Synonyms: Autologous graft vs. host disease, graft-vs-host reaction, cutaneous eruption of lymphocyte recovery syndrome
Etiology: Cytotoxic T-cells attack antigens on keratinocytes
Associations: Bone marrow transplantation
Clinical: Erythematous patches, and papules progressing in some cases to bullae; associated with fevers, diarrhea, elevated liver function tests
Histology: Dying keratinocytes within epidermis, mild perivascular and interface lymphocytic infiltrate
IHC repertoire: Not usually necessary; CD8+ lymphocyte predominate
Staging: Based upon degree of involvement in the gastrointestinal tract, liver, and skin
Prognosis: Correlated with histologic grade of lesions and overall clinical stage; in general, poor
Adverse variables: Histologic subtype of high-grade GVHD
Treatment: Increased corticosteroids
32
Graft-versus-Host Disease
GVHD is a common consequence of allogeneic bone marrow transplantation. Approximately 3 weeks fol- lowing complete marrow eradication and the transplan- tation of allogeneic donor marrow cells, a cutaneous eruption is seen in up to 20% to 80% of patients, and may result in the death of the patient (1,2). The cutaneous manifestations may be the first indication of evolving GVHD.
GVHD is arbitrarily divided into acute and chronic forms. The acute form of the disease ordinarily occurs between 21 and 60 days following bone marrow trans- plantation. Patients develop maculopapular or scarlatini- form eruptions (Figure 32.1). In the more severe forms of the disease, bullae may develop and progress to wide- spread desquamation in a toxic epidermal necrolysis- like pattern. The palms and soles are often involved early in the disease, while the trunk, neck, cheeks, and ears are commonly affected as the disease progresses (Figure 32.2).
The chronic form of the disease occurs more than 100 days following bone marrow transplantation. The histo- logic features consist of a band-like lymphocytic infiltrate similar to lichen planus in the early chronic phase. Well developed lesions of chronic GVHD show epidermal
atrophy with a thickened basement membrane and dermal fibrosis simulating morpheal scleroderma.
GVHD, or a virtually identical process, has been reported in patients receiving autologous blood transfu- sions (3). The process is much milder and does not ordi- narily lead to adverse consequences, but suggests that even the host’s own lymphocytes are capable of causing disease in these immunocompromised patients. The responsible cell is an immunocompetent T cell derived from the bone marrow, be it autologous or allogeneic (4).
The cutaneous eruption of lymphocyte recovery is a similar process that occurs in patients who have not received a transfusion of blood products. This eruption occurs during the time of bone marrow reconstitution, in patients who have had marrow ablative therapy. Again, several weeks following chemotherapy and radiation therapy, patients develop fevers and a cutaneous eruption indistinguishable from that seen in GVHD. The eruption coincides directly with an increasing lymphocyte count and abates as the marrow fully recovers (5).
The histologic features of each of these entities are similar and differ only in degree. There is a well- recognized grading scheme for evaluating histologic changes of GVHD in the skin (Table 32.1).
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32. Graft-versus-Host Disease 155
In all cases, a mild infiltrate of lymphocytes is present surrounding the vessels of the superficial vascular plexus.
Scattered lymphocytes are present within the lower levels of the epidermis, and in grades II–IV, these lymphocytes are present around dying keratinocytes (Figures 32.3 and 32.4).
The histologic differential diagnosis includes an ery- thema multiforme-like drug eruption and a viral exanthem.
A rigorous staging classification has been developed for acute GVHD (7). Higher-stage disease is associated with increased risk for transplant-related mortality (8).
FIGURE 32.1. Acute graft-versus-host disease with erythema-
tous macular rash and blister formation. FIGURE32.2. Acral erythematous plaques seen in acute graft- versus-host disease.
FIGURE32.3. Medium power detail of subacute interface dermatitis with epidermal necrolysis.
Table 32.1. Histologic Grading Scheme for GVHD
Histologic Grade Histologic Features
I Basal vacuolization, mild lymphocytic
infiltrate with exocytosis—nondiagnostic
II Basal vacuolization, dyskeratotic
keratinocytes, mild lymphocytic infiltrate with exocytosis and satellitosis
III Focal clefting at dermal epidermal junction due to basal keratinocyte necrosis; mild lymphocytic infiltrate with satellitosis
IV Epidermis completely separated from
dermis, mild lymphocytic infiltrate with exocytosis and satellitosis
156 Deadly Dermatologic Diseases
Patients who develop GVHD have been shown to have a lower risk for relapse of their primary neoplastic disease.
References
1. Thomas ED, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE, Lerner KG, Glucksberg H, Buckner CD. Bone marrow transplantation. N Eng J Med 1975; 292: 832–843, 895–902.
2. Deeg HJ, Storb R. Graft-versus-host disease: Pathophysiological and clinical aspects. Ann Rev Med 1984; 35: 11–24.
3. Anderson KC, Weinstein HJ. Transfusion-associated graft- vs.-host disease. N Eng J Med 1990; 323: 315–321.
4. Billingham RE. The biology of graft-versus-host reactions.
Harvey Lect 1966–67; 62: 21–78.
FIGURE 32.4. High power detail showing clusters of necrotic kerati- nocytes with adjacent lymphocytes (satellitosis) typical of acute graft- versus-host disease.
5. Bauer DJ, Hood AF, Horn TD. Histologic comparison of autologous graft-vs.-host reaction and cutaneous eruption of lymphocyte recovery. Arch Dermatol 1993; 129:
855–858.
7. Zhou Y, Barnett MJ, Rivers JK. Clinical significance of skin biopsies in the diagnosis and management of graft-vs.-host disease in early postallogeneic bone marrow transplantation.
Arch Dermatol 2000; 136: 717–721.
8. Storb R, Prentice RL, Buckner CD, Clift RA, Appelbaum F, Deeg J, Doney K, Hansen JA, Mason M, Sanders JE, Singer J, Sullivan KM, Witherspoon RP, Thomas ED. Graft-versus- host disease and survival in patients with aplastic anemia treated by marrow grafts from HLA-identical siblings:
Beneficial effect of a protective environment. N Eng J Med 1983; 308: 302–307.
