The Cutting Edge
May 1999

Use of a Permanent Acellular Dermal Allograft in Recessive Dystrophic Epidermolysis Bullosa Involving the Hands

Author Affiliations



Copyright 1999 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.1999

Arch Dermatol. 1999;135(5):503-506. doi:10.1001/archderm.135.5.503

RECESSIVE DYSTROPHIC epidermolysis bullosa (RDEB) is characterized by blistering and scarring of the skin and mucous membranes. The hands are particularly vulnerable because of the contact and shearing forces of normal daily activity.


An 11-year-old white boy presented with RDEB and extensive epidermal scarring around the hand that caused restrictive adduction of the thumbs and pseudosyndactyly. Repeated cycles of blistering and scarring resulted in gradual encasement of the hand in an epidermal "cocoon"(Figure 1). Functional impairments included loss of fine motor manipulation of objects commensurate with the loss of digital prehension.

Figure 1.
Image not available

Characteristic thumb adduction contracture along with epidermal "cocoon" and pseudosyndactyly.


Our goal was to relieve the scar contractures associated with the epidermal encasement of the hand in a patient with RDEB, while minimizing donor site morbidity and graft hypertrophy.


We used a permanent dermal transplant that was developed for full-thickness burn wounds (AlloDerm; LifeCell Corp, The Woodlands, Tex).1 Fresh human cadaveric allograft skin was procured from tissue banks following donor and serological screening in accordance with guidelines of the American Association of Tissue Banks and the Food and Drug Administration.2 Skin was transported, on ice, overnight in Rosewell Park Memorial Institute (RPMI) 1640 medium supplemented with antibiotics. The skin was then aseptically processed to remove the epidermal, fibroblast, and endothelial cells that are the targets for immune response,3,4 leaving a structurally intact (ie, retaining elastin, proteoglycans, and the basement membrane complex), freeze-dried, acellular, dermal allograft.

Preparation of Acellular Dermal Allograft

The permanent dermal transplant package was opened in the operating room, and the freeze-dried dermal matrix was washed twice in a minimum of 100 mL of lactated Ringer solution at room temperature and then rehydrated in 100 mL of normal saline solution or lactated Ringer solution for 10 minutes before application.

Surgical Procedure

The objective of the hand reconstruction in patients with RDEB is usually to reestablish elementary pinch and grasp.5 Accordingly, the highest priority was given to releasing the adduction contracture of the thumb (Figure 1). The thumb adduction contracture involves dermal and subdermal fibrosis, myofascial fibrosis, and shortening of the adductor pollicis and first dorsal interosseous muscles. Epithelial removal, as in "de-cocooning," does not begin to correct the basic functional problems, which are deep fibrosis and scarring.

A complete release of the thumb contracture was accomplished by a generous incision extending from the base of the web at the level of the carpometacarpal joint dorsally, across the web to course volarly on the palm. To maintain abduction during the period of skin graft healing, skeletal stabilization of the thumb was performed by placement of nonparallel Kirschner wires between the first and second metacarpal bones. The allograft was applied. A 150-µm split-thickness skin graft was harvested from the anterior area of the thigh, which was free of blistering, and sewn into place with 6-0 ophthalmic catgut (Figure 2). The thigh donor site was covered with a single layer of scarlet red. A circumferential noncompressive dressing of cotton batting was placed around the hand, followed by volar and dorsal splints for immobilization.

Figure 2.
Image not available

Application of acellular dermal allograft and ultrathin (150-µm) autograft with the thumb in radial and palmar abduction. Percutaneous Kirschner wires keep the digits separate and the thumb in an abducted position.

After 1 week, the dressings were removed with the patient under a short general anesthetic (Figure 3). The Kirschner wires were removed at 4 weeks. An orthoplast splint was used to hold the thumb abducted and the fingers separated. An active range of motion exercises were then encouraged. Passive exercises were avoided for fear of frictional trauma. The patient was gradually weaned from the splint during waking hours. Night splinting was continued for several months.

Figure 3.
Image not available

Six-month follow-up demonstrating epidermal engraftment and marked improvement in thumb abduction.

There was 100% acceptance of the dermal allograft and epidermal autograft. The donor site reepithelialized within 4 days of surgery. The patient was gradually weaned from the splint over several months. A survey of the patient and parents at 6 weeks and 6 months after surgery indicated a high degree of satisfaction. They were particularly pleased with the virtual absence of donor site morbidity and the overall improvement in cosmesis and function (Figure 3).


A variety of operative approaches have been used to deal with the hands of children with RDEB, including the use of split-thickness autograft, human allografts, cross-linked porcine skin, and human cultured epithelial cells.610 These treatments cannot provide a permanent, durable dermal replacement, as they are rejected, do not revascularize, or do not withstand normal wear and tear. Cadaveric human allograft skin has proved effective as a short-term solution in massively burned patients.11 However, its use has not been documented in patients with RDEB. The most immunogenic components of transplanted allograft skin are the cellular elements of the epidermis and dermis. Thus, an allograft may vascularize within 3 days, but it is subsequently rejected in 2 or 3 weeks.

Acellular bone grafts have been routinely used in oral and orthopedic surgery for several years, lending credence to the claim that such tissues will maintain their structural integrity over time.1214 In the skin, the epidermis contains most of the immunogenic components. If it is removed along with dermal cells, the remaining noncellular dermal tissue is relatively inert immunologically. Acellular dermal allografts may serve as a scaffold for ingrowth of host cellular elements, resulting in a normally organized tissue.15 Similarly, the use of allogenic dermis in combination with autogenous cultured epithelial cells that form a permanent coverage for full-thickness RDEB wounds has been explored.1621 However, this technique requires excision of the upper dermis, with sacrifice of epithelial attachment mechanisms, perhaps explaining the fragility of the resulting coverage.

Despite the well-described liabilities of donor site morbidity and graft hypertrophy, split-thickness autografts remain the standard of care for resurfacing full-thickness defects associated with reconstructive procedures in patients with RDEB.5,22 Because of widespread involvement over a large total body surface area, surgeons are required to use thinner autografts than would be ideal in reconstruction because of the routine shortage of adequate donor sites in such patients. Potential donor site morbidity includes pain, delayed wound healing, infection, and hypertrophic scarring. The adverse aspects of split-thickness skin graft procurement are thought to be directly related to the thickness at which the donor skin is harvested. Hypertrophy of grafted skin is related inversely to the thickness of transplanted dermis. Both these liabilities might be lessened by the ready availability of a functioning, "off-the-shelf" dermal substitute.

Biosynthetic dermal substitutes have been widely studied in animal models, but apart from their use in massively burned patients,23 they have gained little clinical acceptance in the treatment of skin injury or disease. The use of biosynthetic dermal substitutes is based on the premise that the matrix or mesh supporting the cultured fibroblasts will degrade in the wound healing process, leaving behind the fibroblasts and their secreted dermal proteins. Studies have shown, however, that only fetal fibroblasts in utero are capable of regenerating dermal extracellular matrix without scarring.24 Mature fibroblasts repair damaged or missing dermis through the formation of granulation tissue, which later matures into scar tissue. Mature fibroblasts do not regenerate the complex architecture of the epidermis and upper dermis. This observation has focused attention on the matrix deficit in full-thickness injury and has prompted the development of a structurally and biochemically intact acellular allograft dermal matrix that is intended to function as a template for dermal regeneration. A matrix template approach has been developed and has proved effective for allografts.13 The putative benefits of an acellular allograft are summarized in Table 1.25

Image not available
Putative Surgical Advantages of Acellular Human Dermal Allograft

A detailed comparison between the dermal graft used in this case and intact dermis indicates that the extracellular matrix of the basement membrane and the dermis of the acellular graft is essentially identical to that of skin, only without the cellular component.15,26 Since the basic skin architecture with its original underlying RDEB defect is unaltered by the operation, a gradual recurrence of the deformity is to be expected. One factor that appears to prevent recurrence of the interphalangeal joint contractures is prolonged use of splinting.27

This case report indicates that cryopreserved acellular human dermis can engraft successfully and support engraftment of an overlying ultrathin autograft in patients with RDEB. With acellular dermal grafts, clinicians may now have an alternative to conventional autografting. While these initial results relating to the effectiveness of cryopreserved acellular human dermis in optimizing appearance and function are encouraging, longer follow-up is required before definitive conclusions can be made.

Back to top
Article Information

Accepted for publication November 9, 1998.

Corresponding author: Peter D. Witt, MD, St Louis Children's Hospital, One Children's Place, Pediatric Plastic Surgery, 2 South 86, St Louis, MO 63110-1077.

Wainwright  D Use of an acellular allograft dermal matrix (AlloDerm) in the management of full-thickness burns. Burns. 1995;21243- 248Article
American Association of Tissue Banks, Technical Manual for Skin Banking.  McLean, Va American Association of Tissue Banks1992;
Yukna  RATurner  DWRobinson  LJ Variable antigenicity of lyophilized allogeneic and lyophilized xenogeneic skin in guinea pigs. J Periodontal Res. 1977;12197- 201Article
Morris  ATomkins  P Interactions of interferons in the induction of histocompatibility antigens in mouse fibroblasts and glial cells. Immunology. 1989;67537- 539
Greider  JLFlatt  AE Surgical restoration of the hand in epidermolysis bullosa. Arch Dermatol. 1988;124765- 767Article
Cuono  CFinseth  F Epidermolysis bullosa: current concepts and management of the advanced hand deformity. Plast Reconstr Surg. 1978;62280- 285
Brown  JFryer  MRonda  ULu  M Post mortem homografts as biological dressings for extensive burns and denuded areas. Ann Surg. 1953;138618Article
Cuono  CLangdon  RBirchall  NBarttebort  SMcGuire  J Composite autologous-allogeneic skin replacement: development and clinical application. Plast Reconstr Surg. 1987;80626- 637
Skivolocki  WHarris  BHBoles  ET A new method for skin grafting a burned patient who has epidermolysis bullosa. Plast Reconstr Surg. 1974;53355- 357
Zarem  HAPearson  RWLeaf  N Surgical Management of hand deformities in recessive dystrophic epidermolysis bullosa. Br J Plast Surg. 1974;27176- 181Article
Wainwright  DMadden  MLuterman  A  et al.  Clinical evaluation of an acellular allograft dermal matrix in full-thickness burns. J Burn Care Rehabil. 1996;17124- 136Article
Mellonig  J Freeze-dried bone allografts in periodontal reconstructive surgery. Dent Clin North Am. 1991;35505- 520
Kreutz  FHyatt  GTurner  TBasset  A The preservation and clinical use of freeze dried bone. J Bone Joint Surg. 1951;33863- 872
Gallico  G Biologic skin substitutes. Clin Plast Surg. 1990;17519- 526
Livesey  SHerndon  DHollyoak  MAtkinson  YNag  A Transplanted acellular allograft dermal matrix. Transplantation. 1995;601- 9Article
Eisenberg  MLlewellyn  DMoran  KKerr  A Successful engraftment of cultured epidermal allograft in a child with recessive dystrophic epidermolysis bullosa. Med J Aust. 1987;147520
Hill  JGrimwood  RParsons  D Treatment of chronic erosions of junctional epidermolysis bullosa with human epidermal allografts. J Dermatol Surg Oncol. 1992;18396- 400Article
McGrath  JSchofield  OMIshida-Yamamoto  A  et al.  Cultured keratinocyte allografts and wound healing in severe recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol. 1993;29407- 419Article
Verplancke  PBeele  HMonstrey  SNaeyaert  JM Treatment of dystrophic epidermolysis bullosa with autologous meshed split-thickness skin grafts and allogeneic cultured keratinocytes. Dermatology. 1997;194380- 382Article
Dunnill  MGEady  RA The management of dystrophic epidermolysis bullosa. Clin Exp Dermatol. 1995;20179- 188Article
Beele  HNaeyaert  JMMonstrey  SKint  A Ulcers in pretibial epidermolysis bullosa: grafting with autologous meshed split-thickness skin and allogeneic cultured keratinocytes. Arch Dermatol. 1995;131990- 992Article
Greider  JLJFlatt  AE Care of the hand in recessive epidermolysis bullosa. Plast Reconstr Surg. 1983;72222- 228
Sheridan  RLChoucair  RL Acellular allogeneic dermis does not hinder initial engraftment in burn wound resurfacing and reconstruction. J Burn Care Rehabil. 1997;18496- 499Article
Lovenz  HAdzick  N Scarless skin wound repair in the fetus. West J Med. 1993;159 ((suppl)) 350- 355
Wainwright  DNag  ACall  TGriffey  SAtkinson  YLivesey  S Normal histological features persist in an acellular dermal transplant grafted in full-thickness burns.  Paper presented at: Federation of American Society of Experiment Biology Summer Research Conference, "Repair and Regeneration: At the Interface" July 9-14, 1994 Saxtons River, Vt
Burgeson  RELunstrum,  GPRokosova  BRimberg  CSRosenbaum  LMKeene  DR The structure and function of type VII collagen. Ann N Y Acad Sci. 1990;58032- 43Article
Ladd  ALKibele  AGibbons  S Surgical treatment and postoperative splinting of recessive dystrophic epidermolysis bullosa. J Hand Surg Am. 1996;21888- 897Article