Shifat Ahmed

Immunopathophysiology of inflammatory bowel disease: how genetics link barrier dysfunction and innate immunity to inflammation

Inflammatory bowel diseases (IBD) comprise a distinct set of clinical symptoms resulting from chronic or relapsing immune activation and corresponding inflammation within the gastrointestinal (GI) tract. Diverse genetic mutations, encoding important aspects of innate immunity and mucosal homeostasis, combine with environmental triggers to create inappropriate, sustained inflammatory responses. Recently, significant advances have been made in understanding the interplay of the intestinal epithelium, mucosal immune system, and commensal bacteria as a foundation of the pathogenesis of inflammatory bowel disease. Complex interactions between specialized intestinal epithelial cells and mucosal immune cells determine different outcomes based on the environmental input: the development of tolerance in the presence of commensal bacterial or the promotion of inflammation upon recognition of pathogenic organisms. This article reviews key genetic abnormalities involved in inflammatory and homeostatic pathways that enhance susceptibility to immune dysregulation and combine with environmental triggers to trigger the development of chronic intestinal inflammation and IBD.

Acute Liver Failure from Herpes Simplex Virus in an Immunocompetent Patient Due to Direct Inoculation of the Peritoneum

Herpes simplex virus (HSV) hepatitis is a rare cause of acute liver failure (ALF). It carries a mortality rate of 80% if untreated, thus early identification and treatment are critical. Without high clinical suspicion, HSV hepatitis is difficult to diagnose. A 48-year-old Hispanic female presented with a 4-day history of abdominal pain and a vaginal cuff tear requiring laparoscopic repair. She subsequently developed postsurgical disseminated HSV, resulting in ALF. Acyclovir was initiated, but she was resistant to treatment. She was given additional foscarnet and responded without requiring a liver transplant.

A Deadly Connection: Aortoenteric Fistula as a Cause of Acute Upper Gastrointestinal Bleeding

A 66-year-old white man with hypertension, hyperlipidemia, COPD, lung cancer, and aortoiliac bypass graft placed 6 years prior for peripheral vascular disease, presented with 3 days of melena and syncopal events associated with bowel movements. The patient reported having coffee ground emesis and dark, tarry stools with onset of his syncope. Physical exam showed bright red blood per rectum and melenic stools. Baseline hemoglobin was 14.5 g/dL, dropping to 7.1 g/dL at admission. He subsequently became hypotensive despite receiving 2 units of packed red blood cells and aggressive intravenous fluid hydration. Emergent esophagogastroduodenoscopy (EGD) showed red blood throughout the esophagus, pale stomach mucosae, and an exposed aortic graft with bright blood in the third part of the duodenum (Figure 1). He underwent emergent laparotomy for takedown of aortoduodenal fistula with repair of duodenal erosion and ligation of the distal aorta. The following day, the patient’s lower extremities had increased pallor and he underwent axillofemoral and femoral-femoral bypass grafting. He went into cardiac arrest perioperatively and died.