ABSTRACT
Biological therapies are safer and more effective against psoriasis than conventional treatments. Even so, 30-50% of psoriatic patients show an inadequate response, which is associated with individual genetic heterogeneity. Pharmacogenetic studies have identified several single nucleotide polymorphisms (SNPs) as possible predictive and prognostic biomarkers for psoriasis treatment response. The objective of this study was to determine the link between several SNPs and the clinical response to biological therapies in patients with moderate-severe psoriasis. A set of 21 SNPs related to psoriasis and/or other immunological diseases were selected and analysed from salivary samples of patients (n = 88). Treatment effectiveness and patient improvement was assessed clinically through Relative Psoriasis Area and Severity Index (PASI), also called 'PASI response', as well as absolute PASI. Associations between SNPs and PASI factors were assessed at 3 and 12 months for every treatment category of IL-17, IL-23, IL-12&23 and TNF-α inhibitors. Multivariate correlation analysis and Fisher's exact test were used to analyse the relationship between SNPs and therapy outcomes. Several SNPs located in the TLR2, TLR5, TIRAP, HLA-C, IL12B, SLC12A8, TNFAIP3 and PGLYRP4 genes demonstrated association with increased short and long-term therapy-effectiveness rates. Most patients achieved values of PASI response ≥75 or absolute PASI<1, regardless of the biological treatment administered. In conclusion, we demonstrate a relationship between different SNPs and both short- and especially long-term effectiveness of biological treatment in terms of PASI. These polymorphisms may be used as predictive markers of treatment response in patients with moderate-to-severe psoriasis, providing personalized treatment.
Subject(s)
Psoriasis , Tumor Necrosis Factor-alpha , Humans , Tumor Necrosis Factor-alpha/genetics , Interleukin-12/genetics , Polymorphism, Single Nucleotide , Tumor Necrosis Factor Inhibitors/therapeutic use , Treatment Outcome , Psoriasis/drug therapy , Psoriasis/genetics , Immunity , Severity of Illness IndexABSTRACT
BACKGROUND/PURPOSE: Recent GWAS studies, mostly performed in populations of North European origin, have identified the genetic loci associated with pigmentation, sun sensitivity, freckling and skin cancer susceptibility. Here, we aimed at addressing the genetic determinants of sunlight sensitivity in Spain, a southern European population. METHODS: Nine SNPs located in 8 pigmentation-related genes (IRF4, TYR, ASP, HERC2, OCA2, BNC2, SLC24A4 and SLC45A2) were genotyped in 456 Spaniards. Additionally, the complete sequence of the MC1R gene was obtained, testing each nonsynonymous mutation supported by the classification as R or r alleles. A standardised questionnaire was used to collect demographic characteristics, pigmentation and sun sensitivity traits, as well as sun exposure habits. RESULTS: MC1R R alleles and IRF4 rs12203592 were significantly associated with sunlight sensitivity at the Bonferroni-corrected level (P-value < 4.54 × 10-3 ). Genetic variants in SLC45A2 (rs16891982) and HERC2 (rs12913832) were also found to be significantly associated with skin photosensitivity in our Spanish sample. Interaction analysis using the MDR method revealed epistatic effects when these four variants were considered together. CONCLUSION: MC1R, IRF4, HERC2 and SLC45A2 play a significant role in skin sensitivity to sunlight in the Spanish population. Moreover, interaction among these four loci seems to modulate the ability of the skin to respond to UV radiation.
Subject(s)
Alleles , Gene Frequency , Photosensitivity Disorders/genetics , Polymorphism, Single Nucleotide , Skin Pigmentation/genetics , Skin , Ultraviolet Rays/adverse effects , Adult , Female , Genome-Wide Association Study , Humans , Male , SpainABSTRACT
BACKGROUND: There are few data to enable us to ascertain whether switching to another systemic agent is useful in patients with psoriasis who have not responded favorably to a first systemic treatment. OBJECTIVE: To evaluate the efficacy and safety of etanercept in patients with moderate-to-severe plaque psoriasis previously treated with infliximab. METHODS: We analyzed data from patients with moderate-to-severe psoriasis and a poor primary or secondary response to infliximab, and who were later treated with etanercept. RESULTS: Data were collected from 8 patients who were first treated with infliximab. At 54 weeks of therapy, 25% had a psoriasis area and severity index (PASI) of 75. At 24 weeks of therapy with etanercept, 75% had a PASI of 75. Consecutive administration of both therapies did not increase the number of adverse events. LIMITATIONS: The data should be regarded with caution due to the scant number of patients. CONCLUSIONS: Switching from infliximab to etanercept can be useful and safe in nonresponders.
Subject(s)
Dermatologic Agents/therapeutic use , Immunoglobulin G/therapeutic use , Psoriasis/drug therapy , Receptors, Tumor Necrosis Factor/therapeutic use , Adult , Aged , Animals , Antibodies, Monoclonal/therapeutic use , Drug Administration Schedule , Etanercept , Humans , Infliximab , Male , Middle Aged , Severity of Illness Index , Treatment Failure , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
ResumenEl liquen plano familiar es una forma rara de liquen plano que se caracteriza por inicio precoz, curso prolongado, afectación de mucosa oral y formasclínicas atípicas. Se han investigado posibles factores ambientales o genéticos en su patogénesis. Presentamos tres miembros de una familia que padecenliquen plano, con características clínicas típicas de la variante familiar. Se realizó un tipaje de HLA en dos miembros afectos. No se identificó ningúnfactor ambiental ni infeccioso
Familial lichen planus is a rare form of lichen planus characterized by an early onset, prollonged course, involvement of oral mucosa and atypical clinicalforms. Different enviromental or genetic factors have been investigated in its pathogenesis. Herewith three members of a familiy affected withlichen planus, with typical clinic features of the familiar variant are reported. HLA typing was performed made in two affected members. No enviromentalnor infectious agent was identified
Subject(s)
Humans , Male , Female , Adolescent , Middle Aged , Lichen Planus/genetics , Lichen Planus/etiology , Histocompatibility Testing/methods , Adrenal Cortex Hormones/therapeutic useABSTRACT
El xantogranuloma necrobiótico es una rara enfermedad granulomatosa que afecta a la piel y a otros tejidos, con frecuencia asociada a disproteinemia. Se presenta el caso de una paciente con sintomatología e histología de xantogranuloma necrobiótico que carecía de alteraciones en el proteinograma y de la típica afectación periocular. La paciente había sido diagnosticada recientemente de leucemia linfática crónica. El caso de nuestra paciente difiere de la mayoría de los descritos en la literatura especializada por asociarse a otro tipo de discrasia sanguínea y no tener afectación periocular. (AU)
Subject(s)
Female , Middle Aged , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Granuloma/complications , Granuloma/diagnosis , Xanthomatosis/complications , Xanthomatosis/diagnosis , Necrobiotic Disorders/complications , Necrobiotic Disorders/diagnosis , Xanthomatosis/pathology , Necrobiotic Disorders/pathology , Granuloma/pathologyABSTRACT
No disponible
Subject(s)
Adult , Male , Humans , Heroin/adverse effects , Scalp Dermatoses/chemically induced , Skin Diseases, Vesiculobullous/chemically induced , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Ecthyma, Contagious , Scalp Dermatoses/drug therapy , Skin Diseases, Vesiculobullous/drug therapyABSTRACT
Los siringomas son tumores benignos anexiales que se presentan como múltiples pápulas de color carne en cuero cabelludo, frente, cuello, parte anterior del tórax, axilas, mitad inferior del abdomen y extremidades. Su aparición en zona genital es infrecuente. Se desarrollan tras la pubertad, con mayor frecuencia en mujeres, y suelen ser asintomáticos. Se presenta el caso de una paciente de 19 años con siringomas, simétricos y bilaterales en la región vulvar (AU)
Subject(s)
Adult , Female , Humans , Syringoma/diagnosis , Sweat Gland Neoplasms/diagnosis , Vulvar Neoplasms/diagnosisABSTRACT
El linfoma primario testicular representa entre el 1 y el 2% de todos los linfomas no hodgkinianos. Se trata del tumor testicular más frecuente en varones mayores de 50 años. Muestra una tendencia a diseminarse sistémicamente a múltiples áreas extranodales, incluyendo testículo contralateral, sistema nervioso central, piel, anillo de Waldeyer, pulmón y pleura. En el 80-90% de los casos se trata de un linfoma de células grandes difuso y con inmunofenotipo B. Se presenta un caso de linfoma primario testicular que se manifestó con lesiones cutáneas (AU)
Subject(s)
Aged , Male , Humans , Lymphoma/pathology , Testicular Neoplasms/pathology , Skin Neoplasms/secondaryABSTRACT
El síndrome de Melkersson-Rosenthal es un trastorno neuromucocutáneo caracterizado por la asociación clínica de edema orofacial recurrente, parálisis facial y lengua fisurada. La tríada clásica no es frecuente en su forma completa, mientras que las formas oligosintomáticas como la queilitis granulomatosa de Miescher son más comunes. Aunque se han propuesto varios mecanismos patogénicos, incluyendo una etiología infecciosa, atopia e hipersensibilidad a aditivos alimentarios, la etiología es todavía incierta. La biopsia durante los estadios iniciales de la enfermedad muestra vasos linfáticos dilatados, agregados perivasculares de histiocitos, linfocitos y células plasmáticas en el interior de un edema no específico, pero los hallazgos más específicos son los granulomas sarcoideos no caseificantes que no siempre están presentes. El manejo terapéutico es difícil. Se han utilizado corticoides orales e intralesionales, minociclina y queiloplastia, todos con éxito limitado (AU)
