Perianal Fistula of Crohn s Disease

Case 3

A 16 year-old boy referred by surgeon due to perianal fistula since 6mo ago CC=perianal pain History of intermittent non-bloody diarrhea and mild abdominal pain and 2-3kg weight loss and without history of fever or chills Ph/E=normal RE=8x3cm perianal lesion

Transsphincteric Fistula

Lab data Hb=13.5, MCV=76, plt=345000, ESR=45 CRP=60 LFT=Nl, FBS, Cr, TG, Chol=nl S/E *3=Nl Stool calprotectin=565

What is your plan?

The main aspects in planning a strategy for the management of CD fistulae are 1. Locate the origin of the fistula and its anatomy 2. Evaluate the originating intestinal loop (inflammation or stenosis) 3. Identify or exclude local sepsis (abscess) 4. Determine which organs are affected and their contribution to systemic symptoms or impairment of the quality of life 5. Assess the nutritional status of the patient.

Initial diagnostic approach Pelvic MRI should be the initial procedure because it is accurate and non-invasive, although it is not needed routinely in simple fistulae

Evaluation - Imaging Fistulography CT U/S MRI <25% accuracy abscess assess sphincters 86% concordance with operative findings for presence of 1o track, 2o extensions and abscess, 97% for horseshoeing

Initial diagnostic approach Examination under anaesthetic is considered the gold standard only in the hands of an experienced surgeon. It may allow concomitant surgery obtain appropriate Informed consent of the patient, since unexpected findings may preclude this

Initial diagnostic approach Anorectal ultrasound requires expertise, but can be equivalent to pelvic MRI in completing examination under anaesthesia if rectal stenosis has been excluded. Fistulography is not recommended

. A prospective, blinded study found high accuracy in diagnosis individually for MRI, EUS and examination under anesthesia. When either of the imaging modalities was combined with examination under anesthesia, the accuracy was 100% and was the most cost effective approach.

Initial diagnostic approach Concomitant rectosigmoid inflammation has prognostic and therapeutic relevance therefor: proctosigmoidoscopy should be used routinely in the initial evaluation

About 20% of patients with Crohn s disease will develop perianal fistulas within 10 years of diagnosis..

Classification of perianal fistulae There is no consensus for classifying perianal fistulae in CD. In clinical practice most experts use a classification of simple or complex. From the surgical point of view Parks' classification is more descriptive and can influence surgical decisions, but it is complicated to use in routine practice

A simple fistula is superficial or begins low in the rectal canal, has a single opening on the skin, is not associated with an abscess, and does not communicate with other organs

In contrast, a complex fistula begins high in the anal canal, is associated with an abscess, has multiple skin openings, connects with adjacent structures or is associated with inflammation of the colonic mucosa.

WCOG Statement on Medical Treatment Aminosalicylates, corticosteroids, antibiotics There is no demonstrable role for corticosteroids or aminosalicylates in perianal Crohn s disease Grade of Recommendation: 1C Antibiotics, namely metronidazole and ciprofloxacin improve symptoms and may contribute to healing. Therefore, antibiotics are only recommended as adjunctive treatments for fistulas. Grade of Recommendation: 1C and 2C. Gecse et al., Gut 2014

Vedolizumab for Crohn s Disease Fistulae Characteristic VDZ/PBO (n=153) VDZ Q8W (n=154) VDZ Q4W (n=154) With concomitant glucocorticoids, n (%) 56 (37) 59 (38) 58 (38) With concomitant immunosuppressants, n (%) 23 (15) 27 (18) 31 (20) With glucocorticoid and immunosuppressive, n (%) 26 (17) 23 (15) 22 (14) No glucocorticoid or immunosuppressive, n (%) 48 (31) 45 (29) 43 (28) Median prednisone equivalent dose, mg (interquartile range) 20.0 (12.5,30.0) 20.0 (15.0,30.0) 20 (15.0,30.0) With prior anti-tnfα use, n (%) 82 (54) 88 (57) 83 (54) With prior anti-tnfα failure, n (%) 1 TNFα antagonist 78 (51) 82 (55) 77 (50) Inadequate response 35 (45) 37 (45) 31 (40) Loss of response 29 (37) 35 (43) 33 (43) Intolerance 14 (18) 10 (12) 13 (17) 2 TNFα antagonists 53 (35) 46 (30) 49 (32) Prior surgery for CD, n (%) 57 (37) 57 (37) 61 (40) History of fistulizing disease, n (%) 57 (37) 47 (31) 49 (32) Draining fistulae at baseline, n (%) 18 (12) 17 (11) 22 (14) GEMINI 35 II MAINTENANCE Sandborn WJ et al. N Engl J Med. 2013

REMAINING QUESTIONS - When to remove the Seton? - When to repeat imaging? - When to stop concomitant antibiotics? - When to consider definitive surgery? - When can you stop medical therapy

Parks Anal Fistula Classification Intersphincteric 45%-70% Transsphincteric 23-30% Suprasphincteric 5-20% Extrasphincteric 2-5% Horseshoe extension 8.8%

Intersphincteric Fistula

Extrasphincteric Fistula

Suprasphincteric Fistula

Transsphincteric Fistula

Evaluation Digital assessment (<85% accurate) H2O2 (97% accuracy) Dyes Goodsall s rule (59% accuracy) Anterior external opening radial track Posterior external opening posterior midline Exception long anterior

Anal Fistula - Management Fistulotomy +/- marsupialisation Fistulectomy open vs core Seton insertion Loose/Draining seton Tight/Cutting seton Chemical seton Rectal Advancement Flap Fibrin Glue

Setons Potential actions of the seton Act as a drain for acute sepsis To allow resolution of inflammation prior to definitive fistula surgery Role in staged fistulotomy Delineation of the amount of muscle caudal to the fistulous track Cutting & Chemical setons: Controlled division of the enclosed sphincter mechanism with minimal separation of the transected ends.

Benefits: Fibrin Glue Sphincter apparatus not disturbed No significant scarring from the treatment Technique EUA; identification of primary and any secondary tract openings. Fistula tract then curetted Fibrin adhesive injected into the secondary tract opening until seen coming from the primary opening. Vaseline gauze applied over the openings

Study Results: Fibrin Glue Lindsay I; Dis Colon & Rectum 2001 55% healed at in the short term (8/12 follow up) Probably little advantage over conventional Rx but may be useful first line treatment for higher fistulas Cintron JR; Dis Colon & Rectum Jul 2000 54% fistula closure at 12 months with autologous fibrin 64% fistula closure at 12 months with commercial fibrin sealant. Most treatment failures occurred within 3 months

Surgical procedures for perianal Crohn's disease Fistulectomy and fistulotomy should be performed very selectively, because of the risk of incontinence. A diverting stoma or proctectomy may be necessary for severe disease refractory to medical therapy

Uncontrolled evidence suggests that local injection of infliximab close to the fistula track may be beneficial in patients not responding to or intolerant of intravenous infliximab

Summary for Successful Management of Anal Fistula 1. Definition of the anatomy. 2. Surgical drainage of abscess and tracks. 3. Eradication of anal gland origin. 4. Preservation of sphincter function.

combination of seton placement and IFX is superior to either strategy alone, probably because of better drainage of abscesses and fistulae. This combination gives better response,longer effect duration and lower recurrence rate. Moreover, reparative surgery (e.g. mucosal flap or fistula plug) during IFX therapy may improve long-term healing rates

Monitoring the therapeutic response Clinical assessment (decreased drainage) is usually sufficient. To quantify treatment efficacy the Perianal Crohn's Disease Activity Index (PCDAI) should be used. In the setting of clinical trials,mri in combination with clinical assessment is now considered mandatory

Continuing therapy for perianal Crohn's disease Azathioprine/6-mercaptopurine,infliximab or adalimumab or seton drainage, or a combination of drainage and medical therapy should be used as maintenance therapy. All mainte-nance therapies should be used for at least one year

There are no data on the effect of AZA/MP as maintenance therapy for fistulae after induction with IFX, or during IFX maintenance therapy

Therapeutic approach in the event of infliximab failure In the event of anti-tnf failure, the use of azathioprine/mercaptopurine or methotrexate,with antibiotics as adjunctive treatment, is the first therapeutic choice Depending on the severity of the disease, a diverting ostomy can be performed and can rapidly restore quality of life, proctectomy is the last resort

Enterocutaneous fistulae There are no randomised-controlled trials on the effect of medical treatment for non-perianal fistulating CD. For the 25 patients (out of 282) with rectovaginal fistulae in the ACCENT II trial, IFX was only modestly effective (45% closure at week 14). The management is a complex,multidisciplinary challenge, and referral to a specialist centre is recommended. Early re-operation to close a fistulous track, is often associated with recurrence or further complications. the nutritional state should be optimised.

question A 30-year-old female with a 5 year history of Crohn s disease comes to you for evaluation of a 3 week history of perianal pain and drainage. On physical exam you find the following [see figure].

Which one of the following is an appropriate treatment option for this patient? A Prednisone B Oral 5-ASA treatment C Infliximab D Budesonide

C is correct Explanation The only agent that has been shown to have activity for Crohn s perianal fistulae is infliximab. In particular, prednisone in this setting has been associated with increased chances of abscess formation and complications associated with treatment.

question Which one of the following is an effective treatment option for a patient with Crohn's disease who has active proctitis and a draining perianal fistula? A EUA with fistulotomy B Prednisone C EUA with placement of a cutting seton D EUA with placement of a draining /non-cutting seton

D is correct Explanation Patients with active proctitis are at increased risk of poor outcomes with aggressive surgical intervention. EUA with fistulotomy and EUA with cutting seton placement are both associated with non-healing wounds and incontinence in the setting of active proctitis.

Prednisone is not effective for fistulizing disease and may increase the risk of abscess. The placement of a draining or non-cutting seton helps control healing and reduces the risk of sphincter injury in this setting.

QUESTION A 19-year-old man presents with 2 months of gradually worsening diarrhea, urgency, fatigue, and right lower quadrant abdominal pain. He has perirectal discomfort. He has lost 15 pounds. Examination reveals mild abdominal tenderness and a simple perianal fistula draining a small amount of purulent material.

He has moderate microcytic anemic, and his serum C-reactive protein concentration is elevated at 25 mg/l (normal < 8 mg/l). Colonoscopy reveals the following findings in the terminal ileum as far as intubated (15 cm) [FIGURE].

Biopsies reveal moderately active chronic ileitis. The colon is endoscopically normal. He is interested in pursuing the therapy with the highest chance of achieving success (steroid-free remission without surgery).

Which of the following do you recommend? A Controlled ileal release budesonide 9 mg by mouth daily, with a taper over 3-4 months B Azathioprine 2.5 mg/kg body weight by mouth daily C Prednisone 60 mg by mouth daily, with a taper over 2-3 months D Mesalamine 2,000 mg by mouth twice daily E Infliximab 5 mg/kg body weight infusions (induction and maintenance dose) along with azathioprine, 2-2.5 mg/kg body weight daily

Answer: E Explanation This patient is at high risk for progression to intestinal complications or surgery. He has young age at diagnosis, male gender, small bowel involvement (as opposed to pure colonic involvement which has a milder clinical course) and perianal disease at diagnosis.

All of these factors have been implicated in various natural history models of Crohn s disease as being associated with progression to disabling Crohn s disease, stricturing and/or penetrating complications, or bowel resection. While budesonide and prednisone are reasonable drugs for induction of remission, they are not indicated as maintenance therapy.

Mesalamine is not effective for induction or maintenance therapy in Crohn s disease. The SONIC trial showed that the combination of infliximab and azathioprine resulted in higher rates of steroid-free remission than infliximab monotherapy or azathioprine monotherapy.

QUESTION A 60-year-old man with a 6-year history of Crohn's disease involving the ileum and left colon presents with new onset of perianal pain for the last week. He has previously been well-controlled on 1.5 mg/kg/day of 6-mercaptopurine, and denies any increase in stool or abdominal pain recently.

On physical exam, he is afebrile and his abdomen is soft and non-tender. His rectal exam is significant for extreme tenderness and a large fluctuant mass [FIGURE].

What is the appropriate next step in his management? A Begin prednisone 40 mg a day B Refer him immediately to a colorectal surgeon for an incision and drainage procedure C Start anti-tnf antibody treatment D Image perianal process with pelvic MRI or rectal EUS

Answer: D Explanation is recommended that patients with either a suspected abscess, failing medical therapy, or who are being referred to surgery, undergo imaging with EUS or MRI.

Similarly, the ECCO guidelines for the management of Crohn's disease recommended imaging with MRI or EUS for all patients with fistulas. This patient has a large fluctuant mass suggestive of an abscess so should have either an MRI or EUS performed according to both guidelines.