Mucosa and Rejection in Facial Vascularized Composite Allotransplantation: A Systematic Review

Abstract

Background. Facial vascularized composite allotransplantation (fVCA) presents an established approach to restore form and function of patients with catastrophic facial defects. Skin is one of the target tissues of the rejection process, and due to its easy accessibility has become the gold standard in the diagnosis of rejection. Mucosal rejection frequently occurs; however, the added value of mucosal rejection assessment for patient management is unknown. Methods. We conducted a systematic review of manuscripts listed in the MEDLINE/PubMed and GoogleScholar databases to identify articles that provide data on mucosal rejection following fVCA. For inclusion, papers had to be available as full-text and written in English. Non-VCA studies and animal studies were excluded. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results. We included 17 articles that described changes in allotransplanted mucosa of fVCAs. These articles yielded data on 168 BANFF graded biopsies of corresponding skin and mucosa biopsies. Rejection grades were consistently higher in mucosal biopsies. Concordance between allograft skin and mucosa biopsy grades increased with an increasing skin-BANFF grade. Mucosa rejection grades were on average lower in the early stages of the posttransplant period (<postoperative mo 12, time of motor, and sensory recovery) when compared to the later stages (>postoperative mo 12). Conclusions. The mucosa of facial allotransplants is one of the primary targets of rejection. The data indicates that higher-grade skin rejection does not occur in absence of mucosal rejection. Further investigations are needed to elucidate the exact role of mucosal biopsies for fVCA patient management.

Pathologies of oral and sinonasal mucosa following facial vascularized composite allotransplantation

“…Although biopsy results were unavailable for most mucosal lesions, published data suggest a collinearity between high-grade skin and mucosa Banff grades. 3 The spectrum of mucosa Banff grades narrows with an increase in skin Banff grade and skin rejection. 3 On histology, skin Banff > grade II was reported to be almost exclusively accompanied by mucosal rejection of equal or higher grade.…”

“…1 , 2 Although an fVCA contains different tissue types, skin is thought to be the most immunogenic and susceptible part of the allograft, and thus, the tissue relied on for routine monitoring of face transplant rejection. 3 Most of our knowledge and investigations on changes in fVCAs are therefore centered around the skin portion of the allograft. Little is known about changes that occur in other tissues.…”

Partial Loss of Nasal Tissue in a Facial Vascularized Composite Allograft Patient

“…A recent study shows that higher grade skin rejection (≥BANFF II) is almost always accompanied by equal or more prominent histological signs of rejection on mucosal biopsy. 4 Therefore, biopsy-proven grade II (sub)-clinical skin rejections in POMs 57, 59, 70, and 74 are likely a surrogate of rejection inside the mucocutaneous tissue of the nasal vestibule (Fig. 1 ) ( see figure, Supplemental Digital Content 1 , which displays normal nasal appearance in POM 12.…”

“…Although mucosal rejection is poorly understood, we hypothesize that rejection of the mucosal lining may have contributed to the severity of these findings and to the changes illustrated in Figure 1 . 4 …”

Biomarker and surrogate development in vascularised composite allograft transplantation: Current progress and future challenges

“…[18][19][20] However, unique to facial transplantation, mucosa appears to be one of the primary targets of acute rejection, and is always present in higher-grade skin rejection samples. 21 Additionally, when VCA skin pathology specimens are reported, there is inherent intra-and inter-observer error, as inflammation seen is not specific to rejection. 22 This issue is not unique to VCA, with borderline changes being a challenge to differentiate from true acute rejection, necessitating clinical correlation.…”