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.

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.

Efficacy and Tolerability of a Cosmetic Skin Care Product With Trans-4-t-butylcyclohexanol and Licochalcone A in Subjects With Sensitive Skin Prone to Redness and Rosacea.

BACKGROUND: Sensitive skin and rosacea are skin conditions, which may affect the quality of life of the patients considerably. In vitro and in vivo data indicated that the combination of trans-t-butylcyclohexanol and licochalcone A is an effective combination for alleviating the increased sensitivity of rosacea subtype I.

OBJECTIVE: Objective of this open dermocosmetic study was to investigate the efficacy and tolerability of a skin care product containing the anti-inflammatory licochalcone A and the TRPV1 antagonist trans-t-butylcyclohexanol in subjects with sensitive skin prone to redness and rosacea.

METHODS: 1221 subjects with sensitive skin and rosacea stage 0-II applied the test product twice daily for 4 weeks. Clinical assessment of sensitive skin and rosacea symptoms were performed at baseline and after 4 weeks. Additionally, at treatment end the test subjects filled a self-assessment questionnaire.

RESULTS: After 4 weeks of application, both, clinical and subjective assessment have shown improvement of all symptoms of sensitive skin and rosacea in a significant number of subjects (P less than 0.001). The test product was efficacious and very well tolerated also when used in conjunction with pharmacological treatments of the skin condition under scrutiny.

Conclusions: The study confirmed the good tolerability and efficacy of the skin care product in the management of sensitive skin prone to redness and rosacea when used alone or in combination with other therapies.

J Drugs Dermatol. 2017;16(6):605-611.

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.

PERIORAL DERMATITIS: STILL A THERAPEUTIC CHALLENGE.

Perioral dermatitis is a common and often chronic dermatosis. In its classic form, it primarily affects women aged 15 to 45 years, but there are also variants including lupus-like and granulomatous perioral dermatitis, where granulomatous form is more common in childhood and affects mostly prepubescent boys. The etiopathogenesis of the disease remains unclear, but there is a frequent finding of prolonged use of topical products, especially corticosteroids, in the treatment of rosacea and seborrheic dermatitis, preceding the clinical manifestation of perioral dermatitis. Other causes important for the occurrence of the disease include various skin irritants, as well as other physical and hormonal factors, which all share the epidermal barrier dysfunction as an underlying main pathogenic factor. Clinical presentation of papulovesicular eruption in the perioral region with a typical narrow spared zone around the edge of the lips is characteristic. Therapeutic approach should be individually addressed, depending on the severity of clinical presentation and patient's age, with special attention to patient's education and continuous psychological support. In mild forms of perioral dermatitis, 'zero therapy' is the treatment of choice. In the initial treatment period, patients with steroid-induced perioral dermatitis should be closely followed up because the rebound phenomenon usually develops after cessation of previous topical treatment. In moderate disease, treatment includes topical metronidazole, erythromycin, and pimecrolimus, whereas in more severe cases the best validated choice is oral tetracycline in a subantimicrobial dose until complete remission is achieved. Systemic isotretinoin should be considered as a therapeutic option for patients refractory to all standard therapies.

Pyridoxine induced rosacea-like dermatitis.

Rosacea is a common chronic inflammatory cutaneous disease of unknown etiology, characterized by remissions and exacerbations, presenting with centrofacial erythema and telangiectasias. It affects mainly adults around the age of 30 years and classically predominates in females. The pathophysiology of rosacea has not yet been fully understood. Risk factors are positive family history, very light skin phototype, sun exposure and consumption of spicy food or alcohol. Recently, there has been some evidence that some drugs or vitamins could be potential factors that can aggravate rosacea or induce rosacea-like symptoms. In this context, we present a 53-year-old female developing rosacea-like dermatitis due to a fixed combination of isoniazid and pyridoxine, which she was receiving along with rifampicin for the treatment of pulmonary tuberculosis.

Advances in a rapidly emerging field of hair follicle stem cell research.

Human skin maintains the ability to regenerate during adulthood, as it constantly renews itself throughout adult life, and the hair follicle (HF) undergoes a perpetual cycle of growth and degeneration. The study of stem cells (SCs) in the epidermis and skin tissue engineering is a rapidly emerging field, where advances have been made in both basic and clinical research. Advances in basic science include the ability to assay SCs of the epidermis in vivo, identification of an independent interfollicular epidermal SC, and improved ability to analyze individual SCs divisions, as well as the recent hair organ regeneration via the bioengineered hair follicular unit transplantation (FUT) in mice. Advances in the clinic include recognition of the importance of SCs for wound repair and for gene therapy in inherited skin diseases, for example epidermolysis bullosa. The study of the HF stem cells (HFSCs) started by identification of epidermal SC in the HF bulge as quiescent "label retaining cells". The research of these cells emerged rapidly after the identification of bulge cell molecular markers, such as keratin 15 (K15) and CD34 in mice and CD200 in humans, which allowed the isolation and characterization of bulge cells from follicles. This paper provides an overview of the current knowledge on epidermal SCs in the HF describing their essential characteristics and the control of follicle SCs fate, their role in alopecia, as well as their use in tissue engineering.

Human papillomavirus status in extragenital nonmelanoma skin cancers.

About 5% of all cancers worldwide can be attributed to human papillomaviruses (HPVs); namely, six sites are strongly associated with HPV infections: cervix, penis, vulva, vagina, anus, and oropharynx. Nonmelanoma skin cancers (NMSC), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) are the most common malignancies in Caucasians. In fact, there is an intense connection between sunlight exposure, fair skin, HPV, and development of NMSC. We have conducted a pilot study that included tissue samples from 26 carcinoma patients, of which there were 13 BCC and 13 SCC. HPV detection and typing was done with DNA amplification and sequencing, respectively. In total, 23.1% of SCC samples (3/13) and 7.7% of BCC samples (1/13) were positive for HPV DNA. The importance of understanding all aspects of NMSC carcinogenesis may be to reveal novel therapeutic options or preventive measures for HPV containing NMSC patients.

Will nonablative rejuvenation replace ablative lasers? Facts and controversies.

Since the early 1980s, the field of skin rejuvenation has evolved rapidly. Traditional ablative resurfacing with carbon dioxide and Er:YAG lasers offered dramatic improvement of the skin tone and texture, but prolonged postoperative period and an increased risk for side effects and complications were unacceptable for the majority of patients. It prompted the development of nonablative lasers and non-laser systems, which stimulate dermal neocollagenesis without epidermal disruption, and therefore, produce less adverse effects with little or no healing time. Recently, fractional nonablative and ablative lasers have been introduced, employing a completely new concept of fractional photothermolysis, which ensures high efficacy and fewer risks. Ablative laser resurfacing still remains the gold standard for treating advanced and severe photoaging providing excellent results in experienced hands. Alternatively, ablative fractional resurfacing can be used, with the results, which are comparable to fully ablative lasers with better standard of safety. Nonablative resurfacing is ideal for patients under the age of 50 years with minimal facial sagging, and for those who are unwilling to undergo expensive and demanding ablative procedures. It can be concluded that the key of therapeutic success is in proper patient selection, setting appropriate expectations and combining different rejuvenation technologies with other therapeutic modalities, such as botulinum toxin and fillers.

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.

[Photoallergic drug reactions]. / Fotoalergijske reakcije na lijekove.

Drug-induced hypersensitivity reactions include phototoxic and photoallergic reactions. Photoallergic reactions, which develop as cell-mediated immune responses to a light-activated compound, are described in this review article. The main topics include photobiology, list of common drugs inducing photoallergic reactions, immune response, clinical features, diagnostic and therapeutic approach. Photoallergic drug reactions can be avoided in most cases if the potential photoallergens are known and appropriate photoprotection is used.

Human papilloma virus associated with genital infection.

Genital human papillomavirus (HPV) infections are among the most common sexually transmitted diseases. HPV is associated with a spectrum of diseases ranging from benign vulgar verrucae and condylomata accuminata to malignant cancers of the cervix, vulva, anus and penis. Genital HPV is in most cases transmitted sexually, but non-sexual routes of transmission, such as perinatal and autoinoculation, are possible. Men can be a reservoir of the virus that lives in latent or subclinical form on genital mucosa. Such an asymptomatic infection may be an oncogenic factor in the development of cervical cancer Colposcopic examination of the genitalia after the application of 3-5% acetic acid is a reliable method for the identification of subclinical HPV infection. Successful therapy of anogenital warts is characterized by their complete clearance, as well as by the lack of recurrence. Current treatments do not reliably eradicate HPV infections. The diagnosis and therapy of HPV infection in men is potentially beneficial because the eradication of penile HPV infection may decrease the reservoir of the virus.

Atypical clinical appearance of pemphigus vulgaris on the face: case report.

Pemphigus vulgaris is an organ-specific autoimmune mucocutaneous disorder. In the majority of cases, the disease manifests initially with oral lesions, and may be limited to a single site for months before spreading. A 78-year-old woman with yellowish crusted areas on her left preauricular region and close to the medial angle of her right eye is presented. Although she described an episode of erosions on her lower lip, the involvement of mucosal surfaces was not noticed on examination. Before she presented to our Department, she was misdiagnosed as an actinic cheilitis and malignant skin tumor. Histopathologic examination and direct immunofluorescence confirmed the diagnosis of pemphigus vulgaris. Immunoblotting of epidermal extracts detected IgG antibodies against desmoglein 3 but not desmoglein 1, which was also confirmed by ELISA test. The patient responded favorably to systemic corticosteroid therapy combined with adjuvant immunosuppressive therapy, with complete clearance of the lesions.

Etiopathogenesis, classification, and current trends in treatment of rosacea.

Rosacea is a common chronic dermatosis characterized by varying degrees of flushing, erythema, telangiectasia, edema, papules, pustules, ocular lesions, and phymas. Etiology and pathogenesis of rosacea are still unknown. Many possible causes have been described as inducing the disease or contributing to its manifestation, such as genetic predisposition, abnormal vascular reactivity, changes in vascular mediating mechanisms, Helicobacter pylori infection, Demodex folliculorum infestation, seborrhea, sunlight, hypertension, and psychogenic factors. However, none of these factors has been proved. Rosacea shows a wide spectrum of clinical presentations, which vary over time and with age. Successful management of rosacea requires careful patient evaluation and individualized therapy with appropriate variations and modifications, as the severity of the disorder fluctuates. In mild cases of rosacea, patients are instructed to avoid sun, to apply sun-protective creams, and to avoid facial irritants and other triggers that provoke symptoms. At later stage, drug therapy is often necessary. The disease commonly requires long-term treatment with topical or oral medicaments. Surgical correction may be required for rhinophyma and telangiectasia. We reviewed the current literature on the aspects of the pathogenesis, diagnostic criteria, and treatment options for rosacea.