autism with gluten

intolerance, that colonic inflammation has also

been described in adult celiac disease (18).

These findings also need to be interpreted with

caution. In particular, one must bear in mind

that this was a highly selected series—children

referred to a highly specialized center being

selected for investigation on the basis of the

presence of gastrointestinal symptoms. Pending

the performance of appropriate studies, which

should include both asymptomatic autistic

children as well as children with other

developmental disorders, these findings cannot

and should not be extrapolated to children with

autism in general. Indeed, a strategy development

subgroup of the Medical Research Council in the

UK recently concluded that the case for " autistic

enterocolitis " had not been proven (16). Nor is

there sufficient evidence to enable us, in any

way, to define the nature of the relationship

between these gastrointestinal findings and the

neurodevelopmental disorder. In particular there

is, at present, insufficient evidence to

establish either a direct or indirect link,

(e.g., through an associated alteration in

intestinal permeability (19) between an inflamed

gut and the brain, in autism. We must, in

particular, resist the temptation to predict

causation without the necessary evidence; to do

so could engender false hope and further burden

families who already have more than their fair

share of crosses to bear. Furthermore, there is

at present no evidence to suggest that the

presence or absence of these features influences

the expression or progression of this distressing

disorder, nor is there any suggestion that

therapy based on these findings might ameliorate

either the developmental disorder itself or the

associated gastrointestinal symptoms.

Ileocolonoscopy should continue to be regarded,

therefore, in the absence of other indications,

as an investigational tool in these patients.

Wakefield et al. (13) are to be congratulated on

opening yet another window onto the

ever-broadening spectrum of gut-brain

interactions. Their findings raise many

challenging questions that should provoke further

much-needed research in this area, research that

may provide true grounds for optimism for affected patients and their families.

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a Department of Medicine, National University of Ireland, Cork, Ireland

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References

1. American Psychiatric Association. Diagnostic

and statistical manual of mental disorders. 4th

ed. Washington, DC: American Psychiatric Association, 1994.

2. Frith U, ed. Autism and Asperger syndrome.

Cambridge: Cambridge University Press, 1991.

3. Rodier PM. The early origins of autism. Sci Am 2000;282:38-45.

4. Rodier PM, Ingram JL, Tisdale B, et al.

Embryological origin for autism: Developmental

anomalies of the cranial nerve motor nuclei. J Compar Neurol 1996;370:247-61.

5. Reichelt KL, H, Ekrem J. Gluten, milk

proteins and autism: The results of dietary

intervention on behaviour and peptide secretion. J Appl Nutr 1990;42:1-11.

6. Wakefield AJ, Murch SH, A, et al.

Ileal nodular hyperplasia, non-specific colitis

and pervasive developmental disorder in children. Lancet 1998;351:637-41.

7. B, E, Farrington CP, et al.

Autism and measles mumps and rubella vaccine: No

epidemiological evidence for a causal association. Lancet 1999;353:2026-9.

8. Anonymous. Measles, MMR, and autism: The

confusion continues. Lancet 2000;355:1379.

9. Horvath K, Papadimitriou JC, Rabsztyn A, et

al. Gastrointestinal abnormalities in children

with autistic disorder. J Pediatr 1999;135:559-63.

10. Lightdale JR, Hayer CA, Duer A, et al.

Evaluation of gastrointestinal symptoms in

autistic children before and following secretin

infusion. Gastroenterology 2000;118:A66.

11. Wakefield AJ, Montgomery SM, Pounder RE.

Crohn's disease: The case for measles virus. Ital

J Gastroenterol 1999;31:247-54.

12. Wakefield AJ, Montgomery SM. Measles virus as

a risk factor for inflammatory bowel disease: An

unusually tolerant approach. Am J Gastroenterol 2000;95:1389-92.

13. Wakefield AJ, A, Murch SH, et al.

Enterocolitis in children with developmental

disorders. Am J Gastroenterol 2000;95:2285-95.

14. Pfeiffer RF, Quigley EMM. Neurogastroenterology. Semin Neurol 1996;16.

15. LL, Pfeiffer RF, Quigley EMM, et al.

Gastrointestinal symptoms in Parkinson's disease. Mov Disord 1991;6:151-6.

16. Medical Research Council. Report of the

strategy development group subgroup on research

into inflammatory bowel disorders and autism. London: MRC, 1999.

17. Fernandez-Banares F, Salas A, Forne M, et al.

Incidence of collagenous and lymphocytic colitis:

A 5-year population-based study. Am J Gastroenterol 1999;94:418-23.

18. McCashland TJ, Donovan JP, Strobach SJ, et

al. Collagenous enterocolitis: A manifestation of

gluten-sensitive enteropathy. J Clin Gastroenterol 1992;15:52-4.

19. D'Eufemia P, Celli M, Finocchiaro R, et al.

Abnormal intestinal permeability in children with

autism. Acta Paediatr 1996;85:1076-9.

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Reprint requests and correspondence: Eamonn M. M.

Quigley, M.D., F.A.C.G., National University of

Ireland, Cork University Hospital, Clinical Sciences Building, Cork, Ireland.

Received June 26, 2000; accepted June 26, 2000.

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Copyright ©2000 the American College of Gastroenterology

Published by Elsevier Science Inc.

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Sheri Nakken, former R.N., MA, Hahnemannian Homeopath

Vaccination Information & Choice Network, Nevada City CA & Wales UK

Vaccines -

http://www.nccn.net/~wwithin/vaccine.htm or

http://www.wellwithin1.com/vaccine.htm

Vaccine Dangers & Homeopathy Online/email courses

http://www.wellwithin1.com/vaccineclass.htm or

http://www.wellwithin1.com/homeo.htm