34 Rete Ridges are Decreased in Dyschromic Burn Hypertrophic Scar: A Histological Study

Introduction Dyschromic hypertrophic scar (HTS) with areas of hyper- and hypo-pigmentation is a common sequelae of burn injury. The mechanism behind the development of dyschromia has not been elucidated. In this study, we provide a histological analysis of these scars with a focus on rete ridge presence. Rete ridges occur in epithelial tissues such as oral mucosa and skin and can be described as undulating “pegs” that are interdigitated with dermal papillae. Rete ridges enhance adhesion of the epidermis to the dermis. We hypothesize that rete ridge presence is important for normal skin physiology, and their absence or presence may hold mechanistic significance in post-burn HTS dyschromia. Methods Subjects with post-burn dyschromic HTS were consented and enrolled (n=27). Punch biopsies of hyper-, hypo-, and normally pigmented scar and skin were collected and stored in formalin. Biopsies were paraffin embedded, sectioned, stained with H&E, and imaged. The number of rete ridges were investigated by calculating a rete ridge ratio from the length of the basement membrane and the length of the epidermis. Results The patient population was predominantly female (55.5%), black (70.4%), and had Fitzpatrick skin Type V (51.9%). The injuries were primarily as a result of flame (37%) and scald (33.3%) and resulted in a median TBSA burn of 7%. The median age of the scar at the time of sample acquisition was 12.2 months. The rete ridge ratio of normally pigmented, un-injured skin was above 1 (1.31 ± 0.04), indicating that normal skin’s basement membrane is longer than its epidermal length due to the presence of rete ridges. HTSs resulting from burn wounds that healed without split thickness autografts were first investigated. The number of rete ridges was higher in normal skin compared to HTS that was either hypo- or hyperpigmented (1.31 ± 0.04 vs. 1.13 ± 0.05 and 1.14 ± 0.04 vs, p< 0.05). This difference was similar despite pigmentation phenotype. When hyper-pigmented scars resulting from wounds that were treated with split thickness autografts (Hyper(+)) were investigated, rete ridge number was significantly higher than in Hyper(-) (1.89 ± 0.23, p< 0.01). Patient age showed a weak correlation (R=-0.33) with rete ridge ratio where older patients had lower rete ridge ratios in normal, un-injured skin. Hyper(+) showed a weak correlation between rete ridge ratio and age of scar (R=-0.38). Conclusions Post-burn HTS that is dyschromic has fewer rete ridges than normal skin. This finding may explain the decreased epidermal barrier function that is associated with HTS.

Cryosurgery as a Single Agent and in Combination with Intralesional Corticosteroids Is Effective on Young, Small Keloids and Induces Characteristic Histological and Immunohistological Changes: A Prospective Randomized Trial

<b><i>Background:</i></b> As the pathogenesis of keloids is poorly understood, there is no sound biological basis of keloid management. Few controlled therapeutic studies have been published, and recurrences are a major reason for treatment failure. <b><i>Objective:</i></b> To detect efficacy and safety of cryosurgery regimens on keloids and the occurring biological changes caused by the treatment. <b><i>Methods:</i></b> This prospective randomized study compared efficacy and tolerability as well as histological/immunohistochemical effects of liquid nitrogen contact cryosurgery as a single regimen (group A) and combined with intralesional corticosteroids (group B) on young (&#x3c;2 years old), small (≤10 cm²) keloids in 40 patients (2-sided effect, α-error 1%, power 95%). <b><i>Results:</i></b> Marked flattening of the lesions was achieved by both regimens. Median lesional volumes decreased from 106 to 7 mm³ in group A (<i>p</i> = 0.001) and from 138 to 6 mm³ in group B (<i>p</i> &#x3c; 0.0001; ns, between groups). Good to excellent responses were registered in 83.3 and 90% of patients in groups A and B, respectively, by evaluating the lesional volume, in 80 and 95% of patients by the physician’s evaluation and in 95% of patients in either group by the patient’s assessment. Follow-up of 6–36 months revealed no further significant changes. Cryosurgery was generally well tolerated, with minor pain during treatment not requiring (27.5%) or requiring local anaesthesia (5%) – but not analgesics –, and hypopigmentation (25%). Histological examination showed increased vessel number and lumen dilatation after treatment in group B and reduction of rete ridge length in both groups with more prominent changes in group A. Tenascin C staining demarcated keloids from normal skin before therapy, while after therapy the entire treated tissue was labelled. Interferon-γ expression was significantly decreased after therapy both regarding positively stained cells and intensity in both groups. <b><i>Conclusion:</i></b> Cryosurgery without and with intralesional corticosteroids is effective and safe on young, small keloids not only as a destructive physical procedure, but also by inducing biochemical and immunological scar rejuvenation.

Psoriasiform Dermatitis Developing during Treatment of Juvenile Idiopathic Arthritis with Tocilizumab

We present a case of psoriasiform dermatitis developing during the treatment of juvenile idiopathic arthritis with tocilizumab (TCZ). The keratotic erythema with central healing showed a periodicity of growing worse 1 week after TCZ infusion, and then disappeared within 3 weeks. Skin biopsy showed parakeratosis, microabscess, rete ridge elongation, and abundant lymphocytes as well as a few neutrophil infiltrate in the upper dermis. TCZ is a humanized monoclonal antibody against interleukin 6 (IL-6) receptor. IL-6 plays a critical role in the differentiation from naïve T cells into Th17 cells in cooperation with transforming growth factor-β. IL-6 may be important in psoriasis pathogenesis, and therefore this phenomenon may be the adverse effect. The mechanism of TCZ-associated psoriasiform dermatitis is unclear. The serum IL-6 level seems to be elevated transitorily after TCZ administration, probably due to the competitive inhibition of IL-6 receptor alpha to IL-6. Excess free IL-6 may effect on other IL-6 family receptors. Since TCZ does not alter serum IL-17F level, another cytokine may be involved in the psoriasis formation in our case. Psoriasiform dermatitis during the use of TCZ may be due to relative cytokine balance disturbance.

A methodology for the production of microfabricated electrospun membranes for the creation of new skin regeneration models

The continual renewal of the epidermis is thought to be related to the presence of populations of epidermal stem cells residing in physically protected microenvironments (rete ridges) directly influenced by the presence of mesenchymal fibroblasts. Current skin in vitro models do acknowledge the influence of stromal fibroblasts in skin reorganisation but the study of the effect of the rete ridge-microenvironment on epidermal renewal still remains a rich topic for exploration. We suggest there is a need for the development of new in vitro models in which to study epithelial stem cell behaviour prior to translating these models into the design of new cell-free biomaterial devices for skin reconstruction. In this study, we aimed to develop new prototype epidermal-like layers containing pseudo-rete ridge structures for studying the effect of topographical cues on epithelial cell behaviour. The models were designed using a range of three-dimensional electrospun microfabricated scaffolds. This was achieved via the utilisation of polyethylene glycol diacrylate to produce a reusable template over which poly(3-hydrroxybutyrate- co-3-hydroxyvalerate) was electrospun. Initial investigations studied the behaviour of keratinocytes cultured on models using plain scaffolds (without the presence of intricate topography) versus keratinocytes cultured on scaffolds containing microfeatures.

Sunitinib Improves Some Clinical Aspects and Reverts DMBA-Induced Hyperplasic Lesions in Hamster Buccal Pouch

Oral squamous cell carcinoma (OSCC) is a public health problem. The hamster buccal pouch model is ideal for analyzing the development of OSCC. This research analysed the effects of sunitinib (tyrosine kinase inhibitor) in precancerous lesions induced by 7,12-dimethylbenz(a)anthracene (DMBA) in this model. Thirty-four male hamsters, divided into six groups: control—C n=7, acetone—A n=12, carbamide peroxide—CP n=5, acetone and CP—A+CP n=8, 1% DMBA in acetone and CP—DA+CP n=6, and 1% DMBA in acetone and CP and 4-week treatment with sunitinib—DA+CP+S n=7. The aspects evaluated were anatomopathological features (peribuccal area, paws, nose, and fur), histological sections of the hamster buccal pouches (qualitatively analyzed), epithelium thickness, and the rete ridge density (estimated). Sunitinib was unable to attenuate the decrease in weight gain induced by DMBA; no increase in volume was detected in the pouch and/or ulceration, observed in 43% of the animals in the DA+CP group. DA+CP groups presented a significant increase in rete ridge density compared to the control groups (P<0.01) which was reverted by sunitinib in the DA+CP+S group. Sunitinib seems to have important benefits in early stage carcinogenesis and may be useful in chemoprevention.