Variations of Hair Follicle Size and Distribution in Different Body Sites

For the evaluation and quantification of follicular penetration processes, the knowledge of variations of hair follicle parameters in different body sites is basic. Characteristics of follicle sizes and potential follicular reservoir were determined in cyanoacrylate skin surface biopsies, taken from seven different skin areas (lateral forehead, back, thorax, upper arm, forearm, thigh, and calf region). The highest hair follicle density and percentage of follicular orifices on the skin surface and infundibular surface were found on the forehead, whereas the highest average size of the follicular orifices was measured in the calf region. The highest infundibular volume and therefore a potential follicular reservoir was calculated for the forehead and for the calf region, although the calf region showed the lowest hair follicle density. The calculated follicular volume of these two skin areas was as high as the estimated reservoir of the stratum corneum. The lowest values for every other parameter were found on the forearm. The present investigation clearly contradicts former hypothesis that the amount of appendages of the total skin surface represents not more than 0.1%. Every body region disposes its own hair follicle characteristics, which, in the future, should lead us to a differential evaluation of skin penetration processes and a completely different understanding of penetration of topically applied drugs and cosmetics

Identification of differentially expressed genes in cutaneous squamous cell carcinoma by microarray expression profiling

BACKGROUND: Carcinogenesis is a multi-step process indicated by several genes up- or down-regulated during tumor progression. This study examined and identified differentially expressed genes in cutaneous squamous cell carcinoma (SCC). RESULTS: Three different biopsies of 5 immunosuppressed organ-transplanted recipients each normal skin (all were pooled), actinic keratosis (AK) (two were pooled), and invasive SCC and additionally 5 normal skin tissues from immunocompetent patients were analyzed. Thus, total RNA of 15 specimens were used for hybridization with Affymetrix HG-U133A microarray technology containing 22,283 genes. Data analyses were performed by prediction analysis of microarrays using nearest shrunken centroids with the threshold 3.5 and ANOVA analysis was independently performed in order to identify differentially expressed genes (p < 0.05). Verification of 13 up- or down-regulated genes was performed by quantitative real-time reverse transcription (RT)-PCR and genes were additionally confirmed by sequencing. Broad coherent patterns in normal skin vs. AK and SCC were observed for 118 genes. CONCLUSION: The majority of identified differentially expressed genes in cutaneous SCC were previously not described

Immunomodulation by Interleukin-10 Therapy Decreases the Incidence of Relapse and Prolongs the Relapse-free Interval in Psoriasis

The ability of interleukin-10 therapy to reduce the severity of exacerbated psoriasis has been demonstrated recently. Considering the immunobiologic properties of this cytokine we investigated the effects of long-term interleukin-10 application on the immune system and duration of psoriasis remission. We performed a placebo-controlled, double-blind, phase II trial using interleukin-10 in patients with chronic plaque psoriasis in remission. Patients received subcutaneous injections with either interleukin-10 (10 µg per kg body weight; n = 7) or placebo (n = 10) three times per week until relapse or study termination after 4 months. The treatment was well tolerated. In the placebo group almost all patients (90%) showed a relapse during the observation period. In contrast to this, only two of seven patients (28.6%) relapsed in the interleukin-10-treated group. Kaplan–Meier analysis revealed a significantly lower relapse incidence in the interleukin-10 than in the placebo group (p = 0.02). The mean relapse-free interval time was 101.6 ± 12.6 d in the interleukin-10 group in comparison with 66.4 ± 10.4 d in the placebo group. Immunologic activity of interleukin-10 application was indicated by an increase in soluble interleukin-2 receptor plasma levels and higher ex vivo interleukin-4 secretion capacities. Remarkably, a significant negative correlation was demonstrated between the interleukin-4 secretion capacity and Psoriasis Area and Severity Index score (r = -0.36, p < 0.01). Our data suggest that interleukin-10 therapy is immunologic effective, decreases the incidence of relapse and prolongs the disease-free interval in psoriasis. Its value should be further determined in larger trials and for the prevention of re-exacerbation of other inflammatory disorders with a similar immunologic profile

Water-filtered infrared-A (wIRA) can act as a penetration enhancer for topically applied substances

Background: Water-filtered infrared-A (wIRA) irradiation has been shown to enhance penetration of clinically used topically applied substances in humans through investigation of functional effects of penetrated substances like vasoconstriction by cortisone

Absence of Microsatellite Instability and Lack of Evidence for Subclone Diversification in the Pathogenesis and Progression of Mycosis Fungoides

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Large molecular systems landscape uncovers T cell trapping in human skin cancer

Immune surveillance of tumour cells is an important function of CD8 T lymphocytes, which has failed in cancer for reasons still unknown in many respect but mainly related to cellular processes in the tumour microenvironment. Applying imaging cycler microscopy to analyse the immune contexture in a human skin cancer we could identify and map 7,000 distinct cell surface-associated multi-protein assemblies. The resulting combinatorial geometry-based high-functional resolution led to discovery of a mechanism of T cell trapping in the epidermis, which involves SPIKE, a network of suprabasal keratinocyte projections piercing and interconnecting CD8 T cells. It appears initiated by clusters of infrabasal T and dendritic cells connected via cell projections across a fractured basal lamina to suprabasal keratinocytes and T lymphocytes

Expression of the B7/BB1 Activation Antigen and its Ligand CD28 in T-Cell-Mediated Skin Diseases

Interactions of CD28 (on T cells) with its recently identified ligand B7/BB1 (on antigen-presenting cells) have been shown to activate T cells via a major histocompatibility complex/Ag-independent “alternative” pathway, leading to an amplification of T- cell – mediated immune responses. The in vivo relevance of these molecules for cutaneous immunity is presently unknown. These findings prompted us to study the expression of B7/BB1 and CD28 in normal human skin and in selected T-cell – mediated inflammatory skin diseases. Biopsies were obtained from lesional skin of patients with allergic contact dermatitis, lichen planus, and, as control, from basal cell carcinoma and from healthy controls. Serial cryostat sections were stained with a panel of MoAbs directed against CD28, B7/BB1, CD3, CD1a, and KiM8 using immunohistochemistry (ABC technique). CD28 expression was observed in the majority of dermal and epidermal CD3+ T cells in contact dermatitis and lichen planus. In normal skin and basal cell carcinoma, CD28 was expressed only occasionally by perivascular T cells. In allergic contact dermatitis and lichen planus, B7/BB1-expression was found on dermal dendritic cells, on dermal macrophages, on Langerhans cells, focally on keratinocytes, and occasionally on dermal T cells. No B7/BB1 immunoreactivity was detected in normal skin and basal cell carcinoma. These findings indicate that T-cell – mediated skin diseases are accompanied by an influx of CD28+ T cells and an upregulation of B7/BB1 on cutaneous antigen- presenting cells, keratinocytes, and on some T cells. We speculate that “alternative” T cell-activation via the B7/CD28 pathway may contribute to the pathogenesis of these skin diseases

Differential Expression of TRAF1 Aids in the Distinction of Cutaneous CD30-Positive Lymphoproliferations

Lymphomatoid papulosis (LyP), primary cutaneous anaplastic large T-cell lymphoma (cALCL), and cutaneous infiltrates of systemic anaplastic large cell lymphoma (sALCL) are CD30-positive lymphoproliferative disorders of the skin that overlap clinically, histopathologically, immunophenotypically, and genetically but differ considerably in their prognosis. In particular, lesions of LyP regress spontaneously, whereas those of cALCL and sALCL persist and may progress and spread to extracutaneous sites. In contrast to patients with cALCL, LyP patients do not benefit from an aggressive radio- and/or chemotherapeutic approach. We generated a novel tumor necrosis factor receptor (TNFR)-associated factor 1 (TRAF1) antibody that recognizes a formalin-resistant epitope (Ber-TRAF1A) and investigated the expression of TRAF1, an intracellular component of TNFR signaling, in LyP and ALCL. We could show a strong TRAF1 expression in the tumor cells of most LyP cases (42/49, 84%). In contrast, tumor cells of primary and secondary cALCL revealed TRAF1 expression in only a few cases (3/41, 7%) as shown for sALCL without skin manifestation. The data indicate that TRAF1 expression reliably distinguishes LyP from primary or secondary cALCL. This might be of crucial diagnostic importance and has a strong impact on the treatment decision for patients with cALCL and LyP

A Potential Link to Skin Destruction and Metabolic Alterations

Acne inversa (AI; also designated as hidradenitis suppurativa) is a chronic inflammatory disease with still unknown pathogenesis that affects the intertriginous skin of perianal, inguinal, and axillary sites. It leads to painful nodules, abscesses, and fistulas with malodorous secretion and is frequently associated with metabolic alterations. Here, we demonstrate that one of the most highly upregulated molecules in AI lesions is matrix metalloproteinase 8 (MMP8), an enzyme specialized in the degradation of extracellular matrix components and the HDL component apolipoprotein A-I. Granulocytes, which were present in AI lesions, secreted high amounts of MMP8 especially after TNF-α stimulation. Furthermore, activated fibroblasts but not keratinocytes were found to express MMP8. The high lesional MMP8 levels were accompanied by elevated blood levels that positively correlated with TNF-α blood levels and disease severity assessed by Sartorius score, especially with the number of regions with inflammatory nodules/abscesses and fistulas. Additionally, we found a negative correlation between blood MMP8 and HDL- cholesterol levels, suggesting a contributory role of MMP8 in metabolic alterations in AI. In summary, we demonstrate elevated MMP8 levels in AI lesions, suggest their role in skin destruction and metabolic alterations, and recommend the use of MMP8 as blood biomarker for AI disease activity assessment