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Colleague's E-mail is Invalid. Your message has been successfully sent to your colleague. Save my selection. Rubin, David T. Correspondence: Millie D. E-mail: drubin medicine. Ulcerative colitis UC is an idiopathic inflammatory disorder. These guidelines indicate the preferred approach to the management of adults with UC and represent the official practice recommendations of the American College of Gastroenterology.
These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios. Ulcerative colitis UC is a chronic disease affecting the large intestine, with an increasing incidence worldwide. Nearly 1 million individuals each in the United States and Europe are affected by this condition and many more globally. Over the past decade, since the publication of the last guideline from the American College of Gastroenterology ACG on this topic, the management of disease has grown increasingly complex with availability of additional therapeutic classes.
In addition, algorithms for initiating, optimizing, and monitoring response to existing therapies have undergone considerable evolution. UC is a chronic immune-mediated inflammatory condition of the large intestine that is frequently associated with inflammation of the rectum but often extends proximally to involve additional areas of the colon. The initial presentation of new UC is characterized by symptoms of an inflamed rectum, namely, bleeding, urgency, and tenesmus a sense of pressure.
The condition may present at any time and at all ages, but there is a predominant age distribution of onset that peaks between ages 15 and 30 years. The pattern of disease activity is most often described as relapsing and remitting, with symptoms of active disease alternating with periods of clinical quiescence, which is called remission. Some patients with UC have persistent disease activity despite diagnosis and medical therapy, and a small number of patients present with the rapid-onset progressive type of colitis known as fulminant disease 2,3.
UC causes significant morbidity and a described low incidence of mortality 4,5. Patients with active disease are more likely to have comorbid psychological conditions of anxiety and depression and are more likely to have impaired social interactions or career progression 6. Long-standing UC is also associated with a defined risk of dysplasia and colorectal cancer, which is believed to be related to long-standing unchecked inflammation 7— Management of UC must involve a prompt and accurate diagnosis, assessment of the patient's risk of poor outcomes, and initiation of effective, safe, and tolerable medical therapies.
The optimal goal of management is a sustained and durable period of steroid-free remission, accompanied by appropriate psychosocial support, normal health-related quality of life QoL , prevention of morbidity including hospitalization and surgery, and prevention of cancer.
An emerging goal in UC management is that of mucosal healing. To achieve these goals, understanding of the most effective diagnostic, treatment, and preventive strategies is necessary As with any medical decision making, involvement of the patients' preferences forms an important component of care.
This clinical guideline addresses the diagnosis, treatment, and overall management of adult patients with UC, including an approach to the evaluation of the hospitalized patient and a separate section on colorectal cancer prevention. Additional recommendations regarding preventive care in inflammatory bowel disease IBD have been published by the ACG previously The guideline is structured in sections, each with recommendations, key concept statements, and summaries of the evidence.
Each recommendation statement has an associated assessment of the quality of evidence and strength of recommendation based on the Grading of Recommendations Assessment, Development, and Evaluation GRADE process. The quality of the evidence is graded from high to low. Key concepts are statements that are not amenable to the GRADE process, either because of the structure of the statement or because of the available evidence.
Symptoms of bloody diarrhea, mucous, urgency, tenesmus, and abdominal cramping should trigger consideration of a UC diagnosis, particularly in the absence of an alternate cause. A full clinical history should include assessment of severity of disease, triggers precipitating onset, and potential alternate etiologies. Symptoms assessed should include frequency of bowel movements, including number of nocturnal bowel movements.
Assessment of bleeding should include the proportion of bowel movements that are mixed with blood. Other important symptoms to assess include urgency, abdominal pain, cramping, and weight loss, a marker of severity of disease.
In addition, a thorough history should assess the presence of extraintestinal manifestations, including joint, skin, ocular, and oral manifestations, and symptoms suggesting hepatobiliary involvement. Potential precipitants of UC may include recent smoking cessation 14 , nonsteroidal anti-inflammatory drug NSAID use 15,16 , and enteric infections Testing for C. Other enteric infections that could mimic UC include infection with Escherichia coli E.
Therefore, an infectious etiology should always be suspected and excluded at the time of diagnosis in the right clinical setting. Several institutions use comprehensive intestinal pathogen testing through PCR-based assays that include many bacterial and viral pathogens. The prevalence and impact of non— C. The diagnosis of UC requires a lower gastrointestinal endoscopic examination with histologic confirmation.
For most patients, a complete colonoscopy including examination of the terminal ileum should be performed. This allows for assessment of the full extent of disease at diagnosis and can rule out distal ileal involvement, which can be seen with CD. Subsequent examinations can then assess response to therapy. However, in individuals with severe disease, a complete colonoscopy may be associated with a greater risk of perforation, and in this case, a sigmoidoscopy with biopsies is sufficient.
Endoscopically, UC most often presents as a continuously inflamed segment involving the distal rectum and extending proximally. Endoscopic features of inflammation include loss of vascular markings, granularity and friability of the mucosa, erosions, and, in the setting of severe inflammation, deep ulcerations and spontaneous bleeding. The index colonoscopy should note involvement of the rectum and complete extent of inflammation.
Proximal histologic extension may be seen even in endoscopically normal-appearing colon and may have implications for defining the extent of disease and subsequent surveillance intervals. Therefore, biopsies should be obtained from the proximal endoscopically normal-appearing colon even if the inflamed segment appears to be restricted to the distal colon. Routine upper endoscopic evaluation is not required in adults with a new diagnosis of UC and should be restricted to those with symptoms of upper gastrointestinal disease.
Gastritis and erosions may be seen in up to one-third of patients with UC Imaging the small bowel with computed tomography CT or magnetic resonance imaging is also not routinely required in all patients with normal appearance of the terminal ileum on colonoscopy.
However, in those with abdominal symptoms not explained by endoscopically active disease, with suspicion of CD such as predominantly watery diarrhea, weight loss, or abdominal pain , or where proximal extent of involvement cannot be evaluated because of severity of inflammation, CT, magnetic resonance imaging, or video capsule endoscopy may be useful. Once a diagnosis of UC is made, determining the severity of disease becomes important.
We have proposed new definitions of mildly, moderately, and severely active disease that incorporate both PROs and laboratory- and endoscopy-based values Table 4 and Figure 1. Although such markers are nonspecific and may be elevated with other causes of systemic inflammation, they often correlate with the endoscopic severity of disease Such markers also have prognostic significance and have a role in predicting the risk of colectomy 31—33 and response to therapy 32— However, up to a quarter of patients with endoscopically active disease may have a normal CRP, and the frequency of elevation is lower in individuals with mild endoscopic activity.
Measurement of hemoglobin and serum albumin levels at diagnosis can be helpful in assessing disease severity and prognosis.
Demonstration of fecal leukocytes alone is not sufficiently sensitive, nor is it specific for the diagnosis or assessment of the activity of UC. FC is a nonspecific neutrophilic marker of inflammation and is elevated in infectious and inflammatory colitis but not in noninflammatory causes of diarrhea such as irritable bowel syndrome. The pooled sensitivity and specificity of elevated FC for diagnosis of UC are 0. In a primary care population, FC in patients with suspected UC diarrhea and rectal bleeding can be used to prioritize patients for colonoscopic evaluation, particularly among children 36, The utility of FC as a marker of inflammation and treatment target is discussed in the management section.
However, the pooled sensitivity of antibody testing for diagnosis of UC is low, and such markers are not used for establishing or ruling out a diagnosis of UC Although pANCA positivity has also been associated with treatment refractory UC, the evidence supporting this is limited, and there is currently no role for such testing to determine the likelihood of disease evolution and prognosis 40, Determination of the extent and severity of disease is important to select the appropriate treatment algorithm.
Extent of the disease should be characterized according to the Montreal classification as proctitis E1 , left-sided colitis E2 , or extensive colitis E3 extension proximal to the splenic flexure 42, Commonly, severity of UC has been classified according to the Truelove and Witts' 44 criteria published in Severe disease is defined by bowel frequency greater than 6 times a day in conjunction with fever, tachycardia, anemia, or an elevation in ESR.
Although simple to use and useful in defining the need for hospitalization, the index does not provide a quantitative or longitudinal measure of severity, excludes other important symptoms such as nocturnal symptoms and extraintestinal manifestations, and does not consider endoscopic severity. Although disease extent broadly affects prognosis, it should not limit therapeutic options. Although most clinical activity indexes have not been rigorously validated, there is broad agreement between most of the indexes 52 , and they generally correlate well with endoscopic disease activity.
The PRO2 derived from components of the Mayo score has been shown to discriminate between active drug and placebo and yielded similar effect sizes for remission when applied to previously collected clinical trial data. This has been proposed as an interim outcome measure when combined with endoscopic data Ongoing efforts also aim to develop and validate PROs that incorporate patients' perception of severity of disease; 55 preliminary work suggests that such PROs correlate well with established disease activity indexes and may improve the ability to predict patient-defined remission.
Previous definitions of disease severity have been used in clinical trials but not in clinical practice. Inclusion criteria for clinical trials of agents for moderately to severely active UC have required components such as i inability to taper off prednisone, ii previous failure of immunosuppressants, and iii moderately to severely active disease defined by the Mayo score including the specific endoscopy subscore.
In clinical trials, the definition of remission has been a Mayo endoscopic subscore of 0 or 1 and lack of rectal bleeding. In clinical practice, the previously used definitions of remission refer to clinical parameters of current relapse number of bowel movements, bleeding, and evidence of toxicity such as vital signs or colonic dilation but do not include objective parameters of increased disease activity other than CRP which lacks sensitivity.
These measures also do not place the current flare in the context of the previous disease course as this guideline now recommends. In addition, when using a newer disease activity definition that takes into account disease course, any patient with more than mildly active disease should be treated according to recommendations for moderately to severely active UC. In the absence of endoscopy, other objective markers of inflammation can be considered such as normalization of CRP and FC.
More recent measures of remission now include symptomatic remission no rectal bleeding and no urgency and endoscopic evidence of mucosal healing. Retrospective data have investigated histologic remission as a potential therapeutic target and have shown histologic quiescence and histologic normalization to be predictive of relapse-free survival However, only a small percentage of patients seem to reach these end points.
The available data do not yet support histologic healing or normalization as a goal of treatment for patients with UC. With increasing recognition of endoscopic mucosal response and remission as treatment targets and their prognostic significance for future relapses, need for hospitalization, and surgery, it is essential to include endoscopic severity assessment in the diagnosis and management of UC 57, There are several tools to quantify endoscopic activity in UC, although few have been rigorously validated The Mayo endoscopic score is frequently used in clinical trials and is simple to use in clinical practice, ranging from 0 for normal or inactive disease to 3 for severely active disease Using a rigorous methodology for derivation and validation using regression models and central readings of recorded procedures, the UC Endoscopic Index of Severity UCEIS has recently been proposed Table 7 This score incorporates 3 items—vascular pattern, bleeding, and erosions and ulcers, quantifying each on a scale of 0—3 0—2 for vascular pattern for a total score ranging between 0 and 8.
The UCEIS demonstrated excellent correlation with disease severity 60 and good intra- and inter-observer reliability 60, Preliminary data suggest that this score is also responsive to therapy, and improvement with treatment predicts medium- and long-term outcomes
Typically ulcerative colitis manifests in young adults years of age and is more prevalent in males but the onset of disease after age of 50 is also common 1,3,5. A combination of environmental and genetic factors are thought to play a role in the pathogenesis, although the condition remains idiopathic. Ulcerative colitis is less prevalent in smokers than in non-smokers. C-reactive protein levels are usually normal 6. Unlike Crohn disease which is characteristically a transmural disease, ulcerative colitis is usually limited to the mucosa and submucosa 5.
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This article summarises the essential facts on the diagnosis and treatment of ulcerative colitis and is aimed at general practitioners who manage this condition. Ulcerative colitis is a form of inflammatory bowel disease characterised by diffuse inflammation of the colonic mucosa. It affects the rectum and extends proximally along a variable length of the colon. The disease can be categorised as left sided colitis inflammation up to the splenic flexure or extensive colitis inflammation beyond the splenic flexure. These categories are useful when formulating treatment options and planning the timing of surveillance colonoscopy, which is used to detect and prevent colorectal carcinoma. Colitis affects about one in people in the Western world.
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