Transmission of Donor-Specific Skin Condition From Donor to Recipient of Facial Allograft

Abstract

To the Editor: Facial allotransplantation allows for unprecedented restoration in the most disfigured patients. We recently reported excellent functional and aesthetic results 1 year after central face transplantation (1). Starting approximately 2 weeks after transplant, the facial allograft developed persistent redness. Biopsies obtained from the facial allograft were always consistent with acute rejection grade I and II, resistant to increases in systemic immunosuppression and topical administration of clobetasol cream (days 27–35 and 37–45) or tacrolimus cream (days 26–33, 38–43 and 76–113). On day 115, a diagnosis of rosacea was made on the basis of pathology reports consistent with incidental chronic folliculitis/rosacea. The patient started treatment with metronidazole gel to the face twice per day, which proved effective in eliminating facial redness. Biopsies at 6 and 12 months demonstrated no signs of rejection. After 6 months of therapy, biopsy showed perivascular and periadnexal lymphocytic infiltrate amongst ectatic vessels, suggestive of rosacea. Similarly at 12-month biopsy revealed superficial perivascular lymphocytic infiltrate with a follicular infundibular component. Dr. Kanitakis comments that ‘pathologically, rosacea manifests with a predominantly neutrophilic infiltrate surrounding/invading the epithelial hair-follicle wall, features that are absent in CTA rejection (and in Figure 4c(1))’. Although we agree that neutrophils can be seen in acute, pustular rosacea, erythrotelangiectatic and inflammatory rosacea most often shows a chronic lymphohistiocytic infiltrate, with some preference for the follicular unit, and with little to no neutrophilic component. Clinical features in our patient were most consistent with erythrotelangiectatic rosacea and not an acute pustular variant. Dr. Kanitakis’ patient developed a rosacea-like eruption of the facial allograft 2.5 years after transplant while on ‘excessive, long-lasting applications of clobetasol’. Clobetasol is a superpotent steroid and prolonged application can induce a rosacea-like eruption (2). Dr. Kanitakis’ patient's rosacea-like eruption subsided after clobetasol was discontinued and she was given an oral cyclin. In contrast, our patient only used clobetasol cream between days 27–35 and 37–45. Therefore we consider it highly unlikely that his rosacea-like symptoms were induced by steroid cream application, as the eruption started on day 14 (prior to treatment with clobetasol) and persisted up until day 115 (70 days after discontinuation of clobetasol). The sustained responsiveness of this facial eruption to metronidazole therapy is further suggestive of the correct diagnosis. We do agree with Dr. Kanitakis that the transmission of rosacea from the donor was a ‘local’ disease process, as it was not really transmitted to the original tissues of the recipient, only the facial allograft. This is to be expected given the well-established dissociation of skin-directed immunity from systemic immunity. That is, skin-homing lymphocytes often take residence in cutaneous tissue, expressing skin-specific markers and often not reentering systemic circulation (3). We agree that the possibility of transmission of dermatological disease from the donor to the recipient in CTA renders the diagnosis of rejection more difficult because of overlap in the clinicopathological features. We hope that by being the first to report such transmission, we will bring awareness to the necessity to include such diseases in the differential diagnosis when evaluating persistent symptoms of rejection. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.