Efficacy of cyclophosphamide in toxic epidermal necrolysis. Clinical and pathophysiologic aspects.
In this article we describe the immunocytochemical and electron microscopic findings in five patients with toxic epidermal necrolysis. They indicate the occurrence of necrotic keratinocytes with nuclear disintegration associated with apposed dendritic cells with the nuclear chromatin configuration of T lymphocytes. These findings, including the presence of blebbing of the keratinocytes and membrane defects associated with cytoplasmic processes from these apposed lymphoid cells, fit known electron microscopic criteria that suggest the involvement of T lymphocyte-mediated cytolysis of drug-altered target keratinocytes in toxic epidermal necrolysis. The effector cell appears to be a dendritic subset, with the phenotypic characteristics (CD3+, CD4-, CD8+, CD2+, DR+) of a T cell subset. There is some evidence that tumor necrosis factor alpha, secreted by activated macrophages, may play a role in necrolysis of the epidermis. The dramatic response of our patients to cyclophosphamide, which is known to inhibit cell-mediated cytotoxicity by inhibiting both the recognition and lethal hit stages, together with the rapid regrowth of the epidermis within 4 days to a week in patients who received adequate dosage of the drug, supports the preceding concepts.
Heng
M C
MC
Department of Medicine, University of California San Fernando Valley Internal Medicine Program, Veterans Administration Medical Center, Sepulveda 91343.
Allen
S G
SG
D000328:Adult; D000368:Aged; D000493:Allopurinol / Q000009:adverse effects; D000667:Ampicillin / Q000009:adverse effects; D001485:Basement Membrane / Q000648:ultrastructure; D002462:Cell Membrane / Q000648:ultrastructure; D002747:Chlorpropamide / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004817:Epidermis / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D015603:Keratinocytes / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010672:Phenytoin / Q000009:adverse effects; D013262:Stevens-Johnson Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000473:pathology
D010672:Phenytoin; D000493:Allopurinol; D000667:Ampicillin; D003520:Cyclophosphamide; D002747:Chlorpropamide