Indeterminate colitis and inflammatory bowel disease unclassified

Abbreviations

Introduction

Disease spectrum of Crohn’s disease (CD) and ulcerative colitis (UC) is beyond the two classic phenotypes. Differential diagnosis between CD and UC is important for medical and surgical management and prognosis. For example, oral antibiotics have been used as a first-line therapy for perianal CD, Crohn’s colitis, and prophylaxis and treatment of postoperative CD, the agents are not recommended in the treatment of UC, with except in superimposed Clostridium difficile infection. Restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) is the surgical treatment of choice for patients with classic UC who require colectomy, whereas the procedure is contraindicated in the CD patients with ileitis, ileocolitis, transmural colitis,perianal disease, or upper gastrointestinal (GI) disease.

Differential diagnosis of CD and UC can be difficult. Endoscopy together with other diagnostic modalities may only differentiate CD from UC in ≥85% of patients . In a prospective study of more than 350 patients with inflammatory bowel disease (IBD) followed up for more than 22 months, index colonoscopy and biopsy were accurate in distinguishing CD from UC in 89% of cases. IBD diagnosis was revised in 4% of cases, and the diagnosis of indeterminate colitis (IC) remained in 7% of cases . A range of clinical, endoscopic, and histologic phenotypes cannot be easily classified into CD or UC. Two terms have been widely used in clinical practice, that is, IC and IBD-type unclassified (IBD-U). They may represent phenotypes of the wide spectrum of IBD ( Chapter 1 : Introduction and classification of inflammatory bowel diseases). However, the characterization of endoscopic features of IC and IBD-U will help guide clinical diagnosis, differential diagnosis, and management of the phenotypes of IBD.

Classic Crohn’s disease and ulcerative colitis

Crohn's disease can affect any part of the GI tract, from the mouth to anus or perianal area, although it is predominantly located at the distal ileum (L1 in the Montreal classification) and/or colon (L2 and L3) . The disease distribution pattern is typically discontinuous or segmental with skip lesions and rectal sparing. Anal or perianal lesions, such as fissures, fistulas, skin tags, abscesses, and perianal dermatitis, are common in CD. It appears that the disease location and length of bowel involved of a given patient remain relatively stable over the natural course. However, the transmural inflammation in CD dictates its progression to both luminal (i.e., formation of strictures) and extraluminal (i.e., formation of fistulae and abscesses). Histologic features of CD are characterized by granulomatous infiltration and transmural disease, in addition to chronic structural changes [e.g., crypt distortion, crypt branching, infiltration of mononuclear cells of any layers of the bowel wall, fibrosis, muscular hyperplasia, and Paneth cells metaplasia (of the large bowel), and pyloric gland metaplasia (of small and large bowel)]. The granulomas in CD are usually small in number and size without central necrosis, that is, epithelioid noncaseating granulomas.

The disease process of classic UC is confined to the large bowel, that is, the rectum with or without the involvement of the left part or majority of the colon, corresponding to E1, E2, and E3 phenotypes in the Montreal classification . In the time of the initial diagnosis, before the exposure to medical therapy, all patients with UC have rectal involvement. Patients with UC can have proctitis, left-sided colitis, or extensive colitis at presentation or initially have E1 or E2 disease with subsequent proximal extension. The disease distribution pattern in UC is typically continuous, with a sharp demarcation between the diseased and nondiseased segments ( Chapter 9 : Ulcerative colitis). On histology, the depth of inflammation in UC is the mucosa, muscularis mucosae, and superficial submucosa. Like CD, UC is characterized by the presence of chronic structural changes with crypt distortion, infiltration of chronic inflammatory cells in the lamina propria and superficial submucosa, basal lymphoplasmacytosis, and Paneth cells or pyloric gland metaplasia.

On histology, acute disease flare-up of CD or UC is featured with the infiltration of acute inflammatory cells such as neutrophils and eosinophils, and the development of erosions, ulcers, and microabscesses. These histologic features of acute disease activity are superimposed on chronic inflammatory structural changes. In clinical practice, mucosal healing or transmural healing after effective medical therapy is defined the absence of these acute histologic disease activities.

Distinguishing endoscopic features of CD and UC are listed in Table 10.1 .

Definitions of indeterminate colitis and inflammatory bowel disease unclassified

The terms of IC and IBD-U are used loosely and almost interchangeably in clinical practice. The working group for the Montreal classification recommended that the term of IC is limited to the setting of surgical histopathology of colectomy specimens . Patients with severe UC or Crohn’s colitis and deep ulcers may have transmural inflammation with lymphoid aggregates or microabscesses, which precludes a clear diagnosis of either disease. The term of colonic IBD-U is applied in the situation in which ileocolonoscopy is inconclusive, and endoscopic inflammation and histologic features of chronic inflammatory changes limited to the colon with the absence of diagnostic features of either CD or UC . Infectious etiologies have to be excluded. IBD-U may be applied to other situations, such as duodenitis, gastritis, aphthous small bowel ulcers, and anal fistulae in UC and Crohn’s colitis with diffuse, continuous proctocolitis. Those conditions may be categorized into CD variants or UC variants.

Crohn’s disease variants

CD may present with superficial lesions in a continuous distribution pattern.