Author(s): Vera Tsetlina, MD, Ray Stanford, MD, Jeremy Roberts, MD, Amy Tenaglia, MD, Hana Azizi, MD
Originally published: December 28, 2012 Last updated: April 29, 2021
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Disease/ Disorder

Definition

Hand and face transplants are vascularized composite tissue allografts (VCA) and comprise of multiple tissue types, such as skin, subcutaneous fat, muscle, bone, joint, cartilage, nerve, and blood vessels. There are unique aspects to hand and face transplantation in terms of surgical technique, immunosuppression, and rehabilitation. Intensive, long-term rehabilitation serves a crucial role in recovering allograft function.

Etiology

Hand and face transplantations are performed for conditions that lead to limb loss or severe facial damage, including trauma, burns, congenital anomalies, or disease processes, such as infections and tumors. The first successful hand transplant was performed in 1998 followed by the first face transplant in 2005. More than 120 hand-upper extremity and 37 face transplant procedures have been performed worldwide since.1

VCA currently falls under the scope of organ transplant legislation in Europe and the United States.1 There are no set indications for hand or face transplants, but the primary goal is to improve quality of life by improving function and cosmesis.2 At present, at any given time, waiting list for VCA contain few candidates who are waiting for a closely matched and compatible donor in terms of gender, age, skin aspects, HLA and blood group.

Pretransplant medical evaluation includes specific morphological studies, immunological and surgical evaluation, and a psychosocial assessment.

Outcome studies report that the post-transplantation period of face transplant recipients with pre-existing mental disorders was challenged by suboptimal adherence, difficulties in social reintegration and higher incidence of rejection episodes; despite overall enhancement of quality of life.3

Patho-anatomy/physiology

Two major issues post-transplantation include risks of infection and rejection.

Infections in the early post-transplantation period (1-4 weeks) are generally donor or recipient-derived (colonization, viremia, candidemia) or associated with technical complications of surgery. In the 1-6-month period, infections are commonly from activation of latent infections, relapsed, or residual opportunistic infections in the setting of immunosuppression. Greater than 6 months post-transplantation, infections tend to be of the community acquired variety.4

From a rejection standpoint, the skin is the prime target, but components other than skin may be affected by rejection too. The changes of rejection in composite tissue allotransplantation usually manifest in the skin or oral mucosa and show erythema and appearance of red macules. Most rejection episodes occur during the first year after transplantation. In the chronic stage, other signs of rejection may include contractures, neuropathy, fibrotic changes to the skin, and diminished blood flow to the graft.5

Specific secondary or associated conditions and complications

Patients are followed regularly to assess for rejection, infections, and monitor side effects resulting from immunosuppressive and prophylactic medications, including nephrotoxicity, neurotoxicity, neutropenia, gastrointestinal side effects, diabetes, hypertension, hyperlipidemia, osteoporosis, and malignancies.

Essentials of Assessment

History

Important parts of inpatient history are the reason for transplant, timing posttransplant, current symptoms, as well as functional and psychosocial history/status.

Physical examination

Physical examination should assess the appearance of the transplanted region (skin color and vascularization, skin texture, hair growth, nail growth, lymphatic drainage, and surgical incision sites). Neurologic examination should assess motor, sensory function (light touch, pain, and 2-point discrimination), and additionally, for face transplants, speech, language function, swallowing and cranial nerve function.

Functional assessment

Tests specific to hand transplants include Tinel sign for median nerve involvement (percussion over carpal tunnel at the wrist reproduces pain and paresthesia in the medial nerve distribution at the palmar hand), shape and texture identification tests, Kapandji thumb opposition scores (score of 0 indicates no opposition, a score of 10 indicates full opposition),  pinch and grip observation, and hand dynamometry. Functional measures, such as the Disabilities of the Arm, Shoulder and Hand score, Carroll test, Hand Transplantation Score System, Hand Registry Functional Score, and Action Research Arm Test Score, can be used to assess impairments.6

In addition to assessing the functions of mastication, swallowing, and phonation, some qualitative tests specific to face transplants, such as the Facial Grading Scale and the Facial Disability Index, can be used to assess facial impairments.7

Laboratory studies

Laboratory studies include immunosuppressant levels, other serologic labs, and surveillance skin/oral mucosa biopsies per transplant team. Skin/mucosal biopsy schedules vary according to the transplant team but will be more frequent in the beginning, generally weekly for the first month, then monthly for 4 months, and every 6 months thereafter.8 The Banff classification for composite tissue allotransplantation is used to classify the severity of skin rejection (0-IV, based on pathologic changes).

Imaging

X-ray and bone scintigraphy are used to assess bone healing. Venous and arterial dopplers, and angiogram are used to explore vessel patency.9 Magnetic resonance imaging (MRI) and computed tomography scans are used to assess healing, rejection, and fusion between the donor’s and recipient’s anatomical structures.10

Supplemental assessment tools

Electrodiagnostic studies are used to assess sensory and motor nerve function. Functional MRI and transcranial magnetic stimulation can be used to assess cortical reorganization, elucidate mechanisms of recovery, determine effects of different therapy programs, and help prognosticate functional recovery.

Early predictions of outcomes

Hand transplants

The more distal the level of hand transplantation, the earlier and better the functional recovery. By 1-year posttransplant, most hand transplant patients have developed tactile sensibility, discriminatory sensibility, are carrying out activities of daily living independently, and are beginning to reintegrate back into the community. Most patients report improvements in quality of life11,12

Face transplants

Factors that affect recovery are the extent of scarring, composition of the flap, thickness of the flap, and innervation density of the flap.13 Sensory recovery occurs as early as 3 months posttransplant, protective sensation is usually reached within 6-12 months, and with further time, tactile and discriminative sensibility can be regained. Further sensory recovery can be expected up to 5 years posttransplant.14 Different surgical techniques have been reported to show various results of sensory recovery: end-to-end neurorrhaphies with nerve grafting or nerve transfer if necessary is considered desirable.3

 Motor recovery is detectable 6–8 months after face transplant and recent outcome reports conclude that one year after transplantation, patients were able to perform the majority of basic movements and daily activities at various degrees, such as opening and closing eyelids, eating, drinking, swallowing, chewing, speaking, smiling, kissing and blowing.1, 3 Various techniques used in general Speech and Swallow therapy may improve motor recovery, and functional motoric outcomes. These include facial muscle reeducation, speech therapy, chewing, and swallowing therapy, starting immediately following the transplantation. To date, motor recovery outcomes of face transplants have been characterized as “somewhat below” the original expectations and as average for sensory recovery outcomes.3

Environmental

Patients should adhere to strategies for safe living following transplantation. These include frequent handwashing, avoiding contact with soil, moss, or animal waste, limiting close contact with others with respiratory illnesses, avoiding tobacco smoke, avoiding unpasteurized milk and juices, avoiding raw or undercooked eggs, meat, and seed sprouts, and only drinking from safe water sources.15

Social role and social support system

Face and hand transplants pose psychologic challenges in the acceptance of the visible allograft. Family support, coping mechanisms, and professional support is necessary through the transplant process and beyond.9

Professional Issues

The success of hand and face transplantation depends a great deal on the selection of appropriate candidates. Patient screening includes an anatomic evaluation, functional, medical, immunologic, psychiatric/psychologic, and social screening. The risk and benefits of the transplant are then weighed. Currently, there are no standardized screening tools used, although work is being done in this area. One example is the FACES scoring system, which was developed as a preliminary assessment tool for identifying optimal face transplant candidates. It is based on the evaluation of 5 categories: functional status, aesthetic deficit, comorbidities, exposed tissue, and surgical history.16 As the field of composite tissue allotransplantation evolves, the adoption of standardized guidelines will aid in the candidate selection process and also potentially facilitate an earlier transplantation, which may contribute to improved outcomes.8

Rehabilitation Management and Treatments

Available or current treatment guidelines

Transplant programs should have defined teams with multidisciplinary protocols that carry a patient through recruitment, informed consent, screening, preoperative planning, transplant surgery, and postoperative long-term follow-up including rehabilitation.10 Patients’ compliance with the life-long immunosuppressive treatment and the long-lasting rehabilitation program is the most important factor in achieving a successful functional recovery.

At different disease stages

Postoperative rehabilitation for hand transplants11,17

  1. New onset/acute: Therapy begins immediately post operation with passive mobilization of digits, elbow, and shoulder. Splints are used to maintain range of motion in the wrist and hand.
  2. Subacute: Rehabilitation includes active range of motion exercises with progressive stretching of the forearm muscles. Sensibility and discrimination training is part of the therapy program. Electric stimulation and electromyogram biofeedback can be incorporated.
  3. Chronic: This includes continuing therapies (beyond 1-year posttransplant) and community reintegration goals. The therapy intensity for hand transplants is often times twice daily initially, with gradual tapering over a 1-year course.

Postoperative rehabilitation for face transplants7

  1. New onset/acute: Initial focus is on basic activities, such as respiratory function, ability to eat/drink, and sleep comfortably. Patient education occurs to maintain compliance with precautions in exercise and daily functional activities. Movement may be restricted for 6-8 weeks postface transplant in order to allow for healing.
  2. Subacute: After 1-3 months and with proper healing, static and dynamic facial exercises begin. Facial muscle therapy includes muscle relaxation or stimulation, mirror exercises, facial expression training, and electromyography biofeedback. Speech and swallow training, olfactory sensation and smell training, and other higher-level functional activities related to activities of daily living and mobility are implemented.
  3. Chronic: Therapy continues to achieve the highest possible level of independence with safety, mobility, activities of daily living, visual processing, speech, and swallowing.

Patient & family education

  1. Ongoing interaction and education with the transplant coordinator/team occurs regarding transplant medications, follow-ups, surveillance biopsies, and labs, including immunosuppressant levels, other blood tests, blood pressure, and blood glucose monitoring.
  2. A working relationship needs to be established with the organ recipient’s primary care physician in order to ensure long-term care of chronic problems that may develop.
  3. Long-term occupational, physical therapy, and speech therapy are indicated.

Emerging/unique Interventions

Some functional tests used are the following:

For hand transplant

  1. The Carroll test assesses the global functional capabilities of the upper limb in everyday use. On a scale of 0-99 points, the test results are considered poor at less than 50 points, fair between 51 and 74 points, good between 75 and 84 points, and excellent above 85 points.11
  2. The Hand Transplantation Score System is based on a value of 100 points, which involve 6 items with different weight: appearance (15), sensibility (20), movement (20), psychologic and social acceptance (15), daily activities and work status (15), and patient satisfaction and general well-being (15). A total result of 81-100 points is graded as an excellent outcome, 61-80 as good, 31-60 as fair, and 0-30 as poor.18

For face transplant7

  1. The Facial Grading Scale evaluates facial impairment in three areas: (1) resting posture of the eye, the nasolabial (cheek) fold, and the corner of the mouth; (2) voluntary movement for 5 expressions in 5 regions of the face (forehead wrinkles, eye closure, open mouth smile, snarl, and pucker); (3) and synkinesis.
  2. The Facial Disability Index is a disease-specific, self-report instrument for the assessment of the disabilities of patients with facial nerve disorders; it is scored as 2 subscales, namely physical and social subscales.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Organ transplant is a lifelong partnership between the transplant center and the organ recipient. Teamwork is key to its success. Starting with patient selection, the team works in coordination with the patient, family, and primary care physician through the various stages of the transplant.10

Cutting Edge/ Emerging and Unique Concepts and Practice

Cell-based therapies, such as antibody therapy and donor bone marrow infusions, may allow for transition of transplant paradigms from immunosuppression to immunoregulation and graft tolerance. Maintaining some level of chimerism with representations of both the donor and recipient immune systems may be required to achieve a balance in which neither graft versus host disease nor host versus graft disease is evident. If the need for immunosuppression can be decreased, the adverse effects of immunosuppressant drugs can be minimized.12

Gaps in the Evidence- Based Knowledge

There is an ethical debate about face and hand transplants, which has implications in the patient selection and timing of transplantation. Because such transplants are not a life-saving operation but a quality of life-giving operation, the ethical issues in the selection of recipients for composite tissue transplants include the consideration of risk versus benefit, nonmaleficence versus beneficence, paternalism versus autonomy, informed consent, and financial considerations.19 When do the risks of surgery and immunosuppression outweigh the improvements in quality of life? How much cost is an improvement in quality of life worth in terms of resources and financial support?12

References

  1. Thoung M, Petruzzo P, Landin L, et al. Vascularized composite allotransplant – a Council of Europe position paper. Tranplant International. 2019:32(3):233–240.
  2. Hollenbeck ST, Erdmann D, Levin LS. Current indications for hand and face allotransplantation. Transplant Proc. 2009; 41:495-498.
  3. Tasigirgos S, Kollar B, Kresdorn N et al. Face transplant – current status and future developments. Transplant International, 2018: 31:677-688
  4. Fishman JA. Introduction: infection in solid organ transplant recipients. Am J Transplant. 2009;9(Suppl 4): S3-S6.
  5. Eghtesad B, Fung JJ. Immunosuppression in composite tissue allotransplantation. In: Siemionow MZ, ed. The Know-How of Face Transplantation. London, UK: Springer Verlag; 2011:427-437.
  6. Ravindra KV, Gorantla VS. Development of an upper extremity transplant program. Hand Clin. 2011; 27:531-538.
  7. Dixon PL, Zhang X, Domalain M, et al. Physical medicine and rehabilitation after face transplantation. In: Siemionow MZ, ed. The Know-How of Face Transplantation. London, UK: Springer Verlag; 2011:151-172.
  8. Gordon C, Siemionow M, Papay F, et al. The world’s experience with facial transplantation. Ann Plastic Surg. 2009; 65:572-578.
  9. Petruzo P, Lucchina S, et al. Patient management and follow up. In: Lanzetta M, Dubernard JM, eds. Hand Transplantation. Italy: Springer Verlag; 2007:167-170.
  10. Bueno EM, Diaz-Siso JR, Pomahac B. A multidisciplinary protocol for face transplantation at Brigham and Women’s Hospital. J Plast Reconstr Aesthet Surg. 2011; 64:1572-1579.
  11. Ninkovic M, Weissenbacher A, Gabl M, et al. Functional outcome after hand and forearm transplantation: what can be achieved. Hand Clin. 2011; 27:455-465.
  12. Shores JT, Imbriglia JE, Lee AW. The current state of hand transplantation. J Hand Surg Am. 2011; 36:1862-1867.
  13. Siemionow MZ, Gharb BB, Rampazzo A. Pathways of sensory recovery after face transplantation. Plast Reconstr Surg. 2011; 27:1875-1889.
  14. Brzezicki G, Siemionow MZ. Assessment methods of sensory recovery after face transplantation. In: Siemionow MZ, ed. The Know-How of Face Transplantation. London, UK: Springer Verlag; 2011:225-233.
  15. Avery RK, Michaels MG. Strategies for safe living following solid organ transplantation. Am J Transplant. 2009;9(Suppl 4): S252-S257.
  16. Losee JE, Fletcher DR, Gorantla VS. Human facial allotransplantation: patient selection and pertinent considerations. J Craniofac Surg. 2012; 23:260-264.
  17. Cavadas PC, Landin L, Ibanez J. Bilateral hand transplantation: result at 20 months. J Hand Surg Eur Vol. 2009; 34:434-443.
  18. Lanzetta M, Petruzzo P. A comprehensive functional score system in hand transplantation. In: Lanzetta M, Dubernard JM, eds. Hand Transplantation. Italy: Springer Verlag; 2007:355-362.
  19. Chang J, Mathes D. Ethical, financial, and policy considerations in hand transplantation. Hand Clin. 2011; 27:553-560.

Original Version of the Topic:

Author(s): John J. Lee, MD Originally published: December 28, 2012 Last updated: December 28, 2012

Author Disclosure

Vera Tsetlina, MD
Nothing to Disclose

Ray Stanford, MD
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Jeremy Roberts, MD
Nothing to Disclose

Amy Tenaglia, MD
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Hana Azizi, MD
Nothing to Disclose