Perianal Fistulizing Crohn’s Disease: A Call to Action

doi:10.1016/j.cgh.2007.10.010

Clinical Gastroenterology and Hepatology

Volume 6, Issue 1, January 2008, Pages 7-10

https://doi.org/10.1016/j.cgh.2007.10.010 Get rights and content

The advent of biological therapies has focused attention on the importance of healing luminal Crohn’s disease, thereby modifying the disease course. Perianal fistulas are common in Crohn’s disease and often have a poor prognosis, with permanent sphincter and perineal tissue destruction. The importance of healing these fistulas has been less well appreciated. Management still often is left in surgical hands alone, rather than the optimal combination of surgery, infection control, and immunosuppression. Drug therapy often is haphazard, and the means of assessing healing over a long time period has been characterized poorly. Recent studies have suggested that many of these patients can achieve fistula healing, at least in the medium term. We therefore call for more active intervention, with the goal of healing, in these sick patients. Perianal fistulas lead to substantial physical and emotional distress because of pain, discharge, incontinence, perineal and genital disfigurement, and slow resolution even with treatment. The advent of accurate anal imaging, improved knowledge of surgical outcomes, and potent biological therapies make it timely to reflect on current best-management strategies.

References (34)

D.A. Schwartz et al.
The natural history of fistulising Crohn’s disease in Olmsted County, Minnesota
Gastroenterology
(2002)
D.A. Schwartz et al.
A comparison of endoscopic ultrasound, magnetic resonance imaging, and examination under anesthesia for evaluation of Crohn’s perianal fistulas
Gastroenterology
(2001)
L.H. Bernstein et al.
Healing of perineal Crohn’s disease with metronidazole
Gastroenterology
(1980)
G.R. Lichtenstein
Treatment of fistulising Crohn’s disease
Gastroenterology
(2000)
W.J. Sandborn et al.
Tacrolimus for the treatment of fistulas in patients with Crohn’s disease: a randomized, placebo-controlled trial
Gastroenterology
(2003)
G.R. Lichtenstein et al.
Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulising Crohn’s disease
Gastroenterology
(2005)
G. Van Assche et al.
Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn’s disease
Am J Gastroenterol
(2003)
E.A. Vasiliauskas et al.
An open-label pilot study of low-dose thalidomide in chronically active, steroid dependent Crohn’s disease
Gastroenterology
(1999)
E.D. Ehrenpreis et al.
Thalidomide therapy for patients with refractory Crohn’s disease: an open-label trial
Gastroenterology
(1999)
J.F. Colombel et al.
Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM Trial
Gastroenterology
(2007)

S.J. Bell et al.

Clinical course of fistulating Crohn’s disease

Aliment Pharmacol Ther

(2003)

A. Armuzzi et al.

Genotype-phenotype analysis of the Crohn’s disease susceptibility haplotype on chromosome 5q31

Gut

(2003)

J. Satsangi et al.

The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications

Gut

(2006)

P.J. Lunniss et al.

Factors affecting continence after surgery for anal fistula

Br J Surg

(1994)

T. Yamamoto et al.

Effect of fecal diversion alone on perianal Crohn’s disease

World J Surg

(2000)

J.G. Guillem et al.

Factors predictive of persistent or recurrent Crohn’s disease in excluded rectal segments

Dis Colon Rectum

(1992)

D.C. Pearson et al.

Azathioprine and 6-mercaptopurine in Crohn diseaseA meta-analysis

Ann Intern Med

(1995)

Cited by (46)

Management of patients with complex perianal fistulas in Crohn's disease: Optimal patient flow in the Italian clinical reality
2020, Digestive and Liver Disease
Citation Excerpt :
PFCD affects overall one third of patients [2] (90% rectal and 12% of isolated ileal CD [3]), it is the only manifestation in 5% [4] and the initial manifestation in 10% [5] of CD cases. PFCD with rectal involvement is associated with higher proctectomy rates compared to CD with rectal sparing (29 %–77.6%% vs 4 %–13.6% respectively) [6–8]. Moreover, PFCD has a prognostic significance being an independent risk factor for a definitive stoma [9] and an independent predictor of disease progression [2].
Perianal fistulizing Crohn’s disease (PFCD) is a common, disabling and aggressive phenotype that negatively impacts on the quality of life of affected patients. Its successful treatment is still a struggle for both physicians and patients. Significant advances in the management of this condition have occurred in the last two decades holding promise for a better future. This culminated into the concept of a collaborative multidisciplinary approach using the latest medical therapies combined with modern surgical and endoscopic techniques. Despite this, PFCD management and treatment have not been standardized yet. Thus the gastroenterologist and surgeon have to be familiar with several approaches and/or techniques. The positioning of each therapeutic option will certainly evolve with new data, but for the time being it should be driven by patient’s characteristics, physician’s preference and/or experience, costs and availability in local practice. Additionally, patient’s perception of benefits and risks of treatment may differ from those of physicians and recognition of this difference is a starting point for difficult clinical decision-making.
In this paper, a multidisciplinary group of Italian IBD experts explore and discuss current medical and surgical therapeutic options, highlighting areas of unmet needs in PFCD, with particular focus on the optimal patient flow within the Italian clinical reality.
Treatment of perianal Crohn's disease
2017, Seminars in Pediatric Surgery
Perianal Crohn’s is a common manifestation of Crohn’s disease. Primary manifestations of perianal disease mirror common anorectal conditions, however treatment is less successful than in those patients without Crohn’s related perianal disease. A multimodal approach to therapy including medical and surgical modalities is often necessary. The goal of treatment is to manage symptoms while maintaining continence.
Current management of perianal Crohn's disease
2017, Current Problems in Surgery
Advances in Use of Endoscopy, Radiology, and Biomarkers to Monitor Inflammatory Bowel Diseases
2017, Gastroenterology
Crohn’s disease and ulcerative colitis are heterogeneous inflammatory bowel diseases, and therapeutic requirements vary among patients. We have a limited capacity to predict disease progression for individual patients, therefore it is important that they are evaluated for the presence of active disease when symptoms are mild or even absent, when patients are more likely to respond to new treatment interventions. It then is important to monitor responses to treatment, to quickly identify those therapies that are ineffective, modify or change therapy, and avoid disease complications. Studies are underway to assess the effects of different monitoring strategies. Because of the heavy burden of severe inflammatory bowel disease on patients’ health and quality of life, and the association between intestinal healing and disease progression in high-risk patients, a treat-to-target strategy (based on tissue healing) is likely to be optimal.
Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial
2016, The Lancet
Complex perianal fistulas in Crohn's disease are challenging to treat. Allogeneic, expanded, adipose-derived stem cells (Cx601) are a promising new therapeutic approach. We aimed to assess the safety and efficacy of Cx601 for treatment-refractory complex perianal fistulas in patients with Crohn's disease.
We did this randomised, double-blind, parallel-group, placebo-controlled study at 49 hospitals in seven European countries and Israel from July 6, 2012, to July 27, 2015. Adult patients (≥18 years) with Crohn's disease and treatment-refractory, draining complex perianal fistulas were randomly assigned (1:1) using a pre-established randomisation list to a single intralesional injection of 120 million Cx601 cells or 24 mL saline solution (placebo), with stratification according to concomitant baseline treatment. Treatment was administered by an unmasked surgeon, with a masked gastroenterologist and radiologist assessing the therapeutic effect. The primary endpoint was combined remission at week 24 (ie, clinical assessment of closure of all treated external openings that were draining at baseline, and absence of collections >2 cm of the treated perianal fistulas confirmed by masked central MRI). Efficacy was assessed in the intention-to-treat (ITT) and modified ITT populations; safety was assessed in the safety population. This study is registered with ClinicalTrials.gov, number NCT01541579.
212 patients were randomly assigned: 107 to Cx601 and 105 to placebo. A significantly greater proportion of patients treated with Cx601 versus placebo achieved combined remission in the ITT (53 of 107 [50%] vs 36 of 105 [34%]; difference 15·2%, 97·5% CI 0·2–30·3; p=0·024) and modified ITT populations (53 of 103 [51%] vs 36 of 101 [36%]; 15·8%, 0·5–31·2; p=0·021). 18 (17%) of 103 patients in the Cx601 group versus 30 (29%) of 103 in the placebo group experienced treatment-related adverse events, the most common of which were anal abscess (six in the Cx601 group vs nine in the placebo group) and proctalgia (five vs nine).
Cx601 is an effective and safe treatment for complex perianal fistulas in patients with Crohn's disease who did not respond to conventional or biological treatments, or both.
TiGenix.
Mass Cytometry of the Human Mucosal Immune System Identifies Tissue- and Disease-Associated Immune Subsets
2016, Immunity
Inflammatory intestinal diseases are characterized by abnormal immune responses and affect distinct locations of the gastrointestinal tract. Although the role of several immune subsets in driving intestinal pathology has been studied, a system-wide approach that simultaneously interrogates all major lineages on a single-cell basis is lacking. We used high-dimensional mass cytometry to generate a system-wide view of the human mucosal immune system in health and disease. We distinguished 142 immune subsets and through computational applications found distinct immune subsets in peripheral blood mononuclear cells and intestinal biopsies that distinguished patients from controls. In addition, mucosal lymphoid malignancies were readily detected as well as precursors from which these likely derived. These findings indicate that an integrated high-dimensional analysis of the entire immune system can identify immune subsets associated with the pathogenesis of complex intestinal disorders. This might have implications for diagnostic procedures, immune-monitoring, and treatment of intestinal diseases and mucosal malignancies.

View all citing articles on Scopus

¹: Michael Kamm has received research support and has acted as a consultant to Schering-Plough, Herts, UK and Abbott, Berkshire, UK.

View full text

PerspectivePerianal Fistulizing Crohn’s Disease: A Call to Action

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Am J Gastroenterol

Gastroenterology

Gastroenterology

Gastroenterology

Clinical course of fistulating Crohn’s disease

Aliment Pharmacol Ther

Genotype-phenotype analysis of the Crohn’s disease susceptibility haplotype on chromosome 5q31

Gut

The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications

Gut

Factors affecting continence after surgery for anal fistula

Br J Surg

Effect of fecal diversion alone on perianal Crohn’s disease

World J Surg

Factors predictive of persistent or recurrent Crohn’s disease in excluded rectal segments

Dis Colon Rectum

Azathioprine and 6-mercaptopurine in Crohn diseaseA meta-analysis

Ann Intern Med

Perspective
Perianal Fistulizing Crohn’s Disease: A Call to Action