Abstract
Chronic granulomatous disease (CGD) is a rare disorder caused by genetic mutations of the nicotinamide adenine dinucleotide phosphate oxidase complex (NADPH), occurring in approximately 1/200,000 individuals. These mutations decrease residual reactive oxygen species (ROS) levels, leading to dysregulated inflammation. Inflammatory manifestations can be widespread, including severe and recurrent infections. The gastrointestinal tract is the most commonly affected organ with resultant inflammatory bowel disease, termed CGD colitis. Manifestations include abdominal pain, diarrhea with or without blood, nausea/vomiting, obstructions, and fistulas which can occur in a perianal distribution. Patients are often misdiagnosed with Crohn’s disease or ulcerative colitis, especially in the absence of extensive infectious history. We aimed to characterize the small bowel involvement in CGD.
Data is presented from a combined retrospective and ongoing prospective observational study of patients with genetically-confirmed CGD who underwent wireless video capsule endoscopy (VCE) at the National Institutes of Health Clinical Center (n = 8). VCEs were performed for clinical indications including abdominal pain (88%), diarrhea (75%), bloody stools (38%), and/or nausea/vomiting (25%). One patient (13%) underwent VCE for otherwise unexplained high inflammatory markers. Laboratory evaluation was significant for leukopenia/leukocytosis (75%), anemia (63%), and elevated C reactive-protein levels (63%). Seven patients (88%) had prior small bowel imaging, however none showed evidence of any abnormality in this organ. The most common VCE findings were ulcers and/or erosions (88%). Most patients also displayed other mucosal changes consistent with inflammation such as erythema and/or edema (88%). There was also evidence of blood or hematin on 63% of the endoscopies.
While therapies for CGD colitis are targeted towards colonic involvement, our findings show that the vast majority of symptomatic patients also have active small bowel disease including ulcers, erosions, evidence of bleeding, and other signs of inflammation. These findings, however, are not specific to CGD. Given that certain biologic medications used for Crohn’s disease and ulcerative colitis have been shown to increase the risk of life-threatening infections in patients with CGD, it is important to keep other forms of IBD, especially CGD-related IBD, in mind when interpreting small bowel capsule endoscopy in patients with suspected IBD. Lastly, in patients with confirmed CGD colitis, small bowel disease should be rigorously investigated, and therapy should also seek to address small bowel involvement. Of note, our patients did not display any radiographic abnormalities of the small bowel. Due to our small sample size, we aim to study additional patients in the future to augment our data.
High levels of Crohn's disease-associated anti-microbial antibodies are present and independent of colitis in chronic granulomatous disease
