Fatal Graft-Versus-Host Disease Presenting as Fever of Unknown Origin in a Pancreas-After-Kidney Transplant Recipient

Abstract

Acute graft-versus-host disease (GVHD) is a rare complication of pancreas transplantation. We describe a 54-year-old male with type 1 diabetes who received a zero-antigen mismatched pancreas-after-kidney transplant from a pancreas donor who was homozygous at the HLA-B, -Cw, -DR, and -DQ alleles. Starting on postoperative day (POD) #22, the patient developed persistent fevers. Workup was notable only for low-grade cytomegalovirus viremia, which was treated. The fevers eventually disappeared. On POD #106, the patient was noted to have a diffuse erythematous rash. A skin biopsy was consistent with GVHD. Short tandem repeat DNA analysis of both peripheral blood lymphocytes and skin demonstrated mixed chimerism, confirming the diagnosis of GHVD. Soon after diagnosis, the patient developed pancytopenia and fevers and died of multiorgan failure on POD #145. Transplant clinicians should consider GVHD as a possible, although admittedly rare, cause of fevers of unknown origin in recipients of pancreas transplants.

Graft-Versus-Host Disease After Simultaneous Pancreas–Kidney Transplantation: A Case Report and Review of the Literature

“…A risk factor for GVHD is an immunocompromised host, who is more susceptible to competent donor T cells (15). Many cases of GVHD after kidney and/or pancreas transplantation occurred in hosts that were receiving their second, third and sometimes fourth transplants and have therefore been on chronic immunosuppression for a long time (7,8,11,12) (Table 1). The optimal treatment of GVHD after solid organ transplantation remains unclear.…”

“…To date, 12 cases of GVHD following pancreas transplantation have been reported. Five were simultaneous pancreas-kidney (SPK) transplants, and only one survived (5)(6)(7)(8)(9)(10)(11)(12). We present the second successfully treated case of GVHD in an SPK recipient and discuss the use of serial short tandem repeats (STR) DNA analyses for early diagnosis and monitoring response to therapy.…”

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“…All HLA mismatches were bidirectional except for one patient whose transplant was mismatched at locus A in the host-versus-graft but not graft-versus-host direction. The median (range) ages of patients and donors were 42 years (36-60 y) and 23 years (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), respectively. Uniform preoperative induction and posttransplant prophylaxis were administered according to our institutional algorithm.…”

“…We found a total of 25 previously reported cases of GVHD following kidney, pancreas, or SPK transplant [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] (Tables 2 and 3). This list was compiled by a search of Medline using the following key word combinations: "graft-versus-host disease" OR "graft versus host disease" OR "GVHD"; AND "kidney" OR "renal" OR "pancreas" OR "pancreatic"; AND "allograft" OR "allograft" OR "transplant."…”

Graft-Versus-Host Disease After Pancreatic Transplantation

“…4,5 There are 15 case reports of GVHD related to pancreas transplants, 7 of which represent simultaneous pancreas-kidney transplants and 2 of which represent sequential pancreas-kidney transplants. 3,6–16 Diagnosis is typically confirmed by performing routine histopathology or polymerase chain reaction (PCR) assays aimed at detecting donor-derived short-tandem repeats (STRs) in involved tissue or peripheral blood to demonstrate the presence of donor T-cell chimerism. Endoscopy is often a critical step in the diagnostic workup because the GI tract is typically affected.…”