Dermoscopy and Early Melanoma.

The lack of effective therapies for patients with advanced melanoma establishes an early recognition as the aim of clinical and dermoscopic examination, which is the most important factor for improving patient survival and decreases the treatment and management costs. Melanoma in situ is the earliest stage of melanoma. The features of early melanomas, especially in those lesions smaller than 3mm, can be very subtle clinically, dermoscopically and pathohistologically, and it is often impossible to discriminate between a melanoma and nevus. Clinically, de novo melanomas are small brown to black macula with an irregular outline. In melanomas developing in a nevus, there is an asymmetry of the lesion with marked change in color and/or shape of the pre-existing nevus. Dermoscopically, early stages of melanoma show the same global features as thicker melanomas, but in a more subtle way. Asymmetry is the most important parameter; multiple colors are rare. Significant local melanoma-specific criteria, especially when present at the periphery, are irregular pigment network, irregular streaks, and irregular dots/globules, while blue-white structures are rarely found.

Photodynamic therapy in dermatology: current treatments and implications.

This article provides an update on photodynamic therapy by discussing each of the essential components in sequence: mechanisms of action, common photosensitizers, typical light sources, and indications. In dermatology, photodynamic therapy (PDT) is mainly used in the treatment of superficial skin cancers: actinic keratoses, Bowen's disease and superficial basal cell carcinomas. However the range of indications has been expanding continuously. PDT is also used for the treatment of other oncological indications and non-malignant conditions such as acne vulgaris and photoaged skin. The 5-aminolevulinic acid (ALA) or its methyl ester (MAL) is applied topically as photosensitizer before activation with visible light. The advantages of topical PDT are: ability to treat multiple lesions simultaneously, low invasiveness, good tolerance and excellent cosmetic results.

The genetics of psoriasis--selected novelties in 2008.

The genetic background of psoriasis is clearly demonstrated by the familial occurrence, data from epidemiological studies, twin studies, and results of genome-wide scan investigations. In the last years, molecular genetics analyses have permitted new insights into psoriasis. A number of studies indicate the likely genomic location of psoriasis susceptibility genes and suggest their possible identity and function. According to current concepts, psoriasis is caused by the interplay of multiple genes and different trigger factors, and the disease is classified in the group of genetically "complex" diseases. The first associated locus (PSORS1) resides within the HLA region (6p21.3). Strong association of HLA-Cw6 allele at this locus was first reported in Finnish population over 26 years ago. However, the exact location of PSORS1 gene remains controversial due to extensive linkage disequilibrium across the region. Two genes lying within this interval have been intensively studied with respect to their role in psoriasis susceptibility: HCR and corneodesmosin (CDSN). The precise location of PSORS 1 is under intense screening. Other candidate loci identified by genetic linkage research include PSORS 2 (17q25), PSORS 3 (4q34), PSORS 4 (1q21), PSORS 5 (3q21), PSORS 6 (19p13), PSORS 7 (1p32), PSORS 8 (16q) and PSORS 9 (4q31). Despite a large body of new data, the extent of genetic heterogeneity and the role of environmental triggers and modifier genes have not yet been clarified. The isolation of novel susceptibility genes will provide an insight into the precise pathways that control the disease. Such pathways will also reveal additional candidate genes that can be tested for molecular alterations resulting in the disease.

Psoriasis in pregnancy: a review of most important literature data.

In women with psoriasis, the course of the disease during conception, pregnancy and delivery generally does not differ from other individuals involved. In psoriasis patients, pre-pregnancy period offers time to learn about the hereditary nature of the disease, the effect of hormonal changes and acceptable treatments during pregnancy. In the majority of patients, psoriasis improved during pregnancy and worsened six weeks after delivery. Women should tell their dermatologist early if they plan to become pregnant and the treatment during pregnancy should be considered carefully. This article provides a short review of the most important literature data on therapeutic options for psoriasis in pregnancy.

Acute phase proteins in psoriasis.

Psoriasis is a chronic, relapsing, inflammatory and hyperproliferative skin disorder. The levels of acute phase proteins are suggested to be elevated in those patients with acute disease. The expression of selected acute phase proteins as the parameters of humoral immunity has been analyzed in 70 patients with acute psoriasis and 40 healthy controls. The aim was to evaluate the inflammatory response in the exacerbation of psoriasis and to determine the correlation of these objective inflammatory parameters with clinical features of disease activity. Main demographic and epidemiologic features were, as well, analysed. The plasma levels of C-reactive protein (CRP) (chi2 = 23.61; p < 0.005), and alpha1-acid glycoprotein (alpha1-AGP) (chi2 = 7.42; p < 0.01) were significantly increased in those patients with acute phase of the disease compared to healthy controls. Our results suggest that psoriasis is an inflammatory disease and therefore its worsening seemed to be linked to the increase in the inflammatory response. It seems that CRP and al-AGP levels could serve as important prognostic factors for the worsening of psoriasis.

Facial changes in the mature patient.

During the aging process, the appearance of the human face changes significantly due to fundamental alterations in the bones, soft tissues, and skin. Both endogenous and environmental factors are involved in age-related transformations of the face; however, facial skin is particularly influenced by environmental factors, and the risk of overexposure and consequent premature facial aging. This review summarizes the current state of knowledge of the most common facial skin changes in the mature patient, including pathogenesis of both intrinsic and extrinsic skin aging, as well as clinical and histologic features of skin aging. Because the majority of facial skin changes in the elderly develop as the consequence of ultraviolet radiation, these can be prevented by adequate photoprotection.

Nonsurgical treatment of nonmelanoma skin cancer in the mature patient.

Nonmelanoma skin cancer (NMSC) is the most common cancer, with the median age at NMSC diagnosis is 71 years. Treatment options for NMSC include surgical therapy, which is usually the first-choice treatment, and nonsurgical modalities. Therapeutic modalities depend on tumor localization, histologic type, and biologic behavior, as well as patient comorbidities, age, and life expectancy. Nonsurgical treatments include cryotherapy, local therapies (imiquimod, 5-fluorouracil, ingenol mebutate, and diclofenac), photodynamic therapy, radiotherapy, and hedgehog inhibitors. Some of these treatments can be combined with curettage and electrodesiccation for better outcomes. Every treatment modality has advantages and disadvantages that must be carefully considered individually. Because the facial area is the most common localization of NMSC, treatment modalities with better cosmetic outcome are preferred. Although NMSC mostly occurs in the elderly, this review is focused on the features and nonsurgical therapy of NMSC in deep old age (≥85) and long-lived persons (aged >95); however, clinical trials very rarely involve this population group due to poor cooperation or poor general condition of these patients; thus, the respective knowledge being generally based on clinical experience.

Psoriasis in the mature patient: Therapeutic approach in the era of biologics.

Management of psoriasis in elderly patients may be challenging due to a small number of studies investigating this specific population. When treating a mature patient, special consideration should be given to multiple comorbidities, progressive functional impairment of several organs, immunosenescence, possible adverse effects, and polypharmacy. Due to the chronic nature of the disease and continuing rise in life expectancy, the prevalence of psoriasis among elderly is also expected to rise. Because many different therapies are available for treatment of psoriasis, we have reviewed those that have been investigated in the aging population. Although biologics have revolutionized the therapy of psoriasis due to targeted mechanism of action, high efficacy and low rate of adverse events, studies on the elderly population with psoriasis are scarce. Further clinical research and development of specific treatment guidelines in geriatric population are needed to optimize the therapeutic approach in this population.

Therapeutic challenges in the mature patient.

With the tremendous increase in the proportion of seniors in the global population, geriatric health care has become of greater interest and concern. Increased emphasis on geriatric medicine, along with the growth in the development of age-related skin disorders, has led to particular attention for geriatric, dermatology and dermatopharmacology. An aging population has brought many therapeutic challenges that we need to recognize and overcome by applying geropharmacologic principles. The purpose of this paper is to inform dermatologists of the age-related changes in the pharmacokinetics of common dermatologic drugs, their various interactions potentially occurring in the elderly, and the principles and evidence-based strategies for detection, management, and prevention to improve medication adherence. By implementing these principles and strategies, we can ensure the best and the safest treatment to promote the desired therapeutic outcome and improved quality of life for this fragile subpopulation.

Poikilodermatous Mycosis Fungoides - Rare Entity, Different Treatment Modalities.

Poikilodermatous mycosis fungoides (PMF) is a rare clinical variant of early-stage MF with peculiar histological features. Poikiloderma occurs in many different clinical conditions, which makes a diagnostic procedure more complicated. PMF belongs to a group of MF variants with low risk of disease progression. We report a case of a 64-year-old woman, who presented with mottled skin aspect of erythema, poikilodermatous patches (hypopigmentation, hyperpigmentation, atrophy, and telangiectasia) on more than 80% of the body. Based on clinical, histopathological, and immunohistochemical findings, we established the diagnosis of PMF. Staging procedure determined stage IIA. As skin-directed therapy was the treatment of choice, the patient was successfully treated with psoralen-UVA (PUVA), nbUVB plus retinoid (Re-nbUVB), and PUVA plus retinoid (Re-PUVA), however, with rapid recurrence.

Visualization of basal cell carcinoma by fluorescence diagnosis and independent component analysis.

Photodynamic detection (PDD) of skin tumours is based on the visualization of a fluorophores, with the ability to accumulate in tumour tissue, by the use of fluorescence imaging. Of particular importance is the application of δ-5-aminolaevulinic acid (ALA) that, through the process of biosynthesis causes formation of the protoporphyrin IX (PpIX). The PpIX has the ability of selective fluorescence after basal cell carcinoma (BCC) has been treated with ALA. Higher concentration of PpIX in tumour tissue compared to surrounding normal skin is the basis for PDD. Our contribution in this preliminary study is application of the independent component analysis (ICA) to extract the BCC spatial map, by processing fluorescent RGB image acquired under excitation with 405nm light. Comparative performance analysis with other two widely used image processing methods: ratio imaging and optimal threshold based imaging, reveals that ICA produces BCC spatial map that is most consistent in term of diagnostic quality by both visual assessment and calculation of the BCC demarcation line. We believe this represents a solid basis for the design of a compact and low-cost multi-spectral fluorescence imaging system, capable for real time calculation of the skin tumour demarcation.

Treatment of vitiligo with narrow-band UVB and topical gel containing catalase and superoxide dismutase.

Narrow-band UVB has been reported to be efficacious in patients with vitiligo. The epidermis of patients with vitiligo showed reduction in the levels of catalase, in association with high levels of hydrogen peroxidase (H2O2) that is toxic for melanocytes. Based on these findings, we studied the efficacy and safety of a topical gel containing catalase and superoxide dismutase (Vitix) in combination with narrow-band UVB. The study included 22 patients of which 19 completed the 6-month study period. Patients applied the gel containing catalase and superoxide dismutase twice a day and received narrow-band UVB 3 times per week. Two different dermatologists evaluated the grade of repigmentation by photograph comparison. At the end of therapy, more than 50% of overall repigmentation was noticed in 11 of 19 (57.9%) patients. More than 75% repigmentation was recorded in three (15.79%), 26%-50% repigmentation in six (31.58%) patients and 1%-25% repigmentation in one (5.26%) patient, whereas one (5.26%) of 19 patients showed no repigmentation at all. The best response was achieved on the face and neck, with more than 50% repigmentation observed in 11 of 14 (78.6%) patients. Development of new lesions was not observed. Adverse events were mild and transient. The study showed that the combination therapy of narrow-band UVB and gel containing catalase and dismutase is a therapeutic option that could be considered in the management of vitiligo. Further evaluation of this combination in multicenter, double-blind, placebo-controlled studies should be undertaken.

Antiproliferative, antiangiogenic and apoptotic effect of photochemotherapy (PUVA) in psoriasis patients.

The aim of the study was to investigate the antiproliferative, antiangiogenic and apoptotic effect of photochemotherapy (PUVA) in psoriatic patients, and to compare it with a control group of psoriatics treated with local corticosteroid therapy. The study included 60 psoriasis patients, 30 of them allocated to PUVA therapy and local corticosteroid each. Immunohistochemical methods of staining with Ki-67, F-8 and bcl-2 antibodies were used to determine proliferative keratinocyte count, to visualize the number of blood vessels in the dermis, and to determine the number of cells exhibiting expression of the antiapoptotic oncoprotein bcl-2, respectively. In all study patients, the values of Ki-67, F-8, bcl-2 and PUVA score were recorded pre- and at six weeks post-therapeutically. Study results showed a statistically significant decrease in the epidermal proliferative keratinocyte count and dermal number of blood vessels after both therapeutic modalities (p < 0.001 both). The value of bcl-2 showed a statistically significant increase in the group of patients treated with PUVA therapy (p = 0.001) and an increase in the control group, demonstrating enhanced keratinocyte apoptosis after treatment. Accordingly, study results demonstrated the antiproliferative, antiangiogenic and apoptotic effect of both PUVA and local corticosteroids. These very mechanisms appear to play a key role in the action of most antipsoriatic therapies.

Histological types of polypoid cutaneous melanoma II.

The aim of this study was to ascertain which histological types of melanoma can clinically and morphologically appear as polypoid melanomas. In 645 cases of primary cutaneous melanoma we have analyzed criteria for diagnosis of polypoid cutaneous melanoma and afterwards we have analyzed growth phase in each polypoid melanoma, histological type of atypical melanocytes, the number of epidermal ridges which are occupied by atypical melanocytes, and distribution according to age, sex and location, as well as the disease free survival. According to the criteria for polypoid melanomas we have found 147 (22.8%) polypoid cutaneous melanomas. Analyzing the growth phases, histological types of atypical melanocytes and the number of affected epidermal ridges in the group of polypoid melanomas we have ascertained 2 (1.4%) ALMs, 4 (2.8%) LMMs, 42 (28.6%) SSMs and 99 (67.2%) NMs. Our conclusion is that polypoid cutaneous melanomas are morphological forms of various histological melanoma types (ALM, LMM, SSM and NM) and they can all display polypoid morphological form. Polypoid cutaneous melanomas are most often of nodular histological type.

Topical Ingenol Mebutate: A New Treatment Modality for Multiple Actinic Keratoses and Field Cancerization.

BACKGROUND: Ingenol mebutate gel is a recent stirring weapon recommended for the treatment of multiple actinic keratoses (AKs) and field cancerization. This review brings a summary of recent data on the treatment of AKs with ingenol mebutate (IM) providing critical commentary with regard to drug's characteristics, drug's safety profile, treatment regimen, treatment outcome, patient compliance, AK recurrence, costeffectiveness and cost-utility, as well as guidelines for the management of the treatment of AK. METHOD: We undertook a structured search of bibliographic databases for peer-reviewed scientific articles, including review articles, original research articles as well as case report articles based on inclusion/exclusion criteria. Reports on ingenol mebutate from U.S. Food and Drug Administration and European Medical Agency were also included. RESULTS: Sixty-six papers were included in this review. We report current data on ingenol mebutate chemical properties, pharmacology, efficacy, safety, and tolerability, potential new indications in dermatology, costeffectiveness, and cost-utility analysis. CONCLUSION: Treatment of AKs is necessary in order to prevent possible transition to invasive SCC. Although the mechanism of action of ingenol mebutate is not fully elucidated, dual mechanism of action is presumed. Ingenol mebutate is an effective and cost-saving topical agent for the treatment of AK, especially multiple AKs and field cancerization, with acceptable safety profile. It may also have perspective in dermatology regarding the treatment of superficial BCC, Bowen disease, actinic cheilitis, and anogenital warts that has to be evaluated in clinical trials. Patients' adherence to recommended treatment regimen and auspicious safety profile make this drug attractive.

Mycobacterium marinum Infection of the Hand in an Immunocompromised Aquarium Hobbyist.

M. marinum, a nontuberculous mycobacterium, is a rare human pathogen widely distributed in the aquatic environment. In the previous century, epidemics took place due to inadequately chlorinated swimming pool water. Nowadays the majority of infections are acquired through contact of previously damaged skin with contaminated fish tank water. We present a case of M. marinum infection of the hand in an aquarium hobbyist which stayed unrecognized for 2 years. After confirming the correct diagnosis, the patient was successfully treated with a regiment containing clarithromycin and rifampicin. The aim of this paper is to raise the awareness of the possibility of M. marinum infection when encountered with non-healing nodular/verrucous/ulcerative lesions of the extremities.

Tofacitinib, an Oral Janus Kinase Inhibitor: Perspectives in Dermatology.

BACKGROUND: Tofacitinib (formerly known as CP-690,550, CP690550, tasocitinib), a novel selective immunosuppressant, is a small molecule classified as Janus kinase inhibitor. The aim of this review article is to present updated data summary on the tofacitinib in the field of dermatology. METHOD: We undertook a structured search of bibliographic databases for peer-reviewed scientific articles, including review articles, original research articles as well as case report articles based on inclusion/exclusion criteria. Technical reports on tofacitinib from U.S. Food and Drug Administration and European Medical Agency were also included. RESULTS: Forty-three papers were included in this review. We report current data on tofacitinib chemical properties, pharmacology, non-clinical toxicity, as well as efficacy and safety in potential new indications in dermatology: psoriasis, alopecia areata, vitiligo, atopic dermatitis and nail dystrophy associated with alopecia areata. CONCLUSION: JAK/STAT pathway has an important role in the pathogenesis of psoriasis, alopecia areata, atopic dermatitis, and vitiligo. Despite encouraging efficacy, due to concerns about the overall safety profile of tofacitinib, additional studies will have to determine the adequate risk-to-benefit ratio.

The Impact of Pyschological Stress on Acne.

Acne is one of the most common skin disorders. It is a multifactorial and complex disease, originating in the pilosebaceous follicle where a hereditary background, androgens, skin lipids, disorders of keratinization, inflammatory signaling, and regulatory neuropeptides seem to be mainly involved. Even though emotional stress has long been suspected to trigger or exacerbate acne, its influence on acne severity has been mostly underestimated until recently when studies have brought new data about the different mechanisms and possible factors involved in this interaction. A point to note is that there have been relatively few studies examining stress as a possible cause of acne or acne exacerbation; more studies have focused on stress and mental health problems occurring as a result of acne. In this review, we have tried to identify the underlying mechanisms that link stress to acne according to the latest scientific findings, and we summarize this perplexing connection. The basis for the association between emotional stress and the onset or exacerbation of acne is in several cutaneous neurogenic factors which interact with a pathogenic cascade in acne. This bidirectional intimate relationship of the skin and the mind emphasizes the importance of a holistic and interdisciplinary approach to caring for patients with acne that involves not only dermatologists but also psychologists and psychiatrists.

Current Therapeutic Approach to Hypertrophic Scars.

Abnormal scarring and its accompanying esthetic, functional, and psychological sequelae still pose significant challe nges. To date, there is no satisfactory prevention or treatment option for hypertrophic scars (HSs), which is mostly due to not completely comprehending the mechanisms underlying their formation. That is why the apprehension of regular and controlled physiological processes of scar formation is of utmost importance when facing hypertrophic scarring, its pathophysiology, prevention, and therapeutic approach. When treating HSs and choosing the best treatment and prevention modality, physicians can choose from a plethora of therapeutic options and many commercially available products, among which currently there is no efficient option that can successfully overcome impaired skin healing. This article reviews current therapeutic approach and emerging therapeutic strategies for the management of HSs, which should be individualized, based on an evaluation of the scar itself, patients' expectations, and practical, evidence-based guidelines. Clinicians are encouraged to combine various prevention and treatment modalities where combination therapy that includes steroid injections, 5-fluorouracil, and pulsed-dye laser seems to be the most effective. On the other hand, the current therapeutic options are usually empirical and their results are unreliable and unpredictable. Therefore, there is an unmet need for an effective, targeted therapy and prevention, which would be based on an action or a modulation of a particular factor with clarified mechanism of action that has a beneficial effect on wound healing. As the extracellular matrix has a crucial role in cellular and extracellular events that lead to pathological scarring, targeting its components mostly by regulating bone morphogenetic proteins may throw up new therapeutic approach for reduction or prevention of HSs with functionally and cosmetically acceptable outcome.