Efficacy of a new antidandruff thermophobic foam: a randomized, controlled, investigator-blinded trial vs. ketoconazole 2% scalp fluid

Background Ketoconazole (K), zinc pyrithione (ZP), and salicylic acid (SA) are compounds active in the treatment of dandruff. A thermophobic foam formulation containing K 1%, ZP 0.5%, and SA 2% is now available. Study aim To compare the efficacy of thermo phobic foam with K 2% scalp fluid in the treatment of moderate to severe dandruff. Patients and methods In a randomized, prospective, parallel‐group, investigator‐blinded, 4‐week treatment trial, a total of 54 patients (mean age 43 ± 8 years) were enrolled. Foam (F group) (n = 37) or K 2% scalp fluid (SF group) (n = 17) was applied daily for 7 days and twice weekly for 3 weeks thereafter. Clinical assessment of the total dandruff severity score (TDSS) was performed at baseline, after 2 and 4 weeks. The TDSS was calculated using a four‐grade quantitative score (0 = no dandruff; 3 = severe dandruff) dividing the scalp area into four zones and adding the single score for each area. Results At baseline, TDSS was 7.1 ± 2 and 5.1 ± 1 in the F and SF groups, respectively. At the end of treatment period, beneficial effects were observed in both groups. The TDSS was reduced to 2.5 ± 1 in the F group and to 3.7 ± 1.2 in the SF group (mean difference in favor of F group: ?1.2; 95% CI: –0.57 to ?1.8) (P = 0.0003). A complete or nearly complete resolution of dandruff was observed in 24 out of 37 (64%: 95%CI: 48–77%) in the F group and in 7 out of 17 (41%: 95% CI: 21–64%) in the SF group (P = 0.06 between groups). Conclusions This new antidandruff thermophobic foam has shown to be more effective than ketoconazole 2% scalp fluid in the treatment of severe dandruff.     

BRAF,KIT and NRAS mutations and expression of c‐KIT,phosphorylated extracellular signal‐regulated kinase and phosphorylated AKT in Japanese melanoma patients

To clarify the status of gene mutation and activation of growth signal in melanoma of Japanese patients in vivo, we analyzed the mutation of BRAF exon 15, NRAS exon 2, and KIT exons 9, 11, 13, 17 and 18 in melanoma cells obtained by laser capture microdissection, and performed direct sequencing in 20 cases of acral lentiginous melanoma (ALM) and 17 cases of superficial spreading melanoma (SSM). In the study of the mutation of BRAF, pyrosequencing was also done. To examine the cell proliferation signaling, immunohistochemistry for phosphorylated extracellular signal‐regulated kinase (pERK), phosphorylated AKT (phosphorylated AKT) and c‐KIT was done. The mutation of BRAF p.V600E was detected in 13 cases of ALM (65.0%) and 12 cases of SSM (70.6%). No NRAS mutation was found in all cases. The mutation in exons 9, 11, and 18 of KIT was detected in nine cases. The mutation of BRAF and KIT showed no correlation with clinical stage, lymph node metastasis, tumor thickness, ulceration and histology. pERK and pAKT was observed in small population of melanoma cells and there was no correlation with gene mutation. Our results indicate that the mutations of BRAF and KIT exist in Japanese melanoma patients, however, the cell growth signaling may be regulated by not only these mutated genes, but by other unknown regulatory factors, which may affect the prognosis of melanoma.     

Shampoos: Ingredients,efficacy and adverse effects

Shampoos are the most frequently prescribed treatment for the hair and scalp. The different qualities demanded from a shampoo go beyond cleansing. A cosmetic benefit is expected, and the shampoo has to be tailored to variations associated with hair quality, age, hair care habits, and specific problems related to the condition of the scalp. The reciprocal relationship between cosmetic technology and medical therapy is reflected in the advances of shampoo formulation that has made applications possible that combine benefits of cosmetic hair care products with efficacy of medicinal products. A shampoo is composed of 10 to 30 ingredients: cleansing agents (surfactants), conditioning agents, special care ingredients, and additives. Since the cleansing activity depends on the type and amount of surfactants utilized, shampoos are composed of a blend of different surfactants, depending on the requirements of the individual hair type. Development time from the concept to the commercial shampoo may take longer than a year. Much effort is invested in the development of conditioning agents, which impart luster, smoothness, volume and buoyancy. Another prerequisite is a scalp free of scaling. Current anti‐dandruff agents primarily have an antimicrobial mode of action, and inhibit growth of Malassezia spp. Recent developments in shampoo technology have led to increased efficacy of anti‐dandruff agents, allowing shorter contact time, and reducing irritation.     

Mutations in mevalonate pathway genes in patients with familial or sporadic porokeratosis

Porokeratosis comprises heterogeneous keratinization disorders that are characterized by one or more atrophic patches surrounded by a ridge‐like cornoid lamella. In this study, we evaluated seven families affected by porokeratosis and five sporadic patients of the disease in a Chinese population. We performed Sanger sequencing of exons and flanking intron–exon boundaries of mevalonate pathway genes (MVD, MVK, PMVK and FDPS) and of SLC17A9. In five familial and three sporadic patients, we detected six variations, including four novel mutations (MVD c.1A>G; p.Met1?, c.916G>A; p.Ala306Thr, c.1013+1G>A, and PMVK c.65A>G; p.Lys22Arg) and two recurrent mutations (MVD c.746T>C; p.Phe249Ser, and MVK c.1028T>C; p.Leu343Pro). We then applied I‐TASSER and iGEMDOCK to assess these variants for probable functional impacts. The findings of this study extend the mutation spectrum of porokeratosis and provide further evidence for the genetic basis of this disease.     

Shiunko and Chuoko,topical Kampo medicines,inhibit the expression of gehA encoding the extracellular lipase in Cutibacterium acnes

Antimicrobial agents have been used for eradication of Cutibacterium (formerly Propionibacterium) acnes that is an exacerbation factor of the skin disease acne vulgaris. However, the use of antibiotics is associated with an increased risk of promoting the emergence of resistant bacteria and leading to skin dysbiosis. Traditional Japanese Kampo medicines, such as Keigairengyoto, are used to treat acne. However, there is incomplete understanding regarding their functional mechanism in treatment of acne. In this study, we examined the antimicrobial and anti‐lipase activity of the Kampo medicines used empirically for acne treatment. Three oral medicines, Keigairengyoto, Seijoboufuto and Jumihaidokuto, were found to inhibit the growth of C. acnes and decrease the lipase activity. Especially, Keigairengyoto caused remarkable decrease of bacterial lipase activity. Furthermore, topical medicines such as Shiunko and Chuoko significantly decreased the lipase activity in a dose‐dependent manner, without inhibiting C. acnes growth. The topical medicines were found to inhibit the expression of gehA, which codes for extracellular lipase. Our results indicate that Shiunko and Chuoko have potential as effective acne therapeutic agents, especially because they do not promote the emergence of antimicrobial‐resistant bacteria and skin dysbiosis.     

Genetic alterations in RAS‐regulated pathway in acral lentiginous melanoma

Studies integrating clinicopathological and genetic features have revealed distinct patterns of genomic aberrations in Melanoma. Distributions of BRAF or NRAS mutations and gains of several oncogenes differ among melanoma subgroups, while 9p21 deletions are found in all melanoma subtypes. In the study, status of genes involved in cell cycle progression and apoptosis was evaluated in a panel of 17 frozen primary acral melanomas. NRAS mutations were found in 17% of the tumors. In contrast, BRAF mutations were not found. Gains of AURKA gene (20q13.3) were detected in 37.5% of samples, gains of CCND1 gene (11q13) or TERT gene (5p15.33) in 31.2% and gains of NRAS gene (1p13.2) in 25%. Alterations in 9p21 were identified in 69% of tumors. Gains of 11q13 and 20q13 were mutually exclusive, and 1p13.2 gain was associated with 5p15.33. Our findings showed that alterations in RAS‐related pathways are present in 87.5% of acral lentiginous melanomas.     

Identification of PTPN22, ST6GAL1 and JAZF1 as psoriasis risk genes demonstrates shared pathogenesis between psoriasis and diabetes

The biological connections between psoriasis and diabetes have been suggested by epidemiological, immunological and genetic studies. To identify additional shared susceptibility loci and investigate shared pathogenesis between these two diseases, we genotyped 89 reported diabetes susceptibility loci in 4456 psoriasis cases and 6027 controls of Chinese population using the MassARRAY system from Sequenom. We discovered three significant associations at rs6679677 on 1p13.2 (P=6.15×10^?5, OR=5.07), rs16861329 on 3q27.3 (P=2.02×10^?4, OR=0.87) and rs849135 on 7p15.1 (P=6.59×10^?9, OR=1.78), which suggested PTPN22, ST6GAL1 and JAZF1 as novel susceptibility genes for psoriasis in Chinese population. Our findings implicated the involvement of T‐cell receptor signalling pathway in the pathogenesis of psoriasis and further confirmed the shared genetic susceptibility between psoriasis and diabetes.     

Distant metastasis due to heavily pigmented epithelioid melanoma with underlying BRAF V600E,NOTCH1, ERBB3, and PTEN mutations

Pigment‐synthesizing melanoma (PSM) describes a morphologically and genetically diverse group of melanomas. In contrast, pigmented epithelioid melanocytoma (PEM) encompasses a spectrum of indolent tumors now classified as borderline/intermediate melanocytic tumors. Herein, we report a case of widely metastatic heavily pigmented epithelioid melanoma with fatal outcome in a 36‐year‐old woman. Next‐generation sequencing identified somatic (tumoral) mutations in BRAF V600E, PTEN, NOTCH1, and ERBB3. By contrast, GNAQ and GNA11 were wild type. Prkar1α and p16 expression were maintained. Identification of mutations in NOTCH1 and ERBB3 may support the diagnosis of heavily pigmented epithelioid melanoma. In contrast, PRKCA fusion genes and PRKAR1A mutations support the diagnosis of PEM. Given the heterogeneity, potential overlap (loss of Prkar1α expression), and evolving genetic profiles of these two distinct groups of tumors, careful appraisal of molecular profiles in the light of histomorphology and clinical history is necessary for distinction between PEM and PSMs including heavily pigmented epithelioid melanomas, with significant potential impact on prognosis and therapy.     

Novel KRT83 and KRT86 mutations associated with monilethrix

Monilethrix is an autosomal dominant hair disorder caused by mutations in the hard keratins KRT81, KRT83 and KRT86. The affected hairs are fragile and break easily, leading to scarring alopecia. Follicular hyperkeratosis in the neck and on extensor sides of extremities is a frequently associated finding. The disorder is rare, but probably underreported because its manifestations may be mild. Mutations in KRT81 and KRT86 are the most common. Here, we report new cases from Venezuela, the Netherlands, Belgium and France. The Venezuelan kindred is special for having patients with digenic novel nucleotide changes, a KRT86 mutation associated with monilethrix and a KRT81 variant of unknown clinical significance. In the French and Dutch patients, we found novel KRT86 and KRT83 mutations. Our findings expand the mutational spectrum associated with monilethrix.     

Dihydroavenanthramide D prevents UV‐irradiated generation of reactive oxygen species and expression of matrix metalloproteinase‐1 and ‐3 in human dermal fibroblasts

Ultraviolet B (UVB) radiation induces photoageing by upregulating the expression of matrix metalloproteinases (MMPs) in human skin cells. Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component in oats. Although anti‐inflammatory, anti‐atherosclerotic and antioxidant effects have been reported, the antiphotoageing effects of DHAvD are yet to be understood. In this study, we investigated the inhibitory effects of DHAvD on UVB‐induced production of reactive oxygen species (ROS) and expression of MMPs, and its molecular mechanism in UVB‐irradiated human dermal fibroblasts. Western blot and real‐time PCR analyses revealed that DHAvD inhibited UVB‐induced MMP‐1 and MMP‐3 expression. It also significantly blocked UVB‐induced ROS generation in fibroblasts. Additionally, DHAvD attenuated UVB‐induced phosphorylation of MAPKs, activation of NF‐κB and AP‐1. DHAvD regulates UVB‐irradiated MMP expression by inhibiting ROS‐mediated MAPK/NF‐κB and AP‐1 activation. DHAvD may be a useful candidate for preventing UV light‐induced skin photoageing.     

Loss of FAS/FASL signalling does not reduce apoptosis in Sharpin null mice

Mice with mutations in SHANK‐associated RH domain interactor (Sharpin) develop a hypereosinophilic auto‐inflammatory disease known as chronic proliferative dermatitis. Affected mice have increased apoptosis in the keratinocytes of the skin, oesophagus and forestomach driven by extrinsic TNF receptor‐mediated apoptotic signalling pathways. FAS receptor signalling is an extrinsic apoptotic signalling mechanism frequently involved in inflammatory skin diseases. Compound mutations in Sharpin and Fas or Fasl were created to determine whether these death domain proteins influenced the cutaneous phenotype in Sharpin null mice. Both Sharpin/Fas and Sharpin/Fasl compound mutant mice developed an auto‐inflammatory phenotype similar to that seen in Sharpin null mice, indicating that initiation of apoptosis by FAS signalling is likely not involved in the pathogenesis of this disease.     

A prospective,open‐label,multicenter, observational,postmarket study of the use of a 15 mg/mL hyaluronic acid dermal filler in the lips

Hyaluronic acid (HA)‐based injectable fillers three‐dimensionally restore the natural contours of the lips and perioral area, thereby reducing some signs of aging lips. To evaluate the short‐term aesthetic impact of treatment with the HA dermal filler Juvéderm^® VOLBELLA^® with Lidocaine, formulated utilizing VYCROSS^? technology, for enhancement or correction of asymmetry of the lips, evaluated using a patient‐centric approach. Sixty‐two subjects were enrolled in this study, conducted at two sites in Germany. Primary endpoints were satisfaction with improvement, look and feel of the lips, assessed by subject and physician at first visit and 4 weeks post‐treatment. Immediately after injection at first visit, 83.6% of subjects were Extremely Satisfied, Very Satisfied or Satisfied with improvement in the lips, which increased to 94.1% and 93.0% of subjects with/without top‐up treatment at follow‐up, respectively. After injection at first visit, 61.7% of subjects rated the look and feel of their lips as Extremely Natural or Very Natural, which increased to 75.0% and 93.0% of subjects with/without top‐up treatment, respectively. The HA dermal filler was associated with minimal discomfort, bruising or swelling of the lips; almost two‐thirds of subjects (62%) returned to social engagements on the same day. The high degree of subject satisfaction with aesthetic improvement in the lips, as well as the natural look and feel, indicates that this HA dermal filler represents an effective treatment option for patients requiring lip enhancement.     

Skin microbiome and acne vulgaris: Staphylococcus,a new actor in acne

Propionibacterium acnes (P. acnes), the sebaceous gland and follicular keratinocytes are considered the three actors involved in the development of acne. This exploratory study investigated the characteristics of the skin microbiota in subjects with acne and determined microbiota changes after 28 days of application of erythromycin 4% or a dermocosmetic. Skin microbiota were collected under axenic conditions from comedones, papulo‐pustular lesions and non‐lesional skin areas from subjects with mild to moderate acne according to the GEA grading using swabs. Samples were characterized using a high‐throughput sequencing approach that targets a portion of the bacterial 16S rRNA gene. Overall, microbiota samples from 26 subjects showed an overabundance of Proteobacteria and Firmicutes and an under‐representation of Actinobacteria. Staphylococci were more abundant on the surface of comedones, papules and pustules (P=.004 and P=.003 respectively) than on non‐lesional skin. Their proportions increased significantly with acne severity (P<.05 between GEA‐2 and GEA‐3). Propionibacteria represented less than 2% of the bacteria on the skin surface. At Day 28, only the number of Actinobacteria had decreased with erythromycin while the dermocosmetic decreased also the number of Staphylococci. A significant reduction (P<.05) from Day 0 of comedones, papules and pustules with no significant difference between the products was observed. The bacterial diversity on all sampling areas was similar. The dermocosmetic decreased the number of Actinobacteria and Staphylococcus spp. after 28 days. Staphylococcus remained the predominant genus of the superficial skin microbiota. No significant reduction in Staphylococcus spp. was observed with the topical antibiotic.     

Two cases of cutaneous gnathostomiasis after eating raw Salangichthys microdon (icefish,shirauo)

Cutaneous gnathostomiasis (CG) is a disease caused by ingestion of third‐stage Gnathostoma larva in raw snakes, freshwater fish or frogs. The common causative organisms of CG in Japan include G. nipponicum, G. spinigerum, G. doloresi, G. binucleatum and G. hispidum. We report two cases of CG after eating many raw Japanese icefishes (Salangichthys microdon). In both cases, linear itchy eruptions on the trunk developed after eating many S. microdon. We performed genetic analysis in the first case, which revealed G. nipponicum. Of note, this is the first case of CG diagnosed based on genetic analysis in Japan. In Japan, eating whole small raw freshwater fish is common. The most popular types of raw small freshwater fish consumed in Japan are S. microdon (shirauo in Japanese) and Leucopsarion petersii (shirouo in Japanese). Usually, S. microdon are born in rivers, but live in both the sea and rivers. They feed on small fish and freshwater water fleas and spawn in rivers in the spring. On the other hand, L. petersii are born in rivers, but move to the sea soon after hatching. They feed on plankton such as copepod in the sea. They do not feed on anything when they return to rivers to spawn in the spring. Therefore, we hypothesize that S. microdon are more easily parasitized by G. nipponicum.     

Melanoma mimicking Rosai‐Dorfman disease

Despite well‐defined clinical and histopathological features of melanoma, atypical presentations mimicking other skin disorders can result in a delayed diagnosis or misdiagnosis and subsequent inappropriate treatment. Rosai‐Dorfman disease (RDD) is a rare histiocytic disorder with unique clinical and histopathological features. We report a case of melanoma treated with cryotherapy that mimicked RDD both clinically and histopathologically. We compare this RDD‐like melanoma to classic RDD, outlining the importance of clinicopathological correlation prior to treatment, as well as the potential pitfalls in diagnosis after cryotherapy of pigmented lesions.