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VEXAS syndrome is an X-linked monogenic disease with adult-onset inflammatory disease and myeloid dysplasia, with clinical presentation ensuing in the fifth decade of life or later. Inflammatory symptoms associated with VEXAS syndrome are treated with several lines of therapy, eventually requiring allogeneic hematopoietic cell transplantation (allo-HCT). No evidence from randomized controlled trials exists on allo-HCT versus other treatments in patients not responding to front-line therapy(ies). We show results of a systematic review/meta-analysis (SR/MA) following a search using EMBASE, PUBMED/MEDLINE and Web of Science on April 5, 2024. We extracted outcomes based on benefits (overall response rate (ORR), complete remission (CR), event-free survival (EFS) and overall survival (OS), and harms (non-relapse mortality (NRM) and acute and chronic graft-versus-host disease (GVHD)). The search identified 88 studies. Four studies (39 patients) met inclusion criteria. Median follow-up time after allo-HCT ranged from 8 to 18.5 months. Pooled EFS and OS rates were 56% and 86%, respectively. Pertaining to harms, pooled NRM rate was 14%. Pooled rates of acute and chronic GVHD were 42% and 13%, respectively. Allo-HCT is an effective treatment for VEXAS syndrome. We hope these results would increase awareness about this underdiagnosed and underreported disease., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

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 compre-hensive 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.

Genodermatoses are a complex and heterogeneous group of genetic skin disorders characterized by variable expression and clinical and genetic heterogeneity, rendering their diagnosis challenging. DNA-based techniques, like whole-exome sequencing, can establish a diagnosis in 50% of cases. RNA-sequencing is emerging as an attractive tool that can obtain information regarding gene expression while integrating functional genomic data with regard to the interpretation of variants. This increases the diagnostic rate by an additional 10-15%. In the present review, we detail the clinical steps involved in the diagnosis of genodermatoses, as well as the current DNA-based technologies available to clinicians. Herein, the intention is to facilitate a better understanding of the possibilities and limitations of these diagnostic technologies. In addition, this review could guide dermatologists through new emerging techniques, such as RNA-sequencing and its applications to familiarizing them with future techniques. Currently, this multi-omics approach is likely the best strategy designed to promote the diagnosis of patients with genodermatoses and discover new skin disease genes that could result in novel targeted therapies., (© 2022 European Academy of Dermatology and Venereology.)

Perifolliculitis capitis abscedens et suffodiens (PCAS) is a chronic skin inflammatory disease characterized by relapsing folliculitis and painful, fluctuant abscesses, sinus tracts, and scars. The treatment of PCAS is challenging and clinical practice varies a lot, and how to choose the best treatment for PCAS is a real problem for clinicians. We reviewed articles providing treatment options for patients with PCAS in different databases. Dermatologists may find this review helpful to meet the challenges of PCAS management, but there is still a lack of authoritative guidelines. In the future, more robust randomized control trials are needed to determine the best treatment for PCAS., (© 2022 Wiley Periodicals LLC.)

Background: Primary localized cutaneous amyloidosis (PLCA) is defined by the deposition of amyloid protein in the skin without systemic involvement. There are four subtypes of PLCA: lichen amyloidosis (LA), macular amyloidosis (MA), biphasic amyloidosis (BA), and nodular amyloidosis (NA). PLCA occurs most frequently in Latin Americans and Asians. Treatment is not standardized., Objectives: To identify subtypes, demographic and clinical features and treatment efficacy in patients with histopathologically confirmed PLCA., Materials and Methods: Data of PLCA patients were extracted from the electronic hospital database and included if diagnosis of PLCA was histopathologically confirmed and if sufficient information regarding treatment and follow-up was available. The evaluation of the treatment efficacy was based on a novel score to assess the reduction of itch and skin lesions., Results: In this retrospective, monocentric study, 37 cases of PLCA diagnosed between 2000 and 2020 were included (21 females) with a mean age of 52 years. LA was the most frequent subtype found in 21 patients (56.8%), followed by MA in 10 patients (28%) and BA in 6 patients (16.2%). No cases of NA were included. 22 patients (59.4%) had skin phototype II or III. Regarding treatment, a combination of UVA1 phototherapy with high-potency topical corticosteroids seemed to show the highest efficacy with complete clearance of symptoms in 4 patients (10.8%). A substantial improvement of symptoms was found in 5 patients (12.7%) treated with high-potency topical corticosteroids alone or in combination either with UVA1 or bath PUVA or monotherapy with UVA1 phototherapy or capsaicin (0.075%) cream. Low-/medium-potency topical corticosteroids alone or in combination with UVBnb (311 nm) phototherapy showed a lower efficacy., Conclusion: Our data show that PCLA is a rare disease in central Europe but can also be expected in a predominantly Caucasian population. The best treatment response was achieved with a combination of UVA1 phototherapy and high-potency topical corticosteroids., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Amyloid is a protein derived from at least 20 different substances. Once misfolded, it results in a group of cutaneous and systemic conditions. Primary localized cutaneous amyloidosis of keratinocyte origin is a very common subtype that can manifest either as lichen or macular amyloidosis, lacking systemic involvement. Lichen amyloidosis often presents as multiple hyperpigmented papules on the lower extremities whereas macular amyloidosis is classically characterized by dark brown rippled macules on the interscapular area. Review of the literature reveals that in addition to the classical presentation of primary localized cutaneous amyloidosis there exists a plethora of various manifestations that can be grouped into either geographic or morphologic categories. This review provides clinicians with the intimate knowledge of these presentations and summarizes the available treatment modalities., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Non-viral gene therapy for hereditary skin diseases is an attractive prospect. However, research efforts dedicated to this area are rare. Taking advantage of the branched structural possibilities of polymeric vectors, we have developed a gene delivery platform for the treatment of an incurable monogenic skin disease - recessive dystrophic epidermolysis bullosa (RDEB) - based on highly branched poly(β-amino ester)s (HPAEs). The screening of HPAEs and optimization of therapeutic gene constructs, together with evaluation of the combined system for gene transfection, were comprehensively reviewed. The successful restoration of type VII collagen (C7) expression both in vitro and in vivo highlights HPAEs as a promising generation of polymeric vectors for RDEB gene therapy into the clinic. Considering that the treatment of patients with genetic cutaneous disorders, such as other subtypes of epidermolysis bullosa, pachyonychia congenita, ichthyosis and Netherton syndrome, remains challenging, the success of HPAEs in RDEB treatment indicates that the development of viable polymeric gene delivery vectors could potentially expedite the translation of gene therapy for these diseases from bench to bedside., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Stiff skin syndrome (SSS) is a rare, scleroderma-like condition that is commonly characterised by stony hard skin and limited joint mobility, in the absence of visceral involvement or immunologic abnormalities. Depending on the distribution of the disease, this disorder can be further categorised into classic (widespread) SSS or its newly described segmental variant. Additional features of this syndrome may include hypertrichosis, lipodystrophy, dysmetria and scoliosis. In this report, we present the case of a patient with segmental SSS and we briefly review the current literature about the topic., (© 2021 The Australasian College of Dermatologists.)

With recent advances in genetic engineering technology, gene therapy is now being considered as a treatment not only for congenital diseases but also acquired diseases, such as cancer. Gene therapeutic agents for hereditary immune disorders, haemophilia, retinal diseases, neurodegenerative diseases, and lymphoma have been approved in the United States and Europe. In the field of dermatology, clinical trials of gene therapy have been conducted, because the skin is an easily accessible organ that represents an attractive tissue for gene therapy. In recent years, gene therapy has been attempted for a variety of skin diseases, such as genodermatoses (including epidermolysis bullosa and Netherton syndrome), cutaneous lymphoma, and malignant melanoma. As a result, it is difficult to grasp the current status of gene therapy in dermatology. This review focuses on each of the gene-transfer techniques currently in use and describes the current status of gene therapy for skin diseases using each technology., Competing Interests: Declaration of Competing Interest The author reports no declarations of interest., (Copyright © 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Genetic skin diseases, also known as genodermatoses, are inherited disorders affecting skin and constitute a large and heterogeneous group of diseases. While genodermatoses are rare with the prevalence rate of less than 1 in 50,000 - 200,000, they frequently occur at birth or early in life and are generally chronic, severe, and could be life-threatening. The quality of life of patients and their families are severely compromised by the negative psychosocial impact of disease, physical manifestations, and the lack or loss of autonomy. Currently, there are no curative treatments for these conditions. Ex vivo gene modification therapy that involves modification or correction of mutant genes in patients' cells in vitro and then transplanted back to patients to restore functional gene expression has being developed for genodermatoses. In this review, the ex vivo gene modification therapy strategies for genodermatoses are reviewed, focusing on current advances in gene modification and correction in patients' cells and delivery of genetically modified cells to patients with discussions on gene therapy trials which have been performed in this area., (© 2021 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Type 1 plasminogen deficiency is a rare genetic disorder. Type 1 plasminogen deficiency is characterized by fibrin-rich pseudomembrane formation on mucosal surfaces, particularly the conjunctiva. Tracheobronchial tree involvement is a less common reported manifestation of type 1 plasminogen deficiency. Pseudomembranes in the tracheobronchial tree may result in respiratory compromise and ultimately fail if not recognized and treated. Currently, there is no specific replacement therapy approved for the treatment of congenital plasminogen deficiency. In the present paper, we report that type 1 plasminogen deficiency with novel frameshift mutation and pulmonary involvement was treated initially with systemic fresh frozen plasma followed by pulmonary lavage with fresh frozen plasma and tissue plasminogen activator., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Significance: Cardiovascular disorders are the most important cause of morbidity and mortality in the Western world. Monogenic developmental disorders of the heart and vessels are highly valuable to study the physiological and pathological processes in cardiovascular system homeostasis. The arterial tortuosity syndrome (ATS) is a rare, autosomal recessive connective tissue disorder showing lengthening, tortuosity, and stenosis of the large arteries, with a propensity for aneurysm formation. In histopathology, it associates with fragmentation and disorganization of elastic fibers in several tissues, including the arterial wall. ATS is caused by pathogenic variants in SLC2A10 encoding the facilitative glucose transporter (GLUT)10. Critical Issues: Although several hypotheses have been forwarded, the molecular mechanisms linking disrupted GLUT10 activity with arterial malformations are largely unknown. Recent Advances: The vascular and systemic manifestations and natural history of ATS patients have been largely delineated. GLUT10 was identified as an intracellular transporter of dehydroascorbic acid, which contributes to collagen and elastin cross-linking in the endoplasmic reticulum, redox homeostasis in the mitochondria, and global and gene-specific methylation/hydroxymethylation affecting epigenetic regulation in the nucleus. We revise here the current knowledge on ATS and the role of GLUT10 within the compartmentalization of ascorbate in physiological and diseased states. Future Directions: Centralization of clinical, treatment, and outcome data will enable better management for ATS patients. Establishment of representative animal disease models could facilitate the study of pathomechanisms underlying ATS. This might be relevant for other forms of vascular dysplasia, such as isolated aneurysm formation, hypertensive vasculopathy, and neovascularization. Antioxid. Redox Signal . 34, 875-889.

The coronavirus disease-19 (COVID-19) has spread over many countries and regions since the end of 2019, becoming the most severe public health event at present. Most of the critical cases developed multiple organ dysfunction, including acute kidney injury (AKI). Cytokine storm syndrome (CSS) may complicate the process of severe COVID-19 patients. This manuscript reviews the different aspects of blood purification in critically ill patients with AKI and increased inflammatory factors, and examines its potential role in severe COVID-19 treatment. Continuous renal replacement therapy (CRRT) has been practiced in many sepsis patients with AKI. Still, the timing and dosing need further robust evidence. In addition to the traditional CRRT, the high-throughput membrane with adsorption function and cytokine adsorption column are two representatives of recently emerging novel membrane technologies. Their potential in removing inflammatory factors and other toxins prospects for the treatment of severe COVID-19.

Stiff skin syndrome is a chronic, rare sclerosing disorder that occurs in childhood, characterized by progressive induration of the skin that can cause thoracic restrictions and respiratory distress, limitations in joint mobility and gait difficulties, with significant deterioration of the quality of life. Because their therapeutic options are scarce and ineffective it is essential to start an early physical therapy to prevent these complications and to continue studying this condition to be able to offer patients more and better treatments. We present the case of a 9-year-old patient with indurated skin syndrome and its therapeutic challenge., Competing Interests: None, (Sociedad Argentina de Pediatría.)

Introduction: Actinic prurigo is a chronic photodermatosis. It affects the Latin American population more frequently, predominantly women, and involves the sun-exposed areas of the skin, conjunctiva, and lips. Objective: To update the information on the clinical-epidemiological characteristics and treatment of patients with actinic prurigo in Colombia. Materials and methods: We conducted a cross-sectional study including the medical records of patients with actinic prurigo treated in the Photodermatology Service of Hospital Universitario Centro Dermatológico Federico Lleras Acosta between 2011 and 2016. We described the demographic, clinical, histopathological, and treatment characteristics of the patients. Results: We included 108 patients, 77 (71.3%) were women and 31 (28.7%) men, mainly with phototypes III-IV (70%). The disease had begun during the first decade of life in 66.4% of the cases and 25% of the patients had a family history with the condition. The lesions predominated on the face (93.5%), forearms (79.6%), and back of the hands (70.4%). Ocular (87.9%) and lip (88.8%) involvement was also documented. A photo-provocation test with UVA was performed in 25% of the cases and skin biopsies in 19.4%. Physical and chemical photoprotection was indicated in all patients. Mild to moderate cases were treated with topical corticosteroids (91.7%) and calcineurin inhibitors (65.7%) while severe cases received thalidomide (33.3%) and pentoxifylline (14.8%). Conclusion: The characteristics of actinic prurigo patients in Colombia are similar to those reported in other Latin American countries: early onset of the disease, predominance in women, frequent involvement of conjunctiva and lips, and adequate response to topical and systemic treatment.

The human genome project yielded a compendium of genetic material that has allowed rapid advancement both in the technique of whole exome sequencing and also in the ability to identify single gene defects. The next generation of genetics has investigated how these genes interact in the development of disease, identifying pathways of illness and end organ tissue abnormal development. From the knowledge of single genes and pathways of genodermatosis development arises the opportunity to produce genetic therapies. This contribution reviews some of the exciting, emerging genetic therapies in genodermatoses., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The hereditary nature of some forms of cancer was recognized long ago. Over time, recognition of associated findings led to the delineation of numerous hereditary cancer syndromes. Many of these syndromes also have cutaneous manifestations, the recognition of which can lead to their early identification. Recognition of these syndromes allows vigilant surveillance and preemptive treatment, which can dramatically impact the risks of morbidity and mortality for affected patients. The rise of rapid and accurate genetic testing now allows the early identification of asymptomatic at risk family members so that monitoring can be initiated as early as possible. The dermatologist plays a critical role in early identification of these syndromes and, in many cases, their treatment. This review summarizes many known hereditary cancer syndromes with cutaneous findings, their etiology, identification, evaluation, and management. Importantly, this is an ever evolving topic and new findings and syndromes will continue to be recognized. The dermatologist must be always alert to ensure they are detected., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Erythema papulatum centrifugum (EPC), also known as erythema papulosa semicircularis recidivans (EPSR), is distinct from eczema and other well-described figurate erythemas characterised by annular erythematous lesions. We report 7 cases of EPC and propose new diagnostic criteria including the following: (i) EPC is characterised by single or multiple recurrent expanding annular or semi annular erythema with central regression, surrounded by tiny red papules; (ii) the lesions regularly relapse and resolve; (iii) the histopathologic feature shows superficial perivascular inflammation with or without mild inflammation around sweat glands in the mid dermis and (iv) patients lack other associated cutaneous or internal abnormalities., (© 2019 The Australasian College of Dermatologists.)

Cutaneous findings that appear in childhood may be the first sign of a hereditary tumor syndrome. Early detection of genodermatoses allows the patient and at-risk family members to be screened for associated malignancies. This article provides a brief description of the pathogenesis and clinical manifestations of various inherited disorders with skin involvement, along with treatment updates. Advances in molecular-based therapy have spurred development of novel treatment methods for various genodermatoses such as xeroderma pigmentosum (XP) and Gorlin-Goltz syndrome. Further studies are needed to better assess the efficacy of many of these new treatment options., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A 41-year-old man presented with an asymptomatic, slowly enlarging plaque on the lower aspect of his left cheek, present for approximately 4 months. His past medical history was remarkable for allergic rhinitis. Three years before, he had had a nearly identical lesion surgically excised by Mohs method at the same site. On examination, there was a waxy, yellowish plaque, measuring 2.1 cm × 1.0 cm on the left cheek in proximity to the oral commissure (Figure 1). A shave biopsy revealed an atrophic epidermis with nodular aggregates of eosinophilic material in the dermis (Figure 2). Higher magnification showed an inflammatory infiltrate composed largely of plasma cells, which stained positively for CD20 and κ light chains (Figure 3). Congo red staining confirmed the diagnosis of nodular amyloidosis (Figure 4).

The discoveries of new genes underlying genetic skin diseases have occurred at a rapid pace, supported by advances in DNA sequencing technologies. These discoveries have translated to an improved understanding of disease mechanisms at a molecular level and identified new therapeutic options based on molecular targets. This article highlights just a few of these recent discoveries for a diverse group of skin diseases, including tuberous sclerosis complex, ichthyoses, overgrowth syndromes, interferonopathies, and basal cell nevus syndrome, and how this has translated into novel targeted therapies and improved patient care., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Many types of genodermatosis exist, with numerous modes of transmission. The development of molecular genetic methods, in particular the most recent sequencing techniques, can be used to identify an increasing number of genes involved in these forms of genodermatosis while providing confirmation or more details regarding clinical diagnosis. Thanks to this approach, it is possible to determine risk of recurrence and to formulate an antenatal strategy. These technologies have led to improved molecular definition and to a better understanding of the physiopathological mechanisms involved in different genodermatoses such as bullous epidermolysis, keratinisation disorders, pigmentation disorders, potentially tumoral conditions, and epidermal and pilar dysplasia. The large amount of information provided by high-throughput sequencing makes it possible to study modifying genes as well as genotype-phenotype correlations. However, this genetic information in its turn poses problems of interpretation and of control of the resulting data. The use of genetics in dermatology for the purposes of diagnosis or research requires a consultation to provide patients with information regarding the genetic tests involved and the potential consequences thereof for them and their families. Furthermore, with pangenomic approaches there is a higher probability of fortuitous discovery of abnormalities such as variants associated with risks predisposing to cancer or neurodegenerative disease. Collaboration between dermatologists and geneticists enables optimisation of patient management in terms of diagnosis and genetic counselling in the event of such rare diseases. Therapeutic applications are beginning to be developed. The scope of therapeutic application includes gene therapy, replacement therapy (enzyme therapy) and targeted therapy., (Copyright © 2019. Published by Elsevier Masson SAS.)

Pseudohypoparathyroidism (PHP), pseudo-PHP, acrodysostosis, and progressive osseous heteroplasia are heterogeneous disorders characterized by physical findings, differently associated in each subtype, including short bones, short stature, a stocky build, ectopic ossifications (features associated with Albright's hereditary osteodystrophy), as well as laboratory abnormalities consistent with hormone resistance, such as hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH) and thyroid-stimulating hormone levels. All these disorders are caused by impairments in the cAMP-mediated signal transduction pathway and, in particular, in the PTH/PTHrP signaling pathway: the main subtypes of PHP and related disorders are caused by de novo or autosomal dominantly inherited inactivating genetic mutations, and/or epigenetic, sporadic, or genetic-based alterations within or upstream of GNAS, PRKAR1A, PDE4D, and PDE3A. Here we will review the impressive progress that has been made over the past 30 years on the pathophysiology of these diseases and will describe the recently proposed novel nomenclature and classification. The new term "inactivating PTH/PTHrP signaling disorder," iPPSD: (1) defines the common mechanism responsible for all diseases, (2) does not require a confirmed genetic defect, (3) avoids ambiguous terms like "pseudo," and (4) eliminates the clinical or molecular overlap between diseases., (© 2019 S. Karger AG, Basel.)

Ligneous conjunctivitis is a rare and poorly understood pathology. Infections and repeated microtraumas are often involved in acute disease flare-ups. This masquerade may lead to misdiagnosis and delayed treatment. We report two cases of ligneous conjunctivitis, describing various presentations of its natural history and focusing on the treatment of this rare disease., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Annular lesions can present in a variety of diseases. Knowledge of the physical appearance and history of presentation of these skin findings can help in the diagnosis. A pruritic, annular, erythematous patch that grows centrifugally should prompt evaluation for tinea corporis. Tinea corporis may be diagnosed through potassium hydroxide examination of scrapings. Recognizing erythema migrans is important in making the diagnosis of Lyme disease so that antibiotics can be initiated promptly. Plaque psoriasis generally presents with sharply demarcated, erythematous silver plaques. Erythema multiforme, which is due to a hypersensitivity reaction, presents with annular, raised lesions with central clearing. Lichen planus characteristically appears as planar, purple, polygonal, pruritic papules and plaques. Nummular eczema presents as a rash composed of coin-shaped papulovesicular erythematous lesions. Treatment is aimed at reducing skin dryness. Pityriasis rosea presents with multiple erythematous lesions with raised, scaly borders, and is generally self-limited. Urticaria results from the release of histamines and appears as well-circumscribed, erythematous lesions with raised borders and blanched centers. Annular lesions occur less commonly in persons with fixed drug eruptions, leprosy, immunoglobulin A vasculitis, secondary syphilis, sarcoidosis, subacute cutaneous lupus erythematosus, and granuloma annulare.

An 8-week-old female infant presented with bilateral eyelid swelling and conjunctival membranes. She was diagnosed as having ligneous conjunctivitis. The membranes were excised but recurred despite topical cyclosporine, heparin, fresh frozen plasma, and systemic fresh frozen plasma transfusions. Topical plasminogen prevented membrane recurrence and intravenous plasminogen therapy treated systemic manifestations of the disease. [J Pediatr Ophthalmol Strabismus. 2018;55:e30-e32.]., (Copyright 2018, SLACK Incorporated.)

Multiple miliary osteoma cutis consists of heterotopic foci of bone tissue in the dermis and subcutaneous tissue. Patients usually present with multiple, asymptomatic facial papules of several millimetres in diameter which cause distress regarding their cosmetic appearance. The condition is described as rare, as only a few cases have been reported since its first description in 1864 by Virchow. We therefore carried out a comprehensive literature search and review, in which 102 published cases were retrieved and analysed. The demographic and clinical aspects, as well as current therapy solutions, of this probably overlooked condition are discussed.

Heterotopic ossification (HO) involves the formation and accumulation of extraskeletal bone tissue at the expense of local tissues including muscles and connective tissues. There are common forms of HO that are triggered by extensive trauma, burns and other bodily insults, and there are also rare congenital severe forms of HO that occur in children with Fibrodysplasia Ossificans Progressiva or Progressive Osseous Heteroplasia. Given that HO is often preceded by inflammation, current treatments usually involve anti-inflammatory drugs alone or in combination with local irradiation, but are not very effective. Recent studies have provided novel insights into the pathogenesis of acquired and genetic forms of HO and have used the information to conceive and test new and more specific therapies in animal models. In this review, I provide salient examples of these exciting and promising advances that are undoubtedly paving the way toward resolution of this debilitating and at times fatal disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Reticulate pigmentary disorders are a group of disorders characterized by hyper- and/or hypopigmented macules with varying sizes and amounts of pigment. Some of the disorders are heritable, such as Dowling-Degos disease, dyschromatosis universalis hereditaria, dyschromatosis symmetrica hereditaria, reticulate acropigmentation of Kitamura and X-linked reticulate pigmentary disorder. Although each condition possesses unique phenotypic characteristics and the prognosis for each is somewhat different, there is a large degree of overlap between the disorders and therefore they are difficult to differentiate in the clinical setting. This updated review provides a clinical and molecular delineation of these genetic reticulate pigmentary disorders and aims to establish a concise diagnostic strategy to allow clinical dermatologists to make an accurate diagnosis, as well as to provide useful information for clinical and genetic counselling., (© 2017 British Association of Dermatologists.)

Background: Primary localized cutaneous amyloidosis (PLCA) is characterized by extracellular deposition of heterogenic amyloid proteins in the skin without systemic involvement. Lichen amyloidosis, macular amyloidosis, and (primary localized cutaneous) nodular amyloidosis are different subtypes of PLCA., Objective: The aim of this study was to review the current reported treatment options for PLCA., Methods: This systematic review was based on a search in the PubMed database for English and German articles from 1985 to 2016., Results: Reports on the treatment of PLCA were limited predominantly to case reports or small case series. There were a few clinical trials but these lacked control groups. A variety of treatment options for PLCA were reported including retinoids, corticosteroids, cyclophosphamide, cyclosporine, amitriptyline, colchicine, cepharanthin, tacrolimus, dimethyl sulfoxide, vitamin D 3 analogs, capsaicin, menthol, hydrocolloid dressings, surgical modalities, laser treatment, and phototherapy., Conclusion: No definitive recommendation of preferable treatment procedures can be made based on the analyzed literature. Randomized controlled trials are needed to offer patients an evidence-based therapy with high-quality standardized treatment regimens for PLCA.

Genodermatoses comprise a clinically heterogeneous group of mostly devastating disorders affecting the skin. To date, treatment options have in general been limited to symptom relief. However, the recent technical evolution in genome editing has ushered in a new era in the development of causal therapies for rare monogenetic diseases such as genodermatoses. The present review revisits the advantages and drawbacks of engineered nuclease tools currently available: zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), meganucleases, and - the most innovative - clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) nuclease 9 (CRISPR/Cas9) system. A mechanistic overview of the different modes of action of these programmable nucleases as well as their significance for causal therapy of genodermatoses is presented. Remaining limitations and challenges such as efficient delivery and off-target activity are critically discussed, highlighting both the past and future of gene therapy in dermatology., (© 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Familiar genetic disorders such as neurofibromatosis type I (NF1), tuberous sclerosis complex (TSC), oculocutaneous albinism (OCA), basal cell nevus syndrome (BCNS), incontinentia pigmenti, ichthyosis, and epidermolysis bullosa (EB) have prominent, cutaneous manifestations. This review describes recent advances in knowledge concerning the pathophysiology, diagnosis, and treatment of these skin features. Specifically, clinical diagnostic criteria for incontinentia pigmenti, ichthyosis, and tuberous sclerosis have been updated. Additionally, there have been considerable advancements in the technology used in the molecular diagnoses of these conditions. In the case of TSC, the discovery that a portion of TSC mutations are missed due to mosaicism is driving the development of new diagnostic methods. Also, scientists are also seeking minimally invasive methods of genetic diagnosis, as in the case of using hair follicles to diagnose autosomal recessive congenital ichythosis (ARCI). Finally, there are innovative targeted medical therapies being developed that serve as promising tools in the care of patients afflicted with conditions including ichthyosis and EB.

Purpose of Review: Childhood skin cancers are relatively rare and may indicate an underlying genetic disorder. The increasing elucidation of genetic pathways is changing the diagnosis and management of genetic skin cancer susceptibility syndromes. In this review, we provide an overview of genetic conditions that predispose to skin cancer development in childhood and signs that providers should assess when evaluating affected individuals., Recent Findings: In basal cell nevus syndrome (BCNS), the patched2 (PTCH2) and suppressor of fused (SUFU) genes have been implicated in disease pathogenesis. The sonic hedgehog (SHH) pathway inhibitor vismodegib was shown in a placebo-controlled phase III randomized trial to reduce the tumor burden in patients with BCNS. Epidermolysis bullosa (EB) has been classified into four major types and more than 30 subtypes based partly on specific mutations, and best clinical practice guidelines for the management of cutaneous squamous cell carcinoma in EB have been developed. Oculocutaneous albinism (OCA) has been associated with new mutations in genes named OCA5, OCA6, and OCA7, bringing to the total number of culprit genes to seven (OCA1-OCA7)., Summary: Advances in our understanding of genetic conditions that predispose to childhood skin cancer include new disease classification systems, management guidelines, and treatment options.

Plasminogen plays an important role in fibrinolysis as well as wound healing, cell migration, tissue modeling and angiogenesis. Congenital plasminogen deficiency is a rare autosomal recessive disorder that leads to the development of thick, wood-like pseudomembranes on mucosal surfaces, mostly seen in conjunctivas named as ''ligneous conjunctivitis''. Local conjunctival use of fresh frozen plazma (FFP) in combination with other eye medications such as cyclosporin and artificial tear drops may relieve the symptoms. Topical treatment with plasminogen eye drops is the most promising treatment that is not yet available in Turkey.

Genetic disorders affecting the skin, genodermatoses, constitute a large and heterogeneous group of diseases, for which treatment is generally limited to management of symptoms. RNA-based therapies are emerging as a powerful tool to treat genodermatoses. In this review, we discuss in detail RNA splicing modulation by antisense oligonucleotides and RNA trans-splicing, transcript replacement and genome editing by in vitro-transcribed mRNAs, and gene knockdown by small interfering RNA and antisense oligonucleotides. We present the current state of these therapeutic approaches and critically discuss their opportunities, limitations and the challenges that remain to be solved. The aim of this review was to set the stage for the development of new and better therapies to improve the lives of patients and families affected by a genodermatosis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

During complete inspection of skin a variety of penile skin alterations may be found. Not all dermatological findings have clinical relevance. Pearly papules and heterotopic sebaceous glands are physiological variations. Most penile melanotic macules, angiokeratoma, fibroma and angioma have not to be treated. However, other more severe diseases such as malignant skin lesions (erythroplasia of Queyrat), infectious disease (human papillomavirus-induced penile warts) or systemic skin diseases (psoriasis) may be detected. Since patients are alarmed by genital skin lesions and their sexuality may be affected, the initiation of adequate therapy is an important task for urologists and dermatologists.