Colonic Bluish–Black Patches in a 57-Year-Old Woman with Crohn’s Disease

Abstract

Question: A 57-year-old woman with a past history of aplastic anemia was diagnosed with Crohn’s disease, Montreal A3, L3, B1, in September 2015. The initial endoscopic examination revealed multiple ulcers over the terminal ileum, ileocecal valve, and proximal ascending colon. She received oral mesalazine 4 g/d and prednisolone 2.5–15.0 mg/d during the first year after diagnosis, but did not respond to the treatment; she continued to experience right lower quadrate abdominal pain and intermittent bloody diarrhea. A follow-up colonoscopy showed progressive ulcers over the terminal ileum and ileocecal valve in July 2016. Given her history of aplastic anemia and sepsis, she hesitated to take azathioprine, methotrexate, or tumor necrosis factor inhibitors. Instead, she started taking indigo naturalis (Qing-Dai) 4.5 g/d in December 2016. She achieved steroid-free clinical remission under the treatment with mesalazine and indigo naturalis. However, a follow-up colonoscopy still revealed a 1.5-cm ulcer over the ileocecal valve in November 2018. In addition, we observed multiple discrete or coalescing irregularly shaped, bluish–black patches from the ileocecal valve to the rectum with a haphazard distribution, reminiscent of the skin markings of Holstein Friesian cattle (Figure A). A colonic biopsy was obtained, and a representative hematoxylin and eosin stain is shown (Figure B). What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Histology of the discolored colonic lesion revealed scattered pigment-laden histiocytes in the lamina propria and submucosa. Higher magnification disclosed bluish, needle-like crystals in the cytoplasm of these histiocytes. In light of the presence of pigment-laden histiocytes, we called the lesions indigo naturalis-related pseudomelanosis. Unlike melanosis coli, which typically shows continuous homogeneous brown or black discoloration of colon mucosa (snake-skin appearance or starry sky appearance), indigo naturalis-related pseudomelanosis exhibits a haphazard distribution of black discoloration reminiscent of the skin markings of Holstein Friesian cattle.1Freeman H.J. “Melanosis” in the small and large intestine.World J Gastroenterol. 2008; 14: 4296-4299Crossref PubMed Scopus (43) Google Scholar Microscopically, melanosis coli is characterized by the deposition of lipofuscin in histiocytes, and deposition of bluish needle-like crystals is noted in indigo naturalis-related pseudomelanosis.2Kimber R.D. Roberts-Thomson I.C. Gastrointestinal: melanosis coli.J Gastroenterol Hepatol. 1999; 14: 1047Crossref PubMed Scopus (6) Google Scholar The distribution of discolored mucosa did not correlate with inflammatory activity, which was most severe over the terminal ileum and ileocecal valve. This finding implies that the absorption of indigo naturalis occurred not only at the inflammatory sites, but also over normal colon mucosa. It remains to be seen whether deposition of indigo naturalis has any long-term adverse effect, although histologically the mucosa with indigo deposition was not accompanied by significant inflammatory activity.