AP/HP Pôle 1

- Dermatologie -

Réponses affichées : 190

Lien PubMed Neonatal and Early Infantile Cutaneous Langerhans Cell Histiocytosis: Comparison of Self-regressive and Non-Self-regressive Forms
BATTISTELLA M, FRAITAG S, TEILLAC DH, BROUSSE N, DE PROST Y, BODEMER C
2010 - Arch Dermatol 146(2):149-56
Objectives To describe clinical and immunohistochemical findings in patients with cutaneous Langerhans cell histiocytosis (LCH) beginning in the first 3 months of life and to define predictors of disease evolution. DESIGN: Observational retrospective survey from July 15, 1989, to April 30, 2007. SETTING: Referral center in pediatric dermatology. Patients Thirty-one patients with a diagnosis of cutaneous LCH in the first 3 months of life and no previous visceral LCH. MAIN OUTCOME MEASURES: Cutaneous lesion characteristics, regulatory T-lymphocyte density, and E-cadherin expression were assessed. Data were compared between the patient groups with self-regressive vs non-self-regressive forms of cutaneous LCH. Pathologic analysis was performed blinded to patient group. RESULTS: Self-regressive cutaneous LCH was found in 21 patients and non-self-regressive cutaneous LCH in 10 patients. Monolesional forms, necrotic lesions, hypopigmented macules at presentation, and distal topography of limb lesions were seen only in patients with self-regressive cutaneous LCH. Regulatory T-lymphocyte density correlated with interleukin 10 expression in lesions (r = 0.77, P = .003) but was not predictive of disease evolution. E-cadherin expression by Langerhans cells was found in 7 patients with disease limited to the skin whether self-regressive or not. One patient with secondary disseminated disease showed loss of E-cadherin expression in Langerhans cells. CONCLUSIONS: Some morphologic traits of skin lesions can orient the diagnosis to a self-regressive form of cutaneous LCH. Regulatory T-lymphocyte density does not seem to be predictive of disease evolution. E-cadherin expression seems to be an indicator of limited skin disease but not of disease regression. Additional immunohistochemical study is required to confirm these data.
Unité(s) : Anatomie Pathologique, Dermatologie
 
Lien PubMed Calcinosis Cutis: A Rare Reaction to Subcutaneous Injections of Calcium-Containing Heparin in Patients With Renal Failure
BOCCARA O, PROST-SQUARCIONI C, BATTISTELLA M, BROUSSE N, RONGIOLETTI F, FRAITAG S
2010 - Am J Dermatopathol 32(1):52-55
Calcinosis of the cutis and the subcutis is a rare complication of calcium-containing heparin cutaneous injections, mostly occurring in a context of severe renal failure. We report 2 cases. The first patient developed firm erythematous nodules on his thighs and right arm, in a context of disseminated tuberculosis and acute severe renal failure related to human immunodeficiency virus nephropathy. Cutaneous location of tuberculosis was suspected. Histological features allowed to establish the diagnosis of calcinosis of the cutis and the subcutis, showing violaceous and crackled von Kossa-positive calcium deposits in the whole reticular dermis and in thin collagenous septa of subcutaneous tissue. A retrospective inquiry confirmed that subcutaneous injections of calcium-containing heparin had been performed on the sites where lesions occurred. The second patient developed similar lesions at injection sites of calcium-containing heparin, in a context of non-Hodgkin lymphoma and end-stage renal failure. Similar histological features were observed. Calcinosis of the cutis and the subcutis after subcutaneous injections of calcium-containing heparin is rare. It always occurs in a context of elevated calcium-phosphate product, a situation mostly encountered in severe renal failure. Early cutaneous lesions do not bear specific clinical features.
Unité(s) : Anatomie Pathologique, Dermatologie
 
Lien PubMed Epidermolysis bullosa in France: management in the National Reference Center for Genodermatosis
BODEMER C
2010 - Dermatol Clin 28(2):401-3, xiv
For more than 20 years, the department of dermatology in the Necker Enfants Malades Hospital (Paris) has been organizing the coordination of an epidermolysis bullosa-specific multidisciplinary management. The French Ministry of Health distinguished this hospital as a reference center for rare diseases. MAGEC-Necker now aims to offer the best medical and social management of epidermolysis bullosa.
Unité(s) : Dermatologie, U781
 
Lien PubMed Pediatric Mastocytosis Is a Clonal Disease Associated with D(816)V and Other Activating c-KIT Mutations
BODEMER C, HERMINE O, PALMERINI F, YANG Y, GRANDPEIX-GUYODO C, LEVENTHAL PS, HADJ-RABIA S, NASCA L, GEORGIN-LAVIALLE S, COHEN-AKENINE A, LAUNAY JM, BARETE S, FEGER F, AROCK M, CATTEAU B, SANS B, STALDER JF, SKOWRON F, THOMAS L, LORETTE G, PLANTIN P, BORDIGONI P, LORTHOLARY O, PROST Y, MOUSSY A, SOBOL H, DUBREUIL P
2010 - J Invest Dermatol 130(3):804-15
Adult mastocytosis is an incurable clonal disease associated with c-KIT mutations, mostly in exon 17 (D(816)V). In contrast, pediatric mastocytosis often spontaneously regresses and is considered a reactive disease. Previous studies on childhood mastocytosis assessed only a few patients and focused primarily on codon 816 mutations, with various results. In this study, we analyzed the entire c-KIT sequence from cutaneous biopsies of 50 children with mastocytosis (ages 0-16 years). A mutation of codon 816 (exon 17) was found in 42% of cases, and mutations outside exon 17 were observed in 44%. Unexpectedly, half of the mutations were located in the fifth Ig loop of c-KIT's extracellular domain, which is encoded by exons 8 and 9. All mutations identified in this study were somatic and caused a constitutive activation of c-KIT. There was no clear phenotype-genotype correlation, no clear relationship between the mutations and familial versus spontaneous disease, and no significant change in the relative expression of the c-KIT GNNK+ and GNNK isoforms. These findings strongly support the idea that, although pediatric mastocytosis can spontaneously regress, it is a clonal disease most commonly associated with activating mutations in c-KIT.JID JOURNAL CLUB ARTICLE: For questions and answers about this article, please go to http://www.nature.com/jid/journalclub.
Unité(s) : Centre de Génétique Médicale Jean Frézal, Dermatologie, Maladies Infectieuses, UMR 8147
 
Lien PubMed Efficacy of tacrolimus 0.03% ointment as second-line treatment for children with moderate-to-severe atopic dermatitis: evidence from a randomized, double-blind non-inferiority trial vs. fluticasone 0.005% ointment
DOSS N, KAMOUN MR, DUBERTRET L, CAMBAZARD F, REMITZ A, LAHFA M, DE PROST Y
2010 - Pediatr Allergy Immunol 21(2):321-29
Tacrolimus 0.03% ointment is licensed for second-line treatment of children with atopic dermatitis (AD). Although data are available from clinical trials, no study has enrolled only second-line patients. This double-blind, non-inferiority study compared tacrolimus 0.03% and fluticasone 0.005% ointments in children with moderate-to-severe AD, who had responded insufficiently to conventional therapies. Children (aged 2-15 yr) were randomized to tacrolimus ointment (n = 240) or fluticasone ointment (n = 239), twice daily until clearance or for a maximum of 3 wk and, if lesions remained, once daily for up to 3 wk further. Primary end-point was week 3 response rate (improvement of >/=60% in modified Eczema Area and Severity Index and not withdrawn for lack of efficacy). Secondary end-points included pruritus and sleep quality, global assessment of clinical response, incidence of new flares and safety. Response rates were 86.3% with tacrolimus ointment and 91.5% with fluticasone. Lower limit of the 95% confidence interval was -11.8%, exceeding the non-inferiority limit of -15% and meeting the primary end-point. Moderate or better improvement on the physicians' global assessment occurred in 93.6% and 92.4% of patients in the tacrolimus ointment and fluticasone arms, respectively, while median pruritus scores improved by 84.0% and 91.5%. Sleep quality improved by approximately 92% in both treatment arms. After day 21, new flare-up occurred in 5.5% and 11.3% of patients receiving tacrolimus ointment and fluticasone, respectively; mean times to new flares were 6.5 +/- 5.0 and 8.6 +/- 5.2 days. Adverse events were similar between the two arms, with the exception of application-site skin burning sensation in the tacrolimus ointment group. In conclusion, efficacy of tacrolimus 0.03% ointment as second-line treatment was not inferior to that of fluticasone 0.005% ointment, with similar benefits on global disease improvement and quality of sleep.
Unité(s) : Dermatologie
 
Lien PubMed Cutaneous Richter's syndrome, prognosis, and clinical, histological and immunohistological patterns: report of four cases and review of the literature
DUONG T, GRANGE F, AUFFRET N, ARACTINGI S, BODEMER C, BROUSSE N, HERMINE O, FRAITAG S
2010 - Dermatology 220(3):226-33
BACKGROUND: Richter's syndrome (RS) corresponds to the transformation of chronic lymphocytic leukemia (CLL) into high-grade lymphoma. RS can involve extranodal sites including the gastrointestinal tract, lungs and skin. Cutaneous RS is rare, we describe 4 cases with clinical manifestations, histological and immunohistological patterns, and outcome. METHODS: Clinical data were analyzed and all patients' skin biopsy samples stained with HE for the CD20, CD5, CD3 and CD30 antigens. Epstein-Barr-virus (EBV)-encoded early RNA and clonal rearrangements were also analyzed. RESULTS: The patients' mean age at CLL diagnosis was 57 years (53-62 years), with a male/female sex ratio of 3:1. The transformation to cutaneous RS occurred between 8 and 75 months after initial diagnosis and progressed to a fatal systemic disease in 3 cases, between 24 and 129 months. Cutaneous CLL was associated with earlier transformation in our series and could not be distinguished from RS on clinical grounds alone. All patients had a large-cell infiltrate and clonal rearrangements. CONCLUSIONS: The precise mechanism of RS is unclear, but a role of EBV has been suggested in fludarabine-treated CLL. For all our patients, the diagnosis of transformation was made on the basis of cutaneous localizations and led to intensified CLL treatment.
Unité(s) : Anatomie Pathologique, Dermatologie, Hématologie Adulte
 
Lien PubMed Unusual presentation of chromoblastomycosis due to Cladophialophora carrionii in a renal and pancreas transplant recipient patient successfully treated with posaconazole and surgical excision
DUPONT C, DUONG TA, MALLET S, MAMZER-BRUNEEL MF, THERVET E, BOUGNOUX ME, DUPONT B
2010 - Transpl Infect Dis 12(2):180-83
C. Dupont, T.A. Duong, S. Mallet, M.F. Mamzer-Bruneel, E. Thervet, M.E. Bougnoux, B. Dupont. Unusual presentation of chromoblastomycosis due to Cladophialophora carrionii in a renal and pancreas transplant recipient patient successfully treated with posaconazole and surgical excision. Transpl Infect Dis 2009. All rights reserved Abstract: Chromoblastomycosis is a chronic, tropical and subtropical, subcutaneous mycosis caused by inoculation of dematiaceous molds. This disease is uncommonly reported in patients who have undergone solid organ transplantation. We describe a case of chromoblastomycosis caused by Cladophialophora carrionii that occurred 7 years after transplantation in a 58-year-old male renal and pancreatic transplant recipient. Diagnosis was based on histopathology and isolation of multiple colonies of the dematiaceous mold in pure culture. Identification was achieved by sequencing of the internal transcribed spacer regions of the rRNA. The patient was successfully treated with posaconazole and surgical excision of a residual lesion.
Unité(s) : Anatomie Pathologique, Dermatologie, Laboratoire de Microbiologie, Maladies Infectieuses, Transplantation Adulte
 
Lien PubMed Neonatal erythroderma
FRAITAG S, BODEMER C
2010 - Curr Opin Pediatr 22(4):438-44
PURPOSE OF REVIEW: Neonatal erythroderma is a potentially life-threatening condition in neonates less than 1 month old. During the first month of life, erythroderma is generally a presentation of genodermatosis, primary immune deficiency, or, more exceptionally, severe psoriasis, metabolic disease or infection. Atopic erythroderma is observed later in life, usually after the age of 1 month. Rapid determination of the underlying cause is crucial for better management. However, the diagnosis is often a challenge for the clinician and is frequently delayed due to the nonspecific nature of the clinical signs. We summarize the different causes of neonatal erythrodermas and list their clinical, biological, histological, and sometimes genetic characteristics. RECENT FINDINGS: Severe erythroderma, typified by early onset, skin induration, severe alopecia and failure to thrive, is immediately suggestive of immunodeficiency or Netherton syndrome. In such cases, an early skin biopsy may be particularly of use in allowing accurate differentiation between these two disorders. SUMMARY: This review outlines the clinical and histological features of these disorders and suggests an approach to their differential diagnosis and management.
Unité(s) : Anatomie Pathologique, Dermatologie
 
Lien PubMed Phacomatosis Pigmentokeratotica with Nephroblastoma and Juvenile Hypertension
JACOBELLI S, LECLERC-MERCIER S, SALOMON R, HARTMANN O, BRUNELLE F, HAPPLE R, BODEMER C, HADJ-RABIA S
2010 - Acta Derm Venereol 90(3):279-282
Phacomatosis pigmentokeratotica is characterized by the coexistence of an organoid epidermal naevus, follow-ing Blaschko's lines, and a large speckled lentiginous naevus, typically arranged in a chequerboard pattern. This entity has been isolated from the group of epidermal naevus syndromes and is frequently associated with extracutaneous anomalies. We report here the first observation of phacomatosis pigmentokeratotica associated with nephroblastoma. In addition to this paediatric renal tumour, the coexistence of juvenile arterial hypertension suggests an associated vascular defect. The link between the extracutaneous manifestations and cutaneous twin spot phenotype is discussed.
Unité(s) : Dermatologie, Radiologie Pédiatrique, U781
 
Lien PubMed Agminated Spitz nevi arising on a nevus spilus after chemotherapy
KHALED A, KHARFI M, SELLAMI A, HAMEL-TEILLAC D, FAAZA B, FRAITAG S, KAMOUN MR
2010 - Pediatr Dermatol 27(4):411-3
Agminated Spitz nevus arising on a background of nevus spilus (NS) is a rare condition. We report here a further case in a child that is original because it is induced by chemotherapy. A 3-year-old boy presented 3 months after the onset of a chemotherapy for a vesico-prostatic rhabdomyosarcoma, multiple pigmented papulo-nodules located on the face, neck, chest wall, and the higher back. These lesions have arose on a pre-existent large congenital histologically confirmed nevus spilus extending along the face, neck, the left shoulder and the left chest wall. Histological examination of three excised nodules led to the diagnosis of Spitz nevus. Our patient may have a high risk for melanoma since he has many criteria predisposing to this risk. Some of these criteria are related to NS but we should also take into account the chemotherapy induction and the high number of Spitz nevi.
Unité(s) : Anatomie Pathologique, Dermatologie
 
  Fibroblastic rheumatism: fibromatosis rather than non-Langerhans cell histiocytosis
KLUGER N, DUMAS-TESICI A, HAMEL D, BROUSSE N, FRAITAG S
2010 - J. Cutan. Pathol. 37(5):587-592
Background: Fibroblastic rheumatism is a unique fibro-proliferative disease affecting the skin and joints. It is characterized by distinctive clinical and histological features related to benign spindle-shaped cells proliferation. Pediatric reports are scarce in the literature. Objective: We describe here a new case in a 10-year-old boy and discuss the potential origin of the cell proliferation. Methods: Clinical findings, radiology, microscopic examination and outcome are reviewed. Histopathology and immunochemistry studies were performed on skin biospies using CD68, CD163, desmin, factor XIIIa, CD34, smooth muscle actin, PS100, epithelial membrane antigen, and calponin. Results: Histological sections disclosed a rather circumscribed nonencapsulated nodular infiltrate, invading the dermis and the upper subcutaneous tissue, consisted of a proliferation of spindle or stellate-shaped cells and thickened collagen fibers. Orcein staining showed disappearance of the elastic network. Aponeurosis and muscle were normal. A mild perivascular lymphohistiocytic infiltrate was noted. Calponin-staining was less strongly expressed as SMA, and some of them but not all were CD68 positive, as well. On the other hand, all were CD34, CD163, FXIIIa, PS100, EMA and desmin-negative. Conclusion: The true origin of these cells remains unclear. Some authors have speculated a histiocytic origin. However, immunochemical staining in our case failed to confirm this hypothesis and instead supported a fibroblastic/myofibroblastic origin. Given the clinical course and the histological and immunohistochemical results, we suggest that FR should be added to the group of fibromatoses.
Unité(s) : Anatomie Pathologique, Dermatologie
 
Lien PubMed Early skin biopsy is helpful for the diagnosis and management of neonatal and infantile erythrodermas
LECLERC-MERCIER S, BODEMER C, BOURDON-LANOY E, LAROUSSERIE F, HOVNANIAN A, BROUSSE N, FRAITAG S
2010 - J Cutan Pathol 37(2):249-255
Background: Erythrodermas are often life-threatening conditions in infants. Determination of the underlying cause is crucial. Microscopic changes in adult erythroderma lack specificity. Objective: To determine if an early skin biopsy is helpful for the diagnosis of neonatal and infantile erythroderma. Methods: Seventy-two patients admitted for erythroderma in the first year of life were retrospectively included. One hundred and eleven skin biopsies (12-year period) were examined by 3 pathologists blinded to the clinical diagnosis, and classified into atopic dermatitis, immunodeficiency (ID), psoriasis, Netherton syndrome (NS), ichthyosis, other. From year 2000, LEKTI antibody was performed when NS was suspected. Pathological diagnosis was then compared with clinical diagnosis. Results: The final diagnosis was made in 69.3% of the cases. In 57.6%, pathological diagnosis was in accordance, and in 11.7%, it was in accordance, but other diagnosis had also been proposed. For ID, sensitivity and specificity were 58.5 and 98.5%, respectively. Before year 2000, NS was frequently misdiagnosed with psoriasis, but with the use of LEKTI antibody, sensitivity and specificity were 100%. Conclusion: Skin biopsy is helpful for etiologic diagnosis of early erythroderma of infancy, particularly in ID and NS, the most severe diseases. Consequently, these results justify an early systematic skin biopsy for a better and earlier management. Leclerc-Mercier S, Bodemer C, Bourdon-Lanoy E, Larousserie F, Hovnanian A, Brousse N, Fraitag S. Early skin biopsy is helpful for the diagnosis and management of Neonatal and Infantile Erythrodermas.
Unité(s) : Anatomie Pathologique, Dermatologie
 
Lien PubMed Segmental and nonsegmental childhood vitiligo has distinct clinical characteristics: a prospective observational study
MAZEREEUW-HAUTIER J, BEZIO S, MAHE E, BODEMER C, ESCHARD C, VISEUX V, LABREZE C, PLANTIN P, BARBAROT S, VABRES P, MARTIN L, PAUL C, LACOUR JP, GROUPE DE RECHERCHE CLINIQUE EN DERMATOLOGIE P
2010 - J Am Acad Dermatol 62(6):945-9
BACKGROUND: Vitiligo often starts in childhood. It is traditionally divided into segmental vitiligo and nonsegmental vitiligo. There are limited data regarding the clinical characteristics of both forms and no comparative study has been performed. OBJECTIVE: To compare the clinical features of nonsegmental and segmental vitiligo in children. PATIENTS AND METHODS: We performed a prospective observational study. Consecutive children with vitiligo seen between October 2005 and December 2007 in the 11 French Departments of Pediatric Dermatology were included. A standardized evaluation was completed after total body clinical examination. A second examination was performed 1 year after inclusion. The clinical characteristics of segmental vitiligo and nonsegmental vitiligo were compared. RESULTS: A total of 114 children with vitiligo were included. Compared with segmental vitiligo, nonsegmental vitiligo was associated with a higher number of lesions (more than 5 patches in 65.17% vs 20% of patients, P < .0001) and a larger body surface area of involvement (9.8% +/- 2.51% vs 3.48% +/- 1.6%, P +/- .01). A higher incidence of the Koebner phenomenon (47.19% vs 24%, P = .03), and more frequent progression of the disease (23.29% vs 5.56%, P = .043) were found in nonsegmental vitiligo. Hyperpigmented rims surrounding patches of vitiligo were only seen in nonsegmental vitiligo (8.99% vs 0% (P = .007). Sixty-four children (56%) had laboratory investigations performed; thyroid abnormalities were found only in nonsegmental vitiligo (11.23% vs 0%, P = .0001). LIMITATIONS: Not all patients underwent laboratory investigations. CONCLUSIONS: Segmental and nonsegmental types of vitiligo have distinguishing clinical characteristics.
Unité(s) : Dermatologie
 
Lien PubMed Efficacy of Propranolol in Hepatic Infantile Hemangiomas with Diffuse Neonatal Hemangiomatosis
MAZEREEUW-HAUTIER J, HOEGER PH, BENLAHRECH S, AMMOUR A, BROUE P, VIAL J, OHANESSIAN G, LEAUTE-LABREZE C, LABENNE M, VABRES P, ROSSLER J, BODEMER C
2010 - J Pediatr 157(2):340-42
We report the rapid and dramatic efficacy of propranolol in 8 infants with infantile hepatic hemangiomas. The degree of response varied from a significant improvement to a complete resolution of hepatic lesions. Heart failure and hypothyroidism resolved, and hepatomegaly decreased. No side-effects of the drug were noted.
Unité(s) : Dermatologie
 
Lien PubMed Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome
NEVEN B, MARVILLET I, TERRADA C, FERSTER A, BODDAERT N, COULOIGNIER V, PINTO G, PAGNIER A, BODEMER C, BODAGHI B, TARDIEU M, PRIEUR AM, QUARTIER P
2010 - Arthritis Rheum 62(1):258-267
OBJECTIVE: Cryopyrin-associated periodic syndromes (CAPS) are a group of rare autoinflammatory diseases. Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic, cutaneous, articular syndrome (CINCA syndrome) is the most severe phenotype, with fever, rash, articular manifestations, and neurologic and neurosensory involvement. CAPS are caused by mutations in CIAS1, the gene encoding NLRP3, which plays a critical role in interleukin-1 (IL-1) processing. Anakinra, an IL-1 receptor antagonist, has been shown to be an effective treatment; however, data on long-term efficacy and safety have been sparse. This study was undertaken to assess the long-term efficacy and safety of anakinra treatment in patients with NOMID/CINCA syndrome. METHODS: We retrospectively analyzed the medical records of NOMID/CINCA syndrome patients referred to 2 centers, who had started anakinra treatment before June 2007. RESULTS: There were 10 patients with NOMID/CINCA syndrome who had been treated with anakinra. The patients' ages at the time anakinra treatment was initiated ranged from 3 months to 20 years. They had been followed up for 26-42 months. Sustained efficacy in the treatment of systemic inflammation and, in some cases, neurologic involvement and growth parameters, was achieved. The dosage of anakinra required for efficacy ranged from 1 to 3 mg/kg/day in the 8 oldest patients and from 6 to 10 mg/kg/day in the 2 youngest. Residual central nervous system inflammation and deafness persisted in some patients, especially if there had been a delay in diagnosis and treatment. Secondary amyloidosis persisted in cases in which it was present at treatment initiation, but no new lesions developed. No effect on overgrowth arthropathy was observed. Adverse events consisted of mild injection-site reactions. CONCLUSION: The present results indicate that anakinra treatment is effective over the long term in NOMID/CINCA syndrome. However, treatment has to be initiated before irreversible lesions develop, and, particularly in very young patients, dosage adjustment is required.
Unité(s) : Dermatologie, Immunologie-Hématologie Pédiatriques, Maladies du Développement, ORL & Chirurgie Cervico-Faciale, Radiologie Pédiatrique, U768
 
Lien PubMed Clinical spectrum of tufted angiomas in childhood: a report of 13 cases and a review of the literature
OSIO A, FRAITAG S, HADJ-RABIA S, BODEMER C, DE PROST Y, HAMEL-TEILLAC D
2010 - Arch Dermatol 146(7):758-63
BACKGROUND: Tufted angioma (TA) is a rare benign vascular tumor that mostly appears during infancy or early childhood. Histologic tufts of capillaries infiltrating the whole dermis in a "cannonball" distribution pattern associated with dilated lymphatic vessels are characteristic of the disease and confirm the diagnosis. Few case series of TA have been published, and the morphologic structure and evolution of TA seem to vary. OBSERVATIONS: We describe the largest series to date of childhood TA, comprising 13 cases. All children developed lesions within the first year of life; 7 cases were congenital. We found a clear male predominance (9 of 13 children). Presentation was a nascent or florid tumor, usually a dusky red to violaceous plaque, that was indurated, firm, and sometimes associated with hyperhidrosis or hypertrichosis. Locations of the lesions included limbs, abdomen, and genitalia. Five children had spontaneous regression, 5 children had Kasabach-Merritt syndrome, and 1 child had a lesion that stabilized. Two children with painful TA had chronic coagulopathy without thrombocytopenia that was controlled by ticlopidine hydrochloride and aspirin. CONCLUSIONS: The following 3 clinical patterns could be distinguished: TA without complications, TA complicated by Kasabach-Merritt syndrome, and TA without thrombocytopenia but with chronic coagulopathy. To our knowledge, this study is the first to describe the third pattern. Because of the aggressive nature of Kasabach-Merritt syndrome, it is essential to obtain a complete blood cell count when evaluating a child with TA.
Unité(s) : Anatomie Pathologique, Dermatologie
 
Lien PubMed Immune reactivity to type VII collagen: implications for gene therapy of recessive dystrophic epidermolysis bullosa
PENDARIES V, GASC G, TITEUX M, LEROUX C, VITEZICA ZG, MEJIA JE, DECHA A, LOISEAU P, BODEMER C, PROST-SQUARCIONI C, HOVNANIAN A
2010 - Gene Ther 17(7):930-37
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe genodermatosis caused by loss-of-function mutations in COL7A1 encoding type VII collagen, the component of anchoring fibrils. As exogenous type VII collagen may elicit a deleterious immune response in RDEB patients during upcoming clinical trials of gene therapies or protein replacement therapies, we developed enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot (ELISPOT) assays to analyze B- and T-cell responses, to the full-length type VII collagen. The ELISA was highly sensitive and specific when tested against sera from 41 patients with epidermolysis bullosa acquisita (EBA), and the IFN-gamma ELISPOT detected a cellular response that correlated with ongoing EBA manifestations. Both tests were next applied to assess the risk of an immune response to type VII collagen in seven RDEB patients with a range of type VII collagen expression profiles. Immune responses against type VII collagen were dependent on the expression of type VII collagen protein, and consequently on the nature and position of the respective COL7A1 mutations. These immunologic tests will be helpful for the selection of RDEB patients for future clinical trials aiming at restoring type VII collagen expression, and in monitoring their immune response to type VII collagen after treatment.Gene Therapy advance online publication, 8 April 2010; doi:10.1038/gt.2010.36.
Unité(s) : Centre de Génétique Médicale Jean Frézal, Dermatologie
 
Lien PubMed Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I
PUEL A, DOFFINGER R, NATIVIDAD A, CHRABIEH M, BARCENAS-MORALES G, PICARD C, COBAT A, OUACHEE-CHARDIN M, TOULON A, BUSTAMANTE J, AL-MUHSEN S, AL-OWAIN M, ARKWRIGHT PD, COSTIGAN C, MCCONNELL V, CANT AJ, ABINUN M, POLAK M, BOUGNERES PF, KUMARARATNE D, MARODI L, NAHUM A, ROIFMAN C, BLANCHE S, FISCHER A, BODEMER C, ABEL L, LILIC D, CASANOVA JL
2010 - J Exp Med 207(2):291-297
Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-gamma, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1beta, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-beta, tumor necrosis factor [alpha], or transforming growth factor beta). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.
Unité(s) : Dermatologie, Immunologie-Hématologie Pédiatriques, U768, U845 (RS), U980
 
Lien PubMed Germline mosaicism in keratitis-ichthyosis-deafness syndrome: pre-natal diagnosis in a familial lethal form
SBIDIAN E, FELDMANN D, BENGOA J, FRAITAG S, ABADIE V, DE PROST Y, BODEMER C, HADJ-RABIA S
2010 - Clin Genet 77(6):587-92
Sbidian E, Feldmann D, Bengoa J, Fraitag S, Abadie V, de Prost Y, Bodemer C, Hadj-Rabia S. Germline mosaicism in keratitis-ichthyosis-deafness syndrome: pre-natal diagnosis in a familial lethal form. Keratitis-ichthyosis-deafness (KID) syndrome is an autosomal dominant congenital ectodermal defect characterized by the association of skin lesions, hearing loss and keratitis. Most of the cases appear to be sporadic. KID syndrome is mostly related to mutations of GJB2 gene encoding connexin-26. Recently, a lethal form of the disease during the first year of life has been reported in two unrelated Caucasian patients. This rare lethal form is caused by the G45E mutation of GJB2 gene. We here report the first pre-natal molecular genetic diagnosis of the lethal form of KID syndrome relating to a G45E mutation. In the same family, the occurrence of this condition in three other siblings born to African non-consanguineous healthy parents lead to perform pre-natal diagnosis for this last pregnancy. Molecular analysis confirms the diagnosis of the lethal form of KID for the fetus. These results establish the role of germline mosaicism in KID syndrome and warrant careful genetic counseling. Furthermore, analysis of our cases and the literature allowed us to define a characteristic severe neonatal phenotype including facial dysmorphy, severe cornification with massive focal hyperkeratosis of the skin with erythroderma, dystrophic nails, complete atrichia and absence of foreskin.
Unité(s) : Anatomie Pathologique, Centre de Génétique Médicale Jean Frézal, Dermatologie, Pédiatrie Générale
 
Lien PubMed A prevalent mutation with founder effect in xeroderma pigmentosum group C from north Africa
SOUFIR N, GED C, BOURILLON A, AUSTERLITZ F, CHEMIN C, STARY A, ARMIER J, PHAM D, KHADIR K, ROUME J, HADJ-RABIA S, BOUADJAR B, TAIEB A, DE VERNEUIL H, BENCHIKI H, GRANDCHAMP B, SARASIN A
2010 - J Invest Dermatol 130(6):1537-42
Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder that is associated with an inherited defect of the nucleotide excision repair pathway (NER). In this study, we investigated the involvement of XP genes in 86 XP patients belonging to 66 unrelated families, most of them consanguineous and originating from Maghreb. Sequencing analysis was performed either directly (44 probands) or after having previously characterized the involved XP gene by complementation assay (22 families). XPC and XPA mutations were respectively present in 56/66 and 8/66 probands. Strikingly, we identified the same homozygous frameshift mutation c.1643_1644delTG (p.Val548AlafsX25) in 87% of XP-C patients. Haplotype analysis showed a common founder effect for this mutation in the Mediterranean region, with an estimated age of 50 generations or 1,250 years. Among 7/8 XP-A patients, we found the previously reported nonsense homozygous XPA mutation (p.Arg228X). Six mutations--to our knowledge previously unreported--(five in XPC, one in XPA) were also identified. In conclusion, XPC appears to be the major disease-causing gene concerning xeroderma pigmentosum in North Africa. As the (p.Val548AlafsX25) XPC mutation is responsible for a huge proportion of XP cases, our data imply an obvious simplification of XP molecular diagnosis, at least in North Africa.
Unité(s) : Dermatologie
 
Lien PubMed Gene therapy for recessive dystrophic epidermolysis bullosa
TITEUX M, PENDARIES V, HOVNANIAN A
2010 - Dermatol Clin 28(2):361-6
Among the severe genetic disorders of the skin that are suitable for gene and cell therapy, most efforts have been made in the treatment of blistering diseases including dystrophic epidermolysis bullosa. This condition can be recessively or dominantly inherited, depending on the nature and position of the mutation or mutations in the gene encoding type VII collagen. At present, there is no specific treatment for recessive dystrophic epidermolysis bullosa, and gene and cell therapy approaches hold great promise. This article discusses the different gene therapy approaches that have been used for the treatment of this disease and the new perspectives that they open.
Unité(s) : Centre de Génétique Médicale Jean Frézal, Dermatologie
 
Lien PubMed Clinical demonstration of skin mildness and suitability for sensitive infant skin of a new baby wipe
ADAM R, SCHNETZ B, MATHEY P, PERICOI M, DE PROST Y
2009 - Pediatr Dermatol 26(5):506-13
BACKGROUND: A cleansing baby wipe with sufficient pH buffering capacity may help to restore the pH balance of skin following exposure to urine and feces in the diaper environment and maintain skin health. OBJECTIVE: To evaluate the skin effects of a novel baby wipe formulation with increased pH buffering. SUBJECTS AND METHODS: A series of clinical studies was designed and conducted to evaluate the skin effects of the new baby wipe, including a 21-day cumulative skin irritation patch study in adults (n = 31), a 4-week study in babies with medically confirmed atopic dermatitis (n = 32), a 2-week study comparing skin pH of babies (n = 15) following use of wipes compared with water and wash cloth, a series of clinical skin pH measurements following fecal exposure and subsequent cleaning with different products (n = 50) and a study evaluating comfort of product application on irritated skin (n = 31). RESULTS: The wipes formulation was well-tolerated, even in babies with atopic dermatitis, and was more comfortable versus water and washcloth. Increased buffering capacity of a wet wipes lotion helps to maintain a physiologically balanced skin pH value in the diaper region.
Unité(s) : Dermatologie
 
Lien PubMed Nonbacterial purpura fulminans and severe autoimmune acquired protein S deficiency associated with human herpesvirus-6 active replication
BOCCARA O, LESAGE F, REGNAULT V, LASNE D, DUPIC L, BOURDON-LANOY E, PANNIER S, FRAITAG S, AUDAT F, LECOMPTE T, HUBERT P, BODEMER C
2009 - Br J Dermatol 161(1):181-183
Nonbacterial purpura fulminans (PF) is rare, usually follows viral infection in young children, and is characterized by specific coagulation disorders, requiring specific therapy. Following a transient rash, a 2-year-old previously healthy girl developed PF without haemodynamic impairment. Laboratory data revealed disseminated intravascular coagulation and a severe transient protein S deficiency. Antiprotein S autoantibodies and active human herpesvirus-6 (HHV6) replication were demonstrated. Purpuric skin lesions spread very rapidly despite broad-spectrum antibiotics and right leg amputation. Plasmapheresis and intravenous immunoglobulins gave complete clinical recovery and normalization of protein S level within 10 days, with progressive clearance of antiprotein S autoantibodies. Transient severe protein S deficiencies have previously been reported in patients with nonbacterial PF, usually after varicella infection. This is the first documented case of PF after HHV6 infection.
Unité(s) : Dermatologie, Laboratoire d'Hématologie, Réanimation Pédiatrique & Néonatologie, Anatomie Pathologique, Traumatologie et Orthopédie Pédiatriques, Transfusion Sanguine
 
  The skin of newborns and care of the seat during the first months
DE PROST Y
2009 - Archives Pédiatrie 16(Sp. Iss.):1
Unité(s) : Dermatologie
 
Lien PubMed First fixed drug eruption due to teicoplanin with a peri-oral distribution
DUONG T, HAMEL D, BENLAHRECH S, LE-QUAN-SANG KH, SAUVE-MARTIN H, DE PROST Y, ROUJEAU JC, HADJ-RABIA S
2009 - J Eur Acad Dermatol Venereol 23(9):1107
Unité(s) : Centre de Génétique Médicale Jean Frézal, Dermatologie
 
Lien PubMed Multiple nodules in a newborn infant
FRAITAG S, BODEMER C
2009 - Ann Dermatol Venereol 136(2):211-3
Unité(s) : Anatomie Pathologique, Dermatologie
 
  Skin biopsy is helpful for the diagnosis of incontinentia pigmenti at late stage (IV): a series of 26 cutaneous biopsies
FRAITAG S, RIMELLA A, DE PROST Y, BROUSSE N, HADJ-RABIA S, BODEMER C
2009 - J. Cutan. Pathol. 36(9):966-971
Background. Hypochromic streaks can be the only cutaneous sign of incontinentia pigmenti (IP) in adulthood (stage IV). Discovery of such lesions in an adult female with no family history of IP is essential for appropriate genetic counselling. Objective. To describe and to validate the histological features of residual skin lesions in adult IP. Methods. The analysis and comparison of skin biopsies of 26 women affected with molecularly confirmed IP. Results. Most biopsies showed slight atrophy and some scattered apoptotic cells in the epidermis, epidermal hypopigmentation and reduced melanocyte number. The dermis appeared thickened and homogeneous and revealed a complete absence of hair follicles (23/26) and sweat glands (22/26). There was no melanin incontinence or inflammatory cells, and the elastic network was normal. Conclusion. These features lead unequivocally to the diagnosis of a stage IV IP skin lesion. Consequently, histology is a major confirmatory criterion for diagnoses of these mild clinical forms of IP. It is therefore a useful tool in genetic counselling and prenatal diagnosis. Moreover, the observations described here may contribute to understanding the physiopathology of the late stages of IP.
Unité(s) : Anatomie Pathologique, Dermatologie
 
  Current concepts and treatment advances in systemic mastocytosis
GEORGIN-LAVIALLE S, BARETE S, SUAREZ F, LEPELLETIER Y, BODEMER C, DUBREUIL P, LORTHOLARY O, HERMINE O
2009 - Rev. Med. Interne. 30(1):25-34
PURPOSE: Mast cell disorders are defined by an abnormal accumulation of tissue mast cells in one or more organ systems. Clinical symptoms in mastocytosis result from mast cells derived mediators and, less frequently, from destructive infiltration of mast cells. Systemic mastocytosis is regressive among children, whereas the disease is persistent among adults. A clonal haematological non-mast cell lineage disease can be associated. The clinical course in these patients is variable ranging from asymptomatic for years to highly aggressive and rapidly devastating. Until recently, the only treatment of this incurable disease was symptomatic. CURRENT KNOWLEDGE AND KEY POINTS: Recent advances were done in understanding the physiopathology of this myeloproliferative syndrome which results from an activating mutation of the stem cell factor receptor: C-Kit. A somatic C-Kit mutation is usually detectable in mast cells and their progenitors. Different mutations were found and the mutation D816V is the most frequent. Their specific transduction paths were also studied. Diagnosis of systemic mastocytosis does not only rest upon pathological examination but also on molecular as well as immunological and immunochemical tools. FUTURE PROSPECTS AND PROJECTS: Physiopathological advancements led to suggest new treatments in order to directly inhibit proliferative paths of masts cells such as tyrosine kinase inhibitors and rapamycin.
Unité(s) : Dermatologie, Hématologie Adulte, Infectiologie, UMR 8147
 
  Cutaneous manifestations of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome
HALABI-TAWIL M, RUEMMELE FM, FRAITAG S, RIEUX-LAUCAT F, NEVEN B, BROUSSE N, DE PROST Y, FISCHER A, GOULET O, BODEMER C
2009 - Br. J. Dermatol. 160(3):645-651
Background Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder characterized by neonatal autoimmune enteropathy, diabetes and thyroiditis, food allergies and skin rash. IPEX syndrome is caused by mutations in FOXP3, a master control gene of regulatory T cells (Tregs), resulting in absent or dysfunctional Tregs. Data in the literature are scarce and the cutaneous manifestations are rarely depicted. Objectives To evaluate the frequency and characteristics of cutaneous manifestations found in IPEX. Methods Retrospective single-centre study of a case series of IPEX. Patients' data were retrieved from medical files and numerous parameters concerning general and cutaneous characteristics of the disease were recorded. Results Ten children with IPEX were studied. Cutaneous involvement was present in seven of 10 chidren; age at onset was 0-4 months, median 1.5. All patients presented with atopic dermatitis (AD). Three presented more psoriasiform lesions. Eczema was severe; most affected areas were lower limbs, trunk and face. Pruritus was present in four of seven, and painful fissurary cheilitis in four of seven. Hyper-IgE was found in seven of 10 and hypereosinophilia in five of 10. Skin biopsies showed eczematiform or psoriasiform features. Affected patients were improved by dermocorticoids; no clear improvement was obtained with immunosuppressive regimens. Other features were urticaria secondary to food allergies and staphylococcal sepsis, mostly Staphylococcus aureus and catheter related. Conclusions AD seems to be a frequent finding in IPEX syndrome, which is characterized by Treg anomalies. This hints to a possible role of Tregs in AD, which is then discussed in this study.
Unité(s) : Anatomie Pathologique, Dermatologie, Gastro-Hépatologie et Nutrition Pédiatriques, U768, U793, Immunologie-Hématologie Pédiatriques
 
Lien PubMed [Establishing the aetiological diagnosis of congenital ichthyosis.]
MAZEREEUW-HAUTIER J, BODEMER C
2009 - Ann Dermatol Venereol 136(12):916-22
Unité(s) : Dermatologie
 
Lien PubMed [Soft tissue tumors in neonates.]
MINARD-COLIN V, ORBACH D, MARTELLI H, BODEMER C, OBERLIN O
2009 - Arch Pediatr 16(7):1039-1048
Soft tissue tumors account for approximately 25% of neonatal tumors and are most often benign (more than 2/3 of cases). Vascular tumors are the most frequent benign tumors and infantile hemangioma accounts for 32% of these tumors, affecting 1 out of 200 children at birth. Kaposiform hemangioendothelioma (KH) is a rare vascular tumor with locally aggressive behavior. More than 50% of KH are associated with the Kasabach-Merritt phenomenon, a condition characterized by thrombocytopenia and consumptive coagulopathy. Malignant soft tissue tumors are, after neuroblastoma, the second cause of cancer in neonates. Infantile fibrosarcoma (IF) is a rare tumor that most often affects the extremities of children aged 4 years or younger. A recurrent t(12;15) (p13;q25) rearrangement fusing the ETV6 gene with the NTRK3 neurotrophin-3 receptor gene has been identified in IF. Complete conservative surgical resection is usually curative. Chemotherapy is indicated when initial surgical removal cannot be accomplished without unacceptable morbidity. Prognosis of IF is excellent, with reported overall survival rates ranging from 80 to 100%. Neonatal rhabdomyosarcoma (RMS) is a rare tumor (0.5-1% of RMS). The primary tumor predominantly involves the limbs and the genitourinary tract. Treatment is based on age-adapted chemotherapy and surgery. Prognosis of RMS in children less than 1 year old appears to be comparable with that of older children.
Unité(s) : Dermatologie
 
Lien PubMed [Cutaneous manifestations of vasculitis in childhood.]
PIRAM M, BODEMER C, KONE-PAUT I
2009 - Arch Pediatr 16(6):526-8
Unité(s) : Dermatologie
 
Lien PubMed Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response
RICE GI, BOND J, ASIPU A, BRUNETTE RL, MANFIELD IW, CARR IM, FULLER JC, JACKSON RM, LAMB T, BRIGGS TA, ALI M, GORNALL H, COUTHARD LR, AEBY A, ATTARD-MONTALTO SP, BERTINI E, BODEMER C, BROCKMANN K, BRUETON LA, CORRY PC, DESGUERRE I, FAZZI E, CAZORLA AG, GENER B, HAMEL BC, HEIBERG A, HUNTER M, VAN DER KNAAP MS, KUMAR R, LAGAE L, LANDRIEU PG, LOURENCO CM, MAROM D, MCDERMOTT MF, VAN DER MERWE W, ORCESI S, PRENDIVILLE JS, RASMUSSEN M, SHALEV SA, SOLER DM, SHINAWI M, SPIEGEL R, TAN TY, VANDERVER A, WAKELING EL, WASSMER E, WHITTAKER E, LEBON P, STETSON DB, BONTHRON DT, CROW YJ
2009 - Nat Genet 41(7):829-32
Aicardi-Goutieres syndrome is a mendelian mimic of congenital infection and also shows overlap with systemic lupus erythematosus at both a clinical and biochemical level. The recent identification of mutations in TREX1 and genes encoding the RNASEH2 complex and studies of the function of TREX1 in DNA metabolism have defined a previously unknown mechanism for the initiation of autoimmunity by interferon-stimulatory nucleic acid. Here we describe mutations in SAMHD1 as the cause of AGS at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral response.
Unité(s) : Neurologie, Dermatologie
 
Lien PubMed Prenatal diagnosis of cardiac rhabdomyomas: incidence of associated cerebral lesions of tuberous sclerosis complex
SAADA J, HADJ-RABIA S, FERMONT L, LE BIDOIS J, BERNADES LS, MARTINOVIC J, SONIGO P, DUMEZ Y, BONNET D, BENACHI A
2009 - Ultrasound Obstet Gynecol 34(2):155-159
OBJECTIVES: To determine the prevalence of specific cerebral lesions of tuberous sclerosis complex (TSC) and neurological outcome in cases diagnosed prenatally with cardiac rhabdomyomas. METHODS: We reviewed all fetuses diagnosed prenatally with cardiac rhabdomyomas which had undergone detailed ultrasound evaluation and cerebral magnetic resonance imaging (MRI) and which were recorded in the database of a single institution covering the period January 1992 to December 2005. RESULTS: Fifty-one fetuses were included in the study. MRI was performed at a mean +/- SD gestational age of 30 +/- 3 gestational weeks and showed specific lesions of TSC in 49% of cases. Termination of pregnancy was chosen by the parents in 26 cases. Neurological development was studied in 20 cases, follow-up lasting 4.8 +/- 2.9 years. Neurodevelopmental events occurred during the follow-up period in 45% of cases. Neurological complications occurred in 67% of patients who had cerebral lesions at MRI and in 33% of patients with normal MRI results. There was no significant difference between the two groups of patients (P = 0.2). CONCLUSION: In fetuses with cardiac rhabdomyomas detailed ultrasound examination and third-trimester cerebral MRI are able to diagnose most TSC cerebral lesions, but fail to determine neurological outcome. Copyright (c) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
Unité(s) : Dermatologie, Obstétrique, Radiologie Pédiatrique, Cardiologie Pédiatrique, Histo-Embryologie - Cytogénétique
 
Lien PubMed Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis
WEN Y, LIU Y, XU Y, ZHAO Y, HUA R, WANG K, SUN M, LI Y, YANG S, ZHANG XJ, KRUSE R, CICHON S, BETZ RC, NOTHEN MM, VAN STEENSEL MA, VAN GEEL M, STEIJLEN PM, HOHL D, HUBER M, DUNNILL GS, KENNEDY C, MESSENGER A, MUNRO CS, TERRINONI A, HOVNANIAN A, BODEMER C, DE PROST Y, PALLER AS, IRVINE AD, SINCLAIR R,
2009 - Nat Genet 41(2):228-33
Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of genetic hair loss. In a large Chinese family carrying MUHH, we identified a pathogenic initiation codon mutation in U2HR, an inhibitory upstream ORF in the 5' UTR of the gene encoding the human hairless homolog (HR). U2HR is predicted to encode a 34-amino acid peptide that is highly conserved among mammals. In 18 more families from different ancestral groups, we identified a range of defects in U2HR, including loss of initiation, delayed termination codon and nonsense and missense mutations. Functional analysis showed that these classes of mutations all resulted in increased translation of the main HR physiological ORF. Our results establish the link between MUHH and U2HR, show that fine-tuning of HR protein levels is important in control of hair growth, and identify a potential mechanism for preventing hair loss or promoting hair removal.
Unité(s) : Dermatologie
 
Lien PubMed Neonatal cases of infantile myofibromatosis do not derive from maternal cells transferred during pregnancy
YOUSEFI P, KHOSROTEHRANI K, OSTER M, DE PROST Y, FRAITAG S, ARACTINGI S
2009 - Br J Dermatol 160(6):1356-7
Unité(s) : Anatomie Pathologique, Dermatologie
 
  Identification of new RECQL4 mutations in Caucasian Rothmund-Thomson patients and analysis of sensitivity to a wide range of genotoxic agents
CABRAL RE, QUEILLE S, BODEMER C, DE PROST Y, NETO JB, SARASIN A, DAYA-GROSJEAN L
2008 - Mutat. Res.- Fundam. Mol. Mech. Mut. 643(1-2):41-47
Rothmund-Thomson syndrome (RTS), a rare recessive autosomal disorder, presents genome instability and clinical heterogeneity with growth deficiency, skin and bone defects, premature aging symptoms and cancer susceptibility. A subset of RTS patients presents mutations of the RECQL4 gene, member of the RecQ family of DNA helicases, including the RECQL2 (BLM) and RECQL3 (WRN) genes, defective in the cancer prone Bloom and Werner syndromes, respectively. Analysis of the RECQL4 gene in six clinically diagnosed RTS patients shows five patients, including two siblings, with eight mutations mainly located in the helicase domain, three patients presenting two mutations. The alterations include four missense mutations, one nonsense mutation and the same frameshift deletion, g.2881delG in exon 9 found in three patients. Seven RECQL4 polymorphisms, two being new, have also been identified. Primary RTS fibroblasts from these RTS patients show no sensitivity to a wide variety of genotoxic agents including ionizing or ultraviolet irradiation, nitrogen mustard, 4NQO, 8-MOP, Cis-Pt, MMC, H2O2, HU, or UV plus caffeine which could be related to the RECQL4 alterations identified here. This is in contrast with the DNA damage sensitive Bloom and Werner cells and highlights the complexity of the numerous RecQ protein functions implicated in the different cellular pathways required for maintaining genomic integrity.
Unité(s) : Dermatologie
 
  Dento-craniofacial phenotypes and underlying molecular mechanisms in hypohidrotic ectodermal dysplasia (HED): a review
CLAUSS F, MANIERE MC, OBRY F, WALTMANN E, HADJ-RABIA S, BODEMER C, ALEMBIK Y, LESOT H, SCHMITTBUHL M
2008 - J. Dent. Res. 87(12):1089-1099
The hypohidrotic ectodermal dysplasias (HED) belong to a large and heterogeneous nosological group of polymalfomative syndromes characterized by dystrophy or agenesis of ectodermal derivatives. Molecular etiologies of HED consist of mutations of the genes involved in the Ectodysplasin (EDA)-NF-kappaB pathway. Besides the classic ectodermal signs, craniofacial and bone manifestations are associated with the phenotypic spectrum of HED. The dental phenotype of HED consists of various degrees of oligodontia with other dental abnormalities, and these are important in the early diagnosis and identification of persons with HED. Phenotypic dental markers of heterozygous females for EDA gene mutation-moderate oligodontia, conical incisors, and delayed dental eruption-are important for individuals giving reliable genetic counseling. Some dental ageneses observed in HED are also encountered in non-syndromic oligodontia. These clinical similarities may reflect possible interactions between homeobox genes implicated in early steps of odontogenesis and the Ectodysplasin (EDA)-NF-kappaB pathway. Craniofacial dysmorphologies and bone structural anomalies are also associated with the phenotypic spectrum of persons with HED patients. The corresponding molecular mechanisms involve altered interactions between the EDA-NF-kappaB pathway and signaling molecules essential in skeletogenic neural crest cell differentiation, migration, and osteoclastic differentiation. Regarding oral treatment of persons with HED, implant-supported prostheses are used with a relatively high implant survival rate. Recently, groundbreaking experimental approaches with recombinant EDA or transgenesis of EDA-A1 were developed from the perspective of systemic treatment and appear very promising. All these clinical observations and molecular data allow for the specification of the craniofacial phenotypic spectrum in HED and provide a better understanding of the mechanisms involved in the pathogenesis of this syndrome.
Unité(s) : Dermatologie
 
  Nodular fasciitis of childhood: A clinicopathological analysis of 10 cases
DAUENDORFFER JN, ORTONNE N, BODEMER C, BROUSSE N, FRAITAG S
2008 - Ann. Dermatol. Vénéréolog. 135(8-9):553-558
BACKGROUND: Nodular fasciitis rarely affects children. To date, apart from isolated cases, only two series comprising respectively 15 and six children have been reported. PATIENTS AND METHODS: We carried out a retrospective study of the clinical and pathological aspects of 10 cases of nodular fasciitis involving children under 15 years of age diagnosed at the pathology laboratory of the Necker Children's Hospital (Paris, France) between 1992 and 2006. RESULTS: In comparison with previously reported data, our study highlights four new factors: (1) nodular fasciitis affected girls more often than boys; (2) it occurred predominantly on the trunk; (3) follow-up showed a high recurrence rate (22%) after surgical removal; (4) immunohistochemical analysis revealed a high level of expression of p53 by tumour cells; this was much higher than in adults. DISCUSSION: The high expression of p53 in nodular fasciitis, which has never been described in children, seems to point towards its preneoplastic rather than reactive nature.
Unité(s) : Anatomie Pathologique, Dermatologie
 
  Syndromic (phenotypic) diarrhea in early infancy
GOULET O, VINSON C, ROQUELAURE B, BROUSSE N, BODEMER C, CEZARD JP
2008 - Orphanet. J. Rare Dis. 3(.):6
Syndromic diarrhea (SD), also known as phenotypic diarrhea (PD) or tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset of severe diarrhea requiring parenteral nutrition (PN). To date, no epidemiological data are available. The estimated prevalence is approximately 1/300,000-400,000 live births in Western Europe. Ethnic origin does not appear to be associated with SD. Infants are born small for gestational age and present with facial dysmorphism including prominent forehead and cheeks, broad nasal root and hypertelorism. Hairs are woolly, easily removed and poorly pigmented. Severe and persistent diarrhea starts within the first 6 months of life (
Unité(s) : Anatomie Pathologique, Dermatologie, Gastro-Hépatologie et Nutrition Pédiatriques
 
  Case-control cohort study of patients' perceptions of disability in mastocytosis
HERMINE O, LORTHOLARY O, LEVENTHAL PS, CATTEAU A, SOPPELSA F, BAUDE C, COHEN-AKENINE A, PALMERINI F, HANSSENS K, YANG Y, SOBOL H, FRAYTAG S, GHEZ D, SUAREZ F, BARETE S, CASASSUS P, SANS B, AROCK M, KINET JP, DUBREUIL P, MOUSSY A
2008 - PLoS ONE 3(5):e2266
BACKGROUND: Indolent forms of mastocytosis account for more than 90% of all cases, but the types and type and severity of symptoms and their impact on the quality of life have not been well studied. We therefore performed a case-control cohort study to examine self-reported disability and impact of symptoms on the quality of life in patients with mastocytosis. METHODOLOGY/PRINCIPAL FINDINGS: In 2004, 363 mastocytosis patients and 90 controls in France were asked to rate to their overall disability (OPA score) and the severity of 38 individual symptoms. The latter was used to calculate a composite score (AFIRMM score). Of the 363 respondents, 262 were part of an ongoing pathophysiological study so that the following data were available: World Health Organization classification, standard measures of physical and psychological disability, existence of the D816V KIT mutation, and serum tryptase level. The mean OPA and AFIRMM scores and the standard measures of disability indicated that most mastocytosis patients suffer from disabilities due to the disease. Surprisingly, the patient's measurable and perceived disabilities did not differ according to disease classification or presence or absence of the D816V KIT mutation or an elevated (> or = 20 ng/mL) serum tryptase level. Also, 32 of the 38 AFIRMM symptoms were more common in patients than controls, but there were not substantial differences according to disease classification, presence of the D816V mutation, or the serum tryptase level. CONCLUSIONS: On the basis of these results and for the purposes of treatment, we propose that mastocytosis be first classified as aggressive or indolent and that indolent mastocytosis then be categorized according to the severity of patients' perceived symptoms and their impact on the quality of life. In addition, it appears that mastocytosis patients suffer from more symptoms and greater disability than previously thought, that mastocytosis may therefore be under-diagnosed, and that the symptoms of the indolent forms of mastocytosis might be due more to systemic release of mediators than mast cell burden.
Unité(s) : Anatomie Pathologique, Dermatologie, Hématologie Adulte, Infectiologie
 
  A familial case of Keratitis-Ichthyosis-Deafness (KID) syndrome with the GJB2 mutation G45E
JONARD L, FELDMANN D, PARSY C, FREITAG S, SINICO M, KOVAL C, GRATI M, COUDERC R, DENOYELLE F, BODEMER C, MARLIN S, HADJ-RABIA S
2008 - Eur. J. Med. Genet 51(1):35-43
Keratitis-Ichthyosis-Deafness (KID) syndrome (OMIM 148210) is a congenital ectodermal defect. KID consists of an atypical ichthyosiform erythroderma associated with congenital sensorineural deafness. A rare form of the KID syndrome is a fatal course in the first year of life due to severe skin lesion infections and septicaemia. KID appears to be genetically heterogeneous and may be caused by mutations in connexin 26 or connexin 30 genes. GJB2 mutations in the connexin 26 gene are the main cause of the disease. Most of the cases caused by GJB2 mutations are sporadic, but dominant transmission has also been described. To date, the rare lethal form of the disease has been only observed in two Caucasian sporadic patients with the GJB2 mutation, with the p.Gly45Glu (G45E) arising de novo. We have reported an African family with dizygotic twins suffering from a lethal form of KID. The dizygosity of the twins was confirmed by microsatellite markers. The two patients were heterozygous for the G45E mutation of GJB2, whereas the mutation was not detected in the two parents. The unusual transmission of the disease observed in this family could be explained by the occurrence of a somatic or more probably a germinal mosaic in one of the parents.
Unité(s) : Anatomie Pathologique, Dermatologie, Département de Pédiatrie
 
  Phenotypic and genotypic characteristics of mastocytosis according to the age of onset
LANTERNIER F, COHEN-AKENINE A, PALMERINI F, FEGER F, YANG Y, ZERMATI Y, BARETE S, SANS B, BAUDE C, GHEZ D, SUAREZ F, DELARUE R, CASASSUS P, BODEMER C, CATTEAU A, SOPPELSA F, HANSSENS K, AROCK M, SOBOL H, FRAITAG S, CANIONI D, MOUSSY A, LAUNAY JM, DUBREUIL P, HERMINE O, LORTHOLARY O
2008 - PLoS ONE 3(4):e1906
Adult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73%) in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001). 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001). Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001). In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy.
Unité(s) : Anatomie Pathologique, Hématologie Adulte, Infectiologie, Dermatologie, UMR 8147
 
  Fixed drug eruption caused by iodixanol
LE BETTER C, FRAITAG S, JACQUOT C, LOUET ALL, AUFFRET N
2008 - Ann. Dermatol. Vénéréolog. 135(10):684-685
Unité(s) : Anatomie Pathologique, Dermatologie
 
  Unusual presentation of a severe autosomal recessive anhydrotic ectodermal dysplasia with a novel mutation in the EDAR gene
MEGARBANE H, CLUZEAU C, BODEMER C, FRAITAG S, CHABABI-ATALLAH M, MEGARBANE A, SMAHI A
2008 - Amer. J. Med. Genet. A 146A(20):2657-2662
We report on an 18-year-old woman, born to first-cousin parents, presenting with a severe form of anhydrotic ectodermal dysplasia (EDA/HED). She had sparse hair, absent limb hair, absent sweating, episodes of hyperpyrexia, important hypodontia, and hyperconvex nails. She also showed unusual clinical manifestations such as an absence of breasts, a rudimentary extranumerary areola and nipple on the left side, and marked palmo-plantar hyperkeratosis. Light microscopy of skin biopsies showed orthokeratotic hyperkeratosis and absence of sweat glands. A novel homozygous mutation (IVS9 + 1G > A) in the EDAR gene was identified. This mutation results in a total absence of EDAR transcripts and consequently of the EDAR protein, which likely results in abolition of all ectodysplasin-mediated NF-kappaB signaling. This is the first complete loss-of-function mutation in the EDAR gene reported to date, which may explain the unusual presentation of HED in this patient, enlarging the clinical spectrum linked to the dysfunction of the ectodysplasin mediated NF-kappaB signaling.
Unité(s) : Anatomie Pathologique, Dermatologie, Génétique Médicale Pédiatrique, U781
 
  CEMARA: a Web Dynamic Application Within a N-tier Architecture for Rare Diseases
MESSIAEN C, LE MIGNOT L, RATH A, RICHARD JB, DUFOUR E, BEN SAID M, JAIS JP, VERLOES A, LE MERRER M, BODEMER C, BAUJAT G, GERARD-BLANLUET M, BOURDON-LANOY E, SALOMON R, AYME S, LANDAIS P
2008 - Stud. Health Technol. Informat. 136(51-56
Rare diseases include a group of conditions characterized by a prevalence lower than 5 per 10,000 in the community. In France, any rare disease affects less than 30,000 patients and often much less. Three to 4% of children and 6% of the population in Europe are affected. It is a true public health stake since most diseases do not have any curative treatment. In France, the Ministry of Health has initiated a National Rare Diseases Plan. Twenty five out of 132 labelled Reference Centres (RC) decided to share a common Information System named CEMARA. It is dedicated to collect continuous and complete records of all patients presenting with a rare disease, and their follow-up. The main objective of CEMARA is to contribute to the missions of the RC regarding the registration and description of their activities, coordination of the network of their correspondents, organization of the follow-up of rare diseases, and analysis of the epidemiological patterns. A description of CEMARA is provided as well as its cooperation with Orphanet and Genatlas, and a presentation of 11803 current records collected by more than 300 health care professionals belonging to more than 70 sites.
Unité(s) : Biostatistique, Dermatologie, Génétique Médicale Pédiatrique, EA 4067
 
  A frequent functional SNP in the MMP1 promoter is associated with higher disease severity in recessive dystrophic epidermolysis bullosa
TITEUX M, PENDARIES V, TONASSO L, DECHA A, BODEMER C, HOVNANIAN A
2008 - Hum. Mutat. 29(2):267-276
Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in the COL7A1 gene encoding type VII collagen. Variations in severity between the different clinical forms of RDEB likely depend on the nature and location of COL7A1 mutations, but observed intrafamilial phenotypic variations suggest additional genetic and/or environmental factors. Candidate modifier genes include MMP1, encoding matrix metalloproteinase 1, the first gene implicated in RDEB before its primary role in the disease was excluded. Type VII collagen is a substrate of MMP1 and an imbalance between its synthesis and degradation could conceivably worsen the RDEB phenotype. Here, we studied a previously described family with three affected siblings of identical COL7A1 genotype but displaying great sibling-to-sibling variations in disease severity. RDEB severity did not correlate with type VII collagen synthesis levels, but with protein levels at the dermal-epidermal junction, suggesting increased degradation by metalloproteinases. This was supported by the presence of increased transcript and active MMP1 levels in the most severely affected children, who carried a known SNP (1G/2G) in the MMP1 promoter. This SNP creates a functional Ets binding site resulting in transcriptional upregulation. We next studied a French cohort of 31 unrelated RDEB patients harboring at least one in-frame COL7A1 mutation, ranging from mild localized RDEB to the severe Hallopeau-Siemens form. We found a strong genetic association between the 2G variant and the Hallopeau-Siemens disease type (odds ratio: 73.6). This is the first example of a modifier gene in RDEB and has implications for its prognosis and possible new treatments.
Unité(s) : Dermatologie
 
  Primary cutaneous Epstein-Barr virus-related lymphoproliferative disorders in 4 immunosuppressed children
WALLET-FABER N, BODEMER C, BLANCHE S, DELABESSE E, ESCHARD C, BROUSSE N, FRAITAG S
2008 - J. Amer. Acad. Dermatol. 58(1):74-80
Primary cutaneous Epstein-Barr virus-related lymphoproliferative disorders are rare. We describe 4 cases in children: two with acquired immunodeficiencies (HIV infection, heart transplantation) and two with congenital immunodeficiencies (ataxia-telangiectasia and an undetermined disease affecting the T lymphocytes). Two of the lymphoproliferative disorders were T-cell types and two were B-cell types. The two T-cell types were also Epstein-Barr virus positive, which is extremely rare. Three of the patients developed extracutaneous disease with poor outcome, resulting in death.
Unité(s) : Anatomie Pathologique, Dermatologie, Immuno-Hématologie-Rhumatologie Pédiatriques
 
  Human epidermal Langerhans cells express the tight junction protein claudin-1 and are present in human genetic claudin-1 deficiency (NISCH syndrome
ZIMMERLI SC, KERL K, HADJ-RABIA S, HOHL D, HAUSER C
2008 - Exp. Dermatol. 17(1):20-23
Claudin-1 (CLDN1) is a structural tight junction (TJ) protein and is expressed in differentiating keratinocytes and Langerhans cells in the epidermis. Our objective was to identify immunoreactive CLDN1 in human epidermal Langerhans cells and to examine the pattern of epidermal Langerhans cells in genetic human CLDN1 deficiency [neonatal ichthyosis, sclerosing cholangitis (NISCH) syndrome]. Epidermal cells from healthy human skin labelled with CLDN1-specific antibodies were analysed by confocal laser immunofluorescence microscopy and flow cytometry. Skin biopsy sections of two patients with NISCH syndrome were stained with an antibody to CD1a expressed on epidermal Langerhans cells. Epidermal Langerhans cells and a subpopulation of keratinocytes from healthy skin were positive for CLDN1. The gross number and distribution of epidermal Langerhans cells of two patients with molecularly confirmed NISCH syndrome, however, was not grossly altered. Therefore, CLDN1 is unlikely to play a critical role in migration of Langerhans cells (or their precursors) to the epidermis or their positioning within the epidermis. Our findings do not exclude a role of this TJ molecule once Langerhans cells have left the epidermis for draining lymph nodes.
Unité(s) : Dermatologie
 
  Autosomal dominant anhidrotic ectodermal dysplasias at the EDARADD locus
BAL E, BAALA L, CLUZEAU C, EL KERCH F, OULDIM K, HADJ-RABIA S, BODEMER C, MUNNICH A, COURTOIS G, SEFIANI A, SMAHI A
2007 - Hum. Mutat. 28(7):703-709
Anhidrotic ectodermal dysplasia (EDA) is a disorder of ectodermal differentiation characterized by sparse hair, abnormal or missing teeth, and inability to sweat. X-linked EDA is the most common form, caused by mutations in the EDA gene, which encodes ectodysplasin, a member of the tumor necrosis factor (TNF) family. Autosomal dominant and recessive forms of EDA have been also described and are accounted for by two genes. Mutations in EDAR, encoding a TNF receptor (EDAR) cause both dominant and recessive forms. In addition, mutations in a recently identified gene, EDARADD, encoding EDAR-associated death domain (EDARADD) have been shown to cause autosomal recessive EDA. Here, we report a large Moroccan family with an autosomal dominant EDA. We mapped the disease gene to chromosome 1q42.2-q43, and identified a novel missense mutation in the EDARADD gene (c.335T>G, p.Leu112Arg). Thus, the EDARADD gene accounts for both recessive and dominant EDA. EDAR is activated by its ligand, ectodysplasin, and uses EDARADD to build an intracellular complex and activate nuclear factor kappa B (NF-kB). We compared the functional consequences of the dominant (p.Leu112Arg) and recessive mutation (p.Glu142Lys), which both occurred in the death domain (DD) of EDARADD. We demonstrated that the p.Leu112Arg mutation completely abrogated NF-kB activation, whereas the p.Glu142Lys retained the ability to significantly activate the NF-kB pathway. The p.Leu112Arg mutation is probably a dominant negative form as its cotransfection impaired the wild-type EDARADD's ability to activate NF-kB. Our results confirm that NF-kB activation is impaired in EDA and support the role of EDARADD DD as a downstream effector of EDAR signaling. Hum Mutat 28(7), 703-709, 2007. (c) 2007 Wiley-Liss, Inc.
Unité(s) : Dermatologie, Génétique Médicale Pédiatrique, U781
 
  Photosensibility and systemic disease in children
BODEMER C
2007 - Ann. Dermatol. Vénéréolog. 134(5 Pt.2):s45-s49
Unité(s) : Dermatologie
 
  Human lipodystrophies linked to mutations in A-type lamins and to HIV protease inhibitor therapy are both associated with prelamin A accumulation, oxidative stress and premature cellular senescence
CARON M, AUCLAIR M, DONADILLE B, BEREZIAT V, GUERCI B, LAVILLE M, NARBONNE H, BODEMER C, LASCOLS O, CAPEAU J, VIGOUROUX C
2007 - Cell Death Differ. 14(10):1759-1767
Lipodystrophic syndromes associated with mutations in LMNA, encoding A-type lamins, and with HIV antiretroviral treatments share several clinical characteristics. Nuclear alterations and prelamin A accumulation have been reported in fibroblasts from patients with LMNA mutations and adipocytes exposed to protease inhibitors (PI). As genetically altered lamin A maturation also results in premature ageing syndromes with lipodystrophy, we studied prelamin A expression and senescence markers in cultured human fibroblasts bearing six different LMNA mutations or treated with PIs. As compared to control cells, fibroblasts with LMNA mutations or treated with PIs had nuclear shape abnormalities and reduced proliferative activity that worsened with increasing cellular passages. They exhibited prelamin A accumulation, increased oxidative stress, decreased expression of mitochondrial respiratory chain proteins and premature cellular senescence. Inhibition of prelamin A farnesylation prevented cellular senescence and oxidative stress. Adipose tissue samples from patients with LMNA mutations or treated with PIs also showed retention of prelamin A, overexpression of the cell cycle checkpoint inhibitor p16 and altered mitochondrial markers. Thus, both LMNA mutations and PI treatment result in accumulation of farnesylated prelamin A and oxidative stress that trigger premature cellular senescence. These alterations could participate in the pathophysiology of lipodystrophic syndromes and lead to premature ageing complications.
Unité(s) : Dermatologie
 
  Transformed juvenile-onset mycosis fungoides: treatment by bone marrow transplantation with graft-versus-lymphoma effect
CARRIE E, BUZYN A, FRAITAG S, HERMINE O, BODEMER C
2007 - Ann. Dermatol. Vénéréolog. 134(5):471-476
BACKGROUND: Mycosis fungoides is the most frequent cutaneous T-cell lymphoma but has been rarely reported in children and teenagers. Although transformation into large-cell T-cell lymphoma has been described in 10% of adult cases, it is seen very rarely in children. We report here the clinical case of mycosis fungoides in a child with an unusual transformed form at presentation and treated by bone marrow allograft.CASE-REPORT: A 13 year-old boy, presenting guttate parapsoriasis for 5 years was referred to our Dermatology Department with a 2-month history of infiltrated plaques throughout the body and face. Large erythematous-squamous plaques on the trunk and face as well as a nodular lesion of the arm were also noted. On histology, typical features of mycosis fungoides were observed, in addition to transformed cells which were CD30-negative. Local treatment comprising caryolysin and dermal corticosteroids allowed initial regression of the lesions. However, a few months later, nodular lesions reappeared as well as axillary lymph nodes. Repeated histology confirmed the diagnosis of transformed mycosis fungoides with large CD30-positive cells. Despite chemotherapy, cutaneous and lymph node disease recurred, and bone marrow allograft was performed, resulting in rapid disease regression. Following the recurrence of skin lesions 2 years later, donor lymphocytes were administered in addition to treatment with interferon alpha, aiming at stimulating a graft-versus-lymphoma reaction. One year post-lymphocyte injection, the patient is in full remission.DISCUSSION: This is a new case report of juvenile mycosis fungoides with unusual clinical features such as rapid course and transformed form at presentation. Juvenile mycosis fungoides represents 2.5 to 5% of cases of mycosis fungoides and transformation to large cell lymphoma is exceptional. Our case illustrates the aggressive pattern observed in some teenage patients as well as the efficacy of bone marrow allograft, most likely thanks chiefly to its graft-versus-lymphoma effect.
Unité(s) : Dermatologie, Hématologie Adulte
 
  Histologic Cutaneous Modifications After the Use of EMLA Cream, A Diagnostic Pitfall: Review of 13 Cases
CAZES A, PROST-SQUARCIONI C, BODEMER C, HELLER M, BROUSSE N, FRAITAG S
2007 - Arch. Dermatol. 143(8):1074-1076
Unité(s) : Dermatologie, Anatomie Pathologique
 
  Clinical management of atopic eczema with pimecrolimus cream 1% (Elidel (R)) in paediatric patients
EICHENFIELD LF, THACI D, DE PROST Y, PUIG L, PAUL C
2007 - Dermatology 215(Suppl.1):3-17
Atopic eczema is predominantly a disease of children and infants, and is often a significant burden for both the sufferer and the family. Pimecrolimus cream 1% (Elidel (R)) is a topical calcineurin inhibitor that has been developed for the treatment of inflammatory skin diseases. When applied twice daily, pimecrolimus has been shown to be effective and well tolerated in paediatric patients with mild to moderate atopic eczema, and appears to be particularly suitable for use on the face, the neck and skin folds. Reduction of pruritus or erythema can be seen within 48 hours of initiating treatment, and when used at the first signs or symptoms of recurrence, pimecrolimus can significantly reduce the incidence of flares and the amount of topical corticosteroid used. Long-term pimecrolimus therapy shows that the initial reduction of disease severity (Eczema Area and Severity Index) is sustained and that most patients have minimal residual disease at 2 years. The most common application-site reaction is a mild to moderate, transient, warm/burning sensation occurring in approximately 10% of patients. Blood concentrations of pimecrolimus following topical administration remain low in all patients. Currently there is no evidence for systemic adverse events, immune suppression or alterations in the vaccine response, after short-term or prolonged treatment. In conclusion, pimecrolimus is an effective treatment option for the short-term treatment and long-term control of atopic eczema in paediatric patients. Copyright (C) 2007 S. Karger AG, Basel.
Unité(s) : Dermatologie
 
  Frequency of plantar dermatophytosis. A retrospective study 2002-2003
FOULET F, CREMER G, BOURDON-LANOY E, WOLKENSTEIN P, CHOSIDOW O, BRETAGNE S, REVUZ J
2007 - Ann. Dermatol. Vénéréolog. 134(4 Pt 1):343-345
BACKGROUND: Plantar dermatophytosis frequently goes unnoticed and can cause relapse or re-infestation at other sites. The purpose of this study was to evaluate the incidence of plantar dermatophytosis in association with onyxis and intertrigo involving dermatophytes. PATIENTS AND METHODS: This was a retrospective study in patients seen at mycology consultations between January 2002 and December 2003 and for whom culture revealed dermatophytes on the soles, interdigital spaces and/or toe nails. Gender, age and culture data were record from the laboratory workbooks. RESULTS: 716 patients were included, giving 1291 samples. The sex ratio M/F was 1.5 with a mean age of 48 years. Samples of toe nail were obtained from 591 patients, with plantar samples from 433 patients and intertrigo samples from 267 patients. Plantar dermatophytosis was seen in 66.6% of patients with interdigital-plantar signs, in 75.1% of those with ungual involvement and in 73.9% of cases involving both. T. rubrum was the most frequently isolated dermatophyte. DISCUSSION: Combine involvement of the sole, nail and/or interdigital space was seen in more than 2/3 of cases. Despite the retrospective nature of our study and the evident bias, our results suggest that plantar dermatophytosis is common and should be sought. The sensitivity and specificity of clinical screening methods merit investigation in a prospective study.
Unité(s) : Dermatologie
 
  Neonatal subcutaneous fat necrosis with hypercalcemia: efficiency of a low dose of corticosteroids
GERMANAUD D, HADJ-RABIA S, PARSY C, ABADIE V
2007 - Archives Pédiatrie 14(2):167-169
We report the case of a newborn with macrosomia, extensive subcutaneous fat necrosis and symptomatic hypercalcemia. Low doses of prednisone were efficient, while dietary intervention, hyperhydratation and furosemide were not. Treatment of hypercalcemia in this specific neonatal condition are discussed.
Unité(s) : Dermatologie, Pédiatrie Générale
 
  Classification of angiomas
HAMEL-TEILLAC D
2007 - Archives Pédiatrie 14(6):705-708
Unité(s) : Dermatologie
 
  Epigallocatechin gallate's protective effect against MMP7 in recessive dystrophic epidermolysis bullosa patients
IGONDJO-TCHEN-CHANGOTADE S, ASSOUMOU A, GUENICHE F, FIORETTI F, SEGUIER S, DE PROST Y, BODEMER C, GODEAU G, SENNI K
2007 - J. Invest. Dermatol. 127(4):821-828
The analysis of phenotype-genotype correlations of patients suffering from recessive dystrophic epidermolysis bullosa (RDEB) evidenced intrafamilial and interfamilial phenotype variability occurring for the same mutation of COL7A1; this underscores the role of other genetics environmental factors in the expressivity of the disease. In this work, we checked whether matrilysin 1 (matrix metalloproteinase (MMP)7) could take part in the epidermal detachment in RDEB. Furthermore, we investigated epigallocatechin 3 gallate (EGCG) to determine whether it could inhibit matrilysin activities on collagen type VII and fibrillin 1 known to be associated with the dermo-epidermal junction. In this work, matrilysin 1 was detected in affected and unaffected skins of the three RDEB patients; furthermore, MMP7 was shown to degrade ex vivo on healthy normal skin collagen VII and fibrillin 1. Thus, we suspect that MMP7 could take an active part in the epidermal detachment occurring during RDEB. We evidenced that EGCG in in vitro as well as in ex vivo experiments was a good inhibitor of MMP7 and developed a good protection of collagen type VII and fibrillin 1 susceptible of being degraded by MMP7. We therefore propose that EGCG could be used beneficially in patients suffering from RDEB.
Unité(s) : Dermatologie
 
  Subcutaneous fat necrosis of the newborn
MAHE E, DE PROST Y
2007 - Ann. Dermatol. Vénéréolog. 134(5 Pt 1):494-498
Unité(s) : Dermatologie
 
  Subcutaneous fat necrosis of the newborn: a systematic evaluation of risk factors, clinical manifestations, complications and outcome of 16 children
MAHÉ E, GIRSZYN N, HADJ-RABIA S, BODEMER C, HAMEL-TEILLAC D, DE PROST Y
2007 - Br. J. Dermatol. 156(4):709-715
Background: Subcutaneous fat necrosis (SFN) of the newborn is a rare acute transient hypodermatitis that develops within the first weeks of life in term infants. It often follows a difficult delivery. Prognosis is generally good except for the development of hypercalcaemia in severe cases. Only several case reports or small patients series have been published. Objectives: To evaluate risk factors, complications and outcomes of SFN in 16 consecutive patients seen from 1996 to 2002 in our Department of Paediatric Dermatology. Methods: On a case-report form created for the study, we recorded putative risk factors concerning the mother, pregnancy and delivery, clinical aspects of SFN, and early and late outcomes. The study was conducted in two stages: the first was a retrospective analysis of the observations and the second analysed data collected on children and their parents during a new consultation (n = 10). Results: All the children were born at term. Lesions appeared a mean of 4 days after delivery. Three-quarters of the children had diffuse SFN. Risk factors identified were newborn failure to thrive (12/16), forceps delivery (7/16), maternal high blood pressure (3/10) and/or diabetes (2/10), and newborn cardiac surgery (1/16). Putative novel risk factors were macrosomia (7/16), exposure to active (4/10) or passive (3/10) smoking during pregnancy, putative or known maternal, paternal or newborn risk factors for thrombosis (5/10), and dyslipidaemia (2/10). Complications were hypercalcaemia (9/16), pain (4/16), dyslipidaemia (1/16), renal insufficiency (1/16) and late subcutaneous atrophy (6/6). Conclusions: This study on 16 newborns with SFN provides new information. Familial or newborn risk factors for thrombosis are frequent. Macrosomia, familial dyslipidaemia and smoking should be evaluated. The main complications identified were severe pain, hypercalcaemia and subcutaneous atrophy.
Unité(s) : Dermatologie
 
  Angioedema in renal transplant recipients on sirolimus
MAHE E, MORELON E, LECHATON S, KREIS H, DE PROST Y, BODEMER C
2007 - Dermatology 214(3):205-209
Background:Most drug-associated angioedemas are induced by angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, or nonsteroidal anti-inflammatory drugs. Recently, the responsibility of immunosuppressive agents given to transplant recipients in the development of angioedema has been discussed. Objective: To describe, in detail, angioedema episodes in renal transplant recipients (RTRs) on sirolimus. Methods: A cross-sectional study in a university hospital. Eighty consecutive RTRs on sirolimus were studied. Results: Angioedema without urticaria occurred a mean of 5 times in 12/80 (15%) RTRs taking sirolimus. It was predominantly located on the face (83%), with mucous membrane involvement in 7 (58%) patients, and was life threatening in 1. Another putative cofactor for angioedema without urticaria was identified in 9 (75%) patients: drugs (n = 8), food allergy or physical activity (n = 3). Tacrolimus intake was significantly associated with sirolimus-associated angioedema. Conclusion: Our results suggested a causal relationship between sirolimus and angioedema in RTRs. Copyright (c) 2007 S. Karger AG, Basel.
Unité(s) : Dermatologie, Transplantation Adulte
 
  A clinical, histologic, and molecular study of 9 cases of congenital dermatofibrosarcoma protuberans
MAIRE G, FRAITAG S, GALMICHE L, KESLAIR F, EBRAN N, TERRIER-LACOMBE MJ, DE PROST Y, PEDEUTOUR F
2007 - Arch. Dermatol. 143(2):203-210
BACKGROUND: The diagnosis of dermatofibrosarcoma protuberans (DFSP) in childhood is often difficult because of the deceptive appearance of the lesions. Little is known about congenital DFSP, the frequency of which is probably underestimated because the initial lesion may pass unnoticed. OBSERVATIONS: We studied 9 DFSP congenital cases (8 plaques and 1 nodule) initially suspected to be benign lesions. The first biopsies or excisions were performed after a delay of 5(1/2) months to 15 years. All cases were CD34+. Histologic patterns were similar to the DFSP adult classic pattern in 4 cases. One case was a Bednar tumor. The histologic diagnosis of the 4 remaining cases was difficult. The collagen, type I, alpha 1-platelet-derived growth factor beta fusion gene (COL1A1-PDGFB) was detected by means of reverse transcriptase-polymerase chain reaction or fluorescence in situ hybridization. CONCLUSIONS: All cases of congenital DFSP were difficult to identify clinically. The diagnosis was suspected by means of histologic and immunohistochemical evaluation and was confirmed using molecular analyses. This study illustrates the difficulties and pitfalls of the recognition of congenital DFSP and emphasizes the value of immunohistochemical study with anti-CD34 and complementary molecular analysis for all cutaneous spindle cell tumors and plaques in neonates and infants.
Unité(s) : Anatomie Pathologique, Dermatologie
 
  Keratitis-ichthyosis-deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients
MAZEREEUW-HAUTIER J, BITOUN E, CHEVRANT-BRETON J, MAN SY, BODEMER C, PRINS C, ANTILLE C, SAURAT JH, ATHERTON D, HARPER JI, KELSELL DP, HOVNANIAN A
2007 - Br. J. Dermatol. 156(5):1015-1019
Background Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital disorder characterized by the association of skin lesions, hearing loss and vascularizing keratitis. KID syndrome is caused by autosomal dominant mutations in the connexin 26 gene (GJB2). Objectives To establish whether there is a correlation between genotype and phenotype in KID syndrome. Methods Clinical examination and molecular analysis of GJB2 were performed in a cohort of 14 patients with KID syndrome originating from 11 families. We also reviewed the 23 cases with molecular analysis previously reported in the literature. Results The patients displayed the classical signs of KID syndrome with the additional finding of inflammatory nodules in six patients (43%); this clinical finding has not been described previously in the literature. One patient presented at the age of 18 years with a fatal carcinoma of the tongue, an extremely rare reported complication. For seven of the 11 families (64%) the disease was sporadic, whereas it was familial in the remaining four families (36%). Twelve patients (86%) were heterozygous for the p.Asp50Asn mutation and two patients (14%) were heterozygous for the p.Ser17Phe mutation. Surprisingly, a family in which we personally examined the healthy parents had two affected children heterozygous for the p.Asp50Asn mutation, suggesting germinal mosaicism. Compared with patients with the p.Asp50Asn mutation, the two patients with the p.Ser17Phe mutation had more severe skin involvement. One of these two patients experienced a carcinoma of the tongue. Conclusions Familial cases appear to be more frequent than reported in the literature. The possibility of germinal mosaicism must be taken into account for genetic counselling. This study also suggests that patients with the p.Ser17Phe mutation may have a more severe phenotype and could be at higher risk for tongue carcinoma.
Unité(s) : Dermatologie
 
  HEALING OF OLD WORLD CUTANEOUS LEISHMANIASIS IN TRAVELERS TREATED WITH FLUCONAZOLE: DRUG EFFECT OR SPONTANEOUS EVOLUTION?
MORIZOT G, DELGIUDICE P, CAUMES E, LAFFITTE E, MARTY P, DUPUY A, SARFATI C, HADJ-RABIA S, DARIE H, LE GUERN AS, SALAH AB, PRATLONG F, DEDET JP, GROGL M, BUFFET PA
2007 - Amer. J. Trop. Med. Hyg. 76(1):48-52
The efficacy of fluconazole was evaluated in 35 travelers with parasitologically proven imported Old World cutaneous leishmaniasis (CL). Leishmania major (mainly MON-25) was identified in 15 patients and strongly suspected given the transmission area in 12 of these patients. Daily oral fluconazole (200 mg/day for adults and 2.5 mg/kg/day for children) was prescribed for six weeks. Outcome definition was based on re-epithelialization rate at day 50. Of the 27 L. major-infected patients, 12 (44.4%) were cured. This cure rate is similar to the placebo cure rate from trials in L. major CL in which, as in the present report, the definition of outcome relied exclusively on re-epithelialization. These data question the assumption that oral fluconazole is consistently effective for treatment of CL caused by L. major.
Unité(s) : Dermatologie
 
  Requests for emergency appointments pendulum of the breast with dermatologists in private practice in France: the ETude Urgences en DErmatologie liberale (ETUDE) study
PENSO-ASSATHIANY D, BOURDON-LANOY E, DERANCOURT C, ROUJEAU JC, BASTUJI-GRAIN S
2007 - Ann. Dermatol. Vénéréolog. 134(1):23-29
Background. Requests for emergency appointments are fairly common in private dermatologic practice in France. To our knowledge the frequency and reasons for such requests have not yet been evaluated. The primary objective of our study was to provide a quantitative and qualitative evaluation of such requests and to assess the underlying reasons. The secondary aim was to investigate for an association between emergency requests where response was justified within 48 hours and the symptoms reported by patients in order to establish a predictive score for the validity of requests. Methods. The study took place during one week in April 2004. Forty French dermatologists took part on a voluntary basis. They deliberately reduced their ongoing schedule to accommodate patients seeking an urgent appointment. We collected data regarding the normal professional activity of each dermatologist, reasons for appointments, symptoms, diagnosis and evaluation of the degree of emergency by the attending dermatologist. Univariate and multivariate analyses were performed and a score was attributed based on the results for the variables used in the logistic regression model. Results. The mean number of patients seen at emergency appointments during the study week doubled in comparison with a normal period. During the week, 613 patients phoned and all questionnaires were completed for 538 (88%) patients. The most common reasons for requesting an appointment were: rash, eczema, pruritus, tumour modification, localized lesion and allergy. The most frequent diagnoses were: eczema, bacterial and viral infection, atopic dermatitis, mycosis and naevus. The dermatologists considered that the consultations were justified within 48 hours for one third of patients. in the multivariate analysis, factors significantly associated with a justified request were of a general medical rather than a dermatological nature: enlarged cysts, blisters, insomnia, impaired activity, onset or aggravation within the previous 7 days, inability to work. The score showed good specificity but poor sensitivity and discriminative value. Discussion. These results suggest that requests for emergency appointments are more frequent than previously suspected (14% of all requests). Physicians considered that emergency appointments within 48 hours were justified for one third of patients. The reasons for consultation and the resulting diagnoses were similar to those seen in emergency hospital consultations. The criteria on which the need for emergency consultation was based were not for the most part dermatologic. The scoring system we established was not sensitive enough to allow reliable pre-selection of patients requiring emergency consultation by telephone.
Unité(s) : Dermatologie
 
  Wells' syndrome after primoinfection by parvovirus B19 in a child
TOULON A, BOURDON-LANOY E, HAMEL D, FRAITAG S, LERUEZ-VILLE M, DE PROST Y, HADJ-RABIA S
2007 - J. Amer. Acad. Dermatol. 56(2 Suppl.):S50-S51
Unité(s) : Dermatologie, Anatomie Pathologique, Laboratoire de Microbiologie
 
  Non-penetrating deep sclerectomy for glaucoma associated with Sturge-Weber syndrome
AUDREN F, ABITBOL O, DUREAU P, HAKIKI S, ORSSAUD C, BOURGEOIS M, PIERRE-KAHN A, BODEMER C, DUFIER JL
2006 - Acta Ophthalmol. Scand. 84(5):656-660
Purpose: To report the results of non-penetrating deep sclerectomy (NPDS) in the treatment of glaucoma associated with Sturge-Weber syndrome (SWS). Methods: We carried out a retrospective case series analysis of patients who underwent NPDS for glaucoma associated with SWS between 1998 and 2003. The control of glaucoma after NPDS, the results of surgery on intraocular pressure, the need for additional medical treatment and surgical complications were studied. Results: Twelve eyes of nine patients, aged 11 days to 24 years, underwent filtering surgery: nine NPDS procedures were performed and three surgical procedures had to be converted to trabeculectomy because NPDS was not technically achievable. The mean follow-up after surgery was 26.3 months (range 6-48 months). Two trabeculectomies were complicated by choroidal effusion, which resolved in both cases. Good control of glaucoma was obtained during follow-up. Conclusions: Non-penetrating deep sclerectomy is transiently efficient in the treatment of SWS-associated glaucoma. Further studies of NPDS for the treatment of glaucoma associated with SWS are warranted.
Unité(s) : Dermatologie, Neurochirurgie Pédiatrique, Ophtalmologie
 
  Atopic dermatitis in children
BOURDON-LANOY E, DE PROST Y
2006 - Rev. Prat. 56(3):258-265
Atopic dermatitis is a chronic inflammatory and recurrent dermatosis, the frequency of which increases regularly in industrialised countries. It begins in the first months of life and the clinical presentation changes with the age of the child. The diagnostic is clinical in the majority of cases. Sometimes allergological explorations are necessary. The treatment has two objectives: treatment of the flares (mainly topical corticosteroids) and preventive adjuvant measures. The use of topical immunosuppressors reinforces the therapeutic management, after failure of topical corticosteroids.
Unité(s) : Dermatologie
 
  Absence of anti-BP180 antibodies in mothers of infants with bullous pemphigoid
CHIAVERINI C, HAMEL-TEILLAC D, GILBERT D, DE PROST Y
2006 - Br. J. Dermatol. 154(5):839-843
Background It is not clear whether bullous pemphigoid (BP) of infancy is linked to maternal transmission of pathogenic autoantibodies. Objectives To search for anti-BP180 antibodies in the sera of infants with BP and their mothers, using sensitive and specific methods. Methods Four infants (< 6 months) with BP and their mothers were tested for anti-BP180 antibodies by indirect immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA). Results We found anti-BP180 antibodies in the sera of the four infants with all methods. These antibodies reacted with the extracellular domain NC16A. In the serum of their mothers we found 180 and 160 kDa proteins, each in one case, but indirect immunofluorescence and ELISA were negative, suggesting the absence of anti-BP180 autoantibodies reacting with the extracellular domain NC16A. Conclusions BP of infants is not due to maternofetal transmission of pathogenic autoantibodies. Other hypotheses for the pathophysiology of BP are discussed.
Unité(s) : Dermatologie
 
  New topical immunological treatments for psoriasis
DE PROST Y
2006 - J. Eur. Acad. Dermatol. Venereol. 20(Suppl.2):80-82
Topical treatments for psoriasis have been used for a very long time. They were designed to reduce epidermal proliferation and hyperkeratosis. Recent pathophysiological data have led to the use of many immunological therapies, initially systemically in severe forms and, in recent years, topically. Calcineurin inhibitors are now a well-established treatment for atopic dermatitis and have also been evaluated in psoriasis. The first trials of tacrolimus (Protopic((R)), Astellas) and pimecrolimus (Elidel((R)), Novartis) failed to demonstrate any positive results on plaque-type psoriasis, but several studies showed a definite efficacy on facial and intertriginous psoriasis. Calcineurin inhibitors do not induce skin atrophy and are therefore particularly useful in sites in which the skin is thinner (face, intertriginous areas). A third substance, sirolimus (Rapamune((R)), Wyeth), has recently been tested topically in psoriasis. A recent study demonstrated that topical sirolimus crosses the cutaneous barrier and is effective on psoriasis lesions. These studies therefore show an indisputable efficacy of calcineurin inhibitors and sirolimus in the treatment of localized psoriasis. The major advantage is the absence of skin atrophy. However, large-scale efficacy and safety studies must be conducted in this indication.
Unité(s) : Dermatologie
 
  Clinical study and physiopathology of diaper rash in the newborn and the infant
DE PROST Y
2006 - Archives Pédiatrie 13(Sp.Iss.3):1
Unité(s) : Dermatologie
 
  Corneodesmosomal Cadherins Are Preferential Targets of Stratum Corneum Trypsin- and Chymotrypsin-like Hyperactivity in Netherton Syndrome
DESCARGUES P, DERAISON C, PROST C, FRAITAG S, MAZEREEUW-HAUTIER J, D'ALESSIO M, ISHIDA-YAMAMOTO A, BODEMER C, ZAMBRUNO G, HOVNANIAN A
2006 - J. Invest. Dermatol. 126(7):1622-1632
SPINK5 (serine protease inhibitor Kazal-type 5), encoding the protease inhibitor LEKTI (lympho-epithelial Kazal-type related inhibitor), is the defective gene in Netherton syndrome (NS), a severe inherited keratinizing disorder. We have recently demonstrated epidermal protease hyperactivity in Spink5(-/-) mice resulting in desmosomal protein degradation. Herein, we investigated the molecular mechanism underlying the epidermal defect in 15 patients with NS. We demonstrated that, in a majority of patients, desmoglein 1 (Dsg1) and desmocollin 1 (Dsc1) were dramatically reduced in the upper most living layers of the epidermis. These defects were associated with premature degradation of corneodesmosomes. Stratum corneum tryptic enzyme (SCTE)-like and stratum corneum chymotryptic enzyme (SCCE)-like activities were increased, suggesting that these proteases participate in the premature degradation of corneodesmosomal cadherins. SCTE and SCCE expression was extended to the cell layers where Dsg1 and Dsc1 immunostaining was reduced. In contrast, a subset of six patients with normal epidermal protease activity or residual LEKTI expression displayed apparently normal cadherin expression and less severe disease manifestations. This suggests a degree of correlation between cadherin degradation and clinical severity. This work further supports the implication of premature corneodesmosomal cadherin degradation in the pathogenesis of NS and provides evidence for additional factors playing a role in disease expression.Journal of Investigative Dermatology (2006) 126, 1622-1632. doi:10.1038/sj.jid.5700284; published online 20 April 2006.
Unité(s) : Dermatologie
 
  Successful allogeneic hemopoietic stem cell transplantation in a child who had anhidrotic ectodermal dysplasia with immunodeficiency
DUPUIS-GIROD S, CANCRINI C, LE DEIST F, PALMA P, BODEMER C, PUEL A, LIVADIOTTI S, PICARD C, BOSSUYT X, ROSSI P, FISCHER A, CASANOVA JL
2006 - Pediatrics 118(1):e205-e211
Anhidrotic ectodermal dysplasia with immunodeficiency is associated with multiple infections and a poor clinical outcome. Hypomorphic mutations in nuclear factor kappaB essential modulator (NEMO)/IkappaB kinase complex and a hypermorphic mutation in inhibitor alpha of nuclear factor kappaB (IkappaBalpha) both result in impaired nuclear factor kappaB activation and are associated with X-recessive and autosomal-dominant forms of anhidrotic ectodermal dysplasia with immunodeficiency, respectively. Autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency is also associated with a severe T-cell phenotype. It is not known whether hematopoietic stem cell transplantation can cure immune deficiency in children with anhidrotic ectodermal dysplasia with immunodeficiency. A boy with autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency and a severe T-cell immunodeficiency underwent transplantation at 1 year of age with haploidentical T-cell-depleted bone marrow after myeloablative conditioning. Engraftment occurred, with full hematopoietic chimerism. Seven years after transplantation, clinical outcome is favorable, with normal T-cell development. As expected, the developmental features of the anhidrotic ectodermal dysplasia syndrome have appeared and persisted. This is the first report of successful hematopoietic stem cell transplantation in a child with anhidrotic ectodermal dysplasia with immunodeficiency. Hematopoietic stem cell transplantation is well tolerated and efficiently cures the profound immunodeficiency associated with autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency.
Unité(s) : Biothérapie, Immuno-Hématologie Pédiatrique, U550, U768, Dermatologie
 
  X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production
FILIPE-SANTOS O, BUSTAMANTE J, HAVERKAMP MH, VINOLO E, KU CL, PUEL A, FRUCHT DM, CHRISTEL K, VON BERNUTH H, JOUANGUY E, FEINBERG J, DURANDY A, SENECHAL B, CHAPGIER A, VOGT G, DE BEAUCOUDREY L, FIESCHI C, PICARD C, GARFA M, CHEMLI J, BEJAOUI M, TSOLIA MN, KUTUKCULER N, PLEBANI A, NOTARANGELO L, BODEM
2006 - J. Exp. Med. 203(7):1745-1759
Germline mutations in five autosomal genes involved in interleukin (IL)-12-dependent, interferon (IFN)-gamma-mediated immunity cause Mendelian susceptibility to mycobacterial diseases (MSMD). The molecular basis of X-linked recessive (XR)-MSMD remains unknown. We report here mutations in the leucine zipper (LZ) domain of the NF-kappaB essential modulator (NEMO) gene in three unrelated kindreds with XR-MSMD. The mutant proteins were produced in normal amounts in blood and fibroblastic cells. However, the patients' monocytes presented an intrinsic defect in T cell-dependent IL-12 production, resulting in defective IFN-gamma secretion by T cells. IL-12 production was also impaired as the result of a specific defect in NEMO- and NF-kappaB/c-Rel-mediated CD40 signaling after the stimulation of monocytes and dendritic cells by CD40L-expressing T cells and fibroblasts, respectively. However, the CD40-dependent up-regulation of costimulatory molecules of dendritic cells and the proliferation and immunoglobulin class switch of B cells were normal. Moreover, the patients' blood and fibroblastic cells responded to other NF-kappaB activators, such as tumor necrosis factor-alpha, IL-1beta, and lipopolysaccharide. These two mutations in the NEMO LZ domain provide the first genetic etiology of XR-MSMD. They also demonstrate the importance of the T cell- and CD40L-triggered, CD40-, and NEMO/NF-kappaB/c-Rel-mediated induction of IL-12 by monocyte-derived cells for protective immunity to mycobacteria in humans.
Unité(s) : U550, U768, Biothérapie, Dermatologie, Immuno-Hématologie Pédiatrique, IRNEM, Avenir
 
  Rapamycin inhibits growth and survival of D816V-mutated c-kit mast cells
GABILLOT-CARRE M, LEPELLETIER Y, HUMBERT M, DE SEPUVELDA P, HAMOUDA NB, ZAPPULLA JP, LIBLAU R, RIBADEAU-DUMAS A, MACHAVOINE F, LETARD S, BAUDE C, HERMANT A, YANG Y, VARGAFTIG J, BODEMER C, MORELON E, LORTHOLARY O, RECHER C, LAURENT G, DY M, AROCK M, DUBREUIL P, HERMINE O
2006 - Blood 108(3):1065-1072
Two classes of oncogenic mutations of the c-kit tyrosine kinase have been described: the juxtamembrane domain V560G mutation, which is preferentially found in gastrointestinal stromal tumors (GISTs), and the kinase domain D816V mutation, which is highly representative of systemic mastocytosis (SM). Here we show that both mutations constitutively activate the mammalian target of rapamycin (mTOR) signaling pathway. Surprisingly, the mTOR inhibitor rapamycin induces only apoptosis in HMC-1 cells bearing the D816V but not the V560G mutation. In support of this unexpected selectivity, rapamycin inhibits the phosphorylation of 4E-BP1, a downstream substrate of the mTOR pathway, but only in D816V HMC-1 cells. Importantly, D816V mast cells isolated from SM patients or from transgenic mice are sensitive to rapamycin whereas normal human or mouse mast cells are not. Thus, rapamycin inhibition appears specific to the D816V mutation. At present there is no effective cure for SM patients with the D816V mutation. The data presented here provide a rationale to test whether rapamycin could be a possible treatment for SM and other hematologic malignancies with the D816V mutation.
Unité(s) : Dermatologie, UMR 8147, Transplantation & Réanimation Adulte, U580, Hématologie Adulte, Infectiologi
 
  Vulvar lichen planus in children
HATUEL H, FRAITAG S, THIBAUD E, HAMEL D
2006 - Ann. Dermatol. Vénéréolog. 133(10):802-803
BACKGROUND: Lichen planus is less common in children about in adults and mostly affects the skin.CASE REPORT: A 9-year-old girl was referred for a purplish blue and violaceous, unilateral and asymptomatic vulvar lesion noted 4 months earlier and stable. Histopathologic examination showed typical features of lichen planus. She responded well and rapidly with topical steroids.DISCUSSION: We report the first case of vulvar lichen planus in a little girl. Mucosal involvement is uncommon in children with lichen planus and genital localisation is extremely rare. Vulvar lichen sclerosis is the principal differential diagnosis. The risk of vulvar synechia and development of vulvar carcinomas warrants regular long-term follow-up.
Unité(s) : Dermatologie, Anatomo-Pathologie, Métabolisme-Neurologie
 
  Presence of chimeric maternally derived keratinocytes in cutaneous inflammatory diseases of children: the example of pityriasis lichenoides
KHOSROTEHRANI K, GUEGAN S, FRAITAG S, OSTER M, DE PROST Y, BODEMER C, ARACTINGI S
2006 - J. Invest. Dermatol. 126(2):345-348
During pregnancy, maternal cells may enter the fetal circulation and persist until adulthood. The fate of these cells remains unknown. As unexplained T-cell-mediated conditions such as pityriasis lichenoides (PL) may occur in children, we aimed at identifying maternal cells in lesional skin of PL and controls. Archived skin biopsy specimens from young males with PL, atopic dermatitis, or normal skin were scanned for the presence of female (presumably maternal) cells using fluorescence in situ hybridization (FISH) with X and Y chromosome-specific probes. Phenotyping of maternal cells relied on FISH combined with anti-CD45, anti-CD1a, or anti-cytokeratin labelling, identifying leukocytes, Langerhans cells, and keratinocytes, respectively. Maternal cells were found in PL (11/12) and controls (4/7), but their average frequency was higher in PL: 99 per million cells as compared to 5 per million cells in controls (P=0.005). In the epidermis, the maternal microchimeric cells were labelled by anti-cytokeratin in all cases. We identified maternally derived keratinocytes in the skin of male children with inflammatory skin disorders. These cells may either help repair the damaged skin or home initially in the skin and trigger a host (child) versus graft (mother) disease.Journal of Investigative Dermatology (2006) 126, 345-348. doi:10.1038/sj.jid.5700060; published online 29 December 2005.
Unité(s) : Anatomo-Pathologie, Dermatologie
 
  Plane warts in areas of atopic dermatitis treated with tacrolimus ointment
MAHE E, HADJ-RABIA S, DE PROST Y
2006 - Ann. Dermatol. Vénéréolog. 133(8-9 Pt 1):705-707
Unité(s) : Dermatologie
 
  Acne in recipients of renal transplantation treated with sirolimus: clinical, microbiologic, histologic, therapeutic, and pathogenic aspects
MAHE E, MORELON E, LECHATON S, DRAPPIER JC, DE PROST Y, KREIS H, BODEMER C
2006 - J. Amer. Acad. Dermatol. 55(1):139-142
We evaluated the clinical characteristics of sirolimus-induced acne in 80 recipients of renal transplantation. It developed in 36 of 48 (75%) men and 2 of 32 (6%) women. Lesion locations and clinical, bacteriologic, and histologic features differentiated sirolimus-induced acne from acne vulgaris, but therapeutic management was similar. The main limitation for this study was the absence of a control group without sirolimus. Epidermal growth factor inhibition by sirolimus is a plausible explanation for this acne.
Unité(s) : Dermatologie, Transplantation & Réanimation Adulte
 
  Sirolimus-induced onychopathy in renal transplant recipients
MAHE E, MORELON E, LECHATON S, KREIS H, DE PROST Y, BODEMER C
2006 - Ann. Dermatol. Vénéréolog. 133(6-7):531-535
INTRODUCTION: A large number of drugs may be responsible for the development of nail changes. Sirolimus is an immunosuppressive drug recently developed in organ transplantation. Herein, we evaluate sirolimus-induced nail abnormalities in renal transplant recipients.PATIENTS AND METHODS: The nails of 80 consecutive renal transplant recipients receiving sirolimus have been evaluated in a systematic dermatological study in 2003. The patients were mainly men (60%) with a mean age of 48 years. The mean duration of the graft was 6 years and of sirolimus treatment 18 months. Mycophenolate mofetil and steroids were combined with sirolimus in 86% of patientsRESULTS: Fifty-seven patients (74%) complained for nail alterations. The most frequent anomalies (88%) were matrix alterations including slow growth, onychomalacia, onychorrexis, and leukonychia. Nail bed alterations (onycholysis), vascular phenomenon (erythema, splinter hemorrhages), and periungual anomalies (mainly pyogenic granulomas) were observed in 42, 42 and 19% of cases respectively. One observation of type 1 photo-onycholysis was described.DISCUSSION: This study reports a new drug-induced onychopathy. Responsibility of sirolimus is highly suggested. The main pathogenesis hypothesis to explain these nail alterations is inhibition of EGF (epidermal growth factor) pathway by sirolimus.
Unité(s) : Dermatologie, Transplantation & Réanimation Adulte
 
  Treatment of paediatric atopic dermatitis with pimecrolimus (Elidel(R), SDZ ASM 981): impact on quality of life and health-related quality of life
MCKENNA S, WHALLEY D, DE PROST Y, STAAB D, HUELS J, PAUL C, VAN ASSCHE D
2006 - J. Eur. Acad. Dermatol. Venereol. 20(3):248-254
Aim To report on quality of life (QoL) and health-related quality of life (HRQL) impacts of pimecrolimus (Elidel(R), Novartis A.G., Basel, Switzerland, SDZ ASM 981) 1% cream in the long-term treatment of paediatric atopic dermatitis. Methods QoL and HRQL data are presented from two 12-month international clinical trials evaluating the efficacy and safety of pimecrolimus 1% cream. Both trials were randomized and double blinded and compared two treatment strategies, one involving the use of emollients, pimecrolimus and topical corticosteroids, the other is 'usual care' (emollients plus topical corticosteroids) with a vehicle cream to maintain study blinding. The first trial (the infant trial) involved patients between ages 3 months and 2 years, whereas the children trial included patients aged 2-17 years. In both trials, QoL of the affected child's parent was evaluated with the parent's index of quality of life in atopic dermatitis (PIQoL-AD). HRQL was assessed in the children trial only with the children's dermatology life quality index (CDLQI). QoL and HRQL assessments were conducted at baseline, 6 weeks, 6 months and 12 months. Results Generalized linear modelling of PIQoL-AD scores at each post-baseline visit showed a greater impact on parent's QoL for pimecrolimus compared with control at all time-points in both trials. HRQL scores showed a greater improvement from baseline for children in the pimecrolimus group compared with those in the control group at all time-points. Conclusions The results show a beneficial impact of pimecrolimus on parents' QoL in paediatric atopic dermatitis, confirming findings from earlier shorter term trials. There was also a clear benefit to the HRQL of the children treated.
Unité(s) : Dermatologie
 
  Safety and tolerability of 1% pimecrolimus cream among infants: experience with 1133 patients treated for up to 2 years
PAUL C, CORK M, ROSSI AB, PAPP KA, BARBIER N, DE PROST Y
2006 - Pediatrics 117(1):e118-e128
Pimecrolimus is a calcineurin inhibitor developed for the topical treatment of atopic dermatitis. During the clinical development of 1% pimecrolimus cream, 1133 patients 3 to 23 months of age with mild to severe atopic dermatitis were treated for up to 2 years. The objective of this review is to discuss the safety and tolerability of 1% pimecrolimus cream among infants, on the basis of the combined results from all studies (4 pharmacokinetic studies and 6 clinical trials) conducted among these patients. Pimecrolimus blood concentrations measured for 35 patients were consistently low (< or =1 ng/mL in >80% of samples), irrespective of the disease severity and extent, and remained low during intermittent treatment for up to 1 year. The level of systemic exposure to pimecrolimus among infants was comparable to that observed for older pediatric patients enrolled in the same studies and treated in the same way with 1% pimecrolimus cream, which indicated that young pediatric patients are not at higher risk of significant percutaneous absorption of topically applied pimecrolimus, despite their large skin surface area/body mass ratio. The 6 clinical trials included a total of 1098 infants, who were treated for periods ranging from 4 weeks to 2 years. Most of these patients (60%) had moderate to severe disease at baseline. The most frequently reported adverse events were common childhood disorders such as nasopharyngitis, pyrexia, upper respiratory tract infections, ear infections, and bronchitis. During the double-blind (DB) studies or DB phases of studies, the incidence rates for the most frequently reported adverse events were similar for patients who received 1% pimecrolimus cream and patients who received the vehicle, except for the incidence of teething, which was higher among the pimecrolimus-treated infants (relative risk: 2.02; 95% confidence interval: 1.32-3.27). Treatment with 1% pimecrolimus cream was not associated with an increase in the overall incidence of nonskin infections, compared with the vehicle (relative risk: 1.015; 95% confidence interval: 0.88-1.18). The incidence density (ID) rates for total bacterial, fungal, parasitic, and viral skin infections during the DB studies or DB phases of studies were comparable for patients treated with 1% pimecrolimus cream and patients who received the vehicle. The ID rate of herpes simplex virus infections was 0.8 cases per 1000 patient-months of follow-up monitoring among patients treated with 1% pimecrolimus cream and 1.7 cases per 1000 patient-months of follow-up monitoring among patients who received the vehicle. Considering all 1098 infants treated with 1% pimecrolimus cream in DB trials and open-label studies, the ID rate of clinically diagnosed eczema herpeticum was 1.3 cases per 1000 patient-months of follow-up monitoring. Burning and erythema were the most frequently reported application site reactions, with ID rates of 2.0 and 1.2 cases per 1000 patient-months of follow-up monitoring, respectively. No sign of immunosuppression was found among infants treated intermittently with 1% pimecrolimus cream for up to 2 years; they demonstrated normal immune responses to vaccinations and did not show increases in the incidence of systemic infections or skin infections over time.
Unité(s) : Dermatologie
 
  Kaposi's sarcoma in a child with Wiskott-Aldrich syndrome
PICARD C, MELLOULI F, DUPREZ R, CHEDEVILLE G, NEVEN B, FRAITAG S, DELAUNAY J, LE DEIST F, FISCHER A, BLANCHE S, BODEMER C, GESSAIN A, CASANOVA JL, BEJAOUI M
2006 - Eur. J. Pediat. 165(7):453-457
INTRODUCTION: Kaposi's sarcoma (KS) is rare in childhood. It may be favored by acquired immune deficiencies, but the predisposing factors to KS in other children are unclear. DISCUSSION: KS has been reported in only two children and one adult with primary immunodeficiency. We report here a Tunisian child with a Wiskott-Aldrich syndrome who developed KS at the age of 14 months. CONCLUSION: This observation expands the spectrum of primary immunodeficiencies associated with KS in childhood.
Unité(s) : Dermatologie, Immuno-Hématologie Pédiatrique, U550, Anatomo-Pathologie, U768, Laboratoire d'Hématolo
 
  Dactinomycin-induced, severe lichenoid eruption in a child
RIDOLA V, MAHE E, FAWAZ O, GALMICHE L, PATTE C, GRILL J
2006 - Ped. Dermatol. 23(5):503-506
There is little information in the medical literature about skin rashes associated with dactinomycin in the absence of radiotherapy. We report a 12-month-old male child who developed a severe cutaneous reaction that consisted of a widespread pruritic papular eruption associated with fever and a poor general state after dactinomycin administration. Skin biopsy specimen findings confirmed the diagnosis of lichenoid eruption. The rash improved with topical steroid treatment and completely resolved within 1 month with persistence of a residual mild hyperpigmentation. Dactinomycin administration was discontinued for the remaining cycles of chemotherapy.
Unité(s) : Anatomo-Pathologie, Dermatologie
 
  Three Severe Cases of EBS Dowling-Meara Caused by Missense and Frameshift Mutations in the Keratin 14 Gene
TITEUX M, MAZEREEUW-HAUTIER J, HADJ-RABIA S, PROST C, TONASSO L, FRAITAG S, DE PROST Y, HOVNANIAN A, BODEMER C
2006 - J. Invest. Dermatol. 126(4):773-776
We report three unrelated patients affected at birth with an unusually severe form of epidermolysis bullosa simplex Dowling-Meara type (EBS-DM) because of mutations in KRT14 encoding keratin 14. Two patients were heterozygous for the previously described p.M119T mutation. The third patient was heterozygous for a novel c.1246delC mutation predicting the replacement of the helix termination peptide and the tail domain by a 25 amino-acid aberrant carboxyterminal sequence. At age 2 years, patients carrying the p.M119T mutation still suffered from severe EBS-DM, whereas the patient harboring the c.1246delC mutation has improved over time. These cases illustrate genotype-phenotype correlations and have implications for genetic counselling of EBS.Journal of Investigative Dermatology (2006) 126, 773-776. doi:10.1038/sj.jid.5700154; published online 26 January 2006.
Unité(s) : Anatomo-Pathologie, Dermatologie
 
  Pseudomonas aeruginosa otochondritis complicating localized cutaneous leishmaniasis: prevention of mutilation by early antibiotic therapy
VAN DER VLIET D, LE GUERN AS, FREITAG S, GOUNOD N, THERBY A, DARIE H, BUFFET PA
2006 - Amer. J. Trop. Med. Hyg. 75(2):270-272
A patient with an ulcerated cutaneous leishmaniasis of the pinna had suppurative otochondritis after a first unsuccessful course of treatment with meglumine antimoniate. Although the Leishmania ulceration healed after a second course of meglumine antimoniate, and despite three oral dicloxacillin or pristinamycin courses, the otochondritis extended and an abscess developed. Pus from the abscess revealed a pure culture of Pseudomonas aeruginosa. Five days of oral ciprofloxacin plus rifampin led to a marked improvement. The P. aeruginosa isolate was sensitive to ciprofloxacin but fully resistant to rifampin. Healing with minimal mutilation was obtained at the end of a six-week course of multiple antibiotic therapy. Pseudomonas aeruginosa otochondritis was a co-factor of cartilage mutilation in this patient. Thus, infection with P. aeruginosa should be promptly treated when present in tender cutaneous or mucosal leishmaniasis lesions near cartilaginous areas.
Unité(s) : Anatomo-Pathologie, Dermatologie, Infectiologie
 
  Consensus statement on the safety profile of topical calcineurin inhibitors
BIEBER T, CORK M, ELLIS C, GIROLOMONI G, GROVES R, LANGLEY R, LUGER T, MEURER M, MURRELL D, ORLOW S, PALLER A, DE PROST Y, PUIG L, RING J, SAURAT JH, SCHWARZ T, SHEAR N, STINGL G, TAIEB A, THESTRUP-PEDERSEN K
2005 - Dermatology 211(2):77-78
Unité(s) : Dermatologie
 
  How should severe and chronic atopic dermatitis in children be managed ?
BODEMER C
2005 - Ann. Dermatol. Vénéréolog. 132(Suppl.1):121-130
Severe atopic dermatitis in children is rare. When prescribing exceptional treatments (because of failure with classical drugs such as topical corticosteroids or topical immunosuppressors), it is important to ensure that the child is not suffering from an atopic dermatitis that has not been handled correctly.This assessment may require short hospitalisation. When the severity and rebellious nature of the atopic dermatitis with regard to routine treatment has been confirmed, exceptional treatment is envisaged. Currently, the treatment that is mastered in children remains cyclosporine, although marketing authorisation has not been granted in this indication. The side effects and notably nephrotoxicity justify the careful prescription of this drug with regular controls, and the opinion of a paediatric nephrologist.Other immunosuppressive treatments such as azathioprine, mycophenolate mofetil or even interferon gamma have rarely been studied in children, nor particularly in adults, and usually only in open studies. Their safe use in children, in the indication of severe atopic dermatitis obviously warrants comparative studies in large cohorts. Phototherapy should not be banned, even in this paediatric population, but modalities should be further defined, taking into account the real practical possibilities of this type of treatment, depending on the patients' age, and with long-term monitoring. Antileucotrienes have not yet sufficiently demonstrated their efficacy.In such severe forms, ideally, there should be the possibility of defining the predictable factors of efficacy and tolerance in each patient (biologically or with in vitro tests) that would optimise the use of these exceptional treatments, or even new molecules, in well targeted indications. The golden rule remains: patience, explanation, education, observation, monitoring and availability.
Unité(s) : Dermatologie
 
  Can the precautionary principle obstruct therapeutic progress ?
DE PROST Y
2005 - Ann. Dermatol. Vénéréolog. 132(8-9 Part 1):633-634
Unité(s) : Dermatologie
 
  The place of topical immunosuppressors in the treatment of atopic dermatitis in children
DE PROST Y
2005 - Ann. Dermatol. Vénéréolog. 132(S1):S68-S72
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.
Unité(s) : Dermatologie
 
  Treatment of atopic dermatitis with local immunosupressors
DE PROST Y
2005 - Rev. Fr. Allergol. Immunol. Clin. 45(1):58-60
Unité(s) : Dermatologie
 
  The GJB2 mutation R75Q can cause nonsyndromic hearing loss DFNA3 or hereditary palmoplantar keratoderma with deafness
FELDMANN D, DENOYELLE F, BLONS H, LYONNET S, LOUNDON N, ROUILLON I, HADJ-RABIA S, PETIT C, COUDERC R, GARABEDIAN EN, MARLIN S
2005 - Amer. J. Med. Genet. A 137(2):225-227
Unité(s) : Dermatologie, Génétique Médicale Pédiatrique
 
  Fetal hemangiopericytoma with an associated cerebral anomaly
HORNOY P, SONIGO P, FALLET-BIANCO C, LARGILIERE P, TEILLAC D, GOMES H, UZAN M, BRUNELLE F
2005 - Ultrasound Obstet. Gynecol. 26(1):81-85
We report the first case of infantile hemangiopericytoma explored prenatally by fetal ultrasonography and magnetic resonance imaging (MRI). It was associated with a developmental cerebral anomaly identified on MRI. The largest lesions of the multifocal hemangiopericytoma were located in the soft tissue adjacent to the left temporal bone, and smaller lesions were found in the lumbar area and in the retroperitoneum. MRI showed no connection between the tumor and the fetal brain but there was anomalous cerebral gyration in the region and the Sylvian fissure beneath the tumor was enlarged. The pregnancy was terminated because of the severe brain anomalies and postmortem examination confirmed the prenatal findings. Microscopic analysis of the tumor tissue showed branching vessels which are typical of hemangiopericytoma. The lesions in our case occurred in association with macrosomia with visceromegaly detected at autopsy, suggesting a possible role of tumor suppressor genes.
Unité(s) : Dermatologie, Radiologie Pédiatrique
 
  Atopic dermatitis: comparison of prevalence in France and Tunisia
KHARFI M, MASMOUDI A, BODEMER C, TURKI H, BEN HMIDA A, ZAHAF A, KAMOUN MR, DE PROST Y, LORETTE G
2005 - Ann. Dermatol. Vénéréolog. 132(5):478-479
Unité(s) : Dermatologie
 
  NEMO mutations in 2 unrelated boys with severe infections and conical teeth
KU CL, DUPUIS-GIROD S, DITTRICH AM, BUSTAMANTE J, SANTOS OF, SCHULZE I, BERTRAND Y, COULY G, BODEMER C, BOSSUYT X, PICARD C, CASANOVA JL
2005 - Pediatrics 115(5):e615-e619
X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency is a developmental and immunologic disorder caused by mutations in nuclear factor-kappaB essential modulator (NEMO), which is essential for nuclear factor-kappaB activation. Early in life, affected boys present a typical appearance, with hypotrichosis or atrichosis, hypohidrosis or anhidrosis, and hypodontia or anodontia with conical incisors. They are also susceptible to various microorganisms, mostly pyogenic bacteria and mycobacteria. Here we report 2 unrelated boys, aged 6 and 11 years, who have novel mutations in NEMO and present conical incisors and hypodontia as their sole and long-unrecognized developmental anomaly. One child had isolated recurrent pneumococcal disease, whereas the other had multiple infections. Our observations indicate that conical incisors should prompt the search for NEMO mutations in boys with unusual infectious diseases.
Unité(s) : Dermatologie, Immuno-Hématologie Pédiatrique, Stomatologie & Chirurgie Maxillo-Faciale, U550
 
  Severe combined immunodeficiency : susceptibility to HPV ?
LE DEIST F, LAFFORT C, ORTH G, BODEMER C, FISCHER A
2005 - M S-Méd. Sci. 21(2):125-127
Unité(s) : Dermatologie, Immuno-Hématologie Pédiatrique
 
  Plexiform fibrohistiocytic tumor: three unusual cases occurring in infancy
LECLERC S, HAMEL-TEILLAC D, OGER P, BROUSSE N, FRAITAG S
2005 - J. Cutaneous Pathol. 32(8):572-576
Background: Plexiform fibrohistiocytic tumor is a soft-tissue tumor of intermediate malignancy occurring in children and young adults but is only rarely found in infants. The tumor usually involves the upper limbs and is slow growing and painless. Recurrence rate is high. Lymph node and systemic metastases can occur, but have never been reported in infants. Clinical behavior in infancy is not known. Histologically, the tumor is characterized by nodules of histiocyte-like and multinucleated cells and fascicles of spindle cells arranged in a plexiform pattern. Mitosis, atypia, and nuclear pleomorphism are common but not pronounced. Methods and Results: We report three cases in infants, one of which is congenital, having an unusual topography and a broad histological spectrum. Conclusion: In infants, wide excision with large safety margins should be performed as the behaviour of this tumor remains uncertain. Leclerc S, Hamel-Teillac D, Oger P, Brousse N, Fraitag S. Plexiform fibrohistiocytic tumor: three unusual cases occurring in infancy.
Unité(s) : Anatomo-Pathologie, Dermatologie
 
  Fabry disease. Role of the dermatologist and therapeutic advance
MAHE E, HADJ-RABIA S, CHAUVEAU D, DE PROST Y
2005 - Ann. Dermatol. Vénéréolog. 132(2):171-176
Unité(s) : Dermatologie, Néphrologie Adulte
 
  Cutaneous Adverse Events in Renal Transplant Recipients Receiving Sirolimus-Based Therapy1
MAHE E, MORELON E, LECHATON S, LE-QUAN-SANG KH, MANSOURI R, DUCASSE MF, MAMZER-BRUNEEL MF, DE PROST Y, KREIS H, BODEMER C
2005 - Transplantation 79(4):476-482
BACKGROUND.: Sirolimus is an immunosuppressive drug recently developed for organ transplantation. Its mechanism of action, independent of calcineurin, is different from that of cyclosporine and tacrolimus, two calcineurin inhibitors (CIs). Because the toxicity of CIs is partly the result of calcineurin blockade, sirolimus exhibits a different toxicity profile. In this study, we evaluated the profile, frequency, and severity of cutaneous adverse events in renal transplant recipients receiving sirolimus-based therapy. PATIENTS AND METHODS.: A systematic and in-depth evaluation of skin, mucous membranes, nails, and hair was performed in 80 renal transplant recipients receiving sirolimus-based therapy. The mean duration of the graft was 6 years and of sirolimus treatment was 18 months. Mycophenolate mofetil and steroids were combined with sirolimus for 74 patients. Sirolimus was used as first immunosuppressive therapy for 36 patients, and 44 patients were switched from CIs to sirolimus. RESULTS.: Seventy-nine patients (99%) experienced cutaneous adverse events. Twenty patients (25%) demonstrated serious adverse events, and six patients (7%) stopped sirolimus during the 3 months after the study because of cutaneous events. The most frequent of these were pilosebaceous apparatus involvement, including acne-like eruptions (46%), scalp folliculitis (26%), and hidradenitis suppurativa (12%); edematous complaints, including chronic edemas (55%) and angioedema (15%); mucous membrane disorders, including aphthous ulceration (60%), epistaxis (60%), chronic gingivitis (20%), and chronic fissure of the lips (11%); and last, nail disorders including chronic onychopathy (74%) and periungual infections (16%). CONCLUSIONS.: Skin disorders are frequent in renal transplant recipients receiving sirolimus as a long-term therapy. Despite the usually mild nature of skin events, they are often the reason for stopping sirolimus.
Unité(s) : Dermatologie, Transplantation & Réanimation Adulte
 
  What is your diagnosis? Annular hypopigmented skin lesions in a 6-year-old child
MARROU K, MAHE E, HADJ-RABIA S, FRAITAG S, FLAGEUL B, BUFFET P, DE PROST Y
2005 - Archives Pédiatrie 12(7):1145-1147
Unité(s) : Dermatologie, Anatomo-Pathologie
 
  Long-term treatment of atopic dermatitis with pimecrolimus cream 1% in infants does not interfere with the development of protective antibodies after vaccination
PAPP KA, BREUER K, MEURER M, ORTONNE JP, POTTER PC, DE PROST Y, DAVIDSON MJ, BARBIER N, GOERTZ HP, PAUL C
2005 - J. Amer. Acad. Dermatol. 52(2):247-253
OBJECTIVE: We investigated whether treatment of atopic dermatitis with pimecrolimus cream 1% in infants affects the development of a normal antibody response to vaccinations. METHODS: In all, 91 patients participated in a 1-year, open-label extension to a 1-year double-blind study: 76 used pimecrolimus twice daily at the first signs or symptoms of the disease until clearance for 2 years and 15 only in the second year. Serum concentrations of antibodies against tetanus, diphtheria, measles, and rubella were measured at months 18 and 24. RESULTS: The seropositivity rates of 93.6% for tetanus, 88.6% for diphtheria, 88.5% for measles, and 84.4% for rubella were comparable with those reported in literature. Seropositivity was not significantly affected by the use of pimecrolimus at the time of vaccinations (+/- 28 days). CONCLUSIONS: Treatment of atopic dermatitis with pimecrolimus cream 1% in early childhood does not appear to interfere with the development of a normal immune response to vaccinations.
Unité(s) : Dermatologie
 
  Long-term control of atopic dermatitis with pimecrolimus cream 1% in infants and young children: a two-year study
PAPP KA, WERFEL T, FOLSTER-HOLST R, ORTONNE JP, POTTER PC, DE PROST Y, DAVIDSON MJ, BARBIER N, GOERTZ HP, PAUL C
2005 - J. Amer. Acad. Dermatol. 52(2):240-246
OBJECTIVE AND METHODS: The safety and efficacy of treatment with pimecrolimus cream 1% was evaluated for up to 2 years in infants and young children with atopic dermatitis. Ninety-one patients participated in a 1-year, open-label extension to a 1-year double-blind study. Of these, 76 received pimecrolimus for 2 years. Pimecrolimus was applied twice daily at the first signs or symptoms of the disease until clearance. Outcome measures included the incidence of adverse events and the Eczema Area and Severity Index (EASI). RESULTS: No patient discontinued because of adverse events. The incidence of systemic and skin infections did not increase over time. Over the 2-year period, 2 patients experienced an episode of clinically diagnosed eczema herpeticum. In patients receiving pimecrolimus for 2 years, the mean decrease in EASI score from baseline was 68.7% at 3 months and 70.8% at 24 months. CONCLUSION: Treatment with pimecrolimus cream 1% for up to 2 years was well tolerated and resulted in a marked and sustained improvement of atopic dermatitis.
Unité(s) : Dermatologie
 
  Guidelines about investigations to be performed at the diagnosis and during the follow-up of childhood-onset systemic lupus erythematosus
BADER-MEUNIER B, HADDAD E, NIAUDET P, LOIRAT C, LEBLANC T, AMOURA Z, BODEMER C, COCHAT P, DESCHENES G, KONE-PAUT I, LEVY M, PRIEUR AM, QUARTIER P, RANCHIN B, SALOMON R, PIETTE JC
2004 - Archives Pédiatrie 11(8):941-944
Childhood-onset systemic lupus erythematosus (SLE) is often severe and has a serious long-term morbidity. Pediatric guidelines about its management do not exist. The French study group of childhood-onset SLE proposes recommendations about the investigation which are needed at diagnosis and during follow-up of SLE, in order to adjust the treatment according to the severity of the disease and to avoid unnecessary investigations.
Unité(s) : Dermatologie, Immuno-Hématologie Pédiatrique, Néphrologie Pédiatrique
 
  Validation of the Eczema Area and Severity Index for atopic dermatitis in a cohort of 1550 patients from the pimecrolimus cream 1% randomized controlled clinical trials programme
BARBIER N, PAUL C, LUGER T, ALLEN R, DE PROST Y, PAPP K, EICHENFIELD LF L, CHERILL R, HANIFIN J
2004 - Br. J. Dermatol. 150(1):96-102
OBJECTIVE: To validate the Eczema Area and Severity Index (EASI) by assessing its internal consistency, reliability and sensitivity to change and by correlating it to other efficacy parameters. DESIGN: Three short-term and two long-term double-blind, randomized, controlled trials, performed in 138 study centres in Europe, South Africa, Australia, New Zealand, and North and South America. PATIENTS AND METHODS: In total, 1550 paediatric patients with atopic dermatitis were studied. Pimecrolimus cream 1% was used twice daily to treat atopic dermatitis. The three short-term studies were placebo controlled. The two long-term studies evaluated the efficacy and safety of early intervention with pimecrolimus to prevent progression to disease flare requiring topical corticosteroid treatment, compared with reactive treatment with topical corticosteroids to treat flares of atopic dermatitis. MAIN OUTCOME MEASURES: Five parameters were measured: (i) the EASI (range of score 0-72); (ii) Investigators' Global Assessment (IGA), using a six-point (0-5) scale; (iii) patients' assessment, using a four-point (0-3) scale; (iv) severity of pruritus assessment, using a four-point (0-3) scale; and (v) a quality-of-life evaluation. RESULTS: The EASI score varied in parallel and in correlation with the IGA, pruritus and patients' assessment. All correlation coefficients were statistically different from 0 (P < 0.05). The EASI correlated well with each of its components, and all paired comparisons were within agreed limits. The EASI showed good sensitivity to changes in severity. CONCLUSION: In a large, multinational patient population with atopic dermatitis, the EASI showed good validity, reliability and sensitivity to change and correlated well with other measures of severity. It therefore qualifies as a valid method of assessment in clinical studies of atopic dermatitis.
Unité(s) : Dermatologie
 
  A Novel Developmental and Immunodeficiency Syndrome Associated With Intrauterine Growth Retardation and a Lack of Natural Killer Cells
BERNARD F, PICARD C, CORMIER-DAIRE V, EIDENSCHENK C, PINTO G, BUSTAMANTE JC, JOUANGUY E, TEILLAC-HAMEL D, COLOMB V, FUNCK-BRENTANO I, PASCAL V, VIVIER E, FISCHER A, LE DEIST F, CASANOVA JL
2004 - Pediatrics 113(1):136-141
Unité(s) : Dermatologie, Endocrinologie et Croissance, Gastroentérologie Pédiatrique, Immuno-Hématologie Pédiat
 
  Cutaneous manifestations of lupus in children
BODEMER C
2004 - Archives Pédiatrie 11(6):509-511
Unité(s) : Dermatologie
 
  Tacrolimus ointment: a topical immunomodulator for atopic dermatitis
DE PROST Y
2004 - Ouvrage 161-183
Clinical experience in children
Unité(s) : Dermatologie
 
  A novel form of syndromic cutis laxa with facial dysmorphism, cleft palate, and mental retardation
GENEVIEVE D, BAUMANN C, HUBER C, FAIVRE L, SANLAVILLE D, BODEMER C, HADJ-RABIA S, ASSOUMOU A, VERLOES A, RAQBI F, MUNNICH A, CORMIER-DAIRE V
2004 - J. Med. Genet. 41(6):E77
Unité(s) : Département de Pédiatrie, Dermatologie, Génétique Médicale Pédiatrique
 
  Skin markers of occult spinal dysraphism in children: a review of 54 cases
GUGGISBERG D, HADJ-RABIA S, VINEY C, BODEMER C, BRUNELLE F, ZERAH M, PIERRE-KAHN A, DE PROST Y, HAMEL-TEILLAC D
2004 - Arch. Dermatol. 140(9):1109-1115
OBJECTIVES: To verify the diagnostic value of lumbosacral midline cutaneous lesions in asymptomatic children to detect occult spinal dysraphism (OSD) and to propose a practical approach for clinical investigations with respect to the type of cutaneous lesions observed. DESIGN: Retrospective study of 54 children referred to the Department of Pediatric Dermatology between 1990 and 1999 for congenital midline lumbosacral cutaneous lesions. SETTING: The private or institutional practices of participating dermatologists and pediatricians. MAIN OUTCOME MEASURES: Evaluation of the diagnostic value of midline cutaneous lesions for the detec-tion of OSD. Association of skin examination findings with spinal anomalies detected by magnetic resonance imaging or ultrasound. RESULTS: Occult spinal dysraphism was detected in 3 of 36 patients with an isolated congenital midline lesion and 11 of 18 patients with a combination of 2 or more different skin lesions. CONCLUSIONS: A combination of 2 or more congenital midline skin lesions is the strongest marker of OSD. Careful dermatologic examination is needed to detect suggestive markers and request a spinal magnetic resonance image, which is the most sensitive radiologic approach to detect an OSD.
Unité(s) : Dermatologie, Neurochirurgie Pédiatrique, Radiologie Pédiatrique
 
  Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease
HADJ-RABIA S, BAALA L, VABRES P, HAMEL-TEILLAC D, JACQUEMIN E, FABRE M, LYONNET S, DE PROST Y, MUNNICH A, HADCHOUEL M, SMAHI A
2004 - Gastroenterology 127(5):1386-1390
BACKGROUND AND AIMS: Most human and animal cholestatic disorders are associated with changes in hepatocyte cytoskeleton and tight junctions (TJs). These changes are usually secondary and nonspecific phenomena, both in intra- and extrahepatic cholestasis. Recently, missense mutations in TJ protein 2 (ZO-2) have been identified in patients with familial hypercholanemia. In the liver, TJs separate bile flow from plasma and are composed of strands of claudins and occludin. We previously assigned a syndrome associating ichthyosis and neonatal sclerosing cholangitis (NISCH syndrome) to chromosome 3q27-q28. We considered claudin-1 to be a strong candidate gene based on its mapping to the minimum interval and on the expression pattern of the mouse ortholog. METHODS: The 4 exons and intron-exon junctions of claudin-1 gene were amplified using standard polymerase chain reaction protocols and specific primers. Western blot analysis on cultured fibroblasts and immunohistochemistry on liver tissue section were performed using rabbit anti-claudin-1 antibodies. RESULTS: We described in 4 patients, of 2 inbred kindred of Moroccan origin, a 2-bp deletion (200-201 TT) in exon 1 of the claudin-1 gene arising in a premature stop codon and resulting in total absence of claudin-1 protein in the liver and skin. CONCLUSIONS: Lack of claudin-1 in NISCH syndrome may lead to increased paracellular permeability between epithelial cells. Bile duct injury may be related to the absence of claudin-1 expression in cholangiocytes. Our observation, in conjunction with ZO-2-associated hypercholanemia, emphasizes the role played by TJ components in hereditary cholestasis.
Unité(s) : Dermatologie, U393
 
  Inflammatory skin disease of vulvovaginal region
HAMEL-TEILLAC D
2004 - Ann. Dermatol. Vénéréolog. 131(10):907-911
Unité(s) : Dermatologie
 
  Vulvo-vaginal disorders
HAMEL-TEILLAC D
2004 - Endocr. Dev. 7(39-56
Unité(s) : Dermatologie
 
  Chronic urticaria in children
HAMEL-TEILLAC D
2004 - Rev. Fr. Allergol. Immunol. Clin. 44(1):108-111
Unité(s) : Dermatologie
 
  Severe cutaneous papillomavirus disease after haemopoietic stem-cell transplantation in patients with severe combined immune deficiency caused by common gammac cytokine receptor subunit or JAK-3 deficiency
LAFFORT C, LE DEIST F, FAVRE M, CAILLAT-ZUCMAN S, RADFORD-WEISS I, DEBRE M, FRAITAG S, BLANCHE S, CAVAZZANA-CALVO M, DE SAINT-BASILE G, DE VILLARTAY JP, GILIANI S, ORTH G, CASANOVA JL, BODEMER C, FISCHER A
2004 - Lancet 363(9426):2051-2054
Haemopoietic stem-cell transplantation is a life-saving treatment for severe combined immune deficiency. However, there has been little long-term follow-up of this treatment. There is evidence for the persistance of partial immunodeficiency associated with significant infections, including severe human papillomavirus (HPV) disease. We did a retrospective analysis of severe HPV disease in a group of 41 patients with severe combined immune deficiency from one centre who were alive 10 years or longer after haemopoietic stem-cell transplantation. Nine of the 41 patients had extensive chronic HPV disease limited to the skin, with a median onset at 8 years after transplantation. Four had lesions typical of epidermodysplasia verruciformis, a rare genodermatosis. Transplant characteristics, immune status, and chimerism of these nine patients did not differ significantly from those of the other patients. The nine patients with HPV disease had severe combined immune deficiency associated with either common gammac receptor cytokine subunit or Janus kinase-3 (JAK-3) deficiency. By contrast, patients with other forms of severe combined immune deficiency did not have any signs of HPV disease. That genetic causes are the only predisposing factor to be identified for severe combined immune deficiency, suggests that natural-killer cells or gammac/JAK-3-dependent signalling in keratinocytes could have a role in anti-HPV immunity.
Unité(s) : Anatomo-Pathologie, Dermatologie, Histo-Embryologie & Cytogénétique, Immuno-Hématologie Pédiatrique,
 
  Drug-induced hypersensitivity syndrome associated with primary Epstein-Barr virus and human herpesvirus 6 infections in a child intestinal transplant recipient
MAHE E, BODEMER C, DUPIC L, HUBERT P, LACAILLE F, GOULET O, LERUEZ-VILLE M, FRAITAG S
2004 - Transplantation 77(3):479-480
Unité(s) : Anatomo-Pathologie, Département de Pédiatrie, Dermatologie, Laboratoire de Microbiologie, Réanimatio
 
  Furunculosis and IgG subclass deficiency
MAHE E, GIRSZIN N, DESCAMPS V, CRICKX B
2004 - Dermatology 208(1):84-85
Unité(s) : Dermatologie
 
  Hereditary cholestasis, an unusual etiology of pruritus in the infant
MAHE E, LACAILLE F, HADJ-RABIA S, BODEMER C, DE PROST Y, HAMEL-TEILLAC D
2004 - Ann. Dermatol. Vénéréolog. 131(12):1092-1094
INTRODUCTION: Pruritus in the infant is predominantly related to common dermatosis. General causes remain exceptional. We report two cases of pruritus in infants revealing anicteric cholestasis.OBSERVATIONS: Case no 1. A thirteen month-old boy had exhibited pruritus since the age of 2 months. The clinical examination was non-specific. Biological explorations revealed an isolated and moderate rise in total bilary acids. The search for mutations in the genes of a familial fibrogenic cholestasis was negative. The diagnosis retained was hypercholanemia. Treatment combined ursodesoxycholic acid and rifampicine, which controlled the pruritus and normalized the bilary acid levels. Case no 2. A twenty-one month-old boy had exhibited pruritus since the age of 2 months and delayed growth. The clinical examination was unspecific. The biological explorations revealed cholestasis with normal delta GT, moderate cytolysis and liposoluble vitamin deficiency. The hepatic biopsy was normal. The diagnosis retained was familial fibrogenic cholestasis. Treatment combined ursodesoxycholic acid and rifampicine, which controlled the pruritus and normalized the hepatic parameters.DISCUSSION: Non-dermatological isolated pruritus is rare in infants. These two observations illustrate two abnormalities in bilary acid transport. Hypercholanemia is a faulty canalization of bilary acids by the hepatocyte. Familial fibrogenic cholestasis is a default in the elimination of these bilary acids. Such pathologies must be evoked because specific treatment will treat the symptoms and avoid the evolution of familial fibrogenic cholestasis towards cirrhosis.
Unité(s) : Dermatologie, Gastroentérologie Pédiatrique
 
  Renal-Transplant Recipients and Sun Protection
MAHE E, MORELON E, FERMANIAN J, LECHATON S, PRUVOST C, DUCASSE MF, MAMZER-BRUNEEL MF, KREIS H, BODEMER C, DE PROST Y
2004 - Transplantation 78(5):741-744
BACKGROUND.: The incidence of skin carcinomas in organ-transplant recipients is high. The main factors implicated in carcinogenesis are immune suppression and ultraviolet radiation. Only the second is avoidable. We have evaluated knowledge of and compliance with sun protection measures among renal-transplant recipients (RTR). METHODS.: A survey by means of a questionnaire including questions about clinical data, knowledge of, and compliance with sun protection was given. The questionnaire was given to 520 consecutive RTR followed up in a single center, and 445 (86%) answered. RESULTS.: Of the responders, 91% have been informed of the need for sun protection, in 80% of cases by dermatologists. Sixty-eight percent used more protective measures abroad than at home, 63% avoided going outside during the hottest midday hours, 63% used sunscreen regularly, but 46% used one or less tube of sunscreen a year. A hat was always worn in the sun by 35% and long sleeves by 36%. Women and fair-skinned individuals complied better with protective measures. A minority of patients knew that ultraviolet radiation carries a risk of skin cancer. CONCLUSIONS.: This survey shows that most RTR are aware of the need for sun protection, but only a minority take adequate protection measures. The better results observed in this study than in previous published investigations may be caused by the great involvement of dermatologists in the care of RTR in our institution. The results of this survey underline the need to inform RTR better about sun-protection measures and the importance of cooperation between transplant physicians and dermatologists.
Unité(s) : Biostatistique, Dermatologie, Transplantation & Réanimation Adulte
 
  Prognosis of subglottic haemangiomas associated with facial haemangiomas in a paediatric population: A preliminary study
MARIANOWSKI R, LE RU Y, HAMEL-TEILLAC D, DE PROST Y, MANACH Y, RASSI S
2004 - Acta Derm. Venereol. 84(1):74-75
Unité(s) : Dermatologie, Oto-Rhino-Laryngologie & Chirurgie Maxillo-Faciale
 
  Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy
NAVARRO CL, DE SANDRE-GIOVANNOLI A, BERNARD R, BOCCACCIO I, BOYER A, GENEVIEVE D, HADJ-RABIA S, GAUDY-MARQUESTE C, SMITT HS, VABRES P, FAIVRE L, VERLOES A, VAN ESSEN T, FLORI E, HENNEKAM R, BEEMER FA, LAURENT N, LE MERRER M, CAU P, LEVY N
2004 - Hum. Mol. Genet. 13(20):2493-2503
Restrictive dermopathy (RD), also called tight skin contracture syndrome (OMIM 275210), is a rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance. We explored nine fetuses/newborns children with RD. Two were found to have an heterozygous splicing mutation in the LMNA gene, leading to the complete or partial loss of exon 11 in mRNAs encoding Lamin A and resulting in a truncated Prelamin A protein. Lamins are major constituents of the nuclear lamina, a filamentous meshwork underlying the inner nuclear envelope. In the other seven patients, a unique heterozygous insertion leading to the creation of a premature termination codon was identified in the gene ZMPSTE24, also known as FACE-1 in human. This gene encodes a metalloproteinase specifically involved in the post-translational processing of Lamin A precursor. In all patients carrying a ZMPSTE24 mutation, loss of expression of Lamin A as well as abnormal patterns of nuclear sizes and shapes and mislocalization of Lamin-associated proteins was evidenced. Our results indicate that a common pathogenetic pathway, involving defects of the nuclear lamina and matrix, is involved in all RD cases. RD is thus one of the most deleterious laminopathies identified so far in humans caused by (primary or secondary) A-type Lamin defects and nuclear structural and functional alterations.
Unité(s) : Dermatologie, U393
 
  Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, and FCU
NEVEN B, CALLEBAUT I, PRIEUR AM, FELDMANN J, BODEMER C, LEPORE L, DERFALVI B, BENJAPONPITAK S, VESELY R, SAUVAIN MJ, OERTLE S, ALLEN R, MORGAN G, BORKHARDT A, HILL C, GARDNER-MEDWIN J, FISCHER A, DE SAINT-BASILE G
2004 - Blood 103(7):2809-2815
NALP proteins are recently identified members of the CATERPILLER (CARD, transcription enhancer, R(purine)-binding, pyrin, lots of LRR) family of proteins, thought to function in apoptotic and inflammatory signaling pathways. Mutations in the CIAS1 gene, which encodes a member of the NALP (NACHT-, LRR-, and PYD-containing proteins) family, the cryopyrin/NALP3/PYPAF1 protein, expressed primarily in phagocytic cells, were recently found to be associated with a spectrum of autoinflammatory disorders. These include chronic infantile neurologic cutaneous and articular (CINCA) syndrome (also known as neonatal-onset multisystem inflammatory disease [NOMID]), Muckle-Wells syndrome (MWS), and familial cold urticaria (FCU). We describe herein 7 new mutations in 13 unrelated patients with CINCA syndrome and identify mutational hotspots in CIAS1 on the basis of all mutations described to date. We also provide evidence of genotype/phenotype correlations. A 3-dimensional model of the nucleotide-binding domain (NBD) of cryopyrin suggested that this molecule is structurally and functionally similar to members of the AAA+ protein family of ATPases. According to this model, most of the mutations known to affect residues of the NBD are clustered on one side of this domain in a region predicted to participate in intermolecular contacts, suggesting that this model is likely to be biologically relevant and that defects in nucleotide binding, nucleotide hydrolysis, or protein oligomerization may lead to the functional dysregulation of cryopyrin in the MWS, FCU, and CINCA/NOMID disorders. (Blood. 2004;103:2809-2815)
Unité(s) : Dermatologie, U429
 
  Childhood-onset systemic lupus erythematosus
BADER-MEUNIER B, QUARTIER P, DESCHENES G, COCHAT P, HADDAD E, KONE-PAUT I, LEBLANC T, PRIEUR AM, SALOMON R, BODEMER C, LEVY M
2003 - Archives Pédiatrie 10(2):147-157
Systemic Lupus Erythematosus (SLE) remains a challenging autoimmune disease in term of etiology, pathogenesis and treatment. It is estimated that 10-17% of lupus patients present before the age of 16. SLE in children appears to have more severe organ involvement than in adults. The outcome of childhood SLE has improved during the last decade, but the morbidity remains high. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
Unité(s) : Immuno-Hématologie Pédiatrique, Dermatologie
 
  Perianal abcess in infant
BARTHES-ANIDJAR L, WOLTER M, BODEMER C, GOUNOD N, KOULOURIS E, DE PROST Y
2003 - Ann. Dermatol. Vénéréolog. 130(3):357-360
INTRODUCTION: Perianal abcess and fistula-in-ano are particular when happening in infants of less than 1 year of age. A congenital abnormality of crypts of Morgagni may be at the origin of the disease. There is no evidence for predisposing condition at this age.CASE REPORT: A 7-week-old boy had a painful swollen perianal lesion suggesting the presence of perianal abcess. Biological tests did not show any neutropenia nor inflammatory syndrome. The infant was admitted to the surgical center to undergo a perianal abcess drainage. During the intervention, no fistula was found. No recurrence was observed.DISCUSSION: Perianal abcess and/or fistula-in-ano are relatively common conditions in infants of less than 1 year of age. This disease is suspected to originate from anal cryptitis, which will later form a perianal abcess. Androgen excess during the foetal stage could be the cause of the formation of abnormal crypts of Morgagni, which encourages cryptitis and abcess formation. In childhood some predisposing factors can exist, as immunodeficiency or colopathy. On the opposite, a predisposing condition is rare in infancy. Twenty-eight to 85 per cent of infants with perianal abcess may progress to form a fistula. The usual treatment of perianal abcess is incision and drainage; it may be completed by fistulotomy or fistulectomy. The antibiotherapy is not systematic. The identification of the corresponding crypt may be important to avoid recurrence. On the opposite, a recent prospective study proposes a non operative management of perianal abcess and fistula-in-ano in healthy infants.
Unité(s) : Dermatologie
 
  LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome
BITOUN E, MICHELONI A, LAMANT L, BONNART C, TARTAGLIA-POLCINI A, COBBOLD C, AL SAATI T, MARIOTTI F, MAZEREEUW-HAUTIER J, BORALEVI F, HOHL D, HARPER J, BODEMER C, D'ALESSIO M, HOVNANIAN A
2003 - Hum. Mol. Genet. 12(19):2417-2430
SPINK5, encoding the putative multi-domain serine protease inhibitor LEKTI, was recently identified as the defective gene in the severe autosomal recessive ichthyosiform skin condition, Netherton syndrome (NS). Using monoclonal and polyclonal antibodies, we show that LEKTI is a marker of epithelial differentiation, strongly expressed in the granular and uppermost spinous layers of the epidermis, and in differentiated layers of stratified epithelia. LEKTI expression was also demonstrated in normal differentiated human primary keratinocytes (HK) through detection of a 145 kDa full-length protein and a shorter isoform of 125 kDa. Both proteins are N-glycosylated and rapidly processed in a post-endoplasmic reticulum compartment into at least three C-terminal fragments of 42, 65 and 68 kDa, also identified in conditioned media. Processing of the 145 and 125 kDa precursors was prevented in HK by treatment with a furin inhibitor. In addition, in vitro cleavage of the recombinant 145 kDa precursor by furin generated C-terminal fragments of 65 and 68 kDa, further supporting the involvement of furin in LEKTI processing. In contrast, LEKTI precursors and proteolytic fragments were not detected in differentiated HK from NS patients. Defective expression of LEKTI in skin sections was a constant feature in NS patients, whilst an extended reactivity pattern was observed in samples from other keratinizing disorders, demonstrating that loss of LEKTI expression in the epidermis is a diagnostic feature of NS. The identification of novel processed forms of LEKTI provides the basis for future functional and structural studies of fragments with physiological relevance.
Unité(s) : Dermatologie
 
  Late recurrence of inflammatory first-stage lesions in incontinentia pigmenti: an unusual phenomenon and a fascinating pathologic mechanism
BODAK N, HADJ-RABIA S, HAMEL-TEILLAC D, DE PROST Y, BODEMER C
2003 - Arch. Dermatol. 139(2):201-224
BACKGROUND: Incontinentia pigmenti (IP) is an X-linked genodermatosis that is manifested by neonatal inflammatory vesicles localized along the lines of Blaschko. These lesions usually clear spontaneously within a few months, leaving hyperpigmentation. Ophthalmologic and neurologic symptoms can be associated with IP. Late recurrences of the first-stage inflammatory lesions after the initial rash are uncommon and have been reported infrequently. The mechanism involved in this phenomenon is unclear. However, the recent identification of NEMO/IKKgamma as the gene responsible for IP sheds new light on its pathophysiologic origins. OBSERVATIONS: We report 5 cases of children who experienced episodes of late reactivation of IP. In all cases, the recurrences occurred on the previously hyperpigmented streaks several months or years after resolution of the initial eruptions. In most cases, the recurrences were preceded by an infectious episode. CONCLUSIONS: These IP recurrences suggest that mutated cells can persist a long time in the epidermis. We theorize that infections trigger the reactivations. The NEMO/IKKgamma gene encodes a protein essential in nuclear factor kappaB activation, which is required for resistance to tumor necrosis factor alpha-induced apoptosis. We discuss the role of a proinflammatory cytokine such as tumor necrosis factor alpha as a triggering factor for the reactivation.
Unité(s) : Dermatologie
 
  New treatments of atopic dermatitis
BODEMER C, LACOUR JP
2003 - Ann. Dermatol. Vénéréolog. 130(2 Pt 2):279-284
Unité(s) : Dermatologie
 
  Skin expression of metalloproteinases and tissue inhibitor of metalloproteinases in sibling patients with recessive dystrophic epidermolysis and intrafamilial phenotypic variation
BODEMER C, TCHEN SI, GHOMRASSENI S, SEGUIER S, GAULTIER F, FRAITAG S, DE PROST Y, GODEAU G
2003 - J. Invest. Dermatol. 121(2):273-279
A number of COL7A1 mutations have now been reported in recessive dystrophic epidermolysis bullosa patients, and the analysis of phenotype-genotype correlations showed evidence for interfamilial and intrafamilial phenotypic variability, occurring for the same mutation. Collagenase and stromelysin activities have been found to be overexpressed in skin cultures of some recessive dystrophic epidermolysis bullosa patients, and tissue destruction in the disease process might result from an imbalance of metalloproteinases (MMP) over tissueinhibitor of metalloproteinases (TIMP). So we suspected that the phenotypic variability for the same mutation could be linked to other genetic or environmental factors, as a particular balance between MMP and TIMP. Organ cultures were performed using explants from the skin of three patients from the same family with recessive dystrophic epidermolysis bullosa to reveal and quantify the expression of MMP-1 (collagenase 1), MMP-2 and MMP-9 (gelatinases A and B), MMP-3 (stromelysin 1), TIMP-1, and TIMP-2, and to compare the results with those obtained with two human control skins, with the same experimental conditions. Increased amounts of all metalloproteinases investigated were observed in the skin of the three recessive dystrophic epidermolysis bullosa affected sibling brothers, both in lesioned and in apparently nonlesioned skin, compared with controls. The amounts of MMP-1, MMP-2, MMP-3, and MMP-9 increased particularly in the skin of the more clinically affected patient. Furthermore for this patient we evidenced higher amounts of MMP-1 and also a lower TIMP-1 amount in his unlesioned and lesioned skin compared with the other two affected patients and with healthy control donors. So we can suspect that recessive dystrophic epidermolysis bullosa phenotypic variability could be related to patients' collagenase activity heterogeneity, linked to imbalance between MMP-1 and TIMP-1.
Unité(s) : Dermatologie
 
  The Rapp-Hodgkin syndrome results from mutations of the TP63 gene
BOUGEARD G, HADJ-RABIA S, FAIVRE L, SARAFAN-VASSEUR N, FREBOURG T
2003 - Eur. J. Human Genet. 11(9):700-704
The Rapp-Hodgkin syndrome (RHS, MIM 129400) corresponds to a rare form of anhydrotic ectodermal dysplasia, which shares some features with the ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome (EEC, MIM 604292) resulting from TP63 mutations. We report here, in two unrelated patients with RHS, the identification of two distinct TP63 mutations, corresponding to a novel frameshift mutation (1709DelA, exon 14) located downstream the sterile alpha motif (SAM) domain and to a missense mutation (R279H, exon 7) within the DNA binding domain. Functional analysis of the R279H mutation, which had previously been reported in several EEC families, shows that this mutation disrupted the dominant negative activity of the DeltaNp63alpha and gamma isoforms on the transcriptional activity of TP53. This report shows, on a molecular basis, that RHS is also an EEC-like syndrome resulting from mutations of the TP63 gene, and highlights the wide phenotypic spectrum associated to TP63 mutations.
Unité(s) : Génétique Médicale Pédiatrique, Dermatologie
 
  Cutaneous necrosis is predictive of cancer in adult dermatomyositis
BURNOUF M, MAHÉ E, VERPILLAT P, DESCAMPS V, LEBRUN-VIGNES B, PICARD-DAHAN C, BELAICH S, CRICKX B
2003 - Ann. Dermatol. Vénéréolog. 130(3):313-316
INTRODUCTION: Adult dermatomyositis is associated with cancer in 15 p. 100 to 50 p. 100 of cases and, hence, investigations should be systematically performed to search for cancer. A number of predictive factors have been reported. The aim of our study was to search for predictive factors of cancer, among adults with dermatomyositis. METHODS: We prospectively assessed 26 adults presenting with dermatomyositis, hospitalised in our department of dermatology from January 1993 to June 2000. The parameters assessed were: association with a cancer, age, gender, cutaneous necrosis, muscular weakness, electromyographic abnormalities, erythrocyte sedimentation rate, and muscular enzyme levels. RESULTS: Mean age was of 52 years and sex ratio (M/F) was of 0.53. Cancers were diagnosed in eight cases (31 p. 100) (mean age: 59.5 years; sex ratio=1; cancer localization: lung (2), breast (2), ovary, endometrium, bladder, and melanoma). Five patients in the cancer group had cutaneous necrosis and only 2 in the without cancer (p=0.01; PPV=71.4 p.100). Elevation of muscular enzyme was also associated with cancer. CONCLUSION: Our report demonstrates that cutaneous necrosis is closely associated with cancer and it suggests that in selected patients with dermatomyositis and cutaneous necrosis, more exhaustive and repeated investigations should be performed to search for cancer. The interest of elevation in muscular enzyme as a predictive factor of cancer is discussed.
Unité(s) : Dermatologie
 
  A hypermorphic I{kappa}B{alpha} mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency
COURTOIS G, SMAHI A, REICHENBACH J, DOFFINGER R, CANCRINI C, BONNET M, PUEL A, CHABLE-BESSIA C, YAMAOKA S, FEINBERG J, DUPUIS-GIROD S, BODEMER C, LIVADIOTTI S, NOVELLI F, ROSSI P, FISCHER A, ISRAEL A, MUNNICH A, DEIST FL, CASANOVA JL
2003 - J. Clin. Invest. 112(7):1108-1115
X-linked anhidrotic ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by hypomorphic mutations in the gene encoding NEMO/IKKgamma, the regulatory subunit of the IkappaB kinase (IKK) complex. IKK normally phosphorylates the IkappaB-inhibitors of NF-kappaB at specific serine residues, thereby promoting their ubiquitination and degradation by the proteasome. This allows NF-kappaB complexes to translocate into the nucleus where they activate their target genes. Here, we describe an autosomal-dominant (AD) form of EDA-ID associated with a heterozygous missense mutation at serine 32 of IkappaBalpha. This mutation is gain-of-function, as it enhances the inhibitory capacity of IkappaBalpha by preventing its phosphorylation and degradation, and results in impaired NF-kappaB activation. The developmental, immunologic, and infectious phenotypes associated with hypomorphic NEMO and hypermorphic IKBA mutations largely overlap and include EDA, impaired cellular responses to ligands of TIR (TLR-ligands, IL-1beta, and IL-18), and TNFR (TNF-alpha, LTalpha1/beta2, and CD154) superfamily members and severe bacterial diseases. However, AD-EDA-ID but not XL-EDA-ID is associated with a severe and unique T cell immunodeficiency. Despite a marked blood lymphocytosis, there are no detectable memory T cells in vivo, and naive T cells do not respond to CD3-TCR activation in vitro. Our report highlights both the diversity of genotypes associated with EDA-ID and the diversity of immunologic phenotypes associated with mutations in different components of the NF-kappaB signaling pathway.
Unité(s) : U550, Immuno-Hématologie Pédiatrique, Génétique Médicale Pédiatrique, Dermatologie, U393
 
  Cutaneous lymphangitic carcinomatosis and acquired ichtyosis associated with prostatic carcinoma
DRAPPIER JC, MAHÉ E, MEMIN A, GROSSIN M, DESCAMPS V, BELAICH S, LEGRAIN S, CRICKX B
2003 - Ann. Dermatol. Vénéréolog. 130(3):345-437
BACKGROUND: Prostatic adenocarcinoma is exceptionally associated with cutaneous lesions. We describe a patient with cutaneous lymphangitis and paraneoplastic ichtyosis related to prostatic cancer. CASE REPORT: A 92 year-old man had been treated for five years for a prostatic carcinoma. An angiomatous lesion developed with in 3 months near the right breast. Physical examination revealed axillary node enlargement, a large skin angiomatous lesion, and ichtyosis. The skin biopsy of the angiomatous skin lesion demonstrated its prostatic origin with carcinomatous metastases in the lymphatic vessels. The ichtyosis was considered as paraneoplastic. DISCUSSION: Cutaneous metastases from prostatic carcinoma are rare. Less than 1 p. 100 of cutaneous metastases are of prostate origin despite the high frequency of this cancer in the general population. The clinical aspects - angiomatous lesion and paraneoplastic ichtyosis - are exceptional.
Unité(s) : Dermatologie
 
  Clinical study of 40 cases of incontinentia pigmenti
HADJ-RABIA S, FROIDEVAUX D, BODAK N, HAMEL-TEILLAC D, SMAHI A, TOUIL Y, FRAITAG S, DE PROST Y, BODEMER C
2003 - Arch. Dermatol. 139(9):1163-1170
OBJECTIVE: To analyze the distribution of manifestations in a pediatric cohort and define guidelines for follow-up of incontinentia pigmenti (IP). DESIGN: Retrospective study of 47 children referred to the Department of Pediatric Dermatology with a diagnosis of IP between 1986 and 1999. SETTING: The private or institutional practice of participating dermatologists and pediatricians. MAIN OUTCOME MEASURES: Evaluation of IP clinical diagnosis using the Landy and Donnai criteria. RESULTS: Because hyperpigmentation following the Blaschko lines may be observed in several pigmented disorders, 7 patients were found misdiagnosed. During the neonatal period, erythema, vesicles, and hyperkeratotic le sions were rarely absent in the patients with IP. Ocular and neurological abnormalities were frequent (20% and 30%, respectively) but rarely severe (8% and 7.5%, respectively). CONCLUSIONS: Clinical diagnosis is the first main step for a correct phenotype/genotype correlation, which remains indispensable to better understand the pathological mechanisms of IP and develop new therapies. In doubtful cases, molecular analysis is helpful but characteristic histological features must be added as major criteria for IP diagnosis. Multidisciplinary follow-up is needed, particularly during the first year of life, to detect possible ophthalmologic and neurological complications. Neuroimaging ought to be performed in the case of abnormal neurological examination results or when vascular retinopathy is detected.
Unité(s) : Dermatologie
 
  Chronic urticaria in children
HAMEL-TEILLAC D
2003 - Ann. Dermatol. Vénéréolog. 130(Hs1):69-72
Chronic urticaria (more than 6 weeks) in childhood is rare; either the history and the clinical examination are very important to make distinction between "isolated chronic urticaria" and "urticaria associated with systemic diseases". The etiologic factors responsible for "isolated chronic urticaria" are parasitologic, infectious diseases, drugs, physical factors. If those are not present, the question of food responsability will be discuss.
Unité(s) : Dermatologie
 
  Identification of mutations in a new gene encoding a FERM family protein with a pleckstrin homology domain in Kindler syndrome
JOBARD F, BOUADJAR B, CAUX F, HADJ-RABIA S, HAS C, MATSUDA F, WEISSENBACH J, LATHROP M, PRUD'HOMME JF, FISCHER J
2003 - Hum. Mol. Genet. 12(8):925-935
Kindler syndrome is a rare autosomal-recessive genodermatosis characterized by bullous poikiloderma with photosensitivity. We report the localization to chromosome 20p12.3 by homozygosity mapping and the identification of a new gene, which we propose to name kindlerin. We found four different homozygous mutations in four consanguineous families from North Africa and Senegal; three are expected to lead to premature stop codons and truncated proteins and the fourth involves a splice site. We were unable to identify a mutation in kindlerin in a fifth consanguineous family from Algeria with a similar phenotype and in which the patient was homozygous for the markers in the 20p12.3 interval. The kindlerin protein contains several domains which are shared by a diverse group of peripheral membrane proteins that function as membrane-cytoskeleton linkers: two regions homologous to band 4.1 domain of which one includes a FERM domain with a NPKY sequence motif, and a third region with a PH or pleckstrin homology domain. Kindlerin might be involved in the bidirectional signaling between integrin molecules in the membrane and the cytoskeleton, and could be involved in cell adhesion processes via integrin signaling.
Unité(s) : Dermatologie
 
  High frequency of detection of human papillomaviruses associated with epidermodysplasia verruciformis in children with psoriasis
MAHÉ E, BODEMER C, DESCAMPS V, MAHÉ I, CRICKX B, DE PROST Y, FAVRE M
2003 - Br. J. Dermatol. 149(4):819-825
Background Psoriasis is a T-cell-mediated immunological disease characterized by epidermal proliferation. The nature of the antigen(s) responsible for T-cell activation is still unknown. It has been suggested that the human papillomaviruses (HPVs) associated with epidermodysplasia verruciformis (EV), including the oncogenic HPV5, may contribute to the pathogenesis of psoriasis. Objectives: To determine whether EV-HPVs may play a role early in the disease, we searched for these viruses in children with psoriasis. The influence of clinical data on EV-HPV infection was investigated. Methods We studied scrapings of involved skin from 26 children aged 1.5-13 years with psoriasis. As controls, we analysed scrapings from 28 adults with psoriasis and 15 children with atopic dermatitis, as well as scrapings from normal skin of 28 adults with no known history of HPV infection. We searched for EV-HPV DNA sequences with a nested polymerase chain reaction method using degenerate primers specific for EV-HPVs and primers specific for HPV5 and HPV36, two EV-HPVs frequently detected in adults with psoriasis. Results Similar high prevalences were observed in children and adults with psoriasis for EV-HPVs (38.5% vs. 35.7%), HPV5 (46.2% vs. 46.4%) and HPV36 (15.4% vs. 25.0%). As in adults, we found several EV-HPV genotypes and HPV5 and HPV36 variants. A novel HPV36 subtype, HPV36b, was identified. Lower prevalences were observed in children with atopic dermatitis and in adults from the general population (6.7-10.1%). No correlation was observed between frequency of detection of HPVs and clinical data. It is noteworthy that HPV5 was identified in an 18-month-old girl and in a boy with psoriasis developing for only 1 week. Conclusions The early detection of several EV-HPV genotypes in children further supports the link between psoriasis and EV-HPVs and suggests a putative role for these viruses in the pathogenesis of psoriasis
Unité(s) : Dermatologie
 
  A helpful clinical sign predictive of cancer in adult dermatomyositis: cutaneous necrosis
MAHÉ E, DESCAMPS V, BURNOUF M, CRICKX B
2003 - Arch. Dermatol. 139(4):539-539
Unité(s) : Dermatologie
 
  Homozygosity Mapping of a Locus for a Novel Syndromic Ichthyosis to Chromosome 3q27-q28
BAALA L, HADJ-RABIA S, HAMEL-TEILLAC D, HADCHOUEL M, PROST C, LEAL SM, JACQUEMIN E, SEFIANI A, DE PROST Y, COURTOIS G, MUNNICH A, LYONNET S, VABRES P
2002 - J. Invest. Dermatol. 119(1):70-76
Ichthyosis is a heterogeneous group of skin disorders characterized by abnormal epidermal scaling. Occasionally, extracutaneous features are associated. A novel autosomal recessive ichthyosis syndrome is described here with scalp hypotrichosis, scarring alopecia, sclerosing cholangitis, and leukocyte vacuolization in two inbred kindreds of Moroccan origin. We also report the mapping of the diseased gene to a 21.2 cM interval of chromosome 3q27-q28. Homo zygosity for polymorphic markers has enabled us to reduce the genetic interval to a 16.2 cM region. Furthermore, comparison of mutant chromosomes in the two families has suggested a common ancestral mutant haplotype. This linkage disequilibrium has reduced the genetic interval encompassing the diseased gene to less than 9.5 cM maximum. Further study of additional families from the same geographic area will hopefully reduce the genetic interval as well as help in the cloning of the gene involved in this rare disorder.
Unité(s) : Dermatologie, Génétique Médicale Pédiatrique, U393
 
  Facial cellulite associated with mandibular osteomyelitis in an infant
BERTOCCHI M, HAMEL-TEILLAC D, EMOND S, BODAK N, DE PROST Y
2002 - Ann. Dermatol. Venereol. 129(4):405-407
INTRODUCTION: The discovery of a jugular tumefaction in an infant evokes several diseases. We report the case of a 4-month-old infant whose jugular cellulite revealed mandibular osteomyelitis.CASE REPORT: A 4-month-old boy was referred for hard, hot tumefaction of the right cheek and multiple cervical adenopathies. The suggested diagnosis was cellulite of cutaneous origin. He presented 21 900/mm(3) hyperleukocytosis associated with an inflammatory biological syndrome. Standard x-ray of the facial mass was normal. Sonography of the face showed thickening of the soft subcutaneous tissues and retro and sub-mandibular adenopathies with abcedation. Antibiotherapy with amoxicillin and clavulanic acid led to rapid improvement. Three days after withdrawal of the antibiotherapy, the tumefaction recurred without fever. A facial scan eliminated cystic lymphangioma and showed osteolysis of the external plateau of the ascending branch of the mandible with periosteal appositions. Histological examination of a surgical bone biopsy showed infectious osteitis and culture revealed hemolytic beta streptococci. Six weeks of antibiotherapy (initially with amoxicillin and gentamycin, then amoxicillin in monotherapy) led to the regression of all cutaneous signs.COMMENTS: When confronted with a tumefaction in this area, malignant or benign tumoral causes such as cystic lymphangioma must be eliminated. Infectious causes (abscess, parotid inflammation and osteomyelitis) must be evoked and distinguished from infantile cortical hyperostosis (Caffey-Silverman's syndrome). Standard radiological imaging, scan or scintigraphy are useful diagnostic tools. If osteolysis is discovered, a biopsy must be taken for anatomopathological and biological examination.
Unité(s) : Dermatologie
 
  Prenatal diagnosis of a lethal form of Netherton syndrome by SPINK5 mutation analysis
BITOUN E, BODEMER C, AMIEL J, DE PROST Y, STOLL C, CALVAS P, HOVNANIAN A
2002 - Prenat. Diag. 22(2):121-126
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. Copyright (C) 2002 John Wiley Sons, Ltd.
Unité(s) : Dermatologie, Génétique Médicale Pédiatrique
 
  Netherton Syndrome: Disease Expression and Spectrum of SPINK5 Mutations in 21 Families
BITOUN E, CHAVANAS S, IRVINE AD, LONIE L, BODEMER C, PARADISI M, HAMEL-TEILLAC D, ANSAI SI S, MITSUHASHI Y, TAIEB A, DE PROST Y, ZAMBRUNO G, HARPER JI, HOVNANIAN A
2002 - J. Invest. Dermatol. 118(2):352-361
Netherton syndrome is a severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. Recently, we identified SPINK5, which encodes the serine protease inhibitor Kazal-type 5 protein (LEKTI), as the defective gene in Netherton syndrome. Here we describe the intron[minus sign]exon organization of the gene and characterize the SPINK5 mutations in patients from 21 families of different geographic origin, using denaturing high performance liquid chromatography and direct sequencing. We identified 18 mutations, of which 13 were novel and seven (39%) were recurrent. The majority of the mutations were clustered between exons 1--8 and exons 21--26. They comprised four nonsense mutations (22%), eight frameshift insertions or deletions (44%), and six splice-site defects (33%). All mutations predict the formation of premature termination codons. Northern blot analysis showed variable reduction of SPINK5 mutant transcript levels, suggesting variable efficiency of nonsense-mediated mRNA decay. Seven patients were homozygotes, eight were compound heterozygotes, and five were heterozygotes with only one identifiable SPINK5 mutation. Five mutations, one of which resulted in perinatal lethal disease in three families, were associated with certain ethnic groups. We also describe 45 intragenic polymorphisms in the patients studied. The clinical features of erythroderma, trichorrhexis invaginata, and atopic manifestations were present in the majority of affected individuals and ichthyosis linearis circumflexa was seen in 12 out of 24 patients. Interfamilial and intrafamilial variation in disease severity was observed, with no clear correlation between mutations and phenotype, suggesting that the degree of severity may be affected by other factors.
Unité(s) : Dermatologie
 
  Cutaneous hydration of the premature and new born
BODAK N, BODEMER C
2002 - Ann. Dermatol. Venereol. 129(1 Pt 2):143-146
The barrier function of the stratum corneum is a fundamental element in maintaining cutaneous hydration. Alteration in the stratum corneum leads to the loss of this barrier function, with increased transdermal water loss, decreased water content and installation of xerosis. Moisturizers correct cutaneous xerosis by restoring the stratum corneum. In the new born, the architectural and biochemical structure of the stratum corneum is identical to that of infants and adults. However, 60 p. cent of new born exhibit physiologic desquamation, demonstrating a transitory functional deficit in the stratum corneum, justifying emollient treatment. After this physiological desquamation period, emollients are reserved for atopic infants or those presenting keratinization disorders. In the premature, the epidermis and particularly the stratum corneum are immature; trans-epidermal water loss is elevated and the skin is dry or even fissural. The interest of applying emollients to the skin of premature new born was recently demonstrated. Emollients improved the aspect of the skin and also decreased the number of infectious episodes.
Unité(s) : Dermatologie
 
  Photosensitivity in children
BODAK N, BODEMER C
2002 - Ann. Dermatol. Venereol. 129(2):244-250
Unité(s) : Dermatologie
 
  Special aspects in pediatric patients
BODEMER C, DE PROST Y
2002 - Atopic Dermatitis. 479-490
Unité(s) : Dermatologie
 
  Subcutaneous skin nodule of an infant's face
BOYE K, BIAGGI A, HAMEL-TEILLAC D, FRAITAG S
2002 - Ann. Pathol. 22(2):141-142
Unité(s) : Dermatologie
 
  Exanthema
CAMBAZARD F, DE PROST Y, LORETTE G, BEYLOT C
2002 - Ann. Dermatol. Venereol. 129(10):S202-S206
Unité(s) : Dermatologie
 
  Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency in a boy and incontinentia pigmenti in his mother
DUPUIS-GIROD S, CORRADINI N, HADJ-RABIA S, FOURNET JC, FAIVRE L, LE DEIST F, DURAND P, DOFFINGER R, SMAHI A, ISRAEL A, COURTOIS G, BROUSSE N, BLANCHE S, MUNNICH A, FISCHER A, CASANOVA JL, BODEMER C
2002 - Pediatrics 109(6):e97
A child with X-linked osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency (OL-EDA-ID) was recently reported. We report the clinical features of a second boy with this novel syndrome and his mother, who presented with signs of incontinentia pigmenti (IP). The child had mild osteopetrosis without neurosensory complications, unilateral lymphedema of the left leg, and characteristic features of anhidrotic ectodermal dysplasia with sparse hair, facial dysmorphy, delayed eruption of teeth, and sweat gland abnormalities. He died at 18 months of severe immunodeficiency with multiple infections caused by Gram-negative (Salmonella enteritidis) and Gram-positive (Streptococcus pneumoniae) bacteria, nontuberculous mycobacteria (Mycobacterium kansasii), and fungi (Pneumocystis carinii). His 30-year-old mother's medical history, together with residual cutaneous lesions, was highly suggestive of IP without neurologic impairment. In this patient with OL-EDA-ID, we detected the same NF-kappaB essential modulator stop codon hypomorphic mutation identified in the previous patient. The occurrence of the same clinical features in 2 unrelated patients with the same genotype demonstrates that OL-EDA-ID is a genuine clinical syndrome. The clinical and biological descriptions of the proband and his mother further corroborate the relationship between IP and EDA. Both syndromes are allelic and are associated with mutations in NF-kappaB essential modulator, with a genotype-phenotype correlation in hemizygous males. In contrast, loss-of-function mutations and hypomorphic mutations may cause IP in females.
Unité(s) : Immuno-Hématologie Pédiatrique, Anatomo-Pathologie, U393, U429, U550, Dermatologie
 
  Cutaneous EBV-related lymphoproliferative disorder in a 15-year-old boy with AIDS: an unusual clinical presentation
FARDET L, BLANCHE S, BROUSSE N, BODEMER C, FRAITAG S
2002 - J. Pediat. Hematol. Oncol. 24(8):666-669
Lymphomas are a well-known malignancy in individuals with human immunodeficiency virus type 1 (HIV-1) infection. Most lymphomas are of B-cell lineage and cutaneous involvement is rare. Cutaneous T-cell lymphomas have been previously described in adults with HIV-1 infection but are exceptional in HIV-1 infected-children. The authors report here the extremely rare case of a large-cell cutaneous lymphoproliferation of T-cell lineage expressing Epstein-Barr virus (EBV) antigens in a 15-year-old boy with AIDS and his uncommon clinical presentation. The atypical clinical evolution with a nonaggressive treatment emphasizes that for immunosuppressed patients, the diagnosis of immunosuppression-related lymphoproliferative disorder should be considered before giving the diagnosis of malignant lymphoma when tumoral lymphoid cells express EBV antigens.
Unité(s) : Anatomo-Pathologie, Dermatologie, Immuno-Hématologie Pédiatrique
 
  Anhidrotic ectodermal dysplasia and Incontinentia pigmenti: pieces of the same puzzle
HADJ-RABIA S, SMAHI A, BODEMER C
2002 - Ann. Dermatol. Venereol. 129(3):277-280
Unité(s) : Dermatologie, U393
 
  Long-term management of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid anti-inflammatory drug
KAPP A, PAPP K, BINGHAM A, FOLSTER-HOLST R, ORTONNE JP, POTTER PC, GULLIVER W, PAUL C, MOLLOY S, BARBIER N, THURSTON M, DE PROST Y
2002 - J. Allergy Clin. Immunol. 110(2 Pt 1):277-284
BACKGROUND: Pimecrolimus cream 1% (Elidel, SDZ ASM 981), a nonsteroid selective inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis (AD). In this study we compared early intervention with pimecrolimus cream with treatment with a vehicle control. OBJECTIVE: The purpose of this investigation was to assess whether early treatment in infants of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares. METHODS: In this 1-year, double-blind controlled study, 251 infants aged 3 to 23 months with AD were randomized 4:1 to a pimecrolimus-based regimen (n = 204) or a conventional treatment regimen (n = 47). Both groups used emollients for dry skin. Early AD signs and symptoms were treated either with pimecrolimus cream to prevent flares or, in the control group, with vehicle. Vehicle was used to maintain blinding conditions. In the event of flares, moderately potent corticosteroid was permitted in both groups. The primary efficacy end point was the incidence of flares at 6 months. RESULTS: Pimecrolimus significantly reduced the incidence of flares compared with control treatment (P <.001), with 67.6% versus 30.4% of patients completing 6 months with no flare and 56.9% versus 28.3% completing 12 months with no flare. Overall corticosteroid use was substantially lower in the pimecrolimus group: 63.7% versus 34.8% of patients did not use corticosteroids at all during the study. Pimecrolimus was also more effective than control treatment in the long-term control of pruritus and the signs of AD. There were no clinically significant differences in incidence of adverse events between the 2 treatment groups. CONCLUSIONS: Treatment with pimecrolimus of early signs and symptoms significantly modified the disease course in infants by reducing the incidence of flares and improving overall control of AD. Pimecrolimus was safe and well tolerated.
Unité(s) : Dermatologie
 
  Severe cardiac involvement in children with systemic sclerosis and myositis
QUARTIER P, BONNET D, FOURNET JC, BODEMER C, ACAR P, OUACHEE-CHARDIN M, LE BIDOIS J, PRIEUR AM
2002 - J. Rheumatol. 29(8):1767-1773
OBJECTIVE: To assess the outcome of children with systemic sclerosis (SSc) and features of polymyositis. METHODS: The charts of 4 children who met the American College of Rheumatology criteria for SSc and had features of polymyositis, as defined by the presence of proximal muscle weakness and elevated serum creatine phosphokinase or aldolase level, were retrospectively reviewed. RESULTS: All children had multivisceral involvement including (1) myocardial perfusion defects in all cases, with mild to severe dilated cardiomyopathy in 3; (2) lung restrictive syndrome in 3; (3) mild to severe esophageal involvement in all cases; and (4) severe intestinal dysfunction in one child. Combination therapy of corticosteroids, methotrexate (MTX), and cyclosporine resulted in improved skin thickness and muscle strength scores in all cases, as well as in lung restrictive syndrome in 2, but was not effective regarding the progression of intestinal malabsorption in one patient, esophageal dysmotility in 3 patients, and dilated cardiomyopathy in 3. Endstage cardiac failure caused 2 deaths. In one child, heart transplantation was performed for the first time in this indication. CONCLUSION: Children with diffuse cutaneous SSc and features of polymyositis are prone to develop severe cardiomyopathy. Combination therapy of corticosteroids, MTX, and cyclosporine seems to be active on muscle, skin, and lung involvement but does not impair progression of esophageal or myocardial dysfunction. Heart transplantation might be considered, as an experimental treatment, in young patients with severe cardiomyopathy and no other irreversible organ damage.
Unité(s) : Cardiologie Pédiatrique, Dermatologie, Immuno-Hématologie Pédiatrique, Anatomo-Pathologie
 
  Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone acetate ointment in children with atopic dermatitis
REITAMO S, VAN LEENT EJM, HO V, HARPER J, RUZICKA T, KALIMO K, CAMBAZARD F, RUSTIN M, TAIEB A, GRATTON D, SAUDER D, SHARPE G, SMITH C, JUNGER M, DE PROST Y
2002 - J. Allergy Clin. Immunol. 109(3):539-546
Background: Vehicle-controlled studies have demonstrated the efficacy and safety of tacrolimus ointment in the treatment of patients with atopic dermatitis (AD).Objective: This study was undertaken to compare 0.03% and 0.1% tacrolimus ointment with 1% hydrocortisone acetate ointment in children 2 to 15 years of age with moderate-to-severe AD.Methods: Treatment was twice daily to affected areas for 3 weeks in this multicenter, randomized, double-blind, parallel-group study. The primary endpoint was the modified eczema area and severity index (mEASI) mean area under the curve (mAUC) as a percentage of baseline.Results: Five hundred sixty patients were randomized and received at least one application of ointment. Discontinuations included 21 of 189 patients from the 0.03% tacrolimus group, 13 of 186 patients from the 0.1% tacrolimus group, and 20 of 185 patients from the hydrocortisone acetate group. The median mEASI mAUC as a percentage of baseline showed 0.03% and 0.1 % tacrolimus to be significantly more effective than 1% hydrocortisone acetate (P < .001) and 0.1 % tacrolimus to be more effective than 0.03% tacrolimus (P = .006). The mEASI mAUC as a percentage of baseline was 44.8%, 39.8%, and 64.0% for patients who received 0.03% tacrolimus, 0.1% tacrolimus, and 1% hydrocortisone acetate, respectively. Transient skin burning was the only adverse event to show a higher incidence in the tacrolimus treatment groups than in the hydrocortisone acetate group (P < .05). Laboratory parameters showed no treatment differences and no marked changes over time.Conclusion: Tacrolimus, 0.03% and 0.1%, was significantly more effective than 1% hydrocortisone acetate and 0.1 % tacrolimus was more effective than 0.03% tacrolimus in the treatment of moderate-to-severe AD in children. No safety concerns were identified.
Unité(s) : Dermatologie
 
  The NF-kappaB signalling pathway in human diseases: from incontinentia pigmenti to ectodermal dysplasias and immune-deficiency syndromes
SMAHI A, COURTOIS G, HADJ-RABIA S, DOFFINGER R, BODEMER C, MUNNICH A, CASANOVA JL, ISRAEL A
2002 - Hum. Mol. Genet. 11(20):2371-2375
The transcription factor NF-kappaB regulates the expression of numerous genes controlling the immune and stress responses, inflammatory reaction, cell adhesion, and protection against apoptosis. Incontinentia pigmenti (IP) is the first genetic disorder to be ascribed to NF-kappaB dysfunction. IP is an X-linked dominant genodermatosis antenatally lethal in males. A complex rearrangement of the NEMO (NF-kappaB essential modulator) gene accounts for 85% of IP patients, and results in undetectable NEMO protein and absent NF-kappaB activation. On the other hand, hypohidrotic/anhidrotic ectodermal dysplasia (HED/EDA) has been ascribed to at least three genes also involved in NF-kappaB activation: ectodysplasin (EDA1), EDA-receptor (EDAR) and EDAR-associated death domain (EDARADD). During hair follicle morphogenesis, EDAR is activated by ectodysplasin, and uses EDARADD as an adapter to build a signal transducing complex that leads to NF-kappaB activation. Hence, several forms of HED/EDA also result from impaired activation of the NF-kappaB cascade. Finally, hypomorphic NEMO mutations have been found to cause anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID), whilst stop codon mutations cause a more severe phenotype associating EDA-ID with osteopetrosis and lymphoedema (OL-EDA-ID). The immunological and infectious features observed in patients result from impaired NF-kappaB signalling, including cellular response to LPS, IL-1beta, IL-18, TNF-alpha, Tlr2 and CD40 ligand. Consistently, mouse knockout models have shown the essential role of NF-kappaB in the immune, inflammatory and apoptotic responses. Unravelling the molecular bases of other forms of EDA not associated with mutations in NEMO will possibly implicate other components of the NF-kappaB signalling pathway.
Unité(s) : Dermatologie, Génétique Médicale Pédiatrique, U393, U550
 
  Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in childreN (art. no. e2)
WAHN U, BOS JD, GOODFIELD M, CAPUTO R, PAPP K, MANJRA A, DOBOZY A, PAUL C, MOLLOY S, HULTSCH T, GRAEBER M, CHERILL R, DE PROST Y
2002 - Pediatrics 110(1):NIL_6-NIL_13
Objective. Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares.
Unité(s) : Dermatologie
 
  Erythème. Orientation diagnostique
BODEMER C
2001 - Rev. Prat. 51(17):1953-1960
Unité(s) : Dermatologie
 
  Genetic bases of severe junctional epidermolysis bullosa presenting spontaneous amelioration with aging
GACHE Y, ALLEGRA M, BODEMER C, PISANI-SPADAFORA A, DE PROST Y, ORTONNE JP, MENEGUZZI G
2001 - Hum. Mol. Genet. 10(21):2453-2461
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. [References: 46]
Unité(s) : Dermatologie
 
  Differentiation of langerhans cells in langerhans cell histiocytosis
GEISSMANN F, LEPELLETIER Y, FRAITAG S, VALLADEAU J, BODEMER C, DEBRE M, LEBORGNE M, SAELAND S, BROUSSE N
2001 - Blood 97(5):1241-1248
Langerhans cell histiocytosis (LCH) consists of lesions composed of cells with a dendritic Langerhans cell (LC) phenotype. The clinical course of LCH ranges from spontaneous resolution to a chronic and sometimes lethal disease. We studied 25 patients with various clinical forms of the disease. In bone and chronic lesions, LCH cells had immature phenotype and function. They coexpressed LC antigens CD1a and Langerin together with monocyte antigens CD68 and CD14. Class II antigens were intracellular and LCH cells almost never expressed CD83 or CD86 or dendritic cell (DC)-Lamp, despite their CD40 expression. Consistently, LCH cells sorted from bone lesions (eosinophilic granuloma) poorly stimulated allogeneic T-cell proliferation in vitro, Strikingly, however, in vitro treatment with CD40L induced the expression of membrane class II and CD86 and strongly increased LCH cell allostimulatory activity to a level similar to that of mature DCs, Numerous interieukin-10-positive (IL-10(+)), Langerin(-), and CD68(+) macrophages were found within bone and lymph node lesions. In patients with self-heating and/or isolated cutaneous disease, LCH cells had a more mature phenotype, LCH cells were frequently CD14(-) and CD86(+), and macrophages were rare or absent, as were IL-10-expressing cells. We conclude that LCH cells in the bone and/or chronic forms of the disease accumulate within the tissues in an immature state and that most probably result from extrinsic signals and may be induced to differentiate toward mature DCs after CD40 triggering. Drugs that enhance the in vivo maturation of these immature DCs, or that induce their death, may be of therapeutic benefit. (Blood. 2001;97:1241-1248) (C) 2001 by The American Society of Hematology. [References: 41]
Unité(s) : Anatomo-Pathologie, Dermatologie, UMR 8603
 
  Melorheostosis associated with arteriovenous malformation of the ear
INGEN-HOUSZ-ORO S, CHIGOT V, HAMEL-TEILLAC D, BRUNELLE F, DE PROST Y
2001 - Ann. Dermatol. Vénéréolog. 128(8-9):915-918
Background. Melorheostosis is a rare bone dystrophy that may be associated with various vascular malformations. We report a case of arteriovenous fistulae of the ear associated with melorheostosis limited to the same side of the body. Case report. A 13 year-old boy presented a congenital port-wine nevus of the right side of the head complicated by an arteriovenous fistulae and angiomatous nodules of the ear. He was treated by laser, surgery of the nodules, arterial embolisations and sclerotherapy. in 1999, he had a benign trauma of the right hand. The X-ray showed hyperostosis resembling wax flowing down a candle reaching the carpus and some of the metacarpals and the phalanges of the right hand, typical of melorheostosis. The complete radiographic check-up showed the same characteristic appearance on the right side of the skull and the long bones of the right upper limb. Except a deformation of the right fingers, there were no others symptoms. Discussion. Melorheostosis is a rare, sporadic and benign bone dysplasia that may be localized to a single limb or disseminated. The diagnosis is usually made in late childhood. Pain, stiffness, deformation of a limb are the main clinical manifestations. The skin may be erythematous and sclerotic. The radiographic appearance is characteristic with hyperostosis on one side of the bone resembling wax flowing down a candle. A vascular abnormality is present in 17 P. 100 Of cases (hemangiomas, aneurysms, renal artery stenosis...). In these cases, melorheostosis is usually limited to the same side of the vascular lesion. We report the first case of arteriovenous fistulae of the ear associated with melorheostosis, on the same side of the body. The physiopathology of melorheostosis is still unknown but the association with a homolateral vascular abnormality suggests a localized defect in embryogenesis of the vascular and skeletal systems. [References: 9]
Unité(s) : Dermatologie, Radiologie Pédiatrique
 
  The role of nurses in the management of children with epidermolysis bullosa
LUSTRE A, LEVE-CORSET I, LEEUWIN G, LAUNAY C, BLONDY MF, MICHAUD MT, MAZE C, BODAK N, BODEMER C
2001 - Rev. Fr. Allergol. Immunol. Clin. 41(7):659-663
The dystrophic form of congenital epidermolysis bullosa causes skin lesions resembling those of patients with severe bums. The loosening of the skin is permanent and occurs repeatedly, in a series of flare-ups. The mucous membranes are particularly severely affected. Skin care requires numerous personnel and pain management is of prime importance. The management of this condition is therefore highly specialised. The prognosis is very poor with dystrophic epidermolysis bullosa typically resulting in the death of the patient. (C) 2001 Editions scientifiques et medicales Elsevier SAS. [References: 4]
Unité(s) : Dermatologie, Pneumologie-Allergologie Pédiatrique
 
  Cyclosporine in childhood psoriasis
MAHE E
2001 - Arch. Dermatol. 137(11):1532-1533
Unité(s) : Dermatologie
 
  Chronic papular onchodermatitis
MAHE E, TORCHET MF, CHRETIENNOT C, BUFFET P, BODEMER C
2001 - Archives Pédiatrie 8(6):604-607
'River blindness' is the main problem of onchocerciasis. Despite a high prevalence of onchocerciasis in endemic countries, cases of imported cutaneous or ocular onchocerciasis in France are rare. Case report, - We report the case of a chronic papular onchodermatitis with voluminous lymphadenopathy in a Cameroonian child, resolving with a treatment of ivermectin. Conclusion, - The main symptom of cutaneous onchocerciasis is pruritus, which symptom may alert physicians when dealing with patients who come from endemic countries for onchocerciasis, Cutaneous aspects may vary depending on length of exposure to antigens and immune responses by the host against microfilariae. Nowadays, onchocerciasis is treated with a single dose of ivermectin, which is sufficient for eye and cutaneous symptoms. However, this therapy is efficient only against microfilariae, and treaments have to be repeated many times to avoid relapses linked to persistence of adult worms. (C) 2001 Editions scientifiques et medicales Elsevier SAS. [References: 8]
Unité(s) : Dermatologie, Département de Pédiatrie, Infectiologie
 
  Methylprednisolone-induced acute generalized exanthematous pustulosis
MUSSOT-CHIA C, FLECHET ML, NAPOLITANO M, HERSON S, FRANCES C, CHOSIDOW O
2001 - Ann. Dermatol. Vénéréolog. 128(3 Part 1):241-243
Background, Acute generalized exanthematous pustulosis is a rare drug allergy. Generalized reactions to systematically administrated corticosteroids are even rarer. We report the first case of acute generalized exanthematous pustulosis due to methylprednisolone. Case report. A thirty year-old-woman presented, a few hours after intravenous administration of methylprednisolone indicated for multiple sclerosis, a maculopapulous rash predominant in the folds rapidly becoming pustulous with malaise, fever and neutrophilia. The histologic examination and negativity of microbiological cultures were consistant with the diagnostic of acute generalized exanthematous pustulosis. The rash cleared spontaneously in one week with normalization of the biology. One month later, epicutaneous tests, confirmed the allergy to group A corticosteroids. The treatment of multiple sclerosis was pursued with dexamethasone. Discussion. Clinical and histological manifestations were consistant with the diagnostic of acute generalized exanthematous pustulosis to methylprednisolone. Generalized reaction to systematically administered corticosteroids are very rare. Immediate reactions are the most frequently reported reactions, only about thirty delayed-type generalized skin eruptions have been reported to date. Group A corticosteroids are the most frequent causal agent. Epicutaneous tests have good sensitivity for acute generalized exanthematous pustulosis, for allergy to corticosteroids, delayed results are very important. [References: 11]
Unité(s) : Dermatologie
 
  Dermoid cysts revealed by meningitis with medullary compression
RAQBI F, ZERAH M, BODEMER C, LENOIR G
2001 - Archives Pédiatrie 8(5):499-503
The spinal dermal sinus tracts in the lumbosacral region are not usually recognized, especially when they are not associated with other cutaneous lesions. In these sites, the sinus tracts communicate with the dura in 90% of cases, leading to an important risk of meningitis. Case reports. - Two infants (9 and 12 months old) were hospitalized for meningitis. The hospitalization was preceded two weeks earlier by stubborn constipation, which revealed a neural compression. The physical and MRI examination showed a lumbosacral sinus in contact with a dermoid or an epidermoid tumor. These cysts were infected with anaerobic organisms. Despite surgery and antibiotic therapy, one child remained paraplegic. Conclusion. - Dermal sinuses above the intergluteal crease should be surgically excised at the time of diagnosis in all patients, regardless of the patient's age or neurologic findings. (C) 2001 Editions scientifiques et medicales Elsevier SAS. [References: 13]
Unité(s) : Département de Pédiatrie, Neurochirurgie Pédiatrique, Dermatologie
 
  Reduced expression of the epithelial adhesion ligand laminin 5 in the skin causes intradermal tissue separation
SPIRITO F, CHAVANAS S, PROST-SQUARCIONI C, PULKKINEN L, FRAITAG S, BODEMER C, ORTONNE JP, MENEGUZZI G
2001 - J. Biol. Chem. 276(22):18828-18835
Laminin 5, the major keratinocyte adhesion ligand, is found in the lamina lucida subregion of the epidermal basement membrane of the skin, where it colocalizes with the anchoring filaments. Mutations in the genes encoding laminin 5 cause junctional epidermolysis bullosa, an inherited skin blistering disease characterized by abnormal hemidesmosomes and cleavage of the lamina lucida leading to epidermal detachment. In this work we describe the genetic basis of a new subtype of lethal inherited epidermolysis bullosa associated with reduced skin reactivity to laminin 5, presence of mature hemidesmosomes, and intradermal cleavage of the skin. The epidermolysis bullosa patients were heterozygous for a nonsense mutation (Q896X) and a splice site mutation (764-10T -->G) in the gene (LAMC2) for the gamma2 chain of laminin 5. The nonsense mutation causes accelerated decay of the corresponding mRNA, while the splice site mutation results in maturation of a cryptic wild-type gamma2 mRNA leading to reduced expression of wild-type laminin 5. In vitro studies using the probands' keratinocytes showed that secretion of reduced amounts of functional laminin 5 in the patient, although permitting formation of hemidesmosomes, fail to restore efficient cell adhesion. Our results provide the first evidence that laminin 5 contributes to the firm adhesion of the epithelial basement membrane to the underlying stroma, They also show that a low expression level of laminin 5 induces assembly of mature hemidesmosomes in vivo but fails to assure a stable cohesion of the dermal-epidermal junction. [References: 56]
Unité(s) : Dermatologie
 
  An umbilical lesion
BENYOUSSEF K, HAMEL-TEILLAC D, SARNACKI S, JAUBERT F, DE PROST Y
2000 - Ann. Dermatol. Vénéréolog. 127(10):847-848
Unité(s) : Dermatologie, Chirurgie Pédiatrique
 
  Role of cytotoxic t cells in chronic alopecia areata
BODEMER C, PEUCHMAUR M, FRAITAIG S, CHATENOUD L, BROUSSE N, DE PROST Y
2000 - J. Invest. Dermatol. 114(1):112-116
Cytokines play a role in alopecia areata. We used immunohistochemical and in situ hybridization studies to demonstrate the persistence of pro-inflammatory as well as apoptotic mechanisms in skin biopsies from patients with chronic alopecia areata. In situ hybridization allows the visualization of the distribution of immunocompetent cells in vivo. We studied skin biopsies from 11 untreated alopecia areata patients and two normal controls. In situ hybridization was performed on frozen sections using S-35-radio-labeled riboprobes, specific for IL-1 beta, IL-2, IL-6, INF gamma, and granzyme B mRNA. Immunohistochemistry was carried out using an anti-IL-1 beta monoclonal antibody, and a monoclonal antibody directed against the human Fas protein. We demonstrated the presence of cells labeled with IL-1 beta, IL-6, INF gamma, and granzyme B antisense probes. Similarly, cells labeled with anti-IL-1 beta were found in 10 of 11 cases. The labeled cells were located in the mononuclear peri- and intrafollicular infiltrate. Cells expressing granzyme B were found in close contact with the follicle. Fas positivity was demonstrated in four of four cases at the level of the cytoplasmic membrane of the hair follicle keratinocytes. These results, based on visualizing the labeled cells, demonstrate that pro-inflammatory cytokines are produced by the mononuclear cell infiltrate in close contact with follicles in alopecia areata. Furthermore, they demonstrate for the first time that apoptotic mechanisms involving granzyme B and Fas-Fas ligand pathways may play a major role in the persistence of chronic alopecia areata. [References: 27]
Unité(s) : U025, Anatomo-Pathologie, Dermatologie
 
  Cd101 expression by langerhans cell histiocytosis cells
BOULOC A, BOULLAND ML, GEISSMANN F, FRAITAG S, ANDRY P, TEILLAC D, BENSUSSAN A, REVUZ J, BOUMSELL L, WECHSLER J, BAGOT M
2000 - Histopathology 36(3):229-232
Aims: Our objective was to study the expression of a recently identified cell surface molecule, CD101 and in Langerhans cell histiocytosis (LCH) patients as CD101 has been shown to be present on dendritic cells. We wanted to determine if CD101 expression could be helpful for the diagnosis of LCH in conjunction with other markers (CD1a, S100 protein), and could be predictive of the evolution and dissemination of the disease. Methods and results: The expression of CD101 was studied by immunohistochemical technique in 11 cases of Langerhans cell histiocytosis on frozen sections. The expression of CD101 was positive in nine cases, high in six cases and low in three cases. There was no expression in the other two cases. No correlation with the evolution, the localization or the dissemination of the disease could be evidenced. Conclusions: CD101 is a new phenotypic marker that might be useful in combination with other markers for the diagnosis of LCH. However, as the anti-CD101 antibody works only in frozen sections, its value is limited compared to anti-CD1a antibody. [References: 18]
Unité(s) : Anatomo-Pathologie, Dermatologie
 
  Facial hemangioma associated with arterial anomalies, coarctation of the aorta, and eye abnormalities: phaces syndrome
BUZENET C, HAMEL TEILLAC D, ACAR P, BECQUET F, CURAN D, MICHAUD V, SIDI D, DE PROST Y
2000 - Ann. Dermatol. Vénéréolog. 127(3):292-295
Background. Hemangiomas are frequent in childhood. Their association with dysmorphic anomalies is rare. Recently, the acronym "PHACES syndrome" was proposed to emphasize the association of Posterior fossa malformations, Hemangiomas, Arterial anomalies, coarctation of the aorta and cardiac defects, Eye abnormalities, and Sternal malformations. Case report. A female child, 3 months old, had a large Facial hemangioma. The physical examination was normal otherwise. A choroidal hemangioma and a papillary abnormality, causing amblyopia, were detected. The brain magnetic resonance imaging was normal. A subglottic hemangioma was Found at endoscopy. At the age of 16 months, physical examination disclosed a heart murmur and coarctation of the aorta was detected. Moreover, the cardiac angiography showed diffuse arterial lesions. Strict surveillance was decided as there were no manifestations. Discussion. Different abnormalities have been described to be associated with large facial hemangiomas. Frieden has grouped these abnormalities under the acronym PHACES. She described 43 hemangiomas and found 74 p. 100 Dandy Walker malformations and other posterior fossa malformations, 41 p. too arterial anomalies, 26 p. too cardiac or aortic malformations, 23 p. too ophthalmologic abnormalities. There is a high risk For the hemangiomas to develop in an airway localization. The prevalence of facial hemangiomas associated with other malformations is, to our knowledge, not known. In our department, 56 children were treated with corticosteroid therapy for severe facial hemangioma. 11 p. 100 had a cerebral abnormality. There were no cases with cardiac malformation or dysmorphism. PHACES syndrome is very rare but easy to remember. Thus in patients presenting a targe facial hemangioma, it is important to conduct an attentive neurological examination completed by brain imaging and an extensive cardiovascular exploration. Special attention should be given to the ophthalmologic and sternal examinations as well as the search for hemangiomas in an airway localization. [References: 12]
Unité(s) : Ophtalmologie, Dermatologie
 
  Mutations in spink5, encoding a serine protease inhibitor, cause netherton syndrome
CHAVANAS S, BODEMER C, ROCHAT A, HAMEL TEILLAC D, ALI M, IRVINE AD, BONAFE JL, WILKINSON J, TAIEB A, BARRANDON Y, HARPER JI, DE PROST Y, HOVNANIAN A
2000 - Nat. Genet. 25(2):141-142
Unité(s) : Dermatologie
 
  Localization of the netherton syndrome gene to chromosome 5q32, by linkage analysis and homozygosity mapping
CHAVANAS S, GARNER C, BODEMER C, ALI M, HAMEL TEILLAC D, WILKINSON J, BONAFE JL, PARADISI M, KELSELL DP, ANSAI S, MITSUHASHI Y, LARREGUE M, LEIGH IM, HARPER JI, TAIEB A, DE PROST Y, CARDON LR, HOVNANIAN A
2000 - Amer. J. Hum. Genet. 66(3):914-921
Netherton syndrome (NS [MIM 256500]) is a rare and severe autosomal recessive disorder characterized by congenital ichthyosis, a specific hair-shaft defect (trichorrhexis invaginata), and atopic manifestations. Infants with this syndrome often fail to thrive; life-threatening complications result in high postnatal mortality. We report the assignment of the NS gene to chromosome 5q32, by linkage analysis and homozygosity mapping in 20 families affected with NS. Significant evidence for linkage (maximum multipoint LOD score 10.11) between markers D5S2017 and D5S413 was obtained, with no evidence for locus heterogeneity. Analysis of critical recombinants mapped the NS locus between markers D5S463 and D5S2013, within an <3.5-cM. genetic interval. The NS locus is telomeric to the cytokine gene cluster in 5q31. The five known genes encoding casein kinase 1 alpha, the alpha subunit of retinal rod cGMP phosphodiesterase, the regulator of mitotic-spindle assembly, adrenergic receptor beta 2, and the diastrophic dysplasia sulfate-transporter gene, as well as the 38 expressed-sequence tags mapped within the critical region, are not obvious candidates. Our study is the first step toward the positional cloning of the NS gene. This finding promises a better understanding of the molecular mechanisms that control epidermal differentiation and immunity. [References: 39]
Unité(s) : Dermatologie
 
  Should immunosuppressants be used in the treatment of atopic dermatitis ?
DE PROST Y
2000 - Rev. Fr. Allergol. Immunol. Clin. 40(1):128-130
Unité(s) : Dermatologie
 
  Linkage of marie-unna hypotrichosis locus to chromosome 8p21 and exclusion of 10 genes including the hairless gene by mutation analysis
LEFEVRE P, ROCHAT A, BODEMER C, VABRES P, BARRANDON Y, DE PROST Y, GARNER C, HOVNANIAN A
2000 - Eur. J. Human Genet. 8(4):273-279
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. [References: 32]
Unité(s) : Dermatologie
 
  Cutaneous involvement in patients with angioimmunoblastic lymphadenopathy with dysproteinemia - a clinical, immunohistological, and molecular analysis
MARTEL P, LAROCHE L, COURVILLE P, LARROCHE C, WECHSLER J, LENORMAND B, DELFAU MH, BODEMER C, BAGOT M, JOLY P
2000 - Arch. Dermatol. 136(7):881-886
Objective: To determine whether cutaneous involvement in patients with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is related to a clonal T-cell proliferation. Design: Retrospective study. Setting: University hospitals. Patients: Ten patients with AILD and cutaneous involvement. Main Outcome Measure: The T-cell receptor-gamma (TCRG) gene rearrangement was studied with the use of polymerase chain reaction and denaturing gradient gel electrophoresis in blood, nodal, and skin samples. Skin and nodal samples were investigated also for the presence of Epstein-Barr virus (EBV) RNA by in situ hybridization. Results: A transient morbilliform eruption of the trunk was seen most often. Other cutaneous features were infiltrated plaques and purpuric or urticarial lesions. A clonal TCRG gene rearrangement was detected in 7 skin samples, corresponding to a maculopapular eruption with a histological pattern of nonspecific mild lymphoid dermal infiltrate in 6 patients, and to erythematous plaques with histological findings of typical cutaneous lymphoma in 1 patient. In the 5 patients in whom a TCRG gene rearrangement was evidenced in skin and lymph node samples, identical clones were detected in both. Five patients died by the end of the study, with a mean survival of 33.2 months. Four of these 5 patients had a clonal infiltrate in skin and lymph nodes. The EBV RNA was detected in only 1 of 10 skin biopsy specimens and in 5 of 8 lymph nodes tested. Conclusions: Cutaneous involvement is often related to a clonal T-cell proliferation in AILD, ec en when clinical and histological features are nonspecific. Cutaneous infiltrate seems to be clonally related to the nodal T-cell proliferation. The role of EBV infection in skin lesions was not evidenced. [References: 36]
Unité(s) : Dermatologie
 
  Association of acute neutrophilic dermatosis and myelodysplastic syndrome with (6;9) chromosome translocation: a case report and review of the literature
MEGARBANE B, BODEMER C, VALENSI F, RADFORD-WEISS I, FRAITAG S, MACINTYRE E, BLETRY O, VARET B, HERMINE O
2000 - Br. J. Dermatol. 143(6):1322-1324
Unité(s) : Hématologie Adulte, Dermatologie, Laboratoire d'Hématologie, Histo-Embryologie & Cytogénétique, Anat
 
  Lichen striatus: histopathological features of 13 cases
MIQUEL C, BROUSSE N, DE PROST Y, FRAITAG S
2000 - Ann. Pathol. 20(4):308-312
Lichen striatus (LS) is an uncommon dermatosis that generally affects children. Sometimes biopsy is required to assess the diagnosis. It is usually mentioned that LS has no specific histopathological criteria. Recently Gianotti et at, in 50 % of the examined cases, found clues to the diagnosis. We have evaluated 13 biopsies of children affected by LS, in order to evaluate histopathological criteria to allow a diagnosis. The features nearly constantly present (12/13) in each specimen were focally bandlike lymphocytic infiltrate with variable exocytosis and necrotic keratinocytes within the epidermis surrounded by lymphocytes. Epidermis hyperplasia, sometimes psoriasiform, was also present. In addition, one of remarkable the features of LS was the alignment of the infiltrate along eccrine ducts and glands and/or follicles. In 3 cases the deep lymphocytic infiltration was particularly dense. These results confirm that helpful clues to histopathological diagnosis of LS exist. [References: 8]
Unité(s) : Dermatologie, Anatomo-Pathologie
 
  Atopy, family and society
PRUSZKOWSKI A
2000 - Rev. Fr. Allergol. Immunol. Clin. 40(1):105-109
Unité(s) : Dermatologie
 
  Neonatal and infantile erythrodermas - a retrospective study of 51 patients
PRUSZKOWSKI A, BODEMER C, FRAITAG S, TEILLAC HAMEL D, AMORIC JC, DE PROST Y
2000 - Arch. Dermatol. 136(7):875-880
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. [References: 30]
Unité(s) : Dermatologie, Anatomo-Pathologie
 
  Staphyloccocal scarlet fever
SENET P, BODEMER C, AMORIC JC, HAMEL TEILLAC D, DE PROST Y
2000 - Ann. Dermatol. Vénéréolog. 127(1):85-87
Unité(s) : Dermatologie
 
  Localized scleroderma in childhood and therapeutic trial with calcitriol: a therapeutic option to define
BODEMER C, AMORIC JC, HAMEL-TEILLAC D, DE PROST Y
1999 - Ann. Dermatol. Vénéréolog. 126(10):725-726
Unité(s) : Dermatologie
 
  Scleroderma in childhood: a retrospective study of 70 cases
BODEMER C, BELON M, HAMEL-TEILLAC D, AMORIC JC, FRAITAG S, PRIEUR AM, DE PROST Y
1999 - Ann. Dermatol. Vénéréolog. 126(10):691-694
Background. Scleroderma is uncommon in childhood. The aim of our study was to analyze the frequency of different clinical forms, their prognostic significance, biological features, and co-morbidities and to assess the pertinence of therapeutic options.
Unité(s) : Anatomo-Pathologie, Immuno-Hématologie Pédiatrique, Dermatologie
 
  Cutaneous nodules in neonates
BODEMER C, FRAITAG S
1999 - Ann. Dermatol. Vénéréolog. 126(12):965-974
Unité(s) : Dermatologie
 
  Should immunosuppressants be used during treatment of atopic dermatitis ?
DE PROST Y
1999 - Rev. Fr. Allergol. Immunol. Clin. 39(8):689-691
Unité(s) : Dermatologie
 
  Skin elastic fibers in Williams syndrome
DRIDI SM, GHOMRASSENI S, BONNET D, AGGOUN Y, VABRES P, BODEMER C, LYONNET S, DE PROST Y, FRAITAG S, PELLAT B, SIDI D, GODEAU G
1999 - Amer. J. Hum. Genet. 87(2):134-138
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. (C) 1999 Wiley-Liss, Inc. [References: 25]
Unité(s) : Anatomo-Pathologie, U393, Cardiologie Pédiatrique, Dermatologie
 
  A prospective study of cutaneous intolerance to topical mechlorethamine therapy in patients with cutaneous T-cell lymphomas
ESTEVE E, BAGOT M, JOLY P, SOUTEYRAND P, BEYLOT-BARRY M, VAILLANT L, DELAUNAY M, AVRIL MF, LAROCHE L, GRANGE F, THOMINE E, WECHSLER J
1999 - Arch. Dermatol. 135(11):1349-1353
Objective: To study the exact frequency and the histological features of cutaneous intolerance to mechlorethamine (CIM) hydrochloride therapy in patients with cutaneous T-cell lymphomas, including Langerhans cell histiocytosis.
Unité(s) : Dermatologie
 
  Prognostic factors in primary cutaneous lymphomas other than mycosis fungoides and the Sezary syndrome
GRANGE F, HEDELIN G, JOLY P, BEYLOT-BARRY M, D'INCAN M, DELAUNEY M, VAILLANT L, AVRIL MF, BOSQ J, WECHSLER J, DALAC S, GROSIEUX C, FRANCK N, ESTEVE E, MICHEL C, BODEMER C, VERGIER B, LAROCHE L, BAGOT M
1999 - Blood 93(11):3637-3642
Prognostic studies of primary cutaneous lymphomas (PCL) other than mycosis fungoides (MF) and the Sezary syndrome (SS; non-MF/SS PCL) have been mainly performed on subgroups or on small numbers of patients by using univariate analyses. Our aim was to identify independent prognostic factors in a large series of patients with non-MF/SS PCL. We evaluated 158 patients who were registered in the French Study Group on Cutaneous Lymphomas database from January 1, 1986 to March 1, 1997. Variables analyzed for prognostic value were: age; sex; type of clinical lesions; maximum diameter, location, and number of skin lesions; cutaneous distribution tie, local, regional, or generalized); prognostic group according to the European Organization for Research and Treatment of Cancer (EORTC) classification for PCL; B- or T-cell phenotype; serum lactate dehydrogenase (LDH) level; and B symptoms. Univariate and multivariate analyses were performed using a model of relative survival. Forty-nine patients (31%) died. The median relative survival time was 81 months. In univariate analysis, EORTC prognostic group, serum LDH level, B symptoms, and variables related to tumor extension tie, distribution, maximum diameter, and number of skin lesions) were significantly associated with survival. When these variables were considered together in a multivariate analysis, EORTC prognostic group and distribution of skin lesions remained statistically significant, independent prognostic factors. This study confirms the good predictive value of the EORTC classification for PCL and shows that the distribution of skin lesions at initial evaluation is an important prognostic indicator. (C) 1999 by The American Society of Hematology. [References: 27]
Unité(s) : Dermatologie
 
  The use of itraconazole to treat cutaneous fungal infections in children
GUPTA AK, NOLTING S, DE PROST Y, DELESCLUSE J, DEGREEF H, THEISSEN U, WALLACE R, MARYNISSEN G, DE DONCKER P
1999 - Dermatology 199(3):248-252
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 =?, 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, 7: 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. [References: 18]
Unité(s) : Dermatologie
 
  Prenatal diagnosis in dermatology
HADJ-RABIA S, BODEMER C, DE PROST Y, LYONNET S
1999 - Ann. Dermatol. Vénéréolog. 126(12):981-991
Unité(s) : Dermatologie, Génétique Médicale Pédiatrique
 
  Angiomas and major dysplasias - Current pathogenic concepts and management
HAMEL-TEILLAC D
1999 - Archives Pédiatrie 6(Suppl 2):299S-302S
Unité(s) : Dermatologie
 
  Bejel: an unusual etiology of childhood stomatitis
VABRES P, ROOSE B, BERDAH S, FRAITAG S, DE PROST Y
1999 - Ann. Dermatol. Vénéréolog. 126(1):49-50
Introduction. Bejel (endemic syphilis) is usually encountered in children living in intertropical areas, although imported cases have been exceptionally reported in Europe.
Unité(s) : Anatomo-Pathologie, Dermatologie
 
  Two unusual tumors in a patient with xeroderma pigmentosum: atypical fibroxanthoma and basosquamous carcinoma
YOUSSEF N, VABRES P, BUISSON T, BROUSSE N, FRAITAG S
1999 - J. Cutaneous Pathol. 26(9):430-435
Xeroderma pigmentosum (XP) is a rare autosomal recessive disease, characterized by a genetic defect in DNA repair. The consequence is a high incidence of skin cancers on sun-exposed cutaneous surfaces of affected children. First lesions appear in the first years of life: telangiectasia, actinic keratosis and keratoacanthomas. Squamous cell and basal cell carcinomas are the most frequent neoplasms. We report the case of a 6-year-old girl affected with XP, who developed two unusual tumors: an atypical fibroxanthoma and a basosquamous carcinoma. In both tumors, immunohistochemical study showed abnormal accumulation of the p53 protein, suggesting the presence of mutation of the p53 tumor suppressor gene. Such p53 mutations may be ultraviolet (UV)-induced, as they are frequently observed in tumors occurring in XP.
Unité(s) : Anatomo-Pathologie, Dermatologie
 
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