Sequential histological and immunohistochemical study of the skin of the first human hand allograft

On September 1998, the first human hand allograft was successfully performed in Lyon. A 48-year-old white man who had suffered accidental amputation of the arm in 1984, received a forearm and hand allograft from a 42-year-old white male cadaveric heart-beating donor. Immunosuppressive therapy included prednisone, mycophenolate mofetil, FK506, and antithymocyte globulins. Sequential skin biopsies were taken from the grafted limb and examined (immuno)histologically to detect a possible graft rejection and to evaluate the structural integrity of the skin of the allograft. The skin showed histologically a normal appearance, except on days 57 and 63, when a mononuclear perivascular cell infiltrate was observed in the dermis; this appeared concomitantly with erythematous lesions of the skin that developed after a slight decrease of the immunosuppressive treatment. These changes were considered as signs of graft rejection, and were reversed by an increase of the immunosuppressive treatment. No skin necrosis was seen at any time. Immunohistochemically, the main cell types of the skin were present throughout the study. From day 77 onward the epidermis of the grafted hand harbored some epidermal Langerhans cells of recipient's origin. This study shows that the skin of the hand allograft maintains overall a normal histological structure and contains most essential cell types, including cells of recipient origin, such as Langerhans cells. Furthermore, it shows that in this system of composite tissue transplantation, skin biopsies may reveal a starting graft rejection, before the appearance of clinically obvious lesions.