Dermatology and Therapy

Correction to: Pathogenesis, Clinical Signs and Treatment Recommendations in Brittle Nails: A Review Unfortunately, the co-author name was incorrectly published as “Jose L. López-Esterbaranz” instead of ‘Jose L. López-Estebaranz” in the original article. The correct version of author name is updated here. The original article has been corrected.

Pathogenesis, Clinical Signs and Treatment Recommendations in Brittle Nails: A Review Abstract Nail plate brittleness (or fragility) is a common complaint affecting up to 20% of the population, especially women over 50 years of age, with fingernail fragility being more prevalent than toenail fragility. Nail brittleness is characterized by nails that split, flake and crumble, become soft and lose elasticity. The main clinical presentations are: onychoschizia, onychorrhexis, superficial granulation of keratin and worn-down nails. According to causative factors, we can distinguish 2 forms of nail fragility (NF): a primary “idiopathic or brittle nail syndrome” form and NF secondary to different causes such as inflammatory nail disorders, infections, systemic diseases and general conditions, traumas and alteration of the nail hydration. Optimal management requires treatment of the primary cause of brittle nails, when possible. In idiopathic NF oral supplementation, vitamins (especially biotin, also known as vitamin B7), trace elements and amino acids (especially cysteine) have been reported to be useful. In addition, several products, such as topical moisturizers and lacquers could be considered to restructure the affected nail plate and to reduce psychological impacts of this common problem.

A Calm, Dispassionate Look at Skin Microbiota in Atopic Dermatitis: An Integrative Literature Review Abstract Atopic dermatitis (AD) is a chronic common inflammatory skin disorder with clinical characteristics of pruritic, dry, and recurrent flares that involve the whole body. Recent studies have demonstrated that the skin microbiota, characterized by an overgrowth of Staphylococcus aureus (S. aureus), plays a critical role in the manifestation of AD. There is striking evidence that skin microbiota can modulate the development and progression of AD. Therefore, more and more therapeutic approaches are adopted for modifying skin microbiota. Here we discuss the role of skin microbiota in the etiology and maintenance of AD; furthermore, we summarize the effects of therapeutic treatments on skin microbiota in AD based on published literature. With the help of the theoretical guidance suggested by microbial metagenome analysis, the reconstitution of microbiota should be a promising way to harness the pathogens of AD and could be used as a brand-new therapeutic strategy in clinical trials. We believe that the targeted therapy of dysbiosis in AD may possibly become a unique approach to an integrated treatment program in the near future.

Safety of Ixekizumab Treatment for up to 5 Years in Adult Patients with Moderate-to-Severe Psoriasis: Results from Greater Than 17,000 Patient-Years of Exposure Abstract Introduction Long-term safety data are critical for evaluating therapies for psoriasis. Ixekizumab has demonstrated efficacy and is well tolerated for the treatment of moderate-to-severe plaque psoriasis. We examined the safety and tolerability of up to 5 years of ixekizumab therapy in patients with psoriasis. Methods Integrated safety data were analyzed from 13 ixekizumab clinical studies. Rates of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest were analyzed for the 12-week induction period in the combined pivotal studies, and for all pooled studies by year(s) of therapy and overall, reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (p-y) and/or frequencies. Results Total ixekizumab exposure was 17,003.4 p-y (N = 5898); 2749 patients had ≥ 4 years of exposure. When compared across years of exposure, rates for AEs remained largely stable or declined, including TEAEs leading to discontinuation (3.8/100 p-y in year 1, declining to 2.0/100 p-y in year 5); SAEs (range 6.2–7.0/100 p-y); serious infections (range 1.3–1.7/100 p-y); nonmelanoma skin cancer (ranging from 0.5/100 p-y in year 1 to 0.2/100 p-y in years 4–5); other malignancies (range 0.4–0.6/100 p-y); inflammatory bowel disease including ulcerative colitis and Crohn’s disease (IR 0.2/100 p-y); and major adverse cardiovascular events (MACE) (range 0.3–0.7/100 p-y). Candidiasis was reported in 327 patients (IR 1.9/100 p-y), with the majority identified as mucocutaneous. The rate of injection site reactions was 15.5/100 p-y during year 1 and 2.0–2.3/100 p-y by years 3–5. Conclusions The decrease in rates of TEAEs and the stable rates of SAEs, other malignancies and MACE during up to 5 years of ixekizumab dosing are consistent with previous reports describing a favorable safety profile of ixekizumab following shorter durations of exposure. Funding Eli Lilly and Company.

Prospective Evaluation of the Efficacy of a Food Supplement in Increasing Photoprotection and Improving Selective Markers Related to Skin Photo-Ageing Abstract Introduction Skin exposure to ultraviolet radiation (UVR) can cause oxidative stress, particularly in the absence of adequate protective measures or in individuals with a sensitive skin type. Most commonly, protection from UVR entails the use of topical sunscreens. Sunscreens, however, have various limitations. The objective of this study was to evaluate the efficacy and tolerability of an oral food supplement containing a combination of actives with mainly antioxidative properties (vitamins A, C, D3, E, selenium, lycopene, lutein, as well as green tea, polypodium and grape extracts) in the context of photoprotection. Methods Photoprotective efficacy was assessed in a 12-week-long, open, prospective and monocentric clinical study with 30 subjects (27 women and 3 men) having a Fitzpatrick skin type I-III and manifesting clinical ageing signs. The study included several visits (14, 28, 56, and 84 days after starting supplement intake), in which photoprotection was evaluated by the measurement of the minimal erythema dose (MED), while the antioxidant capacity of the skin was assessed through ferric reducing antioxidant power (FRAP) and malondialdehyde (MDA) assays. Additionally, several skin parameters (including radiance, elasticity, and moisture) were evaluated. Product evaluation was performed throughout the length of the study by means of a self-assessment questionnaire, and safety was monitored through a self-recording of all observed adverse reactions. Results The MED levels increased significantly compared to baseline throughout the study visits, reaching an increase of + 8.1% at T84, p < 0.001. FRAP results also indicated a significant increase in the antioxidant capacity of the skin compared to baseline (+ 22.7% at T84, p < 0.001), while the MDA assay showed a significant decrease in MDA concentration compared to baseline (− 6.4% at T84, p < 0.001) which, in line with the FRAP results, indicated enhanced antioxidative protection of the skin. All assessed skin parameters, including radiance (+ 36.1% at T84, p < 0.001), gross elasticity (+ 13.2% at T84, p < 0.001), net elasticity (+ 28.0% at T84, p < 0.001), and moisture (+ 13.8% at T84, p < 0.001) were also significantly improved. The product was well tolerated as no adverse events were attributed by the investigators to the use of the product. Additionally, the global score obtained from the self-assessment questionnaires provided overwhelmingly positive feedback from the study subjects. Conclusions The food supplement evaluated in this study was effective and well-tolerated by the subjects, demonstrating a beneficial effect in terms of photoprotection, enhancing the antioxidative status of the skin and improving general skin condition. Trial Registration Retrospectively registered 3rd October 2019, ISRCTN18121679.

Clinical and Instrumental Objective Evidence of the Efficacy of a New Water-Based Nail-Strengthening Solution Containing Pistacia lentiscus and Hyaluronic Acid Applied for Up to 6 Months to Improve the Appearance of Weak, Brittle Nails Abstract Introduction Brittle nails are fragile or split nails; they affect 20% of the population and may be primary or secondary to different conditions. The aim of our studies was to evaluate the efficacy and tolerability of a new water-based nail-strengthening treatment containing hyaluronic acid and Pistacia lentiscus with daily application for a period of 1–3 months for one study (n = 30) and up to 6 months for a second study (n = 30). Methods In total, we enrolled 60 patients of both sexes with brittle and weak nails due to primary or secondary causes and evaluated the efficacy of this new product using subjective and objective methods: clinical evaluation, assessment of photographs, onychoscopy evaluation, investigator and patient global assessment, dynamic optical coherence tomography (D-OCT) and reflectance confocal microscopy (RCM). Results Studies subjects presented a statistically significant improvement in global assessment scale (GAS) scores at 14 days (GAS = 1.7 ± 0.6), 1 month (GAS = 1.4 ± 0.7) and at 3 months (GAS = 1±0.7) versus the GAS score obtained before treatment (1.9 ± 0.5) (p < 0.0001). From the Italian study at 6 months (n = 30) 76% of the patients had an improvement in their nail appearance. Reduction in nail plate roughness with improved nail resistance and decreased distal breakage were the most evident benefits, demonstrated on clinical and instrumental evaluations. No side effects were reported. All patients reported an improvement in nail appearance after using the product for 1 month, 3 months and 6 months, and had a positive opinion on the product. Conclusions This new product is an effective, safe, and easy-to-use option for topical treatment of brittle nails and primary nail fragility and an adjuvant therapy in secondary nail fragility. Moreover, its ease of application and cosmetic qualities allow good compliance. Funding ISDIN.

Trichoscopy of Tinea Capitis: A Systematic Review Abstract Introduction An increased incidence of tinea capitis has been observed over the last few decades. Trichoscopy is a non-invasive, in-office method helpful in establishing the correct diagnosis in patients with hair loss and inflammatory hair disorders. The objective was to review and analyze current data on the trichoscopy of tinea capitis. Methods A systematic review of the literature was conducted using the PubMed, EBSCO and Scopus databases. The search terms included ‘tinea capitis’ combined with ‘trichoscopy’, ‘dermatoscopy’, ‘dermoscopy’, ‘videodermatoscopy’ or ‘videodermoscopy’. Results Of 326 articles, 37 were considered eligible for the quantitative analysis. The most characteristic (with a high predictive value) trichoscopic findings of tinea capitis included comma hairs (51%), corkscrew hairs (32%), Morse code-like hairs (22%), zigzag hairs (21%), bent hairs (27%), block hairs (10%) and i-hairs (10%). Other common, but not characteristic, trichoscopic features were broken hairs (57%), black dots (34%), perifollicular scaling (59%) and diffuse scaling (89%). Morse code-like hairs, zigzag hairs, bent hairs and diffuse scaling were only observed in Microsporum tinea capitis (8/29, 28%; 6/29, 21%; 4/29, 14% and 4/29, 14%, respectively). In Trichophyton tinea capitis, corkscrew hairs were more commonly detected compared to Microsporum tinea capitis (21/38, 55% vs 3/29, 10%). Conclusion The presence of characteristic trichoscopic features of tinea capitis is sufficient to establish the initial diagnosis and introduce treatment before culture results are available. Trichoscopy may be useful in distinguishing between Microsporum and Trichophyton tinea capitis.

Incontinentia Pigmenti Associated with Aplasia Cutis Congenita in a Newborn Male with Klinefelter Syndrome: Is the Severity of Neurological Involvement Linked to Skin Manifestations? Abstract We report a rare case of a newborn male affected by incontinentia pigmenti, Klinefelter syndrome, and aplasia cutis congenita, who developed severe cutaneous, neurological, and ophthalmological manifestations. Genetic analysis showed the presence of the common mutation of NEMO (exon 4–10 deletion), Klinefelter syndrome karyotype (47 XXY), and random X inactivation. This is in accordance with the severity of involvement of the affected tissues (skin, central nervous system, and retina). Indeed, the patient developed typical skin lesions all over the body, except the head. Equally, multiple lesions diffusely involving both the cortical grey matter and subcortical white matter of the cerebellum and cerebral hemispheres were observed. Discussing current knowledge about the etiopathogenesis of skin and brain lesions in incontinentia pigmenti, our case seems to support the proapoptotic origin of central nervous system involvement. Possibly, incontinentia pigmenti patients suffer an impaired protection against apoptosis at the level of cerebral endothelial cells of small vessels, leading to vascular damage and subsequent ischemic brain lesions.

Exploring Anti-Fungal, Anti-Microbial and Anti-Inflammatory Properties of a Topical Non-Steroidal Barrier Cream in Face and Chest Seborrheic Dermatitis Abstract Introduction The pathogenesis of seborrheic dermatitis (SD) is multifactorial and traditional treatments may not target all aspects of it. The aim of this study was to evaluate short-term anti-fungal, anti-microbial, anti-inflammatory and anti-pruritus properties of a novel non-steroidal cream (NSC) containing piroctone olamine, zinc salt of l-pyrrolidone carboxylate (PCA), hydroxyphenyl propamidobenzoic acid, biosaccharide gum-2 and stearyl glycyrrhetinate in patients with face and chest SD. Methods Twelve male subjects affected by SD, presenting face and chest manifestations, were enrolled. Patients were instructed to apply NSC twice a day, performing regular visits at baseline (W0), after 7 (W1) and 14 (W2) days of treatment. A limitation of the study was that no control group treated with the vehicle without active ingredients was enrolled. To evaluate the efficacy of the NSC, investigator’s assessments were represented by scoring index (SI) and investigator’s global assessment score (IGA). In order to assess NSC anti-fungal and anti-microbial effects, skin scale scrapings were collected and used for Malassezia furfur (MF) and Staphylococcus epidermidis (SE) cultures. In parallel, in order to assess NSC anti-inflammatory effects, gene expression of IL-1α, IL-1β, IL-6, IL-8, and TNF-α was assessed. In addition, anti-pruritus effects were also evaluated through gene expression of cathepsin S and l-histidine decarboxylase. Results SI mean scores significantly decreased at W1 and, to a greater extent, at W2 compared with W0. The IGA score registered an important improvement efficacy both for face and chest, from W1 to W2. MF and SE growth was already inhibited at W1, with a more pronounced decrease at W2. Gene expression of all analyzed mediators was significantly reduced at W1 compared to W0. Conclusion In conclusion, our assessment is that NSC is an effective and well tolerated treatment option for SD with anti-fungal, anti-microbial and anti-inflammatory properties. Trial Registration ISRCTN registry, ISRCTN77871064 (retrospectively registered October 17, 2019). EudraCT number, 2019-003813-32. Funding ISDIN.

Anastrozole-Induced Dermatitis: Report of a Woman with an Anastrozole-Associated Dermatosis and a Review of Aromatase Inhibitor-Related Cutaneous Adverse Events Abstract Anastrozole is an aromatase inhibitor. Anastrozole competitively inhibits the aromatase enzyme, which synthesizes estrogen. It is used for estrogen receptor-positive breast cancers. A woman with breast cancer and anastrozole-induced dermatitis is described; the cutaneous side effects associated with aromatase inhibitors are also reviewed. Skin-related adverse events associated with aromatase inhibitor use are uncommon and may be delayed in appearance; the time of onset ranges from less than 5 days to 6 months (median 2 months). They present as either vasculitis, erythema nodosum, subacute cutaneous lupus erythematosus, or other dermatoses. Some patients demonstrate cutaneous lesions at either the original site of the breast malignancy or in areas that were previously treated with surgery or radiotherapy. The skin reactions are usually treated with discontinuation of the aromatase inhibitor; topical corticosteroids or oral corticosteroids or both are also used for some patients. Our patient’s drug reaction occurred 2 months after starting the anastrozole and improved after a course of oral and topical corticosteroids. She was able to be switched to an alternate aromatase inhibitor without a recurrence of her adverse skin reaction.