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Introduction: Neonatal linear immunoglobulin A (IgA) bullous dermatosis (NLABD) is a rare, life-threatening, mucocutaneous bullous disorder. The pathogenesis and optimal treatment remain poorly defined and raise critical clinical challenges., Case Presentation: We present a case of a full-term female infant with severe cutaneous and respiratory symptoms due to NLABD. Diagnosis was confirmed by immunofluorescence on the infant's skin biopsy, while IgAs directed against the basement membrane of the skin and mucosa were identified in the mother's milk. The infant fully recovered after nearly 8 weeks of intensive multidisciplinary care, including non-invasive ventilation, nutritional support, wound care, systemic corticoid treatment, and breastfeeding discontinuation., Conclusion: This case underscores the importance of timely adequate diagnosis and management of this rare and serious condition. Moreover, it adds novel evidence documenting the presence of pathogenic IgAs in breastmilk., Introduction: Neonatal linear immunoglobulin A (IgA) bullous dermatosis (NLABD) is a rare, life-threatening, mucocutaneous bullous disorder. The pathogenesis and optimal treatment remain poorly defined and raise critical clinical challenges., Case Presentation: We present a case of a full-term female infant with severe cutaneous and respiratory symptoms due to NLABD. Diagnosis was confirmed by immunofluorescence on the infant's skin biopsy, while IgAs directed against the basement membrane of the skin and mucosa were identified in the mother's milk. The infant fully recovered after nearly 8 weeks of intensive multidisciplinary care, including non-invasive ventilation, nutritional support, wound care, systemic corticoid treatment, and breastfeeding discontinuation., Conclusion: This case underscores the importance of timely adequate diagnosis and management of this rare and serious condition. Moreover, it adds novel evidence documenting the presence of pathogenic IgAs in breastmilk., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Lymphomatoid papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population are scarce., Objectives: To characterize the epidemiological, clinical, histopathological and prognostic features of paediatric LyP., Methods: This was a retrospective multicentre international cohort study that included 87 children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years at disease onset were included. LyP diagnosis was made in each centre, based on clinicopathological correlation., Results: Eighty-seven patients from 12 centres were included. Mean age at disease onset was 7.0 years (range 3 months-18 years) with a male to female ratio of 2 : 1. Mean time between the onset of the first cutaneous lesions and diagnosis was 1.3 years (range 0-14). Initial misdiagnosis concerned 26% of patients. LyP was most often misdiagnosed as pityriasis lichenoides et varioliformis acuta, insect bites or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned in 21% of patients. The main histological subtype was type A in 55% of cases. When analysed, monoclonal T-cell receptor rearrangement was found in 77% of skin biopsies. The overall survival rate was 100%, with follow-up at 5 years available for 33 patients and at 15 years for 8 patients. Associated haematological malignancy (HM) occurred in 10% of cases (n = 7/73), including four patients with mycosis fungoides, one with primary cutaneous anaplastic large cell lymphoma (ALCL), one with systemic ALCL and one with acute myeloid leukaemia. If we compared incidence rates of cancer with the world population aged 0-19 years from 2001 to 2010, we estimated a significantly higher risk of associated malignancy in general, occurring before the age of 19 years (incidence rate ratio 87.49, 95% confidence interval 86.01-88.99)., Conclusions: We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall, the disease prognosis is good, with excellent survival rates for all patients. Owing to an increased risk of associated HM, long-term follow-up should be recommended for patients with LyP., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Cutaneous epidermal nevi are genotypically diverse mosaic disorders. Pathogenic hotspot variants in HRAS , KRAS , and less frequently , NRAS and BRAF may cause isolated keratinocytic epidermal nevi and sebaceous nevi or several different syndromes when associated with extracutaneous anomalies. Therefore, some authors suggest the concept of mosaic RASopathies to group these different disorders., Methods: In this paper, we describe three new cases of syndromic epidermal nevi caused by mosaic HRAS variants: one associating an extensive keratinocytic epidermal nevus with hypomastia, another with extensive mucosal involvement and a third combining a small sebaceous nevus with seizures and intellectual deficiency. Moreover, we performed extensive literature of all cases of syndromic epidermal nevi and related disorders with confirmed pathogenic postzygotic variants in HRAS, KRAS, NRAS or BRAF ., Results: Most patients presented with bone, ophthalmological or neurological anomalies. Rhabdomyosarcoma, urothelial cell carcinoma and pubertas praecox are also repeatedly reported. KRAS pathogenic variants are involved in 50% of the cases, especially in sebaceous nevi, oculoectodermal syndrome and encephalocraniocutaneous lipomatosis. They are frequently associated with eye and brain anomalies. Pathogenic variants in HRAS are rather present in syndromic keratinocytic epidermal nevi and phacomatosis pigmentokeratotica., Conclusion: This review delineates genotype/phenotype correlations of syndromic epidermal nevi with somatic RAS and BRAF pathogenic variants and may help improve their follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Darier Disease is a rare autosomal dominant inherited skin disorder classified as an acantholytic dermatosis. It manifests around puberty as brownish keratotic papules of skin folds and seborrheic areas, associated with onychopathy and mucosal involvementand have a chronic relapsing-remitting course with frequent exacerbations triggered by sun exposure, heat, friction, or infections. Darier patients have an increased risk of neuropsychiatric disorders, type 1 diabetes and heart failure. Short-term management relies on antibiotics/antiviral, topical corticosteroids and/or retinoids. Moisturizers, sun protection and avoiding triggers are essential for long-term management. Conventional long-term treatment is not standardized and many topical treatments, physical and surgical measures and systemic treatments are described in the literature., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Auto-immune bullous diseases (AIBD) are rare in children. Although their pathogenesis is similar to their adult counterpart, there are differences in the clinical presentation. Moreover certain AIBD prevail at certain ages. There are no guidelines for the treatment of AIBD specific for children. In this review the recent literature is summarised with attention to recent data including diagnostic criteria. We also propose a treatment algorithm., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Psoriasis may present in childhood with skin, nail and scalp lesions but sometimes also articular involvement. It has an import impact on the quality of life of young patients. In this article we present an overview of the treatments that may be used in children according to skin area involved and severity of lesions with special interest for the biological treatments, already available and under investigation., Competing Interests: Le Dr F. Messina a servi en tant que conseiller et/ou a reçu des honoraires de conférencier et/ou a participé à des essais cliniques financés par Almirall, Alphasigma, Amgen, Celgene, Novartis et UCB. Le Pr C. Conrad a été consultant ou conférencier pour : AbbVie, Actelion, Almirall, Amgen, BMS, Böhringer-Ingelheim, Celgene, Eli Lilly, Galderma, Incyte, Janssen-Cilag, Leo Pharma, MSD, Novartis, Pfizer, Samsung, Sanofi, UCB. La dernière auteure n’a déclaré aucun conflit d’intérêts en relation avec cet article.

Background: A popular antiseptic spray in Switzerland (Merfen spray), containing chlorhexidine digluconate, benzoxonium chloride and lauramine oxide, is frequently used to treat skin wounds. However, it is also increasingly reported as a major cause of adverse skin reactions, including allergic contact dermatitis (ACD)., Objectives: To investigate the contact allergens responsible for ACD from this antiseptic., Patients/methods: Patch tests were performed on seven patients with a clinical history compatible with contact dermatitis from this antiseptic mixture., Results: All patients presented with acute eczematous reactions following contact with either Merfen spray alone, or with multiple products including this spray. Patients showed positive reactions to this product in both patch tests and repeated open application tests (ROATs). Four patients showed dose-dependent reactions to both benzoxonium chloride and lauramine oxide. One patient showed a dose-dependent reaction to the former and a non-dose-dependent reaction to the latter. Finally, two subjects showed responses only to lauramine oxide. One patient reacted to chlorhexidine digluconate 0.5% aq. in addition to both other allergens., Conclusions: Two commercially unavailable allergens, that is, benzoxonium chloride and/or lauramine oxide were identified as major causes of ACD from Merfen antiseptic spray, whereas chlorhexidine digluconate was a contributing culprit in only one patient., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Juvenile dermatomyositis is a rare multi-system auto-immune disease, particularly causing inflammation of skin and muscles of children. The diagnosis is based on the clinical picture with typical cutaneous lesions, which frequently are the first signs of the disease in contrast to muscle involvement. Muscular MRI is nowadays the first line investigation to diagnose myositis. Recently specific auto-antibodies have been detected allowing a better understanding of the disease and being important prognostic factors. An early diagnosis and aggressive treatment is crucial to induce remission of the disease, especially restore muscular function and to prevent severe complications such as calcinosis and lipodystrophy, which are difficult to treat as well as vital organ dysfunction., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Tinea capitis is a superficial dermatophytic infection of the scalp. This common dermatosis occurs predominantly in children. The clinical manifestation of the disease is heterogeneous, and vary widely depending on the pathogenic fungal agent. Direct mycological examination and cultures are mandatory for an accurate diagnosis and species identification. Treatment should be both local and systemic, and ideally is tailored to the dermatophytic species identified by the laboratory diagnostic work up. Secondary prophylaxis through supplementary measures is crucial to avoid epidemic outbreak and patient reinfection., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Genodermatoses are rare inherited skin diseases that frequently affect other organs. They often have marked effects on wellbeing and may cause early death. Progress in molecular genetics and translational research has unravelled many underlying pathological mechanisms, and in several disorders with high unmet need, has opened the way for the introduction of innovative treatments. One approach is to intervene where cell-signaling pathways are dysregulated, in the case of overactive pathways by the use of selective inhibitors, or when the activity of an essential factor is decreased by augmenting a molecular component to correct disequilibrium in the pathway. Where inflammatory reactions have been induced by a genetically altered protein, another possible approach is to suppress the inflammation directly. Depending on the nature of the genodermatosis, the implicated protein or even on the particular mutation, to correct the consequences or the genetic defect, may require a highly personalised stratagem. Repurposed drugs, can be used to bring about a "read through" strategy especially where the genetic defect induces premature termination codons. Sometimes the defective protein can be replaced by a normal functioning one. Cell therapies with allogeneic normal keratinocytes or fibroblasts may restore the integrity of diseased skin and allogeneic bone marrow or mesenchymal cells may additionally rescue other affected organs. Genetic engineering is expanding rapidly. The insertion of a normal functioning gene into cells of the recipient is since long explored. More recently, genome editing, allows reframing, insertion or deletion of exons or disruption of aberrantly functioning genes. There are now several examples where these stratagems are being explored in the (pre)clinical phase of therapeutic trial programmes. Another stratagem, designed to reduce the severity of a given disease involves the use of RNAi to attenuate expression of a harmful protein by decreasing abundance of the cognate transcript. Most of these strategies are short-lasting and will thus require intermittent life-long administration. In contrast, insertion of healthy copies of the relevant gene or editing the disease locus in the genome to correct harmful mutations in stem cells is more likely to induce a permanent cure. Here we discuss the potential advantages and drawbacks of applying these technologies in patients with these genetic conditions. Given the severity of many genodermatoses, prevention of transmission to future generations remains an important goal including offering reproductive choices, such as preimplantation genetic testing, which can allow selection of an unaffected embryo for transfer to the uterus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Morren, Legius, Giuliano, Hadj-Rabia, Hohl and Bodemer.)

Background: Contact allergy is increasingly recognized as being important in children with eczema., Objectives: To retrospectively analyse the patch test results in children over the past 10 years, aiming to (1) evaluate demographic characteristics and lesion locations, (2) describe frequencies of positive patch test reactions, and (3) investigate the relationship with atopic dermatitis (AD)., Methods: A total of 329 children were patch tested between January 2010 and December 2019 with the European (children) baseline series and/or other series, and the personal product(s) used., Results: A total of 119 (36%) children presented with at least one positive reaction. Children with AD had a higher prevalence of positive reactions compared with the non-AD group (P = .002), but without statistically significant difference regarding sensitization to more than one hapten (P = .39). The face (20.2%), hands (19.3%), feet (16.8%), arms (12.6%), and body folds (10.9%) were the most common sites of primary localizations. The most frequent contact allergens were nickel sulfate and linalool hydroperoxide (both 16%), limonene hydroperoxide (13.5%), and para-phenylenediamine (10.9%). No statistically significant difference for nickel sulfate was found between the AD and non-AD group (P = .20)., Conclusions: Contact allergy in children with eczema was frequently observed in our tertiary referral centre in Belgium as well, confirming the need for patch testing., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pansclerotic morphea (PSM) is a rare skin disease characterized by progressive stiffening of the skin with or without the typical superficial skin changes usually seen in morphea (localized scleroderma). Standard therapy, consisting of a combination of systemic glucocorticoids and methotrexate or mycophenolate mofetil, does rarely stop disease progression, which may lead to severe cutaneous sclerosis and secondary contractures. Little is known about the efficacy of newer biologicals such as abatacept, a fusion protein antibody against CTLA-4, or tocilizumab, a fully humanized IL-6R antibody, in the treatment of this pathology. We present the case of an 8 years old girl with an unusual, progressive stiffening of the skin, which was eventually diagnosed as pansclerotic morphea. A treatment with systemic glucocorticoids and methotrexate combined with tocilizumab led to a good clinical response within 2 months after initiation. In this paper, we discuss differential diagnoses to be considered and this new promising treatment option based on a case review of the literature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ventéjou, Schwieger-Briel, Nicolai, Christen-Zaech, Schnider, Hofer, Bogiatzi, Hohl, De Benedetti and Morren.)

Background: Gain-of-function mutations in STING1 underlie a type I interferonopathy termed SAVI (STING-associated vasculopathy with onset in infancy). This severe disease is variably characterized by early-onset systemic inflammation, skin vasculopathy, and interstitial lung disease (ILD)., Objective: To describe a cohort of patients with SAVI., Methods: Assessment of clinical, radiological and immunological data from 21 patients (17 families) was carried out., Results: Patients carried heterozygous substitutions in STING1 previously described in SAVI, mainly the p.V155M. Most were symptomatic from infancy, but late onset in adulthood occurred in 1 patient. Systemic inflammation, skin vasculopathy, and ILD were observed in 19, 18, and 21 patients, respectively. Extensive tissue loss occurred in 4 patients. Severity of ILD was highly variable with insidious progression up to end-stage respiratory failure reached at teenage in 6 patients. Lung imaging revealed early fibrotic lesions. Failure to thrive was almost constant, with severe growth failure seen in 4 patients. Seven patients presented polyarthritis, and the phenotype in 1 infant mimicked a combined immunodeficiency. Extended features reminiscent of other interferonopathies were also found, including intracranial calcification, glaucoma and glomerular nephropathy. Increased expression of interferon-stimulated genes and interferon α protein was constant. Autoantibodies were frequently found, in particular rheumatoid factor. Most patients presented with a T-cell defect, with low counts of memory CD8+ cells and impaired T-cell proliferation in response to antigens. Long-term follow-up described in 8 children confirmed the clinical benefit of ruxolitinib in SAVI where the treatment was started early in the disease course, underlying the need for early diagnosis. Tolerance was reasonably good., Conclusion: The largest worldwide cohort of SAVI patients yet described, illustrates the core features of the disease and extends the clinical and immunological phenotype to include overlap with other monogenic interferonopathies., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Epithelioid sarcoma is a rare soft-tissue tumor that occurs mainly in children and young adults. It typically presents as a subcutaneous or deep dermal mass in distal extremities. Due to its benign-appearing clinical presentation, infrequent occurrence, and histologic similarities with other pathologies, the diagnosis of epithelioid sarcoma in its early stages can be extremely difficult and can be easily confused with benign lesions such as warts or foreign body granuloma. In this paper, we report the case of a 12-year-old boy with a distal-type epithelioid sarcoma of the hand and wish to emphasize the difficulties of diagnosing this potentially lethal tumor both clinically and histologically., (© 2020 Wiley Periodicals LLC.)

Birt-Hogg-Dubé syndrome (BHD) is a rare inherited autosomal dominant disorder caused by germline mutations in the tumour suppressor gene FLCN , encoding the protein folliculin. Its clinical expression typically includes multiple pulmonary cysts, recurrent spontaneous pneumothoraces, cutaneous fibrofolliculomas and renal tumours of various histological types. BHD has no sex predilection and tends to manifest in the third or fourth decade of life. Multiple bilateral pulmonary cysts are found on chest computed tomography in >80% of patients and more than half experience one or more episodes of pneumothorax. A family history of pneumothorax is an important clue, which suggests the diagnosis of BHD. Unlike other cystic lung diseases such as lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis, BHD does not lead to progressive loss of lung function and chronic respiratory insufficiency. Renal tumours affect about 30% of patients during their lifetime, and can be multiple and recurrent. The diagnosis of BHD is based on a combination of genetic, clinical and/or skin histopathological criteria. Management mainly consists of early pleurodesis in the case of pneumothorax, periodic renal imaging for tumour detection, and diagnostic work-up in search of BHD in relatives of the index patient., Competing Interests: Provenance: Commissioned article, peer reviewed. Conflict of interest: C. Daccord reports non-financial support from Boehringer-Ingelheim and Roche, outside the submitted work. Conflict of interest: J-M. Good has nothing to disclose. Conflict of interest: M-A. Morren has nothing to disclose. Conflict of interest: O. Bonny has nothing to disclose. Conflict of interest: D. Hohl has nothing to disclose. Conflict of interest: R. Lazor reports personal fees and non-financial support from Boehringer-Ingelheim, and non-financial support from Roche and Vifor, outside the submitted work., (Copyright ©ERS 2020.)

Keratinocytic epidermal nevi (KEN) are characterized clinically by permanent hyperkeratosis in the distribution of Blaschko's lines and histologically by hyperplasia of epidermal keratinocytes. KEN with underlying RAS mutations have been associated with hypophosphatemic rickets and dysplastic bone lesions described as congenital cutaneous skeletal hypophosphatemia syndrome. Here, we describe two patients with keratinocytic epidermal nevi, in one associated with a papular nevus spilus, who presented with distinct localized congenital fibro-osseous lesions in the lower leg, diagnosed on both radiology and histology as osteofibrous dysplasia, in the absence of hypophosphatemia or rickets, or significantly raised FGF23 levels but with distinct mosaic HRAS mutations. This expands the spectrum of cutaneous/skeletal mosaic RASopathies and alerts clinicians to the importance of evaluating for bony disease even in the absence of bone profile abnormalities., (© 2020 Wiley Periodicals LLC.)

Corticophobia is a major problem in adherence to therapy. This study examined corticophobia among healthcare professionals using the Topical Corticosteroid Phobia (TOPICOP) questionnaire. The TOPICOP questionnaire was adapted for use with professionals (TOPICOP-P). Four groups of professionals: pharmacists, paediatricians, general practitioners and dermatologists were observed. The mean global TOPICOP score was 41.9 ± 14.9%. Pharmacists had the highest scores for corticophobia: a global score of 48.5 ± 13.9%, followed by general practitioners, 46.0 ± 13.5%, paediatricians 39.7 ± 14.5%, and dermatologists 32.3 ± 12.1%. Overall, there was a statistically significant difference in the mean score between the 4 groups (p < 0.05). In conclusion, there is prominent corticophobia among healthcare professionals, especially among pharmacists and general practitioners, which is probably based on insufficient knowledge of topical corticosteroids. In order to improve patient compliance, re-education of healthcare providers is suggested.

Case Series Summary: Cutaneous mastocytosis is a disorder rarely reported in veterinary dermatology and usually described as 'urticaria pigmentosa'. This study aimed to evaluate the diagnosis, treatment and outcome of 13 affected cats, selected from the files of a private referral dermatology practice within a period of 14 years. Breeds of the affected individuals included Sphynx (n = 9), Devon Rex (n = 2) and Sphynx/Devon Rex crossbreeds (n = 2). Females (n = 9) were over-represented and the median duration of clinical signs prior to diagnosis was 8 months. The clinical presentation of these 13 cats was compared with cases reported in the veterinary literature and classified according to the current human consensus on cutaneous mastocytosis. Three clinical forms could be distinguished in cats: (1) large papular lesions and wheals, typically localised to the head, shoulders, ventral neck and axillae, and which may spontaneously resolve (termed polymorphic maculopapular cutaneous mastocytosis); (2) erythematous dermatitis, characterised by small maculopapular lesions often associated with crusts and with a poorer prognosis (termed monomorphic maculopapular cutaneous mastocytosis); and (3) more chronic dermatitis characterised by lichenification and hyperpigmentation, similar to the human condition 'urticaria pigmentosa' (termed pigmented maculopapular cutaneous mastocytosis). Histopathology was performed in eight cases and revealed a superficial-to-deep dermatitis characterised by infiltrates of mast cells and eosinophils. The response to various treatments, including antihistamines, steroids and ciclosporin, was variable., Relevance and Novel Information: This article reports 13 new cases of feline cutaneous mastocytosis, confirming the clinical presentation and apparent breed predisposition. The feline maculopapular cutaneous mastocytosis seems to be clinically very close to the human form. This study proposes a new classification system for the feline disease based on the current human consensus, clinical presentation and prognosis, with three different subforms: polymorphic maculopapular cutaneous mastocytosis with eventual spontaneous regression; monomorphic maculopapular cutaneous mastocytosis with chronic evolution; and pigmented maculopapular cutaneous mastocytosis.

Pediatric teledermatology (PTD) allows offering long distance health care advice in pediatric dermatology trough telecommunication technologies. Due to the lack of pediatric dermatologists, the frequency of dermatological questions in general pediatrics, the visual nature of the specialty, and the rare occurrence of vital emergencies in dermatology, PTD appears to be a good option for giving long distance advice in a certain number of skin conditions. In this article, we will discuss benefits and limitations of PTD. We will also talk about diagnostic and therapeutic concordance between PTD and traditional consultations, as well as the most frequent advices asked., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

A retrospective study in which we reviewed the hospital files of a subset of 7 patients with Duchenne muscular dystrophy participating in the open-label phase I/II PRO051-02 study in Leuven. The objective of this study was to describe in detail the injection site reactions in these children treated with drisapersen (PRO-051), a 2'-O-methyl phosphorothioate RNA antisense oligonucleotide, that induces exon 51 skipping in Duchenne muscular dystrophy. Antisense oligonucleotides, restoring the reading frame by skipping of exons, have become a potential treatment of Duchenne muscular dystrophy and other monogenetic diseases. Erythema followed by hyperpigmentation, fibrosis, and calcification were seen at the injection sites in all children. Ulcerations, which were difficult to heal, occurred in 5 of 7 children. Progression still occurred after switching to intravenous administration of drisapersen or even after stopping therapy. Systemic reactions included a reversible proteinuria and α1-microglobulinuria. Moreover, hypotrichosis was a common feature.Conclusion: Subcutaneous administration of drisapersen causes severe and progressive injection site effects. What is known: • Antisense oligonucleotides offer the possibility to convert Duchenne muscular dystrophy to the less severe Becker type. This can potentially be achieved by targeting and skipping specific exons of the Duchenne muscular dystrophy gene to restore the disrupted reading frame and to induce the production of a semi functional dystrophin protein. • Drisapersen is such an antisense oligonucleotides which can be administered subcutaneously. Its use has been tested extensively in the escalating dose pilot study (PRO051-02). What is new: • This report describes the injection site reactions caused by this type of agent in detail which has never been done before. We therefore reviewed the hospital files of 7 patients with Duchenne muscular dystrophy participating in the phase I/II open-label, escalating dose pilot study (PRO051-02) with drisapersen. • Severe side effects starting with erythema, hyperpigmentation, and later fibrosis, calcification, and difficult to treat ulcerations developed in all patients, and these continued to progress even after cessation of drisapersen. We discuss some possible underlying mechanisms. The exact mechanism however is still not known.

Mastocytosis is a unique hematologic neoplasm with complex biology and pathology and a variable clinical course. The disease can essentially be divided into cutaneous mastocytosis (CM) and systemic mastocytosis (SM). In adults, SM is diagnosed in most cases and manifests as either indolent or advanced disease. Patients with advanced SM have an unfavorable prognosis with reduced survival. However, so far, little is known about the prevalence of various categories of SM and about prognostic factors. In an attempt to learn more about the behavior and evolution of various forms of CM and SM, the European Competence Network on Mastocytosis (ECNM) initiated a mastocytosis registry in 2012. In this article, the set up and start phase of this registry are described. Until 2018, more than 3000 patients from 12 countries and 25 centers have been enrolled. In a majority of all patients, robust follow-up data and relevant clinical end points are available. Using this data set, a series of registry projects have been launched, with the aim to validate previously identified diagnostic and prognostic variables and to identify new disease-related and patient-related parameters in various forms of mastocytosis. Moreover, the core data set of the registry will be useful to establish multiparametric scoring systems through which prognostication and individualized management of patients with mastocytosis should improve in the foreseeable future., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chemotherapy-induced skin sclerosis is generally not associated with other manifestations of systemic sclerosis. It is featured by skin sclerosis without visceral involvement (i.e., Raynaud's phenomenon, esophageal dysmotility, and pulmonary fibrosis), temporal association with chemotherapy administration, and the absence of detectable autoantibodies. The clinical course of scleroderma-like changes induced by paclitaxel or gemcitabine are refractory to treatment and commonly progressive, even after discontinuation of the triggering drugs., Objective: Report a case of scleroderma-like cutaneous lesions during combination treatment with nab-paclitaxel and gemcitabine in a patient with pancreatic adenocarcinoma and determine other published cases of scleroderma-like skin changes following treatment with nab-paclitaxel, paclitaxel, or gemcitabine through the period from 2002 to 2018., Methods: Literature search from the year 2002 onwards using combinations of "Scleroderma" AND "paclitaxel," AND/OR "gemcitabine.", Results: Additional to our case report we reviewed 14 other cases in the literature. Most of these cases share three prominent features: skin sclerosis without systemic involvement, temporal association with chemotherapy administration, and absence of detectable scleroderma-specific autoantibodies., Conclusion: To our knowledge, this is the first case report of scleroderma-like cutaneous lesions during combination treatment with nab-paclitaxel and gemcitabine in a patient with pancreatic adenocarcinoma. However, given the current literature, these scleroderma-like lesions are most likely induced by nab-paclitaxel or paclitaxel, rather than by gemcitabine., (© 2018 The International Society of Dermatology.)

Background: Epidermolysis bullosa dystrophica is a rare dermatological disease characterized by extreme skin fragility and elevated risk of developing a squamous cell carcinoma. In some cases, amputation of a limb is necessary. Case description and methods: A 37-year-old man with recessive, severe generalized epidermolysis bullosa dystrophica developed a squamous cell carcinoma on the right forearm requiring a below-elbow amputation. Preoperative advice concerning indication and level of amputation was given. Due to potential skin problems, a conventional prosthesis was not feasible. Findings and outcomes: A custom-designed adaptive prosthesis with an upper arm cuff was trialed and was well tolerated. Multiple working tools, attached with a rotation and inclination system, allowed independence and return to work., Conclusion: Despite multiple potential skin problems of the stump, the patient was successfully fitted with a custom-designed adaptive prosthesis. Preparation for this fitting was done by a comprehensive multidisciplinary patient-centered approach. Clinical relevance Despite severe skin fragility, a patient with epidermolysis bullosa dystrophica was successfully fitted with a custom-designed adaptive upper limb prosthesis allowing good functional outcome. This required a multidisciplinary and patient-centered approach.

A patient with extensive multisystem overgrowth caused by a somatic gain of function PIK3CA-mutation is described. This case is an example of the clinical diversity of the PIK3CA-Related Overgrowth Spectrum (PROS) as the patient had overlapping features of Congenital Lipomatous Overgrowth Vascular malformations Epidermal nevi and Skeletal abnormalities (CLOVES) syndrome and Megalencephaly-Capillary malformation Polymicrogyria (MCAP) syndrome and underlines the utility of this umbrella term., (© 2018 Wiley Periodicals, Inc.)

We describe the characterization of Xeroderma Pigmentosum variant (XPV) in a young Caucasian patient with phototype I, who exhibited a high sensitivity to sunburn and multiple cutaneous tumors at the age of 15 years. Two novel mutations in the POLH gene, which encodes the translesion DNA polymerase η, with loss of function due to two independent exon skippings, are reported to be associated as a compound heterozygous state in the patient. Western blot analysis performed on proteins from dermal fibroblasts derived from the patient and analysis of the mutation spectrum on immunoglobulin genes produced during the somatic hypermutation process in his memory B cells, show the total absence of translesion polymerase η activity in the patient. The total lack of Polη activity, necessary to bypass in an error-free manner UVR-induced pyrimidine dimers following sun exposure, explains the early unusual clinical appearance of this patient., (© 2017 Wiley Periodicals, Inc.)

Background: Gain-of-function mutations in transmembrane protein 173 (TMEM173) encoding stimulator of interferon genes (STING) underlie a recently described type I interferonopathy called STING-associated vasculopathy with onset in infancy (SAVI)., Objectives: We sought to define the molecular and cellular pathology relating to 3 individuals variably exhibiting the core features of the SAVI phenotype including systemic inflammation, destructive skin lesions, and interstitial lung disease., Methods: Genetic analysis, conformational studies, in vitro assays and ex vivo flow-cytometry were performed., Results: Molecular and in vitro data demonstrate that the pathology in these patients is due to amino acid substitutions at positions 206, 281, and 284 of the human STING protein. These mutations confer cGAMP-independent constitutive activation of type I interferon signaling through TBK1 (TANK-binding kinase), independent from the alternative STING pathway triggered by membrane fusion of enveloped RNA viruses. This constitutive activation was abrogated by ex vivo treatment with the janus kinase 1/2 inhibitor ruxolitinib., Conclusions: Structural analysis indicates that the 3 disease-associated mutations at positions 206, 281, and 284 of the STING protein define a novel cluster of amino acids with functional importance in the regulation of type I interferon signaling., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Heightened cutaneous immune surveillance in atopic patients may inhibit development of melanoma. The aim of this study was to analyse the association between atopy and melanoma (development and outcome). A total of 188 cases of melanoma and 596 healthy controls were interviewed by telephone with a standardized questionnaire on atopic, demographic and melanoma characteristics. Cases were matched with controls on important confounders (age, sex, sunburn sensitivity, hair colour, number of moles, sunburn as juvenile, ever solarium, familial melanoma). Melanoma outcome data (disease relapse and death) within cases were retrieved. Analysis showed a general inverse association between atopy and melanoma development, but this was statistically significant only for a history of personal atopy (odds ratio 0.53, 95% confidence interval: 0.30-0.96, p-value = 0.04). Among melanoma patients, atopy did not affect survival or progression. In conclusion, this study suggests an inverse association between a history of atopy and melanoma development, but not with disease progression.

Background: The technical and clinical outcomes of catheter-directed embolization for peripheral arteriovenous malformations (AVM) using Onyx® (ethylene-vinyl alcohol copolymer) are not well documented. The purpose of this study was to retrospectively assess the safety, technical outcomes and clinical outcomes of catheter-directed Onyx® embolisation for the treatment of symptomatic peripheral AVMs., Patients and Methods: Demographics, (pre-)interventional clinical and radiological data were assessed. Follow-up was based on hospital medical records and telephone calls to the patients' general practitioners. Radiological success was defined as complete angiographic eradication of the peripheral AVM nidus. Clinical success was defined as major clinical improvement or complete disappearance of the initial symptoms., Results: 25 procedures were performed in 22 patients. The principal indications for treatment were pain (n = 10), limb swelling (n = 6), recurrent bleeding (n = 2), tinnitus (n = 3), and exertional dyspnoea (n = 1). Complete radiological success was obtained in eight patients (36 %); near-complete eradication of the nidus was achieved in the remaining 14 patients. Adjunctive embolic agents were used in nine patients (41 %). Clinical success was observed in 18 patients (82%). Major complications were reported in two patients (9 %). During follow-up, seven patients (32 %) presented with symptom recurrence, which required additional therapy in three patients., Conclusions: Catheter-directed embolisation of peripheral AVMs with Onyx® resulted in major clinical improvement or complete disappearance of symptoms in the vast majority of patients, although complete angiographic exclusion of the AVMs occurred in only a minority of patients.

Background: Langerhans cell histiocytosis (LCH) is a rare disease, frequently affecting young children., Procedure: We performed a retrospective study in patients younger than 16 years old manifesting with skin symptoms, and documented their different cutaneous lesions and systemic symptoms. We compared subgroups of children with single-system, skin-only, and multisystem disease and sought signs predictive for multisystem disease. In a small sample of patients, BRAF mutations were analyzed in archived biopsies., Results: A wide spectrum of cutaneous presentations varying from crusted nodules and papules, blisters, vascular tumor-like lesions, scaling orange to red macules (frequently in seborrheic regions) to purpuric macules, and papules was documented in our cohort of 32 children. Otitis externa was a common manifestation and mucosal lesions were seen in three patients. A novel manifestation was a red-blue nodule that appeared in a patient after a vaccination. None of the cutaneous lesions was predictive for the classification or final outcome as a single-system or multisystem disease. However, later onset and a more protracted course of skin lesions were more frequent findings in multisystem LCH. Mucosal lesions and otitis externa were almost exclusively seen in patients with multisystem disease, a finding that warrants further investigation. Both wild-type (WT) and mutated BRAF were found not only in multisystem LCH, but also in skin-only LCH. Two cases with rapidly resolving congenital lesions had WT BRAF., Conclusions: Late onset and a protracted course of skin lesions are associated with MS-LCH, whereas WT BRAF is found in rapidly resolving skin lesions., (© 2015 Wiley Periodicals, Inc.)

Linear scleroderma en coup the sabre (LSCS), progressive facial hemiatrophy (PFH) and autoimmune encephalitis are distinct clinical entities, although patients with overlapping features have been reported. We performed a multicenter retrospective review of a series of children with LSCS and/or PFH to explore the relation between these entities. The files of 16 children were reviewed, 11 presented with LSCS, 5 with PFH, with time overlapping cutaneous features were seen. Extracutaneous signs were found in both groups. ANA were present in more than 50 % of patients. Almost half of our patients presented with CNS manifestations comprising unilateral headache, migraine and epilepsy with or without abnormalities on MRI. Brain biopsy in one patient was consistent with Rasmussen encephalitis. In two other children, associated autoimmune manifestations were present., Conclusion: Our patient cohort brings more arguments to consider LSCS and PFH as a single disease entity with LSCS and superficial skin involvement at one end of the spectrum and PFH with involvement of subcutaneous deep tissue at the other end. In both entities, encephalitis can be observed. Our findings of circulating ANA, intradermal lymphocytes and IgG, intrathecal IgG production and clinical improvement with immunosuppressive therapy endorse the concept of a possible common immune-inflammatory pathogenesis., What Is Known: • LSCS, PFH and immune-inflammatory encephalitis are distinct clinical entities, but patients with overlapping features have been reported., What Is New: • We present a unique paediatric cohort with LSCS, PFH and/or encephalitis. • We endorse the concept of a common immune-inflammatory disease process.

Frey's syndrome is characterized by sweating and flushing in the temporal and preauricular areas after a salivary stimulus. It is caused by damage to the auriculotemporal nerve, hence the alternative name of auriculotemporal syndrome. We report the case of a 2-year-old girl presenting with postprandial unilateral flushing that developed after a herpes zoster infection., (© 2015 Wiley Periodicals, Inc.)

Conradi-Hünermann-Happle syndrome (X-linked dominant chondrodysplasia punctata, CDPX2 [Online Mendelian Inheritance in Man 302960]) is a rare genodermatosis that presents with blaschkolinear ichthyosis, cicatricial alopecia, chondrodysplasia punctata, asymmetric shortening of the bones, and cataracts. In this case report we describe a child presenting with a patterned alopecia in which supplementary signs and clinical examination of the mother led to the suspicion of Conradi-Hünermann-Happle syndrome. Mutation analysis revealed a heterozygous novel missense mutation, c.204G>T (p.W68C), in exon 2., (© 2014 Wiley Periodicals, Inc.)

Background: Neurocutaneous melanocytosis is a rare congenital dysplasia of the neuroectodermal melanocyte precursor cells that leads to proliferation of melanin-producing cells in the skin and leptomeninges., Patient: We describe a newborn with a giant congenital melanocytic nevus on his back, buttocks, and thighs. His brain magnetic resonance imaging study revealed bilateral T1 hyperintense lesions in the cerebellum and in the amygdala, hydrocephalus, and a Blake's pouch cyst, consistent with neurocutaneous melanocytosis and Dandy-Walker malformation., Conclusion: Neurocutaneous melanocytosis has a wide clinical spectrum that includes hydrocephalus, epilepsy, cranial nerve palsy, increased intracranial pressure, and sensorimotor deficits., (Copyright © 2014. Published by Elsevier Inc.)

Pimecrolimus 1% cream is an effective, non-corticosteroid, topical anti-inflammatory treatment for atopic dermatitis (AD). The aim of this article was to review published clinical data that have examined how pimecrolimus can address the medical needs of AD patients. Clinical studies have demonstrated that early treatment with pimecrolimus decreases the progression to disease flares, rapidly improves pruritus and significantly enhances quality of life. Patients find the formulation easy to apply, which may result in improved adherence with the treatment regimen. Pimecrolimus, in contrast to topical corticosteroids (TCSs), does not induce skin atrophy or epidermal barrier dysfunction and is highly effective for the treatment of AD in sensitive skin areas. Furthermore, pimecrolimus reduces the incidence of skin infections compared with TCSs and is not associated with other TCS-related side effects such as striae, telangiectasia and hypothalamic-pituitary-adrenal axis suppression. An additional benefit of pimecrolimus is its substantial steroid sparing effect. On the basis of these data, a new treatment algorithm for patients with mild-to-moderate AD is proposed in which pimecrolimus is recommended as a first line therapy for patients with established mild AD at the first signs and symptoms of disease. Pimecrolimus is also recommended for mild-to-moderate AD after initial treatment with a TCS. After resolution of lesions, maintenance treatment with pimecrolimus may effectively prevent subsequent disease flares. In conclusion, the clinical profile of pimecrolimus suggests that it may be considered the drug of choice for the treatment of mild-to-moderate AD in children as well as adults and particularly in sensitive skin areas.

Background: Olmsted syndrome is a rare congenital skin disorder presenting with periorifical hyperkeratotic lesions and mutilating palmoplantar keratoderma, which is often associated with infections of the keratotic area. A recent study identified de novo mutations causing constitutive activation of TRPV3 as a cause of the keratotic manifestations of Olmsted syndrome., Methods: Genetic, clinical and immunological profiling was performed on a case study patient with the clinical diagnosis of Olmsted syndrome., Results: The patient was found to harbour a previously undescribed 1718G-C transversion in TRPV3, causing a G573A point mutation. In depth clinical and immunological analysis found multiple indicators of immune dysregulation, including frequent dermal infections, inflammatory infiltrate in the affected skin, hyper IgE production and elevated follicular T cells and eosinophils in the peripheral blood., Conclusions: These results provide the first comprehensive assessment of the immunological features of Olmsted syndrome. The systemic phenotype of hyper IgE and persistent eosinophilia suggest a primary or secondary role of immunological processes in the pathogenesis of Olmsted syndrome, and have important clinical consequences with regard to the treatment of Olmsted syndrome patients.

Poor adherence is frequent in patients with atopic dermatitis (AD), leading to therapeutic failure. Therapeutic patient education (TPE) helps patients with chronic disease to acquire or maintain the skills they need to manage their chronic disease. After a review of the literature, a group of multispecialty physicians, nurses, psychologists, and patients worked together during two international workshops to develop common recommendations for TPE in AD. These recommendations were structured as answers to nine frequently asked questions about TPE in AD: What is TPE and what are its underlying principles? Why use TPE in the management of AD? Who should benefit from TPE in AD? How can TPE be organized for AD? What is the assessment process for TPE in AD? What is the evidence of the benefit of TPE in AD? Who are the people involved in TPE? How should TPE be funded in dermatology? What are the limits of the TPE process?, (© 2013 Wiley Periodicals, Inc.)

Focal facial dermal dysplasia (FFDD) Type IV is a rare syndrome characterized by facial lesions resembling aplasia cutis in a preauricular distribution along the line of fusion of the maxillary and mandibular prominences. To identify the causative gene(s), exome sequencing was performed in a family with two affected siblings. Assuming autosomal recessive inheritance, two novel sequence variants were identified in both siblings in CYP26C1-a duplication of seven base pairs, which was maternally inherited, c.844&#95;851dupCCATGCA, predicting p.Glu284fsX128 and a missense mutation, c.1433G>A, predicting p.Arg478His, that was paternally inherited. The duplication predicted a frameshift mutation that led to a premature stop codon and premature chain termination, whereas the missense mutation was not functional based on its in vitro expression in mammalian cells. The FFDD skin lesions arise along the sites of fusion of the maxillary and mandibular prominences early in facial development, and Cyp26c1 was expressed exactly along the fusion line for these facial prominences in the first branchial arch in mice. Sequencing of four additional, unrelated Type IV FFDD patients and eight Type II or III TWIST2-negative FFDD patients revealed that three of the Type IV patients were homozygous for the duplication, whereas none of the Type II or III patients had CYP26C1 mutations. The seven base pairs duplication was present in 0.3% of healthy controls and 0.3% of patients with other birth defects. These findings suggest that the phenotypic manifestations of FFDD Type IV can be non-penetrant or underascertained. Thus, FFDD Type IV results from the loss of function mutations in CYP26C1.

Diffuse cutaneous mastocytosis is a less common but potentially life-threatening variant of childhood mastocytosis. Here we report 2 children with diffuse cutaneous mastocytosis in whom an activating somatic KIT mutation was detected. Treatment with imatinib, a KIT inhibitor, resulted in resolution of the lesions and were well tolerated by the patients., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To develop the Leuven Itch Scale (LIS), which measures itching through evaluation of the dimensions of the itch experience; and to provide evidence of the validity, reliability, and responsiveness of the LIS., Materials and Methods: A clinimetric study using a longitudinal design. Patients with burns (n=46), atopic dermatitis (n=63), or chronic urticaria (n=41) were included. Evidence for validity (based on test content, relations with other variables and internal structure), reliability and responsiveness of the LIS was evaluated., Results: Validity evidence based on test content was demonstrated by very low percentages of invalid scores for most items. Validity evidence based on relations with other variables was found, because all hypotheses that were put forward could be accepted. With respect to validity evidence on internal structure, a significant moderate positive correlation was found between itch frequency and itch distress, and between itch frequency and severity. As hypothesized, itch severity and distress were strongly correlated. Test-retest reliability showed a moderate to almost perfect agreement for about half of the items. However, the remaining items could be subject to changes in the itch, rather than reflecting instability of the Leuven Itch Scale. In terms of responsiveness, the Leuven Itch Scale did not suffer from floor or ceiling effects and could detect changes in itch frequency in patients with burns., Conclusion: The Leuven Itch Scale is a useful and clinimetrically sound instrument to measure pruritus in different patient populations affected by itching., (Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.)

Rothmund-Thomson syndrome (RTS)(OMIM 268400) is a rare autosomal recessive genodermatosis characterized by poikiloderma, small stature, skeletal and dental abnormalities, cataract and an increased risk of cancer. It is caused by mutations in RECQL4 at 8q24. Immune deficiency is not described as a classical feature of the disease. Here we report the appearance of granulomatous skin lesions complicating primary Varicella Zoster Virus infection in a toddler with Rothmund Thomson syndrome and immune deficiency. Although granulomatous disorders are sometimes seen after Herpes zoster, they are even more rare after Varicella primary infection. Granulomas have hitherto not been described in Rothmund-Thomson syndrome. With this report we aim to stress the importance of screening for immune deficiency in patients with Rothmund-Thomson syndrome.