Elisabeth M. T. Wurm

Nanoparticles and microparticles for skin drug delivery

Skin is a widely used route of delivery for local and systemic drugs and is potentially a route for their delivery as nanoparticles. The skin provides a natural physical barrier against particle penetration, but there are opportunities to deliver therapeutic nanoparticles, especially in diseased skin and to the openings of hair follicles. Whilst nanoparticle drug delivery has been touted as an enabling technology, its potential in treating local skin and systemic diseases has yet to be realised. Most drug delivery particle technologies are based on lipid carriers, i.e. solid lipid nanoparticles and nanoemulsions of around 300 nm in diameter, which are now considered microparticles. Metal nanoparticles are now recognized for seemingly small drug-like characteristics, i.e. antimicrobial activity and skin cancer prevention. We present our unpublished clinical data on nanoparticle penetration and previously published reports that support the hypothesis that nanoparticles >10nm in diameter are unlikely to penetrate through the stratum corneum into viable human skin but will accumulate in the hair follicle openings, especially after massage. However, significant uptake does occur after damage and in certain diseased skin. Current chemistry limits both atom by atom construction of complex particulates and delineating their molecular interactions within biological systems. In this review we discuss the skin as a nanoparticle barrier, recent work in the field of nanoparticle drug delivery to the skin, and future directions currently being explored.

Teledermatology : An Update

Dermatology is perhaps the most visual specialty in medicine, making it ideally suited for modern telemedicine techniques, as has been shown in a number of recent studies investigating feasibility and reliability of teledermatology. It has generally demonstrated high levels of concordance in diagnosis and management plans compared with face-to-face consultations. Teledermatology also has been used for various purposes, including triage, diagnostic and management services, and second-opinion services for primary care practitioners. It has been set up in a number of ways: (1) direct referral for primary care using images and clinical history sent to secondary care dermatology services for second opinion and for triage referrals and (2) facilitating community-based clinics led by nurses or general practitioners. Moreover, in the last years new fields in teledermatology have grown up. Teledermoscopy is a promising area for melanoma screening as well as for the diagnosis and management of equivocal pigmented skin lesions. The feasibility of mobile teledermatology and mobile teledermoscopy recently has been proven, and these new facilities have the potential to become an easy applicable tool for everyone and may open the door for a new flexible triage system for detection of skin cancer in general and melanoma in particular. The implementation of virtual slide systems for teledermatopathology has allowed avoiding the limitations imposed by conventional microphotography. Finally, web consultations in dermatology are a rather new tool that became available in the last years and teledermatologic services through the Internet offer many possibilities, including continuing medical education, on-line atlases and databases, and specific web application suited for teledermatology (ie, www.telederm.org).

In vivo assessment of chronological ageing and photoageing in forearm skin using reflectance confocal microscopy.

Background  Skin ageing is a complex process due to intrinsic chronological factors (chronoageing) and extrinsic environmental factors. The primary extrinsic factor is cumulative ultraviolet (UV) exposure, and is therefore termed photoageing. The current standards for measuring cumulative sun damage are biopsy histology and skin microtopography. However, skin biopsies are too invasive for population studies and skin replicas render only superficial skin architecture data. Reflectance confocal microscopy (RCM) is a noninvasive imaging tool that allows for in vivo imaging of the skin at quasihistological resolution.

Confocal features of equivocal facial lesions on severely sun-damaged skin: Four case studies with dermatoscopic, confocal, and histopathologic correlation

BACKGROUND Facial skin has a distinct histologic architecture and reveals specific dermatoscopic features. Diagnosis of lentigo maligna on the face is often challenging because of the overlap of clinical and morphologic features with other lesions. OBJECTIVES We aim to show the value of reflectance confocal microscopy (RCM) as a noninvasive diagnostic tool for facial lesions and to increase knowledge of RCM morphologic features among the scientific community. METHODS We describe a series of 4 facial lesions on severely sun-damaged skin that was evaluated via RCM immediately after face-to-face examination, followed by shave biopsy for histopathological analysis. RESULTS Lesions included a lentigo maligna, a pigmented seborrheic keratosis, pigmented basal cell carcinoma, and a pigmented actinic keratosis. In the presented cases, RCM enabled an accurate diagnosis. LIMITATIONS The study describes morphologic features on selected cases, but does not test accuracy of RCM criteria. CONCLUSIONS RCM is a useful adjuvant for the accurate and precise diagnosis of equivocal facial lesions.

Effectiveness and limitations of reflectance confocal microscopy in detecting persistence of basal cell carcinomas: a preliminary study.

Background/Objectives:  Reflectance confocal microscopy (RCM) can accurately and non‐invasively diagnose basal cell carcinoma (BCC). The use of RCM in assessing responses to saucerization or curettage and cautery of BCC has not been established. The aim of the present study was to expound the usefulness of RCM in assessing treatment responses of BCC to saucerization or curettage and cautery 8–12 weeks after treatment.

New insights in naevogenesis: Number, distribution and dermoscopic patterns of naevi in the elderly

Background/Objectives:  It is well recognized that the number and patterns of acquired melanocytic naevi vary with age, but little is known about naevus patterns in the elderly. This is a cross‐sectional study assessing the prevalence, dermoscopic pattern and anatomical distribution of naevus subtypes in a stratified cohort aged between 60 and 89 years.

A blueprint for staging of murine melanocytic lesions based on the Cdk4 R24C/R24C ::Tyr- NRAS Q 61K model

It has been shown that gene mutations which drive the development of malignant melanoma (MM) in humans also lead to emergence of MM when engineered mice. However, little attention has been paid to the clinical and histopathological features of melanocytic lesions and their natural history in a given mouse model. This knowledge is crucial to enable us to understand how engineered mutations influence the initiation and evolution of melanocytic lesions, and/or for the use of mice as a preclinical model to test specific treatments. We recently reported the development of melanocytic proliferations along the spectrum of naevi to MM in a Cdk4 R24C/R24C ::Tyr‐ NRAS Q 61K mouse model. In this study, we followed the development of lesions over time using digital photography and dermoscopy with the aim to correlate the clinical and histopathological features of lesions developing in this model. We identified two types of lesions. The first are slow‐growing dermal MMs that emanate from dermal naevi. The second did not emanate from naevi, grew rapidly, and appeared to be solely confined to the subcutaneous fat. We present a simple staging system for the MMs that progress from naevi, based on depth of extension into the dermis and subcutis. This represents a blueprint for documentation and follow‐up of MMs in the live animal, which is critical for the proper use of murine melanoma models.

Dermoscopy, reflectance confocal microscopy and histopathology of an amelanotic melanoma from an individual heterozygous for MC1R and tyrosinase variant alleles

We present a case of an amelanotic nodular melanoma occurring in a 26‐year‐old woman who carried a heterozygous (melancortin‐1‐receptor) MC1R 160R/W and tyrosinase (TYR) 402R/Q genotype and had a dark hair phenotype. We present dermoscopic, reflectance confocal microscopy (RCM) and histopathological images of the melanoma. We discuss the relationship between MC1R red hair colour (RHC) variants, TYR variants, phenotype and melanoma development. We also discuss the merits of RCM as an additional diagnostic aid for equivocal melanocytic lesions.

An investigation of striae distensae using reflectance confocal microscopy

Background:  Striae distensae, otherwise known as stretch marks, are white or red scar‐like streaks on the skin. Although they are not associated with adverse health outcomes, striae are associated with significant cosmetic morbidity. While they have been well characterised histopathologically, a non‐invasive method of microscopic lesion assessment of striae would be welcome.

In Vivo Confocal Microscopic Pattern of Fibroepithelioma of Pinkus

Caterina Longo, MD, PhD; H. Peter Soyer, MD; Patrizia Pepe, MD; Alice Casari, MD; Elisabeth M. T. Wurm, MD; Pascale Guitera, MD; Giovanni Pellacani, MD; Dermatology Unit, Arcispedale Santa Maria Nuova (Drs Longo and Pellacani), and University of Modena and Reggio Emilia (Drs Longo, Pepe, Casari, and Pellacani), Reggio Emilia, Italy; The University of Queensland School of Medicine, Princess Alexandra Hospital, Brisbane, Australia (Drs Soyer and Wurm); and Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital and Melanoma Institute, Sydney, Australia (Dr Guitera)