Significance of Granulomatous Inflammation Found on Endoscopic Biopsies or Surgical Resections on the Severity of Crohn’s Disease To the Editor: The significance of gran- ulomatous inflammation (GIN) found on mucosal biopsies or in surgical resections on the course of Crohn’s disease (CD) is controversial. A 1979 study postulated that GIN helps localize infectious causes of CD pre- venting future relapses and are an indicator of a good prognosis. 1 More recent studies, however, report that granulomas are associated with a younger age of onset, more extensive inflammation, perianal complications, higher rates of systemic manifestations, and an increased need for surgery. 2–4 The current IRB-approved retro- spective chart review (1996 to 2011) was conducted to examine the sig- nificance of GIN on the severity and prognosis of CD patients. Seventy-four patients with CD and GIN and a sample of 91 patients with CD but without GIN were identified in the pathology database at Boston Medical Center and were included in this anal- ysis. A chart review recorded age, sex, race, surgery, hospitalizations, extra- intestinal manifestations, duration of follow-up after finding GIN, age at diagnosis, duration of the disease, use of 6-mercaptopurine, methotrexate, azathioprine, and anti-tumor necrosis factor agents (TNFs). For statistical analyses, bivariate analyses were ini- tially performed on data followed by multivariate analyses adjusted for race, sex, smoking, duration of follow-up, and age at diagnosis. GIN was identified on endoscopic biopsies in 37% and in surgical resec- tions in 63% of the patients in the cohort. There was no association found between the race, sex, smoking status and extraintestinal manifes- tations, and GIN. After conducting the multivariate analyses, the number of surgical resections per year of follow- up was higher in patients with GIN [relative risk = 1.43; P = 0.046; 95% confidence interval (CI), 1.0-2.0]. In comparison to non-GIN patients, patients with GIN were diagnosed with CD at a younger age (30.4 vs. 34.6; P = 0.082), had a shorter duration of disease from the time of CD diagnosis to the end of follow-up (10 vs. 16.2 y; P = 0.001), and had a shorter period of follow-up after identification of GIN (8.3 vs. 13.3 y; P = 0.005). On multivariate analyses, treatment with methotrexate, 6-mercaptopurine, and azathioprine was higher in patients with GIN (odds ratio = 3.13; P = 0.004; 95% CI, 1.4-6.8). In addition, treatment with multiple anti-TNFs was more likely in patients with GIN (odds ratio = 1.99; P = 0.087; 95% CI, 0.9-4.4). In summary, GIN was associated with younger age of diagnosis and more frequent use of immunomodulators and multiple anti-TNFs. If additional stud- ies verify these results, GIN in patients with CD should be added to the list of factors associated with more aggressive CD. Manasa Kanneganti, BA* Bijan Dehghani, BA* James Steinberg, BAw Sandra Cerda, MDz Denis Rybin, MSy Janice Weinberg, ScDy Francis A. Farraye, MD, MSc* *Boston Medical Center, Section of Gastroenterology, Boston University School of Medicine wBoston University School of Public Health zDepartment of Pathology Boston Medical Center yDepartment of Biostatistics, Boston University School of Public Health Boston, MA REFERENCES 1. Chambers TJ, Morson BC. The gran- uloma in Crohn’s disease. Gut. 1979;20: 269–274. 2. Denoya P, Canedo J, Berho M, et al. Granulomas in Crohn’s disease: does progression through the bowel layers affect presentation or predict recurrence? Colorectal Dis. 2011;13:1142–1147. 3. De Matos V, Russo PA, Cohen AB, et al. Frequency and clinical correlations of granulomas in children with Crohn’s disease. J Pediatr Gastroenterol Nutr. 2008;46:392–398. 4. Molna´r T, Tiszlavicz L, Gyulai C, et al. Clinical significance of granuloma in Crohn’s disease. World J Gastroenterol. 2005;11:3118–3121. Olmesartan-associated Sprue-like Enteropathy To the Editor: The most common cause of villous atrophy of the proximal small bowel is celiac disease, but a wide differential diagnosis exists. We report a case that illustrates an association between olmesartan, an antihypertensive medi- cation, and a sprue-like enteropathy that has not been reported previously in the gastroenterology literature. A 57-year-old woman was trans- ferred to our hospital with 3 weeks of refractory diarrhea and nausea with vomiting. Her symptoms developed concurrently, with up to 5 episodes of bilious emesis and 5 to 10 large-volume, watery bowel movements daily, includ- ing nocturnal and fasting bowel move- ments. Physical examination was remarkable for diffuse mild abdominal tenderness and lower extremity pitting edema. Her serum total protein was 5.7 g/dL (normal, 6.4 to 8.3 g/dL) and serum albumin level was 2.1 g/dL (nor- mal, 3.4 to 4.8 g/dL) at admission. She had been hospitalized for 15 days at the outside facility without improvement; multiple stool infectious studies and a colonoscopy with biopsies were non- diagnostic and her symptoms continued despite a trial of empiric antibiotics including ampicillin, metronidazole, and ertapenem. Her oral intake was severely limited and total parenteral nutrition was started before transfer. Her medical history included hypertension (treated with olmesartan, amlodipine, bisopro- lol, and hydrochlorothiazide) and M.K. was supported by the Boston University Undergraduate Research Opportunities Program. F.A.F. acknowledges financial support provided by Andy and Robin Davis. The authors declare that they have nothing to disclose. The authors declare that they have nothing to disclose. LETTERS TO THE EDITOR 894 | www.jcge.com J Clin Gastroenterol  Volume 47, Number 10, November/December 2013