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Persistence of Human Skin Allograft in a Burn Patient without Exogenous Immunosuppression

Banks, Nia D. M.D., Ph.D.; Milner, Stephen F.R.C.S., F.A.C.S.

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Plastic and Reconstructive Surgery: April 2008 - Volume 121 - Issue 4 - p 230e-231e
doi: 10.1097/01.prs.0000305391.98958.95
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Sir:

A 19-year-old man presented to our burn unit with 75 percent total body surface area deep second- and third-degree flame burns resulting from accidental ignition of toy airplane fuel. His medical history was unremarkable except for bipolar disorder. He was intubated and immediately taken to the burn unit for resuscitation and wound care. After 72 hours, the patient underwent multiple operations for sequential excision of the back, chest, and legs and resurfacing of the wounds with widely meshed autografts. On hospital day 8, the abdomen was excised to subcutaneous fat, and on day 10, fascial excision of the upper extremities was performed. Due to a lack of donor sites, the lower abdomen was resurfaced with 1000 cm2 of allograft and the arms with 1600 cm2, meshed to a ratio of 1:1.

Four weeks later, these areas showed no signs of rejection (Fig. 1). The skin was hyperemic but without scaling, shrinking, sloughing, or necrosis. HLA typing revealed only the patient’s HLA type within an allograft biopsy. Histopathologic analysis showed a moderate dermal perivascular inflammatory infiltrate, fibroplasia, and vascular proliferation consistent with “reparative changes as may be seen in a scar.” There was no evidence of epidermal destruction or thrombosis to suggest rejection (Fig. 2). Seven weeks after allograft placement, the graft continued to provide stable wound closure but had the clinical appearance of hypertrophic scar.

Fig. 1.
Fig. 1.:
Allograft skin on lower abdomen at 4 weeks after grafting. A fresh biopsy site is seen.
Fig. 2.
Fig. 2.:
Skin allograft biopsy specimen taken at 4 weeks (40× magnification) shows moderate to severe dermal inflammatory infiltrates, fibroplasias, and perivascular inflammation. An intact hair follicle next to the inked edge of the specimen and a structurally normal sweat gland are seen in the lower right corner. There is no significant epidermal damage.

The average time to rejection of allograft skin has been reported to be 10 to 14 days.1 As late as 7 weeks after grafting in the patient presented, we did not find clinical or histological evidence of rejection. HLA typing and histologic analysis suggested that the mechanism of allograft persistence was not survival of donor cells but repopulation of the allograft by recipient cells.

Allograft skin persistence by creeping substitution has previously been described. Phipps and Clarke2 used meshed parental allografts and widely meshed autografts in children following thermal injury to provide stable wound closure without acute rejection. Chromosomal analysis demonstrated substitution of male donor cells by female recipient cells. Hypertrophic scar was not seen. Krupp et al.,3 using unrelated allograft skin intermingled with cultured epidermal autografts and temporary cyclosporine treatment, did not see acute rejection after cyclosporine was stopped; chromosomal analysis suggested creeping substitution of allograft by recipient cells. Hypertrophic scarring was not seen. This may have been due to the temporary use of cyclosporine and the avoidance of excessive inflammation.

In cases of composite tissue allotransplantation, episodes of acute rejection of the skin of abdominal wall, hand, and recent face transplants have been managed with increased doses or topical application of immunosuppressive drugs.4,5 With the occurrence of the world’s first face transplant, it is all the more pressing that we find solutions to the challenge posed by skin antigenicity that avoid the risk of life-long immunosuppression and preserve an aesthetically acceptable result. Methods to promote repopulation of allograft skin would greatly affect the management of burn patients and recipients of skin transplants; however, inflammation must be controlled to prevent excessive scar formation.

Nia D. Banks, M.D., Ph.D.

Division of Plastic and Reconstructive Surgery

Johns Hopkins Hospital

Baltimore, Md.

Stephen Milner, F.R.C.S., F.A.C.S.

Division of Burns

Johns Hopkins Burn Center

Baltimore, Md.

REFERENCES

1. Dvorak, H. F., Mihm, M. C., Dvorak, A. M., et al. Rejection of first-set skin allografts in man. J. Exp. Med. 150: 322, 1979.
2. Phipps, A. R., and Clarke, J. A. The use of intermingled autograft and parental allograft skin in the treatment of major burns in children. Br. J. Plast. Surg. 44: 608, 1991.
3. Krupp, S., Wiesner, L., Krstic, R., et al. Mid-term results with cultured epidermal autografts, allogenic skin transplants and cyclosporine A medication. Burns 20: 15, 1994.
4. Bejarano, P. A., Levi, D., Nassiri, M., et al. The pathology of full-thickness cadaver skin transplant for large abdominal defects: A proposed grading system for skin allograft acute rejection. Am. J. Surg. Pathol. 28: 670, 2004.
5. Kanitakis, J., Jullien, D., Petruzzo, P., et al. Clinicopathologic features of graft rejection of the first human hand allograft. Transplantation 76: 688, 2003.

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