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
disease³. 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.⁴  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.⁴

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.⁴ 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.⁵
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.⁴ 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.⁴

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 proctitis⁴ 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.⁴

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.³

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

S3 ASACOL SUPPOSITORIES: Reg No:
Z/11.10/206. Each suppository contains 500 mg mesalazine (5-aminosalicylic
acid)

Further information is available on
request. For full prescribing information refer to the package insert. HCR:
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Route 21 Corporate Park, Nellmapius Drive, Irene, Pretoria, South Africa. Tel:
+27 12 345 1747; Fax: 27 12 345 1412. Under licence from: Tillotts
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