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Patients treated with immunosuppressive agents are prone to developing lymphoproliferative disorders, in particular Epstein-Barr virus-associated lymphoproliferative disease. This complication was reported first in post-transplanted patients treated with cyclosporine, and, more recently, in patients receiving long-term methotrexate therapy for inflammatory disease. We describe the case of a 70-year-old female patient with multifocal cutaneous lymphoproliferative disease occurring in the course of long-term, weekly methotrexate therapy for rheumatoid arthritis. Immunohistochemical study revealed the presence of latent membrane protein within neoplastic cells. Cutaneous lesions initially continued to increase in number and size in the first 2 months and finally disappeared completely within 5 months after discontinuation of methotrexate. The patient is now in complete remission with 12-months' follow-up. Despite initial progression after cessation of immunosuppressive therapy, Epstein-Barr virus-induced lymphoproliferative disease may disappear completely within months, thus avoiding pointless chemotherapy.

Cutaneous side effects from heparin administration are rare and usually located at injection sites. We report 3 cases of intraepidermal hemorrhagic blisters occurring distant from sites of subcutaneous injections of heparin. A causative link is suggested by a temporal relationship between heparin introduction and onset of disease as well as exclusion of other causes, but the mechanism remains unknown.

Background: Because of the explosive nature and the extremely rapid process of hyperacute rejection (HAR), significant infiltration of the xenograft by immunocompetent cells is not observed, and the role and the mechanism of action of cell-mediated rejection in discordant xenografts are therefore still under discussion., Method: We developed an experimental approach using pig kidneys perfused with human peripheral blood lymphocytes (PBL) in which the immunologic barrier of hyperacute rejection was excluded and which mimics the in vivo situation., Results: PBL retention in the kidney was evaluated at 20-minute intervals for 3 hours. Retention increased from 30% to 80% with the time of perfusion and was specific because significantly fewer syngeneic lymphocytes were retained. Phenotype analysis of recovered PBL showed a significant decrease in natural killer (NK) cells. Immunohistochemical studies revealed the presence of NK cells and T lymphocytes in the glomerular and interstitial tubular structures of the kidney. Functional studies showed a progressive cessation of diuresis and augmentation of renal vascular resistance when the kidney was perfused with PBL. Electron microscopy examinations of kidney sections perfused with PBL showed swollen endothelial zones, suggesting alterations to and damage of the endothelium., Conclusions: This system provides a valuable model for the study of early discordant xenogeneic cellular rejection and demonstrates the predominance of xenograft infiltration by NK cells.