A Fatal Case of Gastrointestinal Chronic Graft-versus-Host Disease

Abstract

Chronic graft-versus-host disease (GVHD) is an increasingly common complication of solid organ transplant recipients. It can affect a wide range of epithelial target tissues including the gastrointestinal tract. A 40-year-old female presented to our hospital with two days of frequent high volume and watery diarrhea. Associated symptoms included nausea, vomiting, and diffuse abdominal pain. Her medical history included type I diabetes mellitus and deceased donor kidney-pancreas transplant. She was maintained on immunosuppression with azathioprine, tacrolimus, and prednisone. Her physical examination was notable for cachexia, diffuse abdominal pain, and a confluent and erythematous macular rash. Laboratory values included a white blood cell count of 0.8 x1000/uL (range 4.0-10), absolute neutrophil count 0.7x1000/uL (range 1.0-11), hemoglobin 6.9g/dL (range 12-18), platelet 109x1000/uL (range 140-440), total bilirubin 12.1mg/dL (range <1.20), direct bilirubin 9.3 (range <0.20), alkaline phosphatase 294U/L (range 30-130), and alanine aminotransferase 124U/L (range 0-34). She was started on intravenous immune gamma-globulin and broad spectrum anti-bacterial, viral and fungal agents. Computerized tomography scan of the abdomen and pelvis with IV contrast (Figure 1) showed bowel wall thickening of the colon moreso than small bowel, consistent with GVHD. She underwent a flexible sigmoidoscopy for definitive diagnosis. Pathology from colonic biopsy (Figure 2, 3) showed severe apoptosis, crypt attenuation, and paucity of inflammation without viral inclusions or neutrophils, pathologically characteristic of GVHD. She was started on high dose steroids and ruxolitinib (janus kinase inhibitor) to help control her GVHD. She had an unfortunate hospital course complicated by severe clostridium difficile colitis, enterococcus bacteremia, and eventually hypoxemic respiratory failure. She was transferred to the medical intensive care unit and transitioned to hospice care where she ultimately died. Risk factors for GVHD include HLA disparity and older age upon organ transplantation. Symptoms of gastrointestinal GVHD are nebulous but can include anorexia, weight loss, and chronic diarrhea. Given the myriad symptoms of GVHD the prudent gastroenterologist must always be aware of this diagnosis. Diagnosis is confirmed via biopsy and scored according to the 2014 revised NIH criteria; she had severe chronic GVHD with an expected two year mortality of 38%.1656_A Figure 1. CT abdomen/pelvis, coronal, white arrow points to diffuse colonic bowel wall thickening1656_B Figure 2. Colon biopsy, black arrow points to apoptotic body1656_C Figure 3. Colon biopsy, black arrows points to crypt attenuation