Lymphocytic leiomyositis and myenteric ganglionitis are intrinsic features of cystic fibrosis: studies in distal intestinal obstruction syndrome and meconium ileus.
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
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.
Smith
Virpi V
VV
Department of Gastroenterology, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK.
Schäppi
Michela G
MG
Bisset
W Michael
WM
Kiparissi
Fevronia
F
Jaffe
Adam
A
Milla
Peter J
PJ
Lindley
Keith J
KJ
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000150:complications* / Q000503:physiopathology; D003550:Cystic Fibrosis / Q000150:complications* / Q000503:physiopathology; D004386:Duodenum / Q000503:physiopathology; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D045888:Ganglion Cysts / Q000503:physiopathology; D006801:Humans; D007082:Ileum / Q000503:physiopathology*; D045823:Ileus / Q000150:complications; D007223:Infant; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology; D007409:Intestinal Atresia / Q000150:complications; D007413:Intestinal Mucosa / Q000503:physiopathology; D007418:Intestinal Pseudo-Obstruction / Q000209:etiology* / Q000503:physiopathology; D008214:Lymphocytes; D008297:Male; D008365:Manometry; D008470:Meconium; D032342:Muscle Cells / Q000378:metabolism / Q000473:pathology; D009197:Myenteric Plexus / Q000503:physiopathology*; D012189:Retrospective Studies