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Rejection, but in a Different Direction: Graft-Versus-Host Disease after Solid Organ Transplantation Mimicking an Infection

      A 59-year-old man caucasian with hepatocellular carcinoma and liver cirrhosis due to hepatitis C underwent liver transplantation. Three months later he was admitted to the hospital due to voluminous diarrhea, nausea, and significant weakness. The patient was on immunosuppression with tacrolimus and mycophenolate mofetil, and never experienced transplanted organ rejection. Upon presentation, laboratory values showed a white blood cell count of 6.8 K/mcL, hemoglobin of 13.1 g/dL, platelet count of 207 K/mcL, creatinine of 1.99 mg/dL, aspartate aminotransferase of 22 units/L, alanine aminotransferase of 31 units/L, total bilirubin of 0.4 units/L, and an albumin of 2.7 g/dL. Because of his immunocompromised status, the patient underwent an extensive workup for an infectious etiology. Pending the results of the workup, the patient received treatment with various antibiotics. Computed tomography of the abdomen (Figure A ) showed thickening of the entire intestine and fat stranding. The physical exam did not reveal any rashes. Eventually, testing for cytomegalovirus, herpes simplex virus, acid fast bacteria, adenovirus, Epstein-Barr virus, and other infections returned negative. Colonoscopic examination (Figure B) showed erosions from the rectum to the sigmoid, and severe inflammation and ulceration of the intestinal mucosa. Histopathology (Figure C, x20 objective) revealed evidence of severe colitis with marked crypt apoptosis. Immunostains (Figure D, x20 objective) showed increased numbers of CD8-positive intraepithelial lymphocytes, suggesting graft-versus-host disease (GVHD). To confirm the origin of the cellular infiltrate, polymorphic short tandem repeat loci amplification by polymerase chain reaction was used. Short tandem repeat loci consist of a core DNA sequence that is repeated a variable number of times within a discrete genetic locus and are specific to each individual. Donor-derived short tandem repeats were found by chimerism analysis on the intestinal biopsy sample confirming the cellular infiltrate to be of donor origin. Presence of marked crypt apoptosis, T-cell infiltration, and donor-derived short tandem repeats strongly supported the diagnosis of gastrointestinal GVHD.
      • Castilla-Llorente C.
      • Martin P.J.
      • McDonald G.B.
      • et al.
      Prognostic factors and outcomes of severe gastrointestinal GVHD after allogeneic hematopoietic cell transplantation.
      The patient was initiated on high-dose steroids without sustained improvement. He ultimately died from infectious complications 3 months after his initial presentation after being immunocompromised and on a high dose of steroids for a prolonged period of time. Graft-versus-host disease is rare after solid organ transplantation, with a reported incidence of 1%-5.6%.
      • Murali A.R.
      • Chandra S.
      • Stewart Z.
      • et al.
      Graft versus host disease after liver transplantation in adults: a case series, review of literature, and an approach to management.
      • Smith D.M.
      • Agura E.
      • Netto G.
      • et al.
      Liver transplant-associated graft-versus-host disease.
      • Zhang Y.
      • Ruiz P.
      Solid organ transplant-associated acute graft-versus-host disease.
      Solitary involvement of the gastrointestinal tract, without any skin or bone marrow, involvement is even rarer.
      • Sharma A.
      • Armstrong A.E.
      • Posner M.P.
      • et al.
      Graft-versus-host disease after solid organ transplantation: a single center experience and review of literature.
      This GVHD was likely cell-mediated (T-cells from the donor identify and react to human leukocyte antigen incompatible recipient cells present in the skin, liver, gastrointestinal tract, or bone marrow).
      • Jamieson N.V.
      • et al.
      Graft-versus-host disease in solid organ transplantation.
      Gastrointestinal GVHD can have disastrous consequences, with overall survival for severe gut GVHD estimated at 25% at 2 years.
      • Smith D.M.
      • Agura E.
      • Netto G.
      • et al.
      Liver transplant-associated graft-versus-host disease.
      • Zeiser R.
      • Blazar B.R.
      Acute graft-versus-host disease - biologic process, prevention, and therapy.
      Thus, clinicians should have a high index of suspicion and promptly initiate treatment. The initiation of GVHD-specific treatment was delayed in this case, likely due to high suspicion for an infectious etiology. Crypt apoptosis, epithelial T-cell infiltration, and short tandem repeat analysis can be helpful in the diagnosis of gastrointestinal GVHD and differentiate between infectious, inflammatory, and alloimmune pathology.
      Figure
      Figure(A) CT image demonstrating thickening of the entire intestine with fat stranding; (B) Colonoscopy view demonstrating erosions from the rectum to the sigmoid; (C) Histopathology showing severe colitis with marked crypt apoptosis; (D) Immunostain showing increased numbers of CD8 positive intraepithelial lymphocytes consistent with Graft-Versus-Host Disease.
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      References

        • Castilla-Llorente C.
        • Martin P.J.
        • McDonald G.B.
        • et al.
        Prognostic factors and outcomes of severe gastrointestinal GVHD after allogeneic hematopoietic cell transplantation.
        Bone Marrow Transplant. 2014; 49: 966-971
        • Murali A.R.
        • Chandra S.
        • Stewart Z.
        • et al.
        Graft versus host disease after liver transplantation in adults: a case series, review of literature, and an approach to management.
        Transplantation. 2016; 100: 2661-2670
        • Smith D.M.
        • Agura E.
        • Netto G.
        • et al.
        Liver transplant-associated graft-versus-host disease.
        Transplantation. 2003; 75: 118-126
        • Zhang Y.
        • Ruiz P.
        Solid organ transplant-associated acute graft-versus-host disease.
        Arch Pathol Lab Med. 2010; 134: 1220-1224
        • Sharma A.
        • Armstrong A.E.
        • Posner M.P.
        • et al.
        Graft-versus-host disease after solid organ transplantation: a single center experience and review of literature.
        Ann Transplant. 2012; 17: 133-139
        • Jamieson N.V.
        • et al.
        Graft-versus-host disease in solid organ transplantation.
        Transpl Int. 1991; 4: 67-71
        • Zeiser R.
        • Blazar B.R.
        Acute graft-versus-host disease - biologic process, prevention, and therapy.
        N Engl J Med. 2017; 377: 2167-2179