Fast Facts: Complex Perianal Fistulas in Crohn's Disease

P.G. Kotze, J. Warusavitarne

Description

Over the course of their Crohn's disease, up to half of affected individuals will develop a perianal penetrating complication (either perianal fistula or abscess). Symptoms can be debilitating, and the impact on quality of life significant. This first edition of 'Fast Facts: Complex Perianal Fistulas in Crohn's Disease' explains how fistulas form, who is at risk and the principles of diagnosis and classification. Later chapters explore the medical and surgical options, including innovative therapies. The intention throughout is to emphasize the importance of ‘joined-up thinking’ when caring for patients. Perianal fistulas are often challenging to treat in patients with Crohn’s disease, and a multidisciplinary approach is needed to get the best outcomes. Table of Contents: • Epidemiology, etiology and pathology • Anatomy and classification • Diagnosis • Management principles • Medical treatment Local perianal surgical (sphincter-preserving) interventions • Innovative therapies • Managing complications

Informations

• Publié par: S. Karger AG
• Date de parution: 26 mai 2021
• Nombre de lectures: 0
• EAN13: 9783318068160
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Fast Facts: Complex Perianal Fistulas in Crohn s Disease First published 2021
Text 2021 Janindra Warusavitarne, Paulo G Kotze 2021 in this edition S. Karger Publishers Ltd
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ePDF ISBN: 978-3-318-06816-0
eISBN: 978-3-318-06959-4
Warusavitarne J (Janindra) Fast Facts: Complex Perianal Fistulas in Crohn s Disease/ Janindra Warusavitarne, Paulo G Kotze
Typesetting by Amnet, Chennai, India. Printed in the UK with Xpedient Print.
Takeda provided financial sponsorship towards the development of this edition. Takeda also reviewed the text for factual accuracy.
List of abbreviations
Introduction
Epidemiology, etiology and pathology
Anatomy and classification
Diagnosis
Management principles
Medical treatment
Local perianal surgical (sphincter-preserving) interventions
Innovative therapies
Managing complications
Useful resources
Index
List of abbreviations
ACCENT II: (trial name) A Crohn s disease clinical trial evaluating infiximab in a new long-term treatment regimen in patients with fistulizing Crohn s disease
ADAFI: (trial name) Adalimumab for the treatment of perianal fistulas in Crohn s disease more effective alone or combined to ciprofloxacin
ADMIRE-CD: (trial name) Adipose derived mesenchymal stem cells for induction of remission in perianal fistulizing Crohn s disease
AE: adverse event
AGA: American Gastroenterological Association
CD: Crohn s disease
CERTIFI: (trial name) Crohn s evaluation of response to ustekinumab anti-interleukin-12/23 for induction
CHARM: (trial name) Crohn s trial of the fully human antibody adalimumab for remission maintenance
CI: confidence interval
CT: computed tomography
Cx601: earlier name of darvadstrocel
eASCs: expanded adipose stem cells
EMT: epithelial-to-mesenchymal transition
EUA: examination under anesthesia
GEMINI 2: (trial name) A phase 3, randomized, placebo-controlled, blinded, multicenter study of the induction and maintenance of clinical response and remission by vedolizumab (MLN0002) in patients with moderate to severe Crohn s disease
HBOT: hyperbaric oxygen therapy
HR: hazard ratio
HS: hidradenitis suppurativa
IBD: inflammatory bowel disease
IL: interleukin
JAK: Janus kinase
LIFT: ligation of intersphincteric tract
MAGNIFI-CD: magnetic resonance novel index for fistula imaging in CD
MMP: matrix metalloproteinase
MRI: magnetic resonance imaging
MSC: mesenchymal stem cell
NSAID: non-steroidal anti-inflammatory drug
OR: odds ratio
PDAI: Perianal Disease Activity Index
PFCD: perianal fistulizing Crohn s disease
PRECISE: (trial name) Pegylated antibody fragment evaluation in Crohn s disease: safety and efficacy
RCT: randomized controlled trial
RR: relative risk
TGF: transforming growth factor
TNF: tumor necrosis factor
UNITI: (trial name) A phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the safety and efficacy of ustekinumab induction therapy in subjects with moderately to severely active Crohn s disease (-2); who have failed or are intolerant to TNF antagonist therapy (-1)
VAAFT: video-assisted anal fistula treatment
Introduction
Over the course of their Crohn s disease, up to half of affected individuals will develop a perianal penetrating complication (either perianal fistula or abscess). Symptoms can be debilitating, and the impact on quality of life significant.
In Fast Facts: Complex Perianal Fistulas in Crohn s Disease , we explain how fistulas form, who is at risk and the principles of diagnosis and classification. Later chapters explore the medical and surgical options, including innovative therapies. Our intention throughout is to emphasize the importance of joined-up thinking when caring for patients.
Perianal fistulas are often challenging to treat in patients with Crohn s disease, and a multidisciplinary approach is needed to get the best outcomes. We trust that this book will be of interest and value to a range of health professionals involved in the care of affected patients and perhaps also to some patients. We hope that readers will appreciate our efforts to make our book informative and easy to read.
Finally, we thank our co-authors, Christopher Ma and Fabio Vieira Teixeira, for their invaluable contributions to this first edition.
1
Epidemiology, etiology and pathology
Co-authored by Christopher Ma MD
Department of Gastroenterology, University of Calgary, Canada
While most individuals with Crohn s disease (CD) present for medical attention because of luminal inflammatory features, perianal fistulas are among the most feared disease-related complications and can be extremely challenging to treat.
Epidemiology
Over the course of their disease, 15-50% of individuals with CD will develop a perianal penetrating complication (either perianal fistula or abscess). While 10-20% of patients present with perianal fistulizing CD (PFCD) as an initial manifestation of CD, the cumulative incidence of perianal complications increases over time. In a population-based cohort study from Olmsted County (Minnesota, USA) the cumulative incidence of perianal or rectovaginal fistulas was 18% after 10 years, 23% after 20 years and 24% after 30-40 years from CD diagnosis. 1
Although originally thought to be less common in children, similar incidence rates have been reported in pediatric populations: among 6679 prospectively enrolled children with CD in the multicenter ImproveCareNow Network, 21% developed perianal complications. 2
Over time, despite advances in treatment, the cumulative probability of developing PFCD has remained stable and the rate of recurrent perianal fistulas has not significantly decreased. A population-based study in the Inflammatory Bowel Disease South Limburg (IBDSL) cohort evaluated the cumulative probability of perianal or rectovaginal fistulas by year of diagnosis (1991-1998, 1999-2005 and 2006-2011): whereas the cumulative 5-year probability of PFCD was 14.1% in individuals diagnosed in the 1991-1998 era, this was not significantly lower in patients diagnosed during 2006-2011 (10.3%, p = 0.70). 3 Similarly, cumulative 5-year perianal fistula recurrence rates were stable (19.5% versus 25.5% versus 33.1%, p = 0.28).
Risk factors
Active rectal inflammation is the predominant risk factor associated with the development of PFCD. Correspondingly, patients with colonic disease are significantly more likely to develop PFCD than patients with isolated ileal or ileocolonic inflammation (41%, 12% and 15%, respectively), and approximately 9 in 10 patients will have rectal anatomic involvement. 4
Anorectal stricture. PFCD is associated with the presence of an anorectal stricture, which is hypothesized to increase the intraluminal rectal pressure. In an observational cohort study, 61% of patients with CD and concurrent anorectal stricture had perianal fistulas compared with 34% of patients with CD but without an anorectal stricture ( p = 0.001). 5
Other clinical features associated with the development of PFCD include younger age at diagnosis and the presence of other intestinal stricturing or penetrating complications. 6
Genetic factors have also been associated with PFCD. Single nucleotide polymorphisms in the nucleotide oligomerization domain 2 gene ( NOD2 ) have been associated with perianal fistulas. 7 An analysis of data from the Canterbury Inflammatory Bowel Disease (IBD) database, including information from 190 patients with perianal CD, identified a stronger association between perianal CD and the neutrophil cytosolic factor 4 gene ( NCF4 ) compared with CD without perianal complications and healthy controls: odds ratios (ORs) 1.47 (95% confidence interval [CI] 1.08, 1.99) and 1.47 (95% CI 1.10, 1.95), respectively. 6 Genetic variants in the IBD5 risk haplotype (5q31 cytokine cluster) have been associated with CD, though the relationship with perianal CD has been inconsistently demonstrated. In contrast, the gene for pseudouridine synthase 10 ( PUS10 ) confers a protective effect against development of perianal disease. 8
Pathophysiology
In PFCD, fistulas are caused by an abscess or luminal inflammation penetrating from the gut to the perianal skin ( Figure 1.1 ). This contrasts with the pathophysiology of anorectal fis