面部移植中急性排斥反应的临床表现变化。
The Evolving Clinical Presentation of Acute Rejection in Facial Transplantation.
机构信息
Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Hand, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany.
出版信息
JAMA Facial Plast Surg. 2019 Jul 1;21(4):278-285. doi: 10.1001/jamafacial.2019.0076.
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, ∞; 95% CI, 2.2-∞; 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
重要性：急性排斥反应是面部移植中最常见的并发症之一，如果忽视，可能会对受者造成严重后果。在早期随访阶段，红斑或水肿等临床症状有助于诊断急性排斥反应；然而，在移植后第二年以后，这些临床症状是否仍然是急性排斥反应的可靠标志物尚不清楚。
目的：确定面部移植后临床排斥反应症状随时间的变化的诊断价值。
设计、地点和参与者：这是一项回顾性、单中心队列研究，纳入了 2009 年 4 月至 2014 年 10 月期间在布里格姆妇女医院接受面部移植的患者，随访时间长达 8 年。对患者的病历进行了回顾性分析，直至 2017 年 9 月 30 日。分析了 7 名接受部分或全部面部移植患者的 104 次就诊的排斥症状、免疫抑制治疗和组织病理学发现。
主要结果和测量：评估了 5 种急性排斥反应的临床症状：红斑、水肿、皮疹、缝线红斑和黏膜病变。计算了比值比（ORs）以确定这些症状与组织病理学排斥诊断的统计学显著关联。此外，还评估了作为免疫抑制治疗替代标志物的他克莫司血药浓度。
结果：研究纳入了 7 名男性患者，平均随访时间为 66 个月（范围为 35-101 个月）。在 104 次临床就诊中，46 次（44.2%）为排斥发作，58 次（55.8%）为无排斥发作。移植后 2 年以上，仅红斑（OR，6.53；95%CI，1.84-20.11；P=.004）和皮疹（OR，∞；95%CI，2.2-∞；P=.004）被证明是面部移植中急性排斥反应的可靠临床症状。他克莫司血药浓度低于治疗范围也与晚期排斥发作有统计学显著关联（OR，3.79；95%CI，1.25-12.88；P=.03）。此外，在后期随访中，亚临床排斥的发生率更高（7 [24.1%] 晚期排斥与 1 [5.9%] 早期排斥）。8 次亚临床排斥中有 5 次（62.5%）与他克莫司血药浓度低于治疗范围有关。
结论和相关性：面部移植中急性排斥反应的临床症状似乎诊断价值有限，尤其是在术后第二年以后。在确定替代排斥反应的生物标志物之前，协议性皮肤活检仍将是指导同种异体移植物排斥反应评估所必需的。
证据等级：3 级。
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