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.