[Autoimmune bullous diseases in children]. / Dermatoses bulleuses auto-immunes chez les enfants.

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.

Les maladies bulleuses auto-immunes (MBAI) sont rares chez les enfants. Bien que la pathogenèse soit similaire à celle de l'adulte, il existe des différences concernant la présentation clinique et la prévalence des MBAI selon l'âge. À ce jour, il n'y a pas de recommandations spécifiques pour leur prise en charge chez l'enfant. Dans cet article, nous présentons une revue des données actuelles, des critères diagnostiques et proposons un algorithme de prise en charge.

[Treatment of childhood psoriasis: present and future]. / Thérapie du psoriasis pédiatrique : présent et futur.

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.

Le psoriasis peut déjà se manifester dans l'enfance avec des lésions cutanées, des ongles, du scalp, mais parfois aussi une atteinte articulaire. Cette maladie a un impact important sur la qualité de vie de l'enfant. Dans cet article, nous présentons une revue des traitements en ce moment possibles chez les enfants, selon la surface de peau atteinte, la sévérité des lésions, en mettant surtout en lumière les traitements par biologiques déjà possibles et en étude.

[Clinical, therapeutic and pathophysiological aspects of Darier's disease]. / Aspects physiopathologiques cliniques et thérapeutiques de la maladie de Darier.

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.

La maladie de Darier est une génodermatose rare à transmission autosomique dominante. Elle se manifeste autour de la puberté par des papules kératosiques brunâtres des plis et des zones séborrhéiques, associées à une onychopathie et une atteinte muqueuse, et évolue par poussées déclenchées par les UV, la chaleur, les frottements ou les infections. Les patients atteints présentent un risque accru de diabète de type 1, d'insuffisance cardiaque et de troubles neuropsychiatriques. La prise en charge à court terme consiste en des antibiotiques/antiviraux, des corticostéroïdes topiques et/ou des rétinoïdes. Celle à long terme repose sur les émollients et l'éviction des facteurs déclenchants. Le traitement à long terme n'étant pas codifié, de nombreux traitements locaux et sytémiques, mesures physiques et chirurgicales sont décrits dans la littérature.

Paediatric onset lymphomatoid papulosis: results of a multicentre retrospective cohort study, on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG).

BACKGROUND: Lymphomatoid Papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population is scarce. OBJECTIVES: To characterize epidemiological, clinical, histopathological, and prognostic features of paediatric LyP. METHODS: This was a retrospective, multicentre international cohort study including 87 cases of children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years old at disease onset were included. Diagnosis was made in each centre based on clinical-pathological correlation. RESULTS: Eighty-seven patients from 12 centres were included. The mean age at onset was 7.0 years (range 3 months-18 years) with a male to female ratio of 2:1. The mean time between onset of first cutaneous lesions and diagnosis was 1.3 years (range 0-14 years). Initial misdiagnosis concerned 26.4% of patients. Initially, LyP was most often misdiagnosed as Pityriasis lichenoides et varioliformis acuta (PLEVA), insect bites, or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned for 20.7% of patients. The main histological subtype was type A in 55.1% of the cases. If analysed, monoclonal TCR rearrangement was found in 76.5% of the 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. A development of associated haematological malignancy (HM) occurred in 9.6% of the cases (7/73), including four mycosis fungoides (MF) cases, one primary cutaneous anaplastic large cell lymphoma (pc-ALCL), one systemic ALCL and one case of acute myeloid leukaemia. If we compare incidence rates of cancer with the world 0-19 years old population from 2001-2010, we estimate a significantly higher risk of associated malignancy in general, occurring before the age of 19 years old with incidence rate ratio of 87.49 (CI 86.01-88.99). CONCLUSIONS: We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall the prognosis of the disease is good, with excellent survival rates for all patients. Due to increased risk of associated HM, a long-term follow-up should be recommended for LyP patients.

Mosaic RASopathies concept: different skin lesions, same systemic manifestations?

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.

It is not always chlorhexidine: Identification of benzoxonium chloride and lauramine oxide as culprit allergens in a popular antiseptic in Switzerland.

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.

[Tinea capitis: new insights into an old disease]. / Tinea capitis: actualité d'une pathologie ancienne.

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.

Tinea capitis (ou teigne du cuir chevelu) est une infection fongique superficielle du cuir chevelu par un dermatophyte. Cette dermatose est fréquente et prédomine en population pédiatrique. Le tableau clinique est hétérogène et varie beaucoup en fonction de l'espèce de dermatophyte associée. L'examen mycologique direct et des cultures doivent être effectués pour un diagnostic précis et une identification de l'espèce. Le traitement devrait être à la fois local et systémique, et adapté au diagnostic de l'espèce dermatophyte identifiée en laboratoire de mycologie. La prophylaxie secondaire, par des mesures associées, est déterminante pour limiter l'émergence de foyers épidémiques ou la réinfection du patient.

[Juvenile dermatomyositis, the dermatologist's point of view].

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.

La dermatomyosite juvénile est une maladie auto-immune multisystémique rare caractérisée par une faiblesse musculaire et/ou une éruption cutanée. Le diagnostic se pose par la reconnaissance des signes cutanés caractéristiques qui, contrairement à l'atteinte musculaire, se voit au stade initial de la maladie. L'IRM est l'examen de choix pour détecter la myosite. La mise en évidence récente d'auto-anticorps spécifiques de la maladie a permis de mieux comprendre et d'établir des pronostics sur l'évolution clinique des patients. Un diagnostic précoce et un traitement agressif sont cruciaux pour aider à obtenir une rémission. Ils permettent d'améliorer la fonction musculaire, de prévenir d'importantes séquelles cutanées difficilement traitables comme la calcinose et la lipodystrophie et d'éviter l'atteinte d'organes vitaux.

Contact allergy in a paediatric population observed in a tertiary referral centre in Belgium.

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.

Case Report: Pansclerotic Morphea-Clinical Features, Differential Diagnoses and Modern Treatment Concepts.

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.

Challenges in Treating Genodermatoses: New Therapies at the Horizon.

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.

Distal-type epitheloid sarcoma mimicking a wart in a child: A diagnosis not to be missed.

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.

Overview of STING-Associated Vasculopathy with Onset in Infancy (SAVI) Among 21 Patients.

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.

Birt-Hogg-Dubé syndrome.

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.

Keratinocytic epidermal nevi associated with localized fibro-osseous lesions without hypophosphatemia.

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.

Topical Corticosteroid Phobia Among Healthcare Professionals Using the TOPICOP Score.

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.