Ileal lymphoid nodular hyperplasia, non-specific colitis and regressive behavioural disorder: a new syndrome?

Abstract

Background - 12 children were investigated for a new syndrome comprising chronic enterocolitis & regressive behavioural disorder. Children (mean age 6 years; range 3-10; 11 male) with a history consisting of achievement of developmental milestones followed by loss of acquired skills including language, plus bowel symptoms including diarrhoea, abdominal pain and, in some, food intolerance. Methods - Under sedation, ileo-colonoscopy and biopsy, MRI, EEG & lumbar puncture were performed. Barium follow-through was undertaken where possible & chemistry, haematology and immunology profiles. Results - Onset of behavioural symptoms was associated, by the parents, with MMR vaccination in 8 of the 12 children, & with measles infection in one child & otitis media in another. All 12 children had significant intestinal pathology; this ranged from lymphoid nodular hyperplasia to aphthoid ulceration. Histology revealed patchy chronic inflammation in the colon in 11 cases & reactive ileal lymphoid hyperplasia in 7 cases (no granulomas) 1 case had ileal lymphoid nodular hyperplasia alone, diagnosed on barium follow-through. Behaviourally, they formed a heterogeneous diagnostic group that included autism (9/12), disintegrative psychosis (1/12) & post-viral/vaccinial encephalitis (2/12). All children exhibited features of severe developmental regression. There were no focal neurological abnormalities & MRI & EEG studies were normal. A raised urinary methylmalonic acid was found in 8/8 compared with age-matched controls (p=0.003), low haemoglobin in 5/12 & low serum IgA in 6/12. Conclusions - We have identified significant gastrointestinal pathology in association with behavioural regression in a selected group of previously, apparently normal children. In the majority there is a clear temporal association with possible environmental triggers.