*Drug-Related Enteropathy DOI: http://dx.doi.org/10.5772/intechopen.103734*

current SSRI use increased risk of lymphocytic colitis (OR 2.28). Long-term PPI and/ or NSAID use had the highest odds ratio (4.6 and 4.8 respectively) for developing microscopic colitis [79]. As previously mentioned, NSAID may affect any part of the GI tract, by a number of different pathophysiologic mechanisms. In the small intestine NSAID-associated damage ranges from microscopic enteritis to severe mucosal affection with erosions and/or ulcers. Histologic manifestations of NSAID may resemble those of celiac disease, with villous blunting and intraepithelial lymphocytosis, and can be found in any part of the small intestine [80].

Eosinophilic enteritis and colitis are included in the group of eosinophilic gastrointestinal disorders, and are characterized by a high eosinophilic infiltrate in the gut wall, without evidence of other causes. Pathophysiology involves a combination of genetic predisposition, dysbiosis, and a triggering factor, usually an allergen, that may include drugs, followed by recruitment and activation of eosinophils to sites of inflammation regulated by pro-inflammatory cytokines [81]. Drugs such as clozapine, naproxen, carbamazepine, and rifampicin have been associated with increased eosinophilic infiltrate in the distal ileum and colon [77]. More recently the anti-CTLA-4 check-point inhibitor ipilimumab and the anti-PD1 nivolumab have been link to eosinophilic enteritis [70]. Other immunosuppressant drugs such as mycophenolate mofetil, a drug used to prevent acute allograft rejection may affect both small bowel and colon, causing an eosinophilic-associated damage, with features similar to those of acute graft-versus-host disease [82].

Angiotensin II receptor inhibitors (AT-II RI) are one of the most common drugs for treating high blood pressure, with a generally safe side-effect profile. In 2012 a case series of 22 patients developing chronic diarrhea and weight loss while taking olmesartan was published. None had positive celiac serology, and a combination of villous atrophy and variable degrees of inflammation including collagen deposits was observed in small intestine biopsies, with clinical and histologic recovery after discontinuation of the drug [83]. More recently, other AT-II RI have been also associated with different degrees of enteropathy. A systematic review included 248 cases, most of which were associated with olmesartan (94%), however telmisartan, irbesartan, valsartan, losartan and eprosartan also were reported to be associated with various degrees of enteropathy. Interestingly, despite negative serology in most cases, 71% had a positive HLA-DQ2 or DQ-8, haplotypes associated with celiac disease [84].
