[What is your diagnosis? Annular hypopigmented skin lesions in a 6-year-old child].
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Biopsy↗
Biomedical subjects
Y de Prost
Publications and source records attributed to Y de Prost.
Consensus statement on the safety profile of topical calcineurin inhibitors.
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Administration, Topical↗
[The value of topical immunosuppressors in the treatment of atopic dermatitis in children].
The use of topical immunosuppressors during treatment of atopic dermatitis is an important innovation that reinforces the therapeutic arsenal in this chronic disease in children. Two products have been studied in depth: tacrolimus, which exists in pomade form at a concentration of 0.1 and 0.03% under the trademark Protopic. It is the 0.03% concentration that has been studied in children and obtained official indication in children aged over 2. Pimecrolimus marketed under the trademark Elidel in the form of a 1% cream has also been studied in depth and obtained European marketing authorisation for prescription in children aged over 2. Unfortunately it is not yet available in France, although it is marketed in nearly all countries worldwide. These products decrease the production of cytokines by the T-cell lymphocytes when stimulated by the antigen. This effect is produced by the inhibition of calcineurine. The clinical efficacy of these two products has been demonstrated in many studies in the United States and in Europe. Short term efficacy has been demonstrated in comparisons versus a placebo or versus grade 2 or 3 corticosteroids. Longer term studies (6 months to one year) have confirmed the efficacy. Short-term tolerance to these new treatments has been shown, although, as with any new product, the long-term results are unknown. Nevertheless, tolerance studies after more than 4 years' use exist. The side effects most often reported are local, erythema-like at the start of treatment with burning and pruritus. There has been no significant increase in the number of bacterial and viral infections compared with control groups. Doubt remains regarding viral infections of herpetic origin, notably Kaposi-Juliusberg's disease, although no significant difference has been observed compared with the placebo-treated. No systemic impact has been reported with these two products or inhibition of the effect of vaccinations made in infants or children. However, care should be taken: not to use the products in patients with a history of Kaposi-Juliusberg's disease and any contact with a patient exhibiting herpes should be avoided; the photoprotection measures should be respected as instructed in the patient insert for the use of tacrolimus.
Administration, Topical↗
Prenatal diagnosis of a lethal form of Netherton syndrome by SPINK5 mutation analysis.
Netherton syndrome (NS) is a severe autosomal recessive ichthyosis with no specific treatment or prenatal diagnosis available at present. The recent identification of SPINK5, which encodes a serine protease inhibitor, as the defective gene enables DNA based prenatal diagnosis to be carried out. Here we report the first direct molecular prenatal diagnosis of a lethal form due to a recurrent SPINK5 mutation in three consanguineous Turkish families. XmnI restriction enzyme digestion and DNA sequencing demonstrated that each deceased affected child was homozygous for mutation 153delT inherited from each parent. Analysis of fetal DNA from amniotic fluid cells in Family 1 and from a chorionic villus sampling in Family 3 showed that the fetus was heterozygous for 153delT in both cases. The pregnancies were carried to term and the newborns were unaffected. In Family 2, fetal DNA analysis from chorionic villus biopsy showed in a first pregnancy that the fetus was homozygous for 153delT. The pregnancy was terminated at 13 weeks and DNA analysis of fetal keratinocytes confirmed the prenatal prediction. In a second pregnancy in Family 2, fetal DNA analysis showed heterozygosity for 153delT, and the pregnancy was continued. Direct SPINK5 mutation analysis in families at risk for NS represents the first early, rapid and reliable method for prenatal diagnosis of this life threatening form of ichthyosis.
Amniocentesis↗
[Cutaneous-mucous allergies in children and adults. Atopic dermatitis].
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Adult↗
Genetic bases of severe junctional epidermolysis bullosa presenting spontaneous amelioration with aging.
Change of the clinical picture with aging is noted in some patients suffering from junctional epidermolysis bullosa (JEB), an inherited blistering disorder caused by extensive disadhesion of the epithelia. We have studied a patient born with severe JEB associated with absent expression of laminin 5. A remarkable reduction of the blistering tendency was observed with aging that correlated with a restored expression of immunoreactive laminin 5 molecules. Genetic analysis of the gene LAMB3 detected compound heterozygosity for the nonsense mutation R635X and a novel 2 bp deletion (1587delAG) resulting in a downstream premature termination codon. RT-PCR amplification of total RNA purified from skin biopsies demonstrated that the mutated beta3 mRNAs underwent rapid decay shortly after birth, and that illegitimate splicing of the mRNA carrying mutation 1587delAG generated a new internally shortened beta3 transcript with advancing age. Our genetic and biochemical data show that (i) the illegitimate splicing of the beta3 pre-mRNA results in synthesis and secretion of a laminin 5 heterotrimer with an internally deleted beta3 polypeptide, (ii) expression of the mutated beta3 polypeptide is up-regulated in the basal keratinocytes with high proliferative potential, (iii) absence of the N-terminal region of the beta3 rod domain II thought to stabilize the tertiary structure of the laminin 5 is not required for the assembly of the protein and (iv) the mutant laminin 5 retains its adhesive potential. Our results demonstrate that mRNA rescue may underlie the evolution of the clinical phenotype in inherited skin conditions.
Age Factors↗
Cyclosporine in childhood psoriasis.
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Child↗
Neonatal and infantile erythrodermas: a retrospective study of 51 patients.
OBJECTIVE: To determine the frequency of the various underlying causes of erythroderma in newborns or infants, as well as which clinical or laboratory findings were relevant for the etiological diagnosis. PATIENTS: Fifty-one patients who presented with exfoliative erythroderma during their first year of life were included in this retrospective study. SETTING: Department of Pediatric Dermatology at a university hospital. RESULTS: On average, the etiological diagnosis was established 11 months after the onset of erythroderma. The underlying causes observed included immunodeficiency (30%), simple or complex ichthyosis (24%), Netherton syndrome (18%), and eczematous or papulosquamous dermatitis (20%). Five patients (10%) had erythroderma of unknown origin. The following parameters were of value in determining the underlying cause of erythroderma: congenital onset, skin induration and the presence of large scaling plaques, alopecia with or without hair dysplasia, evolution, response to topical corticosteroid therapy, presence of infections, and failure to thrive. Histological analysis confirmed the diagnosis in only 19 (45%) of 42 cases. However, it proved of great value for the detection of significant lymphocyte infiltration or keratinocyte necrosis indicating a diagnosis of Omenn syndrome or immunodeficiency. The prognosis was poor in this series: the mortality rate was 16%, and severe dermatosis persisted in 29 (67%) of the survivors. CONCLUSIONS: The etiological diagnosis of neonatal erythroderma is difficult to make; some clinical features may be helpful, but no one feature is characteristic of a cause. An immunodeficiency must be suspected in cases of severe erythroderma with skin induration, severe alopecia, failure to thrive, infectious complications, or evocative histological findings. The prognosis is poor, with a high rate of mortality in immunodeficiency disorders and severe chronic disease in Netherton syndrome and psoriasis.
Dermatitis, Exfoliative↗
Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome.
We describe here eleven different mutations in SPINK5, encoding the serine protease inhibitor LEKTI, in 13 families with Netherton syndrome (NS, MIM256500). Most of these mutations predict premature termination codons. These results disclose a critical role of SPINK5 in epidermal barrier function and immunity, and suggest a new pathway for high serum IgE levels and atopic manifestations.
Abnormalities, Multiple↗
Linkage of Marie-Unna hypotrichosis locus to chromosome 8p21 and exclusion of 10 genes including the hairless gene by mutation analysis.
Marie-Unna hypotrichosis (MU) is a rare autosomal dominant congenital alopecia characterised by progressive hair loss starting in early childhood, often aggravated at puberty and leading to scarring alopecia of variable severity. We have studied three multigeneration families of Belgian, British and French descent. The human genome was screened with microsatellite markers spaced at 10-cM intervals and significant evidence for linkage to the disease was observed on chromosome 8p21, with a maximum two-point lod score of 8.26 for D8S1786 at a recombination fraction of 0. Recombinants narrowed the region of interest to a genetic interval of about 12 cM flanked by markers D8S280 and D8S1839. This interval contains the hairless gene which is mutated in autosomal recessive congenital atrichia. Sequencing of the entire coding region and intronic splice sites of the hairless gene in these three families and in two unrelated familial cases revealed several polymorphic changes but failed to identify causative mutations. Nine other genes located within this region and expressed in skin were also excluded by mutation analysis. Together with a recent linkage study performed in a Dutch and a British family by van Steensel et al these results provide evidence for the presence of a gene distinct from hairless in chromosomal region 8p21 playing an important role in hair follicle biology.
Alopecia↗
Skin elastic fibers in Williams syndrome.
The elastin gene is consistently deleted in Williams syndrome and as this protein represents the major component of the elastic fibers of the dermis, we sought to investigate skin elastic fibers in Williams syndrome as a key to unraveling extracellular matrix disorganization in this condition. Both morphometric parameters analyzed by using automated image analysis and immunofluorescence labeling with monoclonal antibodies against elastin and fibrillin 1 showed a disorganized pre-elastic (oxytalan and elaunin) and mature elastic fibers in the dermis of 10 Williams syndrome patients compared with five healthy children and one patient with isolated supravalvular aortic stenosis. Skin biopsies in Williams syndrome patients provide a simple mean to elucidate extracellular matrix anomalies. Hopefully, this method could give clues to the understanding of the elastic network anomalies in this condition and even to the consequences of these latter on elasticity and resilience of other tissues such as the arterial tree.
Adolescent↗
Treatment of cutaneous lymphoid hyperplasia with thalidomide: report of two cases.
Cutaneous benign lymphoid hyperplasia is a B-cell pseudolymphoma of unknown origin. The most favored sites of involvement include the face. We report two cases involving the nose that showed complete and stable regression after a 2-month treatment course with thalidomide.
Adolescent↗
The use of itraconazole to treat cutaneous fungal infections in children.
BACKGROUND: Cutaneous mycoses such as tinea capitis, onychomycosis and some cases of tinea corporis/cruris, and tinea pedis/manus require oral antifungal therapy. There is relatively limited data regarding the use of the newer oral antifungal agents, e.g. itraconazole, in the treatment of these mycoses in children. OBJECTIVE: We wished to determine the efficacy and safety of itraconazole continuous therapy in the management of cutaneous fungal infections in children. METHODS: Children with cutaneous mycoses were treated with itraconazole in an open-label manner in 4 studies. For tinea capitis, the treatment regimens using itraconazole continuous therapy were: study 1, 3 mg/kg/day for 4 or 8 weeks; study 2, 5 mg/kg/day for 6 weeks, and study 3, 5 mg/kg/ day for 4 weeks. In a different trial, study 4, itraconazole continuous therapy 5 mg/kg/day was used to treat toenail onychomycosis (duration: 12 weeks), tinea corporis/ cruris (duration: 1 week) and tinea pedis/manus (duration: 2 weeks). RESULTS: The efficacy rates at follow-up 12 weeks from the start of therapy in children with tinea capitis treated using the itraconazole continuous regimen were: clinical cure (CC) and mycological cure (MC) in study 1 (n = 10, Trichophyton violaceum all patients), CC 50%, MC 86%; in study 2 (n = 35, Microsporum canis 22 patients, Trichophyton sp. 12 patients), CC 82.8%, MC 80%, and in study 3 (n = 16, M. canis 11 patients, Trichophyton sp. 5 patients), (CC 66.7%, MC 78.5%. Itraconazole was also effective in the treatment of dermatomycoses in 24 children (study 4). The CC and MC rates at the follow-up 8 weeks from the start of therapy in children with dermatomycoses and 12 months in children treated for onychomycosis were: onychomycosis (n = 1, T. rubrum), CC 100%, MC 100%; tinea corporis (n = 12, M. canis 10 patients), CC 100%, MC 90%; tinea cruris (n = 3, Trichophyton sp. 2 patients), CC 100%, MC 100%; tinea manus (n = 1, T. rubrum), CC 100%, MC 100%, and tinea pedis (n = 7, T. rubrum), CC 100%, MC 100%). Adverse effects consisted of a cutaneous eruption in 1 (1.2%) of the 85 children, with mild, transient, asymptomatic elevation of liver function tests (less than twice the upper limit of normal) in 2 (3.4%) of 58 children in whom monitoring was performed. CONCLUSIONS: Itraconazole is effective and safe in the treatment of tinea capitis and other cutaneous fungal infections in children.
Antifungal Agents↗
Hair and skin disorders as signs of mitochondrial disease.
OBJECTIVE: To compare and explore the skin manifestations of mitochondrial disorders in 14 children with puzzling and unexpected cutaneous presentations. STUDY DESIGN: One hundred forty children with mitochondrial disorders who had been under observation in our hospital for the last 10 years, were carefully examined by the same physicians. Skin and hair characteristics were investigated by the same dermatologist. All the children developed an early unexplained association of symptoms. Metabolic screening for abnormal oxidative-reduction in plasma and mitochondrial enzyme investigations confirmed the diagnosis of oxidative phosphorylation disorders. RESULTS: Fourteen children with mitochondrial disorders (10% of the original cohort) developed specific hair and skin abnormalities. Their cutaneous manifestations were similar, and could be classified into four categories: hair abnormalities, rashes and pigmentation disorders, hypertrichosis, and acrocyanosis. In 3 cases, skin disorders constituted the puzzling and unexpected manifestations of mitochondrial disease. Respiratory chain deficiencies in the cultured skin fibroblasts of 3 patients and heteroplasmic mitochondrial DNA rearrangement in the skin fibroblasts of 1 patient indicated that mitochondrial disorders may be expressed in the skin. CONCLUSION: Hair abnormalities and pigmented skin eruptions might belong to the broad spectrum of presenting symptoms of mitochondrial disease. The association of these dermatologic lesions with unrelated disorders should lead physicians to consider a diagnosis of mitochondriopathy as early as possible.
Age of Onset↗
[Management of atopic dermatitis].
Management of atopic dermatitis should be based on cooperation among the physician, the child and the parents. There is no "radical" treatment that can eradicate the signs of this chronic affliction, which most often regresses during the first years of life. The aim of treatment is thus to combat infectious factors and to treat flares. In most cases, simple, daily and careful attention, using anti-infectious treatment, anti-inflammatory treatment by local corticosteroid application, and palliating skin dryness will assure the child of normal quality of life.
Anti-Inflammatory Agents↗
Deletions within COL7A1 exons distant from consensus splice sites alter splicing and produce shortened polypeptides in dominant dystrophic epidermolysis bullosa.
We describe two familial cases of dominant dystrophic epidermolysis bullosa (DDEB) that are heterozygous for deletions in COL7A1 that alter splicing, despite intact consensus splice-site sequences. One patient shows a 28-bp genomic deletion (6081del28) in exon 73 associated with the activation of a cryptic donor splice site within this exon; the combination of both defects restores the phase and replaces the last 11 Gly-X-Y repeats of exon 73 by a noncollagenous sequence, Glu-Ser-Leu. The second patient demonstrates a 27-bp deletion in exon 87 (6847del27), causing in-frame skipping of this exon; consensus splice sites, putative branch sites, and introns flanking exons 73 and 87 showed a normal sequence. Keratinocytes from the probands synthesized normal and shortened type VII collagen polypeptides and showed intracellular accumulation of type VII procollagen molecules. This first report of genomic deletions in COL7A1 in DDEB suggests a role for exonic sequences in the control of splicing of COL7A1 pre-mRNA and provides evidence that shortened type VII collagen polypeptides can alter, in a dominant manner, anchoring-fibril formation and can cause DDEB of differing severity.
Adult↗
[Angiomatous and cerulodermic macules: early cutaneous signs of neurofibromatosis type I].
BACKGROUND: Diagnosis of neurofibromatosis type I (NF-1) relies on the NIH consensus conference criteria. However, because of delayed penetrance, they are of limited value in infancy or early childhood. Less frequent signs, namely blue-red and fusco-ceruleus macules, may be clues for diagnosis. CASE REPORTS: We report on two children, aged 2 1/2 and 5, in whom these cutaneous findings were present early in childhood. In addition, they had sufficient criteria for NF1. DISCUSSION: These cutaneous signs, although infrequently reported, are present early in life. Hence they may be useful clues for diagnosis of NF-1 in childhood.
Cafe-au-Lait Spots↗