Case Reports

Acute Graft-vs-host Disease Following Liver Transplantation

Dr. Bitar is from the Department of Dermatology, Tulane University, New Orleans, Louisiana. Dr. Olivier and Dr. Lee are from the Department of Dermatology, Louisiana State University, New Orleans. Drs. Vincent and Martin are from the Department of Dermatology, Ochsner Medical Center, Jefferson, Louisiana.

The authors report no conflict of interest.

Correspondence: Julie Martin, MD, Department of Dermatology, Ochsner Medical Center, 1514 Jefferson Hwy, Jefferson, LA 70121 ([email protected]).




GVHD Subtypes
The 2 types of GVHD are humoral and cellular.5 The humoral type results from ABO blood type incompatibility between donor and recipient and causes mild hemolytic anemia and fever. The cellular type is directed against major histocompatibility complexes and is associated with high morbidity and mortality.

Presentation of GVHD
Acute GVHD following OLT usually occurs 3 to 5 weeks after transplantation,6 as in our patient. Symptoms include rash, fever, pancytopenia, and diarrhea.2 Skin is the most commonly involved organ in acute GVHD; rash is the earliest manifestation.1 The rash can be asymptomatic or associated with pain and pruritus. Initial cutaneous manifestations include palmar erythema and erythematous to violaceous discoloration of the face and ears. A diffuse maculopapular rash can develop, involving the face, abdomen, and trunk. The rash may progress to formation of bullae or skin sloughing, resembling Stevens-Johnson syndrome or toxic epidermal necrolysis.1 The skin manifestation of acute GVHD following OLT is similar to hematopoietic stem cell transplantation (Table).7,8

Pancytopenia is a common manifestation of GVHD following liver transplantation and is rarely seen following hematopoietic stem cell transplantation.7 Donor lymphocytes engraft and proliferate in the bone marrow, attacking recipient hematopoietic stem cells. It is important to note that more common causes of cytopenia following liver transplantation, including infection and drug-induced bone marrow suppression, should be ruled out before diagnosing acute GVHD.6

Acute GVHD can affect the gastrointestinal tract, causing diarrhea; however, other infectious and medication-induced causes of diarrhea also should be considered.6 In contrast to hematopoietic stem cell transplantation, in which the liver is usually involved,1 the liver is spared in acute GVHD following liver transplantation.5

Diagnosis of GVHD
The diagnosis of acute GVHD following liver transplantation can be challenging because the clinical manifestations can be caused by a drug reaction or viral infection, such as cytomegalovirus infection.2 Patients who are older than 50 years and glucose intolerant are at a higher risk of acute GVHD following OLT. The combination of younger donor age and the presence of an HLA class I match also increases the risk of acute GVHD.6 The diagnosis of acute GVHD is confirmed with biopsy of the skin or gastrointestinal tract.

Morbidity and Mortality of GVHD
Because of the high morbidity and mortality associated with acute GVHD following liver transplantation, early diagnosis and treatment are crucial.5 Death in patients with acute GVHD following OLT is mainly attributable to sepsis, multiorgan failure, and gastrointestinal tract bleeding.6 It remains unclear whether this high mortality is associated with delayed diagnosis due to nonspecific signs of acute GVHD following OLT or to the lack of appropriate treatment guidelines.6

Treatment Options
Because of the low incidence of acute GVHD following OLT, most treatment modalities are extrapolated from the literature on acute GVHD following stem cell transplantation.5 The most commonly used therapies include high-dose systemic steroids and anti–thymocyte globulin that attacks activated donor T cells.6 Other treatment modalities, including anti–tumor necrosis factor agents and antibodies to CD20, have been reported to be effective in steroid-refractory GVHD.2 The major drawback of systemic steroids is an increase in the risk for sepsis and infection; therefore, these patients should be diligently screened for infection and covered with antibiotics and antifungals. Extracorporeal photopheresis is another treatment modality that does not cause generalized immunosuppression but is not well studied in the setting of acute GVHD following OLT.6

Acute GVHD following OLT can be prevented by eliminating donor T lymphocytes from the liver before transplantation. However, because the incidence of acute GVHD following OLT is very low, this approach is not routinely taken.2


Acute GVHD following liver transplantation is a rare complication; however, it has high mortality, necessitating further research regarding treatment and prevention. Early recognition and treatment of this condition can improve outcomes. Dermatologists should be familiar with the skin manifestations of acute GVHD following liver transplantation due to the rising number of cases of solid-organ transplantation.


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