Graft vs. Host Disease

Graft vs. Host Disease
Julie E. Jackson, MD
Chandra N. Smart, MD
Key Facts
Terminology
  • Multisystem disease affecting skin and gastrointestinal tract occurring in immunosuppressed transplant recipients
  • Occurs as a result of immunocompetent donor T-lymphocytes responding to incompatible foreign host major histocompatibility complex (MHC) antigens
Clinical Issues
  • Most commonly occurs in allogenic bone marrow transplants
Microscopic Pathology
  • Acute GVHD
    • Focal or diffuse interface dermatitis with scattered apoptotic keratinocytes closely associated with neighboring lymphocytes (satellite cell necrosis)
  • Chronic lichenoid GVHD
    • Parakeratosis, hypergranulosis, and irregular acanthosis with dense dermal lichenoid infiltrate leading to vacuolar interface change with cytoid body formation
  • Chronic sclerodermoid GVHD
    • Epidermal atrophy with flattening of rete ridge pattern and marked dermal fibrosis leading to loss of adnexal structures
  • In either chronic form, other characteristic features of GVHD (including vacuolar interface change, satellite cell necrosis, and perivascular infiltrate) are variably present
Clinical photo of acute GVHD shows ill-defined violaceous papules & macules image with overlying scale image. This was in a generalized morbilliform distribution. (Courtesy S. Worswick, MD.)
Grade I acute GVHD shows sparse interface changes image with few apoptotic keratinocytes image and closely associated lymphocytes (satellite cell necrosis).
TERMINOLOGY
Abbreviations
  • Graft vs. host disease (GVHD)
Definitions
  • Multisystem disease affecting skin and gastrointestinal tract, occurring in immunosuppressed transplant recipients
  • Occurs as a result of immunocompetent donor T lymphocytes responding to incompatible foreign host major histocompatibility complex (MHC) antigens
  • Acute GVHD
    • Classically occurs within 100 days of transplant with peak incidence around day 30
  • Chronic GVHD
    • Typically occurs within 3-5 months after grafting and primarily consists of either lichen planus-like eruption or sclerodermoid form
ETIOLOGY/PATHOGENESIS
Proposed Immunologic Mechanisms
  • Donor T-lymphocytes activate and proliferate in setting of immunocompromised host because the host cannot reject the transplanted cells
  • Pretransplant tissue damage, through radiation or chemotherapy, is thought to increase recognition of host’s antigens by donor’s T-lymphocytes
  • Donor T-lymphocytes cause host cell death through cytotoxic T-cell effects mediated by perforin, granzyme, and apoptosis through Fas/Fas ligand pathway
  • Occurrence related to HLA mismatch but minority of cases develop due to mismatch of minor histocompatibility antigens
CLINICAL ISSUES
Presentation
  • Most commonly occurs in allogenic bone marrow transplants, but also reported in
    • Solid organ transplantation, severely immunosuppressed patients following transfusion of non-irradiated blood products, transplacentally to immunodeficient fetus, and rarely in autologous transplants
  • Acute GVHD
    • Initially, a morbilliform rash characterized by erythematous macules & papules with possible mucosal involvement
    • Begins with punctate lesions around adnexal structures involving face, trunk, palms, & soles
    • Can also present as acral erythema, an eczema-like eruption, ichthyosis, or, in severe cases, erythroderma with diffuse desquamation mimicking toxic epidermal necrolysis
    • Other clinical features include cholestatic hepatitis with increased bilirubin and high-volume diarrhea
  • Chronic GVHD
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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Graft vs. Host Disease

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