Until recently, reconstructive options for disfiguring facial injuries secondary to severe burns were limited to more traditional techniques (i.e., grafts, local and free flaps). The first facial transplantation (FT) was performed in France in 2005 and introduced a revolutionary use of vascularized composite allotransplantation (VCA) to restore facial function and aesthetics. Facial VCA is an ever-evolving field with morbidity and mortality risk, further complicated by additional challenges secondary to burn injury. However, severe facial burns can be an appropriate indication for transplantation, given the extent of injury that can result. VCA can be a powerful tool for reconstruction in the appropriately selected patient.

Facial burn injuries can result in devastating functional and aesthetic deficits and psychosocial distress. Unlike other common indications for a face transplant, such as ballistic injuries or animal attacks, burn injuries result largely in soft-tissue defects. Deeper partial-thickness burns are at high risk for healing with hypertrophic scarring, contracture, and loss of contour, leading to significant functional and aesthetic deformity and often long-term pain. Full-thickness burns require, in general, an excision and coverage. The timing of management of burns for optimal healing requires a balance between early excision and grafting, prompt coverage of exposed critical structures, and preservation of as much native tissue as possible, with the latter consideration being critical to facial burns. Thus face burns are often initially managed conservatively to maximally preserve the dermis and allow for demarcation of the zone of injury. After severe facial burn injury, patients may have impaired respiratory function, orofacial pain and dysfunction (oral incompetence, drooling), and facial disfigurement that affects the quality of life physically, socially, and psychologically. Depending on the scope of damage, head and neck burn reconstruction has historically ranged from a simple contracture release to free flap reconstruction.

When weighing options for facial reconstruction, one must consider the aesthetic units of the face, which are defined by their skin quality, natural borders, and structure: forehead, eyelid, nose, lips, cheek, and chin. Many of the aesthetic units are further divided into subunits. Principles of facial reconstruction dictate that facial units/subunits should be reconstructed entirely when possible for best results. Dermal substitutes and skin grafts are workhorses in burn reconstruction. However, using these techniques for burn injury of the face often produces unsatisfactory cosmetic results, especially in large or deep wounds, primarily because of a mismatch in color and texture of the donor site skin. Local or regional flaps can be useful in the acute and reconstructive setting, but the extent of burn injury and available donor tissue often limits options. Tissue expansion can increase the yield of existing normal local donor tissue. Once patients are stable and scar remodeling is complete, more complex reconstructive techniques like free flaps may be considered with the primary goal of improving aesthetics and function for patients. Free flaps combined with additional modifications such as prelamination or prefabrication for head and neck reconstruction after burns have been described in the literature. ^, However, conventional techniques for reconstruction are often inadequate in restoring appearance and function, especially when multiple central facial units (nose, lips, eyelids) are involved. Central subunits have more distinct three-dimensional (3D) contours, unique anatomic structures, and multiple tissues working in concert for proper function. Aesthetic and functional implications, as compared with their peripheral counterparts (forehead, chin), are more complex, and reconstruction is challenging. Extensively burned patients often do not have suitable local donor tissue and require multiple procedures, resulting in increased morbidity and risk for scarring and unsatisfactory functional and aesthetic outcomes.

VCA involves transferring multiple tissue types such as skin, mucosa, muscle, cartilage, bone, nerves, vessels, salivary glands, and lymphatic tissue. Before the first successful hand transplant in 1998, it was thought that the immunogenicity of skin would not allow for successful allotransplantation. After this innovation, advances were made in VCA, with the first partial facial transplant being performed in France (2005) for a female with a traumatic facial injury. The first facial VCA for a patient with a burn injury was performed by Dr. Bohdan Pomahac in 2009 ( Fig. 59.1 ). Since then, over 50 patients have undergone FT worldwide. Although facial VCA has become more accepted as an appropriate treatment for patients with severe facial injuries, there remain discussions regarding indications, immunosuppression management, surgical technique, and outcomes tracking as experience grows.

(A) Facial injury after severe electrical burns. (B) Patient underwent anterolateral thigh flap for midface coverage. (C) Seven years after vascularized composite allotransplantation.

(From Pomahac B, Diaz-Siso JR, Bueno EM. Evolution of indications for facial transplantation. J Plastic Reconstr Aesthet Surg . 2011;64:1410-1416, with permission from Elsevier.)

The primary indication for a facial transplant is a facial defect that cannot be adequately addressed with conventional reconstructive techniques. In our center, FT is considered in patients who have soft-tissue loss of more than 25% of facial surface area and loss of multiple central facial units such as nose, lips, or eyelids. In practice, finding an appropriate candidate is much more nuanced and requires a comprehensive preoperative workup and evaluation.

Generally accepted contraindications include active or significant medical issues (cancer, kidney, or liver disease), inability to adequately follow up, poor medical compliance, lack of financial and social support, and uncontrolled psychiatric illness that limits a patient’s ability to understand the procedure, cope with recovery and complications, and comply with medical direction. Beyond these contraindications, programs have institution-specific inclusion and exclusion criteria that consider patients individually, including the history of cancer, human immunodeficiency virus (HIV), and self-induced facial injury. ^,

FT may be strongly indicated to restore form and function in cases of extensive burns for which locoregional or even free flaps are suboptimal or unfeasible; this most often presents itself in the form of defects that involve the midface and affect aesthetics and function, including breathing, eating, and oral competence ( Fig. 59.2 ). To date, VCA has only been performed on adults. Although technically feasible and potentially increasing quality of life, ethical and medical considerations further complicate the decision to pursue FT in minors. Further multidisciplinary conversations regarding informed consent, early initiation of lifelong immune suppression, and the potential need for additional procedures or transplants are warranted when considering VCA in this patient population. As we advance in face transplant surgery and transplant immunology and more long-term outcomes studies are performed, the indications for VCA may expand to include a broader subset of patients.

(A) Oral incompetence, ectropion, and total nasal defect after burn injury, after delayed and expanded trapezius free flap to lower-third of face and neck. (B) Three years after vascularized composite allotransplantation.

(From Pomahac B, Diaz-Siso JR, Bueno EM. Evolution of indications for facial transplantation. J Plastic Reconstr Aesthet Surg . 2011;64:1410-1416, with permission from Elsevier.)

Before 2014, facial transplant programs worked with local organ-processing organizations to match donors and recipients, as facial allograft donation was not managed like organs for transplantation. ^, In 2014, the US Department of Health and Human Services amended federal regulations known as the Final Rule of the National Organ Transplant Act to include VCA in the classification of “human organ.” Now, the Organ Procurement and Transplantation Network, overseen by the United Network of Organ Sharing, is responsible for implementing the donation and transplantation process. Standard histocompatibility matching of donor and recipient, including ABO blood-type compatibility and negative crossmatch, are considered when searching for a suitable donor. However, a successful face transplant has been performed on a highly sensitized recipient with a positive donor-recipient crossmatch. ^, Donor selection in facial VCA is further complicated by the need to match donor sex, recipient skin tone, quality, and, ideally, age. Additionally, burn patients who have undergone temporizing coverage with cadaveric allograft and received multiple blood products are at much greater risk for sensitization. Finding compatible donors can pose a significant challenge. It is important to note that consent for VCA donation is considered separate from all other solid organ donations to “preserve the public trust in the process of organ donation” and requires explicit authorization from the appropriate surrogate decision-maker.

Only patients with plans for a closed-casket funeral are currently considered for facial VCA in most centers worldwide. Still, the recovery of facial allograft for transplant leaves behind a disfiguring defect in the donor. Different methods, including silicone molds or 3D imaging and printing, have been described for restoring the likeness of the donor after transplantation. Regardless of the approach used, donor masks are recommended to maintain the dignity of the donors and their families during and after the procurement process.

Finding the appropriate candidate for FT requires attention to many details beyond basic inclusion criteria. Patients must be well informed with realistic expectations and a complete understanding of risks and benefits; a facial transplant is a lifelong commitment to immunosuppressive medication, medical follow-up, and surveillance, with a potential need for admission for episodes of infection or rejection and possible need for further revision surgeries. Patients undergo screening for psychological disorders and alcohol or substance use disorders. Additionally, patients need proof of adequate social and financial support. Evaluation and clearance for surgery requires a multidisciplinary team, including plastic and reconstructive surgeons, head and neck surgeons, transplant surgeons, psychiatrists, transplant medicine physicians, social workers, patient advocates, and rehabilitation therapists.

Preoperative screening to assess transplant viability includes introductory lab and imaging studies, viral screening, cancer screening, and confirmation of standard immunization history ( Box 59.1 ). Generally, preoperative imaging includes CT scans and head and neck angiographic studies.

FT necessitates lifelong immunosuppression to prevent rejection. Most immunosuppression regimens are based on current solid organ transplant (SOT) protocols. Induction protocols vary and include combinations of drugs including but not limited to rabbit antithymocyte globulins (ATGs), corticosteroids, mycophenolate mofetil (MMF), tacrolimus, antiinterleukin-2 receptor antibodies (basiliximab), anti-CD52 antibodies (alemtuzumab), and anti-CD3 monoclonal antibodies. The most used long-term suppressive regimen consists of corticosteroids, tacrolimus, and MMF. Perioperative and postoperative antibiotics, antivirals, antifungals, and antacids are administered for prophylaxis.

Immunosuppressive drugs are accompanied by increased lifelong risks of infection (opportunistic infections including cytomegalovirus, Clostridioides difficile, herpes simplex) following a similar pattern to organ transplant patients. Malignancies are considerably less frequent than in organ transplant patients, especially in the category of the most common skin malignancies. Systemic toxicity (diabetes, hypertension, hyperlipidemia, nephrotoxicity, neurotoxicity, acquired aplastic anemia) secondary to immunosuppressive drugs have also been described. As no reliable biomarkers inform the physician about the patient’s immunologic status, immune suppressive management is often empiric and driven by the side effects from each category: oversuppression leads to infections, whereas undersuppression leads to rejection. Maintaining a balance of the risks and benefits and managing these medications requires patient compliance and consistent monitoring. The gold standard for monitoring rejection is a skin biopsy. Grading of rejection is derived from the Banff consensus conference, and treatment corresponds to the diagnosed grade.

The importance of appropriate preoperative counseling and discussion of risks with the patient cannot be understated. In addition, medical teams should have patient-specific plans for managing immune-mediated complications and operative salvage before pursuing transplant.

A thorough understanding of facial anatomy is imperative for the planning and execution of FT. Preoperative planning should include an assessment of the recipient’s facial tissue defects so they can be adequately addressed with complementary donor tissue. This process is a product of both aesthetic and functional evaluation. As such, no specific formula indicates which subunits to reconstruct and which to remove and replace. For instance, consider the decision to reconstruct a patient’s eyelids. A case of FT after an electrical burn sustained in 2001 presented the problem of an intact orbicularis muscle with thickening of the overlying skin graft, leading to poor eyelid mobility and aesthetics. The decision was not to remove the patient’s eyelids and entirely replace them. Instead, the facial allograft contained a skin-only eyelid component placed over the patient’s intact orbicularis after the removal of the skin graft. Ultimately, the patient had preserved eyelid function and restoration of his eyelid aesthetics. As in all cases of face transplant, the patient’s needs must be elucidated and taken in the context of the whole clinical picture.

The decision of when to remove the recipient’s normal tissues and replace them with a transplant is often driven by aesthetics and must be considered carefully in every patient. Any functionally and esthetically intact tissue removed adds to potential morbidity should the transplant fail. A decision must be made whether to keep residual lips, cheeks, and other intact soft tissue or to replace them. Although removing them and replacing them with transplanted tissue may provide an improved aesthetic result early in the postoperative period, in the case of graft loss, the excised tissue must be reconstructed by other means. These salvage procedures can be daunting and will be discussed later in the chapter.

The complications of FT continue to evolve as more VCA cases are undertaken internationally. The most commonly published complications in the literature are acute and chronic rejection, infection, graft loss, and death.

Infectious complications

Infection is the most common complication of VCA and is more likely to occur during the first postoperative year than in the following years. Among both SOT and VCA patients, there seems to be a shift in early versus late infections. Early infections, roughly within 1 month postoperatively, tend to be donor-derived or related directly to surgery complications. Intermediate infections, ranging from 1 to 6 months after surgery, are usually associated with viral pathogens, endemic fungi, and opportunistic infections. Finally, late infections, developing after 6 months postoperatively, comprise community-acquired infections or opportunistic infections with listeria, Nocardia species, and other unusual organisms.

Local bacterial infections of the allograft are the most common infectious complication in FT, followed closely by opportunistic viral infections, with CMV being the most common cause. Compared with the data for upper-extremity transplantation, FT recipients tend to develop infectious complications more often. One hypothesis explaining the difference in infection rates is the transplantation of microbially colonized tissue, such as oral mucosa, glandular tissue, and nerve tissue in facial VCA, which may result in local infection. Despite the difference in FT versus upper-extremity transplant, VCA recipients tend to experience infections at a similar rate as SOT recipients.

Table 59.1 shows preoperative viral serologies taken to tailor prophylactic antiviral therapy. For instance, the highest-risk combination in CMV prophylaxis is a seronegative recipient and a seropositive donor. There is much debate surrounding the ideal duration of valganciclovir prophylaxis for CMV. A recent multinational review shows that the standard practice of 3 to 6 months of valganciclovir prophylaxis is widely practiced. However, the data suggest extending the prophylaxis beyond 6 months may reduce the incidence of viremia or AR in the first year of transplant.

Table 59.1

The Banff Classification

Grade	Pathologic Findings	Presentation	Treatment
0	No or rare inflammatory infiltrates.	■ Unaffected skin	None
I	Mild perivascular inflammation without involvement of the epidermis.	■ Unaffected skin	Observation without treatment provided immunosuppression levels are in the desired range
II	Moderate to severe perivascular inflammation. The epidermis may or may not be involved. No dyskeratosis or apoptosis of the specimen.	■ Erythematous macules	Increase in maintenance immunosuppression OR Steroid bolus
III	Dense inflammation with epidermal involvement demonstrates epithelial apoptosis, dyskeratosis, and keratinolysis.	■ Erythematous macules ■ Lichenoid changes ■ Mimics cutaneous pseudolymphomas, true cutaneous B-cell lymphomas, and lichenoid dermatoses	Steroid bolus If unresponsive Anti–T-cell agent (e.g., thymoglobulin or alemtuzumab)
IV	Frank necrosis of the epidermis and other structures.	■ Similar to grade III Plus ■ Erosive and necrotic skin zones	Surgical debridement, in addition to grade III treatment modalities

To cover against head and neck flora perioperatively, cefazolin and vancomycin are prescribed. Samples from the nares, respiratory sputum, and blood cultures are evaluated by both the donor and the recipient, and antibiotics can be tailored appropriately. The first burn patient to receive an FT in 2009 had his prophylactic antibiotics changed from cefazolin to imipenem after blood and sputum cultures from the donor grew Proteus mirabilis . Antifungal coverage is also included because of high rates of fungal contamination during the recovery period. Preventative trimethoprim-sulfamethoxazole is given for Pneumocystis jirovecii coverage. These preventative medications can be continued 6 months after the transplant to prevent the development of infection. Antifungal coverage is also started with micafungin. However, this is only used in the immediate postoperative period.

Infections are treated with targeted antibiotics as they develop in the FT postoperative course. Postoperative infections can be devastating and, in rare cases, fatal in FT. Prevention is key, and perioperative prophylaxis is imperative. When indicated, surgical management of infection should be used. The first Black patient to receive a face transplant developed a subgaleal hematoma superinfected with Aspergillus . After debridement, the patient was treated with posaconazole and developed complete resolution.

Malignancy

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