Clinical investigations of Toll-like receptor agonists.

Background: Toll-like receptors (TLR) represent a family of surface molecules that function as primary sensors of the innate immune system to recognize microbial pathogens. Ligand binding to TLR results in activation of cellular signaling pathways that regulate expression of genes involved in inflammation and immunity.

Objective: Use of synthetic TLR ligands (agonists) for treatment and prevention of infectious and neoplastic diseases.

A phase II dose-ranging study of topical resiquimod to treat actinic keratosis.

Background: Resiquimod, a toll-like receptor 7 and 8 agonist, may be effective as a topical treatment of actinic keratosis (AK).

Objectives: To evaluate the effect of resiquimod gel concentration on lesion clearance.

Methods: Patients with AK lesions on the face or balding scalp were randomly assigned to resiquimod 0.

Topical Polyphenon E in the treatment of external genital and perianal warts: a randomized controlled trial.

Background: Benign external genital and perianal warts (condylomata acuminata) are disfiguring, displeasing skin tumours caused by human papillomavirus that may vitally burden affected patients and their partners. Current treatment options are still unsatisfactory due to low efficacy, high recurrence rates or an unfavourable side-effect profile. Although most recently prophylactic vaccines have been recommended for adolescent women, appropriate treatment modalities for anogenital warts are still needed.

Clinical applicability of in vivo fluorescence confocal microscopy for noninvasive diagnosis and therapeutic monitoring of nonmelanoma skin cancer.

Excisional biopsies and routine histology remains the gold standard for the histomorphologic evaluation of normal and diseased skin. However, there is increasing interest in the development of noninvasive optical technologies for evaluation, diagnosis, and monitoring of skin disease in vivo. Fluorescent confocal microscopy is an innovative optical technology that has previously been used for morphologic evaluation of live human tissue.

Clinical applicability of in vivo reflectance confocal microscopy for the diagnosis of actinic keratoses.

Background: In vivo reflectance confocal microscopy (RCM) has been used for evaluation of the morphologic features of nonmelanoma skin cancer. The application of RCM for diagnosis of basal cell carcinoma has been reported; however, the evaluation of actinic keratoses (AKs) has only been the subject of preliminary studies.

Study Goal: The goal of this study was to evaluate the applicability of RCM in the diagnosis of AK in correlation with routine histology.

A novel rodent papillomavirus isolated from anogenital lesions in its natural host.

In the present work we describe both the prevalence and the histopathologic features of a novel papillomavirus (referred as McPV2) that naturally infects the rodent Mastomys coucha. Viral DNA could be isolated not only from anogenital wart-like lesions but also from healthy tissues (e.g.

Novel papillomavirus isolates from Erinaceus europaeus (Erinaceidae, Insectivora) and the Cervidae (Artiodactyla), Cervus timorensis and Pudu puda, and phylogenetic analysis of partial sequence data.

The diversity of papillomaviruses (PVes) infecting stratified squamous epithelia of warm-blooded animals, such as birds and mammals, is only fragmentarily documented. The PV types are sequenced from 9 of 18 placental taxa at the order level to date. Current phylogenetic analyses of PV sequences frequently do not consider evolutionary polarity and statistical evaluation of internal nodes, that are required for robust evolutionary conclusions.

Noninvasive diagnostic tools for nonmelanoma skin cancer.

Minimally invasive diagnostic tools have received increased attention for diagnosis, screening and management of nonmelanoma skin cancer (NMSC). Several modalities are commercially available, including high frequency ultrasound, optical coherence tomography and confocal microscopy. While systematic clinical analyses are often lacking, recent reports have shown promising results for reflectance confocal microscopy (RCM) for diagnosis of actinic keratoses and basal cell carcinoma.

Epidemiology and aetiology of basal cell carcinoma.

Basal cell carcinoma (BCC) is a malignant epithelial neoplasm of the skin preferentially affecting male caucasians and is rarely observed in patients with more intense skin pigmentation. A characteristic feature of BCCs are their extremely low risk to metastasize. Epidemiological data indicate that the overall incidence is increasing worldwide significantly by about 3-10% per annum.

Multicentre, open-label study using imiquimod 5% cream in one or two 4-week courses of treatment for multiple actinic keratoses on the head.

Objective: In the USA, Imiquimod 5% cream is approved for use 2-3 times per week over 16 weeks for the treatment of actinic keratoses (AKs). This study evaluated the efficacy of imiquimod in another treatment schedule, for AKs on the head.

Design: Open-label, phase IIIb.

A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up.

Background: Actinic keratoses (AK) frequently occur on sun-exposed skin and are considered as in situ squamous cell carcinoma. To date, no treatment algorithm exists for first or second line therapies due to the lack of comparative studies.

Objective: This study compared the initial and 12-month clinical clearance, histological clearance, and cosmetic outcomes of topically applied 5% imiquimod (IMIQ) cream, 5% 5-fluorouracil (5-FU) ointment and cryosurgery for the treatment of AK.

Topical immunomodulation under systemic immunosuppression: results of a multicentre, randomized, placebo-controlled safety and efficacy study of imiquimod 5% cream for the treatment of actinic keratoses in kidney, heart, and liver transplant patients.

Objective: In this study the safety and efficacy of imiquimod 5% cream for the treatments of actinic keratoses in kidney, heart and liver transplant recipients is evaluated.

Background: Growing populations of organ transplant recipients face increased risk of developing actinic keratosis (AK) and skin cancer secondary to continuous systemic immunosuppressive therapy. Imiquimod 5% cream is an effective option for the treatment of AK, but the safety of topical immune stimulation in immunocompromised patients has not been widely evaluated.

Pathology and pathobiology of actinic (solar) keratosis - an update.

Actinic keratosis is a UV light-induced lesion and develops mostly in fair-skinned patients being susceptible to solar damage. The term actinic keratosis (AK) describes clinically ill-defined reddish to reddish-brown scaly lesions on erythematous base in areas damaged severely by sunlight. The term does not imply anything about the biology or histopathology.

Imiquimod treatment of papilloma virus and DMBA /TPA-induced cutaneous skin cancer in Mastomys coucha: an unique animal model system useful for preclinical studies.

Background: Immune response modifiers including imiquimod can be topically applied for the treatment of both genital warts and benign and malignant skin tumours (e.g. actinic keratosis).

Immune response profiles in human skin.

In addition to the function as a physical barrier human skin has been shown to be an important immune organ displaying various defense mechanisms, which can be divided into three major functional compartments: (i) Epithelial defense, which is characterized by antimicrobial peptides and proteins (AP) and which can be induced in inflammatory lesions but also in the absence of inflammation. (ii) Innate-inflammatory immunity, which involves recognition of microbial compounds by particular receptors like Toll-like receptors (TLR) and subsequent activation of signalling pathways resulting in expression of pro-inflammatory cytokines and interferons, as well as genes of adaptive immunity. Interferon alpha (IFNalpha) produced by plasmacytoid dendritic cells (DC) may stimulate myeloid DC to produce IL-12 resulting in classical T-cell activation or to produce IL-23 activating IL-17 producing T-cells (IL-23/IL-17 pathway).

Skin infections in organ transplant recipients.

In contrast to the well-described high risk of skin cancer in organ transplant recipients, skin infections in these patients are not as well explored. Skin infections caused by viruses, bacteria or fungi represent a growing diagnostic and therapeutic challenge in the dermatological aftercare of organ transplant recipients. Differing immunosuppressive drugs and their variable dosage in chronologic sequence after transplantation probably influence the type and appearance of skin infections.

Persistence of Mastomys natalensis papillomavirus in multiple organs identifies novel targets for infection.

The high incidence of multiple wart formation and skin cancer in organ-transplant recipients, as well as the question of an involvement of papillomaviruses in a variety of human cancers, require a model system for papillomavirus infections in immunocompetent animals. Such an in vivo model is represented by the multimammate rat Mastomys coucha, which is infected with Mastomys natalensis papillomavirus (MnPV). MnPV primarily induces benign skin tumours, such as papillomas and keratoacanthomas.

Human papillomaviruses and non-melanoma skin cancer: basic virology and clinical manifestations.

Human papillomaviruses (HPV) infect cutaneous and mucosal epithelia and induce benign and malignant lesions. Non-melanoma skin cancer (NMSC), encompassing basal cell carcinoma and squamous cell carcinoma (SCC), is the most frequent cancer in the Caucasian population, and the incidence has increased dramatically worldwide. Ultraviolet (UV) radiation is a major risk factor for NMSC, and cutaneous HPV is also considered to play an active role during the pathogenesis of these cancers.

Extension of the typing in a general-primer-PCR reverse-line-blotting system to detect all 25 cutaneous beta human papillomaviruses.

beta-Papillomaviruses (PV) seem to be involved in the pathogenesis of cutaneous squamous cell carcinoma and its early stage actinic keratosis. In this study, typing was extended of a previously described consensus primer-mediated beta- and gamma-cutaneous HPV PCR method followed by reverse-line-blotting (BGC-PCR/RLB) to detect all 25 known beta-PV and to examine their prevalence in actinic keratosis. The typing format of the BGC-PCR assay was extended by adding hybridization probes of six beta-PV (HPV 75, 76, 80, 92, 93, and 96) to the RLB system.

Current state of vitiligo therapy--evidence-based analysis of the literature.

Unlabelled: Vitiligo is a skin disease with a worldwide prevalence ranging from 0.5% to 4%. Conservative therapies include photochemotherapy, phototherapy with UVB radiation (broadband UVB 290-320 nm, narrow band UVB 311 nm), systemic steroids and pseudocatalase.

Does progression from actinic keratosis and Bowen's disease end with treatment: diclofenac 3% gel, an old drug in a new environment?

Progression from actinic keratosis (AK) and Bowen's disease (BD) to invasive disease involves a complex cascade of events. The preparation of diclofenac 3% gel (Solaraze; Shire Pharmaceuticals) has been shown to be efficacious and well tolerated in AK. The inhibition of the COX enzymes results in a decrease in downstream by-products of arachidonic acid metabolism.

Differentiation between actinic keratoses and disseminated superficial actinic porokeratoses with reflectance confocal microscopy.

Background: Clinical differentiation between actinic keratosis (AK) and disseminated superficial actinic porokeratosis (DSAP) may pose a significant challenge, and histological evaluation is often also required for diagnosis. Distinct morphological features can be distinguished upon histopathological examination, but the use of non-invasive tools, such as reflectance confocal microscopy (RCM), may be an eligible alternative for confirmation of diagnosis.

Objectives: The aim of this study was to determine the relevant RCM criteria for the identification of disseminated superficial actinic porokeratoses (DSAPs) and to define distinguishing criteria for DSAPs compared with actinic keratosis (AKs).

Management of actinic cheilitis using diclofenac 3% gel: a report of six cases.

Background: Actinic cheilitis is a frequent manifestation of actinic dysplasia and requires early therapy to prevent its progression into invasive squamous cell carcinoma (SCC). Several therapies are used, ranging from unspecific lesion-adapted destructive techniques (i.e.

Treatment of multiple actinic keratoses with topical diclofenac 3% gel in organ transplant recipients: a series of six cases.

Background: Non-melanoma skin cancer (NMSC) represents a significant cause of morbidity in organ transplant patients; the relative risk of squamous cell carcinoma and actinic keratosis (AK) is 100 and 250 times higher, respectively, compared with immunocompetent patients.

Objectives: The aim of this study was to investigate the effects of 3% diclofenac gel on the clearance rates of multiple AKs in organ transplant recipients (OTRs).

Patients/methods: An open-label study was conducted in six patients (three kidney, one liver and two heart transplant patients) with histories of multiple NMSCs and extensive actinic keratoses (AKs).