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Lymphocytic Leiomyositis and Myenteric Ganglionitis Are Intrinsic Features of Cystic Fibrosis: Studies in Distal Intestinal Obstruction Syndrome and Meconium Ileus

Smith, Virpi V*; Schäppi, Michela G; Bisset, W Michael; Kiparissi, Fevronia*; Jaffe, Adam§; Milla, Peter J*; Lindley, Keith J*

Journal of Pediatric Gastroenterology and Nutrition: July 2009 - Volume 49 - Issue 1 - p 42–51
doi: 10.1097/MPG.0b013e318186d35a
Original Articles: Gastroenterology

Background: Cystic fibrosis (CF) is a multisystem disorder intrinsically associated with inflammation of mucosal surfaces. Because inflammation can result in enteric neuromuscular dysfunction we hypothesized that terminal ileitis in patients with CF may predispose to distal ileal obstruction syndrome (DIOS).

Methods and Patients: Full-thickness terminal ileal tissues from 6 children with CF and severe DIOS, 6 infants with complicated meconium ileus (MI), and 6 children with non-CF intestinal atresia were studied.

Results: Lymphocyte-predominant mucosal and transmural ileal inflammation was present in 6 of 6 patients with DIOS. Lymphocytic ganglionitis was present in 4 of 6 although numbers of myenteric neurons were not decreased (5/5). Myocyte proteins were preserved (6/6). Mild submucosal fibrosis was common in DIOS (5/6) and transformation of submucosal fibroblasts to a myofibroblastic phenotype was noted in 4 of 6. Inflammatory changes were distinct from those described in fibrosing colonopathy. Antroduodenal manometry in an individual who had experienced MI/DIOS was consistent with a neuropathic pseudo-obstructive process. Submucosal or transmural lymphocyte predominant inflammation was also present in 6 of 6 infants with complicated MI, which, when coupled with submucosal myofibroblast proliferation (5/6), appeared highly predictive of CF rather than non-CF atresia. Histological findings at birth were similar, although milder, than those seen in DIOS, suggesting that these changes are a primary abnormality in CF.

Conclusions: Submucosal or transmural inflammation of the ileum is common in newborns with CF and MI and older children with DIOS. Severe recurrent DIOS should be investigated with seromuscular and mucosal biopsy of the ileum to seek a transmural ileitis potentially amenable to anti-inflammatory therapies.

*Departments of Gastroenterology and Histopathology, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK

Department of Pediatrics, University Hospital of Geneva, Geneva, Switzerland

Department of Paediatrics, Royal Aberdeen Children's Hospital, Aberdeen, UK

§Department of Respiratory Medicine, Sydney Children's Hospital, Sydney, NSW, Australia

Received 2 January, 2008

Accepted 10 July, 2008

Address correspondence and reprint requests to Dr Keith J. Lindley, Gastroenterology Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK (e-mail:

The views expressed on this publication are those of the authors and not necessary those of the NHS Executive.

The authors report no conflicts of interest.

© 2009 Lippincott Williams & Wilkins, Inc.