Psoriasis is an immune-regulated skin disease with various clinical subtypes and disease activities. The majority of patients present with predominantly stable plaques. At the onset of new lesions, plaque-type psoriasis frequently demonstrates pin-sized and highly inflammatory papules sometimes with an inflammatory border. The histopathology of initial psoriasis differs from stable plaque-type psoriasis. Early lesions demonstrate innate immune cells with neutrophils, degranulating mast cells and macrophages. These are followed by interleukin (IL)-1-dependent T helper (Th)17 cells, finally resulting in the Th1-dominated immunopathology of stable plaque-type psoriasis, where mononuclear cells predominate with interspersed neutrophilic (Munro) microabscesses. These features suggest a bimodal immune pathway where alternate activation of either innate (autoinflammatory) or adaptive (autoimmune) immunity predominates. Neutrophilic infiltrations appear during early psoriasis with Munro abscesses. They are time limited and occur periodically, clinically best seen in linear nail pitting. These features strongly suggest a critical role for an IL-1-Th17-dominated autoinflammation in the initiation of psoriasis, followed by a Th1-dominated late-phase reaction. The concept of bimodal immune activation helps to explain results from therapeutic interventions that are variable and previously only partly understood.

BACKGROUND Cutaneous melanoma (CM) incidence and mortality have risen dramatically during the past 2 generations, particularly among Caucasian populations. Detailed, long‐term trends of CM in relation to clinical and pathologic characteristics in a Central European population have not been published to date. METHODS The current study was based on 1980 patients with invasive CM diagnosed in Southern Germany during the years from 1976 to 2003 documented by the Central Malignant Melanoma Registry. The German standard population was used to calculate age‐standardized rates, and the annual percent change was estimated by using age, anatomic site, histologic type, and tumor thickness. RESULTS During the study period, the incidence of CM approximately was tripled for males and females, reaching 10.3 and 13.3 per 100,000 per year, respectively (P < .001). The largest increases occurred for melanoma localized on the upper limbs (annual change, 5.9% for males and 5.0% for females; P < .001) and superficially spreading melanoma (annual change, 7.8% for males and 5.9% for females; P < .001). Thin tumors (Breslow thickness <1 mm) were presented significantly more often during the study period (annual change, 9.8% for males and 6.1% for females; P < .001), predominantly in younger patients. Thick tumors and nodular melanomas were more frequent among older patients (age >70 years), particularly among males. The age‐standardized mortality decreased from 1.5 to 0.8 per 100,000 males and from 2.6 to 0.8 per 100,000 females with a significant downward trend for the female population (P < .001). CONCLUSIONS The current results indicated which diverging trends between incidence and mortality may be explained by improved public awareness regarding suspicious pigmented lesions and the earlier detection of these tumors. Continuation of the current preventive strategy and its expansion to include older age groups in the population are warranted. Cancer 2006. © 2006 American Cancer Society.

BackgroundWe previously showed that the bacterial lipopeptide Pam3Cys-Ser-Ser, meanwhile established as a toll-like receptor (TLR) 1/2 ligand, acts as a strong adjuvant for the induction of virus specific CD8+ T cells in mice, when covalently coupled to a synthetic peptide.Case presentationWe now designed a new water-soluble synthetic Pam3Cys-derivative, named XS15 and characterized it in vitro by a TLR2 NF-κB luciferase reporter assay. Further, the capacity of XS15 to activate immune cells and stimulate peptide-specific CD8+ T and NK cells by 6-sulfo LacNAc+ monocytes was assessed by flow cytometry as well as cytokine induction using immunoassays. The induction of a functional immune response after vaccination of a volunteer with viral peptides was assessed by ELISpot assay and flow cytometry in peripheral blood cells and infiltrating cells at the vaccination site, as well as by immunohistochemistry and imaging.XS15 induced strong ex vivo CD8+ and TH1 CD4+ responses in a human volunteer upon a single injection of XS15 mixed to uncoupled peptides in a water-in-oil emulsion (Montanide™ ISA51 VG). A granuloma formed locally at the injection site containing highly activated functional CD4+ and CD8+ effector memory T cells. The total number of vaccine peptide-specific functional T cells was experimentally assessed and estimated to be 3.0 × 105 in the granuloma and 20.5 × 106 in peripheral blood.ConclusionThus, in one volunteer we show a granuloma forming by peptides combined with an efficient adjuvant in a water-in-oil-emulsion, inducing antigen specific T cells detectable in circulation and at the vaccination site, after one single vaccination only. The ex vivo T cell responses in peripheral blood were detectable for more than one year and could be strongly boosted by a second vaccination. Hence, XS15 is a promising adjuvant candidate for peptide vaccination, in particular for tumor peptide vaccines in a personalized setting.

BackgroundKaposi's sarcoma (KS) in HIV negative patients is rare and has to be distinguished from AIDS associated KS. Two groups are at risk to develop non-AIDS related KS: elderly men mainly of Mediterranean origin and persons with iatrogenic immunosuppression.Patients and MethodsIn order to define risk-groups and major clinical features we retrospectively evaluated clinical data of all patients with non-AIDS associated KS presenting to the Department of Dermatology, University Hospital Tuebingen between 1987 and 2009. Data were extracted from the tumor registry of the Comprehensive Cancer Center Tuebingen and from patient records.Results20 patients with non-AIDS KS have been identified. The average age at KS onset was 66.6 years; the male-to-female-ratio was 3∶1. Most of the patients were immigrants from Mediterranean or Eastern European countries (60%). 15 cases of classic KS versus 5 cases of iatrogenic KS were observed. In 95% of the cases, KS was limited to the skin, without mucosal, lymph node or visceral manifestation. KS lesions were in all cases multiple and mostly bilateral, the most common localization was the skin of the lower extremities. Tumor control was achieved in nearly all cases by the use of local or systemic therapy. No patient died from KS.ConclusionsUnlike KS in AIDS patients, non-AIDS associated KS is a rather localized process which rarely involves lymph nodes or organs. It is mostly seen in elderly males from Mediterranean or Eastern European countries and in most cases responsive on local or systemic therapeutic strategies.

Background: Dermatoscopy (dermoscopy, epiluminescence microscopy) is used for the early detection of malignant tumors and avoidance of unnecessary excisions of benign skin tumors. Objective: Description of the dermatoscopic pattern of clear-cell acanthoma. Methods: Video dermatoscopy at 20-fold magnification of a clear-cell acanthoma and psoriasis vulgaris. Results: Homogeneous, symmetrically or bunch-like arranged, pinpoint-like capillaries were seen in the clear-cell acanthoma and in psoriasis vulgaris. Conclusion: The dermatoscopic psoriasis-like pattern of clear-cell acanthoma is a diagnostic clue which may help the clinician to identify this benign epidermal tumor and to differentiate it from other benign and malignant tumors of the skin.