Mar Llamas-velasco | Universidad Autónoma de Madrid (original) (raw)

Papers by Mar Llamas-velasco

Anales de la Real Academia Nacional de Medicina, Apr 30, 2023

Resumen Durante la pandemia mundial por el coronavirus, se ha observado un aumento de infecciones... more Resumen Durante la pandemia mundial por el coronavirus, se ha observado un aumento de infecciones por herpesvirus en pacientes con COVID-19. Describimos 3 pacientes con presentaciones clínicas atípicas de infección por virus herpes. En dos de ellos se demostró la presencia de varios miembros de la familia Herpesviridae en la misma lesión cutánea, y en el otro encontramos la coexistencia del virus del herpes simple y el de la varicela zoster. Estas coexistencias son hallazgos altamente infrecuentes y escasamente descritos en la literatura. Todos nuestros pacientes presentaban linfopenia. Dado que la infección por el virus SARS-CoV-2 característicamente produce linfopenia, nos planteamos si la COVID-19 puede juega algún papel como factor de predisposición a las infecciones por herpesvirus.

Actas Dermo-Sifiliográficas, Mar 1, 2012

In this article, we review some of the artifacts commonly observed in biopsies and the methods us... more In this article, we review some of the artifacts commonly observed in biopsies and the methods used to prevent their appearance. We describe the basic techniques for taking biopsies of melanocytic lesions, bullous diseases, and from special areas such as the scalp and nail region. We also provide a brief summary of the role of skin biopsy in the diagnosis of neurological diseases and prenatal diagnosis. The aim of this guide is to improve the diagnostic yield of biopsies and to highlight the importance of a correct clinical-histological correlation; we therefore provide clues to the interpretation of the dermatopathology report.

An increased risk of infections has been observed in dermatological patients with immune-mediated... more An increased risk of infections has been observed in dermatological patients with immune-mediated inflammatory diseases under immunosuppressive treatments. Some of these treatments (Interleukin [IL]-23 and IL-17 inhibitors) present a better and safer profile than others (methotrexate, cyclosporine or anti-tumor necrosis factor). The appearance of the coronavirus disease-19 (COVID-19) pandemic has raised serious doubts about their continuation, because they may increase the susceptibility to infections or even worsen the course of SARS-CoV-2 infection itself. Therefore, preventive measures, such as adequate vaccination schedules, are crucial to properly manage these patients. In this review, we discuss the evidence on immunosuppressive treatment in different autoimmune skin diseases, their risk of infections, preventive measures associated to the vaccination status and their impact on patients during COVID-19 infection. Articles reviewed were obtained through searches of relevant databases (PUBMED, MEDLINE, ETHERIA).

Actas Dermo-Sifiliográficas, Sep 1, 2014

American Journal of Dermatopathology, Oct 1, 2019

INTRODUCTION Morbihan disease (MORD) is rare with only 45 clear-cut cases previously reported. Hi... more INTRODUCTION Morbihan disease (MORD) is rare with only 45 clear-cut cases previously reported. Histopathologic findings are supposed to be nonspecific. We report 14 patients and review the previous cases. OBJECTIVES To characterize the clinicopathologic findings, outcomes, and immunophenotype of MORD. MATERIAL AND METHODS Inclusion criteria were a clinical picture of persistent, nonpitting edema affecting the mid and or upper third of the face and histopathological findings fitting previous reports and exclusion of other entities. RESULTS The majority of our patients were males (71.5%) with a male/female ratio of 10/4. The mean age when diagnosed was 58.8 years. Eyelids and forehead were the most frequently involved areas. Two of the patients presented previous rosacea. Most constant histopathological findings were lymphatic vessel dilatations in the upper dermis and the presence of mast cells (7.5 in 10 high-power field as a mean). Mild edema was also present in most of the cases. Granulomas were found in 7 of the cases, and immunostaining with CD68 and CD14 only revealed an additional case. CONCLUSIONS MORD occurs more in middle-aged males, not associated with rosacea and mostly affects eyelids and forehead. Granulomas are not mandatory for the diagnosis. Histopathology of MORD fits within the spectrum of localized lymphedema.

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Actas Dermo-Sifiliográficas, Jun 1, 2023

American Journal of Dermatopathology, Aug 1, 2013

Journal of Personalized Medicine, Sep 4, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Journal der Deutschen Dermatologischen Gesellschaft, Jul 1, 2018

Spontane Besserung einer sekundären Cutis verticis gyrata bei Akromegalie nach chirurgischer Rese... more Spontane Besserung einer sekundären Cutis verticis gyrata bei Akromegalie nach chirurgischer Resektion des Hypophysenadenoms Spontaneous improvement of cutis verticis gyrata secondary to acromegaly following surgical treatment of pituitary adenoma

Actas Dermo-Sifiliográficas, May 1, 2012

Actas Dermo-Sifiliográficas, Jun 1, 2021

BACKGROUND Fibrous hamartoma of infancy (FHI) is a rare soft-tissue tumor usually seen in infants... more BACKGROUND Fibrous hamartoma of infancy (FHI) is a rare soft-tissue tumor usually seen in infants and young children. Histologically, the tumor is characterized by a triphasic morphology, and the clinical course is benign. METHODS We described the histopathologic and immunohistochemical features in a series of 21 cases of FHI and reviewed the main entities to consider in differential diagnosis. RESULTS Most patients in the series were male. The mean age was 3.7 years (range, 5 months-24 years), and lesions were found in locations that have been previously reported. Histopathologically, the tumors were composed of variable proportions of fibroblastic, mesenchymal, and mature adipose tissue. Three of the 13 immunohistochemically stained biopsies (14%) contained hyalinized zones with cracking artifacts, mimicking giant cell fibroblastoma. Eight of the 13 stained with smooth-muscle actin (61%) were positive in the fibroblastic component, 6 of the 8 stained with CD34 (75%) were positive in the immature mesenchymal and fibroblastic components, and all 7 stained with S100 were positive (100%) in adipose tissue. CONCLUSIONS Our histopathologic findings are consistent with those described in larger series. However, in order to reach a precise diagnosis and plan treatment, clinical heterogeneity obliges us to become familiar with variations in the characteristic triphasic histology of FHI.

Dermatologic Therapy, Dec 10, 2020

The ABCD rule has long been proposed as a guidance for malignant melanoma (MM) diagnosis. We aime... more The ABCD rule has long been proposed as a guidance for malignant melanoma (MM) diagnosis. We aimed to define a new simple, straightforward tool that could be useful in early melanoma detection and must be validated in further studies. We conducted a prospective historic cohort study of 200 melanocytic lesions classifying them according to the presence of geometric borders. Sixty-four percent of the MM and 31% of the melanocytic nevi presented with geometric borders. Lesions with two straight borders that formed a noncurvilinear angle presented a 2.1-fold higher risk of being malignant after excision. When comparing melanomas with geometric and nongeometric border, we found a tendency toward better prognostic markers in the geometric lesions. Lesions located in the extremities and melanoma subtype SSM were more common in the geometric group. Regarding pathologic features, a deeper Breslow (mean, 3.8 vs 1.4 mm), presence of ulceration (25% vs 5%) and a higher number of mitosis was found in the nongeometric group. On the other hand, more regression was found in the geometric group while both groups showed similar degree of lymphovascular infiltration. We propose geometric border as another clinical criterion to take into account when suspecting MM, which must be validated in further studies. The ABCDE rule could be completed with a G for geometry.

Dermatologic Therapy, Aug 18, 2022

Scientific Reports, Jul 16, 2021

The interplay between T cells, dendritic cells and keratinocytes is crucial for the development a... more The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and dendritic cells and GADD45a links DNA repair and epigenetic regulation through its demethylase activity. Here, we analyzed the expression of GADD45a and GADD45b in the skin, dendritic cells and circulating T cells in a cohort of psoriasis patients and their regulation by inflammatory signals. Thirty patients (17 male/13 female) with plaque psoriasis and 15 controls subjects (7 male/8 female), were enrolled. Psoriasis patients exhibited a lower expression of GADD45a at the epidermis but a higher expression in dermal infiltrating T cells in lesional skin. The expression of GADD45a and GADD45b was also higher in peripheral T cells from psoriasis patients, although no differences were observed in p38 activation. The expression and methylation state of the GADD45a target UCHL1 were evaluated, revealing a hypermethylation of its promoter in lesional skin compared to controls. Furthermore, reduced levels of GADD45a correlated with a lower expression UCHL1 in lesional skin. We propose that the demethylase function of GADD45a may account for its pleiotropic effects, and the complex and heterogeneous pattern of expression observed in psoriatic disease. Growth Arrest and DNA Damage-inducible proteins, namely GADD45a, GADD45b and GADD45g are small proteins of 18-20 kDa molecular weight. These proteins exert their functions by protein-protein interactions both in the nucleus and the cytoplasm, and are involved in DNA repair, cell proliferation, survival and differentiation among other biological processes 1. GADD45 family members are associated with stress responses through the stimulation of p38-JNK mitogen-activated protein kinases (MAPK) that mediate important functions in both innate and adaptive immune cells. In T cells, T cell receptor (TCR) engagement induces GADD45b and GADD45g expression, promoting a sustained p38 activation and subsequently, leading to IFN-γ production and Th1 differentiation 2,3. In T cells, GADD45b is also induced in response to the pro-inflammatory cytokines IL-12 and IL-18 4. In contrast to GADD45b and GADD45g, GADD45a is expressed in resting T cells. GADD45a has been shown to inhibit the alternative p38 activation pathway, since T cells from GADD45adeficient displayed constitutive p38 activation 5. Regarding the innate immune system, dendritic cells (DCs) from

British Journal of Dermatology, Jan 28, 2018

It has recently been discovered that epigenetic modifications, specially DNA methylation, partici... more It has recently been discovered that epigenetic modifications, specially DNA methylation, participates in the pathology of psoriasis. DNA methylation is a covalent modification dynamic and heritable that takes place in Cytosine-Phosphate-Guanine (CpG) sites and may exert transcriptional effects. Although anti-tumour necrosis factor α (TNF) therapies (adalimumab, etanercept and infliximab) are efficient drugs for moderate-to-severe psoriasis, around 30–50% of psoriasis patients present an inadequate response. This article is protected by copyright. All rights reserved.

Journal of Cutaneous Pathology, Nov 7, 2021

Background: Chronic graft-versus-host disease (GVHD) may present with various cutaneous manifesta... more Background: Chronic graft-versus-host disease (GVHD) may present with various cutaneous manifestations. Isolated case reports describe eruptive angiomas in this setting. Objective: We sought to provide a clinical and pathologic description of vascular proliferations in patients with GVHD.

Actas Dermo-Sifiliográficas, Jul 1, 2015

Introduction: The therapy of patients with psoriasis and liver disease can be a challenge due to ... more Introduction: The therapy of patients with psoriasis and liver disease can be a challenge due to the increased risk of adverse effects from traditional systemic treatments; in addition, although the anti-tumor necrosis factor agents are considered safer, they have also been associated with drug-induced liver injury and reactivation of viral hepatitis. Ustekinumab has a different mechanism of action and the little that is known of its effects on the liver comes from pivotal studies. The objectives of this study were to estimate the incidence of drug-induced liver injury in patients treated with ustekinumab in daily clinical practice and to analyze liver alterations in those patients with pre-existing liver disease. Method: All patients treated with the standard regimen of ustekinumab were included in the study. Variables gathered included age, sex, type of psoriasis, nail involvement, arthritis, previous treatments, history of liver disease, viral serology, Psoriasis Area Severity Index (at baseline and at 12, 16, and 52 weeks), transaminase levels, manifestations of liver disease, liver ultrasound, and factors such as body mass index, alcohol consumption, and ferritin levels. Results: Grade 1 elevation of the transaminases was only observed in 6 patients; no cases of severe hypertransaminasemia were observed. None of the patients with elevation of the transaminases at baseline developed problems during treatment. Conclusions: Ustekinumab-related liver injury is uncommon and mild. From a hepatic point of view, the drug appears safe, even in patients with pre-existing liver disease and those who have developed altered liver function previously with other drugs.

Journal of the European Academy of Dermatology and Venereology

BackgroundTildrakizumab (TIL) is an interleukin (IL)‐23p19 inhibitor for the treatment of moderat... more BackgroundTildrakizumab (TIL) is an interleukin (IL)‐23p19 inhibitor for the treatment of moderate‐to‐severe plaque psoriasis with long‐term efficacy and safety demonstrated in Phase III trials. Studies conducted in conditions closer to clinical practice are needed.ObjectivesThe TRIBUTE study (open‐label, Phase IV) assessed the efficacy and impact on health‐related quality of life (HRQoL) of TIL 100 mg in adult moderate‐to‐severe psoriasis patients (naïve to IL‐23/Th17 pathway inhibitors) in conditions similar to clinical practice.MethodsKey efficacy measure was Psoriasis Area Severity Index (PASI). HRQoL was evaluated using the Dermatology Life Quality Index (DLQI) and Skindex‐16. Additional patient‐reported outcomes included Pain‐, Pruritus‐ and Scaling‐Numerical Rating Scale (NRS), Medical Outcome Study (MOS)‐Sleep, Work Productivity and Activity Impairment (WPAI), Patient Benefit Index (PBI) and Treatment Satisfaction Questionnaire for Medication (TSQM).ResultsOne hundred and se...

Acta Dermato Venereologica

Biological drugs targeting tumour necrosis factor are effective for psoriasis. However, 30-50% of... more Biological drugs targeting tumour necrosis factor are effective for psoriasis. However, 30-50% of patients do not respond to these drugs and may even develop paradoxical psoriasiform reactions. This study search-ed for DNA copy number variations that could predict anti-tumour necrotic factor drug response or the appearance of anti-tumour necrotic factor induced psoriasiform reactions. Peripheral blood samples were collected from 70 patients with anti-tumour necrotic factor drug-treated moderate-to-severe plaque psoriasis. Samples were analysed with an Illumina 450K methylation microarray. Copy number variations were obtained from raw methylation data using conumee and Chip Analysis Methylation Pipeline (ChAMP) R packages. One copy number variation was found, harbouring 1 gene (CPM) that was significantly associated with adalimumab response (Bonferroni-adjusted p-value < 0.05). Moreover, 1 copy number variation was identified harbouring 3 genes (ARNT2, LOC101929586 and MIR5572) related to the development of paradoxical psoriasiform reactions. In conclusion, this study has identified DNA copy number variations that could be good candidate markers to predict response to adalimumab and the development of anti-tumour necrotic factor paradoxical psoriasiform reactions.

Journal of IMIDs