Inflammatory bowel disease–like conditions: other immune-mediated gastrointestinal disorders

Abbreviations

Introduction

Immune-mediated disorders (IMDs) comprise a wide array of gastrointestinal (GI) and extraintestinal phenotypes. Inflammatory bowel disease (IBD), that is, Crohn’s disease (CD) and ulcerative colitis (UC) are the primary forms. Current theories hold that IMD results from dysregulated innate and adaptive immune response to environmental or microbiological factors in genetically susceptible hosts. Multiple layers of the interaction of these factors lead to various forms of IMD. For example, abnormal innate immunity plays a dominant role in the pathogenesis of autoinflammatory diseases (AIDs), while dysregulated adaptive immunity exerts a major role in the development of autoimmune enteropathy (AIE). Abnormalities of both innate and adaptive immunities impact the pathogenesis of IBD.

The etiopathogenetic pathways, clinical presentations, endoscopic features, and histologic characteristics overlap between classic IBD, autoimmune disorders, and AIDs. In addition, IMD can be triggered by factors, such as bowel altering surgery and medications. For example, bariatric surgery or liver or kidney transplantation may be associated with the development of de novo IBD. Immune checkpoint inhibitors (ICPis) are known to cause IBD-like IMD.

The association between GI IMD and extraintestinal IMD is mutual or multilayered. Patients with IBD often present with extraintestinal immune-mediated systemic disorders such as erythema nodosum, pyoderma gangrenosum, and primary sclerosing cholangitis (PSC). IBD may also have concurrent autoimmune disorders, such as rheumatoid arthritis (RA) and psoriasis. On the other hand, systemic autoimmune disorders or AID may affect the GI tract. For example, patients with systemic lupus erythematosus (SLE) may have lupus enteritis resulting from lupus vasculitis.

Within GI manifestations of IMD, there are overlaps of disease phenotypes too. For example, IBD and celiac disease (CeD) or microscopic colitis (MC) may coexist. The coexisting disease phenotypes may develop concurrently or sequentially. For example, lymphocytic colitis (LC) may progress to CD. The complexity of interactions between GI and extraintestinal IMD has led to a new classification of broad-sensed IBD, as outlined in Chapter 1 , Introduction and classification of inflammatory bowel diseases.

Endoscopic features of these IMDs are discussed in this chapter, which include ICPi-associated colitis. Other oncology medicine-associated IBD-like conditions are discussed in a separate chapter ( Chapter 29 : Inflammatory bowel disease–like conditions: medication-induced enteropathy). Immune-mediated vasculitis-associated GI disorders are discussed in a separate chapter ( Chapter 28 : Inflammatory bowel disease–like conditions: ischemic bowel diseases and vasculitides).

Celiac disease

CeD is also called gluten-sensitive enteropathy and nontropical sprue. There is a gradient in the decreasing disease severity from the proximal to the distal small intestine. Therefore duodenal biopsy plays a critical role in the diagnosis and differential diagnosis. Common endoscopic features of CeD are atrophic mucosa with loss of folds or sparse folds, mosaic patterns, visible fissures, granularity, nodularity, scalloping, and prominent submucosal vascularity ( Figs. 26.1–26.4 ). However, these endoscopic features suggestive of CeD yield a low diagnostic sensitivity and high specificity. These endoscopic features can also be seen in CD or UC involving the duodenum, or AIE. Histology is more reliable for the diagnosis of CeD than endoscopy and serology. At least four biopsies of postbulbar duodenum along with 1–2 biopsies of the bulb should be taken and separately labeled. Primary histologic features are mucosal inflammation of lymphocytes, crypt hyperplasia, and villous atrophy ( Fig. 26.3D ).

Collagenous sprue, a rare, little-understood disorder, is characterized by subepithelial collagen deposition. Patients with CeD carry a risk for the development of enteropathy-associated T-cell lymphoma, which shares some of the endoscopic features of duodenal CD, including edema, erythema, granularity, and ulcers of the duodenum ( Fig. 26.5 ).

There is an association between CeD and IBD . The risk of IBD in patients with CeD was elevated . In contrast, the risk for CeD in IBD patients was comparable to controls . Patients may have coexisting CeD and IBD . Patients with coexisting IBD and CeD have been shown to have a higher frequency of PSC, extensive UC, and family history of CeD than those with IBD alone ( Fig. 26.4 ) . Evaluation of CeD should be performed in IBD patients with persistent iron deficiency anemia which poorly responds to iron supplement therapy. IBD-associated surgeries, such as ileal pouch–anal anastomosis, may trigger the development of de novo CeD ( Fig. 26.3 ) .

Microscopic colitis

MC consists of two primary phenotypes, LC and collagenous colitis (CC). Patients with MC often present with chronic nonbloody diarrhea. MC is named for the disease process which is detected under light microscope in the absence of obvious endoscopic abnormalities. However, endoscopic inflammation is common in MC. Association between IBD and MC has several folds: (1) patients with MC can evolve into IBD which is named IBD transformer ; (2) IBD in remission may present in MC pattern on histology; and (3) concurrent IBD and MC may also be encountered with concomitant CC and UC being the most common pattern .

Lymphocytic colitis

Colonoscopy often demonstrates normal-appearing mucosa. However, some patients may present with mild edema, erythema, loss of vascular pattern, mucosal fissures, friability, exudates, granularity, or nodularity ( Figs. 26.6 and 26.7 ). The characteristic histologic feature is intraepithelial lymphocytosis ( Fig. 26.8 ).