Xeroderma pigmentosa is a devastating morbidity for the patient and the family as well as the caring medical team. The author's previous experience with this lethal devastation inspired executing the idea with any prospect of success. The mother having witnessed the life and death of her previously affected offspring, unsurprisingly, accepted with enthusiasm donating her skin. Attempts to resurface their faces have been tried using autologous skin that ended up developing malignant lesions as it still carries the same genetic defect. To the best of the author's knowledge, this is the first attempt of allotransplantation for patients with Xeroderma pigmantosa.
There were two issues as regards timing in this procedure. First, is whether to do the transplantation before or after development of malignant lesion? Second, is whether to do the skin expansion before or after transplantation i.e. in the arm of the mother or in the face of the patient? Prophylactic excision was chosen in this case to avoid the use of immunosuppressants in the face of a coexisting invasive malignancy. It might seem logical and tempting to expand the skin in the arm of the mother to allow harvesting ample tissue with the expander in a rather convenient anatomical site. However, tissue expansion was deferred to a post-transplant stage. The reason was that transferring ample skin would have simply meant excision of ample facial skin as well from the patient. Should removal of the graft prove to be necessary for any reason; a large raw area would have resulted in such a case.
The rationale behind the attempt was that the development of skin malignancy is almost certain in these patients. Standard treatment is excision and split thickness grafting. Therefore, loosing the graft and resurfacing by autologous split thickness graft is not too far from this end point if the patient was left untreated. Immune suppression in a patient well known to be prone to malignancy was an issue of concern. Experience from long term follow up of renal transplant patients pointed to Immune suppression as a risk factor for developing malignancy with an 18-fold rise in risk for developing squamous carcinoma in these patients [4]. This was not enough for the authors to abort the idea as xeroderma pigmentosa patients, when left untreated, they systematically develop malignancy and usually die in the second decade of life, so they simply can not be rendered "more prone" to malignancy. They are already at the height of susceptibility. Given this fact, the authors chose not to loose the grip on the idea and they chose to see whether this theoretical (but certainly relevant) risk will really set in on clinical grounds or not, as this risk has not been assessed clinically in this particular subset of patients. In addition, hepatologists extended the indications for liver transplantation to include some patients with hepatocellular carcinoma. They do receive immunosuppressants in the immediate postoperative period. Whether Immune suppression accelerates the malignant process in this subset of patients or not, reports are conflicting and it seems that the best answer to this question is the answer given Schwartz et al; "we do not know" [5].
We believe that the way out of this morbidity is either prevention by genetic counseling and prenatal diagnosis or by gene therapy for those whom it happened that they are born with the defect. Genetic counseling and prenatal diagnosis are currently available in clinical practice but gene therapy is still investigational. Various methods of correcting the defects in xeroderma pigmentosum have been attempted in vitro and in animal studies using viral vectors (adenoviruses and retroviruses) carrying the gene replacement products. Ex vivo skin gene therapy, which refers to grafting skin that has the genetic defect corrected may be useful in xeroderma pigmentosum in the future [6]. A new approach is to repair DNA damage after UV exposure. This can be accomplished by delivery of a DNA repair enzyme into the skin by means of specially-engineered liposomes [7]. Employing this therapy over a period of 1 year, Yarosh et al [8] demonstrated a reduction in the onset of actinic keratosis and Basal cell carcinoma. Oral retinoids have been shown to decrease the incidence of skin cancer in patients with xeroderma pigmentosum. This therapy is limited by dose-related irreversible calcification of ligaments and tendons.
As mentioned earlier, Skin excision and grafting by an auto graft (total resurfacing) ended up by malignancy developing in the grafted skin when it was transplanted to sun exposed areas. Chemical peeling and dermabrasion represent a less invasive method of resurfacing with reports of a disease free period up to 4 years (free from malignant lesions). However, protection from sun is still mandatory after the procedure [9]. The attempt described in this article can be looked at as an evolution of the total resurfacing approach with the next step seems to be cadaveric total face transplantation. Clinical attempts of composite tissue allotransplantation have been described between identical twins [10, 11]. When the donor is not an identical twin, these reconstructive procedures for non life-threatening indications remain rare due to adverse effects of the associated lifelong immunosuppressive therapy [12]. Face transplantation is emerging as a solution to traumatic events with the first report of a dynamic hemi face transplant following a dog bite performed in France [13]. There are three dissimilarities, however, between the case performed in France and this report. These are; the indication of the procedure, the type of tissue transplanted and lastly the regimen of immune suppression. The indication in our report was prevention of malignancy while in the patient reported in France the indication was reconstruction of a lower face amputated by a dog bite. The graft transplanted in France was a composite graft containing skin, muscles and mucous membrane with their nerve and blood supply harvested from a brain-dead lady in her forties. As mentioned earlier, ethical committees in our country have not yet approved brain-dead patients as donors which made a living-related donor the author's only option which consequently dictated the type of tissue that can be harvested. As regards immune suppression regimen; the author's choice of drugs (described earlier) in the current case was, in part, influenced by the available fund allocated for the attempt. This immunosuppressive regimen was modified from the regimen used by members of the same team who work in the living related liver transplantation program at Cairo University. Because skin is a mixed tissue that is liable to more rejection than the liver, the regimen used a dose of steroids that was higher than that used for liver transplant recipients and was even started earlier pre-operatively. Also, a combination therapy of cyclosporine and mycofenolate mofetil was used from the start. Liver transplant recipients receive monotherapy with tacrolimus (after steroids are discontinued) and mycofenolate is added as rescue therapy if the recipient experiences acute rejections.
At the time of this skin transplant for the xeroderma pigmentosa case, m-TOR inhibitors (sirolimus and everloimus) were unavailable; which is not the condition now. During the last year they were used in liver transplant recipients who experience repeated acute rejections not controlled by proper doses of tacrolimus. The pediatric hepatologists in the liver transplant team have also used sirolimus in one case of chronic rejection (a rare condition) in a child and chronic rejection was successfully controlled.
In the case performed in France, the Immunosuppressive treatment was with thymoglobulin, tacrolimus, mycophenolate mofetil, and prednisone. Two infusions of donor bone-marrow cells were given. They described 2 episodes of rejection in 18 months follow up that were reversed [14]. Another case was reported from China were, in 2006, Guo et al performed a partial face transplant to reconstruct a face of a man who sustained a bear bite. They used Quadraple immunomodulatory therapy containing tacrolimus, mycophenolate mofetil, corticosteroids, and humanized IL-2 receptor monoclonal antibody, and in two years follow up, they reported 3 episodes of rejection controlled by immune suppressive therapy adjustmen [15]. Finally, a report of near total face transplantation came from Cleveland in December, 2008. The patient was a lady who sustained a shotgun [16].
