The Evolving Clinical Presentation of Acute Rejection in Facial Transplantation

Abstract

IMPORTANCE Acute rejection is one of the most frequent complications in facial transplantation, with potentially severe consequences for the recipient if overlooked. Clinical signs, such as erythema or edema, are helpful to diagnose acute rejection in the early follow-up stage; however, it is not well known whether these clinical signs remain reliable markers of acute rejection beyond the second posttransplant year. OBJECTIVE To determine the diagnostic value of clinical signs of acute rejection after facial transplantation over time. DESIGN, SETTING, AND PARTICIPANTS A retrospective, single-center cohort study was conducted of patients who underwent facial transplantation at Brigham and Women's Hospital between April 2009 and October 2014, with up to an 8-year follow-up. Medical records were reviewed until September 30, 2017. The medical records from 104 encounters with 7 patients who underwent partial or full facial transplantation were analyzed for symptoms of rejection, immunosuppressive therapy, and histopathologic findings. MAIN OUTCOMES AND MEASURES The occurrence of 5 clinical signs of acute rejection were evaluated: erythema, edema, exanthema, suture line erythema, and mucosal lesions. Odds ratios (ORs) were calculated to determine the statistically significant association of these signs with the histopathologic diagnosis of rejection. In addition, tacrolimus blood levels, as a surrogate marker of immunosuppressive therapy, were evaluated. RESULTS Of the 7 patients included in the study, 5 were men. The mean follow-up was 66 months (range, 35-101). Of 104 clinical encounters, 46 encounters (44.2%) represented rejection episodes and 58 encounters (55.8%) represented no-rejection episodes. Beyond 2 years posttransplantation, only erythema (OR, 6.53; 95% CI, 1.84-20.11; P = .004) and exanthema (OR, ϱ; 95% CI, 2.2-ϱ; P = .004) were demonstrated to be reliable clinical signs of acute rejection in facial transplantation. There was also a statistically significant association of subtherapeutic tacrolimus levels with late rejection episodes (OR, 3.79; 95% CI, 1.25-12.88; P = .03). In addition, the occurrence of subclinical rejection was more frequent during later follow-up times (7 [24.1%] late rejections vs 1 [5.9%] early rejection). Five of 8 subclinical rejections (62.5%) were associated with subtherapeutic tacrolimus levels. CONCLUSIONS AND RELEVANCE Clinical signs of acute rejection in facial transplantation appear to be of limited diagnostic value, particularly after the second postoperative year. Until alternative biomarkers for rejection are identified, protocol skin biopsies will remain necessary for guiding assessments of allograft rejection. LEVEL OF EVIDENCE 3.

MMP3 Is a Non-invasive Biomarker of Rejection in Skin-Bearing Vascularized Composite Allotransplantation: A Multicenter Validation Study

“…This lack of correlation of histopathological assessment with treatment response might be partially attributed to sampling bias or intra- and inter-observer variability of biopsy evaluation (13). Additionally, the clinical presentation of AR in face transplantation appears to evolve over time, leading to higher rate of subclinical rejection as well as subtler presentation of the traditional clinical signs of AR (e.g., erythema, edema, exanthema) at longer follow-up (14). Taken together, the decision to treat rejection is very complex and may significantly vary among different centers, in particular, if protocol biopsies are performed or not, which makes a standardized approach difficult.…”

Pathologies of oral and sinonasal mucosa following facial vascularized composite allotransplantation

“…A previously published case report, however, suggests that the baseline microscopic mucosal inflammation of fVCAs does not change after discontinuation of MMF. 5 Sub- 20 Infectious etiologies of mucosal lesions must be ruled out by adequate testing. The head and neck mucosa of fVCAs is susceptible to the development of infectious complications due to prolonged duration of high-potency immunosuppression.…”

Noninvasive Identification of Core Gene Biomarkers in Patients with Acute Kidney Transplant Rejection

“…On the basis of pathophysiology, AR fall into two categories, which are antibody-mediated rejection (ABMR) and acute T-cell mediated rejection (TCMR) respectively [22] . On the one hand, In ammation of glomeruli and peritubular capillary are always attributed to ABMR.…”