Diffuse Gastrointestinal Polyposis With Skin, Hair, and Nail Changes

Question: A 54-year-old, previously healthy man presented with a 5-kg weight loss, loss of taste, diarrhea, abdominal cramping, hair loss, skin hyperpigmentation, and fingernail changes over the course of 2 months. He endorsed about 6 bowel movements per day with some blood when wiping. Physical examination showed brittle changes of the fingernails and hyperpigmentation of the palmar aspect of both hands (Figure A) and face (Figure B). He denied any joint pain or eye issues. He worked as a contractor with no known toxic exposures and denied any recent travel. Magnetic resonance imaging of the abdomen showed a benign hepatic cyst and reactive appearing mesenteric lymphadenopathy but otherwise no significant findings. Bloodwork revealed hypoalbuminemia and low levels of ferritin, zinc, and copper. Laboratory evaluations for Addison’s disease, heavy metal toxicity, HIV, viral hepatitis, and thyroid disease were unremarkable. Stool studies to exclude infectious causes of the diarrhea were negative. Esophagogastroduodenoscopy showed multiple large nonbleeding polyps in the gastric incisura (Figure C), antrum (Figure D), pylorus (Figure E), and second portion of the duodenum. The esophagus was spared and normal in appearance. Biopsies of these polyps confirmed hyperplastic polyps. Colonoscopy demonstrated nonspecific inflammatory changes of the entire colon along with diffuse polyposis, with polyps as large as 30 mm in size (Figure F). Capsule endoscopy showed villous edema and polypoid appearance of the entire small bowel. The patient had no family history of polypoid disorders. What is the possible diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Cronkhite-Canada syndrome (CCS) is a rare, noninherited condition associated with widespread gastrointestinal polyps, alopecia, onychodystrophy, skin hyperpigmentation, and diarrhea. Given the patient’s clinical presentation, he was diagnosed with CCS and treated with a course of oral prednisone and pantoprazole. He had a moderate improvement in his abdominal pain and heartburn, but he continued to have severe diarrhea. Azathioprine was added to his regimen and the patient had significant clinical improvement with weight gain and decreased stool frequency. CCS was first described in 1955 and has an estimated incidence of 1 case per million population.1Cronkhite Jr., L.W. Canada W.J. Generalized gastrointestinal polyposis: an unusual syndrome of polyposis, pigmentation, alopecia and onychotrophia.N Engl J Med. 1955; 252: 1011-1015Crossref PubMed Scopus (329) Google Scholar Owing to its rarity, the pathophysiology and optimal treatment of CCS is not well-understood. Chronic diarrhea, diffuse polyposis, and gastrointestinal inflammation can lead to nutritional and electrolyte deficiencies, as was seen in our patient’s case. Prior reports have found success in treatment with nutritional supplementation and immunosuppressive therapy, suggesting an underlying immune mediated mechanism.2Ward E.M. Wolfsen H.C. Pharmacological management of Cronkhite–Canada syndrome.Exp Opin Pharmacother. 2003; 4: 385-389Crossref PubMed Scopus (52) Google Scholar Our patient experienced a significant improvement in his symptoms with corticosteroids and azathioprine. There are also reports of successful treatment with anti-tumor necrosis factor agents such as infliximab.3Watanabe D. Ooi M. Hoshi N. et al.Successful treatment of Cronkhite–Canada syndrome using anti-tumor necrosis factor antibody therapy.Endoscopy. 2014; 46: E476-E477PubMed Google Scholar Patients with CCS are at increased risk for colorectal cancer and should receive frequent endoscopic surveillance of their colon.