Enterocolitis in children with developmental disorders

OBJECTIVE:Intestinal pathology, i.e., ileocolonic lymphoid nodular hyperplasia (LNH) and mucosal inflammation, has been described in children with developmental disorders. This study describes some of the endoscopic and pathological characteristics in a group of children with developmental disorders (affected children) that are associated with behavioral regression and bowel symptoms, and compares them with pediatric controls.METHODS:Ileocolonoscopy and biopsy were performed on 60 affected children (median age 6 yr, range 3–16; 53 male). Developmental diagnoses were autism (50 patients), Asperger's syndrome (five), disintegrative disorder (two), attention deficit hyperactivity disorder (ADHD) (one), schizophrenia (one), and dyslexia (one). Severity of ileal LNH was graded (0–3) in both affected children and 37 developmentally normal controls (median age 11 yr, range 2–13 yr) who were investigated for possible inflammatory bowel disease (IBD). Tissue sections were reviewed by three pathologists and scored on a standard proforma. Data were compared with ileocolonic biopsies from 22 histologically normal children (controls) and 20 children with ulcerative colitis (UC), scored in an identical manner. Gut pathogens were sought routinely.RESULTS:Ileal LNH was present in 54 of 58 (93%) affected children and in five of 35 (14.3%) controls (p < 0.001). Colonic LNH was present in 18 of 60 (30%) affected children and in two of 37 (5.4%) controls (p < 0.01). Histologically, reactive follicular hyperplasia was present in 46 of 52 (88.5%) ileal biopsies from affected children and in four of 14 (29%) with UC, but not in non-IBD controls (p < 0.01). Active ileitis was present in four of 51 (8%) affected children but not in controls. Chronic colitis was identified in 53 of 60 (88%) affected children compared with one of 22 (4.5%) controls and in 20 of 20 (100%) with UC. Scores of frequency and severity of inflammation were significantly greater in both affected children and those with UC, compared with controls (p < 0.001).CONCLUSIONS:A new variant of inflammatory bowel disease is present in this group of children with developmental disorders.

[1]  T. Berney,et al.  Role of neuropeptides in autism and their relationships with classical neurotransmitters , 1990 .

[2]  A. Sabrá,et al.  Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children , 1998, The Lancet.

[3]  C. Heijnen,et al.  Autism and the immune system. , 1997, Journal of child psychology and psychiatry, and allied disciplines.

[4]  V. Singh,et al.  Serological association of measles virus and human herpesvirus-6 with brain autoantibodies in autism. , 1998, Clinical immunology and immunopathology.

[5]  É. Zarifian,et al.  [Immune status in infantile autism. Correlation between the immune status, autistic symptoms and levels of serotonin]. , 1988, L'Encephale.

[6]  A. Dhillon,et al.  Persistent measles virus (MV) infection and immunodeficiency in children with autism, ileo-colonic lymphonodular hyperplasia and non-specific colitis , 1998 .

[7]  J. Panksepp.  A neurochemical theory of autism , 1979, Trends in Neurosciences.

[8]  A. Vandenbark,et al.  Depressed lymphocyte responsiveness in autistic children , 1977, Journal of autism and childhood schizophrenia.

[9]  S. S. Fieber,et al.  Lymphoid hyperplasia of the terminal ileum--a clinical entity? , 1966, Gastroenterology.

[10]  A. Ajdukiewicz,et al.  Nodular lymphoid hyperplasia with hypogammaglobulinaemia , 1972, Gut.

[11]  G. Asherson,et al.  Nodular lymphoid hyperplasia of the bowel in primary hypogammaglobulinaemia: study of in vivo and in vitro lymphocyte function. , 1977, Gut.

[12]  F. Rosen,et al.  Gastrointestinal complications of immunodeficiency syndromes. , 2008, Ciba Foundation symposium.

[13]  Y. Rosen,et al.  Nodular lymphoid hyperplasia of gut in HIV infection. , 1992, The American journal of gastroenterology.

[14]  K. Reichelt,et al.  Biologically active peptide-containing fractions in schizophrenia and childhood autism. , 1981, Advances in biochemical psychopharmacology.

[15]  R. Warren,et al.  Reduced natural killer cell activity in autism. , 1987, Journal of the American Academy of Child and Adolescent Psychiatry.

[16]  A. L. Brown,et al.  Dysgammaglobulinemia associated with nodular lymphoid hyperplasia of the small intestine. , 1966, The American journal of medicine.

[17]  V. Singh,et al.  Deficiency of suppressor-inducer (CD4+CD45RA+) T cells in autism. , 1990, Immunological investigations.

[18]  Sudhir Gupta,et al.  Th1- and Th2-like cytokines in CD4+ and CD8+ T cells in autism , 1998, Journal of Neuroimmunology.

[19]  J. Papadimitriou,et al.  Gastrointestinal abnormalities in children with autistic disorder. , 1999, The Journal of pediatrics.

[20]  G. Grant,et al.  Putrescine as a source of instant energy in the small intestine of the rat , 1998, Gut.

[21]  A. Wakefield,et al.  Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. , 1998, Lancet.

[22]  M. Garbrecht,et al.  Common Variable Immunodeficiency Syndrome and Nodular Lymphoid Hyperplasia in the Small Intestine , 1988, Endoscopy.

[23]  V. Singh,et al.  Antibodies to Myelin Basic Protein in Children with Autistic Behavior , 1993, Brain, Behavior, and Immunity.

[24]  Abraham Weizman,et al.  Abnormal immune response to brain tissue antigen in the syndrome of autism. , 1982, The American journal of psychiatry.

[25]  Y. Fujimura,et al.  Pathogenesis of aphthoid ulcers in Crohn's disease: correlative findings by magnifying colonoscopy, electron microscopy, and immunohistochemistry. , 1996, Gut.

[26]  N. Bhardwaj.  Interactions of  Viruses with Dendritic Cells: A Double-edged Sword , 1997, The Journal of experimental medicine.