Advances in pharmacotherapy for rosacea: what is the current state of the art?

INTRODUCTION: Rosacea is a chronic and relapsing facial dermatosis that encompasses a wide spectrum of clinical phenotypes (transient/persistent erythema, telangiectasias, papules/pustules, edema, phymatous changes, and ocular symptoms) often with uncomfortable symptoms such as flushing, pain, burning, edema, and dryness. Current pharmacological treatment includes topical agents, spanning from several conventional (azelaic acid, metronidazole, sodium sulfacetamide) to new ones (brimonidine, oxymetazoline, ivermectine, minocycline), and systemic agents (doxycycline 40 mg modified-release), all Food and Drug Administration approved. AREAS COVERED: The aim of our article is to review the state of art of pharmacological treatment, either as monotherapy or in combination therapy, tailored to the most common rosacea phenotypes (persistent erythema, inflammatory papules/pustules). Other off-label topical or systemic drugs and several adjuvant phytotherapeutic agents are considered. EXPERT OPINION: Combined therapies to target different phenotypes, when present in the same patient, represent one of the major achievements in the management of vascular and inflammatory papules and pustules of rosacea. Future investigations should be addressed to early inflammatory phyma or ocular rosacea, which have actually been neglected. Finally, there is still an ongoing need for therapeutic interventions able to relieve symptoms and social burden, all factors that greatly contribute to improve rosacea quality of life.

An Overview of the Diagnosis and Management of Seborrheic Dermatitis.

Seborrheic dermatitis (SD) is a common chronic inflammatory skin disorder that mostly affects young adults in areas rich in sebaceous glands (scalp, face, and trunk). In adolescents and adults, SD clinical presentation may range from mild patches to diffuse scalp scaling. In infants, it mainly occurs on the scalp as yellowish, scaly patches ("cradle cap"). In adults, several environmental triggers are likely to promote SD development, along with fungal colonization by Malassezia spp., sebaceous gland activity, as well as immunosuppression, endocrine, neurogenic and iatrogenic factors. In children, early occurrence in the first trimester suggests the role of excessive sebaceous gland activity from maternal hormones, along with cutaneous microbiome alterations. The diagnosis of SD is usually clinical, and specific laboratory and/or instrumental investigations are seldom required. Treatment is aimed at modulating sebum production, reducing skin colonization by Malassezia spp., and controlling inflammation. In adults, mild-to-moderate scalp SD forms can be managed with topical antifungals (ketoconazole, ciclopirox, miconazole) or antiinflammatory (mild-to-moderate potency corticosteroids) or keratolytic/humectant (propylene glycol) agents. Recommended topical therapeutic options for mild-to-moderate facial or body areas SD include topical ketoconazole, ciclopirox, clotrimazole, mild-to-moderate potency corticosteroids, lithium succinate/gluconate, and topical calcineurin inihibitors (off-label use). In severe and/or resistant cases, the use of systemic antifungal drugs (terbinafine, itraconazole), as well as UVB phototherapy, may be considered. In children, scant scientific evidence supports the effectiveness and safety of topical drugs, and "cradle cap" is usually successfully managed with baby shampoos enriched with emollient agents and vegetable oils. Alternatively, similarly to adult scalp SD, medical device shampoos with antiinflammatory and antifungal properties, containing piroctone olamine, bisabolol, alyglicera, telmesteine, may be used. Beyond pharmacological treatments, an appropriate cosmetic approach, if correctly prescribed, may improve therapeutic outcomes.

COVID-19: The Italian experience.

Italy was among the world's earliest and most affected countries by coronavirus disease 2019 (COVID-19). We report the Italian experience with the pandemic. The dermatologic community immediately reduced any type of activities to 80% to 90% of outpatient consultations, both in public hospitals and in private offices. The Italian Society of Dermatology and Sexually Transmitted Diseases and the Italian Forensic Dermatologic Society supported the dermatologic community by reporting recommendations in newsletters (vademecum) regarding the routine management of dermatologic patients either in the hospital or private setting. We have provided an overview of the skin manifestations from the pandemic, including the consequences of the misuse of safety measures. We also have evaluated the recently developed research projects on patients treated with biologics for psoriasis, atopic dermatitis, and hidradenitis suppurativa, as well as on the registries regarding various skin diseases affected by COVID-19.

A novel treatment of intertrigo in athletes and overweight subjects.

BACKGROUND: Intertrigo is a recurrent inflammatory dermatosis involving large/small body folds. Skin barrier products represent the mainstay of treatment in uncomplicated mild/moderate intertrigo. AIMS: To assess by clinical and instrumental evaluation the efficacy and tolerability of a new barrier spray containing zinc gluconate-taurine complex and zinc oxide combined with panthenol, glycerin, and Shea (Butyrospermum parkii) butter in mild-to-moderate intertrigo in athletes and overweight subjects. METHODS: In this open-label prospective trial, 20 adult patients, with mild/moderate intertrigo enrolled at the Dermatology University Clinic of Catania (Italy), were instructed to apply the spray twice daily for 30 days. Degree of erythema was performed clinically and by polarized dermoscopy using a 5-point severity scale (from 0=no erythema to 4=severe erythema) at baseline, and at 15 and 30 days. The measurement of pruritus was carried out by a subject-completed visual analog scale (VAS) (from 0 mm=no pruritus to 100 mm=severe pruritus), at all time points. An Investigator Global Assessment (IGA) using a 6-point scale (from -1=worsening to 4=complete response/clear) was also conducted at 30 days, along with a self-administered tolerability questionnaire. Statistical analysis was performed using SAS version 9. RESULTS: At 15 days, a statically significant reduction from baseline in erythema severity (mean from 3.4 ± 0.3 to 2.5 ± 0.2) along with pruritus intensity (mean from 70 ± 15.4 mm to 40 ± 9.5 mm) was observed. At 30 days, all evaluated parameters showed a further progressive statistically significant reduction from baseline. No relevant side effects were recorded. CONCLUSIONS: Our results suggest that the tested spay containing antiseptic/anti-inflammatory and anti-irritation agents may represent a valid therapeutic option for mild/moderate intertrigo.

Emerging topical drugs for the treatment of rosacea.

Introduction: Rosacea is a common, chronic and relapsing inflammatory skin disease of the centrofacial area. Despite advancing knowledge on its pathogenesis, diagnosis, and treatment, some major unknowns still remain, including systematic evidence-based guidelines useful both for clinical assessment and therapeutic management. Topical treatment is regarded as a first-line option for mild to moderate rosacea and includes traditional and new FDA-approved prescription drugs, as well as off-label alternative topical agents.Areas covered: Since improved awareness of rosacea pathogenetic mechanisms has led to the development of new potential therapeutic agents, a search was performed on the ClinicalTrial.gov registry. The results identified several investigational topical drugs able to target one or more of the pathogenetic factors of rosacea.Expert opinion: The main unmet needs in the topical treatment of rosacea remain the management of vasomotor flushes and telangiectasias, as well as of troublesome symptoms such as burning and/or stinging. No single agent effective on all rosacea phenotypes is available so far, and preventive treatments capable of halting disease progression have not been identified yet. Finally, data on long-term efficacy and tolerability are still incomplete, especially for drugs more recently introduced in the market.

Diet and acne: review of the evidence from 2009 to 2020.

BACKGROUND: Dietary habits may play a non-negligible role in the development, duration, and severity of acne, as shown in past critical review articles on such association. METHODS: The aim of this systematic review is to supplement data available on scientific literature spanning the last 10 years by inserting the keywords "acne" or "acne vulgaris" and "diet", "nutrition", "food", "chocolate", "dairy", "whey protein", "fatty acid", or "drink" in the timeframe "January 2009-April 2020" within the PubMed database. RESULTS: Fifty-three reviewed articles met eligibility criteria. They included 11 interventional clinical trials (seven randomized controlled trials and four uncontrolled open label studies) and 42 observational studies (17 case-control and 22 cross-sectional studies, and three descriptive studies). CONCLUSIONS: This review reinforces the notion of a rapidly growing exponential trend of interest in this subject by the scientific community. Acne-promoting factors include high GI/GL food, dairy products, fat food, and chocolate, whereas acne-protective factors include fatty acids, fruit, and vegetable intake. The role played by specific dietary components pertaining to different foods, as done for milk (full-fat/whole, reduced-fat, low-fat/skim milk), dairy products (milk cream, ice cream, yogurt, cheese, etc.), or chocolate (cocoa, dark/milk chocolate), remains an unsolved issue and objective of future research.

The Influence of Pregnancy on the Clinical Evolution and Prognosis of Pre-Existing Inflammatory and Autoimmune Skin Disorders and Their Management.

BACKGROUND: Although the possible occurrence of typical dermatoses during pregnancy is well recognized, little is known about the influence of pregnancy on the clinical evolution and prognosis of different pre-existing chronic dermatological disorders. SUMMARY: In this study a comprehensive search of the available literature and reviews has been undertaken in order to collect and analyze articles reporting pre-existing chronic skin disorders in pregnant women and report current knowledge on their particular clinical and therapeutic aspects.

Clinical evidences of urea at low concentration.

Urea is a hygroscopic molecule that, because of its moisturising properties, is topically used for the treatment of skin dryness at concentrations ranging from 2% to 12% in different formulations. Based on existing literature, low-concentration urea-containing products are effective in the treatment and/or prevention of xerosis in some skin disorders such as ichthyosis, atopic dermatitis and psoriasis, or unrelated to specific skin diseases. Generally, urea formulations at low concentration are well-tolerated and suited for the treatment of large skin areas, once or twice daily, even for a long period of time. At low concentrations stinging and burning sensation is rare and transient, whit no reported sensitisation despite its widespread use.

Nodular Classic Kaposi's Sarcoma Treated With Neodymium-Doped Yttrium Aluminum Garnet Laser Delivered Through a Tilted Angle: Outcome and 12-Month Follow Up.

BACKGROUND AND OBJECTIVES: Classic Kaposi's sarcoma (KS) is a multifocal angioproliferative disorder with a long and indolent course typically affecting the lower extremities of elderly men. Multiple nodules with a rapid growth may sometimes develop, causing pain, bleeding, and discomfort on walking. In such cases, immediate intervention using different methods, including laser therapy, is advisable. We report our experience in classic KS patients with the use of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser delivered through a tilted angle. STUDY DESIGN/MATERIALS AND METHODS: A total of 81 KS nodules (0.5-3 cm size) located in the feet or lower limbs of nine patients (mean age: 78.8 years; age range: 64-86 years) were selected for treatment with Nd:YAG laser (5-7 mm spot, 140-200 J/cm2 fluence, 5 ms triple pulse with 10 ms delay). The laser beam was delivered at the periphery of each nodule using a tilted angle of 30° to 60° according to lesion size in order to better target the feeding vessels located in the inner and basal depth of the lesion and minimize tissue damage. The treatment outcome was evaluated by clinical photograph, videodermatoscopy, and ultrasound scanning performed before and after treatment, and at each monthly follow-up visit. RESULTS: All treated patients showed full recovery, with negligible scarring, no residual hyperpigmentation, and complete regression of pain. Treatment discomfort was minimal and use of topical anesthetics was not needed. No recurrences were observed at 12-month follow up. CONCLUSIONS: Long-pulse Nd:YAG laser delivered using a tilted angle is a fast, easy, effective, comfortable, and safe treatment option available to promptly shrink bulky, painful, or bleeding nodules with minimal discomfort and gives excellent functional and cosmetic results. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Previously Unreported COL7A1 Mutation in a Somali Patient with Dystrophic Epidermolysis Bullosa.

Epidermolysis bullosa (EB) encompasses a group of inheritable skin disorders characterized by various degrees of epithelial fragility that lead to cutaneous and mucosal blistering following negligible mechanical traumas. These disorders are clinically and genetically heterogeneous, ranging from mild skin involvement to severe disabling conditions with associated manifestations affecting the gastrointestinal and vesico-urinary tracts. EB may be classified into 4 main categories: simplex, junctional, dystrophic, and Kindler syndrome. Clinically, EB may present as syndromic or nonsyndromic forms. EB subtypes have mainly reported a number of mutations in the candidate COL7A1 gene encoding type VII collagen, a major stabilizing molecule of the dermoepidermal junction. Herein, we report a Somali girl with dystrophic EB who showed a previously unreported missense variant c.6797G>T in exon 86 in COL7A1.

A Noninvasive Aid for Office-Based Gynecologists for the Diagnosis of Common External Genital Disorders.

BACKGROUND: Gynecology and dermatology share the diagnosis and the management of some disorders of the female external genital area. In the last decade, clinical diagnosis in dermatology has dramatically improved, thanks to the introduction of dermatoscopy. TECHNIQUE: Dermatoscopy is a noninvasive, rapid, and simple technique performed with an affordable handheld instrument called dermatoscope, endowed with a light source and a high-quality lens achieving 10 times magnification. EXPERIENCE: The use of dermatoscopy for the diagnosis of some common external genital disorders, i.e., genital warts (GW), vestibular papillomatosis (VP), molluscum contagiosum (MC), angiokeratoma (AK), and pediculosis pubis (PP), is presented and discussed. CONCLUSION: The use of dermatoscopy in a gynecologic office may considerably help the specialist to enhance in selected cases the clinical diagnosis and to avoid unnecessary and cumbersome investigations which may be time and money consuming.

Grover's disease: dermoscopy, reflectance confocal microscopy and histopathological correlation.

Grover's disease is a benign condition of unknown origin characterized clinically by an erythematous papulovesicular eruption and histopathologically by intraepidermal clefting and four different patterns of acantholysis: Darier-like, pemphigus-like, spongiotic, and Hailey-Hailey-like. A case of a 54-year-old female affected by Grover's disease and showing a Darier-like histopathological pattern is described. Polarized light dermoscopy (PLD) revealed the presence of polygonal, star-like shaped yellowish/brownish areas of various sizes surrounded by a thin whitish halo. Handheld reflectance confocal microscopy (RCM) showed the presence of intraepidermal dark spaces histopathologically corresponding to intraepidermal clefts, roundish, bright cells correlating to acantholytic keratinocytes, target-like cells with a dark center and a highly reflectant halo corresponding to dyskeratotic cells, and epidermal, polygonal, structureless areas reflecting hyperparakeratosis. In conclusion, the use of PLD and RCM combined with clinical presentation, personal/family history, and genetic evaluation may be useful for the non-invasive diagnosis of Darier-like Grover's disease.

A novel topical agent in the treatment of seborrheic keratoses: A proof of concept study by clinical and dermoscopic evaluation.

In this proof of concept study, 50 lesions from 15 patients with multiple seborrheic keratoses (SKs) were treated with a novel aqueous solution containing nitric acid, zinc and copper salts, and organic acids (acetic, lactic, and oxalic acid). Treatment consisted in the application of an amount of the solution sufficient to obtain a whitening/yellowish reaction. Application of the nitric-zinc solution was performed every other week until clinical and dermoscopic clearance or crust formation, for a maximum of 4 applications. Efficacy evaluation was performed at 8 weeks (T1) and 6 months (T2). All subjects, who reported no or minimal discomfort during and after the application of the solution, completed the study. At T1, a complete clinical and dermoscopic resolution was observed in 37 lesions after an average of 3 applications/lesion (range 2-4). A partial response, with minimal persistent residual spots, was detected in the remaining 13 lesions. All patients with complete clearance showed no relapses at a 6-month follow-up (T2). The positive preliminary results indicate that this novel solution may represent a promising alternative option for SKs especially in patients not keen or eligible to undergo invasive tissue-destructive procedures.

Perforating pseudoxanthoma elasticum with secondary elastosis perforans serpiginosa-like changes: dermoscopy, confocal microscopy and histopathological correlation.

Pseudoxanthoma elasticum is a rare congenital inherited elastolytic disorder that has sometimes been observed in association with transepidermal elimination of altered and calcified elastic fibers resulting in elastosis perforans serpiginosa-like changes. In this case, histopathology is usually performed to rule out other conditions. The case of a 38-year-old woman with two slowly enlarging asymptomatic plaques occurring on the neck and surrounded by coalescing yellowish papules with a typical cobblestone appearance, evaluated by polarized light dermoscopy and reflectance confocal microscopy with histopathologic correlations, is described. Noteworthy, with reflectance confocal microscopy, the transepidermal elimination of the altered elastic fibers in the plaques was detected as hyperreflective material filling the dermal papillae, whereas the transversal cleavage of the calcified elastic fibers yielded a peculiar 'eggs-in-the-basket' feature.