Clinical Presentation

Introduction

Ulcerative colitis (UC) is a chronic immune-mediated idiopathic inflammatory disorder characterized by colonic inflammation which typically begins in the rectum and extends proximally. The disease typically begins gradually and progresses over a period of several weeks. The clinical course is characterized by flares and periods of remission, occurring either spontaneously or in response to treatment.

Typical symptoms include bloody diarrhea, abdominal pain, urgency and tenesmus. Other symptoms may include fecal incontinence, fatigue, mucus discharge and nocturnal defecations. In severe disease, patients may also present with fever, abdominal pain, cramping and weight loss, although weight loss is more common in patient with Crohn’s disease (CD). Physical examination may reveal signs of anemia or abdominal tenderness. Rectal exam may reveal blood, anal fissures, or skin tags. The presence of anal or perianal fistulas are uncommon in UC and may be indicative of CD. Signs of colonic dilation include abdominal distention and tympany on percussion.

Severity and Extent

Unlike CD, inflammation in UC is limited to the colonic mucosa. Ulcerative colitis is classified based on extent of colonic involvement: ulcerative proctitis is limited to the rectum, proctosigmoiditis affects the rectum and sigmoid colon, left-sided colitis extends up to the splenic flexure and extensive colitis extends beyond the splenic flexure (Figure 4-1). Pancolitis refers to contiguous inflammation affecting the entire colon. Symptoms may vary based on disease extent. Patients with ulcerative proctitis may predominantly experience urgency and tenesmus along with rectal bleeding, whereas bloody diarrhea and abdominal pain may be more common in patients with pancolitis. Constipation is a paradoxical symptom that occurs in up to 10% of patients with ulcerative proctitis and left-sided colitis.

At time of diagnosis, approximately a third of patients present with ulcerative proctitis, a third with left-sided colitis and the other third with pancolitis. Up to 50% of patients diagnosed with proctitis or proctosigmoiditis progress to extensive colitis following 25 years of follow-up.

Once a diagnosis of UC is established, determining the severity of disease is important. Published guidelines by the American College of Gastroenterology have proposed new definitions of mildly, moderately and severely active disease that incorporate both patient-reported outcomes and laboratory- and endoscopy-based values (Table 4-1). Up to 15% of patients are initially diagnosed with severe disease.

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Prognosis

In addition to assessment of disease extent and severity, prognosis is an important patient factor to consider. There are several factors which when present have been associated with poor prognosis in patients with UC, including:

• Patient age <40 years at diagnosis
• The presence of extensive colitis
• The presence of severe endoscopic disease (Mayo endoscopic subscore of 3 or UCEIS ≥7)
• Hospitalization for colitis
• Elevated CR
• Low serum albumin.

The greater the number of poor prognostic factors, the worse the prognosis as measured by the patient’s risk for hospitalization or colectomy. The selection of induction and maintenance therapies for patients with UC should therefore be based on disease extent, severity and prognosis.

In 2019, a user-friendly web-based tool was developed to help individualize therapy based upon an individual patient’s calculated risk for colectomy. Their model identified serum albumin, 9-point partial Mayo score >5, Mayo endoscopic sub-score >1, and systemic corticosteroid use within 6 months as the key predictors for future total proctocolectomy. In addition to allowing HCPs to easily identify high-risk patients, the tool promotes greater patient involvement, which may empower patients to contribute to their care plan. This model still requires both prospective and external validation.

Age-Related Differences

Pediatric inflammatory bowel disease (IBD) accounts for between 5% and 10% of cases and elderly-onset IBD (diagnosed at age >60 years) accounts approximately 9% of cases. Genetic factors appear to play a greater role in pediatric IBD, whereas environmental factors are proposed to have a more prominent role in elderly-onset IBD.

UC symptoms are similar between pediatric and adult patients; however, evidence of growth failure or pubertal delay may additionally be observed in younger patients.

Age of onset has a profound effect on clinical presentation and disease course. In general, pediatric UC is considered more severe than disease phenotypes observed in older patients, in terms of severity at diagnosis and disease extension over time. At diagnosis, between 61% and 90% of pediatric UC patients present with pancolitis compared to 24% to 33% of adult patients. In a Hungarian study, 26% and 40.6% of pediatric patients with ulcerative proctitis or left-sided colitis at diagnosis progressed 5 and 10 years later, respectively, compared to only 12.8% and 20.2% of adult patients. Additionally, more pediatric patients had ≥1 acute severe episode compared to adult patients (19.3% vs 8.2%). Risk factors for disease extension in children include delays in diagnosis of >6 months, a family history of IBD, the presence of extraintestinal manifestations and a higher pediatric UC activity index score (PUCAI).

In elderly patients who present with ulcerative proctitis at diagnosis, approximately 8% progress to left-sided colitis and 3% to extensive colitis. Therefore, UC disease distribution appears to remain stable in >80% of elderly patients.

Extraintestinal Manifestations

Extraintestinal manifestations of UC are present in approximately a third of patients with UC. Skin, joint, eye and liver manifestations are the most frequent and include arthritis (21%), aphthous stomatitis (4%), primary sclerosing cholangitis (4%), uveitis (4%), erythema nodosum (3%), ankylosing spondylitis (2%), pyoderma gangrenosum (2%) and psoriasis (1%). The presence of extraintestinal manifestations is associated with greater disease extent and worse prognosis. Extraintestinal manifestation will be discussed in more detail in Comorbidities.

Arthritis, either peripheral or axial, is the most common extraintestinal manifestation. Peripheral arthritis can either be acute, flaring with colitis, or be more chronic, polyarticular (involving >6 joints) and with symptoms lasting for months. Axial arthritis includes ankylosing spondylitis and sacroiliitis, which can cause symptoms of pain and stiffness and limit spinal flexion. Exercise can help relieve these symptoms.

The two most common skin manifestations of UC are erythema nodosum and pyoderma gangrenosum. Erythema nodosum usually coincides with luminal disease, whereas pyoderma gangrenosum is often independent of disease activity.

Primary sclerosing cholangitis (PSC) is more common in patients with UC than CD, and is more common in males and in those with more extensive disease. PSC can be progressive, with a disease course that does not parallel that of UC. Additionally, PSC is a risk factor for cholangiocarcinoma and colorectal cancer. In a meta-analysis, the presence of PSC in patients with UC was associated with an increased risk of dysplasia and colorectal cancer (OR = 4.79). The cumulative risk of developing colorectal cancer in patients with UC and PSC is estimated to be 25%, 33% and 40% at 10, 20 and 30 years post-diagnosis, respectively, thus the importance of surveillance is emphasized in these patients.

The risk of venous thromboembolism is 3- to 4-fold greater in patients with IBD, with greater risk in patients treated with corticosteroids or experiencing flaring. Due to this risk, venous thromboembolism prophylaxis should be considered in hospitalized patients with UC.

Extraintestinal Manifestations in Children

At the time of diagnosis, 28% of pediatric patients exhibit extraintestinal manifestations. The most common are peripheral arthritis (2% to 50%), aphthous stomatitis (3% to 42%), osteoporosis/osteopenia (25%), arthralgia (15%), erythema nodosum (1% to 13%), growth failure (6% to 10%), pyoderma gangrenosum (8%), anemia (5%), pancreatitis (1% to 5%) and primary sclerosing cholangitis (2%). Since joint and mucocutaneous disease are the most common, physicians should look for tender swollen joints, erythema nodosum and aphthous stomatitis at evaluation. Up to 35% of pediatric patients with IBD manifest extraintestinal manifestations prior to having intestinal symptoms. As such, IBD should be suspected in children with extraintestinal manifestations, that may be the initial presenting symptoms, to prevent a delay in diagnosis.