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arising from a healed anal fissure, ulcer, or hemorrhoid. The etiology arises from lymphatic obstruction and they often coexist with intestinal inflammation.
11.6.1.2 Clinical Course
STs are usually asymptomatic, but when they become painful they should be clinically
investigated for perianal lesions, such as ulceration. Exceptionally, they may undergo
malignant transformation.
12
STs may increase in size and thickness and may become firmer during an active CD flare. ST can be found in distal involvement of the colon and ileal
location in 36.7% of the patients with CD.
13
11.6.1.3 Treatment
Spontaneous regression of STs has been reported, so the treatment should be directed at
treating disease activity. There is no effective medical management for these lesions; however, excision can lead to nonhealing and persistence of surgical wounds, therefore excision should be avoided.
3
11.6.2 Hemorrhoids
Hemorrhoids are infrequent in patients with CD. Hemorrhoids are present in only 7% of
patients with CD, which is lower than the estimated prevalence of 24% in the general
population.
14
Surgical intervention in a patient with relapse of CD should be avoided because a significantly high rate of delayed wound healing, inflammation, infection, and stenosis can
develop. In a retrospective study, Jeffery et al.
15
showed that the complication rate of surgical treatment of hemorrhoids in patients with CD was high (11 complications after 26
courses of treatment). Complications included anal stenosis and nonhealing, 30%
required proctectomy as a direct result of the complications. Hemorrhoidal disease in
the setting of CD is best managed with medical therapy and if surgery is required CD this
must be carried out when the patient is in endoscopic remission.
11.6.3 Perianal Ulcerations
Anal ulcerations were common in CD, with a reported incidence of between 5% and
43%.
16
These can be initial manifestations of IBD and must be distinguished from other
anorectal complications, including syphilis, herpes, acquired immunodeficiency syndrome (AIDS), Neisseria gonorrhoeae, Chlamydia trachomatis, tuberculosis, leukemic
infiltrates, carcinoma, and radiotherapy may also cause anal ulcerations. In 30% of
patients with perianal CD the anal manifestations precede any evidence of intestinal disease that could lead to a differential diagnosis, since concomitant proctitis is present in
75%–96% of cases.
17
Ulcerations can also occur along the entire length of the anal canal, the anal margin,
and even the lower rectum leading to extensive and devastating loss of substance.
The edges of the ulcerations are often edematous, irregular, and detached. Extension of
140 ANORECTAL DISORDERS
the ulcerations outside the anal canal to the perianal skin is rare but may occur in the
acute aggressive form of the disease. In order to diagnose the etiology of the ulcers, it
is important to perform biopsy and bacteriological analyses.
11.6.3.1 Clinical Course
Many of the ulcers heal spontaneously, although in some cases they can lead to the formation of a fistula or abscess and/or anal stenosis. The most common clinical feature of
anal ulceration in CD is pain, which has been reported in up to 70% of the patients.
18
Other
symptoms include discharge, pruritus, and bleeding.
In the most severe cases, in patients with cavitating ulcers, proctectomy has been
reported in up to 83%.
19
Half of all patients with ulcerations have been shown to progress
in anal stenosis with indurations.
11.6.3.2 Treatment
Topical treatments may improve symptoms while complete healing can occur in patients
with perianal ulcerations receiving infliximab therapy. Anti-tumoral necrosis factor
(anti-TNF) therapy has become the “gold standard” in the treatment of perianal CD.
20
In a recent study, 42.5% of patients with perianal ulceration had a complete clinical
response after anti-TNF therapy induction, which was defined as lack of sympto ms such
as anal pain and soiling. After a median follow-up period of 175 weeks healing of perianal
ulcers was maintained in 73% of cases.
20
For this reason anti-TNF therapy should be considered as first-line therapy for cavitating ulcers that have not responded to conventional
medical treatment.
11.6.4 Fissures
An anal fissure is defined as a cut, tear, or defect in the anoderm. It can be acute or chronic,
and is present in up to 19% of patients with CD.
21
The CD fissures are thought to result
from direct ulceration produced by a local inflammatory process. In the setting of CD, anal
fissures can be idiopathic, similar to those seen in non-CD patients. Atypical fissures are
often located on the anterior and posterior midline. In some cases multiple fissures can be
found that extend beyond the anal verge to the perianal skin.
11.6.4.1 Clinical Features
The fissures are diagnosticated with a clinical history and physical exam. The clinical presentation is anal pain, bleeding, discharge, and pruritus. Fissures may further lead to
abscess or fistula formation. When pain and fever are present suspicions should be raised
for an underlying abscess.
11.6.4.2 Treatment
Idiopathic fissures in CD patients can be treated similarly to those in non-CD patients.
Limiting toilet time and the use of antidiarrheal medications, when appropriate, are helpful. Anal fissures spontaneously heal in 80% of cases. However, in patients with persistent
Chapter 11 • Anorectal Disorders in Inflammatory Bowel Disease 141
fissure, the medical agents that have been shown to be effective include topical nitroglycerine (0.2% ointment applied twice a day or three times a day for 6–8 weeks), calcium
channel blockers (diltiazem 2% ointment tid applied for 6–8 weeks), and botulinum toxin
(20 units injected into the intersphincteric groove or into the internal sphincter on either
side) or local analgesics. In the case of nonhealing symptomatic fissure, proctitis should
be ruled out. However, in the presence of proctitis, surgery should be avoided, and the
therapeutic option is to optimize medical treatment of CD.
21
Surgical treatment with
sphincterotomy should be reserved for CD patients with a single, midline fissure, elevated
resting sphincter tone, and after sepsis has been excluded.
11.6.5 Stricture
Anal or rectal strictures may arise as complications of ulceration of the anal canal or rectum, perianal abscess, and fistula. There is an association between rectal inflammation
and the development of complex perianal fistula or rectovaginal fistula, which are considered to be bad prognostic indicators. Stricture of the anorectum has been reported in 17%
of patients with perineal CD.
19
11.6.5.1 Clinical Features
Most of the patients with strictures are asymptomatic. When they bec ome symptomatic
this is characterized by the presence of tenesmus, fecal incontinence or urgency, and
intestinal obstruction. The presence of strictures is more frequent in patients who have
had previous surgical treatment, including hemorrhoidectomy, wide manual dilatation,
or unroofing of a fistula track. The presence of an anorectal stricture is associated with
an increased prevalence of fistulizing perianal disease in 61% of patients with CD compared to 34.3% of patients with CD matched for age, gender, and duration of disease without anorectal strictures (P ¼.0001).
22
Furthermore, the presence of perianal abscesses was
more frequent in patients with CD and anorectal strictures than those without them (61%
vs 34.3%, P ¼.001).
11.6.5.2 Treatment
When strictures are symptomatic, anal dilatation should be performed by gentle digital
examination and also using a coaxial balloon technique, but this may be complicated
by delayed wound healing in 47% of patients.
23
Initially, anal dilatation should be performed under anesthesia and judiciously owing to the risk of sepsis, especially in the presence of severe disease activity in the rectum. Of patients with proctitis 43% had anal severe
stricture that required proctectomy.
16
11.6.6 Abscess and Fistula
Abscess and fistula are the most common presentations of anorectal CD. The prevalence
varies according to disease location, for example, the development of fistulas is less common in isolated ileal locations (12%) and ileocolonic disease (15%), but significantly
higher in colonic disease (41%) and rectal involvement (92%).
24
142 ANORECTAL DISORDERS
A fistula is an abnormal communication between two epithelial-lined surfaces. Fistulas arising from the anus or rectum can ter minate on the perianal or buttock skin, the
vagina and labia, the scrotum and penis, or the thighs and groins.
25
The course of perianal
fistulizing CD is characterized by prolonged periods of active pus drainage through the
external fistula openings and frequent disease relapses with a major negative effect on
the patient’s quality of life. The presence of perianal fistulizing disease is a predictor of
poor long-term outcome and optimal care requires a multidisciplinary approach for
assessment and treatment.
Among the factors influencing fistula outcome, the presence of proctitis has a major
effect. Active proctitis is an independent predictor of reduced fistula healing and
increased recurrence rates. Furthermore, rectal involvement is associated with higher
proctocolectomy rates compared with rectal sparing.
25
The tract of the fistula also has prognostic implications, as complex fistulas are less
likely to heal than simple fistulas (64.4% vs 88.2%),
26
and durable remission at the end
of a 10-year period is less likely to occur in complex fistulas compared with simple fistulas.
Perirectal and perianal abscesses can be expected to occu r in up to 80% of CD
patients.
27
The majority of abscesses involve the perianal and ischiorectal spaces. The
patient complains about anorectal pain, worsened by sitting, coughing, walking, and
bowel function. Fever, chills, and signs of systemic sepsis may also be present. Physical
examination shows erythema and swelling of the affected side.
11.6.6.1 Classification of Perianal Fistulas
Some classifications have been developed for perianal fistulas such as Parks classification,
14
which is shown in Table 11.2, and the St. James University Hospital Classification,
28
which is illustrated in Table 11.3.
The Parks classification
14
provides a detailed description of the course of the fistula
tract in relation to the external sphincter and the elevator plate. However, this classification does not provide any information regarding the complexity of the fistula and the presence of proctitis.
In contrast the St. James Hospital classification
28
offers detailed information on the primary fistula tract and its relation to the sphincter, and also considers secondary tracts and
the presence of abscesses. However, this classification is not simple to use in daily clinical
practice.
Table 11.2 Parks Classification
Superficial Superficial fistula without crossing any sphincter or muscular structure
Intersphincteric Fistula tract between the internal anal sphincter and external anal sphincter, in the intersphincteric
space
Transsphincteric Fistula tract crosses the external anal sphincter
Suprasphincteric Fistula tract penetrates the intersphincteric space and continues over the top of the puborectalis and
penetrates the elevator muscle before reaching the skin
Extrasphincteric Fistula tract outside the external anal sphincter and penetrating the elevator muscle
Chapter 11 • Anorectal Disorders in Inflammatory Bowel Disease 143
In order to simplify the classifications of perianal fistulas, the American Gastroenter-
ological Association (AGA)
29
proposed a classification that aimed to generate a practical
approach for perianal lesion assessment, in which perianal fistulas are divided into two
categories: simple or complex, as shown in
Table 11.4. This division is made on the basis
of fistula-tract anat omy, number of external openings, presence of abscesses and/or proctitis. This classification has prognostic relevance for fistula healing in patients with complex fistula that are less likely to achieve clinical remission than for patients with simple
fistulas. However, the “complex fistula” category is based on multiple variables such as
complexity based on the tract anatomy, presence of abscess, and active proctitis.
It is important to consider perianal fistula activity in relation to CD disease severity. In
clinical practice the approach to the assessment of perianal fistulas includes physical
examination, endoscopy, and pelvic MRI. Some clinical indices have been developed to
measure the activity of perianal disease. The Perianal Disease Activity Index
(
Table 11.5) is based on the assessment of quality of life and perianal disease severity (fis-
tula discharge, type of perianal disease and degree of induration , rating each item on a
five-point scale). This index is used in clinical practice and clini cal trials; however, the
major limitation is the lack of an established optimal cut-off for determining a substantial
clinical response.
Table 11.3 St. James Hospital Classification
Grade 1 Simple linear intersphincteric fistula
Grade 2 Intersphincteric fistula with intersphincteric abscess or secondary fistulous tract
Grade 3 Transsphincteric fistula
Grade 4 Transsphincteric fistula with abscess or secondary tract within ischioanal or ischiorectal fossa
Grade 5 Supralevator or translevator disease
Table 11.4 AGA Classification
Simple fistula
- Low (superficial or low intersphincteric or low transsphincteric origin of the fistula tract)
- Single external opening
- No pain or fluctuation to suggest perianal abscess
- No evidence of a rectovaginal fistula
- No evidence of anorectal stricture
Complex fistula
- High (high intersphincteric or high transsphincteric or extrasphincteric or suprasphincteric origin of the fistula tract)
- Multiple external openings
- Presence of pain or fluctuation to suggest a perianal abscess
- Rectovaginal fistula
- Anorectal stricture
144 ANORECTAL DISORDERS
11.6.6.2 Diagnosis
Perianal CD should be evaluated clinically by visual examination of the anus and rectum.
The diagnosis of perianal abscess and ischiorectal abscesses is usually easy to establish,
whereas submucosal and supralevator abscesses may require imaging studies, such as
MRI or endorectal ultrasound.
25
In those patients where fistula is suspected an EUA should be the first diagnostic test in
order to detect the presence of abscess, fistula, hemorrhoids, STs, fissures, ulcers, strictures, and malignancy. Metallic probes can be used to delineate the tract of the fistula,
and m ethylene blue or hydrogen peroxide instillation may be of benefit in further defining
the internal and external openings. Proctoscopy should also be performed at this time to
look for the presence of active proctitis.
11.6.6.3 Imaging
Computed tomography and fistulography have been replaced by MRI and endoanal ultrasound (EAUS).
30
Pelvic MRI is the gold standard for detecting fistula anatomy, complexity,
Table 11.5 Perianal Crohn’s Disease Activity Index (PCDAI)
Item Score
Discharge 0
1
2
3
4
No discharge
Minimal mucous discharge
Moderate mucous or purulent discharge
Substantial discharge
Gross fecal soiling
Pain and restriction of activities 0
1
2
3
4
No activity restriction
Mild discomfort, no restriction
Moderate discomfort, some limitation activities
Marked discomfort, marked limitation
Severe pain, severe limitation
Restriction of sexual activity 0
1
2
3
4
No restriction sexual activity
Slight restriction sexual activity
Moderate limitation sexual activity
Marked limitation sexual activity
Unable to engage in sexual activity
Type of perianal disease 0
1
2
3
4
No perianal disease or skin tags
Anal fissure of mucosal tear
< 3 perianal fistulas
> 3 perianal fistulas
Anal sphincter ulceration of fistula with significant undermining of skin
Degree of induration 0
1
2
3
4
No induration
Minimal induration
Moderate induration
Substantial induration
Gross fluctuance or abscess
Total
Chapter 11 • Anorectal Disorders in Inflammatory Bowel Disease 145
and activity. It has an accuracy of approximately 90% in defining fistula tracts and sphincter involvement and an important role in the evaluation of perianal disease in CD patients.
As an alternative to MRI, EUAS has been suggested to be useful in the detection of lesions
distant to the anal canal. A prospective triple-blinded study of 34 patients for the assessment of the accuracy of EUS, pelvic MRI, and EUAS in the evaluation of perianal fistulas
reported that rectal EUS correctly classified in 91%, pelvic MRI in 87%, and EUAS in 91% of
patients. A combination of two of these modalities is ideal, reaching 100% accuracy in
classification with a combination of the three.
31
11.6.6.4 Treatment
The goals of perianal disease management include preservation of continence, complete
healing, a reduction in the number of septic events, and improvement in the quality of life.
General treatment includes control of diarrhea, perianal hygiene using showers or sit
baths, and the application of protecting barrier creams.
32
In patients with suspected perianal abscess and fistula, the first step is to control the
active infection, which includes incision and drainage of the abscess and placement of
drains or setons under general anesthesia. Setons are used to avoid recurrent abscess formation and FI from damage to the sphincter complex.
10
Once acute infection is treated the next step is medical optimizat ion (particularly if
proctitis is present) or surgical treatment in those patients that are refractory to medical
treatment, including biological agents.
Medical treatment includes antibiotic, immunomodulator, and anti-TNF therapy. Corticosteroids are ineffective in anorectal CD and should be avoided. Antibiotics improve
symptoms of perianal fistulas and might contribute to healing.
33
Several studies demonstrated that when ciprofloxacin or metronidazole was administered for 4–8 weeks 50% of
patients had a complete resolution of their fistula and around 80%–100% of patients experienced a reduction in symptoms.
34
A metaanalysis that evaluated the efficacy of thiopurines such as azathioprine or
6-mercaptopurine in CD patients showed that 54% of patients had fistula healing compared to 21% with placebo (odds rati o: 4.44, 95% CI: 1.5–13.2).
34
Lastly, infliximab is an efficacious treatment for perianal fistulas in patients with CD.
Present et al. performed a study in 94 patients with perianal fistulas, where 68% of the
patients who received 5mg of infliximab per kilogram and 56% of those who received
10mg per kilogram had fistula closure compared to 26% of the patients in the placebo
group (P ¼.002 and P ¼.02, respectively).
Some trials have evaluated the efficacy of adalimumab in the healing of draining fistulas
in patients with active CD. The Crohn’s Trial of the Fully Human Antibody Adalimumab
for Remission Maintenance (CHARM) study
35
demonstrated that adalimumab was
effective in the closure of perianal fistulas after 1 year of treatment. The Additional LongTerm Dosing with Humira to Evaluate sustian Remission and Efficay in Crohn´s Disease
(ADHERE) study
36
showed that adalimumab maintained fistula closure for at least 2
more years. A retrospective study of 218 patients showed clinical improvement in 36% of
patients treated with surgery alone (seton, fistulotomy, flap, combination, or other)
146 ANORECTAL DISORDERS
vs. 71% of patients treated with surgery and medical therapy.37The surgical management
of complex fistulas may include permanent seton, fibrin glue, fistula plug, endorectal
advancement flap, and the ligation of the intersphincteric fistula tract (LIFT) procedure.
38
The efficacy of local injection of mesenchymal stem cells (MSCs) into perianal fistulas
of patients with CD was first tested in open-label studies using autologous cells from an
adipose or bone marrow origin; high fistula closure rates (75%–77%) were observed in all
studies. MSCs represent an efficacious local intervention that might not only be optimal
for patients with active perianal fistulizing disease, but also for patients with quiescent
luminal disease naı¨ve to immunomodulators or anti-TNF therapy.
39
Fig. 11.1 summarizes
a treatment algorithm for perianal fistulizing CD.
11.6.7 Fecal Incontinence
FI is one of the main anorectal complaints in patients with IBD. Besides being attributable
to diarrhea, this is often due to damage of the anal sphincter caused by perianal fistulas,
anal fibrosis, or surgical interventions to the anus. Furthermore, FI can be caused by proctitis due to a reduced rectal capacity and in patients with ileal pouch anal anastomosis
(IPAA). The capacity and distensibility of the pouch plays a role in the continence. Soiling
can be caused by a fistula due to damage to the anal sphincter.
The prevalence of FI in patients with IBD during relapse of IBD might be higher than
during the remission state, presumably because liquid stools are more difficult to control
than solid stools. FI is reported in up to 25% of patients and is higher than in the general
population. Some studies based on anorectal manometry testing have found increased
rectal hypersensitivity and contractility, whereas rectal compliance is impaired in those
with active UC suggesting that chronic changes in the rectal wall with deposition of fibrosis may be responsible. Patients with active IBD had lower rectal compliance and higher
risk of FI.
Criteria diagnostics for FI include recurrent uncontrolled passage of fecal material in
an individual for the last 3 months.
40
It is necessary to perform a digital anorectal examination to identify rectal masses, gauge anal sphincter tone at rest and during voluntary
contraction of the anal sphincter, and assess pelvic-floor mus cles during simulated
defecation.
11.6.8 Complications After Restorative Proctocolectomy
IPAA is the procedure of choice for continent reconstruction in patients with UC requiring
a total proctocolectomy. However, this procedure results in poor outcomes in patients
with CD. The pouch can fail in 36%–55% of patients with CD due to leaking at the anastomosis site. Patients typically present with symptoms consistent with poor pouch function: chronic pouchitis and fistulizing pelvic or perianal disease. Endoscopy showing
ulcerations in the afferent limb has been shown to be helpful in diagnosis.
41
Medical treatment based on a combination of azathioprine and infliximab improved pouch perineal
fistula in 85% of patients. Local advancement flaps can improve as many as 50% of cases
Chapter 11 • Anorectal Disorders in Inflammatory Bowel Disease 147
- History and examination
- Endoscopy (luminal activity)
- MRI (fistula anatomy, abscess)
- Abscess -->Drain/seton
Stenosis -->Dilatation
Fistula anatomy
Simple
fistula
Proctitis
Complex
fistula
Antibiotic + seton
+ IMS + anti-TNF
Yes
No
Antibiotic +
IMS
Antibiotic + IMS + anti-
TNF
Remission
Remission
- MSCs + IMS or
fistulotomy or
LIFT
- Treat as complex
IMS maintenance
Remission
IMS + anti-TNF
maintenance
- IMS + anti-TNF
maintenance
- Switch biological to
vedolizumab
- Switch IMS to
tacrolimus/ciclosporin
Proctitis
MSCs add on or
LIFT
- Mucosal
advancement flap
IMS + anti-
TNF
maintenance
Yes
Yes
Yes
Yes
No
No
No
No
FIG. 11.1 Treatment algorithm for perianal fistulizing disease. IMS, immunosuppressant; LIFT, ligation of the intersphincteric fistula tract; MSCs, mesenchymal
stem cells.
148 ANORECTAL DISORDERS
with perianal fistulas, but 3%–6% of patients require pouch excision and permanent
ileostomy, which can result in good long-term outcomes.
42
Total proctocolectom y with IPAA is the current gold standard for the surgical treatment
of UC refractory to medical management.
43
A procedure of significant magnitude, it
carries its own risks, including anastomotic failure, pelvic sepsis, and a low rate of neoplastic degeneration over the time. Recent studies have shown that total colectomy with ileorectal anastomosis (IRA) has been associated with good long-term functional results in a
selected group of UC patients amenable to undergoing strict surveillance for the potential
development of rectal cancer. A metaanalysis of 43 observational studies showed a pouch
failure risk of 6.8% (95% CI: 5.4%–8.4%), increasing to 8.5% (95% CI: 5.4%–13.2%) when
only patients with a minimal follow-up of 5 years were considered.
44
Other complications
such as pelvic sepsis and pouch fistulas are major postoperative complications that were
observed in 9.5% (95% CI: 8.2%–10.9%) and 5.5% (95% CI: 4.3%–7.0%), respectively. Sexual
dysfunction was present in 3.4% (95% CI: 2.7%–4.7%), while pouchitis was reported in
18.8% (95% CI: 15.7%–22.4%).
44
11.7 Conclusions
Several anorectal disorders can be diagnosed in IBD patients. Perianal CD is a major problem and early treatment of perineal sepsis is required in all cases. Other anorectal manifestations include STs, hemorrhoids, simple fistula, abscess, and FI. A multidisciplinary
approach is required in the diagnosis and treatment of these disorders.
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Chapter 11 • Anorectal Disorders in Inflammatory Bowel Disease 149
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