Hospital Muñiz

Los biológicos anti-interleucina-17 (anti-IL-17) fueron aprobados mediante ensayos clínicos pivotales para pacientes con psoriasis vulgar de moderada-severa y artritis psoriásica. Sin embargo, su indicación en otras variedades de psoriasis menos frecuentes se ha notificado en diversos estudios en el entorno de la vida real. Se presentan cuatro casos de pacientes con variedades especiales de psoriasis tratados con secukinumab con excelentes resultados: tres con psoriasis pustulosas, dentro de las cuales dos formas eran generalizadas y una localizada (acrodermatitis continua de Hallopeau), y un paciente con psoriasis eritrodérmica. En nuestra experiencia, el secukinumab demostró ser eficaz y seguro en estas formas de psoriasis al igual que en las series publicadas previamente en la literatura.

Abstract Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), has evolved strategies to evade innate immunity and establish persistent infection. However, the mechanisms by which M. tuberculosis reprograms human macrophage metabolism remain incompletely defined. Tuberculous pleural effusion (TB-PE), a common extrapulmonary manifestation that frequently coexists with pulmonary TB, offers a unique, clinically relevant immunometabolic window into the TB microenvironment. Here, using patient-derived TB-PE samples, we demonstrate that this microenvironment induces a metabolic state in human macrophages that compromises their antimicrobial function. Lipidomic analysis identified an enrichment of the specialized pro-resolving mediator Resolvin D5 (RvD5), which signals through GPR32 to suppress macrophage microbicidal activity. The acellular fraction of TPE was sufficient to induce RvD5 secretion by monocytes, correlating with increased expression of RvD5 biosynthetic enzymes in pleural monocytes from TB patients. Mechanistically, RvD5-GPR32 signaling inhibited glycolysis without promoting oxidative phosphorylation, reducing HIF-1α activity and impairing intracellular M. tuberculosis control. HIF-1α stabilization restored antimicrobial function. These findings uncover the RvD5-GPR32-HIF-1α axis as a mechanism of metabolic immune suppression and a potential target for host-directed TB therapy. Significance statement Tuberculosis (TB) persists as a global threat because Mycobacterium tuberculosis hijacks host lipid metabolism to subvert immunity. This study investigates how TB-induced host lipids reprogram macrophage metabolism to weaken their antimicrobial activity. We show that tuberculous pleural effusion, a fluid accumulation in the pleural cavity, is enriched with the lipid mediator Resolvin D5 (RvD5). RvD5 impairs macrophage function by blocking glycolysis via the GPR32 receptor, leading to an energy-deficient state that compromises bacteria killing. Remarkably, restoring the metabolic regulator HIF-1α rescues this antimicrobial defect. By revealing a mechanism through which TB exploits host-derived lipids to evade immune control, this work deepens our understanding of infection-induced immune dysfunction and highlights potential therapeutic targets for TB and other infectious diseases.

The stability of messenger RNA (mRNA) is controlled by proteins that bind to adenosine-uridine-rich sequences (AREs) in their 3' untranslated regions (3'UTR), known as AU-binding proteins. One of these proteins is tristetraprolin (TTP; encoded by Zfp36), which promotes degradation of mRNAs with AREs in their 3'UTR. TTP accelerates the decay of its target transcripts, many of which encode proinflammatory mediators that promote tumorigenesis. TTP underexpression has been reported in multiple cancer types. Oral squamous cell carcinoma is an aggressive disease characterized by high morbidity and few therapeutic options. The role of TTP has not been studied in oral epithelium homeostasis nor in its carcinogenesis. Herein, using tissue-specific TTP knockout mice (TTP-KO), we show that TTP expression is relevant for oral epithelium homeostasis. TTP-KO mice developed dysplastic lesions in the tongue along with inflammatory infiltrates in the connective tissue. Analysis of the inflammatory infiltrate revealed the presence of mast cells (MCs), CD45+ cells, and CD11b+ cells, with the MCs being the most abundant cell type and associated with cyclooxygenase-2 expression. Recruitment of MCs was dependent on tumor necrosis factor-α (TNFα) upon TTP ablation in the tongue. Although the infiltration of MCs was dependent on TNFα activity, this did not affect the development of tongue dysplasia. We analyzed the status of the NF-κB pathway, finding its activation. In addition, we demonstrate that K-ras activation combined with Zfp36 deletion leads to the rapid onset of the oral tongue phenotype and significantly reduces mouse survival. Our results support the notion that TTP expression protects against oral carcinogenesis, regulates the inflammatory infiltrate, and maintains the epithelial microenvironment, potentially serving as a barrier to tumorigenesis.

DiHS/DRESS (drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms) syndrome due to antituberculosis drugs is a rare but serious adverse reaction that affects both adults and children and can compromise the success of treatment and ultimately the patient's life. The most frequently associated drug was rifampicin. It is crucial to identify the causative agent(s) early, since the manifestations can progress rapidly and lead to potentially fatal complications, such as multiorgan failure. DiHS/ DRESS is caused by a hypersensitivity reaction to drugs, manifested by fever, adenopathy, rash, eosinophilia and visceral involvement. This heterogeneous syndrome with systemic and potentially fatal involvement must be addressed by a multidisciplinary team. There is no unique protocol for the management of DiHS/DRESS, and in this narrative review we analyze the international literature in light of the accumulated experience in its management in a reference centre for tuberculosis.

Chromoblastomycosis, an implantation mycosis, is a neglected tropical disease that causes decreased quality of life, stigma, and disability. The global burden of disease is unknown and data on disease epidemiology and outcomes are severely limited by a lack of access to needed diagnostic tools and therapeutics. The World Health Organization outlined targets for chromoblastomycosis in the Road Map for Neglected Tropical Diseases 2021-2030, but little progress has been made in initiating and implementing an effective control program globally. This lack of guiding policy and progress led to the recent formation of a Global Chromoblastomycosis Working Group which has developed a global chromoblastomycosis strategy. We describe this strategy, which outlines specific steps needed to improve technical progress, strategy and service delivery, and enablers. Clinicians, researchers, public and government officials, patients, and policy makers can align their time, expertise, and resources to improve the lives of communities affected by chromoblastomycosis through this strategy.

During tuberculosis, migration of dendritic cells (DCs) from the site of infection to the draining lymph nodes is known to be impaired, hindering the rapid development of protective T-cell mediated immunity. However, the mechanisms involved in the delayed migration of DCs during TB are still poorly defined. Here, we found that infection of DCs with Mycobacterium tuberculosis triggers HIF-1α-mediated aerobic glycolysis in a TLR2-dependent manner, and that this metabolic profile is essential for DC migration. In particular, the glycolysis inhibitor oxamate and the HIF-1α inhibitor PX-478 abrogated M. tuberculosis-induced DC migration in vitro to the lymphoid tissue-specific chemokine CCL21, and in vivo to lymph nodes in mice. Strikingly, we found that although monocytes from TB patients are inherently biased toward glycolysis metabolism, they differentiate into poorly glycolytic and poorly migratory DCs, compared with healthy subjects. Taken together, these data suggest that because of their preexisting glycolytic state, circulating monocytes from TB patients are refractory to differentiation into migratory DCs, which may explain the delayed migration of these cells during the disease and opens avenues for host-directed therapies for TB.