RESUMEN
BACKGROUND: Psoriasis has been related to a large number of cardiovascular risk factors such as hypertension, diabetes mellitus and arteriosclerosis. The increased carotid intima-media thickness (IMT) could be considered to be a marker of generalized arteriosclerosis. OBJECTIVE: To assess the effect of systemic and biological drugs on psoriatic patients' carotid IMT. METHODS: A prospective study was performed. We studied 53 patients with moderate and severe psoriasis from our psoriasis dermatological unit, analysing lipid and glucose metabolism and performing a carotid IMT sonography before introduction of systemic and biological drugs. After that, we performed an 8-month closely analytic and sonographic follow-up. RESULTS: The IMT of the patients with psoriasis treated with biological drugs tended to decrease, although this occurrence was not statistically significant (P = 0.086). The subgroup analysis revealed that patients treated with methotrexate (P = 0.045) and anti-IL-12/23 (P = 0.010) presented a decrease in their IMT levels. This analysis also showed a decrease in glycaemia and insulin levels in patients treated with TNF-alpha inhibitors and ustekinumab. CONCLUSIONS: Our study suggests that the carotid IMT may benefit from treatment with biological drugs, particularly anti-IL-12/23 and methotrexate in patients suffering from moderate and severe psoriasis. However, larger longitudinal studies should be performed to fully confirm these results.
Asunto(s)
Grosor Intima-Media Carotídeo , Fármacos Dermatológicos/farmacología , Metotrexato/farmacología , Psoriasis/tratamiento farmacológico , Ustekinumab/farmacología , Adulto , Productos Biológicos/uso terapéutico , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Fármacos Dermatológicos/uso terapéutico , Femenino , Humanos , Insulina/sangre , Lipoproteínas LDL/sangre , Estudios Longitudinales , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Túnica Íntima/efectos de los fármacos , Túnica Media/efectos de los fármacos , Ustekinumab/uso terapéuticoRESUMEN
Overgrowth syndromes are characterized by global or localized disproportionate growth associated with other anomalies, including vascular malformations and neurological and/or visceral disorders. CLOVES (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined-type Vascular malformations, Epidermal naevi, Scoliosis/Skeletal and spinal anomalies) is an overgrowth syndrome caused by mosaic activating mutation in gene PIK3CA, which gives rise to abnormal PI3K-AKT-mTOR pathway activation. These mutations are responsible for the clinical manifestations of the syndrome, which include low- and high-flow vascular malformations, thoracic lipomatous hyperplasia, asymmetric growth, and visceral and neurological disorders. These common anomalies are illustrated with figures from two personal cases. Identification of the clinical and genetic characteristics of CLOVES syndrome is crucial for the differential diagnosis with other overgrowth syndromes, such as Proteus or Klippel-Trenaunay (K-T) syndromes, and for the therapeutic management of the different anomalies. In this context, a new entity comprising different syndromes with phenotypic mutations in PIK3CA has been proposed, designated PIK3CA-related overgrowth spectrum (PROS), with the aim of facilitating clinical management and establishing appropriate genetic study criteria.
Asunto(s)
Anomalías Múltiples/genética , Lipoma/patología , Anomalías Musculoesqueléticas/patología , Nevo/patología , Fosfatidilinositol 3-Quinasas/genética , Malformaciones Vasculares/patología , Anomalías Múltiples/patología , Fosfatidilinositol 3-Quinasa Clase I , Trastornos del Crecimiento/patología , Humanos , Mutación , SíndromeRESUMEN
This review describes the current understanding and the potential use of mesenchymal stromal cells (MSCs) in cell-based therapies for clinical management of difficult wounds and other dermatoses. MSCs have been shown to possess many advantageous properties that make them a promising therapeutic modality in dermatology still under investigation. In fact, MSCs' ability to promote wound healing through its paracrine function and pro-angiogenic properties have generated increasing interest for treating acute and chronic wounds. There is also great interest in utilizing MSCs' immunological characteristics for therapeutic use especially for patients with debilitating systemic autoimmune and inflammatory skin conditions who have failed other therapies. Its role in aesthetics has also been explored with clinical data showing improvement of acne scars and wrinkles from photoaging. Clinical trials are underway investigating the safety and efficacy of MSCs in the treatment of different skin conditions such as acute burns, diabetic and venous stasis ulcers, epidermolysis bullosa and systemic sclerosis, among others. We anticipate that as our understanding of the characteristics and function of MSCs grow, so will its role in cell-based treatments of dermatological conditions.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/fisiología , Enfermedades de la Piel/terapia , Cicatrización de Heridas , Acné Vulgar/terapia , Enfermedades Autoinmunes/terapia , Quemaduras/complicaciones , Comunicación Celular , Cicatriz Hipertrófica/terapia , Contractura/etiología , Contractura/terapia , Dermatitis Atópica/terapia , Epidermólisis Ampollosa/terapia , Humanos , Células Madre Mesenquimatosas/inmunología , Psoriasis/terapiaRESUMEN
BACKGROUND: MicroRNAs (miRNAs) gene expression regulators are altered in psoriasis suggesting their role in the pathogenesis. OBJECTIVE: To study expression changes of inflammation and toll-like receptor (TLR)-related miRNAs, miRNA-155, let-7i, miRNA-21, miRNA-146a and miRNA-223 in peripheral mononuclear cells (PBMCs) and miRNA-21, miRNA-146a and miRNA-223 in plasma, from chronic plaque-type psoriasis patients who were treatment-naive or had undergone a washout period (n = 11). MiRNAs were evaluated at baseline and after 11 (9-12) months [median (25th-75th percentile range)] of methotrexate (MTX) or topical (betamethasone plus calcipotriene) treatment. METHODS: MiRNA expression was analysed with quantitative real-time reverse transcription-polymerase chain reaction. Matched controls were studied. RESULTS: Psoriasis patients presented, at baseline, increased expression of miRNA-155, let-7i, miRNA-146a, miRNA-21 and miRNA-223 in PBMCs, plus miRNA-21, miRNA-146a and miRNA-223 in plasma. Receiver-operator characteristic (ROC) curve analysis and area under the curve (AUC) showed that expression of these miRNAs have the potential to distinguish between psoriasis and controls. At baseline, miRNA-155 expression in PBMCs correlated with Psoriasis Area Severity Index (PASI) [12 (8-14)] (Spearman r: 0.7140, P < 0.05) suggesting a role in psoriasis. After MTX or topical treatment, reduction in PASI was observed [87.5% (75-100)]; miRNA-155 expression in PBMCs decreased; plasma miRNA-21, miRNA-146a and miRNA-223 were down-regulated. ROC analysis showed that miRNA-155 expression in PBMCs from psoriasis patients have the potential to distinguish between patients' samples at baseline and after treatment (AUC: 0.942, sensitivity: 0.91; specificity: 0.91 values; maximum likelihood ratio =10). After treatment, miRNA-146a expression in PBMCs increased; miRNA-155/miRNA-146a ratio decreased, suggestive of a regulatory feedback; let-7i expression decreased; miRNA-21 and miRNA-223 remained elevated. CONCLUSION: In this exploratory study, psoriasis patients presented increased expression of miRNA-155 in PBMCs that correlated with PASI and decreased with disease remission. MiRNA-21, miRNA-146a and miRNA-223 in PBMCs and plasma were increased at baseline and differentially modulated, underscoring different roles of TLR-related miRNAs in psoriasis.
Asunto(s)
MicroARNs/sangre , Monocitos/metabolismo , Psoriasis/sangre , Adulto , Femenino , Humanos , MasculinoRESUMEN
Extramammary Paget disease (EMPD) is a very rare form of intraepithelial adenocarcinoma. We report the cases of EMPD diagnosed in a referral hospital over a 5-year period from 2009 to 2013. Ten cases of EMPD were diagnosed in 4 men and 6 women aged between 50 and 79 years. Erroneous clinical diagnoses led to diagnostic delays of 1 to 5 years in all cases. Six patients had in situ lesions and dermal invasion was observed in the other 4 cases. Four patients had a second neoplasm and 2 of the patients with invasive EMPD died. Because EMPD is rare and its clinical presentation is nonspecific, a high degree of clinical suspicion is required to avoid delays in diagnosis and treatment.