Journal Club Article, March 2019

March, 2019:  Update on Hand Transplantation

Park SH et al: Hand Transplantation: Current Status and Immunologic Obstacles. Exp Clin Transplant 2019 Feb;17(1):97-104        full text, free

Coincidentally, this recently published article appeared almost simultaneously with a long and detailed investigative journalism report in Wired Magazine. Even though very few of us have treated or have even seen a patient with a hand transplant, we should be conversant with the current state of affairs in order to respond intelligently when patients and other acquaintances ask our professional opinion.

Hand transplantation was first performed in 1964 in Ecuador. The graft was quickly rejected and required removal three weeks later. The next one was performed in 1998 in France, and subsequently 88 more cases worldwide have been reported. Currently there are at least 19 hand transplant centers, including one or more in Australia, Belgium, China, Iran, Mexico, Poland, Taiwan, Turkey, United Kingdom, and United States.

Although the surgical techniques of harvesting the limb from a cadaver and attaching the part to the recipient’s amputation stump are demanding and time consuming, they pale in complexity to the immunological issues of preventing the host from rejecting the graft. Sometimes too, the graft (transplanted hand) tries to reject the recipient host.

Perhaps the most important recent shift in thinking has been from the concept of immunosuppression to one of immunoregulation—convincing the body to tolerate the graft with minimal pharmacologic persuasion.

Both acute and chronic rejection are problems, especially for grafts as complex as the upper extremity, which includes multiple tissues of varying antigenicity, particularly skin. Clinical signs of acute rejection include rash, edema, blisters, and ulcers. Because the skin is visible to the patient and to the treatment team, rejection episodes can be quickly identified and treated. Often topical treatment is all that is required.

Eighty-five percent of recipients have experienced at least one episode of acute rejection, and 56% have experienced multiple episodes.

Long term loss of graft function is related to the body’s ongoing immunologic inclination to reject the graft. Predisposing factors include the timing and intensity of acute rejection episodes and their resistance to steroid treatment, older or unstable donors, atherosclerosis, prolonged cold ischemia, and recipients with hypertension, diabetes, obesity, hypercholesterolemia, and noncompliance with the anti-rejection medication regimen.

A triple-drug immunosupressive treatment is commonly used. One of the drugs, tacrolimus, enhances nerve regeneration but accentuates kidney toxicity, hypertension, and diabetes.

An improved ability to perform activities of daily living is nearly universal among patients with viable transplants. Recovery of protective sensation is universal.

Early complications have included death, acute limb loss, vessel thrombosis, skin necrosis, pneumonia, and sepsis. Late complications have been mostly related to the immunosuppressive treatment and include opportunistic infections, diabetes, end-stage kidney disease, hypertension, avascular necrosis of the femoral heads, skin cancer, and hyperparathyroidism. In Europe and the US, six hands have required removal. In China, at least seven hands have been removed.

Comment: Dr. Park and colleagues paint a generally optimistic future for hand transplantation despite the monumental issues of cost, complications, and compliance. The ethics of committing a healthy person with a missing hand to lifelong risks of early death, kidney failure, and skin cancer remain questionable. The decision for a patient who is missing both hands is more nuanced. Before deciding whether you would undergo a hand transplant yourself, read the Wired Magazine article for further perspective.