Dermatology Online Journal

Delayed and recurring blisters in the donor graft site of a burn patient
Robert Anolik MD, Aaron Loyd MD, Rishi Patel MD, Cynthia Magro MD, Andrew G Franks Jr MD
Dermatology Online Journal 16 (11): 13

Department of Dermatology, New York University, New York, New York

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Abstract

A 79-year-old woman presented for evaluation of non-healing skin graft donor sites. The patient underwent split thickness skin graft repair two-and-a-half years ago as a consequence of severe burns from a fire that affected 10 to 15 percent of her body. Donor sites included her thighs and flanks. After initial healing, intermittent and paroxysmal, eroded and crusted, erythematous plaques have continued to arise at various donor sites. Normal skin has remained uninvolved. Histopathologic analysis showed a poor basement membrane zone. The patient’s findings represented delayed and recurring blistering in the donor graft site that is uncommonly observed in burn patients.

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History

Figure 1

A 79-year-old woman presented to NYU School of Medicine Dermatologic Associates for evaluation of non-healing skin graft donor sites. The patient underwent split thickness skin graft repair two-and-one-half years ago as a consequence of severe burns from a fire that affected 10 to 15 percent of her body. Donor sites included her thighs and flanks. After initial healing, intermittent and paroxysmal, eroded and crusted, erythematous plaques have continued to arise at various donor sites. Normal skin has remained uninvolved.

Prior to her evaluation at NYU, wound cultures, two skin biopsies, and both direct and indirect immunofluorescence studies failed to disclose an etiology. The skin biopsy specimens showed non-specific serum crust with neutrophils. Direct immunofluorescence study was negative for IgG, C3, IgM, IgA, and fibrinogen. Indirect immunofluorescence tests for intercellular and basement membrane zone antibodies were negative. Topical treatments included numerous antibiotics, antifungals, and glucocorticoids. Oral treatments included azithromycin, cephalexin, and dicloxacillin. These treatments yielded little to no effect.

At NYU, a skin biopsy as well as indirect and direct immunofluorescence studies were repeated. At the same time, efforts to rule out allergic contact dermatitis led to patch testing, which yielded negative results. Minocycline was started to prevent secondary infection of the eroded skin in tandem with topical EpiCeram.

Medical history included cataracts, hypertension, coronary artery disease, and coronary artery bypass graft surgery. Medications include simvastatin, enalapril, carvedilol, aspirin, and a multivitamin. Family history is not contributory.

Physical examination

A discrete, erythematous plaque that consisted of erosions, crust, and scale was noted on the skin graft donor site on the right thigh.

Laboratory data

Wound cultures showed normal mixed cutaneous flora. Enhanced North American Contact Dermatitis Group Standard Allergen Series showed no positive patch test reactions.

Histopathology

Within the dermis, there is a zone of older scarring fibrosis and more recent fibroplasia that is associated with separation at the dermoepidermal junction. The overlying epidermis is thin with scale-crust. An immunohistochemical stain for collagen IV shows a focal diminution in expression at the area of separation.

Comment

Delayed blister formation in the skin of burn victims is an unusual event that can arise within donor or recipient graft sites, spontaneously healed burns, or any combinations of these sites [1, 2, 3, 4]. The process is not reported to include otherwise uninvolved skin. After extensive analysis by one group using light microscopy as well as direct and indirect immunofluorescence tests, the authors concluded that the process most closely mimicked recessive dystrophic epidermolysis bullosa or immunofluorescence-negative epidermolysis bullosa aquisita [2]. Similar blistering events have been described in graft sites after repair of chronic leg ulcers [5].

A study of the delayed blistering phenomenon in burn patients was performed in 13 patients [4]. Nine of these patients experienced recurrent blisters in either the donor or recipient graft sites or in the spontaneously healed sites after the skin had completely healed. Four developed blisters in at most two of these locations. The eruption appeared 19 to 55 days after sustaining burns and recurred over a period of weeks to months. Blisters were tense and expanded to between three to 30 mm in size. Nine additional patients, none of whom had blistering complications after graft or spontaneous healing, served as controls. The edge of blisters were compared to the edge of burn or graft wounds from controls. On light microscopy, the control biopsy specimens showed a well-formed basement membrane zone (BMZ) by day ten and a normal pattern on a direct immunofluorescence test. No antibodies to the BMZ were detected in the serum of controls. In contrast, light microscopy from the edge of blisters showed a split at the dermoepidermal junction. A periodic acid-Schiff stain showed that an irregular and discontinuous basement membrane existed along the blister roof with a pauci-inflammatory infiltrate and dermal edema. On electron microscopic examination, blistering developed immediately below the dermoepidermal junction and consisted of gradually enlarging vacuoles as they approached the blister’s center. These vacuoles appeared on occasion as distended rough endoplasmic reticulum within enlarged fibroblasts. The lamina densa and anchoring fibrils sporadically lost continuity and became absent toward the center. Immunofluorescence studies showed variable levels, from faint to normal, of BP antigen, laminin, and type IV collagen around the blister, but normal levels of EBA antigen. Within the blister itself, all four antigens were irregular and inconsistent in pattern. The authors concluded that the delayed blistering in burn patients develops as a result of aberrantly expressed components of the BMZ. The aberrant expression is attributed in part to an improper contribution by dermal fibroblasts, which are critical to BMZ development [6].

A recent review of literature that addresses subepidermal blistering associated with grafting of burns and chronic leg ulcers suggests that many reports to date are misleading [7]. There are a lack of details in past reports and the observation that the blistering only is occurring on areas of spontaneous healing or areas not covered by grafts. Uncovered areas would include those that exist within the spaces of mesh grafts, those between adjoining graft edges, or peripheral margins of grafted wounds. The grafting, instead, is thought by the authors to be protective against blistering as it limits need for reepithelialization, and, instead, it is the scarred, open, reepithelializing skin that is likely the precipitant of blisters in these patients.

The patient presented in this report reflects the delayed blistering phenomenon that is observed in burn patients. It shares characteristics with past reports by relapsing after healing only within burn-related sites, which in this patient are the donor graft sites. Additionally, the histopathologic features are consistent with earlier reports of poorly forming basement membranes. However, it differs by its prolonged duration as it has recurred persistently for more than two-and-one-half years as compared to most reports in which resolution occurs by one year. Although it is possible if the patients in those reports were followed longer, they might have experienced additional recurrences. Furthermore, the case presented in this report differs in its presentation and the skin lesions appear as eroded, erythematous plaques with crust as opposed to tense bullae. Nevertheless, it highlights the poorly understood phenomenon of inappropriate basement-membrane development in some patients after burns.

References

1. Barker DJ, et al. Development of subepidermal bullae in the split-skin graft donor site of a psoriatic. Dermatologica 1980; 160: 311 [PubMed]

2. Epstein A, et al. Persistent subepidermal blistering in split-thickness skin graft sites: ultrastructural and antigenic features simulating dystrophic or immunofluorescence-negative acquired epidermolysis bullosa. Arch Dermatol 1988; 124: 244 [PubMed]

3. Woodley DT, et al. Burn wounds resurfaced by cultured epidermal autografts show abnormal reconstitution of anchoring fibrils. JAMA 1988; 259: 2566 [PubMed]

4. Chetty BV, et al. Basement membrane and fibroblast aberration in blisters at the donor, graft, and spontaneously healed sites in patients with burns. Arch Dermatol 1992; 128: 181 [PubMed]

5. Baran R, et al. Bullae in skin grafts. Br J Dermatol 1984; 111: 221 [PubMed]

6. Delvoye P, et al. Fibroblasts induce the assembly of the macromolecules of the basement membrane. J Invest Dermatol 1988; 90: 276 [PubMed]

7. Gomez DS, et al. The problem of subepidermal blisters in neoformed integuments. Burns 2005; 31: 811 [PubMed]

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