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Home Books Fitzpatrick's Dermatology in General Medicine, 8e

Chapter 28. Graft-versus-Host Disease

Edward W. Cowen

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Graft‐versus-Host Disease at a Glance
  • Acute graft-versus-host disease (GVHD) is a serious and potentially life-threatening sequelae of allogeneic hematopoietic stem cell transplantation. Skin manifestations range from a mild, asymptomatic exanthem-like eruption to full-thickness skin loss resembling toxic epidermal necrolysis. Hepatic involvement is characterized by elevated total bilirubin. Gastrointestinal disease manifests as abdominal pain, nausea/vomiting, and secretory diarrhea.
  • The most important risk factor for chronic GVHD is a history of acute GVHD. Traditionally, acute features present prior to day 100 posttransplantation, and chronic manifestations after 100 days; however, overlap between “classic” acute and chronic features may occur.
  • Chronic GVHD of the skin is remarkably variable in clinical presentation. Epidermal involvement may resemble lichen planus, keratosis pilaris, or psoriasis. Sclerotic changes may resemble lichen sclerosus, morphea, systemic sclerosis, or eosinophilic fasciitis.
  • The pathogenesis of chronic GVHD is poorly understood and nearly every organ system is at risk. The skin, oral mucosa eyes, gastrointestinal tract, and lungs are most frequently involved. In many cases, organ system disease resembles known autoimmune conditions.
  • Optimal dermatologic management of chronic GVHD of the skin requires an understanding of other organ involvement, infection status, and cancer relapse risk. Close communication with the transplant physician and a “team approach” to multispecialty management is needed.

Approximately 50,000 hematopoietic stem cell transplantation (HCT) procedures are performed worldwide each year for an expanding array of hematologic malignancies and marrow failure syndromes, metabolic disorders, and immunodeficiencies. HCT may utilize autologous, syngeneic, or allogeneic donor hematopoietic stem cell (HC). During autologous transplantation the patient's own HC are returned to the patient following preparative chemotherapy. Syngeneic transplantation is the transfer of HC between identical twins. Allogeneic HCT (allo-HCT) is the transfer of HC from a related (nonidentical) or unrelated donor to a recipient. Graft-versus-host disease (GVHD) is the primary cause of nonrelapse-related morbidity and mortality in allo-HCT and also rarely occurs following transplantation of solid organs or transfusion of blood products.

Transplantation regimens have advanced rapidly since the first successful allo-HCT was performed in 1968.1 Peripheral blood, rather than bone marrow, is now the primary source of donor HC at many transplant centers, and reduced intensity (nonmyeloablative) conditioning has permitted older patients and others who would not tolerate myeloablative chemotherapy a chance for cure with HCT. More recently, umbilical cord blood has gained prominence as a stem cell source in both pediatric and adult HCT. Donor leukocyte infusions (DLI), the administration of additional donor HC to the recipient weeks or even months after HCT, are also frequently utilized to augment graft-versus-malignancy effect.

These evolving trends in HCT, in conjunction with other known donor/recipient risk variables (Box 28-1), contribute to a wide range of reported GVHD incidence. Nevertheless, the degree of HLA-mismatch between donor and recipient remains the single most important predictor of GVHD.2 Acute GVHD develops in approximately 40% of fully matched sibling donor HCT, whereas 80% of mismatched unrelated HCT result in acute GVHD.3,4...

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