CFDB - Cystic Fibrosis DataBase

Gastrointestinal complications therapy

Fibrosing colonopathy in cystic fibrosis

Background

Fibrosing colonopathy (FC) is a rare usually iatrogenic disease associated to shortening and fibrosis of the colon, which almost exclusively occurs as a gastrointestinal complication in patients with CF. FC is characterized by severe submucosal thickening in distal caecum and ascending colon with mild or negligible signs of inflammation and absence of other lesions evocative of Crohn’s disease. Small bowel is never involved. Epithelium border is intact.

The pathogenic mechanisms leading to FC remain unclear. Previous studies have suggested that this complication is prevalent among people receiving large doses of high-strength pancreatin preparations (>50000 IU lipase per Kilogram per day), regardless of formulation. Since guidelines agreed to reccomend restrictions on PERT dose, FC has virtually disappeared.

Other predisposing factors are still under discussion, including young age (2-13 years), history of gastrointestinal complications (DIOS, meconium ileus), previous intestinal surgery, HdPE and use of histamine H2-receptor blockers, corticosteroids or recombinant human deoxyribonuclease (dNase), cases where high doses of PERT have not been described . Therefore a causal relationship is still debated.

Clinical manifestations of FC include abdominal pain, diarrhea, bloody stools, and, in some cases, partial or complete abdominal obstruction as the result of narrowing or colon strictures. Treatment of FC ranges from reduction of pancreatic enzyme supplementation to surgery, consisting of either partial or total colonic resection.

FC  is a complication quite different from constipation (a gradual faecal impaction of the colon) and distal intestinal obstruction syndrome (DIOS) that is considered as both incomplete or complete accumulation of faeces and sticky mucus, forming a mass in the distal part of the small intestine, a well-recognised complications in CF that may share  with FC similar symptoms, e.g. abdominal pain, at least at the onset (Munck A et al, 2016). DIOS affected adults more than children, risk factors include a severe CF genotype, deydration, high ambiet temperature, history of meconium ileus, organ transplantation and Cf related diabetes. Many different strategies are used in clinical practice, but no consent has yet been reached for treatment of DIOS. An update on DIOS has been published (Mavilia M, 2019)

Issues

  • to define risks factors 
  • to evaluate therapeutical options

What is known

DIOS

1 CDSR (Carroll W, 2021) was performed in order to evaluate trials comparing laxative therapy for preventing DIOS (including osmotic agents, stimulants, mucolytics and substances with more than one action) at any dose to placebo, no treatment or an alternative laxative therapy, in people of any age with pancreatic sufficient or insufficient CF and any stage of lung disease. Only 1  cross‐over trial including 17 patients with a duration of 12 months, was selected in which participants were randomly allocated to either cisapride (a gastro‐prokinetic agent) or placebo for 6 months each. No  significant differences  at 6 months between cisapride and placebo were registered for abdominal distension, MD ‐0.90 (95% CI ‐2.39 to 0.59) or abdominal pain, MD ‐0.4 (95% CI ‐2.05 to 1.25). The global symptom scores (whether individuals felt better or worse) were reported in the paper to favour cisapride and be statistically significant (P < 0.05).  The authors concluded that there is an absence of evidence for interventions for the prevention of DIOS. Furthermore,  cisapride is no longer licensed for use in several  countries due to the risk of serious cardiac events. Therefore, the limited findings from the trial are not applicable in current clinical practice.

1 CDSR (Gilghrist FJ, 2021) was performed in order to evaluate  the effectiveness and safety of different treatment regimens for the treatment of DIOS (complete and incomplete) in children and adults with CF. Only 1 double‐blinded, randomised cross‐over trial performed in 1993, which had a duration of 12 months ,included 20 subjects (16 females,mean age  13.1 years) that  were randomly given either high‐dose or low‐dose pancreatic enzymes for six months each. Trial investigators measured the difference in acute episodes of DIOS, presence of an abdominal mass and abdominal pain. Other outcomes measured in the trial included the coefficient for fat absorption and weight gain. There were no numerical data available for these outcomes, but the authors stated that there was no difference between treatment with high‐dose or low‐dose pancreatic enzymes. The overall certainty of the evidence was found to be very low.

Several Authors (Modlin SE et al, 2019) evaluated the impact of osteopathic manipulative treatment (OMT) to improve bowel symptoms and prevent DIOS  in 5 patients with CF  by releasing myofascial restrictions found in the abdomen and somatic structures, with the intent to optimize the autonomic and lymphatic systems and improve range of motion. These preliminary findings support the use of OMT as a method for the management of chronic constipation and DIOS in the CF population. 

Unresolved questions

One long-term prospective observational study (NCT01652157) in US has  recruited subjects with CF receiving different formula of digestive enzyme supplements from US Registry with the purpose to assess any narrowing of the large intestine causing adverse intestinal symptoms. Patients have be followed at their regular clinical care visits over a 10-year period. It has been estimated to include in this follow-up 21.960 patients with CF. It is estimated that the study will be posted within 2022.

Keywords: Fibrosing colonopathy;