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Richard P MacDermott, MD
Paul Rutgeerts, MD, PhD, FRCP
Shilpa Grover, MD, MPH
INTRODUCTION — Ulcerative colitis is a chronic inflammatory condition characterized by relapsing and remitting episodes of inflammation limited to the mucosal layer of the colon. It almost invariably involves the rectum and may extend in a proximal and continuous fashion to involve other portions of the colon.
This topic will review the management of mild to moderate ulcerative colitis. The management of severe ulcerative colitis, steroid-dependent, and steroid-refractory ulcerative colitis are discussed separately. (See "Management of severe ulcerative colitis in adults" and "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis".)
PRETREATMENT EVALUATION — Patients may present with active symptoms of ulcerative colitis as the initial manifestation or as a clinical recurrence of their disease. The clinical manifestations and diagnosis of ulcerative colitis are discussed separately. (See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults".)
When a patient presents with recurrent symptoms, some aspects of the initial evaluation should be repeated in order to exclude alternative or comorbid conditions as a cause for the symptoms, as well as to assess the current extent and severity of disease. These features are important to guide treatment. In most cases, laboratory studies and endoscopy are required.
Definitions of disease extent — Different terms are used to describe the extent of involvement of ulcerative colitis [1,2]:
●Ulcerative proctitis refers to disease limited to the rectum
●Ulcerative proctosigmoiditis refers to disease limited to the rectum and sigmoid colon and not involving the descending colon
●Left-sided or distal ulcerative colitis refers to disease that extends beyond the rectum and as far proximally as the splenic flexure
●Extensive colitis refers to disease extending proximal to the splenic flexure but sparing the cecum
●Pancolitis refers to disease extending proximal to the splenic flexure and involving the cecum
Extension of colonic disease may occur over time [3,4]. While clinical symptoms can suggest probable sites of disease activity, colonoscopy is required to determine the extent of involvement. (See 'Colonoscopy' below.)
Assessment of clinical severity — Patients can present with mild, moderate, or severe disease. Stratification based on clinical severity is important in guiding management [1]. (See 'Treatment of mildly or moderately active disease' below.)
●Mild – Patients with mild clinical disease have four or fewer stools per day with or without blood, no signs of systemic toxicity, and a normal erythrocyte sedimentation rate (ESR). Mild crampy pain, tenesmus, and periods of constipation are also common, but severe abdominal pain, profuse bleeding, fever, and weight loss are not part of the spectrum of mild disease.
●Moderate – Patients with moderate clinical disease have frequent loose, bloody stools (>4 per day), mild anemia not requiring blood transfusions, and abdominal pain that is not severe. Patients have minimal signs of systemic toxicity, including a low-grade fever. Adequate nutrition is usually maintained and weight loss is not associated with moderate clinical disease.
●Severe – Patients with a severe clinical presentation typically have frequent loose bloody stools (≥6 per day) with severe cramps and evidence of systemic toxicity as demonstrated by a fever (temperature ≥37.5°C), tachycardia (HR ≥90 beats/minute), anemia (hemoglobin <10.5 g/dL), or an elevated ESR (≥30 mm/hour). Patients may have rapid weight loss. The management of severe ulcerative colitis is discussed separately. (See "Management of severe ulcerative colitis in adults".)
Laboratory testing — Blood counts, liver tests, and measurement of C-reactive protein (CRP) and ESR should be performed. CRP and ESR can help determine the severity of the underlying inflammation [5-7] (see 'Assessment of clinical severity' above). In addition, CRP levels may have a role in distinguishing between patients with active ulcerative colitis from those with symptoms caused by concomitant functional disorders [7-11]. (See 'Management of persistent symptoms' below.)
In addition, specific serologic testing for sexually transmitted diseases including Neisseria gonorrhea, HSV, and Treponema pallidum should be considered, particularly in patients with severe rectal symptoms including urgency and tenesmus and with risk factors for these diseases. (See "Clinical manifestations and diagnosis of Neisseria gonorrhoeae infection in adults and adolescents" and "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus in HIV-infected patients" and "Syphilis: Screening and diagnostic testing".)
Stool studies — Stool studies should include stool Clostridium difficile toxin, routine stool cultures (Salmonella, Shigella, Campylobacter, Yersinia), and specific testing for E. coli O157:H7. Microscopy for ova and parasites (three samples) and a Giardia stool antigen test should also be performed, particularly if the patient has risk factors such as recent travel. (See "Approach to the adult with acute diarrhea in resource-rich settings", section on 'Etiology' and "Clostridium difficile infection in adults: Clinical manifestations and diagnosis", section on 'Diagnosis'.)
Colonoscopy — Endoscopic evaluation is required to confirm the presence, severity, and extent of inflammation and to exclude the presence of an infection such as CMV with histology and culture of the tissue obtained on biopsy. Cultures for Neisseria gonorrhea and HSV should be performed in patients with severe rectal symptoms. Ileocolonoscopy with biopsies in the ileum and the colon is also important in differentiating between ulcerative colitis and Crohn disease. (See "Clinical manifestations and diagnosis of Neisseria gonorrhoeae infection in adults and adolescents" and "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus in HIV-infected patients" and "Endoscopic diagnosis of inflammatory bowel disease", section on 'Role in differential diagnosis' and "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults".)
A full colonoscopy should be avoided in hospitalized patients with severe colitis because of the potential to precipitate toxic megacolon. (See 'Assessment of clinical severity' above.) In such patients, a flexible sigmoidoscopy should be performed and evaluation limited to the rectum and distal sigmoid colon. (See "Endoscopic diagnosis of inflammatory bowel disease" and "Toxic megacolon".)
TREATMENT OF MILDLY OR MODERATELY ACTIVE DISEASE — Initial treatment of ulcerative colitis is based upon disease severity and extent. (See 'Assessment of clinical severity' above and 'Definitions of disease extent' above and 'Colonoscopy' above.)
Ulcerative proctitis or proctosigmoiditis
Initial approach — Topical 5-aminosalicylic acid (5-ASA) medications are first-line treatment in those who are willing to use rectal therapy. 5-ASA suppositories and/or enemas given rectally induce remission in more than 90 percent of patients with mild to moderate proctitis or proctosigmoiditis [12-18]. Remission rates as high as 93 percent have been reported with mesalamine enemas [14,17]. Furthermore, they can maintain remission in approximately 75 percent of patients. Topical therapies also provide a quicker response time than oral preparations and typically require less frequent dosing [2].
5-ASA agents are widely available as suppositories or enemas (table 1). 5-ASA foam and gel preparations, available in many countries around the world, are not available in the United States [19,20]. Enemas reach the proximal sigmoid colon and splenic flexure in virtually all patients who are able to retain them [21]. In contrast, foam preparations generally reach only the mid-sigmoid colon [22], while suppositories are effective only in the distal 5 to 8 cm of the rectum.
Topical 5-ASA medications are preferred over topical steroids in those who are willing to use topical therapy. A meta-analysis of seven trials concluded that 5-ASA enemas were significantly superior to corticosteroid enemas for the induction of remission and improving endoscopic and histologic severity (odds ratio [OR] 2.4, 1.9, and 2.0, respectively) [23]. A second meta-analysis concluded that the efficacy and side effect profile of topical mesalamine were dose-dependent and superior to oral therapies and topical steroids. Topical 5-ASA therapy was also associated with lower overall patient costs [24]. The side effects of 5-ASA medications are discussed separately. (See "Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease", section on 'Side effects'.)
For patients with mild to moderate disease confined to the distal 5 to 8 cm of rectum, we recommend treatment with mesalamine suppository twice daily (table 1) [25]. Although there are data to suggest that once daily dosing of a 5-ASA suppository may be sufficient [26], we find that twice daily administration of topical medications is often needed initially to treat severe urgency and tenesmus.
For patients with mildly to moderately active disease that involves greater than 8 cm of distal rectum, or the rectum plus sigmoid colon (proctosigmoiditis), we begin treatment with 5-ASA enemas given twice daily in addition to 5-ASA suppositories twice daily (table 1).
Patients who cannot retain enemas due to rectal irritability should be treated with 5-ASA foam preparations where available.
Symptomatic improvement and a decrease in bleeding can be seen within a few days. However, complete healing usually requires four to six weeks or longer, and we recommend continued treatment for six to eight weeks followed by a gradual taper and discontinuation as tolerated. (See 'Maintenance therapy' below.)
Subsequent and alternative approaches — Other treatment approaches may be required for patients whose symptoms do not respond to topical treatment with 5-ASA medications, who cannot tolerate topical 5-ASA medications, or who cannot tolerate topical therapy in general:
●Patients who are unwilling or unable to tolerate topical medications can be treated with oral 5-ASA medications alone (table 1). Although oral therapy alone is effective in the induction of remission in patients with proctitis and proctosigmoiditis, response rates are lower than topical therapy alone [27].
●Patients who cannot tolerate topical 5-ASA medications should be treated with steroid suppositories for the induction of remission, if ulcerative proctitis involves 5 to 8 cm of the distal rectum. Steroid foam preparations or enemas twice daily in combination with steroid suppositories twice daily should be used if the colitis involves greater than 8 cm of the rectum or the sigmoid colon (table 1) [28-31]. A response is usually seen three to four weeks. In patients with a clear improvement in symptoms, topical steroid treatment can be tapered gradually to a nightly regimen. (See "Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease", section on 'Side effects'.)
●For patients who do not respond to topical 5-ASA medications alone in four to six weeks, a combination of topical 5-ASA and topical steroids should be used [31]. However, this strategy is supported by limited evidence from one controlled trial in which patients treated with beclomethasone dipropionate and 5-ASA enemas had higher rates of clinical, histologic, and endoscopic improvement after four weeks of treatment compared with patients who used single-agent therapy [32].
●Patients who do not have an adequate response to topical therapy should be treated with the combination of oral 5-ASA and topical 5-ASA enemas or suppositories (table 1) [27,33]. Controlled trials have demonstrated the efficacy of both sulfasalazine and oral forms of 5-ASA in the induction and maintenance of remission in mildly to moderately active ulcerative colitis [34-43]. In one randomized trial, for example, 4.8 g/day of oral 5-ASA was significantly more likely than placebo to induce complete (24 versus 5 percent) or partial remission (50 versus 13 percent) in patients with mild to moderate ulcerative colitis [34]. We suggest the use of oral 5-ASAs to sulfasalazine, except in patients with arthritis associated with IBD, because of their better side effect profile. (See "Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease", section on 'Side effects' and "Arthritis associated with gastrointestinal disease", section on 'Treatment'.)
In patients with mild symptoms, oral 5-ASA medications should be started at the lower dose and increased to the maximum tolerated dose in patients who remain symptomatic (table 1). Patients with moderate symptoms, those with previous steroid use, those with frequent relapses, and those previously treated with oral mesalamine, rectal therapy, or multiple medications are more likely to benefit from a higher dose [44,45].
Oral mesalazine generally acts in two to four weeks [27]. Patients who fail to respond to combination therapy with oral 5-ASA and topical 5-ASA/steroids require treatment with oral glucocorticoids, as discussed under left-sided colitis below. (See 'Subsequent approach' below and 'Management of persistent symptoms' below.)
Maintenance therapy — Maintenance therapy is not recommended in patients with a first episode of mild ulcerative proctitis that has responded promptly to treatment. Many such patients may continue for long periods of time without a relapse and, if it does occur, the response to therapy is often prompt and complete.
Maintenance therapy is recommended in patients with ulcerative proctitis who have more than one relapse a year and in all patients with proctosigmoiditis [46]. Discontinuation of medication in these patients should only be considered if they have been in remission for two years and are averse to taking medication [46].
For patients on topical therapy for induction of remission, we recommend a maintenance regimen of one 5-ASA suppository in patients with proctitis and 5-ASA enema every night in patients with proctosigmoiditis (table 1) [47-51]. In our experience, patients treated with less frequent maintenance therapy (every other day) often have poor compliance and risk relapse; we therefore rarely recommend a maintenance regimen less frequent than one every night [52]. Steroid enemas should be avoided for the maintenance of remission as their efficacy has not been established and they may be associated with steroid side effects [53].
Patients who require an oral 5-ASA to achieve remission or have multiple relapses on topical therapy should be continued on oral 5-ASAs to maintain remission (table 1). Patients with frequent relapses may benefit from a higher dose of maintenance therapy [43]. A systematic review estimated that oral 5-ASA medications were associated with more than a 50 percent decrease in the risk of relapse compared with placebo [53].
Left-sided colitis, extensive colitis, and pancolitis — Patients with mildly or moderately active left-sided colitis and pancolitis benefit most from combination therapy with oral 5-ASA medications, 5-ASA or steroid suppositories, and 5-ASA or steroid enemas or foam (table 1) [54].
Initial approach — Combination of oral plus rectal 5-ASA has been associated with a higher rate and a reduced time to remission compared with either therapy alone [27,54]. In a placebo-controlled trial, 127 ambulatory patients with mild/moderate extensive ulcerative colitis received 4 g/day oral mesalamine for eight weeks [54]. During the initial four weeks, they additionally received an enema at bedtime containing 1 g of mesalamine or placebo. Remission rates were higher in patients treated with oral and topical mesalamine compared to oral mesalamine alone both at four weeks (44 versus 34 percent) and eight weeks (64 versus 43 percent). The increased response with combination therapy may be due to the additive effects of oral plus rectal 5-ASA, since the efficacy of 5-ASA is dose-dependent.
A number of different formulations of oral 5-ASA have been developed that permit site-specific, targeted delivery of higher concentrations of 5-ASA. All mesalamine preparations appear to be equally effective [55-59]. However, a 2009 meta-analysis suggested that balsalazide may be marginally more effective than mesalamine in the induction of remission, but not in rates of relapse or adverse events [60]. (See "Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease".)
Oral 5-ASA medications can be started at the lowest dose (table 1). In patients who remain symptomatic despite combination therapy (oral 5-ASA and topical 5-ASA/steroids), the dose of oral 5-ASA medications should be increased to the maximum tolerated dose [61].
In addition to oral 5-ASA, we recommend treatment with 5-ASA enemas given twice daily in addition to 5-ASA suppositories twice daily (table 1). Patients who cannot retain enemas due to rectal irritability should be treated with 5-ASA foam preparations where available. These patients may have an improvement in urgency or tenesmus with topical treatment aimed at the rectum despite also having more proximal disease [62].
5-ASA medications exert their effect in two to four weeks and are effective in 40 to 80 percent of patients [24,63]. Patients who do not respond in two weeks should be treated with topical rectal therapy with steroid-containing foam twice daily and/or suppositories twice daily combined with oral 5-ASA therapy.
Subsequent approach — For patients with mild to moderate ulcerative colitis who do not tolerate or who have an inadequate response to the combination of oral 5-ASA and topical 5-ASA/steroids within two to four weeks, we suggest multimatrix (MMX) budesonide prior to the use of other oral glucocorticoids (table 1). Budesonide-MMX uses colonic release technology to extend the application of budesonide throughout the colon. In two large randomized trials, budesonide at a dose of one 9 mg daily for eight weeks was significantly more effective in inducing endoscopic and clinical remission in patients with mild to moderate active ulcerative colitis as compared with placebo [64,65]. There were no significant steroid-related side effects [64,65].
In patients with severe symptoms and those who fail to respond to budesonide-MMX, we suggest oral prednisone. Oral glucocorticoids are highly effective in inducing remission in patients with active ulcerative colitis [12,64,66,67]. In one study, oral prednisolone induced remission in 77 percent of 118 patients with mild to moderate disease within two weeks, compared with 48 percent treated with sulfasalazine [68]. Prednisone is usually effective within 10 to 14 days, after which the dose can be tapered gradually. (See 'Maintenance therapy' below.)
Patients who have an inadequate response to glucocorticoids should be carefully evaluated to determine the cause for persistent symptoms (see 'Management of persistent symptoms' below).
Maintenance therapy — Maintenance therapy is recommended in all patients with left-sided colitis, pancolitis, or extensive colitis [46]. 5-ASA medications are highly effective in the maintenance of remission in patients with ulcerative colitis [69-74]. In a 2011 meta-analysis of 11 randomized controlled trials, the risk of relapse was significantly lower in patients with quiescent ulcerative colitis treated with 5-ASAs as compared with placebo (relative risk 0.65, 95% CI 0.55-0.76) [74]. Combination therapy with oral and intermittent rectal therapy may be better than oral therapy alone for maintaining remission [33].
After an adequate clinical response and/or remission has been achieved, usually in six to eight weeks, oral 5-ASAs should be continued to maintain remission (table 1). In our experience, a dose of at least 3 g/day is efficacious in maintaining remission, but in some patients, tapering the dose below 3 to 3.6 g/day can lead to earlier relapse. Patients with exacerbations on lower maintenance doses will often require higher doses to prevent recurrence [43].
The frequency of 5-ASA enemas and/or suppositories can be gradually reduced from twice daily to once daily for long-term maintenance therapy. In our experience, patients treated with less frequent maintenance therapy (every other day) often have poor compliance and risk relapse. Steroid enemas should be avoided for the maintenance of remission as their efficacy has not been established and they may be associated with steroid side effects [53].
Although maintenance therapy with budesonide-MMX has not yet been proven, additional eight-week courses can be given for recurring episodes of active, mild to moderate ulcerative colitis. Oral glucocorticoids including prednisone should not be used for maintenance of remission, since they have not been proven to be beneficial [64,75]. Glucocorticoids should be tapered after the patient has been stable for two to four weeks. Steroids should be tapered over eight weeks by decreasing the dose by 5 to 10 mg every week until a daily dose of 20 mg is reached, and then by 2.5 mg every week [76]. More rapid reduction has also been associated with early relapse and may be associated with adrenal insufficiency [46]. (See "Major side effects of systemic glucocorticoids" and "Glucocorticoid withdrawal".)
If glucocorticoids cannot be tapered to less than 10 mg daily within three months of starting steroids without recurrent disease, or if relapse occurs within three months of stopping glucocorticoids, patients are considered to have steroid-dependent ulcerative colitis [77]. Such patients should be carefully evaluated to determine the cause of persistent symptoms (see 'Management of persistent symptoms' below and "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Steroid-dependent ulcerative colitis').
MANAGEMENT OF PERSISTENT SYMPTOMS — Despite the approaches described above, some patients continue to have severe gastrointestinal symptoms. Patients with continued symptoms should be carefully reassessed, paying specific attention to the type of ongoing symptoms, the degree to which symptoms have improved or worsened, and compliance with medications.
Reassessment of the extent of disease is indicated if a patient has a recurrence of symptoms after initial improvement that does not mimic the initial presentation. (See "Endoscopic diagnosis of inflammatory bowel disease", section on 'Role in differential diagnosis'.)
Patients who fail to respond fall into the following categories:
●Those whose symptoms are not due to inflammatory bowel disease. These patients may have an alternative or concomitant diagnosis. (See 'Pretreatment evaluation' above.)
It is important to recognize that some symptoms in patients with chronic ulcerative colitis are not directly due to the underlying inflammatory process. Many patients have both inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). (See "Irritable bowel syndrome in patients with inflammatory bowel disease" and "Nutrition and dietary interventions in adults with inflammatory bowel disease", section on 'Dietary interventions'.)
●Patients who are noncompliant or incompletely compliant with therapy [78]. Compliance with medications and enemas in particular should be sought, as many patients have difficulty with retention of enemas. Such patients can be treated with topical steroid preparations in the form of foams, and steroid-containing suppositories can be useful in patients with severe rectal symptoms of urgency and tenesmus. (See 'Ulcerative proctitis or proctosigmoiditis' above.).
●Regardless of the extent of colonic involvement, some patients remain symptomatic despite optimal doses of oral 5-ASA drugs, topical therapy with either 5-ASA or steroids, and systemic glucocorticoids.
Patients without a meaningful clinical response to glucocorticoids up to doses of prednisone 40 to 60 mg/day (or equivalent) within 30 days for oral therapy or 7 to 10 days for intravenous therapy are considered to have steroid-refractory disease. For patients with steroid-refractory ulcerative colitis, additional medical therapy with cyclosporine as a short-term "bridge" to therapy with longer acting medications (AZA or 6-MP) or an anti-tumor necrosis factor (anti-TNF) agent should be considered. The management of patients with steroid-refractory ulcerative colitis is discussed in detail separately. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Steroid-refractory ulcerative colitis'.)
SYMPTOMATIC TREATMENT — Concomitant symptomatic treatment for diarrhea and abdominal pain may be used for a short duration (7 to 10 days) only while waiting for anti-inflammatory medications to take effect in patients with mild ulcerative colitis symptoms and no signs of systemic toxicity.
●In patients who have mild intermittent diarrhea without signs of systemic toxicity, antidiarrheal agents may be beneficial, particularly at night to decrease the frequency of nocturnal episodes (see 'Assessment of clinical severity' above). Loperamide is preferred because of its safety and efficacy [79].
In the author’s experience, bulk agents such as psyllium or methylcellulose or pectin may also be helpful while avoiding the risk of precipitating toxic megacolon.
●Abdominal cramping in patients with mildly active ulcerative colitis without signs of systemic toxicity can be relieved by anticholinergic medications such as propantheline, dicyclomine, and hyoscyamine sulfate (see 'Assessment of clinical severity' above). However, systemic side effects are common since these agents do not selectively affect the intestine.
Opiates should be avoided because they can mask the signs and symptoms of an acute abdomen, and their addiction potential. Nonsteroidal antiinflammatory drugs should be avoided because they can exacerbate IBD.
OTHER MANAGEMENT ISSUES — It is important to consider routine health maintenance, including screening and prevention of other diseases as well as monitoring for side effects of therapy in patients with inflammatory bowel disease (IBD) [80-82].
Immunization — Patients with IBD are at increased risk for infections due to their underlying disease, malnutrition, surgery, or immunosuppressive medications [83-85]. Routine vaccination status should be reviewed at the time of diagnosis, and patients should be immunized in accordance with guidelines (figure 1). Regardless of immunosuppression, all patients should be vaccinated for influenza and pneumococcal infection. In patients on immunosuppressants, live vaccines (eg, MMR, varicella, zoster) are contraindicated (figure 2). If live vaccines are required, they should be administered 4 to 12 weeks prior to the initiation of immunosuppression. Patients should be screened for hepatitis B before initiating anti-TNF therapy, and individuals who are seronegative should be vaccinated for hepatitis B [86]. (See "Approach to immunizations in healthy adults", section on 'Immunization schedule for healthy adults'.)
Cancer screening
Colorectal cancer — Patients with IBD are at increased risk for colorectal cancer (CRC) and should undergo CRC screening with colonoscopy based on the extent and duration of their disease [87-95]. (See "Colorectal cancer surveillance in inflammatory bowel disease", section on 'Surveillance' and "Colorectal cancer surveillance in inflammatory bowel disease", section on 'Recommendations of major societies'.)
It is unclear if 5-ASA medications confer a protective effect against CRC and dysplasia risk in patients with ulcerative colitis. While the reduction in CRC risk is biologically plausible by reduction of inflammation, the results of two meta-analyses have been conflicting. A 2005 meta-analysis, which largely included case-control studies, estimated that the risk of CRC was reduced by approximately 50 percent (0.51, 95% CI 0.37-0.69) [96]. However, the results of a 2012 meta-analysis varied based on the referral population included in the analysis. The results of pooled analysis of non-referral populations, although limited by heterogeneity, failed to demonstrate a protective effect of 5-ASAs (odds ratio [OR] 0.82, 95%, CI 0.54-1.26). Whereas a pooled analysis of nine clinic-based studies demonstrated a 42 percent decrease in CRC risk with 5-ASAs (OR 0.58, 95% CI 0.45-0.75). (See "Colorectal cancer surveillance in inflammatory bowel disease".)
Cervical cancer — The prevalence of abnormal Pap smears is higher in women with IBD on corticosteroids and immunosuppressants [97]. Compliance with cervical cancer screening is low in women with IBD [98]. Screening for cervical cancer, in accordance with guidelines, should therefore be recommended. (See "Screening for cervical cancer".)
Skin cancer — Patients with IBD on 6-MP/azathioprine are at an increased risk of nonmelanoma skin cancer. Patients should be advised to avoid excessive sun exposure and use a high-strength sunscreen and sun protective measures [31]. (See "Dermatologic and ocular manifestations of inflammatory bowel disease", section on 'Rare dermatologic diseases' and "Selection of sunscreen and sun-protective measures", section on 'Selection of sunscreen products'.)
Osteoporosis screening — Patients with IBD are at increased risk for bone loss [99]. Screening for osteoporosis should be performed in all IBD patients who meet one of the following criteria: postmenopausal, ongoing corticosteroid treatment, cumulative prior use of corticosteroids exceeding three months, history of low-trauma fractures, or age over 60 years. Our approach is consistent with current guidelines [100].
IBD patients on glucocorticoids (any dose with an anticipated duration of ≥3 months) should maintain a total calcium intake of 1200 mg/day and vitamin D intake of 800 international units/day through either diet and/or supplements. Treatment with bisphosphonates in patients with IBD, based on age, gender, and the presence of existing osteoporosis, is discussed in detail separately. (See "Prevention and treatment of glucocorticoid-induced osteoporosis", section on 'Candidates for pharmacologic therapy'.)
Anxiety/depression screening — Many IBD patients suffer from anxiety and depression secondary to their disease process and should be screened for these conditions [101-103]. Patients with underlying anxiety and depression may benefit from other specific pharmacologic interventions. In addition, tricyclic antidepressants, even in low doses, can improve sleep quality while decreasing cramping and diarrhea due to their anticholinergic effects. (See "Unipolar major depression in adults: Choosing initial treatment".)
Laboratory monitoring — Periodic laboratory monitoring is necessary to detect complications associated with IBD and side effects of medical therapy. Approximately 35 to 90 percent of adults with IBD are iron deficient. Other potential causes of anemia in patients with IBD include anemia of chronic disease, vitamin B12 deficiency, folic acid deficiency, or drug-induced anemia (eg, in patients treated with sulfasalazine or thiopurines). (See "Nutrient deficiencies in inflammatory bowel disease", section on 'Iron'.)
In patients with IBD, hematocrit should be measured every 6 to 12 months [31]. In patients with anemia or those with low MCV, ferritin, transferrin saturation, and C-reactive protein (CRP) should also be checked. The CRP is important in the interpretation of the ferritin level, as ferritin is an acute phase reactant. Ferritin levels less than 100 mg/L are suggestive of iron deficiency. (See "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults" and "Anemia of chronic disease/inflammation", section on 'Concomitant iron deficiency'.)
For patients on 5-ASA agents, serum creatinine should be measured at 6 and 12 months after initiation of therapy and then annually [104]. For patients on 6-mercaptopurine/azathioprine, weekly blood monitoring (ie, hemoglobin, white blood cell count, platelet count, liver blood tests [serum aminotransferases and total bilirubin], and amylase) should be performed for the first month or until the maintenance dose is reached. Monitoring should be continued for the duration of therapy and performed at least every three months. (See "Azathioprine and 6-mercaptopurine in inflammatory bowel disease", section on 'Laboratory testing' and "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Cyclosporine'.)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Ulcerative colitis in adults (The Basics)")
●Beyond the Basics topics (see "Patient education: Ulcerative colitis (Beyond the Basics)" and "Patient education: Sulfasalazine and the 5-aminosalicylates (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Ulcerative colitis is a chronic inflammatory condition characterized by relapsing and remitting episodes of inflammation that involves the rectum and may extend in a proximal and continuous fashion to involve other portions of the colon. (See 'Introduction' above.)
●When a patient with ulcerative colitis presents with recurrent symptoms, some aspects of the initial evaluation, including laboratory studies and endoscopy, need to be repeated in order to exclude alternative and/or comorbid conditions as a cause for their symptoms, as well as to assess the current extent of disease involvement and disease severity in order to best guide treatment. (See 'Pretreatment evaluation' above.)
Ulcerative proctitis or proctosigmoiditis
●In patients with mildly or moderately active proctitis or proctosigmoiditis, we recommend topical 5-aminosalicylic acid (5-ASA) to induce remission (table 1) (Grade 1A). Suppositories alone are effective in managing proctitis, while patients with proctosigmoiditis require enemas in addition to suppositories. (See 'Initial approach' above.)
●Alternative treatment approaches may be required for patients who cannot tolerate topical 5-ASA medications, topical therapy in general, or who do not respond to topical treatment with 5-ASA medications (table 1):
•For patients who cannot tolerate topical 5-ASA medications, we recommend steroid foam preparations and steroid suppositories (Grade 1B).
•For patients unwilling or unable to tolerate any topical medication, we recommend oral 5-ASA medications (Grade 1A).
•For patients who do not respond to topical 5-ASA medications, we suggest combination topical 5-ASA and steroid foam preparation (Grade 2B).
•For patients who do not respond to topical medications, we recommend combination therapy with oral and topical 5-ASA agents and topical steroids (Grade 1A).
●For maintenance of remission in patients who have more than one relapse a year and in all patients with proctosigmoiditis, we recommend 5-ASA enemas (table 1) (Grade 1A). Patients who required oral 5-ASAs to achieve remission or who have multiple relapses on topical therapy should be continued on oral 5-ASAs to maintain remission. (See 'Maintenance therapy' above.)
Left-sided colitis, extensive colitis, or pancolitis
●In patients with mildly or moderately active left-sided colitis/extensive/pancolitis, we recommend combination therapy with oral 5-ASA medications, rectal 5-ASA or steroid suppositories, and 5-ASA or steroid enemas or foam preparations (table 1) (Grade 1A). (See 'Initial approach' above.)
●In patients who fail to respond to combination therapy with oral 5-ASA medications and topical 5-ASA and steroids, we recommend oral glucocorticoids (table 1) (Grade 1B). (See 'Subsequent approach' above.)
●We recommend maintenance therapy with combination oral and topical 5-ASA therapy (table 1) (Grade 1A). After an adequate clinical response and/or remission has been achieved, the dose of oral 5-ASA should be continued to maintain remission and topical 5-ASA therapy can be tapered to once a day. Glucocorticoids should be tapered after the patient has been stable for two to four weeks. (See 'Maintenance therapy' above.)
Patients with persistent symptoms despite glucocorticoids or steroid-dependent ulcerative colitis should be carefully evaluated to assess medication compliance, rule out other concomitant diseases, and to determine the need for additional medical therapy. (See 'Management of persistent symptoms' above.)
●It is important to consider health maintenance issues in patients with inflammatory bowel disease (IBD). This includes vaccination to prevent infections, screening for cancer and anxiety/depression, prevention of and monitoring for bone loss, and laboratory monitoring for complications of IBD and medication side effects. (See 'Other management issues' above.)
REFERENCES
Contributor Disclosures: Richard P MacDermott, MD Nothing to disclose. Paul Rutgeerts, MD, PhD, FRCP Consultant/Advisory Boards: Johnson & Johnson; UCB; AbbVie; Takeda; Genentech; Bristol-Myers Squibb; Tillotts Pharma; Parexel; Quintiles; Amgen/Medimmune/AstraZeneca; [IBD treatment (infliximab, ustekinumab, certolizumab pegol, adalimumab, vedolizumab, etrolizumab, mesalamine)]. Shilpa Grover, MD, MPH Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
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