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294 H. Tulchinsky, I. Dotan, Z. Halpern, M. Rabau
ease extent also correlates with an increased risk of
cancer, with the risk being most significant in
patients with pancolitis [24]. Another two independ-
ent risk factors for CRC in UC patients are family his-
tory of CRC [25, 26] and primary sclerosing cholan-
gitis
(PSC)
(PSC) [27]. Common practice is to start an
annual or biannual surveillance colonoscopy, as can-
cer risk increases over that of the background popu-
lation. This would usually mean 8–12 years after dis-
ease onset for patients with pancolitis or upon diag-
nosis of concomitant PSC. Confirmed precancerous
lesions, such as high-grade dysplasia or dysplasia-
associated lesion or mass (DALM) would be an indi-
cation for proctocolectomy [28, 29]. In most inflam-
matory bowel disease (IBD) referral centres, con-
firmed low-grade dysplasia would also be an indica-
tion for surgery [30] although strict follow-up is an
optional alternative suggested by others [31].
Diagnosis of already existing colorectal carcinoma
is an obvious indication for surgery, and if curable
intent is possible, surgery should include removal of
the entire colon and rectum, as the presence of one
proven cancer puts the patient in a significant risk of
having a synchronous or developing a metachronous
carcinoma [32]. In patients with good operative risk
and adequate anal sphincter mechanism, IPAA is the
most suitable procedure for cancer prophylaxis as
well as preservation of reasonable quality of life.
Short- and Long-Term Complications of IPAA
While restoring the natural route of defecation, usu-
ally with improved quality of life and good long-term
functional outcomes [33–35], IPAA may also be asso-
ciated with various complications that, depending on
duration of follow-up and diagnostic criteria, may
occur in 10–60% of patients [36]. Complications may
appear early or late and may be surgical or medical.
Of note, clear distinction between purely medical or
surgical complications seems to be artificial. Several
complications are a combination of the two and thus
require the surgeon’s, as well as the gastroenterolo-
gist’s, insight. Pouch dysfunction is the most fre-
quent end result of a range of complications.
Amongst the various complications reported that
lead to pouch dysfunction are mechanical causes,
functional disorders, pelvic sepsis and pouch inflam-
mation. Systemic complications include new onset or
persistent EIM as well as haematological, nutritional
and electrolyte disturbances. The most dreaded con-
dition, despite its rarity, is pouch and rectal-stump
dysplasia or cancer [37]. However, the most common
and frustrating long-term consequence is pouch
inflammation [38]. A careful case selection is essen-
tial for a good outcome. Poor functional result or
pouch failure are usually the end result of major
unmanageable complications [39].
The Concept of a Comprehensive Pouch Clinic
At present, colorectal surgeons usually conduct the
follow-up of patients after IPAA although this dis-
tinct patient population often requires medical as
well as surgical follow-up, as shall be discussed in the
following sections. With a primary goal of improving
quality of patient care, we have established a multi-
disciplinary pouch clinic comprised of a colorectal
surgeon and an IBD-oriented gastroenterologist.
Patients are interviewed, examined and treated by
both surgeon and gastroenterologist simultaneously
at their outpatient clinic visit. Laboratory blood tests,
pouch endoscopy and biopsies are done routinely 1
year post-IPAA or at the beginning of follow-up at
the clinic and yearly thereafter or upon demand. Our
experience, based on the follow-up of 125 UC
patients after IPAA in such an approach, is integrat-
ed in the following sections.
Complications of IPAA that May End in Pouch
Dysfunction
“Normal” or acceptable pouch function is hard to
define since it varies from one person to another and
from day to day in the same individual. Most patients
with pouch dysfunction have an increased stool fre-
quency, which is often associated with small amounts
of stools. Incontinence may be the predominant
symptom or may occur in association with frequency
and urgency. The causes of pouch dysfunction can be
divided into four categories: septic complications,
mechanical or surgical complications, functional dis-
orders and inflammation, mainly pouchitis and, to a
lesser, extent cuffitis. Diagnosis is based on accurate
history and physical examination combined with one
or more auxiliary assessments, such as evaluation
under anaesthesia, pouch endoscopy, anorectal
physiology tests and various imaging techniques. The
major conditions that may result in pouch dysfunc-
tion are described below.
Pelvic Sepsis
Pelvic abscess is usually the result of a leak or dis-
ruption of the ileoanal anastomosis, leak from the
pouch suture line, or an infected haematoma. The
prevalence of postoperative pelvic sepsis varies
between 5% and 25% [40–42], this wide range being
partially attributable to the lack of a standard defini-
Follow-Up of Restorative Proctocolectomy: Clinical Experience of a Specialised Pouch Clinic 295
tion. Symptoms and signs include fever, anal pain,
tenesmus, purulent discharge, bleeding from the
anus and leukocytosis. Diagnosis may be established
by examination under anaesthesia alone or in combi-
nation with imaging studies such as contrast pou-
chography, computerised tomography (CT) and
magnetic resonance imaging (MRI). Pelvic sepsis
may be clinically evident in the immediate postoper-
ative period, after ileostomy closure or after a long
follow-up period. Late sepsis may be expressed as
pouch dysfunction with frequency, urgency, inconti-
nence or pouch-related fistula without systemic signs
of sepsis. The treatment is modified according to the
severity of sepsis. Some patients can be managed suc-
cessfully with antibiotic treatment while others will
need operative or CT-guided percutaneous drainage.
It is clear that severe pelvic sepsis with extensive
anastomotic breakdown results in a high failure rate
despite salvage attempts [43].
Pouch Fistulae
Fistula originating from the ileoanal anastomosis or
the pouch itself is a serious complication. The inci-
dence varies between 5% and 17% and depends on
the accuracy and duration of follow-up [44, 45]. It
often requires further surgery and may alter ultimate
functional outcome and lead to pouch excision. Fis-
tulae may occur to the perineum, vagina, bladder or
abdominal wall skin. Aetiologic factors include anas-
tomotic dehiscence, pelvic sepsis, surgical experi-
ence, localised ischaemia, entrapment of the posteri-
or vaginal wall in the stapling device and Crohn’s dis-
ease. Pelvic sepsis is probably the major predisposing
factor. Patients may be asymptomatic, some may
have only minor symptoms whereas others may have
disabling symptoms. Symptoms consist of purulent
discharge and flatus or stool passing through the
vagina, perineum or abdominal wall. Diagnosis is
based on history and physical examination and may
be confirmed by examination under anaesthesia.
Other diagnostic modalities may be used to assess the
tract, including endoanal ultrasound, pouchography,
fistulography, CT and MRI. Initial management
includes local procedures to drain the sepsis, and
Crohn’s disease must be excluded [46]. Most
pouch–perineal fistulae originate from the ileoanal
anastomosis. When superficial, these fistulae can be
managed by fistulotomy. If the fistula is transsphinc-
teric, it can be managed by staged fistulotomy using
a seton or by a pouch advancement procedure. At
our clinic, nine patients (7.6%) had a perineal fistula
at a mean follow-up of 57 months. All were treated by
staged fistulotomy. In none of these patients was the
diagnosis changed to Crohn’s disease.
Pouch-vaginal fistula (PVF) occurs in 6.3% (range
3–16%) of women who undergo IPAA [47]. Symptoms
are discharge of flatus and faeces through the vagina.
PVF are classified in relation to the ileoanal anasto-
mosis (above, below or at the anastomosis), and man-
agement is challenging. Diversion may be considered
in order to alleviate symptoms and control sepsis.
Several surgical procedures have been described for
the repair of PVF with variable success rates [48, 49].
Local procedures, such as transvaginal repair or
endoanal ileal advancement flap, are appropriate for
low fistulae whereas combined abdominoperineal
procedures should be considered for high fistulae.
Overall, more than 50% of patients maintain a func-
tioning pouch without fistula recurrence, and about
20% require pouch excision [50]. Among the pouch
clinic patients, four developed a PVF: two occurred
early after a one-stage IPAA and were successfully
treated by loop ileostomy. The other two patients had
very mild symptoms and refused surgery.
Ileoanal Anastomotic Stricture
Stenosis of the ileoanal anastomosis is the most com-
mon perineal complication after IPAA. The precise
definition is unclear and contributes to the wide
range of incidence reported in the literature. Narrow-
ing, which requires at least one dilatation under
anaesthesia, has been reported in 4–40% of cases [51,
52]. The main causative factors are pelvic sepsis with
subsequent fibrosis and tension on the anastomosis
leading to ischaemia. Patients most frequently pres-
ent with symptoms of straining, increased number of
bowel movements per day, watery stool, urgency of
defecation, a feeling of incomplete evacuation and
abdominal or anal pain. Rectal examination and con-
trast pouchography if needed confirm the diagnosis.
Anastomotic strictures can be noted before or after
ileostomy closure. Most strictures, especially those
found during an outpatient clinic visit before ileosto-
my closure, are annular and web like due to lateral
adhesions across the anastomosis and can be treated
successfully with a simple digital anal dilatation.
Severe strictures usually require repeat dilatations. If
a stricture persists in spite of repeated dilatations,
surgery is required. Despite all salvage attempts, up
to 15% of patients with severe anastomotic stricture
will eventually come to pouch excision and perma-
nent ileostomy [53].
Pouchitis
Pouchitis, defined as nonspecific inflammation of the
ileal pouch, is the most common long-term compli-
296 H. Tulchinsky, I. Dotan, Z. Halpern, M. Rabau
cation of IPAA in UC patients [54]. Aetiology is poor-
ly understood, and several mechanisms have been
suggested, such as genetic susceptibility, immune
alterations, faecal stasis resulting in bacterial over-
growth, lack of mucosal nutrients, ischaemia and
missed diagnosis of Crohn’s disease, none of which
have been proved. Pouchitis may be a form of IBD
that recurs in the pouch or a novel third form of IBD.
It tends to occur in equal frequency irrespective of
the pouch configuration. A number of factors have
been studied as potential predictors for the develop-
ment of pouchitis. A positive association was found
between the presence of EIM and PSC and the risk of
developing pouchitis [55, 56]. Smoking appears to
protect from developing pouchitis [57]. Data regard-
ing other predictive factors are more controversial
and include previous course of extensive colonic dis-
ease, backwash ileitis and serum perinuclear anti-
neutrophil cytoplasmic antibody (pANCA) staining
pattern [58]. The true incidence of pouchitis in
patients operated for UC is difficult to determine as it
depends on diagnostic criteria used to define the syn-
drome, accuracy and intensity of evaluation as well
as length and method of follow-up. Reported inci-
dence varies between 5% and 59% [59–61]. Diagnosis
should be based on clinical, endoscopic and histolog-
ic criteria [62]. To address this issue, a pouchitis dis-
ease activity index (PDAI) was developed taking into
account clinical symptoms, endoscopic findings and
histological changes, with pouchitis defined as a
score greater than or equal to 7 points [63]. The use
of clinical symptoms alone leads to overdiagnosis of
pouchitis and unnecessary antibiotic use [62]. Pou-
chitis may appear late in the postoperative course,
and its incidence increases with increased length of
follow-up [64].
Clinically, patients present with a marked increase
of stool frequency, usually watery but occasionally
bloody, urgency and incontinence. Abdominal pain
and pelvic discomfort, fever, fatigue, anorexia and
malaise are often present. Pouchitis is a heteroge-
neous disease and can be classified depending on the
activity (remission, mild to moderate or severe) and
pattern (acute, acute relapsing and chronic persist-
ent). It is usually well controlled with medical thera-
py and a variety of agents have been used. For the
majority of patients, 10–14 days of antibiotic treat-
ment will rapidly control symptoms [65]. Metronida-
zole is probably the most commonly used first-line
agent and has been shown to be effective for active
chronic pouchitis in a meta-analysis [66]. However,
long-term use of metronidazole may be hazardous
and cause peripheral neuropathy. Ciprofloxacin has
been widely used as an alternative or in combination
with metronidazole [67].
Relapse is common. About 60% of patients who
experience one episode of acute pouchitis will devel-
op recurrent attacks [68]. In patients with chronic
pouchitis who respond to antibiotic treatment and
are in remission, the use of probiotics seems to be
effective in the prevention of further episodes.
Gionchetti et al. [69] in a double blind, placebo-con-
trolled trial found that oral administration of a mix-
ture of probiotic bacterial strains (VSL3) was effec-
tive in secondary prevention of pouchitis. In total,
about 4.5–21.5% of UC patients develop chronic pou-
chitis, which is defined as symptoms that persistent
for more than 3 months or chronic antibiotic treat-
ment [59, 70]. Chronic pouchitis may eventually lead
to persistent use of anti-inflammatory agents, corti-
costeroids or immunosuppressive therapy [71]. A
recent study found that patients who had suffered
from chronic pouchitis had poorer functional results
and general health perception when compared with
patients with no or acute pouchitis [72]. About 1% of
the patients develop chronic persistent pouchitis
refractory to any medical treatment. In these
patients, pouch excision is thus the only alternative
since no other surgical approach has proved to alle-
viate symptoms and prevent recurrent pouchitis
[60].
In our group of patients, the cumulative risk of
developing at least one episode of pouchitis (that is,
PDAI 艌7) was 50%. Of the patients who developed
pouchitis,
28% had a single acute episode that
responded to antibiotics, 45% had recurrent acute
attacks and 27% had chronic pouchitis that required
long-term maintenance antibiotic therapy. Patients
with pouchitis were followed for a statistically signif-
icantly longer period of time compared with patients
without pouchitis. This finding supports the observa-
tion that the incidence of pouchitis tends to increase
with time. Thus, we recommend that patients be fol-
lowed up on a regular basis after the operation.
Cuffitis
A stapled ileoanal anastomosis without mucosecto-
my is done routinely at the level of the anorectal
junction; hence, a 1- to 2-cm strip of rectal columnar
cuff is retained. Some degree of persistent inflamma-
tion of the rectal cuff is common. This may be severe
enough to cause local symptoms of bleeding, burning
and urgency in up to 15% of patients [73]. There may
be disordered evacuation with frequency. Diagnosis,
as with pouchitis, is based on clinical symptoms,
endoscopy and histology taken from the rectal-cuff
mucosa. In some patients, cuffitis coexists with pou-
chitis. Treatment consists of topical corticosteroids
or 5-aminosalicylate. A few patients may need fur-
ther systemic treatment or a salvage surgery [74]. In
Follow-Up of Restorative Proctocolectomy: Clinical Experience of a Specialised Pouch Clinic 297
our group of patients, three (3%) were diagnosed
with cuffitis. All were treated with corticosteroids or
5-aminosalicylate enemas with good response; no
one needed a salvage operation.
Irritable Pouch Syndrome (IPS)
IPS is a functional disorder diagnosed in sympto-
matic patients who suffer mainly from increased
bowel frequency, urgency and abdominal pain with-
out endoscopic or histologic evidence of rectal cuff or
pouch inflammation [75]. Clinical features overlap
with those of pouchitis and resemble those of irrita-
ble bowel syndrome. The aetiology is unclear, and is
probably multifactorial in nature. Brain–gut factors
may play a role in the pathophysiology of IPS. It is
currently a diagnosis of exclusion. A recent study by
Shen et al. [76] reported that patients with IPS have
significantly poorer quality-of-life scores than
patients with normal pouches. Treatment is empiric
and symptom oriented. Some authors had reported
that dietary modifications, antidiarrhoeal medica-
tions (e.g. loperamide) or tricyclic antidepressants
might be effective in treating these patients [75]. In
our series, the incidence of IPS where patients had
symptoms but pouch endoscopy and biopsies did not
demonstrate a significant pathology (thus PDAI was
<7) was 5.1%.
Small-Bowel Obstruction
Small-bowel obstruction is a common complication
after major abdominal surgery. After IPAA, it may
occur before ileostomy closure; however, it is more
common after closure. The cumulative probability of
developing small-bowel obstruction increases with
longer duration of follow-up. The risk varies between
14% and 27% at 5 years after ileostomy closure
whereas at 10 years, it increases to 31% [77]. While
most patients may be treated conservatively, up to
17% of patients after IPAA require laparotomy with
adhesiolysis or small-bowel resection due to this
complication [78].
Nonsurgical Complications of IPAA
In contrast to IPAA complications that may result in
pouch dysfunction or small-bowel obstruction, there
are various complications that usually do not end in
pouch dysfunction or excision. However, they may
produce various signs and symptoms that interfere
with the patients’ health and quality of life and may
require investigation, follow-up and treatment by
both surgeon and gastroenterologist. Some of these
conditions are related to the defunctionalised stage,
i.e. the ileostomy, which are not discussed herein.
Amongst the complications that may occur in the
long-term follow-up of these patients, some merit
specific attention.
Vitamin Deficiency
Patients after IPAA may develop vitamin B12 defi-
ciency that often requires the exogenous addition of
this vitamin; the mechanism is unknown [79]. A pos-
sible explanation for this complication is change in
bacterial flora in the neoterminal ileum and pouch.
Iron-Deficiency Anaemia
Chronic pouchitis was reported as a risk factor for
the development of iron-deficiency anaemia [79, 80].
Iron deficiency occurred in 10.4% of patients after
IPAA. Massive, overt bleeding is a rare complication
of patients after IPAA. Iron-deficiency anaemia was
found in 22% of our patients. They were treated with
oral or intravenous iron supplements. There was no
correlation between pouch inflammation and iron-
deficiency anemia. In the follow up of pouch
patients, including those with a good pouch function,
we recommend on periodic laboratory evaluation
that should include a complete blood count, elec-
trolytes and renal function tests, liver function tests
and vitamin B12 and folic acid determinations.
New Onset or Persistent Extraintestinal Manifestations (EIM)
Cutaneous, peripheral articular, ocular, haematologic
and vascular EIM are linked to exacerbation of UC, so
by excision of the entire diseased colorectal mucosa,
EIM amelioration is anticipated. Nevertheless, these
manifestations may persist or be aggravated in some
patients whereas others may even develop EIM for
the first time after surgery, with or without pouchitis
[81–83]. It was shown that 31% of colitic patients
post-IPAA had joint symptoms. In two thirds, joint
involvement was polyarticular and the symptoms
were intermittent. Forty percent reported that their
symptoms interfered with daily life. No relationship
was found between pouchitis and the presence of
joint symptoms [81]. Goudet et al. [82] assessed the
clinical evolution of pre-IPAA EIM after surgery in a
retrospective study. As expected, ocular manifesta-
tions and PSC were unaffected. Arthralgia, erythema
nodosum and thromboembolic events benefited the
most from IPAA and tended to improve or disappear.
298 H. Tulchinsky, I. Dotan, Z. Halpern, M. Rabau
Dysplasia
Dysplasia in the ileoanal pouch or the rectal cuff is a
very rare complication after IPAA [84, 85]. Reported
potential risk factors are cancer or dysplasia in the
colectomy specimen, chronic pouchitis, and the time
after IPAA [86]. The risk of developing dysplasia or
cancer after IPAA had promoted us to perform annu-
al surveillance by pouch endoscopy with random
mucosal sampling from the pouch and the rectal cuff.
Of note, in our pouch clinic, out of 105 patients
screened of which 17% had diagnosed dysplasia or
cancer in the colectomy specimen, none had cancer
or dysplasia in the pouch or rectal cuff after a mean
follow-up of 57 months (range 1–258) post IPAA.
Perspective
IBD patients after IPAA may well present with both
medical and surgical complications. A comprehen-
sive pouch clinic is a novel approach in their man-
agement. It seems to be more efficient and beneficial
to patients as well as provide an ideal milieu for sur-
gical and gastroenterological teamwork. We believe
that it should be applied to all major centres treating
pouch patients.
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Introduction
Total proctocolectomy with ileal pouch-anal anasto-
mosis (IPAA) proposed for the first time by Parks in
1978 [1], represents nowadays the surgical treatment
of choice for the management of patients with famil-
ial adenomatous polyposis (FAP) and ulcerative coli-
tis (UC) [2, 3]. This procedure allows the removal of
the whole diseased colorectal mucosal and has the
great advantage of preserving the anal sphincter
function. Most patients undergoing IPAA for severe
colitis or for chronic continuous disease will achieve
excellent functional results and physical well-being.
In a prospective evaluation of health related quality
of life (HRLQ) after IPAA, a significant improvement
of HRQL has been shown, assessed with both generic
and disease-specific measures, with many patients
experiencing improvements as early as 1 month post-
operatively [4]. However pouchitis, a non-specific
(idiopathic) inflammation of the ileal reservoir, is the
most common long-term complication after pouch
surgery for UC [5].
Epidemiology,Risks Factors and Etiology
Frequency
The true incidence is still difficult to determine,
depending on the diagnostic criteria used to define
the syndrome, the accuracy of the evaluation and,
particularly, on the duration of the follow-up.
Reported incidence rates vary between 10 and 59%;
most patients experience their first episode of acute
pouchitis within 12 months after surgery, but some
may suffer their first attack some years later [6].
Recently, Simchuk et al. performed a retrospective
review of patients who underwent IPAA with a mean
follow-up of 3 years: the incidence of pouchitis was
59%, but it increased with the duration of follow-up
[7].
Risk Factors
The risk of developing pouchitis is much higher in
patients with pre-operative extra-intestinal manifes-
tations [8] and primary sclerosing cholangitis [9].
More controversial is the predictive role of anti-neu-
trophil cytoplasmic antibody with a perinuclear pat-
tern (p-ANCA) [10-15] and of the pre-operative
extent of UC [16-17]. Similarly to UC, smoking may
be protective against the development of pouchitis
(Table 1) [18]. The surgical technique (different type
of reservoir) does not influence the frequency of pou-
chitis [19-20].
Etiology
The etiology is still unknown and is likely to be mul-
tifactorial; a variety of hypotheses have been suggest-
ed, including bacterial overgrowth due to faecal sta-
sis, mucosal ischemia of the pouch, missed diagnosis
of Crohn’s disease, recurrence of UC and a novel
form of IBD. Most likely pouchitis is the results of the
interaction of a genetical and immunological suscep-
tibility and an ileal mucosa that has adapted from its
absorptive function to a new role of that of a reser-
voir with a colon-like morphology in response to fae-
cal stasis [21].
Management of Pouchitis
Paolo Gionchetti, Claudia Morselli, Fernando Rizzello, Rosy Tambasco, Gilberto Poggioli,
Silvio Laureti, Federica Ugolini, Filippo Pierangeli, Massimo Campieri
Table 1. Pouchitis: predictive factors
Positive Association
Extra-intestinal manifestations
Primary sclerosing cholangitis
Antineutrophil cytoplasmic antibody with a perinuclear
staining pattern (p-ANCA)
Extent of preoperative UC
Negative Association
Smoking
302 P. Gionchetti, C. Morselli, F. Rizzello, R. Tambasco, G. Poggioli, S. Laureti, F. Ugolini, F. Pierangeli, M. Campieri
Diagnosis
The diagnosis of pouchitis should be based on clini-
cal, endoscopic and histologic criteria; the key point
is that endoscopic and histopathologic evaluation is
required to make the diagnosis of pouchitis.
Clinical Diagnosis
The most frequent symptoms which characterise this
syndrome include increased stool frequency and flu-
idity, rectal bleeding, abdominal cramping, urgency,
malaise and tenesmus, and in most severe cases,
incontinence and fever [21]. Patients with pouchitis
may also have extra-intestinal manifestations such as
arthritis, ankylosing spondylitis, pyoderma gan-
grenosum, erythema nodosum and uveitis [8]. These
extra-intestinal manifestations may develop for the
first time with pouchitis, but frequently patients have
previously experienced these extra-intestinal mani-
festations before surgery.
Endoscopic Findings
A clinical diagnosis should be confirmed by
endoscopy and histology. With endoscopy the
mucosa of the neo-terminal ileum above the pouch
should be normal. Inflammation of the pouch
mucosa, with mucosal erythema, edema, friability,
petechiae, granularity, loss of vascular pattern,
mucosal haemorrhages, contact bleeding, mucus
exudates, erosions and small superficial mucosal
ulcerations can be present with varying degrees of
severity [22-23]. Inflammation may be uniform or
more severe to the distal part of the pouch.
Histologic Findings
Histologic examination shows acute inflammatory
cell infiltrate with crypt abscesses and ulcerations on
a background of chronic inflammatory changes with
villous atrophy and crypt hyperplasia [24-25].
Disease Activity Score and Classification
Because of the great variability in the results of reports
on the incidence of pouchitis and in the assessment of
therapy due to the lack of standardised diagnostic cri-
teria, Sandborn and colleagues developed a pouchitis
disease activity index (PDAI). This 18-point index, cal-
culated via three separate 6-point scales based on clin-
ical symptoms, endoscopic appearance and histologic
findings, represents an objective and reproducible
scoring system for pouchitis [26]. Active pouchitis is
defined by a total PDAI score ⱖ7 and remission is
defined as a score <7. Once diagnosis is made, pouch-
itis can be further classified. The disease activity can be
defined as remission, mild-moderate (increased stool
frequency, urgency, infrequent incontinence) or
severe (dehydration, frequent incontinence). Pouchi-
tis can also be defined on the basis of the duration of
disease: acute (ⱕ4 weeks) or chronic (>4 weeks).
Another way to classify this syndrome considers the
following patterns: infrequent (a single or two acute
episodes), relapsing (more than three acute episodes)
in about two thirds of cases, continuous or chronic
disease (a treatment responsive form requiring a
maintenance therapy or a treatment-resistant form).
About 15% of patients have a chronic disease and
some of them require surgical excision or exclusion of
the pouch because of impairment of reservoir function
and poor quality of life.
The PDAI, nowadays, is the most frequently used
scoring system in clinical studies to determine pou-
chitis disease activity. The validity of PDAI and the
necessity of its application in epidemiological, patho-
physiological or clinical studies, as well as in clinical
practice in order to make a correct diagnosis of pou-
chitis, have been shown by Shen et al. [27] in a study
evaluating the correlation between symptoms,
endoscopy and histologic findings in patients with
IPAA for UC. They found that symptoms alone do
not reliably diagnose pouchitis, whereas an evalua-
tion including symptoms, endoscopy and histology is
the best way to make the diagnosis. In fact, 25% of
patients with a high symptom score did not, in any of
the cases, reach the PDAI diagnostic criteria and 36%
of patients with minimal symptoms achieved a PDAI
score 艌7 because of significant endoscopic and his-
tologic inflammation [27].
Differential Diagnosis
Before treatment is started, it is important to exclude
other less frequent causes of pouch dysfunction or
pouch inflammation, and this is particularly neces-
sary in the case of a refractory patient. An anasto-
motic stricture, with consequent outlet obstruction
and faecal stasis, is a common complication of IPAA;
this increases stool frequency, makes the defecation
painful with an incomplete evacuation predisposing
to pouchitis. Diagnosis could be made by evacuation
pouchography, while the stricture can usually be
dilated with a finger or a rubber dilator.
Infectious etiology, caused by intestinal pathogens
such as Shigella, Escherichia coli, Salmonella, Clostridi-
Management of Pouchitis 303
um difficile, should be ruled out by microbiology ana-
lysis and pouch biopsy. Multiple cases of
cytomegalovirus infection have been reported showing
the need for using monoclonal immunofluorescent
staining for CMV for the examination of pouch biopsies
when treatment with antibiotics has proven unsuccess-
ful. In these patients the CMV infection must be exclud-
ed before starting immune modifier therapy [28-29].
Cuffitis is the inflammation of the retained rectal
mucosa (columnar cuff) above the anal transitional
zone (ATZ) after stapled anastomosis between the
pouch and the top of the anal canal; this kind of
inflammation, usually mild and not related to inflam-
mation of the pouch, can cause anal discomfort, peri-
anal irritation and pouch dysfunction. Clinically sig-
nificant cuffitis should be defined using a triad of
diagnostic criteria including clinical symptoms, endo-
scopic inflammation and acute histologic inflamma-
tion [30]. This syndrome rarely reaches dramatic pro-
portions and clinical improvement can be obtained
with topical corticosteroid, mesalazine suppositories
and lidocaine gel applications. Scintigraphic pelvic
pouch emptying scans can be used to evaluate
patients who have inadequate pouch evacuation.
Fistulae and perianal abscesses should be suspect-
ed as being the expression of misdiagnosed Crohn’s
disease. Review of the proctocolectomy specimen
and new biopsy samples are needed to make a correct
diagnosis. If Crohn’s disease is suspected, a small-
bowel follow-through x-ray will rule out disease
above the pouch. Approximately 5% of IPAA surgery
is performed in patients whose primary diagnosis of
UC is revised at some point after surgery to a defini-
tive diagnosis of Crohn’s disease. Other disorders
that are able to mimic pouchitis symptoms are bile
acid malabsorption, irritable pouch syndrome [31],
and chronic pelvic sepsis.
Medical Treatment
Until now, few small placebo-controlled trials and
small controlled comparisons of two active agents
have been carried out and, as a consequence, the
medical treatment of pouchitis is still widely empiric.
The reason for this small amount of randomised
double-blind controlled clinical trials may be found
in the lack of a general agreement about the criteria
for definition, diagnosis, classification and disease
activity [32].
Antibiotics
The awareness of the crucial importance that faecal
stasis and bacterial overgrowth may have in the
pathogenesis of acute pouchitis has led clinicians to
treat patients with antibiotics, which have become
the mainstay of treatment, in absence of controlled
trials. Usually metronidazole represents the most
common first therapeutic approach, and most
patients with acute pouchitis respond quickly to
administration of 1–1.5 g/day [33-34]. A double-
blind, randomised, placebo-controlled, crossover
trial was carried out in 1993 by Madden et al. [22] to
assess the efficacy of 400 mg three times a day of
metronidazole per os in 13 patients (11 completed
both arms of the study) with chronic, unremitting
pouchitis, defined by the presence of recurrent or
persistent symptoms with almost six bowel move-
ments a day and typical endoscopic findings. Patients
were treated for 2 weeks, with a 7-day wash-out peri-
od before the crossover to the second treatment.
Metronidazole was significantly more effective than
placebo in reducing the stool frequency (73 vs. 9%),
even without improvement of endoscopic appear-
ance and histologic grade of activity. Some patients
(55%) experienced side effects from metronidazole
including nausea, vomiting, abdominal discomfort,
headache, skin rash and metallic taste [35]. Dysgeu-
sia and peripheral neuropathy may limit long-term
administration of metronidazole, while patients
drinking alcohol may have a disulfiram-like reaction.
Recently Shen and colleagues have compared the
effectiveness and side effects of ciprofloxacin and
metronidazole in a randomised clinical trial regard-
ing the treatment of acute pouchitis. Seven patients
received ciprofloxacin 1 g/day and nine patients
metronidazole 20 mg/kg/day for a period of 2 weeks.
The results of this study have shown that both
ciprofloxacin and metronidazole are efficacious in
the treatment of acute pouchitis; they reduced the
total PDAI scores and led to a significant improve-
ment of symptoms and endoscopic and histologic
scores. However, ciprofloxacin led to a greater degree
of reduction in the total PDAI score and to a greater
improvement in symptoms and endoscopic scores;
furthermore ciprofloxacin was better tolerated than
metronidazole (33% of metronidazole-treated patients
reported adverse effects; none were reported in the
ciprofloxacin-treated group). The authors have sug-
gested that ciprofloxacin should be considered the
first-line therapy for acute pouchitis [36].
Other Agents
Anedoctal reports have suggested that oral or topical
conventional corticosteroids may be of benefit to
patients with pouchitis. Recently a double-blind,
double-dummy, 6-week-controlled trial investigated
the efficacy and tolerability of budesonide enema in
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