The histological diagnosis of cutaneous graft versus host disease: relationship of skin changes to marrow purging and other clinical variables

Abstract

Punch biopsies of skin were taken from allogeneic marrow recipients routinely before transplantation, at 14-22 and 90-107 d after grafting and in the event of a clinical rash. Three histological appearances were encountered: graft versus host disease (GvHD), epidermal abnormalities, and normal. Graft versus host disease was characterized by epidermal basal vacuolation, spongiosis and individual cell necrosis associated with mononuclear cell infiltration of the upper dermis and lower epidermis, while epidermal abnormalities were identical to GvHD but without the mononuclear cell infiltrate. Graft versus host disease occurred only in patients receiving marrow unpurged of T-cells while epidermal abnormalities occurred with equal frequency in recipients of purged and unpurged marrow and were also noted in a high proportion of pre-transplant biopsies. Patients whose skin biopsies exhibited epidermal abnormalities showed no greater incidence of subsequent clinical or histological GvHD than those with normal biopsies. For these reasons, we conclude that epidermal abnormalities cannot be regarded as a minor manifestation of GvHD as has often been previously assumed. We also conclude that they cannot be regarded as the cause of a rash as, unlike GvHD, the incidence was not significantly different in patients with and without rashes. The cause of epidermal abnormalities is not entirely clear; cytotoxic drugs and irradiation appear to play a part but their occurrence in patients with previously normal post-transplant biopsies suggests that other factors may also be important. Some patients with strong clinical evidence of GvHD had negative biopsies; these should be regarded with caution especially within the first 24 h after the onset of a rash as the diagnostic histological picture may take time to develop. In some cases, GvHD was confined to pilosebaceous units; this seems to represent a minor form of the disease with only a limited capacity for progression. Dysplastic epidermal changes which have previously been attributed to the use of cyclosporin A were found with equal frequency in patients who did not receive this drug and must therefore have some other cause.

Cyclosporin A-induced graft-versus-host disease following autologous bone marrow and stem cell transplantation in hematological malignancies of childhood

“…The histological diagnosis of acute cutaneous GVHD was established when at least grade 2 acute GVHD changes were present, including basal vacuolar degeneration, spongiosis, dyskeratosis, and an infiltration of lymphocytes in the upper dermis and lower epidermis. 22,23 The cryostat sections of skin biopsies were stained with two monoclonal mouse antibodies to human CD4 and CD8 antigens (MT310 and DK25; Dako, Hamburg, Germany), using standard immunohistochemical examination by means of an alkaline phosphatase/anti-alkaline phosphatase technique to detect antibody binding.…”

Clinical Significance of Skin Biopsies in the Diagnosis and Management of Graft-vs-Host Disease in Early Postallogeneic Bone Marrow Transplantation

“…17,[19][20][21] The situation is further complicated by the fact that frequently there is a lack of correlation between clinical features and histologic findings. 16,17 For example, the skin in a clinically affected area may seem unremarkable histologically, or clincally uninvolved skin can display basal keratinocyte vacuolization and necrosis consistent with well-established GVHD. 17 Therefore, the diagnostic value of skin biopsies has been questioned.…”

Severe Drug-Induced Skin Reactions: Clinical Pattern, Diagnostics and Therapy

“…Moreover, adnexal involvement in SJS/TEN seems to be restricted to infundibular epidermis and epithelia of acrosyringia, whereas in GVHD lower parts of the hair follicle and epithelia of sebaceous glands may be involved (figures 6B and 6C). [Elliott, et al, 1987] 3. Generalized bullous fixed drug eruption…”