Mixed connective tissue (face and hand)

Author(s): John J. Lee, MD

Originally published:12/28/2012

Last updated:12/28/2012

1. DISEASE/DISORDER:

Definition

Hand and face transplants are vascularized composite tissue allografts, because they comprise of multiple tissue types, such as skin, subcutaneous fat, muscle, bone, joint, cartilage, nerve, and blood vessels. Thus, 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 through cortical reorganization.

Etiology

Hand and face transplantations are performed for conditions that lead to limb loss or severe facial damage, such as trauma, congenital anomalies, ordisease processes, such as infections and tumors. 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.1

Patho-anatomy/physiology

Two major issues posttransplantation are the risks of infection and rejection.

Infections in the early posttransplantation 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. Greater than 6 months posttransplantation, infectionstend to be of the community acquired variety.2

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.3

Specific secondary or associated conditions and complications

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

2. ESSENTIALS OF ASSESSMENT

History

Important items inpatient history are the reason for transplant, timing posttransplant, sign and symptoms,and 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, and cranial nerve function.

Functional assessment

Tests specific to hand transplants include Tinel sign, shape and texture identification tests, Kapandji test, pinch and grip observation, and hand dynamometer. 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.4

In addition to assessing the functions of mastication, deglutination, 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.5

Laboratory studies

Laboratory studies include immunosuppressant levels, other serologic labs, and surveillance skin/oral mucosa biopsies per transplant team.Skin/mucosalbiopsy schedules vary according to the transplant team but will be more frequent in the beginning, generally every week for the first month, then every month for 4 months, and then every 6 months thereafter.6 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, arterial dopplers, and angiogram are used to explore vessel patency.7Magnetic resonance imaging (MRI) andcomputed tomographyscans are used to assess healing, rejection, and fusion between the donor’s and recipient’s anatomical structures.8

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, andhelp 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 outactivities of daily livingindependently, and are beginning to reintergrate back into the community.Most patients report improvements in quality of life.9,10

Face transplants

Factors that affect recovery are extent of scaring, composition of the flap, thickness of the flap, and innervation density of the flap.11 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.12

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, not drinking unpasteurized milk and juices, not eating raw or undercooked eggs, meat, and seed sprouts, and only drinking from safe water sources.13

Social role and social support system

Face and hand transplants posepsychologic challenges in the acceptance of the visible allograft. Family support, coping mechanisms, and professional support is necessary through the transplant process and beyond.7

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 is then weighed. Currently, there are no standardized screening tools used universally, 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 5categories: functional status, aesthetic deficit, comorbidities, exposed tissue, and surgical history.14 As the field of composite tissue allotransplantation evolves, the adoption of standardized guidelineswill aid in the candidateselectionprocess and also potentially facilitate an earlier transplantation, which may contribute to improved outcomes.6

3. 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.8

At different disease stages

Postoperative rehabilitation for hand transplants9,15

  1. New onset/acute: Therapy begins immediately postoperation 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 thetherapy program.Electric stimulation and electromyogram biofeedback can be incorporated.
  3. Chronic: This includes continuing therapies (beyond1-year posttransplant) andcommunity reintegration goals. The therapy intensity for hand transplants is often times twice daily initially, with gradual tapering over a1-year course.

Postoperative rehabilitation for face transplants5

  1. New onset/acute: Initial focus is on basic activities, such as respiratory function, ability to eat/drink, and sleeping 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 orderto 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, andelectromyography 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 toachieve the highestpossible levelofindependence 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 relationshipneeds 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 resultare considered poor at less than 50 points, fair between 51 and 74 points, good between 75 and 84 points, and excellent above 85 points.9
  2. The Hand Transplantation Score System is based on a value of 100 points, which involve6 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.16

For face transplant5

  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 for5 expressions in5 regions of the face (forehead wrinkles, eye closure, open mouth smile, snarl, and pucker); (3) and synkinesis.
  2. The Facial Disability Index isa disease-specific, self-report instrument for the assessment of the disabilities of patients with facial nerve disorders; it isscored as2 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. Team work is key to its success. Starting with patient selection, the teamworks in concert with the patient, family, and primary care physician through the various stages of the transplant.8

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Cutting edge concepts and practice

Cell-based therapies, such as antibody therapy and donor bone marrow infusions, may allow 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.10

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

There isan 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 considerations of risk versus benefits, nonmaleficence versus beneficence, paternalism versus autonomy, informed consent, and financial considerations.17When 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?10

REFERENCES

  1. Hollenbeck ST, Erdmann D, Levin LS. Current indications for hand and face allotransplantation. Transplant Proc. 2009;41:495-498.
  2. Fishman JA. Introduction: infection in solid organ transplant recipients. Am J Transplant. 2009;9(Suppl 4):S3-S6.
  3. 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.
  4. Ravindra KV, Gorantla VS. Development of an upper extremity transplant program. Hand Clin. 2011;27:531-538.
  5. 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.
  6. Gordon C, Siemionow M, Papay F, et al. The world’s experience with facial transplantation. Ann Plastic Surg. 2009;65:572-578.
  7. 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.
  8. 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.
  9. 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.
  10. Shores JT, Imbriglia JE, Lee AW. The current state of hand transplantation. J Hand Surg Am. 2011;36:1862-1867.
  11. Siemionow MZ, Gharb BB, Rampazzo A. Pathways of sensory recovery after face transplantation. Plast Reconstr Surg. 2011;27:1875-1889.
  12. 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.
  13. Avery RK, Michaels MG. Strategies for safe living following solid organ transplantation. Am J Transplant. 2009;9(Suppl 4):S252-S257.
  14. Losee JE, Fletcher DR, Gorantla VS. Human facial allotransplantation: patient selection and pertinent considerations. J Craniofac Surg. 2012;23:260-264.
  15. Cavadas PC, Landin L, Ibanez J. Bilateral hand transplantation: result at 20 months. J Hand Surg Eur Vol. 2009;34:434-443.
  16. 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.
  17. Chang J, Mathes D. Ethical, financial, and policy considerations in hand transplantation. Hand Clin. 2011;27:553-560.

Author Disclosure

John J. Lee, MD
Nothing to Disclose

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