Ipilimumab is a human monoclonal antibody that functions as a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor that is used to treat malignant melanoma. Due to ipilimumab’s removal of immune regulation, specifically through the inactivation of CTLA-4, it is commonly associated with inflammatory and autoimmune events. Gastrointestinal (GI) related immune-related adverse events such as diarrhea occur in 29% of patients with 7.6% of patients specifically suffering from colitis. We describe a case of colonic perforation with ipilimumab use. Our goal is to raise awareness and alert practicing gastroenterologists of this particular adverse effect.A 74-year-old male patient presented to the emergency department with complaints of hematochezia, abdominal pain and decreased appetite. The patient’s past medical history included desmoplastic BRAF mutation negative melanoma with metastatic disease to the face, liver, and trigeminal nerve. He underwent his last treatment of ipilimumab three weeks prior to presentation. In total, the patient received four doses of 3 mg/kg of ipilimumab every three weeks. Since the initiation of ipilimumab, he reported diarrhea as its adverse effect, which was treated with tapering doses of prednisone one month at a time. Colonoscopy revealed mucosal ulceration and erosion in the rectum, sigmoid colon, and remaining descending colon up to the splenic flexure and cecum. After the colonoscopy, the patient became tachycardic, hypotensive and complained of sudden abdominal pain. A computed tomographic (CT) scan of the abdomen showed free intraperitoneal air. He was immediately taken to the operating room (OR) for an emergent laparotomy. In the operating room, perforations were noted at the splenic flexure and the cecum with large amounts of succus spilling from the perforations. The majority of the large bowel appeared cyanotic and dusky; consequently, a sub-total colectomy with terminal ileostomy was performed. After the procedure, the patient was started on antibiotics for severe peritonitis and admitted to the intensive care unit (ICU) with septic shock. His clinical status continued to deteriorate due to acute respiratory failure, nosocomial pneumonia, severe protein calorie malnutrition and coagulopathy from disseminated intravascular coagulation (DIC). The patient did not recover from his illness and died a few days later.It is imperative that physicians caring for patients receiving treatment with CTLA-4 inhibitors frequently monitor for and promptly treat possible immune-related adverse effects. For patients with ipilimumab-related colitis, prompt identification of symptoms and early treatment with steroids are crucial in preventing harmful or possibly fatal immune-related adverse events. Gastroenterologists should be wary of this adverse side effect in this high-risk population when performing colonoscopy and take necessary precautions.
INTRODUCTION: Capsule endoscopy (CE) is indicated in the evaluation of suspected Crohn's disease (CD) when ileocolonoscopy and radiographic studies are negative or inconclusive. However, it should be recognized that mucosal breaks or ulcers alone are not always diagnostic of CD. CASE DESCRIPTION/METHODS: A 55 year-old man from India who immigrated to the US as a child was admitted to an outside hospital with 6 months of bilateral lower quadrant abdominal pain and iron-deficiency anemia. After normal upper endoscopy and colonoscopy, CE showed an ulcer and inflamed mucosa in the ileum. On this basis he was diagnosed with CD and treated with prednisone. The next month he was admitted to our institution with ongoing abdominal pain and unintentional weight loss but no diarrhea or hematochezia. On exam his vital signs and body mass index were normal. His abdomen was soft without organomegaly or palpable mass. He was tender to palpation in the bilateral lower quadrants. Stool was brown. Laboratory results were Hgb 8.3 g/dL, iron studies consistent with iron-deficiency, albumin 2.8 g/dL, C-reactive protein 150 mg/L, and erythrocyte sedimentation rate 45 mm/hr. CT enterography showed wall thickening of the mid-ileum with mucosal enhancement and mesenteric root adenopathy. Retrograde double balloon enteroscopy 90 cm into the ileum revealed a 15 mm shallow ulcer 80 cm proximal to the ileocecal (IC) valve and a similar ulcer 15 cm proximal to the IC valve. Biopsies showed ulcerated mucosa with infiltrating atypical cells that stained positive for ERG, a highly specific endothelial marker, and negative for other immunostains, leading to a diagnosis of primary intestinal angiosarcoma. DISCUSSION: Primary intestinal angiosarcoma is a rare soft tissue sarcoma that may present with abdominal pain, GI bleeding, obstruction, or weight loss. Tumors, detected on 2-4% of CEs, are in the differential diagnosis for small bowel CD along with infection, ischemia, vasculitis, lymphoma, Behcet disease, radiation enteritis, and drug-induced enteritis. In suspected CD, there is no reference standard or uniform criteria for diagnosis by CE. And, many of the lesions that lead to a diagnosis of CD are non-specific with the specificity of CE for CD as low as 53% and the positive predictive value <60% in some studies. Thus, findings of CE should be interpreted with an adequate degree of skepticism and a broad differential diagnosis considered to minimize mimics being mistaken for CD.
We report a case of a 34-year-old woman who presented with an ST-segment elevation myocardial infarction with acute heart failure and a subsequent diagnosis of mosaic Turner syndrome (TS). The report also discusses cardiovascular disease in patients with TS and the current recommendations for screening and follow-up in these patients. ( Level of Difficulty: Beginner. )
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