We searched PubMed for articles published up to Aug 31, 2017. We used general search terms, such as “[inflammatory bowel diseases OR Crohn OR ulcerative colitis] AND [differential]”, and specific search terms were used to identify further differential diagnoses, including “[colitis OR proctitis OR enteritis] AND [intestinal tuberculosis OR Yersiniases OR Y enterocolitis OR Actinomycosis OR Actinomyces israelii OR chlamydiasis OR Chlamydia trachomatis OR herpes simplex OR syphilis OR Treponema
ReviewDifferential diagnosis of inflammatory bowel disease: imitations and complications
Introduction
Ulcerative colitis and Crohn's disease, also known as inflammatory bowel disease (IBD), are characterised by episodes of relapse and periods of remission. The clinical features typically include abdominal pain, diarrhoea, and rectal bleeding. However, many other intestinal or systemic symptoms can occur, such as weight loss, fever, fatigue, nausea or vomiting, or even extra-intestinal disease manifestations.1, 2 Available biomarkers do not have the specificity to differentiate IBD from other causes of ileocolitis.3 Serological tests, such as anti-neutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibodies, have low diagnostic accuracy and are therefore used as adjunct measures to diagnosis.1 Characteristic endoscopic findings of ulcerative colitis include confluent colonic inflammation commencing from the anal verge, which typically involves the rectum, and a clear demarcation of the inflammation.4 Crohn's disease features patchy inflammation with so-called skip lesions and areas of macroscopically normal mucosa in between. Inflammation in Crohn's disease is represented by aphthous, deep, linear, stellate, or serpiginous ulcers, which can be associated with a cobblestone appearance.4 Two representative biopsies from each of the six segments that are visualised during colonoscopy are recommended to obtain a diagnosis of Crohn's disease.4 Basal plasmacytosis is the earliest histopathological feature with the highest predictive value for diagnosis of ulcerative colitis.5 Mucosal or crypt architectural distortion appear afterwards during progression of the disease. Non-caseous granulomas are detectable in about 50–60% of cases of Crohn's disease, with detection depending on the severity of inflammation and the number and location of biopsies taken.6
Although these characteristic diagnostic findings are well known, none of the individual items is solely specific for IBD. Therefore, diagnosis is always based on the combination of clinical symptoms, serology, imaging and endoscopy appearance, and histopathology.1, 2 The differential diagnosis includes a broad spectrum of inflammatory diseases that mimic IBD or others that can complicate existing IBD.
The purpose of this Review is to provide an overview of various causes of ileocolitis that are relevant for the differential diagnosis of IBD. We highlight the importance of patient profiling and provide a practical approach to identify factors that should trigger the search for a specific cause of intestinal inflammation. Additionally, special consideration is dedicated to the differential diagnosis of perianal disease.
Section snippets
Intestinal tuberculosis
Tuberculosis is a primary differential diagnosis of IBD in patients in endemic areas, in patients migrating or travelling from endemic areas, and in immuno-compromised individuals.7 The pathophysiological mechanisms of intestinal tuberculosis transmission include the ingestion of infected sputum or contaminated beverages, but the disease can also be haematogenous or spread directly from adjacent organs in an individual with tuberculosis.8 The clinical presentation of intestinal tuberculosis can
Ischaemic colitis
Ischaemic colitis arises when blood supply is acutely compromised in a setting of low flow state, such as cardiac insufficiency or dehydration. However, in most cases, no specific cause can be identified.34 Transient ischaemia leads to mucosal damage first at the most vulnerable sites, such as the splenic flexure and the rectosigmoid junction, where the so-called watershed areas of vascular supply are located.35 By contrast with other inflammatory or infectious conditions, symptoms of ischaemic
Non-steroidal anti-inflammatory drugs (NSAIDs)
The upper gastrointestinal damage caused by NSAIDs is well known. However, lower gastrointestinal injury is also common, although frequently subclinical.44 Diaphragm-like strictures are pathognomonic of NSAID injury.45 Multiple lesions can occur and cause obstructive symptoms, which can require balloon dilation—if the area is endoscopically accessible—or surgical resection. Further non-specific findings can include erosions, ulcers, and colitis, all of which should improve after drug
Monogenic diseases that mimic IBD
Children with very early disease onset (ie, aged 6 years or younger) have a particularly high risk of having an IBD-like intestinal inflammation induced by an underlying monogenic disease.55 Although challenging, diagnosis should be sought, because mortality and morbidity is high for these monogenic diseases and treatment options can differ from those for IBD.
Monogenic diseases have been found to alter intestinal immune homoeostasis through several mechanisms; for example, X-linked ectodermal
Segmental colitis associated with diverticulosis (SCAD)
Patients with SCAD usually present with rectal bleeding and, occasionally, with abdominal pain and diarrhoea. The endoscopic appearance of SCAD is typically segmental colitis restricted to the sigmoid colon, in the area of the diverticular disease (figure 3).63 Histological examination can reveal non-specific mucosal inflammation. SCAD has a self-limited course and usually resolves spontaneously without further recurrence.
Diversion colitis
Diversion colitis occurs in segments of the bowel that have been excluded
Clostridium difficile infection
C difficile infection has become increasingly common in patients with IBD and is associated with increased hospital admissions, colectomy rates, and mortality.68 Risk factors are similar to those in people without IBD, including antibiotic use, older age, and immunosuppressive treatment. Additionally, patients with IBD are at increased risk of a recurrent episode of C difficile infection.69 Therefore, screening for C difficile is recommended at every flare in patients with IBD and colonic
Perianal disease
During the course of Crohn's disease, approximately 30% of patients develop at least one fistulising episode.74 Perianal disease is frequently accompanied by luminal activity, but can also be the initial manifestation of Crohn's disease, preceding the onset of luminal disease in about 10% of patients.74 Additionally, non-fistulising perianal manifestations, such as skin tags, fissures, ulcers, and strictures are also associated with Crohn's disease in up to a quarter of patients. However, in
Conclusions
The clinical presentation of IBD is not specific, and diagnosis is based on the combination of symptoms, laboratory findings, imaging and endoscopy, and histopathology. The differential diagnosis includes a broad spectrum of inflammatory diseases that mimic IBD and others that can aggravate inflammation in existing IBD. In this Review, we have highlighted specific patient profiles that should trigger the search for an underlying cause, different from that of IBD. Careful profiling and
Search strategy and selection criteria
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