Gastrointestinal Computed Tomography Findings in Chronic Granulomatous Disease with Subgroup Clinicopathologic Analysis.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency which can lead to gastrointestinal (GI) complications including inflammatory bowel disease. Radiographic findings in this cohort have not been well described. AIMS: To describe the frequency and spectrum of gastrointestinal abnormalities seen on computed tomography (CT) in patients with CGD and determine whether radiography was predictive of endoscopic or histopathologic inflammatory findings. METHODS: A retrospective review was conducted on 141 consecutive CGD patients seen at the National Institutes of Health between 1988 and 2011. All corresponding CTs were reviewed for gastrointestinal abnormalities including wall thickening. Endoscopic and histopathologic findings were reviewed in subjects with documented endoscopy within 30 days of an imaging study. Findings were compared between patients with and without wall thickening on CT to determine whether bowel wall thickening was predictive of endoscopic or histologic inflammatory findings. RESULTS: Two hundred and ninety-two CTs were reviewed. GI wall thickening was present on CT in 61% of patients (n = 86). Among a subgroup of 20 patients who underwent endoscopy at the time of their imaging, there was a statistically significant correlation between radiographic gastrointestinal wall thickening and endoscopic inflammation in the same intestinal segment (p = 0.035). Additionally, there was a significant correlation between radiographic gastrointestinal wall thickening and inflammatory features on histopathology (p = 0.02). CONCLUSIONS: GI abnormalities are commonly observed on CT in CGD patients. Bowel wall thickening correlates with endoscopic and histopathologic evidence of inflammation. These findings may be used to better facilitate directed endoscopic assessment and histopathologic sampling in patients with CGD.

Gastrointestinal Features of Chronic Granulomatous Disease Found During Endoscopy.

BACKGROUND & AIMS: Chronic granulomatous disease (CGD) is an inherited disorder of the reduced nicotinamide adenine dinucleotide phosphate oxidase complex within phagocytic cells that predisposes people to bacterial and fungal infections. Approximately 40% of patients with CGD have gastrointestinal involvement. We aimed to characterize the endoscopic features of gastrointestinal CGD and define the role of endoscopy in patients. METHODS: We created a database of all patients with CGD seen at the National Institutes of Health from 1990 through 2010. We identified patients who had an endoscopy, and collected information from those with CGD-associated inflammatory bowel disease. We analyzed clinical data (demographic information and symptoms), endoscopic data (indication, preparation quality, degree of inflammation, mucosal findings, and complications), and pathologic data. RESULTS: A total of 211 endoscopies (96 esophagogastroduodenoscopies, 82 colonoscopies, and 33 flexible sigmoidoscopies) were performed at the National Institutes of Health on 78 patients with CGD. Esophageal, gastric, and duodenal inflammation were detected in 21%, 74%, and 37% of patients, respectively. Esophageal dysmotility and structural abnormalities were noted in 26%. Of the patients who had colonic CGD-inflammatory bowel disease, 74% had skip lesions and 93% had anorectal disease. Enteric fistulae were found in 18% of patients; 73% of these were perianal. Colonic strictures were observed in 24% of patients; 80% were in the anorectal area. CONCLUSIONS: Based on an analysis of clinical and endoscopic data from 78 patients, CGD-inflammatory bowel disease is a distinct entity, primarily involving the anus and rectum, with skip lesions in the remaining bowel. Bowel strictures and fistulae are present in a significant number of patients. Upper gastrointestinal tract inflammatory disease is common, although typically not as severe as colonic disease. Upper and lower endoscopies are important in characterizing the gastrointestinal features of CGD.

Gastrointestinal histopathology in chronic granulomatous disease: a study of 87 patients.

Gastrointestinal (GI) involvement in chronic granulomatous disease (CGD), a rare genetic immunodeficiency, mimics other inflammatory bowel diseases. We report GI pathology from 87 CGD patients seen at the NIH Clinical Center, with vague to severe clinical symptoms, in whom biopsies (313) had been evaluated (esophagus [23], stomach [71], small bowel [52] including duodenum [39], ileum [12], and jejunum [1], and colon [167]). Additionally reviewed was GI tissue from 15 autopsies. In our patient cohort, the mean age was 22 years (age range, 3 to 44 y; 2:1 male to female ratio). There were pathologic changes in 83/87 (95%) patients; with colon being the most commonly involved site and esophagus the least. There were microgranulomas in 53/87 (61%), pigmented macrophages in 64/87 (74%), tissue eosinophilia in 31/87 (36%), and chronic and/or acute inflammation in 57/87 (66%) patients. A subset of patients had villous shortening in the duodenum (8/39) and ileum (5/12). We identify microgranulomas in 76/167 (46%) colon, 12/52 (23%) small bowel, and 4/71 (6%) gastric biopsies; pigmented macrophages in 109/167 (65%) colon and 7/52 (13%) small bowel biopsies and 14/15 autopsies; chronic and/or acute inflammation in 97/167 (58%) colon, 13/52 (25%) small bowel, 42/71 (59%) gastric, and 5/23 (22%) esophageal biopsies; tissue eosinophilia in 43/167 (26%) colon, 7/52 (13%) small bowel, and 2/71 (3%) gastric biopsies. Only 4/87 (5%) patients had normal histology. No infectious etiology was identified in the majority of inflammatory lesions. We found that mild to severe GI pathology was common in CGD. In addition, microgranulomas, pigmented macrophages, and eosinophilia are not associated with acute (neutrophilic) inflammation.

The role of surgery in the management of patients with refractory chronic granulomatous disease colitis.

BACKGROUND: Chronic granulomatous disease is a rare immunodeficiency complicated by dysregulated inflammation and granulomatous complications of the GI tract. The management of chronic granulomatous disease colitis presents the dilemma of an immunocompromised host requiring immunosuppressive therapy which can potentiate fatal infections. OBJECTIVE: The aim of this study was to identify the types of GI surgery performed in patients and determine the role of surgery in the management of refractory colitis. DESIGN AND SETTINGS: A retrospective single-institution chart review was performed. PATIENTS: Of 268 patients with chronic granulomatous disease treated at the National Institutes of Health between 1985 and 2011, 98 (37%) were identified as having colitis; 27 (10%) had a history of GI luminal surgery. MAIN OUTCOME MEASURES: Patient characteristics, type of GI surgery, and clinical outcomes were documented. RESULTS: A total of 62 GI luminal surgeries were performed in 27 patients with chronic granulomatous disease and colitis. All 27 had a history of perineal disease requiring intervention. Four (15%) had additional surgery performed for reasons other than colitis. Otherwise, 12 (44%) had surgery limited to the perineum, 2 (7%) had a segmental resection, and 13 (48%) underwent fecal diversion with ileostomy or colostomy. Despite local procedures, 7 (58%) patients in the perineal-only group remained symptomatic. Both patients with a segmental resection had persistent perineal disease, and 1 had a recurrent colovesicular fistula. Of the 13 ostomy patients, 11 initially received a diverting ostomy. Eight (73%) of these ultimately required additional procedures for refractory disease, and 4 (36%) developed peristomal pyoderma gangrenosum. Four patients who underwent proctocolectomy with end ileostomy, either initially (2) or as a definitive procedure (2), experienced resolution of colitis and perineal disease. LIMITATIONS: This study is limited by its retrospective design, small sample size, and highly selected patient population. CONCLUSIONS: Proctocolectomy with end ileostomy may offer a definitive treatment in a patient with refractory chronic granulomatous disease colitis given current therapeutic limitations.

Endoscopic management of esophageal cancer after definitive chemoradiotherapy.

BACKGROUND: Concurrent chemoradiotherapy (CRT) is a potentially curative non-surgical option for locally advanced esophageal cancer, with pathological complete response (CR) ranging from 13 to 49 %. The rate of persistent and recurrent disease within the esophagus remains high at 40-60 %, and treatment of these tumors may improve disease-free survival. The aim of this review is to assess the efficacy of salvage endoscopic therapies for recurrent esophageal cancer. METHODS: Medline and Embase were searched for relevant studies published in the English-language literature that reported use of endoscopic modalities, including photodynamic therapy (PDT), endoscopic mucosal resection (EMR), and spray cryotherapy, as salvage therapies for esophageal cancer. RESULTS: A total of 12 studies were identified. In small case series of PDT, CR varied from 20 to 100 %, with 1-, 3-, and 5-year overall survival rates of 65-80, 34-47, and 36 %, respectively. Data from three studies of EMR in squamous cell cancer show CR in 50 % of cases, with 3- and 5-year overall survival of 56-81 and 49 %, respectively. Endoscopic spray cryotherapy has recently been used in this setting with an observed CR of 37.5 %. CONCLUSIONS: Endoscopic salvage therapies are options for those patients with disease limited to the superficial esophageal wall and those who are unfit to undergo salvage esophagectomy. Widespread application of endoscopic salvage therapies is limited by the lack of awareness and guidelines for endoscopic surveillance post-CRT and limited data on the effectiveness of endoscopic therapies.

An unusual method of diagnosing a common disease.

A 34-year-old woman presented with non-bloody diarrhoea of 14 days duration and vomiting. Physical examination was unremarkable. She had hypokalaemia and metabolic acidosis. Stool studies were negative for Clostridium difficile toxin, faecal leucocytes and parasites. Colon appeared normal on colonoscopy. Pronounced scalloping of ileal folds was noted on ileoscopy. Ileal biopsies revealed villous blunting, crypt hyperplasia, marked intraepithelial lymphocytosis and lymphocytic infiltration of the lamina propria, consistent with lymphocytic ileitis in coeliac disease. Serology revealed elevated antitissue transglutaminase IgA antibodies (>100 U/ml). Institution of a strict gluten free diet resulted in complete resolution of symptoms. Although rare, coeliac disease can present as an acute diarrhoeal illness and should be considered after infectious aetiologies are excluded.