Beda Mühleisen

IL-31 expression by inflammatory cells is preferentially elevated in atopic dermatitis.

Interleukin-31 (IL-31) is a recently discovered cytokine expressed in many human tissues, and predominantly by activated CD4(+) T cells. IL-31 signals through a heterodimeric receptor consisting of IL-31 receptor alpha (IL-31RA) and oncostatin M receptor beta (OSMR). Earlier studies have shown involvement of IL-31 and its receptor components IL-31RA and OSMR in atopic dermatitis, pruritus and Th2-weighted inflammation at the mRNA level. The aim of this study was to investigate IL-31 protein expression in skin of such conditions. Immunohistochemical staining for IL-31, IL-31RA and OSMR was performed in formalin-fixed paraffin-embedded biopsy specimens. IL-31 expression was increased in the inflammatory infiltrates from skin biopsies taken from subjects with atopic dermatitis, compared with controls (p ≤ 0.05). IL-31, IL-31RA and OSMR protein immunoreactivity was not increased in biopsies from subjects with other Th2-weighted and pruritic skin diseases. Our results confirm, at the protein level, the relationship between IL-31 expression and atopic dermatitis. Our results do not support a general relationship between expression of IL-31/IL-31R and pruritic or Th2-mediated diseases.

Progression of cutaneous squamous cell carcinoma in immunosuppressed patients is associated with reduced CD123+ and FOXP3+ cells in the perineoplastic inflammatory infiltrate.

Aims:  Squamous cell carcinoma of the skin (SCC) increases dramatically in organ transplant recipients (OTRs). The aim was to determine whether qualitative and quantitative differences in perineoplastic inflammation in OTRs contribute to the increased carcinogenesis.

Immunosuppression affects CD4+ mRNA expression and induces Th2 dominance in the microenvironment of cutaneous squamous cell carcinoma in organ transplant recipients.

Squamous cell carcinoma (SCC) is the most frequent cancer in organ transplant recipients (OTRs). The immune system plays a major role in the fight against SCC, however, little is known about the local inflammatory response in SCC at all. We analyzed quantity and quality of the perineoplastic inflammatory SCC microenvironment in immunocompetent patients and immmunosuppressed OTRs. RNA expression profile of SCC patients was analyzed for 8 different sets of genes relating to Th1 versus Th2 response using Gene Set Enrichment Analysis. SCC from immunocompetent patients and OTRs were analyzed by real-time polymerase chain reactions for CD4, CD8, TBET, GATA-3, FOXP3, RORC, IFN-γ, IL-4, TGF-&bgr;, IL-10, and IL-17A mRNA expression. Immunohistochemistry was carried out in SCC for CD3, CD4, CD8, and FOXP3 expression. Considerable inflammation was seen in both patient groups. SCC in immunocompetent patients and OTRs was associated with a mixed Th1 and Th2 gene expression signature. CD4+ mRNA was diminished in immunosuppression. Skin adjacent to SCC in OTRs showed Th2 expression pattern as compared with immunocompetent patients. T-BET and IFN-γ mRNA expression were decreased in the OTR group. Although Th17-weighted inflammation was unchanged, IL-17A mRNA level was markedly decreased with immunosuppression. Regulatory T cells, characterized by FOX-P3 and TGF-β mRNA level, were decreased in OTRs. Our findings support the hypothesis that nontumor-bearing skin adjacent to SCC in OTRs is not necessarily normal and that the local microenvironment may contribute to a field effect contributing to higher recurrence rates and more aggressive behavior observed in these patients.

Pictorial Representation of Illness and Self Measure (PRISM) A Novel Visual Instrument to Measure Quality of Life in Dermatological Inpatients

OBJECTIVES To validate the PRISM (Pictorial Representation of Illness and Self Measure) tool, a novel visual instrument, for the assessment of health-related quality of life in dermatological inpatients compared with the Dermatology Life Quality Index (DLQI) and the Skindex-29 questionnaires and to report qualitative information on PRISM. DESIGN In an open longitudinal study, PRISM and Skindex-29 and DLQI questionnaires were completed and HRQOL measurements compared. SETTING Academic dermatological inpatient ward. PARTICIPANTS The study population comprised 227 sequential dermatological inpatients on admission. INTERVENTION Patients completed the PRISM tool and the Skindex-29 and DLQI questionnaires at admission and discharge. MAIN OUTCOME MEASURES PRISM Self-Illness Separation (SIS) score; Skindex-29 and DLQI scores; and qualitative PRISM information by Mayring inductive qualitative context analysis. RESULTS The PRISM scores correlated well with those from the Skindex-29 (rho = 0.426; P < .001) and DLQI (rho = 0.304; P < .001) questionnaires. Between PRISM and Skindex-29 scores, the highest correlations were for dermatitis (rho = 0.614) and leg ulcer (rho = 0.554), and between PRISM and DLQI scores, the highest correlations were for psoriasis (rho = 0.418) and tumor (rho = 0.399). The PRISM tool showed comparable or higher sensitivity than quality of life questionnaires to assess changes in the burden of suffering during hospitalization. Inductive qualitative context analysis revealed impairment of adjustment and self-image as major aspects. Patients overall expected symptomatic and functional improvement. In patients with psoriasis and leg ulcers, many expected no treatment benefit. CONCLUSIONS The PRISM tool proved to be convenient and reliable for health-related quality of life assessment, applicable for a wide range of skin diseases, and correlated with DLQI and Skindex-29 scores. With the PRISM tool, free-text answers allow for the assessment of individual information and potentially customized therapeutic approaches.

Squamous cell carcinoma of the skin induces considerable sustained cost of care in organ transplant recipients

BACKGROUND Squamous cell carcinoma (SCC) is the most frequent cancer in organ transplant recipients (OTR). OBJECTIVE We retrospectively analyzed the cost of dermatologic care in our OTR specialty clinic. METHODS We collected billing data for OTR (n = 198) seen at the Dermatology Department of Zurich University Hospital over 4 years (2004-2007). Grouping by histology yielded the groups: SCC (n = 70), with SCC occurring within the observation period; past SCC (n = 40), with SCC before the observation period; in situ SCC (n = 13), when only in situ SCC had been diagnosed; biopsy negative (n = 49) for SCC and in situ SCC; and no biopsy ever (n = 26) within the observation period. RESULTS Median annual costs for dermatologic care were US

Ecthyma-Gangrenosum-Like Bullous Pemphigoid

1398 for SCC; US

Retinoic Acid Receptor Isoform mRNA Expression Differs Between BCC and SCC of the Skin

776 for past SCC; US

Pronounced Allelic Imbalance at D9S162 in Skin Squamous Cell Carcinoma of Organ Transplant Recipients

308 for in situ SCC; US

Weight of decision-making impairs clinical assessment of melanocytic lesions.

211 for biopsy negative; and US

Iconography : Squamous cell carcinoma of the skin induces considerable sustained cost of care in organ transplant recipients

156 for no biopsy ever. Median cost per case of invasive SCC (US