Unmet needs in patients with moderate-to-severe plaque psoriasis treated with methotrexate in real world practice: FirST study.

BACKGROUND: Methotrexate (MTX) is frequently used in the treatment of moderate-to-severe psoriasis, however, there is limited data on health-related quality-of-life (HRQoL), psoriasis clinical outcomes and hepatic fibrosis in MTX-treated patients in routine clinical practice. OBJECTIVES: To investigate the impact of moderate-to-severe psoriasis in MTX-treated patients in Spain regarding to HRQoL, psoriasis clinical data and risk of hepatic fibrosis. METHODS: Observational, non-interventional, cross-sectional, retrospective, multicentre study, performed in Spain in moderate-to-severe plaque psoriasis patients treated with MTX > 16 weeks prior to inclusion. RESULTS: Despite ongoing treatment, 17.1% of 457 evaluable patients reported moderate-to-extreme impact on HRQoL (DLQI > 5); 21.4% BSA > 5 and 35.2% moderate-to-severe pruritus (VAS ≥ 4). Persistent severe psoriasis (PASI ≥ 10 and/or DLQI ≥ 10) was observed in 10.7%. Hepatic steatosis was identified in 64.1% of patients (HSI ≥ 36) and 37.2% of the patients were at-risk of advanced fibrosis which was associated to the MTX treatment duration. CONCLUSIONS: The study identified unmet needs in moderate-to-severe plaque psoriasis patients treated with MTX, revealing a significant proportion of sub-optimally controlled patients in terms of HRQoL and different domains of the disease. This study also found patients at-risk of advanced fibrosis, with evidence suggesting a correlation between longer exposures to MTX and higher risk of advanced fibrosis.

Capillary malformation-arteriovenous malformation syndrome: a multicentre study.

BACKGROUND: Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a rare syndrome with characteristic skin lesions that are associated with fast-flow vascular malformations (FFVMs) in one-third of patients. Few case series have been described, and none in Spain. AIM: To identify the prevalence of dermatological parameters, FFVMs and associated features in a large series of patients with CM-AVM. METHODS: We conducted an observational study of patients with CM-AVM syndrome diagnosed in 15 Spanish hospitals over 3 years. The main clinical, radiological, genetic findings and associated diseases were analysed. RESULTS: In total, 64 patients were assessed. In 26.5% of cases, the diagnosis was incidental. In 75% of patients, there was one significantly larger macule, which we termed the 'herald patch'. FFVMs were detected in 34% of the patients, with 30% located on the skin, 7.8% in the brain and in 1.5% in the spine. There was a positive family history in 65% of the 64 patients. Genetic analysis was performed for RASA1 mutations in 57 patients, of whom 42 (73%) had a positive result. All 4 patients tested for EPHB4 mutations had a positive result. No tumour lesions were detected in the series, except for five infantile haemangiomas. CONCLUSIONS: Our data on clinical lesions, associated FFVM, family history and genetics are similar to those previously published in the literature. An extensive data analysis failed to demonstrate any statistically significant association between the presence of an FFVM and any clinical, familial or genetic parameter that could predict its onset, although a link between the presence of a herald patch on the midline face and the presence of a brain FFVM was observed. We did not detect any genotype-phenotype correlation.

Síndrome de Sturge-Weber: revisión / Sturge-Weber Syndrome: A Review

El síndrome de Sturge Weber es un trastorno neurocutáneo congénito, esporádico causado por una mutación somática activadora en el gen GNAQ, con una incidencia de uno de cada 20,000-50,000 nacidos. Se caracteriza por la presencia de una mancha en vino de Oporto facial, angiomatosis leptomeníngea y glaucoma. La manifestación neurológica más común son las convulsiones, que suelen comenzar en los primeros meses de vida. El glaucoma puede estar presente desde el nacimiento o desarrollarse posteriormente. Los estudios de neuroimagen permiten visualizar la angiomatosis leptomeníngea, ayudando al diagnóstico del síndrome de Sturge Weber. El tratamiento estándar incluye láser para la mancha en vino de Oporto facial, anticonvulsivantes y tratamiento médico o quirúrgico del glaucoma. El pronóstico de la enfermedad dependerá de la extensión de la malformación leptomeníngea y del grado de afectación ocular (AU)

Sturge-Weber syndrome is a sporadic congenital neurocutaneous disorder caused by a somatic activating mutation in GNAQ; it affects 1 in every 20,000 to 50,000 newborns. It is characterized by a facial Port-wine stain, leptomeningeal angiomatosis, and glaucoma. Seizures are the most common neurological manifestation and typically present in the first months of life. Glaucoma may be present at birth or develop later. Neuroimaging studies show leptomeningeal angiomatosis, supporting diagnosis. Standard treatment for Sturge-Weber syndrome includes laser treatment for the Port-wine stain, anticonvulsants, and medical or surgical treatment for the glaucoma. Prognosis depends on the extent of leptomeningeal involvement and the severity of the glaucoma (AU)

Sturge-Weber Syndrome: A Review. / Síndrome de Sturge-Weber: revisión.

Sturge-Weber syndrome is a sporadic congenital neurocutaneous disorder caused by a somatic activating mutation in GNAQ; it affects 1 in every 20,000 to 50,000 newborns. It is characterized by a facial Port-wine stain, leptomeningeal angiomatosis, and glaucoma. Seizures are the most common neurological manifestation and typically present in the first months of life. Glaucoma may be present at birth or develop later. Neuroimaging studies show leptomeningeal angiomatosis, supporting diagnosis. Standard treatment for Sturge-Weber syndrome includes laser treatment for the Port-wine stain, anticonvulsants, and medical or surgical treatment for the glaucoma. Prognosis depends on the extent of leptomeningeal involvement and the severity of the glaucoma.

Síndrome malformaciones capilares-malformaciones arteriovenosas: presentación de 2 casos, claves diagnósticas y manejo / Capillary Malformation-Arteriovenous Malformation Syndrome: A Report of 2 Cases, Diagnostic Criteria, and Management

El síndrome malformaciones capilares-malformaciones arteriovenosas es un tipo de malformación vascular poco frecuente que se describió en 2003. Se hereda de forma autosómica dominante, y se ha objetivado que está causado por mutaciones heterocigotas en el gen RASA1, que codifica la proteína RASp21. Dicho síndrome se caracteriza por malformaciones capilares pequeñas y múltiples que se asocian con malformaciones arteriovenosas o fístulas arteriovenosas, tanto en los individuos afectos como en sus familias. Describimos aquí 2 nuevos casos familiares de este síndrome que hemos diagnosticado y estudiado en nuestro centro, tanto desde el punto de vista clínico como genético (AU)

Capillary malformation-arteriovenous malformation syndrome is a rare type of vascular malformation first described in 2003. It is an autosomal dominant inherited disorder that has been reported in association with heterozygous mutations in the RASA1 gene, which encodes the protein RASp21. The clinical picture is characterized by multiple small capillary malformations which are associated with either arteriovenous malformations or arteriovenous fistulas in both the affected individual and other members of their family. We describe 2 new familial cases of this syndrome that were clinically and genetically diagnosed and studied in our hospital (AU)

Capillary malformation-arteriovenous malformation syndrome: a report of 2 cases, diagnostic criteria, and management.

Capillary malformation-arteriovenous malformation syndrome is a rare type of vascular malformation first described in 2003. It is an autosomal dominant inherited disorder that has been reported in association with heterozygous mutations in the RASA1 gene, which encodes the protein RASp21. The clinical picture is characterized by multiple small capillary malformations which are associated with either arteriovenous malformations or arteriovenous fistulas in both the affected individual and other members of their family. We describe 2 new familial cases of this syndrome that were clinically and genetically diagnosed and studied in our hospital.

Pharmacologic inhibition of MEK signaling prevents growth of canine hemangiosarcoma.

Angiosarcoma is a rare neoplasm of endothelial origin that has limited treatment options and poor five-year survival. As a model for human angiosarcoma, we studied primary cells and tumorgrafts derived from canine hemangiosarcoma (HSA), which is also an endothelial malignancy with similar presentation and histology. Primary cells isolated from HSA showed constitutive extracellular signal-regulated kinase (ERK) activation. The mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor CI-1040 reduced ERK activation and the viability of primary cells derived from visceral, cutaneous, and cardiac HSA in vitro. HSA-derived primary cells were also sensitive to sorafenib, an inhibitor of B-Raf and multireceptor tyrosine kinases. In vivo, CI-1040 or PD0325901 decreased the growth of cutaneous cell-derived xenografts and cardiac-derived tumorgrafts. Sorafenib decreased tumor size in both in vivo models, although cardiac tumorgrafts were more sensitive. In human angiosarcoma, we noted that 50% of tumors stained positively for phosphorylated ERK1/2 and that the expression of several MEK-responsive transcription factors was upregulated. Our data showed that MEK signaling is essential for the growth of HSA in vitro and in vivo and provided evidence that the same pathways are activated in human angiosarcoma. This indicates that MEK inhibitors may form part of an effective therapeutic strategy for the treatment of canine HSA or human angiosarcoma, and it highlights the use of spontaneous canine cancers as a model of human disease.

Low serological positivity in patients with histology compatible with celiac disease in Perú.

OBJECTIVE: To study the frequency of positive serology for celiac disease (CD) in patients with duodenal biopsies suggestive of this disease. MATERIAL AND METHODS: Cross sectional study. We included patients with duodenal biopsies histologically compatible with CD and antigliadin, antiendomysial and IgA antitransglutaminase antibodies. We defined a "case" of CD if there was a positive biopsy and either antiendomisial or antitransglutaminase positive antibodies. RESULTS: Thirty one patients were included in our study. Six were antiendomysial positive and 5 antitransglutaminase positive while the antigliadin was positive in 14 cases. Therefore, out of 31 patients only 10 had a serology compatible with CD and only one had positive both antibodies, antiendomysial and antitransglutaminase. CONCLUSIONS: a) We have found that most of the duodenal biopsies compatible with CD are not diagnosed with positive serology; and b) we found a low correlation between serological diagnostic tests.

Baja frecuencia de positividad serológica en pacientes con biopsias histológicamente compatibles con enfermedad celiaca en Perú / No disponible

Objetivo: estudiar la frecuencia de positividad de las pruebasserológicas en pacientes con biopsias compatible con enfermedadceliaca.Material y métodos: estudio transversal. Se incluyeron pacientescon biopsia duodenal histológicamente compatible con enfermedadceliaca y determinación de anticuerpos antigliadina, antiendomisioy antitransglutaminasa IgA. Definimos como caso deenfermedad celiaca a quienes tuvieran biopsia positiva y anticuerposantiendomisio y/o antitransglutaminasa positivos.Resultados: 31 pacientes fueron incluidos de los cuales 6 fueronantiendomisio positivo, 5 fueron antitransglutaminasa positivoy antigliadina fue positivo en 14. Por lo tanto de 31 pacientes concambios histológicos compatibles con enfermedad celiaca sólo 10tuvieron serología diagnóstica. Sólo uno de los pacientes tuvo positividadtanto para antitransglutaminasa como para antiendomisio.Conclusiones: a) encontramos que la mayoría de biopsias deduodeno con un cuadro histológico sugerente de enfermedad celiacano se corresponden con serología diagnóstica de esta enfermedad;b) encontramos baja coincidencia en la positividad serológicaentre antiendomisio y antitransglutaminasa(AU)

Objective: to study the frequency of positive serology for celiac disease (CD) in patients with duodenal biopsies suggestive of this disease. Material and methods: cross sectional study. We included patients with duodenal biopsies histologically compatible with CD and antigliadin, antiendomysial and IgA antitransglutaminase antibodies. We defined a “case” of CD if there was a positive biopsy and either antiendomisial or antitransglutaminase positive antibodies. Results: thirty one patients were included in our study. Six were antiendomysial positive and 5 antitransglutaminase positive while the antigliadin was positive in 14 cases. Therefore, out of 31 patients only 10 had a serology compatible with CD and only one had positive both antibodies, antiendomysial and antitransglutaminase. Conclusions: a) we have found that most of the duodenal biopsies compatible with CD are not diagnosed with positive serology; and b) we found a low correlation between serological diagnostic tests(AU)

Bone density and fragility fractures in patients with developmental disabilities.

UNLABELLED: We investigated prior fractures, osteoporosis risk factors, and bone mineral density (BMD) in 107 institutionalized adults with developmental disabilities. We found a very high prevalence of BMD in the osteoporotic range and a significant correlation between lower BMD and prior fragility fractures. INTRODUCTION: The purpose of this study was to investigate factors contributing to osteoporosis and fragility fractures among developmentally disabled adults. METHODS: Adults from a residential center participated in a prospective study in which bone mineral density (BMD) at the forearm and heel were measured with a portable X-ray densitometer. Prior fragility fractures were identified from chart review. RESULTS: Among 107 participants, 84 (78.5%) had a measurement within the osteoporotic range. The heel was more severely abnormal (mean T-score -3.1 +/- 1.5) than the forearm (-1.6 +/- 1.3, p < .0.0001). Radiographically confirmed prior fragility fractures (17 [16.3%]) were associated with lower heel (p = 0.0155) and forearm (p = 0.0172) T-scores. In multiple regression analysis, there were independent associations between forearm BMD and prior fragility fractures (p = 0.0126) and between heel BMD and prior fragility fractures (p = 0.0291). The odds ratio for prior fracture increased by 2.02 (95% CI 1.12-3.64) for each standard deviation (SD) decrease in heel T-score and by 2.39 (95% CI 1.08-5.32) for each SD decrease in forearm T-score. CONCLUSIONS: We found a very high prevalence of osteoporotic BMD measurements in institutionalized adults with developmental disabilities. Lower heel and forearm BMD measurements were significantly and independently associated with prior fragility fractures in this population.

Efalizumab treatment of psoriasis vulgaris: a cohort study in outpatient clinical practice.

BACKGROUND: Efalizumab is approved by the European Medicines Evaluation Agency for the treatment of adult patients with moderate to severe plaque psoriasis who fail to respond to, have a contraindication for, or cannot tolerate other systemic therapies. OBJECTIVES: To evaluate the efficacy and safety of efalizumab treatment in daily practice at a dermatology department in a teaching hospital in Barcelona, Spain. METHODS: A cohort study was carried out for patients treated with efalizumab for at least 3 months between May 2005 and July 2007. In total, 31 patients [21 men, 10 women; mean psoriasis and severity index (PASI) 12.9] were treated with efalizumab. Data were collected prospectively, including PASI, and recorded at the start of treatment and at follow-up visits with a frequency of at least every 3 months. RESULTS: At the end of the study period, efalizumab treatment was ongoing in 18 of the 31 patients (58.1%), and 7 of these patients had been treated for > or = 24 months. At week 12, 67.7% of the patients treated with efalizumab had achieved an improvement of 50% in PASI (PASI 50), 41.9% reached PASI 75, and 16.1% reached PASI 90 (intention to treat and as-treated analyses). In all, 19 patients (61.3%) received treatment for > or = 24 weeks. At week 24, 89.5% of these patients reached PASI 75, and 26.3% reached PASI 90 (as-treated analysis). During efalizumab treatment, mainly mild adverse effects were reported, including transient papular or circinate exacerbations of psoriasis, which were seen in five patients (16.1%). Rebounds (defined as PASI > or = 125% of baseline, leading to erythroderma in two patients) occurred in 7/31 patients (22.6%); this occurred while on treatment in 5/11 nonresponding patients (45.5%) and after discontinuation of treatment in 2/20 patients with good response (10.0%). CONCLUSION: Efalizumab is an effective and safe treatment for psoriasis in most patients of a high need population in routine practice, and provides maintained improvement in 'responders'. Combination treatment was transiently used in 48.4% of patients to optimize therapeutic results. Special consideration must be given to possible rebound in patients with an inadequate response or after discontinuation of treatment.