Ulcerative Proctitis (UP) is part of the
clinical entity recognised as ulcerative colitis which overall is the more
common form of inflammatory bowel disease in most parts of the world. The
prevalence rates and studies in various parts of the globe have shown that
ulcerative colitis is now a world wide problem. From a large systematic review
indicates that the highest prevalence is seen in Europe and North America (505
per 100,000 in Norway, 286 per 100,000 in the USA). While, the majority of
studies suggest that a stable or decreasing incidence in North America and
Europe since the early 1900s there has been a documented rise in the incidence
of the disease in the developing countries of North America, Africa and Asia.
¹

Ulcerative
proctitis forms a significant cohort of the total ulcerative colitis
population. A recent Swiss study has shown a ratio of 4.2-3.7-2.2 for extensive
UC distal UC and Ulcerative proctitis and diagnosis. This taken with other
studies from Europe
and North America suggest that 22-33% of ulcerative colitis
cases present as ulcerative proctitis.²

Much can be
written concerning the effects of genetics and environmental factors in the
development of Ulcerative colitis. Little however is certain. Concordance for
the disease in identical twins is only 16 % and far from the 100% that could be
expected if the cause was entirely genetic. The only environmental factors that
stand up to scrutiny are the increased risk associated with enteric infections
and the protective effects of current smoking and appendectomy.

The course of
Ulcerative Proctitis is highly variable. Some 30-40% of patients will
experience an extension of their disease towards the caecum in the 5-10 years
from diagnosis. Chronically active disease, refractory disease and the need for
corticosteroids or immune-modulators and smoking predispose to proximal
extension. Age at onset and gender do not appear to influence such disease
progression. There are no trials which look specifically at the clinical
behaviour of ulcerative proctitis over time but if one can assume it mirrors
that of ulcerative colitis in general then around 55 % of cases will have a
mild course after initial severe episode. Around 40% a chronic relapsing course
and 5% continuous disease activity.

The cardinal
symptoms of ulcerative proctitis are diarrhoea and rectal bleeding although
some patients may present with relative constipation. Increased flatulence and
the passage of mucus often precede bowel changes and bleeding. Perianal
discomfort especially on sitting may be prominent in some patients. The disease
can be recognised endoscopically and indeed proctoscopically by red granular
mucosa with adherent mucus and bleeding on light touch by the examining
instrument or biopsy forceps (friability). In severe cases spontaneous bleeding
and superficial ulceration may be present. Deep ulceration is uncommon and
indicates a poor prognosis. These endoscopic changes extend from the anal
sphincter concentrically in a confluent manner towards the sigmoid colon.
³

Histology might
be expected to offer a definite confirmation of the diagnosis but this is not
always possible. In the early stages distinction from infectious colitis may
not be possible. Infiltration of plasmacytes into the basal layers of the
mucosa have been identified as the best predictive value for the diagnosis of
ulcerative colitis.  Distortion of the
mucosal crypts, mucosal atrophy and an irregular mucosal surface appear only
after a month or so of disease
³. Frequently the histology report is
only one of acute on chronic inflammation. Biopsies are more helpful in excluding
other diseases. Ulcerative proctitis needs to be distinguished from Crohn’s
disease, radiation proctitis, diversion proctitis and enteric infections such
as C-difficile, sexually transmitted diseases and cytomegalovirus.

The foundation of
the treatment of UP is topical mesalamine, (5-ASA) using either a suppository
or a rectal formulation. 5-ASA suppositories should be the first line of
treatment as they target the site of inflammation directly and are more
acceptable to patients than enema preparations.
 Two types of 5-ASA suppositories are available
in South Africa: Pentasa suppositories and Asacol suppositories. Suppository doses
of 1 gram of 5-ASA daily are likely to achieve the maximum response and
increasing the dose above this does not provide any demonstrable advantage. A combination
of topical 5-ASA and oral treatment is more effective than either alone when
treating left sided ulcerative colitis⁴ but there are no trials of combination
therapy at present available in the treatment of UP. Studies have reported an
earlier cessation of bleeding with topical 5-ASA compared with oral
preparations. In addition topical 5-ASA is more effective than topical
steroids.

Although intermittent
therapy is acceptable in some patients with UP most will benefit from long term
maintenance treatment. As far as the dose of 5-ASA compounds in maintaining
remission is concerned no clear dose response has been established.
However
it appears that patients taking 2.4 grams daily are in remission longer than
those taking 1.2 grams with rectal 5-ASA preparations dosing three times weekly
may be sufficient to maintain remission. 
The suppository formulation is superior to dose escalation of oral mesalamine
for patients with a flare of UP treated with a maintenance dose of oral 5-ASA
alone.
When used alone 5-ASA rectal formulations appear equivalent to or
slightly superior to oral 5-ASA. Once again a combination of oral 5-ASA and
rectal 5-ASA appears to provide further benefit although long-term tolerability
and acceptance of rectal treatment is variable.
When
patients with UP fail to improve on oral plus topical 5-ASA or when relapses
are frequent, therapy compliance and endoscopic activity should be investigated.

Refractory
patients who have not responded to a combination of oral and rectal 5 –ASA
compounds require systemic treatment with oral corticosteroids Treatment in
ulcerative proctitis has not been assessed separately from ulcerative colitis in
general in any clinical trial. Initially 40-60 mg is given daily tapering over
6-8 week. Responding patients are then continued on oral and rectal 5-ASA
medication.
² If a non steroid free remission cannot be induced an immune-modulator
such as Azathiaprin or 6 –mercaptopurine should be added. Methotrexate has not
been shown to have any benefit in this context.
² Escalation
of treatment to biological agents may be required. However patients with
ulcerative proctitis are generally excluded from the trials of such agents and
their uses therefore are rather more problematic. However in a series of 13
patients with steroid and immunomodulator resistant ulcerative proctitis inflexemab
response rate was 85 %.
² There is some evidence that
appendicectomy is associated with a decreased incidence of ulcerative colitis.
This may be helpful in the treatment of resistant ulcerative proctitis
allowing
some people to maintain a remission over several years and to stop other
medication.

Many patients on
the advice of family and friends will be taking probiotics. An equivalence
study of  327 patients with ulcerative
colitis in remission, the probiotic E.coli Nissle was found to be not inferior
to 5-ASA for the maintenance of remission in ulcerative colitis. This
probiotics has extremely limited availability. There is no evidence to suggest
that any other probiotic is effective in maintaining remission in patients with
colitis and the use of these often expensive preparations should not be
encouraged.

Though the risk
of colorectal cancer in ulcerative colitis is increased over the general
population with recently reported cumulative incidence of 1% at 10 years, 3 %
at 20 years and 67 % at 30 years the risk of colorectal cancer is not increased
in patients with ulcerative colitis limited to the rectum. Inclusion in a
surveillance colonoscopy programme for such patients is not necessary

For both patient and physician the
achievement and maintenance of a longstanding remission in ulcerative proctitis
may be a difficult goal but one which is undoubtedly well worth achieving.
Patients with inadequately treated proctitis can become anxious and depressed
when bleeding and diarrhoea are not controlled. There is a reluctance to leave
the house and severe strains can be placed on ability to work and on the
relationship with friends and family. The bar for treatment of all forms of
ulcerative colitis is being raised well beyond clinical remission into
endoscopic and histological remission. 
The means are available to achieve these goals. It is adherence to an
effective regimen of maintenance treatment and the help and support of a
specialist Gastroenterologist that are the key to achieving them.

References:

1.      
Worldwide incidence and
prevalence of inflammatory bowel disease in the 21st century: a
systematic review of population-based studies. Ng SC, Shi HY, Hamidi N et al
Lancet 2018 Dec 23:390(10114):2769-2778.

2.      
Refractory Ulcerative Proctitis
– A Brief Review. Shmuel Odes Open Journal of Gastroenterology,

2016, 6,239 – 248.

3.      
Third European Evidence-based
Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1:
Definitions, Diagnosis., Extra-intestinal Manifestations, Pregnancy, Cancer
Surveillance, Surgery and Ileo-anal Pouch Disorders. Fernando Magro, Paolo
Gionchetti, Rami Eliakim et al Journal of Crohn’s and Colitis, 2017,1-39

4.      
Third European Evidence-based
Consensus on Diagnosis and Management of Ulcerative Colitis. Part 2: Current
Management Marcus Harbord, Rami Eliakim, Dominik Bettenworth et al Journal of
Crohn’s and Colitis, 2017, 1-24

5.      
Optimized Management of
Ulcerative Proctitis: When and How to Use Masalazine Suppository Kato S,
Ishibashi A, Kani K Digestion 2018;97:59-63


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 SUPPOSITORIES: Reg No:
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