Dermatologic manifestations in paediatric neurofibromatosis type 2: a cross sectional descriptive multicentric study.

BACKGROUND: Neurofibromatosis type 2 (NF2) is characterized by bilateral vestibular schwannoma (VS) more often in adults but a severe paediatric form with multiple neurological tumours is also described. In this population, a early diagnosis is important to prevent the onset of neurological complications but is difficult, particularly without a familial history. Cutaneous manifestations, which may precede VS or neurological tumours by several years, may contribute to an early diagnosis, but specific studies are lacking. The objective of this study was to characterize cutaneous manifestations of NF2 in a paediatric population. RESULTS: This observational, descriptive and multicentric study was conducted from April 2019 to April 2020 in seven academic French hospitals. We included patients ≤ 18 years old who fulfilled the Manchester diagnostic criteria or had a pathogenic mutation identified in the NF2 gene. All patients underwent a dermatological examination guided by a standardized questionnaire. 21 children were included, of whom 20 had at least one skin tumour (mean number 5 ± 4.6 [range 0-15]), which led to a diagnosis in four cases. In the other 17 cases, the diagnosis of NF2 was based on neurosensory complications (n = 10), family screening (n = 4) or ocular signs (n = 3). Before the NF2 diagnosis, 15 children had at least one "undiagnosed" cutaneous tumour that did not lead to a specific management. Patients' dermatological examination also revealed < 6 non specific café au lait macules (n = 15), hypopigmented macules (n = 12) with more than 3 lesions in 4 cases, and purple reticulated macules of the trunk (n = 4). CONCLUSION: Dermatological lesions are frequent and early in children with NF2 but rarely lead to the diagnosis. Cutaneous schwannomas are the most frequent but are often underdiagnosed. Café au lait macules are frequent, but atypical and mostly in small numbers. Multiple hypopigmented macules seem suggestive although inconsistent. The sensitivity of reticulated capillary malformation-like lesions remains to be assessed by further studies.

Epidermolysis bullosa simplex generalized severe induces a T helper 17 response and is improved by apremilast treatment.

BACKGROUND: Epidermolysis bullosa simplex generalized severe (EBS-gen sev) is a genetic disorder caused by mutation in the KRT5 or KRT14 genes. Although it is usually considered a mechanical disease, recent data argue for additional inflammatory mechanisms. OBJECTIVES: To assess the inflammation in the skin of patients with EBS-gen sev. METHODS: A first immunohistochemical retrospective study was performed on frozen skin samples from 17 patients with EBS-gen sev. A second multicentre prospective study was conducted on 10 patients with severe EBS-gen sev. Blister fluid and epidermis were processed for immunochemical analysis and quantitative real-time polymerase chain reaction. Cytokine expression was analysed in blister fluid and compared with that in controls. RESULTS: Histological analysis showed a constant dermal perivascular CD4+ lymphocyte infiltrate in skin biopsies of both blister (n = 17) and rubbed skin (n = 5), an epidermal infiltration of neutrophils and eosinophils in 70% of cases, and increased immunostaining for CXCL9 and CXCL10 in blistering skin. High levels of T helper 17 cytokines were detected in lesional skin. Three adult patients with EBS-gen sev were treated with apremilast, with a dramatic improvement of skin blistering and good tolerance. CONCLUSIONS: Our study demonstrates the importance of inflammation in patients with EBS-gen sev and underlines the key role for T helper 17 cells in its pathogenesis. In addition, this study provides promising new therapeutic approaches for this disabling disorder.

Aplasia cutis congenita with dystrophic epidermolysis bullosa: clinical and mutational study.

BACKGROUND: Aplasia cutis congenita (ACC) has been associated with all clinical forms of inherited epidermolysis bullosa (EB), including dominant and recessive dystrophic EB (DDEB and RDEB). To date, only a few patients with DEB specifically combined with ACC have been described and genotyped and almost all cases represent dominant forms of the condition. OBJECTIVES: The aim of this study was to describe new mutations of COL7A1 in patients with DEB and ACC and investigate possible genotype-phenotype correlations. METHODS: Twenty-two patients with DEB and ACC were included among the 123 patients with DEB whose COL7A1 mutations have been identified in the Reference Centre in Nice. RESULTS: Seven patients presented a severe generalized RDEB phenotype (RDEB-sev-gen), while the other 15 suffered from milder phenotypes. We identified 28 mutations in COL7A1, of which nine are novel. Patients with severe phenotypes have mostly mutations leading to premature termination codon (PTC) and/or splice-site or missense mutations. Patients with the milder phenotypes have mostly glycine or arginine substitutions associated or not with other types of mutations. All amino acid substitutions fell within the carboxyl portion of the triple helix domain (THD) of collagen VII, close to the THD interruptions. CONCLUSIONS: Our findings suggest that ACC is a frequent manifestation in patients with DEB irrespective of the severity of the disease, and is due to leg rubbing in utero. In children with a moderate form of DEB with no or moderate skin fragility, a glycine substitution near the THD interruption domain of the collagen VII leading to thermolabile protein could explain this phenomenon.

[Atypical onset of Churg and Strauss syndrome in a child]. / Révélation atypique d'un syndrome de Churg et Strauss chez l'enfant.

We report the case of a 13-year-old boy who had been treated since the age of 6 for moderate asthma. Except asthma, his past medical history was uneventful. The patient was referred for the sudden onset of bilateral leg edemas with peripheral purpuric lesions. Blood tests showed increased blood eosinophilia (9000/mm(3)) with no fever. The antineutrophil cytoplasmic antibodies (ANCA) were negative. The skin biopsy showed extensive ischemic subcutaneous necrosis related to necrotizing vasculitis. The general secondary symptoms occurred with multiorgan involvement (pulmonary infiltrates, peripheral neuropathy, gastrointestinal tract symptoms, and arthralgia). Genital infiltration was also noted. The child's general health was preserved. Neither cardiac nor renal involvement were found. The patient showed favorable clinical progression after oral prednisone therapy.

Efficacy and tolerability of methotrexate in severe childhood alopecia areata.

BACKGROUND: Alopecia areata (AA) occurring in childhood is associated with a poorer prognosis than adult AA and may severely affect quality of life. The efficacy of methotrexate (MTX) was reported in adults with AA but there is little information about its use in children. OBJECTIVES: We aimed to assess the efficacy and safety of MTX in severe childhood AA. METHODS: We conducted a retrospective study including children with severe AA treated with MTX in the Departments of Paediatric Dermatology in France between November 2005 and December 2009. RESULTS: Fourteen children (eight girls and six boys) aged between 8 and 18 years (mean 14·7) were included. AA was present for a mean duration of 5·7 years (range 2 months-11 years 8 months). The treatment was administered once weekly, the mean maximal dose was 18·9 mg weekly (range 15-25) and the mean duration of treatment was 14·2 months (range 1-31). Thirteen children were assessable. Of these 13 children, MTX was considered as successful (regrowth >50% of hair) for five of them. The remaining eight children were considered treatment failures. No serious side-effects were reported. CONCLUSIONS: The efficacy of MTX in children with severe AA is variable. MTX may be considered for severe childhood AA in the absence of alternative effective treatments.

[Pilar dysplasias]. / Les dysplasies pilaires.

Pilar dysplasias are congenital or acquired disorders, they are characterized by hair abnormalities in color, density, length and structure. Optic microscopy and polarized light microscopy analysis of piliary shafts provides important informations and contribute to the diagnosis of complex syndromes. Many pathological profiles can be visualized, some are specific, other are not. Some authors use a particularly convenient classification including 3 groups: in the first, piliary shaft abnormalities are isolated, in the second the abnormalities correspond to complex syndromes, and in the third they are associated with various malformations. Based on some clinical cases, we will describe various types of pilar dysplasias and we present recent advances, particularly in genetics.

[Xerosis]. / La xérose.

The clinical characteristic of xerosis is rough or coarse skin. Physiopathologically, the structure of the stratum corneum is modified and abnormalities in keratinization, proliferation, surface lipid, water metabolism and also pH and sebum exist. There are two forms of xerosis: dry skin forms and ichtyosis or ichtyosis-like forms. Xerosis has many etiologies including external aggression, senescence, drugs, infection, atopy, deficiencies, malignant diseases, endocrine affections, eating disorders and renal failure in dialyzed patients. It provokes cutaneous discomfort and unaesthetic appearance that justify appropriate treatment. Treatment is essentially local, symptomatic and must be accompanied by general measures. Many products include moisturizers and emollients (keratolytics: salicylic acid, urea and alpha-hydroxy acid).

[Drug hypersensitivity syndrome to valproic acid]. / Syndrome d'hypersensibilité médicamenteuse à l'acide valproïque.

BACKGROUND: Drug-induced hypersensitivity syndrome is an uncommon but potentially life-threatening idiosyncratic drug reaction. It is usually due to aromatic anti-convulsants. We report the second case induced by sodium valproate, a non-aromatic anticonvulsant. CASE REPORT: A 28-year-old woman was treated with sodium valproate for 5 weeks. She suddenly developed a generalized maculo-papulous eruption with fever, node enlargement, hypereosinophilia and altered liver function. DISCUSSION: Drug-induced hypersensitivity is rarely induced by valproic acid. The time-course and positive patch tests using the diluted drug establish the diagnosis.

Efficient in vitro regeneration of leek (Allium ampeloprasum L.) via flower stalk segments.

A new simple, efficient and rapid in vitro method for mass clonal propagation of leek (Allium ampeloprasum L.) plants, using small (5 mm) flower stalk (peduncle) explants, was established. Adventitious shoots were produced from single subepidermal cells. A wide variation in the percentage of regenerating explants and number of regenerated shoots per explant between individual plants within one cultivar was observed. The concentration of the growth regulators 6-benzylaminopurine and α-naphthalene-acetic acid influenced the percentage of regenerating explants and the average number of regenerated shoots per explant. A combination of 10 mg.l(-1) 6-benzylaminopurine and 10 mg.l(-1) α-naphthalene-acetic acid, resulted in a maximum percentage of regenerating explants and a high average number of regenerated shoots per explant. The percentage of regenerating explants and the average number of regenerated shoots per explant decreased with increasing flower stalk length (age). The basal explants gave both the highest percentage of regenerating explants and average number of regenerated shoots per explant. An average of 300 shoots per flower stalk was obtained for all plants, making this new in vitro method a powerful tool in hybrid leek breeding.