Involvement of IL-1 and oncostatin M in acanthosis associated with hypertensive leg ulcer.

Hypertensive leg ulcer (HLU) is an inflammatory disease characterized by intense pain, alteration of vascularization, and skin necrosis. The optimal treatment relies on surgical removal of necrotic tissues covered by a split-skin graft. We studied the histomorphology of the lesions and investigated the involvement of inflammatory cells and cytokines to further define the physiopathology of HLU. We report epidermis acanthosis and a preferential occlusion of the precapillary arterioles with infiltration of neutrophils, macrophages, and T lymphocytes in the dermis. OSM, IL-1ß, and IL-6 were overexpressed in the ulcer, whereas the Th17-derived cytokines were not. In vitro, the addition of IL-1ß and OSM promoted acanthosis and destructuring of reconstructed epidermis. Exogenous IL-1ß and OSM synergistically induced epidermal acanthosis in mice. These data show that OSM and IL-1ß are not only a biological characteristic signature of HLU, but these cytokines reflect a specific inflammatory state, directly involved in the pathogenesis. We suggest that anti-cytokine biotherapies could be an alternative strategy to surgery to treat HLU.

A 3-year causative study of pompholyx in 120 patients.

OBJECTIVE: To assess the relative frequency of the different causes of pompholyx evoked in the literature. DESIGN: Prospective survey. SETTING: Clinical outpatient setting. PATIENTS: A total of 120 consecutive patients with pompholyx referred to our department from 2000 through 2003. MAIN OUTCOME MEASURES: Systematic investigation of different causes of pompholyx: fungal intertrigo, hyperhidrosis, atopy, contact eczema, and internal reactions with systematic provocation tests to metals, balsam of Peru, and food allergen when suspected. RESULTS: The present study found the following causes of pompholyx in the 120 patients: mycosis (10.0%); allergic contact pompholyx (67.5%), with cosmetic and hygiene products as the main factor (31.7%), followed by metals (16.7%); and internal reactivation from drug, food, or haptenic (nickel) origin (6.7%). The remaining 15.0% of patients were classified as idiopathic patients, but all were atopic. (Percentages do not total 100 because of rounding.) CONCLUSIONS: Our data confirm the existence of reactional pompholyx to interdigital-plantar intertrigos and endogenous reactions to metals or other allergens, but they mainly point at the unexpected importance of a so-called contact pompholyx in which cosmetic and hygiene products play a preponderant role compared with metals. The great frequency of atopic conditions, even if idiopathic pompholyx is not inferred as an equivalent of atopy, should lead to further causative investigations before undertaking more expensive or extensive treatments of refractory pompholyx.

Oncostatin M secreted by skin infiltrating T lymphocytes is a potent keratinocyte activator involved in skin inflammation.

Cutaneous inflammatory diseases such as psoriasis vulgaris and atopic dermatitis are associated with altered keratinocyte function, as well as with a particular cytokine production profile of skin-infiltrating T lymphocytes. In this study we show that normal human epidermal keratinocytes express a functional type II oncostatin-M (OSM) receptor (OSMR) consisting of the gp130 and OSMRbeta components, but not the type I OSMR. The type II OSMR is expressed in skin lesions from both psoriatic patients and those with atopic dermatitis. Its ligand, OSM, induces via the recruitment of the STAT3 and MAP kinase pathways a gene expression profile in primary keratinocytes and in a reconstituted epidermis that is characteristic of proinflammatory and innate immune responses. Moreover, OSM is a potent stimulator of keratinocyte migration in vitro and increases the thickness of a reconstituted epidermis. OSM transcripts are enhanced in both psoriatic and atopic dermatitic skin as compared with healthy skin and mirror the enhanced production of OSM by T cells isolated from diseased lesions. Results from a microarray analysis comparing the gene-modulating effects of OSM with those of 33 different cytokines indicate that OSM is a potent keratinocyte activator similar to TNF-alpha, IL-1, IL-17, and IL-22 and that it acts in synergy with the latter cytokines in the induction of S100A7 and beta-defensin 2 expression, characteristic of psoriatic skin. Taken together, these results demonstrate that OSM and its receptor play an important role in cutaneous inflammatory responses in general and that the specific effects of OSM are associated with distinct inflammatory diseases depending on the cytokine environment.

Bi-acromial dimples: a series of seven cases.

Seven patients with bi-acromial dimples are reported, with a family history in only one. This skin condition presented as an anatomic peculiarity without associated abnormalities. Although it has been previously documented as a finding in malformation syndromes such as the 18q syndrome, we point out that it may be found quite frequently in isolation and without morbidity. Therefore, it should be mainly considered as an anatomic variation without pathologic significance.

Artificial skin as a valuable adjunct to surgical treatment of a large squamous cell carcinoma in a patient with epidermolysis bullosa.

BACKGROUND: Among tissue-engineered skins, two bilayered cellular constructs and one cryopreserved dermal substitute have been approved for the treatment of epidermolysis bullosa. Nevertheless, the application of artificial skin technology to surgical treatment of squamous cell carcinomas in a patient with epidermolysis bullosa has never been reported. OBJECTIVE: To reconstruct the large defect remaining after squamous cell carcinoma excision in a patient with dominantly inherited dystrophic epidermolysis bullosa. METHODS: To apply a 10 x 15 cm Integra sheet (Integral Life-sciences Corporation, Plainsboro, NJ, USA) (an acellular collagen matrix coated with a thin polysiloxane elastomer) to the excised area and 3 weeks later to cover the Integra sheet with an ultrathin meshed skin graft. RESULTS: The graft take was complete, and the donor site totally regenerated, except for three small bullae at 7 weeks postoperatively. CONCLUSION: Integra offers the advantage of filling huge defects with its dermal layer of collagen fibers and provides an optimal graft bed. This first step makes it possible to use very thin grafts 3 weeks later.

Peninsular conchal axial flap to reconstruct the upper or middle third of the auricle.

BACKGROUND: The reconstruction of partial amputations of the auricle is a continuous subject of publications, in particular, the techniques of ear reconstruction with postauricular flaps. OBJECTIVE: To present in detail the surgical procedure of a new peninsular conchal transposition flap. MATERIALS AND METHODS: This new conchal transposition flap has been used since 1998 to reconstruct seven partial amputations of the upper or middle third of the auricle. If we compare the flap to a tennis racket, the head corresponds to a skin-cartilage-skin flap harvested from the concha and the shaft to a post- and supra-auricular cutaneous and subcutaneous pedicle based around the posterior auricular artery and the superior auricular branch of the superficial temporal artery. The blood supply is reliable because the superior branch of the posterior auricular artery anastomoses with the superior auricular branch of the superficial temporal artery. RESULTS: There have been no significant complications, except one case of partial rim necrosis, which responded well to wound healing by secondary intention. CONCLUSION: Our peninsular flap could be an alternative to more complex procedures involving costal cartilage harvesting, provided that auricle amputations are confined to the upper or middle third of the peripheral structures and spare the concha.

Keratinocytes as targets for interleukin-10-related cytokines: a putative role in the pathogenesis of psoriasis.

Cytokines are key factors in the cross talk between the immune system and other systems including hepatic, nervous, cardiac and cutaneous systems, leading to an adaptive and integrated response of the organism to stress. They are also involved in the regulation of many processes, including hematopoiesis, the immune response and inflammation. IL-10 is one of the most important anti-inflammatory cytokines. Five cytokines structurally related to IL-10 have been described and presently form this family of cytokines: IL-19, IL-20, IL-22, IL-24 and IL-26. In contrast to IL-10, these cytokines display pro-inflammatory activities in different tissues, including skin. Indeed, some of them induce an inflammatory keratinocyte gene expression profile and an epidermis histology resembling psoriatic lesions. In this review, we discuss recent knowledge about the effects of cytokines of the IL-10 family on keratinocytes and their potential role in psoriasis, a cutaneous inflammatory disease.