Allergen sensitization stratifies IL-31 production by memory T cells in atopic dermatitis patients

Background:The role of allergen sensitization in IL-31 production by T cells and specifically in the clinical context of atopic dermatitis (AD) has not been characterized. MethodsThe response to house dust mite (HDM) in purified memory T cells cocultured with epidermal cells from AD patients (n=58) and control subjects (n=11) was evaluated. AD-associated cytokines from culture supernatants, plasma proteins and mRNA expression from cutaneous lesions were assessed and related with the clinical features of the patients. ResultsHDM-induced IL-31 production by memory T cells defined two subsets of AD patients according to the presence or absence of IL-31 response. Patients in the IL-31 producing group showed a more inflammatory profile, and increased HDM-specific (sp) and total IgE levels compared to the IL-31 non-producing group. A correlation between IL-31 production and patient's pruritus intensity, plasma CCL27 and periostin was detected. When the same patients were analyzed based on sp IgE and total IgE levels, an increased IL-31 in vitro response, as well as type 2 markers in plasma and cutaneous lesions, was found in patients with sp IgE levels > 100 kUA/L and total IgE levels > 1000 kU/L. The IL-31 response by memory T cells was restricted to the cutaneous lymphocyte-associated antigen (CLA)(+) T-cell subset. ConclusionIgE sensitization to HDM allows stratifying IL-31 production by memory T cells in AD patients and relating it to particular clinical phenotypes of the disease

Genetics Abnormalities with Clinical Impact in Primary Cutaneous Lymphomas

Primary cutaneous lymphomas comprise a heterogeneous group of extranodal non-Hodgkin lymphomas (NHL) that arise from skin resident lymphoid cells and are manifested by specific lymphomatous cutaneous lesions with no evidence of extracutaneous disease at the time of diagnosis. They may originate from mature T-lymphocytes (70% of all cases), mature B-lymphocytes (25-30%) or, rarely, NK cells. Cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of T-cell malignancies including Mycosis Fungoides (MF) the most frequent subtype, accounting for approximately half of CTCL, and Sézary syndrome (SS), which is an erythrodermic and leukemic subtype characterized by significant blood involvement. The mutational landscape of MF and SS by NGS include recurrent genomic alterations in the TCR signaling effectors (i.e., PLCG1), the NF-κB elements (i.e., CARD11), DNA damage/repair elements (TP53 or ATM), JAK/STAT pathway elements or epigenetic modifiers (DNMT3). Genomic copy number variations appeared to be more prevalent than somatic mutations. Other CTCL subtypes such as primary cutaneous anaplastic large cell lymphoma also harbor genetic alterations of the JAK/STAT pathway in up to 50% of cases. Recently, primary cutaneous aggressive epidermotropic T-cell lymphoma, a rare fatal subtype, was found to contain a specific profile of JAK2 rearrangements. Other aggressive cytotoxic CTCL (primary cutaneous γδ T-cell lymphomas) also show genetic alterations in the JAK/STAT pathway in a large proportion of patients. Thus, CTCL patients have a heterogeneous genetic/transcriptional and epigenetic background, and there is no uniform treatment for these patients. In this scenario, a pathway-based personalized management is required. Cutaneous B-cell lymphoma (CBCL) subtypes present a variable genetic profile. The genetic heterogeneity parallels the multiple types of specialized B-cells and their specific tissue distribution. Particularly, many recurrent hotspot and damaging mutations in primary cutaneous diffuse large B-cell lymphoma of the leg type, involving MYD88 gene, or BCL6 and MYC translocations and BLIMP1 or CDKN2A deletions are useful for diagnostic and prognostic purposes for this aggressive subtype from other indolent CBCL forms

Carga de la psoriasis en Cataluña : datos epidemiológicos, comorbilidades asociadas, uso de recursos sanitarios e incapacidad laboral

Disponer de datos epidemiológicos y de carga de una enfermedad es crucial para su control y óptima planificación. El objetivo es estimar la carga de la psoriasis en términos epidemiológicos, las comorbilidades asociadas, el uso de recursos sanitarios y la incapacidad laboral. Se han analizado los datos de la encuesta de salud de Cataluña (ESCA) del 2016, el registro de morbilidad y utilización de servicios sanitarios de Cataluña (MUSSCAT) del 2016 y los datos recopilados entre el 2012 y el 2016 del sistema integrado de gestión de la incapacidad temporal (IT) del Instituto Catalán de Evaluaciones Médicas. La prevalecía de la psoriasis en Cataluña con base en los datos de la ESCA se sitúa en el 1,8%. Los datos del MUSSCAT muestran que el número de casos incidentes se ha mantenido estable en los últimos años. Las comorbilidades más frecuentes en el paciente con psoriasis son la hipertensión arterial (35%) y la diabetes (15%). La estratificación de la población con psoriasis por niveles de riesgo situó al 40% en riesgo moderado-alto. El uso anual de recursos sanitarios de las personas con psoriasis es elevado (8,7 visitas de atención primaria; 2,8 consultas externas; 0,5 de urgencias y hospital de día; 0,2 de salud mental y 6,1 medicamentos). Los procesos de IT asociados con la psoriasis o artropatía psoriásica representaron el 0,04% del total de registros. La prevalencia de la psoriasis en Cataluña es del 1,8%. La carga de la enfermedad es elevada, tanto en términos de comorbilidades del paciente como en el requerimiento del uso de recursos

Allergic contact dermatitis from transdermal buprenorphine.

BACKGROUND: Buprenorphine is a low-molecular-weight, lipophilic, opioid analgesic. The transdermal delivery system (TDS) containing it has skin irritation potential, but at least two cases of contact allergy to the active principal have been described previously. OBJECTIVE: To confirm allergic contact dermatitis from transdermal buprenorphine (TDB) in five older patients suffering from chronic pain and who developed persistent, pruritic erythematous plaques at the contact sites, with two of them also presenting with a generalized skin eruption. METHODS: Besides the baseline patch test series, all five patients were tested with the TDB, four of whom were also tested with the placebo transdermal delivery system as provided by the manufacturer; one patient was also tested with other preparations containing buprenorphine. RESULTS: All reacted to the TDB containing the active principal, the placebo being negative in the four patients tested. The patient tested with the other buprenorphine preparations did react positively to them as well. Tests with TDB in 28 healthy controls were negative. CONCLUSION: We report five cases of delayed hypersensitivity reactions to a TDS containing buprenorphine. Such adverse reactions might be under-reported. A fentanyl-containing TDS is a good alternative in these cases

Basophil FcεRI expression in chronic spontaneous urticaria: A potential immunological predictor of response to omalizumab therapy.

Although the efficacy of omalizumab has been clearly demonstrated in the treatment of chronic spontaneous urticaria (CSU), its mechanism of action, which results in improvement in CSU symptoms, is not entirely understood. This study investigated the effect of omalizumab on expression of the high-affinity IgE receptor (FcεRI) on blood basophils from patients with active CSU, and its association with the clinical response. Patients exhibiting significant clinical improvement showed a sharp reduction in the levels of basophil FcεRI after 4 weeks, which was maintained throughout the total duration of the treatment. Such evolution was not observed in non-responder patients. Furthermore, non-responders showed significantly lower baseline levels of FcεRI than responders. Baseline basophil FcεRI expression was found to be a potential immunological predictor of response to omalizumab (100% sensitivity and 73.2% specificity). The results of this study contribute to our knowledge of the therapeutic benefit and mechanism of action of anti-IgE therapy in CSU

Identification of Gene Mutations and Fusion Genes in Patients with Sézary Syndrome

Sézary syndrome is a leukemic form of cutaneous T-cell lymphoma with an aggressive clinical course. The genetic etiology of the disease is poorly understood, with chromosomal abnormalities and mutations in some genes being involved in the disease. The goal of our study was to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sézary cells, 14 of them fulfilling the diagnostic criteria of Sézary syndrome. We have discovered genes that could be involved in the pathogenesis of Sézary syndrome. Some of the genes that are affected by somatic point mutations include ITPR1, ITPR2, DSC1, RIPK2, IL6, and RAG2, with some of them mutated in more than one patient. We observed several somatic copy number variations shared between patients, including deletions and duplications of large segments of chromosome 17. Genes with potential function in the T-cell receptor signaling pathway and tumorigenesis were disrupted in Sézary syndrome patients, for example, CBLB, RASA2, BCL7C, RAMP3, TBRG4, and DAD1. Furthermore, we discovered several fusion events of interest involving RASA2, NFKB2, BCR, FASN, ZEB1, TYK2, and SGMS1. Our work has implications for the development of potential therapeutic approaches for this aggressive disease

Study of excipients in delayed skin reactions to mRNA vaccines: Positive delayed intradermal reactions to polyethylene glycol provide new insights for COVID-19 arm

Background: Skin local reactions to mRNA COVID-19 vaccines have been linked to the use of vaccine excipients. The aim of the study is to evaluate the role of skin testing excipients in delayed skin reactions due to mRNA COVID-19 vaccines. Methods: Skin testing among a group of healthcare workers with skin reactions due to mRNA vaccines was performed. Patch testing and intradermal testing (IDT) with polyethylene glycol (PEG)-400, PEG-2000, trometamol, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine were performed. Healthcare workers without skin reactions to vaccines were used for skin testing as controls. Results: Thirty-one healthcare workers (from a total of 4315 vaccinated healthcare workers) experienced cutaneous adverse vaccine reactions. Skin testing was performed in sixteen of the healthcare workers (11 delayed large local reactions (DLLR) and 5 widespread reactions). Positive IDT for PEG-2000 1% in DLLR was seen in 10 (90.9%) patients, in comparison with one (16.6%) individual with a delayed widespread reaction. Delayed positive IDT reactions for PEG-2000 1% on day 2 were observed in three (27.3%) patients with DLLR. Patch testing of the excipients was negative. Among 10 controls, only one exhibited a transient positive IDT reaction to PEG-2000 1%. Conclusions: Immediate and delayed reactions to IDT are frequently detected in patients with DLLR. The observation of positive delayed intradermal reactions to PEG disclosed only in patients with DLLR reinforces a possible role of PEG in the development of these reactions. Skin testing of other excipients is of little importance in clinical practice