Clinical, molecular and biochemical characterization of nine Spanish families with Conradi-Hünermann-Happle syndrome: new insights into X-linked dominant chondrodysplasia punctata with a comprehensive review of the literature.

BACKGROUND: Conradi-Hünermann-Happle syndrome (CDPX2, OMIM 302960) is an inherited X-linked dominant variant of chondrodysplasia punctata which primarily affects the skin, bones and eyes. CDPX2 results from mutations in EBP (emopamil binding protein), and presents with increased levels of sterol precursors 8(9)-cholesterol and 8-dehydrocholesterol. OBJECTIVES: To expand the understanding of CDPX2, clinically, biochemically and genetically. METHODS: We present one of the largest series reported to date, including 13 female patients belonging to nine Spanish families. Patients were studied biochemically using gas chromatography-mass spectrometry, genetically using polymerase chain reaction and in their methylation status using the HUMARA assay. RESULTS: In our cases, there was a clear relationship between abnormal sterol profile and the EBP gene mutation. We describe three novel mutations in the EBP gene. EBP mutations were inherited in three out of nine families and were sporadic in the remaining cases. CONCLUSIONS: No clear genotype-phenotype correlation was found. Patients' biochemical profiles did not reveal a relationship between sterol profiles and severity of disease. A skewed X-chromosome inactivation may explain the clinical phenotype in CDPX2 in some familial cases.

Clinical and epidemiological characteristics of adult patients hospitalized for erysipelas and cellulitis.

The purpose of this investigation was to analyze the clinical and epidemiological aspects of all cases of erysipelas and infectious cellulitis admitted to a tertiary hospital during a period of five years. All patients admitted with the main diagnosis of erysipelas or cellulitis to the Department of Dermatology of the author's institution from January 2005 to May 2010 were included. Seventy patients were identified and their medical records were retrospectively reviewed so as to record the epidemiological and clinical data. Univariate and multivariable analyses were performed to analyze variables that predicted longer length of stay. The frequency of cellulitis in the lower limbs was higher in men and patients older than 65 years. Moderate/severe cellulitis in patients with basal comorbidity followed by a poor response to oral antibiotic therapy for 48 h were the most common reasons for admission. At arrival, four patients had abscessed areas. Fourteen patients developed local complications and 18 cases developed general in-hospital complications. Most patients improved or were healed with intravenous amoxicillin-clavulanate 1 g-200 mg/8 h. Intravenous amoxicillin-clavulanate 1 g-200 mg/8 h may be a good choice for empiric treatment in our setting. The development of in-hospital complications and the need for changing empiric antibiotic therapy were significant and independent variables associated with longer length of stay.

A novel EDA gene mutation in a Spanish family with X-linked hypohidrotic ectodermal dysplasia.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterized by abnormal development of the hair, teeth, and sweat glands. It is caused by mutations in the EDA gene, which maps to the X chromosome and encodes a protein called ectodysplasin-A, a member of the tumor necrosis factor-related ligand family. Affected males typically exhibit all the typical features of HED, but heterozygous carriers may show mild to moderate clinical manifestations. We describe the case of a Spanish family in which a novel heterozygous c.733_734insGA mutation at the EDA gene was identified. It was located in exon 5 and consisted of a frame-shift mutation at codon 245, which gave rise to an abnormal protein with a premature stop codon after 35 residues. Genetic analyses in families with XLHED are useful for checking carrier status, but they also provide information for genetic counseling and prenatal diagnosis.

Analysis of the STS gene in 40 patients with recessive X-linked ichthyosis: a high frequency of partial deletions in a Spanish population.

BACKGROUND: Recessive X-linked ichthyosis (RXLI) (OMIM 308100) is a genodermatosis characterized by polygonal, dark, adherent and mild-to-moderate scales that normally improve during summer. RXLI is caused by a deficiency in steroid sulphatase (STS), whose gene has been located on the X chromosome (locus Xp22.3). Up to 90% of the mutations described in this gene are complete deletions. OBJECTIVES: Previous reports of partial deletion of STS gene in cases of RXLI prompted us to determine the incidence of these abnormalities in a Spanish population. METHODS: We have studied exons 1, 5 and 10 of the STS gene by polymerase chain reaction in 40 patients with clinical features of RXLI. RESULTS: Our results revealed that 30 patients presented complete deletions (75%) while 10 patients had partial deletions (25%) a rate higher than that reported in the previous studies. CONCLUSIONS: Amplification of exons 1, 5 and 10 is reliable in screening RXLI in the population studied here. No correlation was found between phenotype and the extent of the deletions.

[Leonine facies in carcinoid syndrome]. / Facies leonina en el síndrome carcinoide.

Carcinoid syndrome is a rare disorder caused when elevated levels of vasoactive substances secreted by a carcinoid tumor fail to be metabolized by the liver. This can occur for a variety of reasons including metastatic invasion of the organ. Carcinoid syndrome results in elevated levels of 5-hydroxyindoleacetic acid in the urine. Clinical manifestations include: flushing, diarrhea, bronchospasm, and heart failure. We describe a patient with carcinoid syndrome and hepatic metastases, in whom the key symptom of persistent facial edema resulted in conspicuous leonine facies; there was a partial response to treatment with oral isotretinoin and intramuscular lanreotide. Differential diagnosis was made with other conditions causing facial edema. A review is performed of the various skin manifestations of carcinoid syndrome, highlighting their role in the early diagnosis and treatment of the disorder.

Primary cutaneous T-cell lymphoproliferative disorder of donor origin after allogeneic haematopoietic stem-cell transplantation.

A 56-year-old male patient had a history of mantle-cell lymphoma, which was treated with polychemotherapy and reduced-intensity conditioning allogeneic haematopoietic stem cell transplantation (ASCT) from his healthy sister with an identical human leucocyte antigen profile. Six years after transplantation, the patient developed asymptomatic eczema-like cutaneous lesions. Histologically the lesions contained a dense superficial lichenoid infiltrate, mainly consisting of CD4+ atypical medium to large lymphocytes showing indented hyperchromatic nuclei. In situ hybridization for Epstein-Barr virus was negative. PCR amplification of the T-cell receptor-gamma chain gene from several lesions revealed a monoclonal rearrangement without clonal variation. Two-colour fluorescence in situ hybridization (X and Y chromosomes) and microsatellite genotyping were used to compare samples from the patient (transplant recipient), his sister (donor) and the skin biopsy sample, which confirmed that the origin of the neoplastic cells was the donor graft. To our knowledge, this is the first case of post-transplant primary cutaneous T-cell lymphoproliferative disorder after ASCT.

Altered expression of immunoreactive involucrin in lamellar ichthyosis.

In some cases of lamellar ichthyosis, mutations in the epidermal transglutaminase gene and a reduction in the thickness of the cornified envelope have been documented. Involucrin is a major component of the cornified envelope and a substrate for epidermal transglutaminase. The aim of the present work was to analyse the expression of involucrin in lamellar ichthyosis. An ultrastructural study and/or immunohistochemical and biochemical techniques with anti-involucrin antibody were carried out on the epidermis of fifteen patients (12 families) suffering from lamellar ichthyosis. The effect of in vivo retinoid treatment on the involucrin epidermal expression was also investigated. Four cases with normal skin, seventeen cases of other ichthyoses and ten cases of psoriasis were used as controls. In all these cases of lamellar ichthyosis, a thin or absent cornified envelope, electron-dense granules inside corneocytes and a decrease of the epidermal involucrin expression were observed. In the patients receiving treatment with retinoids, western blot and ELISA revealed an increase in the involucrin expression. The decreased expression of involucrin in lamellar ichthyosis could contribute to the altered desquamation process accompanying the disease, since the clinical improvement associated with retinoid treatment is accompanied by an increase in the expression of involucrin.

Verrucous plaque on the back of a hand.

We report the case of a 44-year-old slaughter-house operator with a skin lesion that had been present for two years on the back of his left hand. The lesion had increased progressively in size despite numerous topical treatments. Physical examination revealed an infiltrated erythematous-violet plaque with a verrucous surface featuring numerous orifices draining purulent material. Histologic study of the lesion disclosed tuberculoid granulomatous infiltrates at the dermoepidermal limit. Presence of Mycobacterium tuberculosis, together with other epidemiologic, clinical, histologic, and immunologic data, permitted a diagnosis of tuberculosis verrucosa cutis to be made. The excellent response of the patient to treatment confirmed this hypothesis. However, polychemotherapy withdrawal was temporarily needed due to analytical abnormalities.

[Apocrine cystadenoma. About 3 observations with one balanic localization (author's transl)]. / Cystadénoma apocrine. A propos de 3 observations dont une de siège balanique.

Description of three apocrine cystadenomas: two of the face and scalp and one of the glans (urethral meatus and left anterior surface of the navicular fossa) with no bibliographical precedent. From a clinico-histological standpoint the importance of objective data which make possible the clinical diagnosis is stressed allowing light microscope differentiation from eccrine hydrocystoma. The histogenesis is exposed and it appears convenient to name (eccrine or apocrine) cystadenoma the authentic cystic adenoma (among the organoid hamartoma of the cutaneous appendages, while reserving the term (eccrine or apocrine) hydrocystoma for glandular cysts. Due to the esthetic and occasionally functional repercussion, surgical excision is indicated.

[Ehlers-Danlos syndrome (1 case)]. / Sindrome de Ehlers-Danlos.

A male patient is presented is clinical and histopathological characteristics are typical of Ehlers-Danlos Syndrome (cutaneous and articular hyperelasticity and cutaneous fragility with the presence of atrophic scars). Looking into the family history we think that other relatives had the same disease and they had died during their childhood due to internal hemorrhages. The patient we present did not have significant hemorrhages in any moment. The elastic fibers in the dermal papilla are reduced giving rise to the appearance of being increased in the middle and deep dermis.

Patología de las uñas en la infancia. Cómo interpretar los cambios en la superficie ungueal / Nail alterations in children. How to interpret the changes in the ungueal surface

La patología ungueal en la infancia es muy amplia y su conocimiento es imprescindible para el diagnóstico de variados procesos que muestran en las uñas su seña de identidad propia. En muchos casos la afectación ungueal es la pionera de la enfermedad, permitiendo un diagnóstico precoz. A nivel de la atención pediátrica extrahospitalaria, el conocimiento de la semiología ungueal permite orientaciones diagnósticas en las que no es preciso el uso de complejas y costosas técnicas complementarias. Revisaremos los cambios en la superficie de la lámina ungueal (cambios en la lisura, curvatura, grosor...) y su implicación clínica, mostrando especial interés en recalcar los procesos dermatológicos o sistémicos que acompañan a cada síntoma ungueal

Ungueal pathology in children is very extensive and its knowledge is essential to diagnose varied processes that leave an identifying mark on the nails. In many cases, the affected nail is the pioneer of the disease, allowing for an early diagnosis. In regards to outpatient pediatric care, knowledge of nail semiology allows for diagnostic orientations in which the use of complex and costly complementary techniques is not necessary. We review the changes on the nail plate surface (changes in smoothness, curvature, thickness, etc.) and its clinical implication, showing special interest in emphasizing the dermatological or systemic processes that accompany each ungueal symptom