Each individual patient serves as a control in establishing the degree of abnormality in stool frequency. The daily bleeding score is based on the most severe bleeding episodes of the day. Patients should be queried regarding current symptoms such as abdominal pain and distension, bowel habits frequency, nocturnal movements, blood in stool , urgency or tenesmus, presence of extraintestinal manifestations, nausea, vomiting, fever, and weight loss.
Potential inciting factors include cessation of cigarette smoking or use of concurrent medications such as nonsteroidal anti-inflammatories or oral contraceptives. Close physical examination with attention to vital signs, mentation, and clinical status is paramount to rule out sepsis or hypovolemia. Abdominal inspection particularly for distension or hernias should precede auscultation for bowel sounds and palpation for abdominal tenderness, organomegaly, rebound, or guarding. A rectal examination with investigation of the perianal region, stool, and rectal vault should always be performed.
Examination of the skin, eyes, and joints can determine the presence of extraintestinal manifestations. Exclusion of alternate etiologies and concomitant infection are crucial steps in initial evaluation. Stool microbiologic testing with bacterial culture and ova and parasite assay should be undertaken with inclusion of specific stool assays for Escherichia coli H7 and Clostridium difficile toxin.
Initial laboratory evaluation should include a complete blood count with differential, comprehensive metabolic profile including liver function panel, erythrocyte sedimentation rate, and C-reactive protein. Colonoscopy with biopsy is the first-line investigation in diagnosing UC and assessing disease extent and severity.
Visual inspection can identify alternate or concomitant pathology including pseudomembranous colitis associated with C.
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Deep ulcerations could indicate the presence of cytomegalovirus colitis, CD, or severe UC. The general safety of colonoscopy in patients with acute colitis has been documented 26 without an increased major complication rate based on disease activity. The benefits of completing a full endoscopic examination to the terminal ileum must be weighed against the risks to the patient on an individual basis.
Early flexible sigmoidoscopy with biopsy, perhaps coupled with abdominal imaging, may provide a safer alternative to full colonoscopy in selected cases. Endoscopy is generally contraindicated in the presence of toxic megacolon. Although imaging is not required for the diagnosis of UC, abdominal plain films should be considered in all patients presenting with colitis to exclude colonic dilation or free air. In cases when conventional colonoscopy may not be completed or is not feasible due to the risk of complications such as perforation or toxic megacolon, a less invasive imaging modality may be considered.
MR enterography is one such example and has advanced in recent years as a preferred imaging technique for providing a comprehensive view of intraluminal and extraluminal pathology without the use of ionizing radiation. In many North American sites, MR enterography has replaced gastrointestinal fluoroscopy and computed tomography enterography and has become a first-line imaging test for suspected or extant IBD. Indications for hospitalization include severe disease, toxic megacolon, failure of outpatient medical therapy, profound extraintestinal manifestations, or complications related to IBD such as thromboembolism or its pharmacotherapy.
Supportive inpatient management includes intravenous IV fluid administration, electrolyte and hemoglobin monitoring with repletion as needed, and IV corticosteroids if indicated. Anti-peristaltic and narcotic agents should be avoided, as they can potentially contribute to ileus, exacerbate colitis severity, and precipitate toxic megacolon.
Patients should undergo early colonoscopy typically within initial 48 hours as the preferred endoscopic test to evaluate the full extent of disease and to obtain mucosal biopsies. As aforementioned, colonoscopy should be pursued with caution in cases of severe colonic ulceration or dilation to avoid precipitation of a perforation or toxic megacolon.
Consideration of medical options for acute severe UC should be undertaken, and early surgical consultation should be requested.
Careful frequent examinations and assessments are required to determine the response to pharmacotherapy and to assess the need for additional rescue measures including colectomy. Careful monitoring for disease-related complications such as arterial or venous thromboembolism VTE is warranted. IBD is associated with a roughly 1. Among hospitalized patients, the excess mortality associated with VTE is 2. Treatment for UC can become quite complex and requires an individualized and multidisciplinary approach.
Collaboration among medical and surgical teams, nutritionists, psychiatrists, and social support services is important particularly in new-onset acute cases and those requiring complex decision making. Professional recommendations must then be synthesized and translated with a patient-centered, educational focus. Patients with mild-to-moderate disease can usually be managed in the outpatient setting, while severe UC warrants inpatient care. In general, sequential therapy Figure 1 based on disease severity and subsequent response is recommended for both new-onset cases and periods of flare.
The goal of treatment in the acute setting is to induce remission and avoid complications.
Ideally, the agent selected to achieve remission is carried forward to maintain disease control. Figure 1 Sequential therapy in the treatment of ulcerative colitis based on disease severity at presentation blue boxes, left. Initial treatment options based on disease category are shown purple boxes. Therapy is escalated based on severity at presentation or failure to respond to prior step.
Red arrow signifies time, and maintenance options are shown yellow boxes. Colectomy orange box is considered in fulminant or recalcitrant disease. Table 2 provides a summary of 5-aminosalicylic acid aminosalicylates [5-ASAs] formulations used in the treatment of UC with details including indication, delivery site, acute disease characteristics, typical dosing for active disease and maintenance of remission , and common adverse reactions.
Table 3 outlines the major categories of immunosuppressant medications used in treating UC corticosteroids, thiopurines, biologics, and calcineurin inhibitors with details including indication, typical dosing, efficacy, and common side effects. Table 2 5-Aminosalicylate preparations in the treatment of ulcerative colitis Notes: Treatments for mild-to-moderate UC.
Choice of 5-ASA formulation s depends on disease indication and location, patient preference, and compliance, cost, and drug availability. Combination therapy with oral and rectal 5-ASA is more effective than oral formulation alone for extensive mild-to-moderate UC. Induction of remission for mild-to-moderate distal colitis can be achieved with topical mesalamine, oral 5-ASAs, or topical steroids with topical mesalamine as a superior first-line agent.
Oral 5-ASA preparations have varying sites of delivery with the intent to deliver medication directly to sites of colonic inflammation with minimal systemic side effects. A systematic review examining mesalamine formulations and prodrugs demonstrated no differences in absorption and systemic exposure to 5-ASA. Olsalazine is dosed from 1. The MMX mesalamine formulation provides comparable results with a convenient dosing regimen of 2.
Higher doses of mesalamine appeared to be effective and well-tolerated. At 6 weeks, patients receiving 4. Both dosing regimens had similar reported tolerability and side effects. Historically, early registration trials used four times daily or three times daily 5-ASA dosing to mirror the regimen used for sulfasalazine. However, post-marketing data suggests that less frequent dosing of agents for induction and maintenance is possible, 48 , 52 — 55 and newer agents are indicated for once daily dosing.
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Patients who fail to respond to the first 8 weeks of mesalamine therapy may achieve clinical and endoscopic remission with an 8-week, high-dose MMX mesalamine extension before being considered for step-up therapy with steroids or immunosuppressants. Topical agents as an alternative or supplement to oral 5-ASAs include mesalamine suppositories or enemas and hydrocortisone foam or enemas.
In general, suppositories reach the upper rectum 10 cm above the anal verge , while enemas can extend as far as the splenic flexure and distal transverse colon. Foams can be effective for disease involving the rectum and distal sigmoid 15—20 cm above the anal verge but do not reach as far as enemas. Patients intolerant of or unresponsive to rectal mesalamine after 2 weeks can be switched to hydrocortisone formulations.
Other effective rectal corticosteroids include beclomethasone and budesonide. Beclomethasone dipropionate and mesalamine foam and enema have similar efficacy and tolerability in mild active distal colitis.
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Topical therapy generally provides a more rapid response with less frequent dosing and less systemic side effects versus oral therapy. Agents are determined by both patient preference and proximal disease extent. Administration can be inconvenient, especially while outside of the home or in social situations.
Patients can also experience anal leakage that could be uncomfortable and embarrassing; foam modalities may be easier to tolerate in this regard. Sulfasalazine is a prodrug composed of sulfapyridine bonded to active mesalamine, and up to one-third of treated patients experience side effects thought to be attributed to the sulfur moiety. More severe but less frequent effects include pancreatitis, hepatotoxicity, allergic reactions, bone marrow suppression, drug-induced connective tissue disease, hemolytic or megaloblastic anemia, and interstitial nephritis.
A double-blind, non-placebo-controlled outpatient trial of 58 patients with active mild UC examining optimal oral prednisone dosing at 20, 40, and 60 mg daily found that 40 or 60 mg daily dosing achieved greater symptomatic improvement with two times the remission rate versus 20 mg daily over 2 weeks.
Additionally, patients in the 40 mg arm experienced fewer side effects than those in the 60 mg arm. Thus, oral prednisone starting at 40 mg daily has been considered optimal. Sixty percent of patients hospitalized for severe UC will achieve clinical remission within 5—7 days of treatment initiation.
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Steroids carry a significant side effect profile and can distort metabolic activity in a multitude of organ systems. Such adverse effects include diabetes, cushingoid features, glaucoma, cataracts, and psychiatric instability. Adrenal insufficiency can develop and requires consideration when tapering. Drug-related adverse events are low, and serious side effects leading to treatment abortion are infrequent.
AZA and 6-mercaptopurine have limited utility in the acute setting. The active drug metabolites have a half-life of approximately 3—5 days.
A steady state can be achieved after about 2—4 weeks, but maximal clinical effect can take up to 8—10 weeks. Thiopurine methyltransferase enzyme activity should be assessed prior to inception of the therapy to determine recommended starting dose and potential for early severe side effects. It is indicated for moderate-to-severely active UC in the outpatient setting. Two randomized double-blind, placebo-controlled trials Active UC Trials 1 and 2 [ACT 1 and ACT 2, respectively] evaluating the efficacy of IFX versus placebo for induction and maintenance therapy in moderate-to-severe UC with failed medical therapy have demonstrated sustained clinical response and remission at 8 and 30 weeks in both trials and at 54 weeks in ACT 1; patients receiving IFX were significantly more likely to have endoscopic mucosal healing at these landmarks.
Adverse events were similar in placebo compared to IFX groups. IFX is contraindicated for use in patients with active uncontrolled infection, moderate-to-severe congestive heart failure, untreated latent tuberculosis, preexisting demyelinating conditions, optic neuritis, and active malignancies.
Acute transfusion reactions characterized by chest pain, shortness of breath, palpitations, flushing, headache, fever, and sometimes urticarial rash or hypotension and delayed-type sensitivity reactions may occur with administration.