bubble_chart Overview

Ulcerative colitis is a diffuse inflammation of the colonic and rectal mucosa, characterized clinically by unexplained, recurrent bloody diarrhea. It is difficult to imagine such a destructive disease without a definitive cause or a specific medical treatment. Although complete removal of the affected colon and rectum can cure the disease, the potential cost is a permanent abdominal ileostomy.

bubble_chart Epidemiology

Chronic ulcerative colitis is a disease found worldwide but is more common in Western countries. Its incidence ranges from 5 to 12 per 100,000, with a prevalence of 50 to 150 per 100,000. It is slightly more prevalent in women than in men. The age of onset shows a bimodal distribution, with the first peak occurring between 15 and 30 years old and the second peak between 50 and 70 years old. The first peak accounts for more cases, and 15–40% of patients have a family history of chronic ulcerative colitis or Crohn's disease. In the United States, Jewish patients are more affected than non-Jewish individuals, but Jews in Israel have a lower incidence of the disease. There is no comprehensive statistical data on this disease in China, but based on clinical observations, it is not rare and appears to be increasing in frequency.

bubble_chart Etiology

The cause of ulcerative colitis remains unknown to this day. Although there are multiple theories, no definitive conclusion has been reached. Bacterial causes have been ruled out, and viral causes seem unlikely since the disease does not spread epidemically, and viral particles have not been confirmed. Serum lysosomes are elevated in Crohn's disease patients but normal in ulcerative colitis patients.

Genetic factors may play a role, as the incidence among white Jews is 2–4 times higher than among non-Jews, while non-whites have about 50% lower incidence than whites. Recently, Gilat et al. reported a significantly lower incidence of ulcerative colitis in Jews in Tel Aviv (3.8 per 100,000) compared to Copenhagen, Denmark (7.3 per 100,000), Oxford, UK (7.3 per 100,000), and Minnesota, USA (7.2 per 100,000). Additionally, the female-to-male ratio was only 0.8, whereas other reports indicate 1.3. Clearly, geographical and racial differences influence the occurrence of this disease.

Psychological factors are important in disease exacerbation. It is now clear that ulcerative colitis patients do not exhibit abnormal predispositions compared to matched controls. Moreover, pre-existing psychological conditions such as depression or social withdrawal significantly improve after colectomy.

Some suggest that ulcerative colitis is an autoimmune disease, as many patients have antibodies in their blood that cross-react with normal colonic epithelial cells and specific bacterial lipopolysaccharide antigens. Furthermore, lymphocytes cultured with serum from colitis patients can become cytotoxic to colonic epithelial cells. Additionally, alterations have been observed in the T and B lymphocyte populations of colitis patients. However, it was later recognized that these abnormalities are not necessary for disease onset but rather a result of disease activity. In fact, Brandtzueg et al. clearly demonstrated that there is no defect in tissue-level immunoglobulin activity in the residual glands of ulcerative colitis patients. IgA transport is normal, while IgG immunocyte responses are five times higher than in controls. Thus, IgG may play a role in the chronic phase of the disease but is unrelated to its onset.

In summary, current thinking holds that the pathogenesis of inflammatory bowel disease results from the interaction of exogenous substances, host responses, and genetic and immune influences. According to this view, chronic ulcerative colitis and Crohn's disease represent different manifestations of the same disease process. Due to the host's hypersensitivity to exogenous antigens—once intestinal immune priming is established (possibly during the microbial colonization period in infancy)—any injury that increases mucosal permeability to these antigens may trigger an inflammatory response in the intestinal wall. The type of antigen and other factors determine the nature of the inflammatory process, leading to either Crohn's disease or ulcerative colitis.

bubble_chart Pathological Changes

Ulcerative colitis is a disease confined to the colonic mucosa and submucosa. This is distinctly different from the transmural inflammatory changes seen in Crohn's disease of the colon, where all layers of the intestinal wall are involved in a granulomatous inflammatory process. However, the pathological changes observed in ulcerative colitis are nonspecific and can also be seen in bacterial dysentery, amebic dysentery, and gonococcal colitis.

The lesions begin with infiltration of round cells and polymorphonuclear neutrophils into the Lieberkühn crypts at the base of the mucosa, forming crypt abscesses. Under light microscopy, the overlying epithelial cells appear pale-stained and vacuolated. Electron microscopy reveals mitochondrial swelling, widened intercellular spaces, and dilated endoplasmic reticulum. As the disease progresses, crypt abscesses coalesce and the overlying epithelium sloughs off, forming ulcers. Adjacent to the ulcers, the mucosa appears relatively normal but edematous, giving it a pseudopolypoid appearance, becoming isolated between adjacent ulcers. The ulcerated areas are occupied by exuberant growth of collagen and granulation tissue, extending into the ulcers but rarely penetrating the muscular layer. In fulminant ulcerative colitis and toxic megacolon, these lesions can penetrate the entire intestinal wall, leading to perforation. Fortunately, these types of lesions are uncommon, accounting for 15% and 3% of cases, respectively. The pathological changes provide a clear explanation for the clinical manifestations. Patients may experience more than 20 bloody stools per day. Because the denuded and severely distorted mucosa can no longer absorb water and sodium, each peristaltic movement squeezes out large amounts of blood from the exposed granulation tissue surface. Early radiographic findings of loss of haustrations are due to paralysis of the muscularis mucosae, while the shortening and rigid "lead pipe" appearance of the colon on barium enema are the result of scarring from repeated injury.

Most cases of ulcerative colitis involve the rectum, but if the lesions are confined to the rectum, it is termed ulcerative proctitis. It remains unclear why some cases are limited to the rectum while others involve the entire colon. In most cases, the inflammation extends proximally, affecting the left colon, and approximately one-third of patients develop pancolitis, where the entire colon is involved. In 10% of pancolitis patients, the distal few centimeters of the ileum also develop ulcers, termed backwash ileitis. The diseased areas in ulcerative colitis are contiguous, rarely showing segmental or skip distribution. The factors determining the severity and duration of the disease are unclear, but they may be related to the extent of immune dysregulation. There is evidence suggesting that prostaglandins may play a significant role in the acute stage of the disease. Unfortunately, there are no reports of favorable responses to prostaglandin synthase inhibitors such as indomethacin.

bubble_chart Clinical Manifestations

The initial manifestations of ulcerative colitis can take many forms. Bloody diarrhea is the most common early symptom. Other symptoms, in order of frequency, include abdominal pain, hematochezia, weight loss, tenesmus, vomiting, and so on. Occasionally, the primary manifestations may involve arthritis, iridocyclitis, liver dysfunction, and skin lesions. Fever is relatively uncommon as a presenting sign. In most patients, the disease follows a chronic, low-grade course, while in a minority (approximately 15%), it presents as an acute, catastrophic outbreak. These patients exhibit frequent bloody stools, up to 30 times per day, along with high fever and abdominal pain. Thus, the clinical spectrum of the disease is extremely broad, ranging from grade I diarrhea to a fulminant, life-threatening condition requiring immediate treatment.

Signs are directly related to the disease stage and clinical presentation. Patients often exhibit weight loss and pallor. During active disease, tenderness is commonly noted upon abdominal examination over the colon. Signs of acute abdomen may be present, accompanied by fever and reduced bowel sounds, particularly in acute episodes or fulminant cases. In toxic megacolon, abdominal distension and fullness, fever, and signs of acute abdomen may be observed. Due to frequent diarrhea, perianal skin may show abrasions or excoriation. Perianal inflammation, such as anal fissures or fistulas, may also occur, although the latter is more common in Crohn's disease. Digital rectal examination is invariably painful and should be performed gently in cases with perianal inflammation. Examination of the skin, mucous membranes, tongue, joints, and eyes is crucial, as the presence of lesions in these areas may indicate that the cause of diarrhea is ulcerative colitis.

Diagnosis primarily relies on fiberoptic colonoscopy, as the rectum and sigmoid colon are affected in approximately 90–95% of patients. Therefore, fiberoptic sigmoidoscopy alone can often confirm the diagnosis. During endoscopy, congested and edematous mucous membranes, which are fragile and prone to bleeding, can be observed. In advanced cases, ulcers surrounded by raised granulation tissue and edematous mucosa may be seen, resembling polyps or forming pseudopolyps. In chronic progressive cases, the rectal and sigmoid lumens may significantly narrow. To determine the extent of the disease, a full colonoscopy with multiple biopsies is recommended to differentiate it from Crohn's colitis.

Double-contrast barium enema is another useful diagnostic tool, particularly for assessing the extent and severity of the disease. Barium enema may reveal loss of haustration, irregular bowel walls, pseudopolyps, and luminal narrowing and rigidity. Although barium enema is valuable, caution is advised during preparation to avoid bowel cleansing, as it may exacerbate colitis. For patients without diarrhea, a 3-day liquid diet before the examination is sufficient. Barium enema is contraindicated in cases with abdominal signs; instead, plain abdominal X-rays should be performed to check for toxic megacolon, colonic dilation, and signs of free air under the diaphragm.

Due to the chronic, protracted course of the disease and its high risk of malignancy, patients with a history of more than 10 years should undergo annual barium enema or biannual fiberoptic colonoscopy for surveillance.

bubble_chart Treatment Measures

(1) Medical Treatment

The outcome of acute exacerbation of ulcerative colitis primarily depends on the severity of the disease (Grade III), manifested by systemic symptoms, and is unrelated to the disease duration or extent of involvement, with the exception of ulcerative proctitis, which is not considered here.

Medical treatment should include four aspects: (1) Bed rest and systemic supportive therapy: This includes maintaining fluid and electrolyte balance, especially potassium supplementation, with correction for hypokalemia. Attention should also be paid to protein supplementation to improve overall nutritional status. Total parenteral nutrition support may be necessary in some cases. Blood transfusion may be given for anemia, and dairy products should be avoided as much as possible during gastrointestinal intake.

(2) Sulfasalazine (Azulfidine, SASP): Initially, 0.25g orally four times daily, gradually increasing to 1g four times daily. After efficacy is achieved, the dose can be reduced to 1g three times daily or 0.5g four times daily. Concurrently, metronidazole 0.2g three times daily may be given. After three weeks, switch to metronidazole suppositories 0.2g twice daily, then reduce to 0.2g once daily, and continue for 3–6 months.

(3) Corticosteroids: The usual dose is prednisone 5–10mg three times daily. After 1–2 weeks, taper the dose by reducing 5mg weekly until a maintenance dose of 5mg once daily or 2.5mg twice daily is reached. Alternatively, dexamethasone 0.75–1.5mg three times daily may be used, similarly tapering to 0.75mg once daily or 0.375mg twice daily as maintenance. However, long-term steroid maintenance is not currently believed to prevent relapse. During acute exacerbations, hydrocortisone 100–300mg or dexamethasone 10–30mg may be administered intravenously, along with nightly hydrocortisone 100mg in 60ml saline for retention enemas. The value of corticosteroid therapy during acute attacks is well-established, but its continued use in chronic stages remains controversial due to potential side effects, and long-term use is generally not recommended. In addition to corticosteroids, ACTH 20–40U may also be administered intravenously.

(4) Immunosuppressants: Their role in ulcerative colitis remains questionable. According to Rosenberg et al., azathioprine does not control disease progression during exacerbations but may help reduce corticosteroid use in chronic cases.

In addition to the above treatments, anticholinergic drugs or compound diphenoxylate (Lomotil) may be given for severe diarrhea or nocturnal diarrhea. However, opioid drugs such as codeine and compound camphor tincture should be avoided due to the risk of inducing acute colonic dilation.

(2) Surgical Treatment

Approximately 20–30% of ulcerative colitis patients will eventually require surgical intervention. Previously, surgery was considered a last resort after all medical treatments had failed, with patients often in a state of severe malnutrition and debilitation due to acute or chronic illness. Nowadays, earlier surgical intervention is advocated. This shift in treatment approach is due to the availability of several surgical options with favorable outcomes.

⑴Indications for surgery: The indications requiring emergency surgery include: ①Massive, uncontrollable bleeding; ②Toxic megacolon with impending or confirmed perforation, or toxic megacolon unresponsive to treatment within hours rather than days; ③Fulminant acute ulcerative colitis unresponsive to steroid therapy, i.e., no improvement after 4-5 days of treatment; ④Obstruction caused by stenosis; ⑤Suspected or confirmed colorectal cancer. Additionally, several non-emergency conditions should also be considered for surgery, such as: ⑥Refractory chronic ulcerative colitis, characterized by recurrent exacerbations, chronic persistent symptoms, malnutrition, weakness, inability to work, and inability to participate in normal social activities and sexual life; ⑦Disease exacerbation upon reduction of steroid dose, making it impossible to discontinue steroid therapy for months or even years—this is an indication for colectomy; ⑧Chronic colitis in children affecting growth and development; ⑨Severe extraintestinal manifestations such as arthritis, pyoderma gangrenosum, or hepatobiliary diseases that may respond to surgery.

⑵ Surgical Options: Currently, there are four surgical options available for chronic ulcerative colitis. Each has its advantages and disadvantages, so strict indications must be applied. Only rational selection can achieve the best results.

① Total proctocolectomy with ileostomy: This is the oldest and most definitive procedure, with no risk of recurrence or malignancy, and no need for postoperative medication. It has fewer complications and can be completed in the initial stage (first stage). However, the permanent ileostomy brings significant inconvenience, psychological distress, and physical suffering to patients, making it the least desirable option. Therefore, this procedure should be limited to patients with low rectal cancer requiring rectal resection, those with anal diseases or a history of anal surgery, or those who have undergone small intestine resection or are suspected of having Crohn’s disease and are unsuitable for pelvic ileal pouch surgery.

② Total colectomy with ileorectal anastomosis: This is a controversial procedure because retaining the diseased rectum carries the risk of disease reactivation and malignancy. However, it is technically simpler, avoids a permanent ileostomy, and has fewer complications. Before the advent of Koch ileostomy and ileal pouch-anal anastomosis, this was the only option to avoid a permanent ileostomy. Proponents argue that it at least spares patients from ileostomy-related suffering for several years. This procedure is mainly suitable for patients without rectal involvement. It is contraindicated in cases of colon or rectal cancer or dysplasia, rectal fibrosis preventing dilation, perianal diseases, or patients unable to undergo regular postoperative follow-up.

③ Continent ileostomy (Koch pouch): Koch pioneered the creation of a reservoir pouch and a nipple valve from the terminal ileum to achieve fecal continence. This is a relatively complex procedure with more complications, particularly those related to the nipple valve, such as fistula formation, valve slippage, necrosis, and prolapse. Valve slippage is the most common and challenging issue. Although many modifications have been made to reduce its occurrence, it cannot be entirely eliminated. The role of the Koch ileal pouch has become more limited. Generally, patients wishing to avoid ileostomy should opt for pelvic ileal pouch surgery. If a patient has already undergone total proctocolectomy or is unsuitable for pelvic ileal pouch surgery due to low rectal cancer or anal dysfunction, the Koch ileal pouch may be considered. However, previous small intestine resection or small intestine involvement in Crohn’s disease contraindicates this procedure.

④ Total proctocolectomy with ileal pouch-anal anastomosis (IPAA): This procedure is primarily indicated for chronic ulcerative colitis cases refractory to medical therapy, persistent extraintestinal manifestations, continuous minor bleeding, strictures, or severe mucosal dysplasia. It is also suitable for cases of rectal cancer above the mid-rectal level without dissemination. This surgery should never be performed in acute settings. Additionally, during emergency colectomy, the rectum does not necessarily need to be removed, especially in younger patients. If clinically indicated, the rectum can be preserved, allowing for subsequent proximal rectal resection, distal rectal mucosal stripping, and ileal pouch-anal anastomosis.

Ileal pouch-anal anastomosis can be broadly classified into three types: double-loop ileal pouches (including J-pouch, modified J-pouch, and lateral pouch), triple-loop ileal pouch (S-pouch), and quadruple-loop ileal pouch (W-pouch). Each type has its own advantages and disadvantages.

The S-shaped ileal pouch-anal anastomosis was the earliest pelvic ileal pouch procedure, proposed by Parks and Nicholls in 1978. Initially, they used a 30cm segment of terminal ileum folded into three loops, which was later modified to use a 50cm length divided into three 15cm segments and a 5cm efferent limb. The results showed that 50% of patients required catheterization for emptying, with pouchitis being the most common complication. Many scholars have pointed out that an oversized pouch and an excessively long efferent limb are the two main causes of retention and pouchitis. Therefore, it is currently recommended to use three 10-12cm ileal segments to form the pouch, with an efferent limb length of 2-4cm being optimal.

The J-pouch anal anastomosis was advocated by Utsunomiya in 1980. Its advantages include good emptying, minimal retention, and enhanced reservoir function due to two intestinal segments with antagonistic peristaltic directions. The pouch consists of two 12–15 cm segments of terminal ileum, with the apex of the ileal pouch pulled down for an end-to-side anastomosis with the anal canal.

The modified J-pouch anal anastomosis, designed by Balcos, involves cutting the original J-pouch at its heel and pulling the distal segment down for an anti-peristaltic end-to-end ileoanal anastomosis. The length of the efferent limb should not exceed 4 cm. This procedure retains the advantages of the J-pouch while correcting its major drawback by converting the anastomosis from end-to-side to end-to-end.

The side-to-side ileal pouch anal anastomosis, proposed by Peck in 1980, is another double-lumen ileal pouch procedure performed in two stages. The first stage involves an end-to-end ileoanal anastomosis, followed by an end ileostomy 30–40 cm from the terminal ileum. After 3–6 months, the ileostomy is closed, and the proximal ileum is pulled down into the pelvis for a side-to-side anastomosis with the distal ileum, forming the ileal pouch. Theoretically, both ileal segments exhibit peristalsis in the same direction, reducing retention and retaining all the advantages of the J-pouch without its disadvantages. However, the second-stage surgery is extremely challenging and constitutes a major operation, leading Peck to abandon this procedure.

The W-pouch anal anastomosis involves folding and incising four 12 cm segments of terminal ileum to form a large reservoir, which is then pulled down for an end-to-side anastomosis with the anal canal. This procedure is more time-consuming and technically demanding but offers superior reservoir function due to the larger capacity. Nicholls and Pezim (1985) reported 104 IPAA cases, comparing the postoperative function of J-, S-, and W-pouches in terms of continence, spontaneous evacuation, and capacity, with the W-pouch outperforming the others in all three metrics. Keighley et al. (1989) compared complications and function between J- and W-pouches in 65 IPAA cases, concluding no significant difference. Wexner (1989) reported on 114 primarily S-pouch cases with a 5-year follow-up, showing 92% spontaneous evacuation, 91% daytime continence, 76% nighttime continence, and an 8% overall failure rate. Silva et al. (1991) reviewed 88 IPAA cases, finding the W-pouch superior and the S-pouch inferior. Recently, Gratz and Pemberton (1993) reported Mayo Clinic’s experience with 1400 IPAA cases, mostly J-pouches, with only two postoperative deaths (one from steroid-induced gastric ulcer perforation and one from pulmonary embolism). Long-term satisfaction was 95%, though continence was imperfect, with some patients experiencing fecal leakage and up to one-third developing pouchitis, for which no effective long-term prevention or treatment exists. Further research is needed. Nevertheless, among the four existing procedures, total proctocolectomy with ileal pouch-anal anastomosis remains a reasonable and viable option.