CLINICAL REVIEW ARTICLE

Pathogenesis, Diagnosis, and Management of Ulcerative Proctitis,

Chronic Radiation Proctopathy, and Diversion Proctitis
Xian-rui Wu, MD, PhD,* Xiu-li Liu, MD, PhD,† Seymour Katz, MD,‡ and Bo Shen, MD§

Abstract: Chronic proctitis refers to persistent or relapsing inflammation of the rectum, which results from a wide range of etiologies with various

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pathogenic mechanisms. The patients may share similar clinical presentations. Ulcerative proctitis, chronic radiation proctitis or proctopathy, and
diversion proctitis are the 3 most common forms of chronic proctitis. Although the diagnosis of these disease entities may be straightforward in the most
instances based on the clinical history, endoscopic, and histologic features, differential diagnosis may sometimes become problematic, especially when
their etiologies and the disease processes overlap. The treatment for the 3 forms of chronic proctitis is different, which may shed some lights on their
pathogenetic pathway. This article provides an overview of the latest data on the clinical features, etiologies, diagnosis, and management of ulcerative
proctitis, chronic radiation proctopathy, and diversion proctitis.
(Inflamm Bowel Dis 2015;21:703–715)
Key Words: radiation proctitis, proctopathy, diagnosis, diversion proctitis, management, ulcerative proctitis

ETIOLOGIES AND RISK FACTORS

C hronic proctitis is defined as a persistent or relapsing
inflammatory process that occurs in the rectum. Common
symptoms of proctitis include bloody diarrhea, urgency, tenes-
mus, and rectal pain. A wide range of pathogenic changes under-
lie chronic proctitis, including infection, side effects of
medications, ischemia, fecal diversion, radiation, and ulcerative
proctitis (UP).1–4 All these forms of proctitis have a significantly
adverse impact on patients’ quality of life. Their diagnosis and
differential diagnosis is often based on history, along with clin-
ical, endoscopic, and histologic features. The exact pathogenesis
of the aforementioned disease entities remains mostly elusive.
The treatment for the different forms of chronic proctitis varies
depending on the underlying disease diagnosis. This article
summarizes the latest data on the clinical features, etiology,
diagnosis, and management of chronic proctitis, particularly
focusing on the 3 most frequently encountered forms in the
clinical settings, i.e., UP, radiation proctitis (RP) or proctopathy,
and diversion proctitis (DP).
Received for publication July 14, 2014; Accepted August 20, 2014.
From the *Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun
Yat-sen University, Guangzhou, China; †Department of Anatomic Pathology, The
Cleveland Clinic Foundation, Cleveland, Ohio; ‡Department of Gastroenterology,
Hepatology and Nutrition, North Shore University Hospital-Long Island Jewish
Medical Center, New York University School of Medicine, New York, New York;
and §Department of Gastroenterology & Hepatology, The Cleveland Clinic Founda-
tion, Cleveland, Ohio.
Supported in part by the Ed and Joey Story Chair (to B.S.) and the National
Natural Science Foundation of China (81400603).
The authors have no conflicts of interest to disclose.
Reprints: Bo Shen, MD, Department of Gastroenterology & Hepatology-A31,
The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195
(e-mail: shenb@ccf.org).
Copyright © 2014 Crohn’s & Colitis Foundation of America, Inc.
DOI 10.1097/MIB.0000000000000227
Published online 3 December 2014.
Ulcerative Proctitis
As a form of ulcerative colitis (UC), the precise cause of
UP is unknown. Current theory holds that genetically suscepti-
ble individuals seem to have a dysregulated mucosal immune
response to altered commensal gut flora or dysbiosis, resulting in
chronic bowel inflammation.5,6 Patients with different genetic
mutations may be predisposed to certain clinical phenotypes of
UC7 (Table 1). For example, Toll-like receptor polymorphisms
and human leukocyte antigen alleles have been shown to influ-
ence the disease extension in UC.8–11 The demographics of UP
also mirror those of UC. A family history of inflammatory bowel
disease (IBD) may be the most important risk factor for UC,
including UP.12 The risk is particularly high in the first-degree
relatives: 5.7% to 15.5% of patients with UC were found to have
the first-degree relative with the same disease.13,14 People of
Jewish descent have a rate of UC that is 3 to 5 times higher
than non-Jews counterparts.15 Furthermore, monozygotic twins
have concordance rates for UC of 6% to 13%.16,17 Therefore,
multiple lines of evidence suggest genetic links, although less
than previously thought, and contributions from environmental
factors in the cause of the disease18 (Table 1).
The incidence of UC is higher in developed countries than
that in developing countries and in urban than rural areas.
Improved sanitation in industrialized countries or urban areas
might reduce the chance of exposure to enteric infections during
early childhood, thus restricting maturation of the mucosal
immune system and resulting in a dysregulated immune response
to infectious microorganisms later in life.19,20 Several other envi-
ronmental factors act as triggers or protective factors for UC, with
cigarette smoking (protective) being the most consistent one.21–23

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Wu et al
TABLE 1. Purported Etiopathogenetic Factors and Cancer Risk for Chronic Proctitis
Characteristics Ulcerative Proctitis
Genetic factors ECM1, IL10, IL22, IFN-gamma, IL2/IL21, FCGR2A,
IL17REL/PIM3, CAPN10/GPR35, LAMB1/SCL26A3,
OTUD3/PLA2G2E, ARPC2, HNF4-alpha, CDH1, IL26,
13q12, 1p36, CARD9, CEP72/TPPP, 13q13, SMURF1/
KPNA7, IFN-g/IL26/IL22
Environmental Smoking (protective), diet, hydrogen sulfate, estrogen,
factors appendectomy (protective), gastrointestinal infection,
non-steroidal anti-inflammatory drugs
Gut Dysbiosis
microbiome
Vascular Angiogenesis, alterations in microvascular physiology and
factors function, lymphogenesis
Cancer risk Not increased
NA, not applicable.
Similarly, a number of studies have indicated a decreased preva-
lence of UC in those having undergone an appendectomy for
acute appendicitis.24–26 Episodes of previous gastrointestinal
(GI) infection (e.g., Salmonella spp, Shigella spp, and Campylo-
bacter spp) may increase the risk for the development of UC,
suggesting the role of acute intestinal infection and alterations
in gut flora in triggering chronic inflammatory process in genet-
ically predisposed individuals.27,28 There is also epidemiological
evidence suggesting an association between exposure to nonse-
lective non-steroidal anti-inflammatory drugs and onset or relapse
of UC29 (Table 1).
Accumulating evidence suggests that both innate and
adaptive immune responses are dysregulated and play a role in
the pathogenesis of UP, resembling that in UC.6,30 Intestinal
homeostasis requires a controlled innate immune response to pro-
vide defense against pathogens and protection from epithelial
injury, which is recognized by Toll-like receptors and
nucleotide-binding oligomerization domain–like receptors on
immune cells, including macrophages and dendritic cells.31 How-
ever, the recognition process is altered in UC and in Crohn’s
disease (CD), featured by overactivated innate immune response
resulted from increased number of activated and mature dendritic
cells.32 Therefore, the expression of proinflammatory cytokines,
including interleukin (IL)-1b, IL-6, tumor necrosis factor a (TNF-
a), and tumor necrosis factor–like ligand 1, in the involved seg-
ments of bowel is increased. Abnormal activation in humoral and
cellular adaptive immune responses also exists in UC. Higher
levels of immunoglobulin M (IgM), IgA, and IgG are reported
in patients with UC and CD than those in healthy counterparts.
Patients with UC are more likely to have a disproportionate ele-
vation in IgG1 antibodies.33 In contrast to CD, an atypical Th2
response is identified in UC, as indicated by the presence of
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Chronic Radiation Proctopathy Diversion Proctitis
NA NA
Pelvic radiation, smoking, previous Proximal fecal diversion
abdominal surgery, concomitant
chemotherapy, and comorbidities
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Dysbiosis Reduction in obligate
anaerobes, increase in
nitrate-reducing strains
Vascular injury, angiectasia, arterial NA
venous malformation
Increased Depending on underlying
etiology
natural killer T cells in the lamina propria of the inflamed colon,
secreting IL-13.34,35 IL-13 can exert a positive feedback effect on
natural killer cells, which is important in the initiation of UC
lesions.36 The potential role of Th17 cells, which are capable of
producing the proinflammatory cytokine IL-17, has also been
extensively investigated in the pathogenesis of UC.37 Because
the level of IL-17 is increased in the mucosa of patients with
UC, target therapy directed against the Th17/IL-17 axis may have
a therapeutic role in the treatment of UC. However, future studies
are warranted to further validate the hypothesis and elucidate its
underlying mechanisms.
Chronic Radiation Proctopathy
Radiation injury of the rectum is attributed to the direct
mucosal damage from radiation exposure characterized by
inflammation or cell death. Although acute injury usually resolves
after radiation is discontinued,38,39 the pathological process of the
chronic form of injury is different from that of the acute phase.
Subsequent activation of the cytokine system in the rectal sub-
mucosa, which is induced by persistent pelvic radiation, can lead
to progressive epithelial atrophy, fibrosis associated with obliter-
ative endarteritis, chronic mucosal ischemia, and the loss of stem
cells.40,41 These complex ischemic and fibrotic changes can impair
gastrointestinal physiological function and predispose the
involved rectum to bleeding and stricture or even fistula forma-
tion.42–44 Inflammation itself plays a “supporting role” in the
development of chronic symptoms after the leading cause of radi-
ation injury to the rectum. Therefore, the descriptive term “proc-
titis” is somewhat misleading because it inaccurately implies
a chronic inflammatory condition. In the recent literature, the term
“proctitis” has been replaced by “proctopathy.44” There is a gen-
eral agreement that the frequency and severity of chronic radiation
Inflamm Bowel Dis  Volume 21, Number 3, March 2015
proctopathy are likely related to the type and dosage of radiation,
the route of delivery, and the way of radiation energy dissipating
through tissues.45–47 In the past decade, various techniques have
been developed to deliver a higher dose of radiation-targeting
tumor mass, such as 3-dimensional conformal radiation therapy,
intensity-modulated radiotherapy, and brachytherapy. Those
modalities of radiation therapy have been shown to decrease the
likelihood of radiation-induced toxicities, although their long-
term side effects are yet to be investigated.48–54 Furthermore,
patient-related factors, including smoking, previous abdominal
surgery, concomitant chemotherapy, and comorbidities (diabetes,
hypertension, pelvic inflammatory disease, human immunodefi-
ciency virus infection, connective tissue disorders, and IBD)
may increase the risk of acute and chronic problems after pelvic
radiotherapy55–61 (Table 1).
Diversion Proctitis
The etiology of DP is not entirely clear. But, it is known
that the deficiency in nutritional factors, especially short-chain
fatty acids (SCFAs), plays a crucial role in the pathogenesis.3,62
SCFAs, predominantly acetate, propionate, and n-butyrate, are
derived from anaerobic bacterial fermentation of unabsorbed die-
tary carbohydrates and form the main source of metabolic fuels
for colonocytes, particularly in the distal large bowel.63 They are
absorbed from the lumen by a combination of simple diffusion
and ion exchange and oxidized by colonocytes in the preferred
order of butyrate, propionate, and acetate. This hypothesis is sup-
ported by the fact that the total bacterial count in the excluded
colon and rectum was only slightly lower than controls, but the
diversity of the flora was significantly reduced and the reduction
was confined to the obligate anaerobes64 (Table 1). However, the
inconsistent response of patients to SCFAs in reported case series
and the almost uniform response to the restoration of fecal con-
tinuity suggest that other factors may also be involved.62,65–67
Conventional bacterial cultures of luminal contents of bypassed
segments in symptomatic patients have consistently failed to dem-
onstrate a predominant microorganism.64,68
Clinical, Endoscopic, and Histologic Features
Although patients with UP, RP, or DP may show similar
clinical presentations, clinical history and endoscopic and histo-
logic features may be different.
Ulcerative Proctitis
UC is an idiopathic and chronic inflammatory disorder of
the colorectal mucosa. The extent of colitis in UC varies, with
approximately 30% of patients having inflammation involving the
rectum only,69–71 termed “ulcerative proctitis” or E1 by the Mon-
treal Classification.72,73 Proximal extension after the diagnosis of
UP is common, with the reported 5-, 10-, and 15-year probabil-
ities for any progression being 27%, 41%, and 53%, respec-
tively.74,75 Patients’ main symptoms are rectal bleeding, rectal
urgency, and tenesmus (Table 2). The clinical course is unpredict-
able, marked by alternating periods of exacerbation and
2015
Diagnosis and Management of Chronic Proctitis
remission.76,77 Endoscopic features of UP include mucosal edema,
erythema, friability, granularity, and loss of the typical vascular
pattern. Spontaneous hemorrhage, mucopurulent exudates, and
ulceration may also occur78–81 (Fig. 1 and Table 2). A sharp
demarcation of diseased and nondiseased segments of the distal
large bowel can be a specific feature, which helps to differentiate
UP from proctitis caused by other etiologies. On histology, there
are epithelial injury (ranging from mucin depletion, cryptitis,
crypt abscess, to erosion or ulceration), and features of chronicity,
such as chronic inflammation including prominent basal lympho-
plasmacytosis, crypt distortion, and Paneth cell metaplasia1,82–85
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(Fig. 2 and Table 2).
Chronic Radiation Proctopathy
Pelvic malignancies, including rectal cancer, prostate
cancer, and uterine or cervical cancer, are among the most
frequently diagnosed cancers worldwide.86 Their treatment re-
quires a multimodality approach, frequently involving radiother-
apy. Radiation-induced GI toxicity is a common complication
with the rectum as the most common site of injury because of
its topographic location and its relatively fixed position.41,61,87–89
The injury of the rectum from pelvic radiation has 2 forms, acute
and chronic. The acute form occurs in nearly all patients, but it is
often self-limiting, lasting up to 3 months after the onset of ther-
apy.90 Chronic radiation proctopathy can derive from the acute
phase or begin months to years after the radiation exposure with
the median interval of onset ranging between 8 and 13 months in
most reported series,91–96 but the latency may last as long as 30
years.97 The reported prevalence of the chronic form ranged from
2% to 20%.41,43,98 However, chronic radiation proctopathy may be
underreported. The most common and bothersome complaint
from patients with chronic radiation proctopathy is rectal bleed-
ing. Other symptoms are diarrhea, tenesmus, urgency, inconti-
nence, and pain99–102 (Table 2). Endoscopic findings in chronic
radiation proctopathy mainly consist of 3 forms: inflammation-
predominant form (edema, mucosal pallor, and ulcer), bleeding-
predominant form (friability, spontaneous hemorrhage, and
angiectasia or arteriovenous malformation–like lesions), and the
mixed form (having both bleeding- and inflammation-
predominant forms’ features)103,104 (Fig. 3 and Table 2). Biopsies
often show dilated and tortuous mucosal capillaries lined by endo-
thelial cells with prominent nuclei and surrounded by a cuff of
hyalinized lamina propria, fibrosis of the lamina propria, variable
degree of epithelial injury, crypt distortion, and Paneth cell meta-
plasia. Microthrombus may be seen. In cases with generous tissue
sampling, subintimal fibrosis or sclerosis of submucosal arteries,
atypical stellate fibroblasts, and submucosal fibrosis may be
found105–107 (Fig. 2 and Table 2).
Diversion Proctitis
DP was first described as a special disease entity in 1981 by
Glotzer et al.108 It is an inflammatory disorder that arises in the
excluded rectum, which is diverted from the fecal stream by sur-
gery. In most instances, inflammatory changes are confined to the
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TABLE 2. Clinical, Endoscopic, and Histologic Features

Characteristics Ulcerative Proctitis Chronic Radiation Proctopathy Diversion Proctitis

Shared clinical Rectal bleeding, diarrhea, urgency, tenesmus, incontinence, pelvic pain
features
Disease-“specific” Risk of proximal extension of Excessive bleeding; inflammation persists even after Bloody mucus discharge;
clinical features inflammation; ulcerative proctitis fecal diversion inflammation resolves after re-
improves after fecal diversion establishment of GI continuity
Shared endoscopic Edema, erythema, friability, ulcer, granularity, exudates
features

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Disease-“specific” Sharp demarcation of diseased and Angiectasia or arteriovenous malformation–like Anal or distal rectal stricture,
endoscopic nondiseased segments of distal lesions bleeding induced by
features large bowel; inflammatory polyps endoscopic air insuflation
Shared histologic Acute and chronic inflammatory changes, including mucin depletion, erosion, cryptitis ulceration, crypt distortion, and Paneth
features cell metaplasia
Disease-“specific” Prominent basal lymphoplasmacytosis Dilated and tortuous capillaries have prominent Follicular lymphoid hyperplasia
histologic features endothelial cell nuclei and are surrounded by a cuff
of hyalinized lamina propria
Other histologic Hypertrophy of muscularis mucosae Sclerosis of submucosal arteries, the presence of Lymphoplasmacytic infiltrate
features in some cases atypical stellate fibroblasts, and secondary chronic most dense in the upper
ischemic changes, such as crypt atrophy mucosa

distal rectum and resolved when intestinal continuity is restored.
The incidence of DP is unknown but may be almost universal to
a certain degree.109–113 Although endoscopy reveals signs of
inflammatory changes in most patients, fewer than 50% of the
patients have clinical symptoms, with the onset typically occur-
ring between 3 and 36 months after fecal diversion.62,110,114 Symp-
tomatic patients typically have rectal bleeding, tenesmus, mucus
discharge, abdominal or pelvic pain, or low-grade fever112,115–118
(Table 2). Those symptoms usually resolve after re-establishment
of GI continuity in almost all the patients with DP. On endoscopy,
colon mucosa show diffuse erythema, granularity, and friability—
features similar to those of active UP. In more advanced cases,
aphthous ulcers, spontaneous bleeding, nodularity, edema, inflam-
matory polyps, and strictures can be found108,112,116,119 (Fig. 4 and
Table 2). Notably, rectal bleeding can also be induced or wors-
ened by inappropriate air insufflation during endoscopic exami-
nation. Histologic changes of DP do not depend on the length of
diversion but more on the condition of the rectum before
diversion.120 Endoscopic biopsy of the previously normal rectum
may reveal follicular lymphoid hyperplasia and diffuse acute
inflammation, a lymphoplasmacytic infiltrate most dense in the
upper mucosa, with or without mild crypt architectural abnormal-
ities, cryptitis, crypt abscesses, and atrophy2,111,121,122 (Fig. 2 and
Table 2). Lymphoid follicular hyperplasia, with lymphoid fol-
licles located in the mucosa—often associated with chronic
plasma-cell-rich inflammation, has been considered as a distinctive
pathologic finding in patients with DP despite previous conditions
of the rectum.119
DIAGNOSIS
A combined assessment of history, clinical presentation,
endoscopy, and histology is critical for the diagnosis of the 3
forms of chronic proctitis. History, such as radiation and diversion
surgery, is critical for the diagnosis. The UP, RP, and DP
occasionally overlap. For example, patients with UP may have

FIGURE 1. Endoscopic features of UP.

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FIGURE 2. Histology of UP, chronic radiation proctopathy, and DP. A, UP is characterized by a combination of cryptitis, crypt distortion, Paneth cell
metaplasia, and basal lymphoplasmacytosis (H&E stain, ·100). B, Chronic radiation proctopathy is characterized by ectatic capillary, crypt dis-
tortion, and fibrosis of the lamina propria (H&E stain, ·100). C, DP is characterized by reactive lymphoid hyperplasia (H&E stain, ·40). Crypt atrophy
is also present.
rectum, prostate, cervix, or uterine cancer, which may require
pelvic radiation therapy. Severe patients with UP may be treated
with temporary fecal diversion surgery, which predisposes them
to the development of DP.
Ulcerative Proctitis
Signs and symptoms of UP may be indistinguishable from
those of UC. The diagnosis of UP is suspected on clinical grounds
and supported by the appropriate findings on proctosigmoido-
scopy or colonoscopy, biopsy, and by negative stool examination
for infectious etiologies.6,123 In classic UP, endoscopy typically
show diffuse inflammation with edema, erythema, exudate, gran-
ularity, friability, and ulceration starting from the anal verge and
a sharp demarcation of inflamed rectum and noninflamed mucosa
of the sigmoid colon. The distribution pattern may be altered after
the treatment with topical, oral, or intravenous anti-inflammatory
drugs. Barium enema has a limited utility in the diagnosis of UP.
Serological markers, such as perinuclear antineutrophilic antibody
(p-ANCA), and anti-Saccharomyces cerevesiae antibody (AS-
CA), are generally not indicated in the diagnosis of UP.
A meta-analysis analyzing the performance characteristic of
p-ANCA and ASCA in the differential diagnosis between UC
and CD found a sensitivity of 59% p-ANCA for UC and a sensi-
tivity of 55% ASCA for CD.124 The low sensitivity of p-ANCA
for the diagnosis of UC prevents it from serving as a useful diag-
nostic tool. These antibodies are also found at varying levels in
other disease conditions such as collagenous colitis and infectious
colitis, further limiting their diagnostic utility.
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Diagnosis and Management of Chronic Proctitis
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Chronic Radiation Proctopathy
Chronic radiation proctopathy should be considered in all
patients who have the suspected clinical features developing 3
months or later after pelvic radiation. The majority of cases can be
diagnosed with colonoscopy or sigmoidoscopy. The endoscopic
changes tend to be continuous without skip lesions but may be
patchy in intensity.125 Mucosa is friable with bleeding from even
just air insufflation. Mucosal biopsy is performed for the purpose of
differential diagnosis and to rule out other causes of chronic proc-
titis, such as infectious colitis or IBD, despite the fact that histologic
changes may not be diagnostic.106 Biopsies should be directed at
the posterior and lateral walls to avoid the irradiated areas because
of the concerns about fistula formation from obtaining rectal biopsy
over the prostate or vagina.126 Stricture and fistula could be late in
presenting symptoms of chronic radiation proctopathy usually pre-
ceded by other symptoms.127–130 In such cases, contrasted enema
studies, computed tomography, or magnetic resonance imaging are
recommended to have a better understanding of the disease extent
and to exclude recurrent malignancy.43,131
It is well known that radiation pouchitis can occur if
radiation is given after the construction of ileal pouch–anal anas-
tomosis (IPAA) in patients with rectal cancer with underlying UC
or familial adenomatous polyposis, predisposing the patients to
the development of pouch failure.132,133 When absolutely indi-
cated, radiation is usually preferably administered before rather
than after IPAA surgery. However, a recent study from our group
showed that pelvic radiation administered even before ileal pouch
construction might be associated with an increased risk for pouch
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Wu et al
FIGURE 3. Endoscopic features of chronic radiation proctopathy. A,
Shows the inflammatory form. B, Shows the bleeding form. C, Shows the
management of the bleeding form using argon plasma coagulation.
failure.134 Therefore, we should balance the potential oncological
benefits of radiation with any adverse effects on functional results
on a case-by-case basis, when considering the management of
patients with rectal cancer who are potential candidates for IPAA
surgery.
Diversion Proctitis
DP should be suspected in any individual who complains of
cramping abdominal pain with a mucous or bloody discharge
coming from the defunctionalized diverted rectum. The clinical
onset may begin within a few months after surgery or after a long
delay. The long-term exclusion of fecal stream from the lumen of
the rectum can cause distal rectum or anal stricture. In some
patients, the rectum may be completely “sealed” (Fig. 5). The
diagnosis is based on compatible clinical features and endoscopic
or radiographic findings. Endoscopic and histologic examinations
may be needed to confirm the diagnosis. It is important to exclude
other etiologies that can manifest similar clinical symptoms, such as
acute self-limited colitis, Clostridium difficile infection, and preex-
isting IBD with fecal diversion.1–3 A response to the restoration of
intestinal continuity or SCFA therapy supports the diagnosis.
TREATMENT
Ulcerative Proctitis
The treatment for UP is tailored to the needs of individual
patients to achieve more stringent goals, including maintenance
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of steroid-free remission, mucosal healing, prevention of
hospital admission and surgery, improved quality of life, and
avoidance of complications and disability.135 Medications for
the management of UP are similar to those used to treat UC,
mainly consisting of topical or oral mesalamines and cortico-
steroids, systemic immunosuppressive drugs and monoclonal
antibodies to TNF-a, or integrins. There are differences pertain-
ing to the drug delivery forms and doses and the treatment
algorithm (Table 3). Treatment success is dependent on
several factors, such as the use of the right drug for the right
indication, optimization of the dose, and maximization of drug
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adherence.136
5-Aminosalicylates
Rectally administered preparations of 5-aminosalicylic acid
(5-ASA) should be considered as the first-line treatment for mild-
to-moderate UP.1,123,137–139 Topical treatment offers the advantage
of delivering a high dosage of the active compound directly to the
site of inflammation, minimizing the systemic absorption of the
drug and therefore limiting the frequency of systemic adverse
effects. Several delivery forms of rectal 5-ASA have been tested
in clinical trials, including suppositories, enemas, foams, and gel.
These differ not only in their chemical properties and dosage but
also particularly in their potential proximal coverage.139–142
Although no specific topical 5-ASA formulations have demon-
strated clinical superiority over the others in inducing remission in
UP, suppositories are generally better tolerated and preferred by
patients.143
The administration of rectal 5-ASA preparations have
demonstrated efficacy in the induction and maintenance of
remission in the distal colon and rectum. Results from 3 meta-
analyses suggest that topical 5-ASA is superior to topical
corticosteroids by all measures of remission, clinically, endoscop-
ically, and histologically.144–146 Because topical 5-ASA drugs
exert their therapeutic effects at a mucosal level, it would seem
that an important aim of medication delivery would be to provide
high topical concentrations of 5-ASA to areas of mucosal inflam-
mation. However, there is no evidence supporting a dose-response
effect for rectal 5-ASA therapy. There seem no differences in the
efficacy and speed of onset of action between 5-ASA 500 mg
enemas varying between 1 and 4 g/d.147–149
Oral 5-ASA is also effective in the treatment of active
distal colitis.150 Although the oral forms are often preferred for
their convenience and compliance by some patients, topical me-
salamine has been shown to be superior to oral 5-ASA in achiev-
ing clinical improvement in patients with mild-to-moderate
distal UC and UP.146,151 This may be due to the asymmetric
distribution of 5-ASA within the colon that is exaggerated in
active left-sided disease resulting in proximal colonic stasis and
fast colonic transit through inflamed colon.152 However, combi-
nation therapy with rectally and orally delivered 5-ASA may be
more effective than either administration route used alone and
may be useful in refractory patients, although this may be simply
a dose-response effect.147,153,154
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FIGURE 4. Endoscopic features of DP. A–D, The spontaneous bleeding becomes worse with during air insufflation during endoscopy.
Corticosteroids
Patients with UP who fail the topical and/or oral 5-ASA
therapies should be reevaluated to ensure proper diagnosis and to
exclude a 5-ASA reaction or concurrent superimposed infections.
Inadequate dosing, inappropriate type and duration of treatment, and
noncompliance with therapy should also be taken into account.1,139
After careful evaluation, the use of topical glucocorticoids can be
considered, although it has been indicated to be less effective than
topical 5-ASA therapy and holds the potential disadvantage of side
FIGURE 5. “Sealed” rectum in a patient with DP.
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Diagnosis and Management of Chronic Proctitis
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effects, particularly regarding suppression of the pituitary–adrenal
axis.144–146 New steroids with enhanced topical potency and less
systemic activity, such as prednisolone–metasulphobenzoate, beclo-
metasone dipropionate, tixocortol pivalate, fluticasone, and budeso-
nide, may represent an even more valuable alternative.155 They have
been shown to be significantly superior to placebo and to have an
efficacy similar to systemic corticosteroids.156,157 Once remission
has been achieved, however, there is no evidence supporting that
topical steroids are effective in maintaining remission.158
Oral corticosteroids therapy may be used when patients lose
response to or only have a suboptimal response to treatment with
5-ASA compounds and/or to topical steroids. Oral prednisone
demonstrates a dose-response effect between 20 and 60 mg/d, with
60 mg/d being modestly more effective than 40 mg/d but at the
expense of a greater risk for adverse effects.159–161 No randomized
trials are available to evaluate corticosteroid-tapering schedules, but
it is recommended to the use of 40 to 60 mg/d until a substantial
clinical improvement has been obtained and then a dose taper of
5 to 10 mg weekly until a daily dose of 20 mg is reached.162
Steroid-refractory or Steroid-dependent UP
Patients who develop steroid-refractory or -dependent UP
present a treatment dilemma. There are limited evidence-based data
available to guide the treatment of these patients. Immunomodu-
lators (such as azathioprine, 6-mercaptopurine, and cyclosporine)
and/or monoclonal antibodies to TNF-a (such as infliximab,
adalimumab, and golimumab) or even antibody to integrin
(vedolizumab) may be considered in these cases.1,5,6,154 Should
these treatments fail, surgical intervention with proctectomy or
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Wu et al Inflamm Bowel Dis  Volume 21, Number 3, March 2015

TABLE 3. Management of Ulcerative Proctitis, Chronic Radiation Proctopathy, and Diversion Proctitis
Characteristic Ulcerative Proctitis Chronic Radiation Proctopathy Diversion Proctitis

Medical treatment Oral or topical 5-ASA Topical sucralfate Topical SCFAs

Oral or topical steroids Oral metronidazole Topical 5-ASAs
Immunomodulators Topical formaldehyde Topical steroid
Anti TNF-a Hyperbaric oxygen
Endoscopic NA Argon plasma coagulation NA
treatment Lasers (Nd:YAG and argon)
Bipolar electrocoagulation

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Heater probe
Surgical intervention Restorative proctocolectomy with Colostomy or ileostomy Surgical restoration of intestinal continuity
IPAA Proctectomy with or without reconstruction
Others

NA, not applicable.

proctocolectomy with an ileostomy or colostomy may be required.
Langholz et al75 reported that 12% of patients with an initial diag-
nosis of UP eventually underwent colectomy. The restoration of
intestinal continuity with the construction of IPAA may remain an
option for those whose resected rectum shows no evidence of CD6
(Table 3).
Chronic Radiation Proctopathy
The therapy for chronic radiation proctopathy includes 3
broad categories: medical, endoscopic, and surgical163 (Table 3).
For inflammation-predominant form of RP, medical therapy is the
main stay of treatment. For bleeding-predominant form of RP
with discrete arteriovenous malformation–like lesions, endoscopy
is the main treatment modality. It should be pointed out that RP is
rarely curable, and no therapy stands out as clearly superior.
Furthermore, there are no published randomized controlled trials,
and the majority of studies were of case series.
Medical Treatment
Medical therapy is used to target mainly the endoscopically
“inflammatory form” of RP. Sucralfate seems to be the best avail-
able medical therapy for chronic RP. The rationale for the use is its
favorable effects on epithelial microvascular injury.164,165 The find-
ings of several studies have suggested that topical sucralfate may
improve symptoms of chronic radiation proctopathy,166–169 including
one comparing sucralfate enemas versus sulfasalazine plus prednis-
olone enemas, which indicated that sucralfate enemas produced with
overall superior clinical outcome.170 However, sucralfate seems to
have no benefit in preventing radiation-induced toxicities.171,172 Oral
metronidazole may enhance this effect. A single study of mesala-
zine/betamethasone enema with or without the addition of oral met-
ronidazole showed that the frequency of rectal bleeding and mucosal
ulcers was lower in the metronidazole group.173
Topical formaldehyde is considered to be a safe and effective
way to treat RP with significant bleeding, through inducing
coagulative tissue necrosis on contact.174–178 Although this procedure
is well tolerated, serious complications including the development of
fistulas requiring colostomy and bowel necrosis requiring resection
have been described.179 The potential role of hyperbaric oxygen in
patients with chronic radiation proctopathy has been described in
several observational studies and in at least one randomized con-
trolled trial.180–184 Hyperbaric oxygen therapy seems to be safe and
well tolerated and may improve symptoms. Unfortunately, hyper-
baric oxygen facilities are not always available, and treatments are
time-consuming and expensive.
The efficacy of topical and/or oral 5-ASAs in UP has
prompted their use in RP. Although some reports and anecdotal
experience have suggested that this approach is promising, the
results were not found to be reproducible by other series.185,186
The addition of rectally administrated steroids to oral sulfasala-
zine seems to have improved symptoms in a controlled trial.166
However, the efficacy of corticosteroid enemas alone is not sys-
temically studied. SCFA enemas have been shown to be effective
in the treatment of diversion colitis, prompting their study in RP.
Although previous case reports suggest a possible benefit of
SCFA,187 no significant improvement in symptoms was found
in a case-control study.188
Endoscopic Treatment
A variety of endoscopic techniques have been applied to
treat “the bleeding form” in RP163,189–191 among which argon
plasma coagulation (APC) is the most frequently used (Fig. 3).
The technique involves the use of high-frequency energy transmit-
ted to the tissue through an ionized gas in a noncontact fashion. The
catheter is introduced through the working channel of the scope,
and the gas flow and energy are controlled. The advantages of APC
over other techniques are that it is a noncontact method, easy to use,
and has limited depth of tissue penetration.192 The efficacy of APC
to control bleeding has been suggested in several case series.193–196
It is generally believed that APC may be helpful when bleeding
occurs from a limited number of identifiable ectatic vessels,
whereas a larger field of arteriovenous malformations or oozing

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2015
Inflamm Bowel Dis  Volume 21, Number 3, March 2015
may be more difficult to control.190 Complications are not common
but may include stricture, rectovaginal fistula, tenesmus, and rectal
pain. The lasers (Nd:YAG and argon) have been used to coagulate
bleeding ecstatic vessels throughout the GI tract. The Nd:YAG
laser is a high-power infrared laser, and its potential benefit was
illustrated in a report in which it was used in 9 patients, in 8 of
whom symptoms significantly improved.197 However, the use of
Nd:YAG in the treatment of chronic radiation proctopathy has
declined because of its cost, the need to aim directly at telangiec-
tasias, and the possibility of severe endoscopic damage if the laser
strikes the endoscope in retroflexion.190,198–200 The argon laser has
less penetration than Nd:YAG (2 versus 5 mm) and is generally
more suitable for the treatment of vascular ectasia of any
cause.201,202 The argon beam laser also seems to be safer than the
Nd:YAG laser with less fibrosis, stricture formation, and transmural
inflammation.192 Bipolar electrocoagulation or heater probe are also
useful in the treatment of active bleeding. A study comparing bipo-
lar electrocoagulation and a heater probe found both to be equally
effective.203 Their advantages over laser therapies include less tis-
sue injury, permit tangential application of cautery, and the equip-
ment needed is widely available and relatively inexpensive.
According to authors’ experience, endoscopic intralesional
injection of D-50 glucose injection seems to be another promising
treatment modality for RP, particularly for “the bleeding form,”
although there only are limited data in the literature and the
underlying mechanism for its efficacy is unknown. We recently
reported one patient with RP, who was not amendable to a com-
bination of medical and endoscopic APC therapies, using the
D-50 glucose injection. On endoscopy, the patient was shown
to be featured by mixed friable mucosa and diffuse bleeding spots.
The patient’s symptoms responded to the D-50 glucose injection.
Surgical Intervention
Surgery is the last resort for chronic RP and is generally
reserved for patients with persistent rectal bleeding or when
medical and endoscopic approaches are inappropriate, as in cases
of stricture, fistula, or abscess. Fewer than 10% of patients
presenting with chronic RP ultimately require surgery, although
a higher rate has also been reported in the past.91,93,204,205 Surgical
interventions may be technically demanding due to adhesions and
other radiation damage in the pelvis. Fecal diversion with either
a colostomy or ileostomy is a common reason patients are referred
to surgeons.191 Diverting the stool stream decreases symptoms of
pain, tenesmus, drainage, and infection but rarely eliminates them
completely. An ostomy can also improve symptoms related to
incontinence and stricture, but it has a limited effect on bleed-
ing.92,96 In cases of complicated fistulous disease, intractable
bleeding or sever strictures, surgical proctectomy with or without
reconstruction may be required. Although this is a definitive treat-
ment, it is accompanied by significant morbidities, including an
exceedingly high rate of anastomotic leaks in cases of reconstruc-
tion or frequent perineal wound complications when reconstruc-
tion is not attempted.91,97,204,206 A detailed discussion with patients
with underlying UC will be needed before the construction of
2015
Diagnosis and Management of Chronic Proctitis
IPAA is undertaken, because previously published studies,
including the one from our group, show that pelvic radiation even
before pouch construction will put the patients at risk for pouch
failure.133,134,207
Diversion Proctitis
Surgical restoration of intestinal continuity is the treatment of
choice for symptomatic patients with DP.119 Early reanastomosis is
preferred because patients with long-term DP are at the risk of
disease progression and involution of the defunctionalized anorec-
tum. Patients who are not candidates for reanastomosis may be
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considered for SCFAs (Table 3). However, there are no published
randomized controlled trials on the efficacy of SCFAs. There have
been inconsistent results in its use in treatment of DP.3,62,65–67,208,209
The 5-ASA compounds have been shown beneficial in a case
report. Such an approach may be best suited for patients who have
underlying IBD.210
CONCLUSIONS
Ulcerative proctitis, chronic radiation proctopathy, and DP
are the 3 most common forms of chronic proctitis. Clinical
symptoms are similar, although the etiologies of the 3 disease
entities are different. The diagnosis is based on a combined
evaluation of history, clinical, endoscopic, and histologic features.
Topical 5-ASA compounds with or without oral 5-ASA or topical
steroids is the first-line treatment for UP. Patients who do not
respond to the above agents may require treatment with oral
prednisone, immunomodulators, or anti TNF-a biological ther-
apy, even surgery with total proctocolectomy. There are limited
data pertaining to the appropriate medical therapy for chronic RP.
Sucralfate seems to be the best available drug, and additional use
of oral metronidazole may enhance the therapeutic effect. Endo-
scopic treatment seems to be an effective modality, particularly
for patients with rectal bleeding resulting from chronic RP. Sur-
gical intervention should be considered as the last resort for the
management of chronic RP and is generally associated with a high
rate of postoperative complications. Surgical restoration of gut
continuity remains the treatment of choice for DP. Patients who
are not candidates for stoma closure and reanastomosis may be
treated with SCFA enemas as the first-line therapy.
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