Scoring of skin rejection in a swine composite tissue allograft model

Background. For the first time, we define and correlate visual and histolog ic grading systems of composite tissue allograft (CTA) skin rejection in a large-animal model and determine the utility of these grading systems for e arly diagnosis and monitoring of rejection. Materials and methods. Sixteen pairs of outbred swine underwent transplant of a forelimb osteomyocutaneous free flap. Group I (n = 6) did not receive immunosuppressive therapy. Group II (n = 10) received oral cyclosporin A, m ycophenolate mofetil, and prednisone. The flap was visually inspected and p rotocol skin biopsies were taken at frequent intervals over a 90-day period . Visual Grades 0 (no rejection) to 4 (severe rejection) were assigned base d on skin color, bleeding from biopsy site, and blister formation. Histolog ic Grades 0 to 4 were assigned based on the degree of vasculitis, folliculi tis, dermal inflammation, and epidermal degeneration present. Results. All Group I animals progressively rejected their graft by Day 7. G roup II grafts survived from 19 and 90 days; 93% of 115 biopsy specimens we re read to be within +/-1 histologic score of their assigned flap visual gr ade. Visual assessment carried an 8% false positive and 39% false negative rate with regard to biopsy-proven rejection. However, 81% of missed rejecti on specimens were histologic Grade 1. Biopsy, when visually indicated, woul d detect all rejection episodes when histologically Grade 1 or 2 and still potentially reversible. Conclusions. Visual scoring of CTA skin serves as a useful tool for initial ly detecting rejection, but repeated histologic evaluation is necessary for monitoring the subsequent course of the graft. (C) 1999 Academic Press.