Association between several immune response-related genes and the effectiveness of biological treatments in patients with moderate-to-severe psoriasis.

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.

Genetic variants associated with skin photosensitivity in a southern European population from Spain.

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.

A customized pigmentation SNP array identifies a novel SNP associated with melanoma predisposition in the SLC45A2 gene.

As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date.

Efficacy of etanercept in psoriatic patients previously treated with infliximab.

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.

Liquen plano familiar / Familial lichen planus

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

Reticular telangiectatic erythema associated with an implantable cardioverter defibrillator.

Reticular telangiectatic erythema (RTE) is a skin reaction associated with implantable cardiac devices (ie, pacemakers and cardioverter defibrillators). We present a patient who developed an erythematous patch over the implantable cardioverter defibrillator site. We discuss the clinical features, histologic findings, and patch testing of this entity.

[Papillary dermal elastolysis similar to pseudoxanthoma elasticum]. / Elastolisis dérmica papilar similar a pseudoxantoma elástico.

Papillary dermal elastolysis similar to pseudoxanthoma elasticum is an elastolytic disorder characterized by cutaneous lesions on the neck and in the supraclavicular region that are clinically similar to pseudoxanthoma elasticum, with no systemic complications. The histological examination shows a loss of elastic fibers in the papillary dermis. We report a case in a 76-year-old woman with typical lesions on the neck.

[Treatment of severe refractory pemphigus vulgaris with rituximab]. / Tratamiento de pénfigo vulgar grave resistente con rituximab.

Pemphigus vulgaris is a potentially fatal autoimmune bullous disease. High doses of immunosuppressive drugs are used in managing severe cases of pemphigus. Rituximab, an anti-CD20 monoclonal antibody, has proven to be effective in patients with refractory pemphigus vulgaris and pemphigus foliaceus. We review cases of pemphigus vulgaris and pemphigus foliaceus not associated with lymphoma that were treated with rituximab, and we report a new case of severe refractory pemphigus vulgaris successfully treated with rituximab.

Elastolisis dérmica papilar similar a pseudoxantoma elástico / Papillary dermal elastolysis similar to pseudoxanthoma elasticum

La elastolisis dérmica papilar similar a pseudoxantoma elástico es un trastorno elastolítico caracterizado por lesiones cutáneas en el cuello y en la región supraclavicular que clínicamente se asemejan al pseudoxantoma elástico, sin complicaciones sistémicas. El examen histológico muestra una pérdida de fibras elásticas en la dermis papilar. Comunicamos un caso en una mujer de 76 años con lesiones típicas en el cuello

Papillary dermal elastolysis similar to pseudoxanthoma elasticum is an elastolytic disorder characterized by cutaneous lesions on the neck and in the supraclavicular region that are clinically similar to pseudoxanthoma elasticum, with no systemic complications. The histological examination shows a loss of elastic fibers in the papillary dermis. We report a case in a 76-year-old woman with typical lesions on the neck

Tratamiento de pénfigo vulgar grave resistente con rituximab / Treatment of severe refractory pemphigus vulgaris with rituximab

El pénfigo vulgar es una enfermedad ampollosa autoinmune potencialmente mortal. En el tratamiento de los casos graves de pénfigo se utilizan fármacos inmunosupresores en dosis altas. Rituximab, un anticuerpo monoclonal anti-CD20, ha demostrado eficacia en pacientes con pénfigo vulgar y pénfigo foliáceo refractarios. Revisamos los casos de pénfigo vulgar y de pénfigo foliáceo tratados con rituximab no asociados a linfoma, y comunicamos un nuevo caso de pénfigo vulgar grave refractario tratado con éxito con rituximab

Pemphigus vulgaris is a potentially fatal autoimmune bullous disease. High doses of immunosuppressive drugs are used in managing severe cases of pemphigus. Rituximab, an anti-CD20 monoclonal antibody, has proven to be effective in patients with refractory pemphigus vulgaris and pemphigus foliaceus. We review cases of pemphigus vulgaris and pemphigus foliaceus not associated with lymphoma that were treated with rituximab, and we report a new case of severe refractory pemphigus vulgaris successfully treated with rituximab

Tumefacción labial de 2 meses de evolución / Labial swelling which had developed over two months

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Pápulas verrugosas en el dorso de las manos / Verroucous papules on the back of the hands

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Escleredema de Buschke asociado a diabetes mellitus. Estudio de cuatro casos / Scleredema of Buschke associated with diabetes mellitus. Study of four cases

El escleredema de Buschke se caracteriza por un engrosamiento de la dermis con depósito de mucina entre las fibras de colágeno, que se manifiesta como un endurecimiento de la piel, predominantemente en la mitad superior del tronco. Se ha relacionado con diabetes mellitus de larga evolución y mal controlada, gammapatías monoclonales e infecciones estreptocócicas. Se estudiaron los pacientes con el diagnóstico clínico de escleredema confirmado mediante estudio histopatológico y asociado a diabetes mellitus. Se revisaron las enfermedades asociadas, las características clínicas e histopatológicas, el curso evolutivo y la respuesta al tratamiento. El escleredema se caracteriza por un endurecimiento cutáneo que afecta a la mitad superior del tronco. En una gran proporción de casos se asocia a diabetes mellitus mal controlada, de curso prolongado durante años y con escasa respuesta al tratamiento

Scleredema of Buschke is characterized by a thickening of the dermis with mucin deposits among the collagen fibers, which manifests as a hardening of the skin, predominantly on the upper trunk. It has been associated with long-standing, poorly controlled diabetes mellitus, monoclonal gammopathies and streptococcus infections. We studied patients with a clinical diagnosis of scleredema confirmed by means of a histopathological study, and associated with diabetes mellitus. We reviewed associated diseases, clinical and histopathological characteristics, evolution and response to treatment. Scleredema is characterized by hardening of the skin, affecting the upper trunk. A large proportion of cases are associated with long-standing, poorly controlled diabetes mellitus, with little response to treatment