Roberto Gomes Tarlé

Vitiligo - Part 1

Vitiligo is a chronic stigmatizing disease, already known for millennia, which mainly affects melanocytes from epidermis basal layer, leading to the development of hypochromic and achromic patches. Its estimated prevalence is 0.5% worldwide. The involvement of genetic factors controlling susceptibility to vitiligo has been studied over the last decades, and results of previous studies present vitiligo as a complex, multifactorial and polygenic disease. In this context, a few genes, including DDR1, XBP1 and NLRP1 have been consistently and functionally associated with the disease. Notwithstanding, environmental factors that precipitate or maintain the disease are yet to be described. The pathogenesis of vitiligo has not been totally clarified until now and many theories have been proposed. Of these, the autoimmune hypothesis is now the most cited and studied among experts. Dysfunction in metabolic pathways, which could lead to production of toxic metabolites causing damage to melanocytes, has also been investigated. Melanocytes adhesion deficit in patients with vitiligo is mainly speculated by the appearance of Köebner phenomenon, recently, new genes and proteins involved in this deficit have been found.

Vitiligo - Part 2 - classification, histopathology and treatment

In an unprecedented effort in the field of vitiligo, a global consensus resulted on a suggested new classification protocol for the disease. The main histopathological finding in vitiligo is the total absence of functioning melanocytes in the lesions, while the inflammatory cells most commonly found on the edges of the lesions are CD4+ and CD8+ T lymphocytes. Physical and pharmacological treatment strategies aim to control the autoimmune damage and stimulate melanocyte migration from the unaffected edges of lesions and the outer hair follicle root sheath to the affected skin; moreover, surgical treatments can be combined with topical and physical treatments.

Topography of basal cell carcinoma and their correlations with gender, age and histologic pattern: a retrospective study of 1042 lesions

BACKGROUND Basal cell carcinoma accounts for 75% of skin cancer. Sun exposure and genetics are related to its etiology. Its expected that biological and behavioral differences provide different patterns of involvement between sexes. OBJECTIVES To evaluate the topography of lesions and their correlations with gender, age and histological type. METHODS Retrospective study of basal cell carcinoma patients treated between 1999 and 2008 in the Skin Cancer Clinic of Santa Casa de Misericordia of Curitiba. We evaluated sex, age, location, histological type, margins commitment, sun exposure and family skin cancer history. RESULTS We found 1042 lesions in 545 patients (61% women), being more numerous in men (p<0.01). Their ages ranged between 27 and 95 years (median=65). Men had more sun exposure (p<0.01). The lesions were more frequent extra-cephalic recently (p<0.01). The margin involvement was higher in the head (p<0.01). The superficial type was less frequent on the head (p<0.01) and was associated with younger ages in women (p<0.01). The head housed 74% of lesions and the legs 2%. Women had a predilection for the legs, nose and upper lip and men to trunk, ears and scalp (p <0.05). The surgeries in the medial epicanthus and scalp occurred at younger ages (p=0.01). CONCLUSIONS We identified significant associations between the topography of lesions, gender, age and histological type, demonstrating the possible pathophysiological diversity and differential risk factors operation. In the period studied we found no trend of increase in the proportion of young or women among patients.

Genetic risk factors for human susceptibility to infections of relevance in dermatology

BACKGROUND In the pre-microbiological era, it was widely accepted that diseases, today known to be infectious, were hereditary. With the discovery of microorganisms and their role in the pathogenesis of several diseases, it was suggested that exposure to the pathogen was enough to explain infection. Nowadays, it is clear that infection is the result of a complex interplay between pathogen and host, therefore dependant on the genetic make-up of the two organisms. Dermatology offers several examples of infectious diseases in different stages of understanding of their molecular basis. In this review, we summarize the main advances towards dissecting the genetic component controlling human susceptibility to infectious diseases of interest in dermatology. Widely investigated diseases such as leprosy and leishmaniasis are discussed from the genetic perspective of both host and pathogen. Others, such as rare mycobacterioses, fungal infections and syphilis, are presented as good opportunities for research in the field of genetics of infection.

Indication guidelines for Mohs micrographic surgery in skin tumors

Mohs micrographic surgery is a technique used to excise skin tumors based on comprehensive surgical mapping, in which the surgeon removes the tumor, followed by a complete histological evaluation of the tumors margins. The correlation of the presence of a tumor in histological examinations and its precise location on the surgical map result in a complete removal of the tumor with maximum normal tissue preservation. The present article seeks to provide general practitioners and healthcare specialists with guidelines regarding recommendations for Mohs micrographic surgery to treat skin tumors, based on the most reliable evidence available in medical literature on the subject. This bibliographic review of scientific articles in this line of research was conducted based on data collected from MEDLINE/PubMed. The search strategy used in this study was based on structured questions in the Patient, Intervention, Control, and Outcome (PICO) format. MeSH terms were used as descriptors. The indications of this technique are related to recurrence, histology, size, definition of tumor margins, and location of tumors. These guidelines attempt to establish the indications of Mohs surgery for different types of skin tumors.

Polymorphism of the E‐cadherin gene CDH1 is associated with susceptibility to vitiligo

Vitiligo is a depigmenting disorder characterized by loss of functional melanocytes from the epidermis. Experimental data suggest that defective melanocyte adhesion may underlie the pathogenesis of the disease. In particular, association between vitiligo and genetic variants of the DDR1 gene involved in melanocyte adhesion has been recently published. A subsequent, independent study revealed lower expression of DDR1 in vitiligo lesions. Here, we expand this investigation by testing for association between vitiligo and polymorphisms of CDH1, IL1B and NOV (formerly CCN3), genes belonging to the DDR1 adhesion pathway, in two population samples of distinct design. Our results reveal that alleles of marker rs10431924 of the CDH1 gene are associated with vitiligo, especially in the presence of autoimmune comorbidities.

Squamous Cell Carcinoma

Squamous cell carcinoma (SCC) is the second most commonly detected skin cancer. SCC is mainly detected in the head, neck, limbs, and areas of higher photoexposition. Both extrinsic and intrinsic individual factors account for the development of skin epidermoid carcinoma. Among the main factors there are ultraviolet radiation exposure, immunosuppression, human papilloma virus, genodermatosis, chronic dermatosis, arsenic exposure, and ionizing radiation. Its subtypes are actinic keratosis, epidermoid carcinoma in situ, and invading epidermoid carcinoma. The main aims of SCC treatment are: total removal of the tumor thus minimizing the risk for recurrence and metastasis; preservation of function; and provision of the best possible aesthetic outcome.