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Pruritic papular eruption is a dermatosis characterized by pruritic symptoms in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Similarly, nodular prurigo is an itchy dermatosis with lesions and histopathological features that resemble those of pruritic papular eruption. Both conditions share a common etiopathogenesis, which involves the cytokines produced by T helper 2 (Th2) cells. Nodular prurigo and pruritic papular eruption are chronic and frequently recalcitrant, thus posing challenges in treatment. The use of biological agents represents a treatment development for chronic and recalcitrant dermatoses. This study aimed to determine the difference in the mean percentage of interleukin-4 (IL-4) and interleukin-5 (IL-5) expressions between nodular prurigo and pruritic papular eruption lesions, which may establish a basis for further biological agent therapy. A cross-sectional study was conducted using paraffin block preparations of the skin lesions of patients diagnosed with nodular prurigo (n=16) and pruritic papular eruption (n=16). Each paraffin block preparation involved immunohistochemical staining using IL-4 and IL-5 monoclonal antibodies. The expressions of IL-4 and IL-5 were assessed through ImageJ for Windows, version 1.53 (National Institutes of Health and the Laboratory for Optical and Computational Instrumentation, University of Wisconsin, USA) by pathologists. The data were analyzed using an unpaired t-test with a significance level of p<0.05. The analytical results indicated that data on the average age of the two groups, disease duration, and storage sample duration followed a normal distribution (p>0.05). The mean percentage of IL-4 expression was significantly different between the nodular prurigo and pruritic papular eruption groups (p=0.000). However, the mean percentage of IL-5 expression was not significantly different between the two groups (p=0.060). In conclusion, the expression of IL-4 was higher in the nodular prurigo group in comparison to the pruritic papular eruption group. Nonetheless, the expression of IL-5 was comparably high in both the nodular prurigo and pruritic papular eruption groups. [ABSTRACT FROM AUTHOR]

Genodermatoses are diseases with significant psychosocial impact despite being relatively rare conditions, with a reported incidence that varies between 1:6000 and 1:500,000 [1] and is continually increasing, most likely due to the development of more effective diagnostic methods. Severity of the clinical expression of the genetic defects responsible for the occurrence of genodermatoses varies widely, with some cases taking the form of serious diseases that cause significant alteration of patients' quality of life, as well as that of their families, and also reduce the patients' life expectancy. Given the fact that genodermatoses are chronic, incurable diseases that are frequently associated with incapacitating disabilities and even with malignant degeneration potential, their management requires collaboration among members of a multidisciplinary team and a complex therapeutic regimen, which also demands considerable resources. Therefore, taking into account all these considerations, genodermatoses represent important public health issues. In the current paper we present the results of a prospective and retrospective study conducted between 2013 and 2023 on a number of 253 newly diagnosed patients with various clinical forms of genodermatoses, admitted to Dermatology departments in Bucharest. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a skin disorder caused by the dysfunction of a multitude of genetic components. This paper reviewed three main genetic factors leading to the pathogenesis of atopic dermatitis including: the epidermal barrier, the body's immune system, and the filaggrin protein. [ABSTRACT FROM AUTHOR]

Background. Genodermatoses are rare heterogeneous genetic skin diseases with multiorgan involvement. They severely impair an individual's well-being and can also lead to early death. Methods. During the progress of this review, we have implemented a targeted research approach, diligently choosing the most relevant and exemplary articles within the subject matter. Our method entailed a systematic exploration of the scientific literature to ensure a comprehensive and accurate compilation of the available sources. Results. Among genodermatoses, X-linked ones are of particular importance and should always be considered when pediatric males are affected. Regardless of other syndromic forms without prevalence of skin symptoms, X-linked genodermatoses can be classified in three main groups: keratinization defects, pigmentation defects, and inflammatory skin diseases. Typical examples are dyskeratosis congenita, keratosis follicularis spinulosa decalvans, hypohidrotic ectodermal dysplasia, chondrodysplasia punctata, hypohidrotic ectodermal dysplasia, incontinentia pigmenti, chronic granulomatous disease, CHILD syndrome and ichthyosis. In this field, genetic diagnosis of the specific disease is important, also considering that numerous clinical trials of orphan drugs and genetic therapies are being proposed for these rare genetic diseases. Conclusions. Thus, this chapter starts from clinical to molecular testing and ends with a review of all clinical trials on orphan drugs and gene therapy for genodermatoses. [ABSTRACT FROM AUTHOR]

Ectoparasite infestations are one of the most important but neglected diseases of birds. Ectoparasites cause sirious harmful effects such as; irritation, feathers and skin damage, restlessness, anemia, weight loss, transmission of other pathogens, reducing overall fitness and decreasing long term survival depending on the intensity of the infestation. This study was performed to investigate the ectoparasites of budgerigars and canaries in the center district of Burdur city, Turkey. For this purpose, we randomly selected 555 budgies from 192 cages and 121 canaries from 49 cages owned by 12 different breeders. The feathers of head, neck, abdomen, legs, tail, beak, under the wings, around the cloaca and feet of all birds, in addition cages and cage equipments were examined in terms of ectoparasite infestations. As a result; no ectoparasite species were found on/between feathers and other body parts of overall 676 cage birds, however, a large number of Dermanyssus gallinae were found in cages and cage equipments. Dermanyssus gallinae detected in rates of 28.65% and 28.57% in budgerigar and canary cages, respectively. The present study is the first investigation on ectoparasites of budgerigar and canaries in Turkey and rarely in the world. In addition, within this study, D. gallinae infestation was reported for the first time from budgerigar and canaries from Turkey. [ABSTRACT FROM AUTHOR]

Objective: Familial Mediterranean fever (FMF) is the most common genetic autoinflammatory disease presenting as recurrent fever episodes, and inflammation of serosal surfaces, joints, and skin. During attacks, erysipelas-like erythema (ELE) may occur on the dorsum of the foot, ankle, or lower leg. Although the skin involvement is less common, ELE is pathognomonic. We aimed to review the frequency and characteristics of ELE in children diagnosed with FMF and to identify genotypic and phenotypic differences between patients with and without ELE, if any. Methods: This study included children aged 0-18 years diagnosed with FMF followed up by two tertiary pediatric rheumatology units. The data were collected by two pediatric rheumatology fellows from the patients' files and electronic records. We divided the cohort into two groups according to whether they had ELE. Those with ELE were included in group 1 and those without ELE were in group 2. Results: Two thousand-three patients participated in the study. There were 197 (9.8%) patients with ELE in group 1 and 1806 (90.1%) patients without ELE in group 2. The mean age of onset of symptoms in group 1 was significantly lower than in group 2 [4.85 (minimum-maximum: 0.1-17) vs. 5.98 (minimum-maximum: 0.1-17) years, p<0.001]. The median age at diagnosis was significantly higher in group 1 [8 (0.6-18) vs. 6 (0.5-18) p<0.001]. The diagnostic delay time was 24 months in group 1, 13 months in group 2, and the duration was significantly longer in group 1 [24 (0-150) vs. 13 (0-192) p<0.001]. M694V homozygosity was more frequent in group 1 [n=116 (58.9%), n=484 (26.8%), p<0.001]. Conclusion: Because ELE is an uncommon clinical presentation, clinicians should be alert. The clinical course of patients presenting with ELE may have a more severe disease course. [ABSTRACT FROM AUTHOR]

Trace elements (microminerals) play a role in many physiological functions, including hormone production and cellular growth. However, their importance in diagnosing and treating dermatologic disease has not been well examined. In this review, we discuss the functions, sources, and recommended requirements of each micromineral. In addition, we analyze the systemic and dermatologic manifestations associated with micromineral imbalances. The pathogenesis of genodermatoses, such as Wilson disease, Menkes disease, acrodermatitis enteropathica, and allergic dermatitis, are also discussed. Included are studies examining the potential therapeutic role of zinc, selenium, and copper in inflammatory diseases, skin cancer, and photoaging. [ABSTRACT FROM AUTHOR]

Angioma serpiginosum (AS) is a rare, benign, nevoid vascular anomaly that usually starts in childhood or early adolescence with a predilection for extremities and spares mucosal areas. The blaschkolinear variant of this condition has rarely been described in the literature. We report a case of AS in a unique blaschkolinear configuration and discuss the dermoscopic differentials for dermatoses with similar presentation. [ABSTRACT FROM AUTHOR]

Collodion baby is usually a manifestation of autosomal recessive congenital ichthyosis, a heterogeneous group of congenital hyperkeratotic genodermatoses with highly variable severity and genetic background. Herein, we report a case of selfimproving collodion ichthyosis, a rare subtype of autosomal recessive congenital ichthyosis, characterized by an almost-complete spontaneous resolution of symptoms. [ABSTRACT FROM AUTHOR]

Le syndrome du canal carpien est rare chez l'enfant. Nous avons réalisé une étude rétrospective chez 10 enfants. L'objectif est de montrer qu'il s'agit d'un diagnostic ardu et de rapporter nos résultats après chirurgie. Nous avons identifié tous les enfants ayant eu une compression du nerf médian au niveau du canal carpien entre 2010 et 2020, pris en charge dans notre service. Dix enfants ont été inclus soit 20 mains. Cinq enfants avaient une maladie métabolique, 4 canaux carpiens étaient d'origine idiopathique, un enfant avait une génodermatose, un autre un syndrome de Byler et le dernier était atteint du syndrome de VACTERL. Les principaux symptômes étaient la douleur (5 patients), la sous-utilisation des doigts (5 patients). Deux enfants avaient un déficit de l'opposition du pouce. L'âge moyen au diagnostic était de 4 ans et 7 mois. Nous avons opéré 19 mains. Un enfant soit deux mains ont eu une réanimation de l'opposition du pouce à l'aide d'un transfert du fléchisseur commun superficiel du 4e rayon. Tous les enfants ont eu une régression complète des douleurs, une amélioration de l'utilisation des doigts et une récupération de l'opposition du pouce. Le syndrome du canal carpien est de diagnostic complexe chez l'enfant. Il n'est pas rare d'être confronté à des symptômes évolués. Les symptômes atypiques peuvent retarder le diagnostic. En raison de la qualité des résultats cliniques obtenus, nous recommandons une neurolyse du nerf médian à ciel ouvert – y compris lorsque le diagnostic semble retardé. IV. The carpal tunnel syndrome is rare in children. We performed a retrospective study of 10 children. The aim is to show that the diagnosis of carpal tunnel syndrome is difficult in children. We identified all children with median nerve compression in the carpal tunnel between 2010 at 2020, managed in our service. Ten children with 20 hands included. There was different etiologies of carpal tunnel syndrome: 5 lysosomal storage diseases, 4 idiopathic carpal tunnel syndrome, 1 genodermatose, 1 Byler syndrome and 1 VACTERL syndrome. Common presenting symptoms were pain (five patients) and under use of fingers (five patients). Two children had opposition deficit of the thumb. We operated 19 hands. Median age at diagnosis was 4 years and 7 months. One children or 2 hands had a reanimation of opposition by tendinous transfer of flexor digitorum superficialis tendon of the ring finger. All children had a complete regression of the painful symptoms, a use improvement of fingers and recovery of the opposition of the thumb. The diagnosis of carpal tunnel syndrome is difficult in children. It is common to be confronted with an advanced clinical symptoms. The atypical symptoms may cause diagnostic delay. Due to the quality of the clinical results obtained, we recommend open carpal tunnel release even when the diagnosis seems delayed. IV. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we analyzed the whole exomes of CTSC gene in a family with history of PLS. Materials and methods: Genomic DNA was extracted from peripheral blood and genotype analysis was performed. The mutated protein sequence was used to find the best possible tertiary structure for homology modeling. The homology modeling of the novel mutation was then performed using the online Swiss‐Prot server. The results were also analyzed for to verify its validity. Results: The analysis of CTSC gene elucidated a novel insertion GAC. The novel mutation was proved by analyzing 50 healthy control volunteers. Modeling of the novel found mutation in CTSC gene revealed structural defects that may have caused the functional abnormalities. Conclusions: The structural analysis of the mutated protein model identifies changes in the stereo‐chemical and the energy level of the mutated protein. Since this protein play a role in the activation of granule serine proteases from cytotoxic T lymphocytes, natural killer cells, mast cells, such structural defects may lead to its malfunction causing dysfunctioning of immune defense mechanisms. [ABSTRACT FROM AUTHOR]

Dowling-degos disease (DDD) is a rare genodermatose inherited as autosomal dominant trait characterized by brown to black macules located symmetrically in flexural sites. Lesions are not congenital, and the age of onset is highly variable. It is more common in women. Herein, we present the case of a male patient whose clinical and histopathological findings are consistent with DDD and then review existing literature. A 35-year-old male patient presented to the dermatology clinic with black lesions in his flexural sites since childhood. He had no subjective symptoms such as itching or pain in his symmetrically located lesions. His mother and cousins had similar lesions. On the histopathological examination of the lesion sample taken from the inguinal region, fine filiform branchings were found in the epidermis, the rete ridges showed tendency to merge, and there was budding in the rete ridges, which showed hyperpigmentation. The adjacent epidermis showed keratin cysts and mild perivascular mononuclear inflammatory cell infiltration in the superficial dermis. Based on these histopathological findings, the diagnosis was DDD. Fractional erbium YAG laser yielded good clinical outcome. DDD should be kept in mind in the differential diagnosis of hyperpigmented lesions in flexural sites. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify the pattern of pediatric dermatoses of patients evaluated at a dermatologic clinic of a reference center in Brazil and to compare these results to similar surveys conducted in other countries. Methods: A retrospective study was performed of patients up to 18 years old, evaluated at a dermatologic clinic between January 1, 2017 and December 31, 2017. Variables collected for analysis included age, gender, dermatological diagnosis, multidisciplinary follow-up, hospitalization, and complementary exams. Results: A total of 2330 patients were included for analysis, with a mean age of 9.7 years. 295 patients were diagnosed with more than one skin disease, leading to a total of 2668 diagnoses. Skin diseases were organized into categories and inflammatory dermatoses corresponded to the largest group (31.2%), mostly due to atopic dermatitis (18.3%). The other main categories were: genodermatoses (14.2%), infectious diseases (12.6%), adnexal disorders (12.5%), cysts and neoplasms (10.7%), and vascular disorders (7.0%). Fifty-six patients needed to be admitted to the dermatology ward; 25 of them (44.6%) for management of worsening of the skin disease, mainly atopic dermatitis, psoriasis, and drug reactions. There were 885 biopsies performed in 38.0% of the subjects and 751 patients (32.2%) required multidisciplinary care; most of them had some genodermatoses. Conclusions: Dermatologic disorders are very common in the pediatric age group and differ from those in adults, suffering influence from cultural, ethnic, socioeconomic, and environmental factors. Knowing the magnitude and distribution of these dermatoses is important to better plan healthcare policies. [ABSTRACT FROM AUTHOR]

Epidermodysplasia verruciformis is a rare genodermatosis associated with mutations in the EVER1/TMC6 and EVER2/TMC8 genes. The inheritance is considered to be autosomal recessive, but reports suggesting an autosomal dominant inheritance indicate disease genetic heterogeneity. Its onset occurs in early childhood and presents as a combination of pityriasis versicolor-like, flat wart-like and seborrheic keratosis-like lesions, with a potential for malignant transformation, mainly squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Lupus erythematosus (LE) is an autoimmune disease with a strong influence of genetic and environmental factors. C-C motif chemokine receptor 5 (CCR5) gene expression may affect the development and intensity of LE. Aim: To evaluate the possible association between the 32bp deletion in rs333 locus located within the CCR5 gene and the development of LE or the occurrence of various clinical symptoms in the course of the disease. Material and methods: One hundred and twenty patients with LE (77 with systemic lupus erythematosus (SLE) and 43 with discoid lupus erythematosus (DLE)) and 100 healthy controls from the Polish population were genotyped for deletion in rs333. Results: 32 bp deletion in the rs333 was significantly more frequent among healthy individuals than DLE patients. Moreover, heterozygotes and homozygotes with deletion in rs333 were significantly more frequent within the control group than the group of patients with discoid lupus erythematosus. In contrast, any statistically significant differences in allele or genotype frequencies between healthy persons and SLE patients were observed. Furthermore, nucleotide sequence variability of rs333 was not associated with certain clinical symptoms of LE patients. Conclusions: Deletion in the rs333 might be a protective factor for DLE, but not SLE in the Polish population. Nevertheless further studies performed on larger populations are needed to confirm these observations. [ABSTRACT FROM AUTHOR]

Introduction: Single nucleotide polymorphisms (SNPs) of the HLA-C and ERAP1 genes were recently determined to contribute to psoriasis susceptibility. However, data regarding the association of these genes with specific subgroups of psoriasis are scarce. Aim: To examine the possible association of the HLA-C and ERAP-1 polymorphisms with early and late onset psoriasis and psoriatic arthritis. Material and methods: Five ERAP1 SNPs and two HLA-C SNPs were genotyped in 105 psoriatic arthritis patients, 214 cutaneous psoriasis patients and 200 healthy individuals. Haplotypes were constructed for three ERAP1 SNPs (rs17482078, rs10050860, rs30187), and interaction between HLA-Cw*0602 and ERAP1 was also analysed. Results: The HLA-Cw*0602 rs10484554 SNP was found to be a strong susceptibility factor for early onset cutaneous psoriasis and early onset psoriatic arthritis. ERAP1 SNPs (rs10050860, rs17482078, rs27525) appear to have a protective function for early onset psoriatic arthritis. The haplotype B was identified as a susceptibility factor for late onset psoriatic arthritis. In HLA-C positive individuals the rs27524 ERAP1 SNP was associated with a significantly increased risk of psoriatic arthritis development, whereas the rs27525 ERAP1 SNP had the opposite effect. Conclusions: These results suggest that the HLA-C and ERAP1 genes contribute to the pathogenesis of psoriasis and psoriatic arthritis in an age-dependent manner. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. AD affects 10--20% of children worldwide and persists into adulthood in a minority of cases, affecting approximately 2--3% of the adult population, with an increased prevalence over the past decades in developed countries. Atopy is a genetic tendency to overproduce IgE class antibodies in response to common antigens found in the environment. Concurrence of different atopy such as allergic rhinitis or asthma in children with AD is estimated at 80%. AD is characterized by a vicious cycle of an allergic immune response. The emerging picture of the AD is a complex disorder with barrier dysfunction, immunological, genetic and environmental factors all playing key roles. Patients with severe or persistent disease and their families experience significant impairment in their quality of life, and in addition, AD places a heavy economic burden on society as a whole. Pathogenesis, the role of the epidermal barrier, mechanisms of cells apoptosis, the role of T cells and cytokines in AD are discussed in this article. [ABSTRACT FROM AUTHOR]

Introduction: Actinic keratosis (AK) is a skin condition arising from chronic exposure to ultraviolet light and may lead to the development of malignancies. This trial aimed to evaluate efficacy and safety of ingenol disoxate gel (IngDsx, 0.018% for face/chest [FC]; 0.037% for scalp [S]), versus vehicle. Methods: Four identical phase 3 trials in patients with AK on the full face/up to 250cm2 of chest or full balding scalp, with an initial 8-week period and 12-month follow-up, were conducted. FC and S trials were pooled for analysis. The primary endpoint was complete clearance at Week 8. Results: Across trials, 616 patients were randomized to FC and 626 to S, with 410 and 420 assigned to receive IngDsx, respectively. In the FC and S trials, 25.9% and 24.5% of patients in the IngDsx group, respectively, achieved the primary endpoint. IngDsx was relatively well tolerated. During extended follow-up, there were more identified non-melanoma skin malignancies in the IngDsx group than vehicle group; HR: 2.38 (95% CI: 1.28, 4.41). Conclusion: Treatment with IngDsx was superior to vehicle on all clinical endpoints, patient-reported and cosmetic outcomes. During the 12-month follow-up, slightly increased skin malignancies in the treatment area were identified, potentially due to unintentional detection bias. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic disease affecting 10–30% of children and 2–10% of adults worldwide. It is manifested by the pruritus eczema lesions on the skin. Immune thrombocytopenic purpura (ITP) is the most common cause of acute onset of thrombocytopenia in childhood. The aim of this study was association of primary immune thrombocytopenic purpura and atopia among children. This case control study was performed on patients with acute and chronic ITP who were confirmed by a hematologist. The control group was also selected from the siblings of the patients who were healthy and almost matched by age and sex with the patient group. Data were entered into a questionnaire under the SPSS-20 program, and demographic data were analyzed descriptively. In the present study, 120 patients were enrolled, 60 of whom were in the patient group and 60 in the control group. Mean age was 95 and 98 months for patients and control. This study showed a significant association of ITP with allergic rhinitis (P = 0.02), atopic dermatitis (P = 0.004), itching (P = 0.042), and dry skin (P = 0.015). However, no significant relationship was found between ITP and asthma (P-value = 0.18). This study does not reveal the causality between atopy and ITP but clearly shows the association between atopy and ITP disease, so the prevalence of atopy in ITP patients is higher than the normal population. According to the results of this study, it is necessary to investigate the cause of atopy and ITP and to find other immunological and possibly genetic commonalities. [ABSTRACT FROM AUTHOR]

Epidermodysplasia verruciformis (EV) is a genodermatosis related to human beta-papillomavirus (beta-HPV), with a high risk of cutaneous squamous cell carcinoma (cSCC). Claudins are transmembrane proteins expressed in epithelia and may be altered during carcinogenesis. For a better understanding of the role of beta-HPV in cutaneous carcinogenesis, this claudin expression study was conducted on lesions of patients with and without EV. In this study, claudins-1, -2, -3, -4, -5, -7 and -11 expressions were analyzed by applying the immunohistochemistry technique, in samples of 108 normal skin, 39 flat warts and 174 cSCC. The cSCC samples were organized in tissue microarrays. We found that claudin-1 and claudin-3 focal expressions were associated with cSCC (p < 0.001), and claudin-2 focal or negative expression with flat wart (p < 0.001), in EV and NEV (non-EV) groups. For claudin-5, EV group showed a lower chance of focal and negative expression (p < 0.001), and its negative expression was associated with flat wart (p < 0.001) and lower mean age (p < 0.001). Claudins-4, -7 and -11 showed a diffuse expression in almost all studied samples. Our findings suggest that claudin-5 increased expression observed on normal skin, flat wart and cSCC showed association with EV. Claudin-1 and -3 down expression were also observed, but they could not be related to beta-HPV infection. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis is a chronic inflammatory skin disease with a strong genetic basis. Recent GWASs have identified a single nucleotide polymorphism on chromosome 11q13.5 (rs7927894) as novel susceptibility loci of atopic dermatitis. Aim: To evaluate the association of this genetic variant with atopic dermatitis and to investigate its possible interaction with filaggrin null mutations in children population. Material and methods: One hundred eighty-eight children less than 2 years old were screened for the variant of allele of rs7927894 on chromosome 11q13.5 and for the 4 most prevalent filaggrin mutations. The variant of allele of rs7927894 and all filaggrin mutations were genotyped by real-time PCR assays with subsequent melting curve analysis using SimpleProbe® probes. Results: The allele of rs7927894[T] was associated with a significantly increased risk of atopic dermatitis (OR = 2.21; 95% CI: 1.14-4.28; p = 0.015). Both allergic and non-allergic patient groups had rs7927894[T] allele significantly more frequently than the control group, however, the frequency of alleles did not differ in these two groups. Interestingly, when rs7927894 variant and filaggrin mutations were considered together, the risk of atopic dermatitis was the most increased in the subjects who combined both rs7927894[T] allele and filaggrin mutations (OR = 16.41; p = 0.003). Conclusions: Our results indicate that the rs7927894 variant on chromosome 11q13.5 may play a role in the development of atopic dermatitis, but this effect seems to be independent of allergic sensitization and of the wellestablished filaggrin risk alleles, but may be modulated by gene-gene interactions. [ABSTRACT FROM AUTHOR]

Background: Stimulator of interferon genes (STING)–associated vasculopathy with onset in infancy (SAVI) was first described in 2014 as a type I interferonopathy resulting from heterozygous mutations in the transmembrane protein 173 (TMEM173) gene. SAVI is characterized by the neonatal onset of systemic inflammation, severe cutaneous vasculopathy, and interstitial lung disease. Janus kinase inhibitors are considered effective therapeutics. We sought to describe 2 patients who were diagnosed with SAVI only at postmortem to increase awareness of this disorder. Methods: Clinical data were collected, and Sanger sequencing of the TMEM173 gene was performed in 2 patients suspected of SAVI. This article reviews details of these cases and lessons learned from clinical review and postmortem studies. Results: Two male children shared similar manifestations, including recurrent skin abscesses in winter, skin lesions, and recurrent respiratory tract infections, since birth. Computed tomography of the chest revealed pulmonary fibrosis, but no mutations in relevant genes (including ABCA3 and SFTPC) were discovered in patient 1 (P1). Joint pain was significant in P2 and he was diagnosed with arthritis. Antibiotic treatment yielded little improvement and did not prevent progression. Finally, P1 and P2 died of respiratory and circulatory failure in 2016 and 2012, respectively. In 2018, mutations (P1: c.463G>A, p.V155M; and P2: c.461A>G, p.N154S) in exon 5 of the TMEM173 gene were discovered, confirming the diagnosis of SAVI. Conclusions: The experience with these 2 patients suggests that SAVI should be considered in children with systemic inflammation, chilblain skin lesions, and pulmonary fibrosis, and TMEM173 gene analysis can be beneficial in the diagnosis of SAVI. [ABSTRACT FROM AUTHOR]

Atypical fibroxanthoma (AFX) is a rare cutaneous fibrohistiocytic tumor that typically arises on chronically sun-damaged skin, such as the head and neck, as a nondescript ulcerated papule, nodule, or tumor. The clinical prognosis is usually favorable and metastasis is rare. Pleomorphic dermal sarcoma (PDS), or undifferentiated pleomorphic sarcoma, is a recently introduced diagnostic moniker for AFX-like tumors with more aggressive clinical and histologic features such as necrosis and vascular invasion. The exact relationship between AFX and PDS has been debated. Diagnosis of these tumors is generally based on immunohistochemical staining to exclude other mimics. A wholly specific marker for this tumor does not exist, leading to diagnostic ambiguity in certain cases. Herein, we present a case of pleomorphic dermal sarcoma in a 53-yearold man with human immunodeficiency virus that displayed patchy S100 staining concerning for melanoma upon hospital pathology review. Nextgeneration sequencing analysis confirmed a mutation pattern consistent with published molecular signatures of AFX/PDS. In discussing this case, we review the current understanding of AFX/PDS and discuss diagnostic pitfalls, as well as emphasize on how next-generation sequencing techniques might improve accuracy in the diagnosis of tumors in the spectrum of AFX/PDS. [ABSTRACT FROM AUTHOR]

Immunodeficiency is most commonly related to inherited syndromes, infections, chemotherapy, or aging. As the population of individuals with immunodeficiency continues to grow, physicians are confronted with the task of diagnosing dermatologic disease in this population. Cutaneous involvement in immunodeficiency disorders serves as a useful tool that aids diagnosis and provides prognostic value. Given that cutaneous manifestations often herald an underlying immunodeficiency disorder, understanding the complexities of these diseases is important for appropriate clinical management. Although certain diseases may present with stereotypical cutaneous lesions, others may involve more variable lesions that require specialized consultation for diagnosis and treatment recommendations. In this review, we discuss a number of cutaneous findings associated with primary immunodeficiencies. Awareness of these cutaneous associations may aid in the early detection and prompt treatment of these potentially serious immunologic disorders. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Netherton syndrome (NS) is a rare and debilitating severe autosomal recessive genetic skin disease with high mortality rates particularly in neonates. NS is caused by loss-of-function SPINK5 mutations leading to unregulated kallikrein 5 (KLK5) and kallikrein 7 (KLK7) activity. Furthermore, KLK5 inhibition has been proposed as a potential therapeutic treatment for NS. Identification of potent and selective KLK5 inhibitors would enable further exploration of the disease biology and could ultimately lead to a treatment for NS. This publication describes how fragmentation of known trypsin-like serine protease (TLSP) inhibitors resulted in the identification of a series of phenolic amidine-based KLK5 inhibitors 1. X-ray crystallography was used to find alternatives to the phenol interaction leading to identification of carbonyl analogues such as lactam 13 and benzimidazole 15. These reversible inhibitors, with selectivity over KLK1 (10–100 fold), provided novel starting points for the guided growth towards suitable tool molecules for the exploration of KLK5 biology. [ABSTRACT FROM AUTHOR]

Collagenous and elastotic marginal plaques of the hand (CEMPH) is a rare, chronic keratoderma characterized by hyperkeratotic linear plaques located along the radial and ulnar aspects of the hands bilaterally. As an isolated finding, CEMPH occurs secondarily to chronic trauma and photodamage. Herein, CEMPH is described as a manifestation of alkaptonuria (AKU). In addition to keloidal collagen, ochronotic fibers and fragmented, thickened elastic fibers were observed. Additionally, mucin deposition—not previously described in this clinical context—was also identified. Given their overlapping clinicopathologic features, CEMPH due to AKU should be distinguished from the acquired variant as well as acrokeratoelastoidosis. [ABSTRACT FROM AUTHOR]

Background: 11β HSD1 generates cortisol from cortisone. 11β HSD1 single-nucleotide polymorphism (SNP) was associated with metabolic syndrome (MeTS). Although the relation of acne vulgaris (AV) and skin tags (STs) with MeTS has been reported, the relationship between 11β HSD 1 SNP and cortisol activity in those patients has not studied till now. Aims: To investigate, two 11β-HSD1 SNPs (rs846910 and rs12086634), serum lipid profile and cortisol levels in patients with AV and STs in an Egyptian population. Patients and methods: This case–control study was performed on 50 patients having STs and 50 complaining of AV and 50 sex- and age-matched controls. We searched for serum lipid profile, cortisol levels, and 11β-HSD1 rs846910 and rs12086634 SNPs using real time-PCR. Results: Compared to controls,11β-HSD1 rs846910 GA genotype carriers had significantly higher risks for developing AV and STs by 3.4- and 4.9-fold, respectively, and its A allele increases these risks by 3.1 and 4.4 times, respectively. Also, 11β-HSD1 rs12086634 TG genotype increases the risk of AV by 3.2-fold, as well as STs by 3.5-fold, and its G allele increases the risk of AV by 3.2-fold and STs by 7-fold. In AV and ST patients, rs846910 GA genotype demonstrated significant associations with elevated body mass index (BMI), and cholesterol, low density lipoprotein (LDL), cortisol, and decreased high density lipoprotein serum levels, respectively. However, rs12086634 GG genotype was significantly associated with increased BMI, cholesterol, and LDL serum levels in patients with AV and STs, in addition to the number of STs and serum cortisol levels in ST patients. Conclusion: 11β-HSD1 rs846910 and rs12086634 gene polymorphisms may contribute to AV and STs pathogenesis, that may be mediated through enhancing the enzymatic activity (increasing cortisol levels). AV and STs are associated with obesity and atherogenic lipid profile. Diagnosis of AV and STs may play a role in early detection of the MeTS. [ABSTRACT FROM AUTHOR]

Purpose: Congenital epidermolysis bullosa (CEB) is a group of rare monogenic genodermatoses. Phenotypically, the diseases vary in both severity and dissemination, which complicates studies of their epidemiology. To investigate the potential of using the Danish National Patient Registry (DNPR) for epidemiological research on CEB, we examined the positive predictive value (PPV) of a first-time diagnosis of CEB. Methods: We identified patients with a record of CEB in DNPR and the Danish Pathology Registry (DPR) during January 1, 1977, until December 31, 2015. We restricted diagnoses from two dermatological departments and one regional hospital. Diagnoses in the DNPR are coded by the eighth and tenth revisions of the ICD (ICD-8 and ICD-10) and in the DPR by the Systematized Nomenclature of Medicine (SNOMED). We used clinical description in medical records, family history, histological findings, and molecular genetic investigations to validate diagnoses and classified them as rejected and confirmed. We estimated PPVs for any diagnosis, according to coding systems used, and for additional subdivisions of ICD-10 codes. Results: We identified 116 cases from the hospital departments investigated and evaluated 96 medical records for validity. The overall PPV for probable CEB was 62.5% (95% CI: 52.5–71.5). For ICD-8, ICD-10, and SNOMED codes, the PPVs were 30.8% (95% CI: 11.4–57.7), 76.7% (95% CI: 65.8–84.9), and 0.0% (95% CI: 0.0–21.7), respectively. For the ICD-10 codes, we found the highest PPVs for diagnoses arising from the dermatological departments. For subdivisions of ICD-10 codes, PPVs were high for epidermolysis bullosa simplex and dystrophica. Conclusion: The PPVs for first-time diagnoses of CEB registered in the two Danish nationwide registries investigated, DNPR and DPR, ranged from low to average. We therefore recommend that these data be used with caution and restricted to ICD-10 diagnoses from specialized dermatological departments. [ABSTRACT FROM AUTHOR]

SHARPIN is an important component of the linear ubiquitin chain assembly complex (LUBAC). Loss of function of SHARPIN results in eosinophilic inflammation in multiple organs including skin with Th2‐dominant cytokines and dysregulated development of lymphoid tissues in mice. The clinicopathological features are similar to atopic dermatitis (AD) in humans. In order to investigate the potential role of SHARPIN in the pathogenesis of AD, we performed genetic association study of the genotypes and haplotypes as well as SHARPIN's expression between AD cases and controls. We found three mutations (g.480G>A, g.4576A>G and g.5070C>T) in patient group, and significantly decreased expression in AD lesions, suggesting a primary role of SHARPIN during AD development. Lentivirus‐mediated in vitro assays identified that knockdown of SHARPIN can induce elevated expression of IL‐33 and its orphan receptor ST2, FLG and STAT3 and NF‐κB inactivation in HaCaT keratinocytes, which has been widely evidenced in regulating AD development. ST2 expression was highly induced in SHARPIN‐silenced HaCaT keratinocytes after the combined stimulation of IL‐4 and IL‐13. Our in vivo and in vitro findings implicated that SHARPIN may be a novel participant in the pathogenesis and/or new therapeutic target of AD. SHARPIN is an important component of the LUBAC. Loss of function of SHARPIN can lead to inflammation. We found mutations of SHARPIN and significantly decreased expression in atopic dermatitis (AD) patients. Knockdown of SHARPIN can induce elevated expression of IL‐33 and ST2, FLG and STAT3 in HaCaT keratinocytes, suggesting a primary role of SHARPIN during AD development. [ABSTRACT FROM AUTHOR]

The article presents the case study of two patients suffering from multiple sulfatase (MSD) deficiency, also called Austin disease, caused by the rare similar mutation of their genes. The topics discussed include the manifestations and symptoms of MSD, results of their medical and laboratory examinations, and the medications given to treat MSD.

Abstract: The pharmacological modulation of collagen turnover is a strategy potentially useful in different skin conditions. The serine protease inhibitor Serpin A1 and portions of its C‐terminal region have been investigated as collagen modulators. To clarify the mechanisms by which the C‐terminal 409–418 peptide SA1‐III increases extracellular type I collagen levels, to compare its activities range with that of the originator molecule Serpin A1, and to evaluate its efficacy in primary cultures from adult and aged human subjects. The different forms of type I collagen were analyzed by means of western blot in cell lysates and cell‐conditioned media of primary human dermal fibroblasts obtained from subjects of different ages. Gelatin zymography was used to investigate the degrading enzymes. Cell viability and in vitro wound healing tests were used to evaluate cell proliferation. The SA1‐III peptide increased extracellular collagen levels by reducing degradation, with no effect on cellular biosynthesis or cell proliferation mechanisms. A reduced level of MMP‐2 and MMP‐9 was also found in cell media upon peptide treatment. No peptide effect was detected on inflammatory mediators gene expression in resting and LPS‐stimulated fibroblasts, or in the wound healing test. The SA1‐III peptide is a good collagen modulator candidate, protecting collagen against degradation without detectable actions on biosynthesis, acting at reasonably low concentrations, and non‐interfering with cell proliferation. It is effective in primary fibroblasts from young and aged subjects. These effects can prove useful in pathological and physiological skin conditions in which collagen degradation is excessive compared to the synthetic capacity. [ABSTRACT FROM AUTHOR]

Abstract: Bazex‐Dupré‐Christol syndrome is a rare genodermatosis that manifests with the classical triad of basal cell carcinoma, follicular atrophoderma, and hypotrichosis; yet it may be accompanied by milia, ichthyosis, neurological symptoms, and visceral malignancies. Symptom onset is nonsimultaneous, and hence the diagnosis is often made late and the opportunity of counseling and following up is missed. This article aims toward providing a comprehensive review of the clinical perspective of Bazex‐Dupré‐Christol syndrome, highlighting the major clinical variants to facilitate reaching a prompt diagnosis. In addition, the molecular aspects are discussed. Though the gene responsible for this syndrome is yet nonspecified, it is confirmed to be localized to the long arm of chromosome X. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Epidermodysplasia verruciformis (EV) is an extremely rare hereditary skin disease characterized by an abnormal susceptibility to the human papilloma virus (HPV) with an increased risk of cutaneous malignancy. Here we report the first female severe EV case in Bangladesh, a 10‐year‐old girl with a nonsense somatic mutation impacting ANKRD26 gene. [ABSTRACT FROM AUTHOR]

The article focuses on the study of epidermolysis bullosa (EB) that refers to the collection of genetically heterogeneous group of genodermatoses being characterized by blisters or erosion on skin. It mentions that EB is classified as epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis bullosa (DEB).

Immunotherapies targeting cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) and the programmed cell death 1 (PD‐1) receptor and its ligand (PD‐L1) have showed significant therapeutic benefit in patients with clinically advanced solid malignancies, including melanoma. However, immune‐related adverse events (irAE) are common, and novel dermatologic toxicities continue to emerge as more patients are treated with immunotherapy. Here we describe a patient treated with combination immunotherapy of ipilimumab and pembrolizumab, who developed asymptomatic erythematous patches on both legs. Histopathologic examination revealed a cutaneous interstitial granulomatous dermatitis. Notably, our patient did not require cessation of immunotherapy for these lesions, which subsequently remained stable, while the patient's melanoma remained controlled. This case expands the dermatologic toxicity profile of immune checkpoint blockade, as recognition of such toxicities is critical to optimal patient management. [ABSTRACT FROM AUTHOR]

Juvenile xanthogranuloma (JXG) is a non‐Langerhans cell histiocytosis (non‐LCH) affecting normolipemic infants and children most frequently in the first year of life, often showing spontaneous regression within 3 to 6 years. Classic JXG is characterized by a yellowish asymptomatic papule or nodule, often located in the skin of the head, neck and upper trunk. Oral JXG has been reported, but is rare. Histologically, JXG is composed mainly of an infiltrate of macrophages with a variable degree of lipidization (foamy macrophages), and (most of the time) scattered Touton‐type giant cells. Because of the rarity of oral lesions and possible variations in the clinical and histological presentation, the correct diagnosis can be challenging, requiring a careful clinical and histopathological evaluation with adjuvant immunohistochemical studies. Our review of the English‐language literature disclosed 33 cases of oral JXG, including this case report. The purpose of this study is to present a new case of this uncommon entity as well as to review and discuss its main clinicopathologic features and immunohistochemical findings. [ABSTRACT FROM AUTHOR]

Background: There are patients with recalcitrant psoriasiform plaques that do not fit into conventional categories of facial dermatoses. Our study aims to describe the clinicopathological characteristics of several patients with a unique presentation of persistent psoriasiform facial rashes. Methods: This retrospective cross‐sectional study analyzed clinical and histological data of known cases of recalcitrant psoriasiform dermatosis of the face diagnosed at National Skin Centre, Singapore, over 10 years. Results: There were 8 Chinese patients with mean age at onset of 29 years. Majority had pink to pink‐orange well‐defined plaques with dry scale (n = 6, 75%), distributed mostly on the cheeks (100%) and chin (n = 7, 88%). Hyperkeratosis, parakeratosis, preserved granular layer and psoriasiform hyperplasia were showed in all biopsies. Other common findings included subtle subcorneal acantholysis, “checkerboard” alternating ortho‐/parakeratosis, vacuolated keratinocytes and follicular plugging. All patients showed little treatment response. One patient eventually developed features of type II pityriasis rubra pilaris (PRP). Our study was limited by its small sample size and lack of a pre‐existing diagnostic code. Conclusions: This recalcitrant psoriasiform facial dermatosis seems to be a distinct entity, with consistent and reproducible clinical features and a PRP‐like histology, bearing some resemblance to the recently described condition—facial discoid dermatosis. [ABSTRACT FROM AUTHOR]

Abstract: Ganoderma lucidum is an edible medicinal mushroom known as “Lingzhi” in China and “Reishi or Manetake” in Japan. It is a highly prized vitality‐enhancing herb for more than 2000 years. G. lucidum polysaccharide (GLPS) has been identified as one of the major bioactive components and developed into a drug named “Ji 731 Injection” in China since 1973. The large‐scale production of the drug began in 1985 and approved by the Chinese FDA as “Polysaccharidum of G. lucidum Karst Injection” (Ling Bao Duo Tang Zhu She Ye) in 2000, which is applied intramuscularly. After more than forty years of clinical use, its efficacy, safety and long‐term tolerability have been recognized by neurologists. It is one of a few non‐hormonal drugs used for treating refractory myopathy. It is also used for combination therapy, which reduces the amount of glucocorticoid required for myopathy patient who is in remission. In addition, it reduces adverse reactions and improves the quality of life for cancer patients during chemotherapy. We found 81 qualified chemical, biochemical, preclinical and clinical studies of GLPS both in English and in Chinese spanning from 1973 to 2017 by searching CNKI (China National Knowledge Infrastructure), Wanfang database and PubMed. The molecular mechanisms underlying GLPS's antioxidant, anti‐tumour, immune‐modulatory, hypoglycaemic, hypolipidaemic and other activities are discussed. Both preclinical and clinical studies are either deliberated or indexed in the current article. We aimed at providing a molecular picture as well as a clinical basis to comprehend GLPS as one of few polysaccharide‐based modern medicines with complicated chemical and pharmacological properties that prevent it from entering the world's market. [ABSTRACT FROM AUTHOR]

Background: Melasma (facial dermatoses) is an acquired chronic disorder of hyperpigmentation over sun exposed parts and continues to be a therapeutic challenge due to the presence of melanin at varying depths in the epidermis and dermis, and many researchers are working hard to find a solution. The main culprit to remain is direct sun exposure, with other factors like drugs, genetic predisposition, thyroid abnormalities, pregnancy, phototoxic and photoallergic cosmetics. Melasma continues to have a remarkable impact on the well-being of affected patients causing deep psychological and social anguish, and with the expansion of cosmetic dermatology globally, treatments that are successful against skin diseases and boost beauty without prolonged recovery periods, or exposing patients to the risks of surgery, are increasingly recognised and acknowledged. Many clinicians have used various peeling in facial acne, scarring, and hyperpigmentations, and there have been no well-controlled studies comparing them with other conventional agents. Case presentation: a unique case of facial hyperpigmentation in a black female who presented seeking help which can be attributed to increased aesthetic awareness among people nowadays. A single session of black peel several passes was performed and the lady noted a lightening effect in the following weeks. Objective: The aim of this paper is to improve, advance and expand our understanding and the knowledge beyond what is already known to wider colleagues, to impact society at large and to disseminate the findings to wider audiences. Also, the objective of the present paper is to examine the different effect of black peel in the treatment of facial dermatoses, and it gives realistic tips on performing black peeling safely and effectively in ethnic skin groups. This is meant to shed light on some ways for clinical handling and improving our understanding scientifically and educationally. It is the first original case report of interest in the existing literature for the best of my knowledge that had a positive impact for my female patient. Method: A single pass of black peel was applied on the lady's face. Results: A pleasing brightening effect was examined and boosted the lady confidence. Conclusion: The patient had a positive pleasing experience that she had noticed from a single session application of the black peel. [ABSTRACT FROM AUTHOR]

Abstract: Hereditary palmoplantar keratodermas (PPKs) comprise a large and heterogeneous group of disorders characterized by persistent thickening of the epidermis at palmar and plantar surfaces. Clinical and genetic features of isolated and complex PPKs have been reviewed in part I of this 2‐part review. Here we focus on clinical and molecular classification of syndromic PPKs which are recognized by additional extracutaneous manifestations, in particular deafness, specific mucosal lesions, cardiomyopathy, inborn errors of metabolism, involvement of internal organs or disorders of sexual development. Other genetic diseases, which may show palmoplantar involvement, such as selected subtypes of hereditary epidermolysis bullosa, various hereditary ichthyoses and other keratinization disorders, several ectodermal dysplasias and some multisystem genetic disorders, are also briefly summarized. PPK diagnosis is based on inheritance pattern, age at onset, morphology, distribution and severity of hyperkeratosis, pattern of additional dermatological and systemic manifestations and laboratory findings. Molecular analysis is at present the gold standard to confirm the diagnosis in PPK forms due to mutations in known causative genes. No specific and curative therapy is currently available for PPKs which highly impair patients’ quality of life. Topical treatments are symptomatic and offer only temporary relief. Among systemic treatments, retinoids improve disease symptoms in the majority of patients. [ABSTRACT FROM AUTHOR]

Pityriasis rubra pilaris (PRP) is an idiopathic, papulosquamous inflammatory dermatosis. It is characterized by hyperkeratotic follicular papules coalescing into orange-red scaly plaques, islands of sparing, and palmoplantar keratoderma. PRP can be subdivided into six clinical subtypes according to Griffiths’ classification, based on age of onset, disease extent, prognosis, and other associated features. The sixth subtype of PRP occurs in individuals affected by HIV infection, and retroviral screening in all de novo cases of PRP is advised. Other reported associations include various infections, autoimmunity, drugs, and malignancies, although the true significance of these is still unclear. The genetic basis for familial cases, most commonly categorized under the fifth subtype, has been mapped to gain of function mutations in the caspase recruitment domain family, member 14 (CARD14) gene. Treatment of PRP remains a challenge to this day due to a paucity of high-quality evidence. Therapeutic regimens have been guided mostly by case reports and case series, with the mainstay of treatment being oral retinoids. Recently, biologics have emerged as a promising treatment for PRP. We present a review of the clinicopathologic features, pathogenesis, associated disorders, and treatment of PRP, with an emphasis and critical appraisal of the existing literature on the latter. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background and objective: Birt–Hogg–Dubé syndrome (BHDS) is a rare hereditary disease that presents with multiple lung cysts and pneumothorax (PTX). Although some reports propose that findings from chest computed tomography enable one to distinguish BHDS from primary spontaneous pneumothorax (PSP), it is still unclear whether clinical features are useful for identifying patients with suspicion of BHDS from those with PTX. Methods: We retrospectively reviewed the medical records of patients with PTX who underwent video‐assisted thoracoscopic surgery at Nissan Tamagawa Hospital from January 2012 to December 2015. Results: We identified a total of 1141 patients with PTX, including 54 with BHDS and 517 with PSP. Among them, logistic regression analysis segregated five features that were significantly associated with BHDS: familial history of PTX, past history of bilateral PTX, age at the first episode of PTX (≥25 years old (y.o.)), body mass index (≥18.5) and gender (female). We assigned scores of 3, 3, 2, 2 and 1 to the five features, respectively, to establish a system with a calculated score from 0 to 11. The cut‐off value of a calculated score ≥ 4 yielded the highest sensitivity of 93% and specificity of 86%. Receiver operating characteristic (ROC) analysis showed the area under the curve reflecting an accuracy of this diagnostic test as 0.953. Conclusion: BHDS has several clinical features distinct from PSP. Our scoring system consists of only five clinical variables that are easily evaluated and efficiently separate BHDS patients from those who have PTX without relying on an imaging study. Further prospective study is needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Chronic wounding as a result of recurrent skin blistering in the painful genetic skin disease epidermolysis bullosa, may lead to life-threatening infections, increased risk of tumor formation, and other serious medical complications. Therefore, epidermolysis bullosa patients have an urgent need for optimal wound care and tissue regeneration. Therapeutic strategies using gene-, protein-, and cell-therapies are being developed to improve clinical symptoms, and some of them have already been investigated in early clinical trials. The most favorable options of functional therapies include gene replacement, gene editing, RNA targeting, and harnessing natural gene therapy. This review describes the current progress of the different approaches targeting autologous skin cells, and will discuss the benefits and challenges of their application. [ABSTRACT FROM AUTHOR]

New Findings: What is the topic of this review? This review concerns current gene editing strategies for blistering skin diseases with respect to individual genetic constellations and distinct conditions. What advances does it highlight? Specificity and safety dominate the discussion of gene editing applications for gene therapy, where a number of tools are implemented. Recent developments in this rapidly progressing field pose further questions regarding which tool is best suited for each particular use. The current treatment of inherited blistering skin diseases, such as epidermolysis bullosa (EB), is largely restricted to wound care and pain management. More effective therapeutic strategies are urgently required, and targeting the genetic basis of these severe diseases is now within reach. Here, we describe current gene editing tools and their potential to correct gene function in monogenetic blistering skin diseases. We present the features of the most frequently used gene editing techniques, transcription activator‐like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein 9 (CRISPR/Cas9), determining their preferential application for specific genetic conditions, including the type of mutational inheritance, the targeting site within the gene or the possibility to target the mutation specifically. Both tools have traits beneficial in specific situations. Promising developments in the field engender gene editing as a potentially powerful therapeutic option for future clinical applications. [ABSTRACT FROM AUTHOR]

The article presents a study of the differences among skin microbiome depending on the level of urbanization in China, exploring whether the residential environments in five Chinese cities is linked with divergent microbial community assembly processes and heterogeneity among skin microbiomes. It compares the skin microbiomes of Chinese women living in Chinese cities using 16S ribosomal RNA (rRNA) gene amplicon sequencing, reporting higher prevalence of skin diseases in urban areas.

De novo monoallelic mutations in the GNB1 gene, encoding a β subunit of heterotrimeric G proteins, cause a newly recognized disorder with the typical clinical picture of severe developmental delay/intellectual disability, hypotonia and extrapyramidal symptoms. We describe another case of the condition with manifestations of cutaneous mastocytosis associated with a novel do novo mutation GNB1 NM_001282539.1 : c.230G > T; p.(Gly77Val). We also present the detailed clinical and etiopathogenetic discussion on previously diagnosed patients as well as suggestions for the link of the mutation with skin disease. [ABSTRACT FROM AUTHOR]

The galectin family comprises β-galactoside-binding proteins widely expressed in many organisms. There are at least 16 family members, which can be classified into three groups based on their carbohydrate-recognition domains. Pleiotropic functions of different galectins in physiological and pathological processes through extracellular or intracellular actions have been revealed. In the skin, galectins are expressed in a variety of cells, including keratinocytes, melanocytes, fibroblasts, dendritic cells, lymphocytes, macrophages and endothelial cells. Expression of specific galectins is reported to affect cell status, such as activation or death, and regulate the interaction between different cell types or between cells and the extracellular matrix. In vitro cellular studies, in vivo animal studies and studies of human clinical material have revealed the pathophysiologic roles of galectins in the skin. The pathogenesis of diverse non-malignant skin disorders, such as atopic dermatitis, psoriasis, contact dermatitis and wound healing, as well as skin cancers, such as melanoma, squamous cell carcinoma, basal cell carcinoma and cutaneous haematologic malignancy can be regulated by different galectins. Revelation of biological roles of galectins in skin may pave the way to future development of galectin-based therapeutic strategies for skin diseases. [ABSTRACT FROM AUTHOR]

Background/purpose Hailey-Hailey disease is a rare inherited acantholytic skin disorder characterized by heterogeneous clinical presentation. Its differential diagnosis might be wide, including other genodermatoses, inflammatory, and infectious skin diseases. Although histopathology remains as diagnostic gold standard, noninvasive techniques such as dermoscopy and reflectance confocal microscopy may assist clinical examination. Herein, we aim to further characterize the dermoscopic and reflectance confocal microscopic presentation of Hailey-Hailey disease with histologic correlation. Methods Eight patients with Hailey-Hailey disease were consecutively recruited. All patients were examined using dermoscopy and reflectance confocal microscopy. Results In all cases, dermoscopy enabled the visualization of polymorphous vessels, including glomerular and linear-looped vessels, within a pink-whitish background. Reflectance confocal microscopy revealed wide suprabasilar partial acantholysis and clefting, crusts, dilated papillae with tortuous vessels, and inflammatory cells. Dyskeratosis, uplocated papillae, and adnexal sparing were also observed. Conclusion Although definite diagnosis was obtained by histopathology in all cases, dermoscopy and reflectance confocal microscopy allowed the identification of common features (even in cases with dissimilar clinical presentation) that may support an early diagnosis of Hailey-Hailey disease, and its differentiation from other more frequent skin disorders. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic systemic inflammatory disease causing erythematosus and scaly skin plaques; up to 30% of patients with psoriasis develop Psoriatic Arthritis (PsA), which is characterised by inflammation and progressive damage of the peripheral joints and/or the spine and/or the entheses. The pathogenic mechanisms driving the skin disorder in psoriasis and the joint disease in PsA are sustained by the activation of inflammatory pathways that can be overlapping, but also, at least partially, distinct. Cytokines members of the IL-23/IL-17 family, critical in the development of autoimmunity, are abundantly expressed within the cutaneous lesions but also seem to be involved in chronic inflammation and damage of the synovium though, as it will be here discussed, not in all patients. In this review, we will focus on the state of the art of the molecular features of psoriatic skin and joints, focusing on the specific role of the IL-23/IL-17 pathway in each of these anatomical districts. We will then offer an overview of the approved and in-development biologics targeting this axis, emphasising how the availability of the “target” in the diseased tissues could provide a plausible explanation for the heterogeneous clinical efficacy of these drugs, thus opening future perspective of personalised therapies. [ABSTRACT FROM AUTHOR]