Keratoacanthoma formation after skin grafting: A brief report and pathophysiological hypothesis

Keratoacanthoma formation after skin grafting is rare. We report the third case in the literature of multiple keratoacanthomas developed at both split‐thickness skin graft donor and recipient sites. We provide possible explanations for this poorly understood phenomenon and highlight its implications on treatment options.     

Glove imprint templating: A versatile tool in skin graft surgery and more

Measurement of the shape and size of skin lesions is an important component of skin excision and repair, especially in full‐thickness skin grafting. Current templating methods can be time‐consuming and may lead to inaccurate sizing of both full‐thickness and split‐thickness skin grafts. A novel, accurate, and time‐efficient method has been employed for 10 years in a dermatology clinic, in addition demonstrating utility in additional applications. A surgical glove is used to gain an imprint of a marked surgical incision site, to transcribe to the donor site for graft harvest. Further, the size of lesions in difficult‐to‐see areas of the body can be shown to patients. This method has been found to be clinically useful in reducing procedure times and providing accurate graft templates, as well as improving patients' satisfaction by helping them to understand the procedure. This method is also advantageous in obtaining informed consent by helping to clearly demonstrate the size of simple elliptical excisions.     

Burow''s grafts in the facial region

BACKGROUND: Full-thickness skin grafts are an important tissue source for reconstructive surgery. Burow's grafts are full-thickness skin grafts that use adjacent lax skin as the donor site. This technique has also been referred to as island grafts, dog-ear grafts or adjacent-tissue skin grafts. OBJECTIVE: The objective was to describe the technique of Burow's grafts for reconstruction of facial defects taking account of its benefits and limitations. METHODS: The operative technique is simple: after a circular excision of the cutaneous lesion, we enlarged the excision line (towards one or both sides of the defect) following the relaxed tension lines. We created a secondary triangular defect by excising skin that is then used for the graft (as donor site). After adequate undermining, we proceeded to direct linear closure of this secondary defect. Finally, the graft was placed and sutured in the remaining defect. RESULTS: The proximity of the donor site provides an excellent tissue match because colour, hair density, texture, sebaceous features and thickness are similar to the recipient site. A good cosmetic result is therefore ensured. CONCLUSION: Burow's grafts can be a good choice for reconstruction of extensive facial surgical defects because of aesthetic results. In addition, it is a simple technique that can be performed in one sole surgical act, with local anaesthesia and without changing the operative site.     

High‐voltage electrical injury: Modified surgical technique for optimal defect closuring of extra‐large cranial defect

Electrical burns are group of traumatic injuries with a mortality rate of 3–15%. High‐voltage induced extensive electric burns are rarely seen in the cranial area, compared to upper and lower limbs, but extremely difficult for treatment, due to the limited flexibility in this area. The spectrum of therapeutic interventions in electrical burns in general, evolving initial necrectomy, decompression, and aggressive debridement with early skin coverage is usually not enough in cases of extensive cranial defects. The performance of a suitable flap combined with skin graft in donor site, and further implantation of expander is challenging in this area. We present a case of a high‐voltage induced extra‐large cranial injury in a 38‐year‐old man, treated with modified single large rotation flap and a split skin‐thickness graft technique, for optimal defect closuring with satisfied aesthetic result.     

One‐stage reconstruction of deep facial defects with a single layer dermal regeneration template

Background The reconstruction of deep facial wounds in oncological surgery is challenging. Especially for elderly multimorbid patients, a rapid procedure with acceptable aesthetic and reliable functional outcome is required. Recently, a new single layer skin substitute was developed. Integra^® dermal regeneration template single layer (IDRT‐SL) allows one‐stage surgery in combination with split thickness skin grafting. However, no study has yet analysed the efficiency of IDRT‐SL treatment. Objectives To evaluate applicability and efficiency of the IDRT‐SL treatment in combination with split thickness skin grafting for a one‐step closure of deep facial surgical wounds in elderly multimorbid patients. Patients/Methods This prospective study analysed the functional and aesthetic outcome after reconstruction with an IDRT‐SL template and an immediate split thickness skin graft in the face (80 ± 3 years; >3 concomitant diseases). Results Nine tumours, four basal cell carcinoma, two lentigo maligna, one spinal cell carcinoma, one lentigo maligna melanoma and one Bowen carcinoma were resected. Five defects were located on the nose and four on the cheek. The mean defect size was 11 ± 3 cm². All but one graft were taken completely without any complication. One patient suffered from a partial graft loss (30%). All defects showed significant shrinkage of 61 ± 4%. Conclusions One‐stage reconstruction with a combination of IDRT‐SL and split thickness skin grafting is an elegant, easy and rapid method to treat deep skin defects. The take rates, functional and early cosmetic outcome are promising. This new method should be considered for selected cases of elderly multimorbid patients with deep facial wounds.     

Primary cutaneous T‐cell lymphoproliferative disorder of donor origin after allogeneic haematopoietic stem‐cell transplantation

A 56‐year‐old male patient had a history of mantle‐cell lymphoma, which was treated with polychemotherapy and reduced‐intensity conditioning allogeneic haematopoietic stem cell transplantation (ASCT) from his healthy sister with an identical human leucocyte antigen profile. Six years after transplantation, the patient developed asymptomatic eczema‐like cutaneous lesions. Histologically the lesions contained a dense superficial lichenoid infiltrate, mainly consisting of CD4+ atypical medium to large lymphocytes showing indented hyperchromatic nuclei. In situ hybridization for Epstein–Barr virus was negative. PCR amplification of the T‐cell receptor‐γ chain gene from several lesions revealed a monoclonal rearrangement without clonal variation. Two‐colour fluorescence in situ hybridization (X and Y chromosomes) and microsatellite genotyping were used to compare samples from the patient (transplant recipient), his sister (donor) and the skin biopsy sample, which confirmed that the origin of the neoplastic cells was the donor graft. To our knowledge, this is the first case of post‐transplant primary cutaneous T‐cell lymphoproliferative disorder after ASCT.     

A question of persistence: Langerhans cells and graft‐versus‐host disease

Langerhans cells (LCs) have been scrutinized many times in studies of the pathogenesis of graft‐versus‐host disease (GVHD). As migratory dendritic cells, LCs are capable of direct antigen presentation to cytotoxic T cells. Their self‐renewal capacity has led to speculation that persistent recipient LCs could provide a continuous source of host antigen to donor T cells infused during hematopoietic stem cell transplantation (HSCT). In this issue of Experimental Dermatology, a new study examines at the relationship between recipient LCs and chronic GVHD.     

Delayed and recurring blisters in the donor graft site of a burn patient

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.     

Comparative Measurement of Biophysical Parameters in Consideration of Skin Graft Donor Site for Nasal Defects

BackgroundIn planning a skin graft, the texture, color, and size of the recipient and donor site tissues should be considered.ObjectiveWe determined the optimal donor sites for nasal full-thickness skin grafting based on biophysical parameters.MethodsThirty women over the age of 60 were selected for this study. Four recipient sites (nasal root, dorsum, tip, ala) and three donor sites (preauricle, postauricle, forehead) were considered. Biophysical parameters such as transepidermal water loss (TEWL), capacitance, sebum output, erythema/melanin value, and skin replica technique were tested.ResultsThe nasal root was correlated with the forehead in terms of TEWL and sebum output. The nasal dorsum was correlated with the preauricle in terms of TEWL, erythema/melanin value, and skin replica measurements. The nasal tip was correlated with the preauricle in terms of TEWL, sebum output, erythema/melanin value, and skin replica measurements. The ala was correlated with the forehead in terms of TEWL and skin replica measurements.ConclusionThe preauricule is the optimal donor site for resurfacing of the nasal dorsum and tip. The forehead is a good donor site for alar defects. For resurfacing of the nasal root, the forehead and postauricle are good choices.     

IL‐1 signalling determines the fate of skin grafts expressing non‐self protein in keratinocytes

Please cite this paper as: IL‐1 signalling determines the fate of skin grafts expressing non‐self protein in keratinocytes. Experimental Dermatology 2010; 19 : 723–729. Abstract: Although IL‐1 is a known inflammatory cytokine during pathogen infection, the role of IL‐1 in skin graft rejection, particularly where foreign antigen is expressed exclusively in keratinocytes, is less understood. Here, we use a syngeneic skin graft system, where antigens are expressed in epithelial cells via either a keratin 14 or keratin 5 promoter, to explore the role of IL‐1 in graft rejection and induction of epithelial antigen‐specific effector CD8⁺ T‐cell function. Keratin 5 ovalbumin (K5mOVA) transgenic skin grafts destined for rejection demonstrated increased expression of IL‐1β and its receptors compared to K14 HPV16 E7 transgenic grafts that do not reject spontaneously. Rejection of OVA grafts lacking the IL‐1 receptor (IL‐1R1) was delayed and associated with decreased numbers of antigen‐specific CD8 T cells. In contrast, K14E7 grafts survived on immunocompetent, syngeneic recipients with decreased graft levels of IL‐1β and IL‐1R1 and 2. However, in the absence of the IL‐1 receptor antagonist, IL‐1Ra, skin grafts were spontaneously rejected and an E7‐specific CD8 T‐cell response was primed. Thus, expression of the HPV16E7 oncoprotein in epithelial cells prevents IL‐1β‐associated skin graft rejection and induction of antigen‐specific CD8 T‐cell responses. Enhancing IL‐1β signalling, via blocking of the IL‐1 receptor antagonist, may represent an alternative strategy for treatment of HPV16E7‐associated cancers.     

A case of chronic perianal pyoderma treated with the recycled skin graft method

We present here a case of chronic perianal pyoderma (CPP), who was treated with a novel skin graft. The patient was a 28-year-old male who had suffered from painful abscesses and nodules on his buttocks for over 10 years. Although the abscesses and nodules were initially restricted to one buttock, they gradually spread over both buttocks. He visited our hospital in July of 2000. He was clinically diagnosed as CPP and treated with oral doses of antibiotics. When admitted to our hospital in September of 2000, an anal fistula was also found. The operations for CPP and anal fistula were simultaneously performed. After the anal fistula treatment, the lesions of CPP were totally resected. In this procedure, we removed the epidermis and upper dermis from the excised CPP lesions and grafted them on the defects of the excised lesion. There has been no recurrence of the CPP. This operation procedure, which we call the "recycled skin graft method" is less invasive, because a donor site for the skin graft is unnecessary. We considered it to be as one of the effective treatments for CPP.     

Combination of 5‐aminolevulinic acid and iron prevents skin fibrosis in murine sclerodermatous graft‐versus‐host disease

Scleroderma or systemic sclerosis (SSc) is a clinically heterogeneous rheumatological autoimmune disease affecting the skin, internal organs and blood vessels. There is at present no effective treatment for this condition. Our study investigated the effects of 5‐aminolevulinic acid (5‐ALA), which is a precursor of haem synthesis, on graft‐vs‐host disease (GvHD)‐induced SSc murine model. Lymphocytes were intravenously injected from donor mice (B10.D2) into recipient BALB/c mice (recombination‐activating gene 2 (Rag‐2)‐null mice) deficient in mature T and B cells to induce sclerodermatous GvHD (scl‐GvHD). To investigate the effect of 5‐ALA on scl‐GvHD, combination of 5‐ALA and sodium ferrous citrate (SFC) was orally administered to the recipient mice for 9 weeks. 5‐ALA/SFC treatment significantly reduced progressive inflammation and fibrosis in the skin and ears. Furthermore, 5‐ALA/SFC suppressed mRNA expression of transforming growth factor‐β, type I collagen and inflammatory cytokines. These results indicate that the 5‐ALA/SFC combination treatment has a protective effect against tissue fibrosis and inflammation in a murine scl‐GvHD‐induced skin and ear inflammation and fibrosis. Furthermore, the efficacy of 5‐ALA/SFC suggests important implications of HO‐1 protective activity in autoimmune diseases, and therefore, 5‐ALA/SFC may have promising clinical applications. These findings suggested that the 5‐ALA/SFC treatment may be the potential strategies for SSc.     

Meshed split skin graft for extensive vitiligo

A 30 year old female presented with generalized stable vitiligo involving large areas of the body. Since large areas were to be treated it was decided to do meshed split skin graft. A phototoxic blister over recipient site was induced by applying 8 MOP solution followed by exposure to UVA. The split skin graft was harvested from donor area by Padgett dermatome which was meshed by an ampligreffe to increase the size of the graft by 4 times. Significant pigmentation of the depigmented skin was seen after 5 months. This procedure helps to cover large recipient areas, when pigmented donor skin is limited with minimal risk of scarring. Phototoxic blister enables easy separation of epidermis thus saving time required for dermabrasion from recipient site.     

Negative‐pressure closure was superior to tie‐over technique for stabilization of split‐thickness skin graft in large or muscle‐exposing defects: A retrospective study

Skin grafts are frequently used for the reconstruction of skin defects, and optimal stabilization of the graft is essential for successful reconstruction. Although the tie‐over technique has been widely used as a standard method in Japan, we sometimes encounter cases with significant graft loss due to suboptimal stabilization of the graft. Reported risk factors for increased graft loss include the following: defects of a large size, with muscle exposure, and located in the trunk and extremities. Recent studies have demonstrated the usefulness of negative‐pressure closure (NPC) for the stabilization of skin grafts due to the uniform pressure it provides across the graft. Therefore, since March 2017, we have used NPC for skin graft stabilization in patients with defects in the trunk and extremities of more than 10 cm in size or with muscle exposure. We carried out a retrospective comparative study of the outcome of the conventional tie‐over technique versus NPC. Mann–Whitney U‐test revealed that NPC showed significantly higher graft survival rate than tie‐over method (P = 0.0012). In addition, NPC showed a tendency toward shorter operative times (from skin graft harvest to the completion of the graft stabilization) than the tie‐over method (P = 0.0931). These results suggest that NPC may be superior to the tie‐over method for stabilization of skin grafts especially in large or muscle‐exposing defects in the trunk or extremities.     

Early‐onset lichenoid graft‐vs.‐host disease: a unique variant of acute graft‐vs.‐host disease occurring in peripheral blood stem cell transplant recipients

Background: A complication of stem cell transplantation is chronic graft‐vs.‐host disease (GvHD), developing months to years after transplant; the two commonest manifestations are lichenoid GvHD and scleroderma. The purpose of this study was to characterize early‐onset lichenoid GvHD. Methods: A retrospective study identified patients diagnosed with early‐onset lichenoid GvHD. This diagnosis was correlated with type of transplant and concurrent or prior episodes of acute GvHD. Results: Patients in whom a sex mismatch was present between donor and recipient were included, representing a study population of 17. All received an allogeneic peripheral blood stem cell transplant (PBSCT). All patients had biopsy proven lichenoid GvHD within 60 days or less following transplantation. All had concurrent gastrointestinal symptoms which was biopsy proven GvHD in thirteen of the cases. FISH XY studies revealed that the infiltrating lymphocytes were of donor origin in 12 of the cases, mixed in three and of host origin in two cases. Conclusions: Early‐onset lichenoid GvHD is exclusive to the PBSCT setting and appears to be mediated by donor lymphocytes, reflecting the higher numbers of donor T cells encountered in PBSCT. We consider this reaction pattern a distinctive subtype of acute GvHD. Magro CM, Kerns MJ, Votava H, Vasil KE, Dyrsen ME, Morrison CD. Early‐onset lichenoid graft‐vs.‐host disease: a unique variant of acute graft‐vs.‐host disease occurring in peripheral blood stem cell transplant recipients.     

Real‐time polymerase chain reaction analysis of a 3895‐bp mitochondrial DNA deletion in epithelial swabs and its use as a quantitative marker for sunlight exposure in human skin

Background The use of mitochondrial DNA (mtDNA) damage as a reliable and highly sensitive biomarker of ultraviolet (UV) radiation exposure in both the dermis and epidermis has now been well developed by our group and others. We have previously identified a 3895‐bp mtDNA deletion which occurred more frequently and to a higher level in usually sun‐exposed skin as opposed to occasionally sun‐exposed skin. This work focused on older‐aged individuals and, in particular, perilesional, histologically normal skin biopsies taken from patients with skin cancer. Objectives To develop novel, less‐invasive methods of obtaining skin samples (i.e. epidermis) from volunteers covering a much wider age range and larger number of individuals (n = 239). Methods The 3895‐bp deletion was quantified by a specific real‐time polymerase chain reaction assay in normal human epidermis samples taken from three body sites with differing sun exposure. Results The results show a statistical increase of the level of the 3895‐bp deletion with increasing sun exposure in the epidermal swabs of human skin (P < 0·001) and with increasing age of the donor in the needle biopsy samples. Conclusions These data suggest that the upper layers of the epidermis are an accessible and reliable site for assessing mtDNA damage caused by UV exposure.     

Use of the Y-body for identification of skin source on a successfully grafted burn patient.

The use of the interphase male Y-body (fluorescent Y chromosome segment) technique with cryostat sections of both fresh and frozen-stored skin biopsies is described. A female burn patient appeared to retain her donor homografts, thereby negating the need for autografts. Since a retained homograft of this sort challenged our understanding of immunologic barriers, we applied the Y-body technique to cutaneous biopsies obtained from the patient's burn area that had been homografted with skin from a male donor, as well as control biopsies from the patient's unburned skin and normal control male and female skin. Based on clinical and cytogenetic observations, it was concluded that the most reasonable explanation for this case was that the regenerating tissue at the graft site was that of the recipient and not that of the originally grafted male skin.     

Fibrin Glue Fixation for Suction Blister Epidermal Grafting in Two Patients with Stable Vitiligo

Vitiligo is a chronic disorder characterized by depigmented macules which can slowly enlarge with the concurrent development of new lesions. Although autologous suction blister epidermal grafting is an established technique for the treatment of recalcitrant, stable vitiligo, the donor tissue graft is not easy to fix at the recipient site, especially in areas such as the joints, face, cutaneous folds, hands, feet, and hair-bearing areas. Therefore, various methods of donor tissue fixation have been attempted. We report two cases of vitiligo treated with suction blister epidermal grafting, with fibrin tissue adhesion. The first case is that of 16-year-old female patient presented with hypopigmented patches on the forehead and frontal scalp area. The other case is that of 32-year-old female patient presented with hypopigmented patches on the chin. We treated them with phototherapy for 1~4 years; however, the lesions were recalcitrant. Therefore, we tried treatment with a suction blister epidermal graft. Because graft fixation is difficult at the recipient sites, fibrin glue was sprayed on the grafts. Thereafter, we applied a porous silicone wound contact layer over the graft area and applied sterile gauze dressing that was left for a week. One week after the procedure, firm fixation of the donor tissue was observed in both cases. Fibrin glue seemed to improve the graft fixation, providng protection against infection and an optimal environment for wound healing. This report suggests that the application of an epidermal graft with fibrin glufixation, can provide the best result in the surgical treatment of stable vitiligo.     

Characterization of pigmented dermo‐epidermal skin substitutes in a long‐term in vivo assay

In our laboratory, we have been using human pigmented dermo‐epidermal skin substitutes for short‐term experiments since several years. Little is known, however, about the long‐term biology of such constructs after transplantation. We constructed human, melanocyte‐containing dermo‐epidermal skin substitutes of different (light and dark) pigmentation types and studied them in a long‐term animal experiment. Developmental and maturational stages of the epidermal and dermal compartment as well as signs of homoeostasis were analysed 15 weeks after transplantation. Keratinocytes, melanocytes and fibroblasts from human skin biopsies were isolated and assembled into dermo‐epidermal skin substitutes. These were transplanted onto immuno‐incompetent rats and investigated 15 weeks after transplantation. Chromameter evaluation showed a consistent skin colour between 3 and 4 months after transplantation. Melanocytes resided in the epidermal basal layer in physiological numbers and melanin accumulated in keratinocytes in a supranuclear position. Skin substitutes showed a mature epidermis in a homoeostatic state and the presence of dermal components such as Fibrillin and Tropoelastin suggested advanced maturation. Overall, pigmented dermo‐epidermal skin substitutes show a promising development towards achieving near‐normal skin characteristics and epidermal and dermal tissue homoeostasis. In particular, melanocytes function correctly over several months whilst remaining in a physiological, epidermal position and yield a pigmentation resembling original donor skin colour.     

Classification and pathophysiology of skin grafts

Flaps and grafts are the 2 main surgical procedures to repair losses of skin tissue. A flap is a full-thickness portion of skin sectioned and isolated peripherally and in depth from the surrounding skin, except along one side, called the peduncle. A graft is a section of skin, of variable thickness and size, completely detached from its original site and moved to cover the zone to be repaired. According to their thickness, skin grafts are classified as split thickness (or partial) and full thickness. The former is further divided into thin, intermediate and thick. Split-thickness skin grafts usually take well, whereas a full-thickness graft only takes if it is relatively small. Grafts are also divided, on the basis of their origin, into the following: autografts, when the donor and recipient are the same individual; homografts, when the donor and recipient are different subjects belonging to the same species; hetero- or xenografts, when the donor and recipient belong to different species. Only autografts can take, whereas homo- and heterografts are rejected. Homo- and heterografts, however, can be useful in particular conditions, for example, extensive burns, because they temporarily ensure vital skin functions.