Ulcerative proctitis

Ulcerative proctitis is a form of ulcerative colitis (a type of inflammatory bowel disease [IBD]) where the inflammation and ulcers is limited to the rectum (see Table 1 below) ¹⁾, ²⁾. Ulcerative proctitis typically affects less than six inches of the rectum, and it is not associated with an increased risk of cancer ³⁾. American Gastroenterological Association (AGA) Institute Guidelines defined proctitis as an in inflammation limited to the rectum or less than 15–20 cm from anus. Although it is generally assumed that ulcerative proctitis represents the benign end of the spectrum of ulcerative colitis, it is responsible for many distressing symptoms. Patients with ulcerative proctitis have rectal bleeding, rectal pain, urgency in your bowel movements, and tenesmus (feeling that you need to pass stools, even though your bowels are already empty), and endoscopy typically shows diffuse inflammation of the rectum only ⁴⁾, ⁵⁾, ⁶⁾, ⁷⁾.

Ulcerative colitis is a chronic inflammatory disease of the large intestine (colon) and rectum. Ulcerative colitis is a chronic disease in which abnormal reactions of the immune system cause inflammation and ulcers on the inner lining of your large intestine. In population-based studies, 25%–55% of patients had ulcerative proctitis at diagnosis ⁸⁾. The Montreal classification divides the distribution of ulcerative colitis into ulcerative proctitis (E1: limited to the rectum), left-sided colitis (E2: up to the splenic flexure) and extensive colitis (E3: beyond splenic flexure) ⁹⁾.

Table 1. Montreal classification of extent of ulcerative colitis (UC)

Extent		Anatomy
E1	Ulcerative proctitis	Involvement limited to the rectum (that is, proximal extent of inflammation is distal to the rectosigmoid junction)
E2	Left sided ulcerative colitis (distal ulcerative colitis)	Involvement limited to a proportion of the colorectum distal to the splenic flexure
E3	Extensive ulcerative colitis (pancolitis)	Involvement extends proximal to the splenic flexure

[Source ¹⁰⁾ ]

A study found that 28 percent of ulcerative proctitis cases had proximal extension, which proceeded to left-sided or pancolitis during five years ¹¹⁾, ¹²⁾, ¹³⁾, ¹⁴⁾, ¹⁵⁾. Therefore effective and timely management of patients with ulcerative proctitis is important not only to control symptoms and improve quality of life, but also potentially to delay or prevent proximal extension of inflammation ¹⁶⁾, ¹⁷⁾, ¹⁸⁾, ¹⁹⁾, ²⁰⁾.

First-line treatment for mild or moderately active ulcerative proctitis is rectal therapy with 5-aminosalicylic acid (5-ASA) ²¹⁾, ²²⁾, ²³⁾, ²⁴⁾, ²⁵⁾. Topical 5-aminosalicylic acid (5-ASA) is more effective than topical steroids and oral 5-ASA ²⁶⁾, ²⁷⁾. When there is insufficient response, the next step is to combine topical 5-ASA with topical corticosteroids and/or with oral 5-ASA ²⁸⁾.

In patients who fail to improve despite combination therapy, oral corticosteroids are often necessary ²⁹⁾, ³⁰⁾. Refractory ulcerative proctitis is defined as active ulcerative proctitis which fails rectal and oral therapy with 5-ASA and corticosteroids ³¹⁾. Treatment of refractory ulcerative proctitis remains challenging because these patients are systematically excluded from randomized controlled trials with drugs with new modes of action ³²⁾. In the absence of controlled data, recommendations for the management of ulcerative proctitis are therefore often extrapolated from data in more extended ulcerative colitis or from small real-world evidence ³³⁾. Refractory ulcerative proctitis may require treatment with intravenous steroids, immunomodulators or biologicals ³⁴⁾. A small retrospective multicentre study assessed short- and long-term outcomes of refractory ulcerative proctitis treated with azathioprine. Only 20% had treatment success at last follow-up, with a median follow-up of 46 months ³⁵⁾. Another retrospective multicenter study analysed the efficacy of anti-tumour necrosis factor (anti-TNF) therapy in patients with refractory ulcerative proctitis ³⁶⁾. After a median follow-up of 24 months, 64% (67/104) of patients were in clinical remission ³⁷⁾. There are no data with other biologicals or small molecules in ulcerative proctitis. A small randomized, placebo controlled, double-blinded trial showed that topical tacrolimus was more effective than placebo for achievement of clinical remission and mucosal healing in patients with ulcerative proctitis ³⁸⁾.

Figure 1. Ulcerative proctitis

[Source ⁴⁰⁾ ]

The anus

The anus is connected to the rectum by the anal canal. The anus is the continuation of the large intestine (the colon or large bowel) inferior to the rectum. It’s where the end of the intestines connect to the outside of the body.

The anal canal is about 1-1/2 inches (about 3 to 5 cm) long, it begins where the rectum passes through the levator ani (the muscle that forms the pelvic floor) and goes to the anal verge. The anal verge is where the anal canal connects to the outside skin at the anus. This skin around the anal verge is called the perianal skin (previously called the anal margin). The anal canal has two ring-shaped muscles (called sphincter muscles – an internal and external anal sphincter) that keep the anus closed and prevent stool from leaking out.

As food is digested, it passes from the stomach to the small intestine. It then moves from the small intestine into the main part of the large intestine (called the colon). The colon absorbs water and salt from the digested food. The waste matter that’s left after going through the colon is known as feces or stool. Stool is stored in the last part of the large intestine, called the rectum. From there, stool is passed out of the body through the anus as a bowel movement.

The inner lining of the anal canal is the mucosa. Most anal cancers start from cells in the mucosa. Glands and ducts (tubes leading from the glands) are found under the mucosa. The glands make mucus, which acts as a lubricating fluid. Anal cancers that start from cells in the glands are called adenocarcinomas.

The anal canal changes as it goes from the rectum to the anal verge. The parts of the anus include the:

• Cells above the anal canal (in the rectum) and in the part of the anal canal close to the rectum are shaped like tiny columns.
• Most cells near the middle of the anal canal are shaped like cubes and are called transitional cells. This area is called the transitional zone – this is where the rectum meets the anal canal.
• About midway down the anal canal is the dentate line, which is where most of the anal glands empty into the anus.
• Below the dentate line are flat (squamous) cells.
• At the anal verge, the squamous cells of the lower anal canal merge with the skin just outside the anus. This skin around the anal verge called the perianal skin or the anal margin, is also made up of squamous cells, but it also contains sweat glands and hair follicles, which are not found in the lining of the lower anal canal. The anal margin is the lower part of the anal canal and it contains muscles called the anal sphincters. You have an internal and external anal sphincter. They are the muscles that control your bowel movements.

Figure 3. Rectum

Figure 4. Anus anatomy

Ulcerative proctitis causes

The precise cause of ulcerative proctitis is unknown. Current theory holds that genetically susceptible individuals seem to have a dysregulated mucosal immune response to altered commensal gut flora or dysbiosis, resulting in chronic bowel inflammation ⁴¹⁾, ⁴²⁾. Patients with different genetic mutations may be predisposed to certain clinical phenotypes of ulcerative colitis ⁴³⁾. For example, Toll-like receptor polymorphisms and human leukocyte antigen alleles have been shown to influence the disease extension in ulcerative colitis ⁴⁴⁾, ⁴⁵⁾. The demographics of ulcerative proctitis also mirror those of ulcerative colitis. A family history of inflammatory bowel disease (IBD) may be the most important risk factor for ulcerative colitis, including ulcerative proctitis ⁴⁶⁾. The risk is particularly high in the first-degree relatives: 5.7% to 15.5% of patients with ulcerative colitis were found to have the first-degree relative with the same disease ⁴⁷⁾, ⁴⁸⁾. People of Jewish descent have a rate of ulcerative colitis that is 3 to 5 times higher than non-Jews counterparts ⁴⁹⁾. Furthermore, monozygotic twins have concordance rates for ulcerative colitis of 6% to 13% ⁵⁰⁾, ⁵¹⁾. Therefore, multiple lines of evidence suggest genetic links, and contributions from environmental factors in the cause of ulcerative proctitis ⁵²⁾.

Genes

Ulcerative colitis sometimes runs in families. Research suggests that certain genes increase the chance that a person will develop ulcerative colitis.

Abnormal immune reactions

Abnormal reactions of the immune system may play a role in causing ulcerative colitis. Abnormal immune reactions lead to inflammation in the large intestine.

Microbiome

The microbes in your digestive tract—including bacteria, viruses, and fungi—that help with digestion are called the microbiome. Studies have found differences between the microbiomes of people who have inflammatory bowel disease (IBD) and those who don’t. Researchers are still studying the relationship between the microbiome and inflammatory bowel disease (IBD).

Environment

Experts think a person’s environment—one’s surroundings and factors outside the body—may play a role in causing ulcerative colitis. Researchers are still studying how people’s environments interact with genes, the immune system, and the microbiome to affect the chance of developing ulcerative colitis.

Ulcerative proctitis symptoms

Ulcerative proctitis signs and symptoms may include:

• A frequent or continuous feeling that you need to have a bowel movement (tenesmus)
• Rectal bleeding
• Passing mucus through your rectum
• Rectal pain
• Pain on the left side of your abdomen
• A feeling of fullness in your rectum
• Diarrhea
• Pain with bowel movements.

Ulcerative proctitis complications

Proctitis that isn’t treated or that doesn’t respond to treatment may lead to complications, including:

• Anemia. Chronic bleeding from your rectum can cause anemia. With anemia, you don’t have enough red blood cells to carry adequate oxygen to your tissues. Anemia causes you to feel tired, and you may also experience dizziness, shortness of breath, headache, pale skin and irritability. Ulcerative colitis may lead to more than one type of anemia, including iron-deficiency anemia and anemia of inflammation or chronic disease.
• Ulcers. Chronic inflammation in the rectum can lead to open sores (ulcers) on the inside lining of the rectum.
• Fistulas. Sometimes ulcers extend completely through the intestinal wall, creating a fistula, an abnormal connection that can occur between different parts of your intestine, between your intestine and skin, or between your intestine and other organs, such as the bladder and vagina.
• Bone problems include low bone mass, such as osteopenia or osteoporosis, because ulcerative proctitis and corticosteroids used to treat the disease can affect the bones.
• Problems with growth and development in children, such as gaining less weight than normal, slowed growth, short stature, or delayed puberty.

Some people with ulcerative colitis also have inflammation in parts of the body other than the large intestine, including:

• joints, causing certain types of arthritis
• skin
• eyes
• liver and bile ducts, causing conditions such as primary sclerosing cholangitis

People with ulcerative colitis also have a higher risk of blood clots in their blood vessels.

Ulcerative proctitis diagnosis

Doctors will ask about your medical history, perform a physical exam, and order tests to diagnose proctitis and find the cause.

Tests and procedures used to diagnose proctitis include:

• Blood tests. These can detect blood loss or infections.
• Stool test. You may be asked to collect a stool sample for testing. A stool test may help determine if your proctitis is caused by a bacterial infection.
• Scope exam of the last portion of your colon (flexible sigmoidoscopy). During this test, your doctor uses a slender, flexible, lighted tube to examine the last part of your colon (sigmoid), as well as the rectum. During the procedure, your doctor can also take small samples of tissue (biopsy) for laboratory analysis.
• Scope exam of your entire colon (colonoscopy). A colonoscopy allows your doctor to view your entire colon using a thin, flexible, lighted tube with an attached camera. Your doctor can also take a biopsy during this test.
• Tests for sexually transmitted infections. These tests involve obtaining a sample of discharge from your rectum or from the tube that drains urine from your bladder (urethra).

Medical history

Your doctor will review your symptoms and ask about your medical history, including:

• current and past medical conditions
• family history of digestive diseases, such as inflammatory bowel disease (IBD)
• history of radiation therapy for cancer
• history of, or risk factors for, sexually transmitted diseases (STDs)
• history of travel to areas where some infections that cause proctitis are more common
• use of medicines, including antibiotics or nonsteroidal anti-inflammatory drugs (NSAIDs)

Physical exam

Your doctor will perform a physical exam, which may include a digital rectal exam, to check for signs of proctitis or other problems in the rectum.

Blood tests

A health care professional will take a blood sample from you and send it to a lab. Blood tests can show signs of infections or other conditions that may cause proctitis.

Stool tests

A doctor will give you a container for catching and storing stool. You will receive instructions on where to send or take the container for analysis. Stool tests may show signs of infections that can cause proctitis.

Rectal cultures

A doctor will use a cotton swab to collect a sample of the bacteria and other microbes inside your rectum. A rectal culture can show signs of infections that cause proctitis.

Endoscopy

A doctor uses an endoscope—a long, flexible, narrow tube with a light and tiny camera on one end—to view the lining of your anus, rectum, and colon. The doctor may pass a tool through the endoscope to take biopsies of the lining of your rectum and colon. A pathologist will examine the biopsied tissue under a microscope.

Common endoscopy procedures that doctors can use to diagnose, find the cause, and check for complications of proctitis include:

• Colonoscopy to view the lining of your rectum and your entire colon
• Flexible sigmoidoscopy to view the lining of your rectum and lower colon

Doctors may also view the inside of your anus or rectum with a shorter, rigid scope, such as a proctoscope or anoscope.

Endoscopic features of ulcerative proctitis include mucosal edema, erythema, friability, granularity, and loss of the typical vascular pattern. Spontaneous hemorrhage, mucopurulent exudates, and ulceration may also occur ⁵³⁾, ⁵⁴⁾, ⁵⁵⁾, ⁵⁶⁾. A sharp demarcation of diseased and nondiseased segments of the distal large bowel can be a specific feature, which helps to differentiate ulcerative proctitis 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 lymphoplasmacytosis, crypt distortion, and Paneth cell metaplasia ⁵⁷⁾, ⁵⁸⁾, ⁵⁹⁾, ⁶⁰⁾.

Figure 5. Ulcerative proctitis endoscopic features

[Source ⁶¹⁾ ]

Figure 6. Ulcerative proctitis histology

Footnote: Ulcerative proctitis is characterized by a combination of cryptitis, crypt distortion, Paneth cell metaplasia, and basal lymphoplasmacytosis (H&E stain, ×100).

[Source ⁶²⁾ ]

Ulcerative proctitis treatment

Doctors prescribe medicines to treat ulcerative proctitis due to inflammatory bowel disease (IBD)—ulcerative colitis. Medicines may reduce inflammation in the rectum and help bring on and maintain ulcerative proctitis remission—a time when your symptoms disappear.

Medicines to treat ulcerative proctitis include:

• aminosalicylates, also called 5-aminosalicylic acid (5-ASA)
• corticosteroids, also called steroids
• immunosuppressants
• biologics

Ulcerative proctitis is treated with topical mesalazine in the form of suppositories, enemas, foams and gels and in severe cases combined with oral mesalazine with topical steroids or systemic corticosteroids in more severe cases. For patients with mild to moderate ulcerative proctitis, guidelines from American College of Gastroenterology (ACG) and American Gastroenterological Association (AGA) recommend using rectal 5-aminosalicylic acid (5-ASA) mesalamine rather than oral mesalamine ⁶³⁾. 5-aminosalicylic acid (5-ASA) suppositories are more effective than enemas. For induction of remission, the dose is 1 g/day and this is to be continued at the same dose to maintain remission. In cases of intolerance, refractoriness, hypersensitivity to mesalamine suppositories, inability to retain rectal therapy, rectal corticosteroid therapy is suggested for induction of remission rather than no therapy, despite the superiority of rectal 5-ASA over rectal steroids ⁶⁴⁾. Corticosteroids are not recommended and are not effective in maintenance of remission secondary to side effects and long-term complications. Up to 46% of patients with ulcerative proctitis may develop extensive colitis. This should be especially suspected in patients refractory to topical treatment and follow-up is recommended ⁶⁵⁾, ⁶⁶⁾.

In steroid resistant ulcerative proctitis cases, the addition of cyclosporine or immunomodulators; thiopurines as azathioprine (AZA) and 6-mercaptopurine (6-MP) is considered. Other options include anti TNF-α (infliximab, adalimumab, and golimumab), anti-integrin antibodies as vedolizumab and etrolizumab, or oral tacrolimus ⁶⁷⁾, ⁶⁸⁾.

Doctors may recommend surgery to treat ulcerative proctitis if medicines don’t work or if you develop complications. To treat ulcerative proctitis, surgeons typically remove the colon and rectum and change how your body stores and passes stool. The most common types of surgery for ulcerative colitis are:

• ileoanal reservoir surgery. Surgeons create an internal reservoir, or pouch, from the end part of the small intestine, called the ileum. Surgeons attach the pouch to the anus. Ileoanal reservoir surgery most often requires two or three operations. After the operations, stool will collect in the internal pouch and pass through the anus during bowel movements.
• ileostomy. Surgeons attach the end of your ileum to an opening in your abdomen called a stoma. After an ileostomy, stool will pass through the stoma. You’ll use an ostomy pouch—a bag attached to the stoma and worn outside the body—to collect stool.

5-Aminosalicylates (5-ASA)

Rectally administered preparations of 5-aminosalicylic acid (5-ASA) should be considered as the first-line treatment for mild-to-moderate ulcerative proctitis ⁶⁹⁾, ⁷⁰⁾, ⁷¹⁾, ⁷²⁾. 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-aminosalicylic acid (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 ⁷³⁾, ⁷⁴⁾. Although no specific topical 5-aminosalicylic acid (5-ASA) formulations have demonstrated clinical superiority over the others in inducing remission in ulcerative proctitis, suppositories are generally better tolerated and preferred by patients ⁷⁵⁾.

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, endoscopically, and histologically ⁷⁶⁾, ⁷⁷⁾, ⁷⁸⁾. 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 inflammation. 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/day ⁷⁹⁾, ⁸⁰⁾, ⁸¹⁾.

Oral 5-ASA is also effective in the treatment of active distal colitis ⁸²⁾. Although the oral forms are often preferred for their convenience and compliance by some patients, topical mesalamine has been shown to be superior to oral 5-ASA in achieving clinical improvement in patients with mild-to-moderate distal ulcerative colitis and ulcerative proctitis ⁸³⁾, ⁸⁴⁾. 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 ⁸⁵⁾. However, combination 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 ⁸⁶⁾, ⁸⁷⁾, ⁸⁸⁾.

Corticosteroids

Patients with ulcerative proctitis 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 ⁸⁹⁾, ⁹⁰⁾. 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 effects, particularly regarding suppression of the pituitary–adrenal axis ⁹¹⁾, ⁹²⁾, ⁹³⁾. New steroids with enhanced topical potency and less systemic activity, such as prednisolone–metasulphobenzoate, beclometasone dipropionate, tixocortol pivalate, fluticasone, and budesonide, may represent an even more valuable alternative ⁹⁴⁾. They have been shown to be significantly superior to placebo and to have an efficacy similar to systemic corticosteroids ⁹⁵⁾, ⁹⁶⁾. Once remission has been achieved, however, there is no evidence supporting that topical steroids are effective in maintaining remission ⁹⁷⁾.

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/day, with 60 mg/day being modestly more effective than 40 mg/day but at the expense of a greater risk for adverse effects ⁹⁸⁾, ⁹⁹⁾, ¹⁰⁰⁾. No randomized trials are available to evaluate corticosteroid-tapering schedules, but it is recommended to the use of 40 to 60 mg/day 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 ¹⁰¹⁾.

Steroid-refractory or Steroid-dependent ulcerative proctitis

Patients who develop steroid-refractory or -dependent ulcerative proctitis present a treatment dilemma. There are limited evidence-based data available to guide the treatment of these patients. Immunomodulators (such as azathioprine, 6-mercaptopurine, and cyclosporine) and/or monoclonal antibodies to TNF-α (such as infliximab, adalimumab, and golimumab) or even antibody to integrin (vedolizumab) may be considered in these cases ¹⁰²⁾, ¹⁰³⁾, ¹⁰⁴⁾, ¹⁰⁵⁾. Should these treatments fail, surgical intervention with proctectomy or proctocolectomy with an ileostomy or colostomy may be required. Langholz et al ¹⁰⁶⁾ reported that 12% of patients with an initial diagnosis of ulcerative proctitis eventually underwent colectomy. The restoration of intestinal continuity with the construction of ileal pouch–anal anastomosis may remain an option for those whose resected rectum shows no evidence of Crohn’s disease ¹⁰⁷⁾.

Ulcerative proctitis diet

If you have ulcerative proctitis, you should eat a healthy, well-balanced diet. Talk with your doctor about a healthy eating plan.

Ulcerative proctitis symptoms may cause some people to lose their appetite and eat less, and they may not get enough nutrients. In children, a lack of nutrients may play a role in problems with growth and development.

Researchers have not found that specific foods cause ulcerative proctitis symptoms, although healthier diets appear to be associated with less risk of developing inflammatory bowel disease (IBD). Researchers have not found that specific foods worsen ulcerative proctitis. Talk with your doctor about any foods that seem to be related to your symptoms. Your doctor may suggest keeping a food diary to help identify foods that seem to make your symptoms worse.

Depending on your symptoms and the medicines you take, your doctor may recommend changes to your diet.

Ulcerative proctitis prognosis

The clinical course of ulcerative proctitis is unpredictable, and most patients experiencing alternating periods of exacerbation and remission ¹⁰⁸⁾, ¹⁰⁹⁾, ¹¹⁰⁾. Long-term epidemiological studies have revealed that ulcerative proctitis often extends to more proximal colitis and even to total colitis. It was shown that nearly 22% of patients with ulcerative proctitis had disease progression within 12 to 24 months of initial diagnosis despite medical treatment ¹¹¹⁾. This is in line with other studies, showing proximal extension of ulcerative proctitis in 28% during 5 years of follow-up ¹¹²⁾, ¹¹³⁾, ¹¹⁴⁾. The recognition of ulcerative proctitis and left-sided ulcerative colitis is important because it has been suggested that effective local treatment may prevent or delay proximal spread of the inflammation ¹¹⁵⁾.