Perianal Crohn's Disease

Trivial disease or Trivial symptoms

The mere presence of skin tags and or fistulation, including minimally symptomatic anovaginal fistulation, does not mandate a therapeutic intervention. If the patient is untroubled by symptoms then irrespective of the clinical findings it seems difficult to recommend any therapy that might be associated with morbidity. Long term antibiotics may be useful in reducing discharge and perianal discomfort. The commonly used antibiotics to suppress perianal sepsis in PCD are metronidazole and ciprofloxacin.
Both are associated with 60-80% symptomatic improvement in unselected patients with PCD sepsis. Relapse of symptoms is common after cessation of antibiotics and this therapy if helpful, is often maintained indefinitely. Patients on metronidazole must be told to discontinue metronidazole if they develop paresthesiae in fingers or toes (6) as this indicates the development of peripheral neuropathy.

Antibiotics for PCD

Severe painful disease without Sepsis
Painful Anal Canal Ulcer

An unusual but dramatic presentation. The patient usually has no background of Crohns disease but presents with severe and disabling anal pain. MRI imaging does not show a collection, but EUA demonstrates an anal canal ulcer which responds well to Depomedrone injection. (7).

Severe ulcerating perineal disease without sepsis

This is an unusual surgical presentation and is most often seen in children with severe Crohns disease (8,9) – “Highly Destructive Perianal Crohn Disease”. Surgical drainage, once MRI scanning has excluded a deep collection, has no role. The management is using immunomudlators such as azathioprine or tacrolimus followed by infliximab infusion. If this fails to control anal symptoms then the only useful surgical intervention is defunctioning. This well help control symptoms, but is very rarely associated with re-establishing continuity and more usually is the stepping stone to proctectomy. (see the Failing/ Failed Bottom)

Symptomatic septic collection due to perianal fistula/abscess
A symptomatic septic collection requires surgical drainage with or without prior MRI imaging. If the track of a fistula is identified, then surgeon could consider fistulotomy or insertion of a draining seton.

Fistulotomy or Seton
Laying open a perianal Crohn’s fistula is not associated with problems of healing in the large majority of patients (10). But the large majority of Crohn’s fistulae involve significant sphincter thickness (11,12). Preservation of function with relief of sepsis are the two prime aims in dealing with PCD. For this reason the large majority of patients with an identified fistula tract are managed by seton insertion and not fistulotomy (11,12).

The successful seton – Whither next ?
In the large majority of patients, seton drainage controls their perianal sepsis and makes life much more tolerable. After the initial relief of symptom improvement, most patients are keen to know when the seton will removed. From the patient’s perspective the seton is associated with continuing perineal drainage, it can be uncomfortable and for young patients seeking sexual partners – it is the one body piercing that takes a bit or explaining. It can also be difficult for the patient to understand that the seton is not curing the fistula, but by allowing skin drainage it is a palliative measure preventing abscess formation.

Faced with these dilemmas the clinician has the following possibilities to discuss with patient.

• remove seton after sepsis settled
• leave seton indefinitely
• remove seton &close fistula- glue/plug - flap
• remove seton + give Infliximab infusions long term

3) REMOVE SETON – GO ON LONG TERM INFLIXIMAB INFUSIONS
First some more questions
Infliximab – What the hell is it ?

• Infliximab - a chimeric antibody (25% mouse derived, 75% human protein)
• Infliximab - binds and neutralizes both soluble and membrane bound TNFα -inhibits further activity

{Tumour Necrosis Factor-α (TNF-α)

• Identified in 1970s by Lloyd Old et al., as a serum factor that
caused necrosis of some murine tumours.

• TNFα is a multifunctional pro-inflammatory mediator
a) Induction of further cytokine production
b) Activation or expression of adhesion molecules
c) Growth stimulation}

Infliximab – Does it close the external opening of PCD perianl fistulae
= YES 50-60% of all comers (18)

Infliximab – Does maintenance therapy KEEP CLOSED the external opening of PCD perianal fistulae [ACCENT II TRIAL] (19)
= YES 50-60% those that respond

Infliximab – Does it completely heal the fistula track on radiological follow up.
= PROBABLY NOT (20-22). [ie palliative]

Infliximab – Does it prevent the need for surgery and hospital admission for PCD fistulae (23)
YES BY ABOUT 10% AT 12 MONTHS IN RESPONDERS

Infliximab – Finally does it have any downsides.[360,000 plus patients, RA mainly]

• £2000 per infusion
• Allergy
• Tuberculosis
• Lymphoma
• Lupus
• Demyelinating disease

so if we REMOVE THE SETON AND PUT PATIENT ON INFLIXIMAB – WHAT HAPPENS ?

Oxford Study (24)

• 21 patients, setons removed
• 3 Infliximab infusions – NOT maintenance; 21 months FU
• 4 healed, 4 well on repeat infusions
• 8 symptomatic fistula – 6 given new setons
• 5 diversion/ proctectomy
• question remains whether maintenance infliximab in conjunction with a seton will further improve outcome ??

• 21 patients, setons removed
• Maintenance Infliximab infusions – median 5 (range 3-19): 20 months FU
• 0 no response
• 11 partial response
• 10 complete response
• seton drainage and infusion of infliximab completely healed the perineum of 47% patients with complex fistulating perianal Crohn’s disease.

Minnesota Study (26)

• comparison of overall outcomes in two patient cohorts (ie historical controls)
• 147 managed pre-1999 without Infliximab
• 79 managed post-1999 with Infliximab
• PCD outcomes different after access to infliximab = NO

My view of this data, which we can discuss, is that the pros and cons of  three options with the patient who is well after seton drainage, are  as follows:

The Failing/ Failed Bottom – just 3 didactic points.
RECOGNITION – it is for the patient to decide.

…IT IS NOT FOR US TO IMPOSE THIS VIEW.
DIVERSION – HELPS SYMPTOMS BUT IS (USUALLY) FOREVER
Diversion in a patient with severe symptomatic perianal Crohn’s fistulation is associated with a significant improvement in the quality of life for the patient. (27). But it is important for the patient offered diversion to realise that it is very likely that faecal diversion is usually for good – barely 10% of patients being put back to intestinal continuity (28). In the large majority of patients in whom faecal diversion is required for symptoms, the diverting stoma is simply a stepping stone to proctectomy.

MUST CONSIDER RECONSTRUCTION AFTER PROCTECTOMY FOR BAD PCD

Proctectomy in the setting of severe perianal Crohns disease is associated with very poor perineal healing in 35-40% of patients (29). While in some patients the end result is simply an occasional perineal discharge in others the non-healing perineal wound can re-establish considerable discharge and sepsis. Reconstruction with a vertical rectus mycocutaneous flap (30) or gracilis myocutaneous flap should be considered in cases of bad PCD at the time of prcotectomy. Because of this eventuality, transverse abdominal incisions in certainly young Crohns patients, because they compromise future rectus muscle flap use, should be avoided.

Summary Points

REFERENCES

1. Crohn BB, Ginzburg L, Oppenheimer GD. Regional ileitis. A pathologic and clinical entity. J Am Med Ass 1932; 99:1323 – 1329.
2. Bissell AD. Localized chronic ulcerative ileitis. Ann Surg 1934; 99:957 – 966.
3) Hughes LE. Clinical classification of perianal Crohn's disease.
Dis Colon Rectum 1992;35:928-932.
4) Keighley MRB, Allan RN Current status and influence of operation on perianal Crohn's disease Colorectal Disease 1986;1:104-107
5) The Natural History of Fistulizing Crohn's Disease in Olmsted County, Minnesota GASTROENTEROLOGY 2002;122:875-880
6) Peripheral neuropathy in Crohn's disease patients treated with metronidazole. Gastroenetrology 1985;88(3):681-684.
7) Hughes LE, Donaldson DR, Williams JG, Taylor BA, Young HL. Local depot methylprednisolone injection for painful anal Crohn’s disease. Gastroenterology 1988; 94: 709-1 1.
8) Metastatic Crohn's disease presenting as chronic perivulvar and perirectal ulcerations in an adolescent patient. Pediatrics 1999 Feb;103(2):500-2
9) Highly Destructive Perianal Crohn Disease J Pediatr Gastroenterol Nutr 2005;41(5):667-669.
10) Williams JG, Rothenberger DA, Nemer FD, Goldberg SM. Fistula-in-ano in Crohn's disease: results of aggressive surgical treatment. Dis Colon Rectum 1991;34:378-384.
11) J.G. Williams, C.A. MacLeod, D.A. Rothenberger and S.M. Goldberg, Seton treatment of high anal fistulae, Br J Surg 78 (1991), 1159–1161
12) Long-term outcome following loose-seton technique for external sphincter preservation in complex anal fistula British Journal of Surgery 2004; 91: 476–480
13) Long-term outcome following loose-seton technique for external sphincter preservation in complex anal fistula British Journal of Surgery 2004; 91: 476–480
14) Long-term outcome following loose-seton technique for external sphincter preservation in complex anal fistula British Journal of Surgery 2004; 91: 476–480
15) Initial experience on efficacy in closure of cryptoglandular and Crohn’s transsphincteric fistulas by the use of the anal fistula plug Int J Colorectal Dis (2008) 23:319–324
16) A randomized, controlled trial of fibrin glue vs. conventional treatment for anal fistula. Dis Colon Rectum 2002;45:1608–1615.
17) Mizrahi N, Wexner SD, Zmora O, Da Silva G, Efron J, Weiss EG, Vernava AM III, Nogueras JJ. Endorectal advancement flap: are there predictors of failure? Dis Colon Rectum 2002;45:1616–1621
18) Infliximab for the Treatment of Fistulas in Patients with Crohn's Disease NEJM 1999;340(18):1398-1405
19) Infliximab Maintenance Therapy for Fistulizing Crohn's Disease
NEJM 2004;350(9):876-885
20) van Bodegraven AA, Sloots CEJ, Felt-Bersma RJF, Meuwissen SGM. Endosonographic evidence of persistence of Crohn’s disease-associated fistulas after infliximab treatment, irrespective of clinical response. Dis Colon Rectum 2002:45: 39–46
21) Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn's disease The American Journal of Gastroenterology 2003:98(2);332-339
22) Response of fistulating Crohn’s disease to infliximab treatment
assessed by magnetic resonance imaging Alimentary Pharmacology & Therapeutics 2003;17(3):387-393
23) Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn’s disease Gastroenterology 2005;128(4):862-869
24) Fistulating Anal Crohn’s Disease: Results of Combined Surgical and Infliximab Treatment Dis Colon Rectum 2006;49:1837-41
25) Infliximab in the surgical management of complex fistulating anal Crohn's disease Colorectal Disease 2004; 7 (2) , 164–168
26) Does Infliximab Infusion Impact Results of Operative Treatment for Crohn’s Perianal Fistulas? Dis Colon Rectum 2007; 50(11):1754-1760
27) Long -Term Quality of Life in Patients with Crohn’s Disease and Perianal
Fistulas: Influence of Fecal Diversion Dis Colon Rectum, 2007 :50(12):2067-2074
28) Effect of Fecal Diversion Alone on Perianal Crohn’s Disease
World J. Surg. 24, 1258–1263, 2000
29) Yamamoto T, Allan RN, Keighley MRB. Audit of single-stage proctocolectomy for Crohn's disease: postoperative complications and recurrence. Dis Colon Rectum 2000;43:249-256
30). Brough WA, Schofield PF (1991) The value of the rectus abdominis myocutaneous flap in the treatment of complex perineal fistula. Dis Colon Rectum 34:148–150