Search Results (2,751)

Dermatomyositis (DM) is a prototypic idiopathic inflammatory myopathy in which characteristic skin disease frequently precedes or parallels muscle involvement and signals risks such as interstitial lung disease (ILD) and malignancy. This literature review integrates recent advances across dermatology, neuromuscular medicine, and immunology to refine diagnosis and management. We surveyed the literature from 2000 to 2025, prioritizing randomized trials, large cohorts, and translational studies that spanned classic and juvenile DM, amyopathic/hypomyopathic variants, and overlap phenotypes. Key insights include the diagnostic weight of pathognomonic cutaneous lesions with nailfold microangiopathy; the utility of myositis-specific autoantibodies for endotyping and risk (e.g., anti-TIF1-γ/anti-NXP2 and cancer, anti-MDA5 and rapidly progressive ILD); and the value of myxovirus-resistance protein A (MxA) immunohistochemistry and muscle MRI patterning (including distinctions from immune-mediated necrotizing myopathy) when enzymes are normal, or biopsies are treatment-modified. Management is anchored in early steroid-sparing immunosuppression tailored to phenotype, with evidence for IVIG in active DM and growing support for JAK inhibition, particularly in interferon-high or anti-MDA5 ILD, alongside selective use of calcineurin inhibitors and rituximab, with plasma exchange considered for refractory, rapidly progressive ILD. We highlight risk-stratified malignancy screening (IMACS 2023) and complications, including calcinosis, lipodystrophy, and chronic cutaneous damage. Skin-led recognition coupled with antibody-guided, phenotype-directed therapy and interdisciplinary care offers a pragmatic precision framework to improve outcomes and reduce long-term disability. Full article

Background: Liver transplant recipients are highly susceptible to invasive fungal infections, particularly candidemia, due to intensive immunosuppressive therapy and postoperative complications. However, few studies have comprehensively examined postoperative antimicrobial and immunosuppressive factors in this context. Aim: This study aimed to identify perioperative and postoperative factors associated with the development of candidemia in living donor liver transplant (LDLT) recipients, with a particular focus on antimicrobial and immunosuppressive regimens during initial hospitalization. Methods: A retrospective case–control analysis was conducted involving 36 LDLT recipients who developed candidemia (candidemia group) and 72 matched controls without candidemia (non-candidemia group) between January 2019 and November 2023. Demographic and clinical variables were compared using univariate and multivariate logistic regression analyses to identify independent associations. A post hoc power analysis demonstrated a high statistical power (97.3%) to detect large effect sizes. Results: Univariate analysis revealed significant associations with prolonged intubation (p < 0.001), bile leaks (p < 0.001), relaparotomy (p < 0.001), chronic renal disease (p = 0.011), hepatocellular carcinoma (p = 0.011), and the use of antimicrobials including meropenem (p = 0.048), linezolid (p = 0.005), tigecycline (p = 0.045), third-generation cephalosporins (p = 0.003), anidulafungin (p < 0.001), fluconazole (p = 0.006), mycophenolate (p = 0.011), and total parenteral nutrition (TPN) (p = 0.049). CMV prophylaxis (p < 0.001) and CMV-PCR positivity (p = 0.015) were also significantly associated with candidemia. Multivariate logistic regression analysis identified prolonged intubation (OR = 1.07; p = 0.019), bile leaks (OR = 10.9; p = 0.002), anidulafungin use (OR = 4.70; p = 0.032), fluconazole use (OR = 35.8; p = 0.005), and absence of CMV prophylaxis (OR = 11.7; p = 0.021) as independent factors associated with increased odds of candidemia. Conclusions: Prolonged intubation, bile leaks, antifungal exposure, and lack of CMV prophylaxis are independently associated with higher odds of candidemia after LDLT. Targeted prophylaxis, prudent antimicrobial stewardship, and timely biliary intervention may reduce fungal morbidity and mortality in post-transplant patients. Full article

Pure membranous lupus nephritis (pMLN, ISN/RPS-class V) is a rare form of lupus nephritis (LN). Despite being associated with significant comorbidities, it has traditionally been considered a less aggressive subtype. Emerging data challenges this perception, highlighting its potential for chronic kidney disease progression and kidney failure. pMLN is pathologically defined by subepithelial immune-complex deposits and typically presents with nephrotic syndrome, preserved renal function, and fewer systemic/immunologic manifestations compared to proliferative LN (ISN/RPS-classes III/IV). Repeat biopsies reveal frequent histological class switching from pMLN to proliferative and mixed LN forms, underscoring the dynamic nature of the disease and the limitations of clinical markers in reflecting histological activity. While the ISN/RPS kidney biopsy classification provides important prognostic insight, it does not fully capture underlying molecular heterogeneity. Recent advances in precision medicine, including proteomic and biomarker studies (e.g., EXT1/2, NCAM1), offer promising tools for patient stratification and tailored treatments. International guidelines now recommend immunosuppressive therapy for pMLN, aligning treatment strategies more closely with those for proliferative and mixed LN. Overall, pMLN should be considered a distinct but clinically relevant LN subtype requiring personalized management based on clinical, histological and molecular features. Long-term monitoring is essential, as baseline presentation does not reliably predict treatment response or disease trajectory. Full article

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetically determined disorders that lead to immune dysfunction, recurrent infections, and organ-specific complications. The lungs are among the most commonly affected organs, with both infectious and noninfectious manifestations that significantly contribute to morbidity and mortality. This study aimed to provide a comprehensive overview of pulmonary manifestations in IEI, with emphasis on pathophysiological mechanisms, diagnostic approaches, and therapeutic strategies. Methods: A narrative review and synthesis of current literature and clinical guidelines were conducted, focusing on pulmonary involvement in IEI as classified by the International Union of Immunological Societies (IUIS). The analysis included data on infectious and noninfectious complications, imaging findings, immunological assessments, and management strategies, supported by clinical evidence and expert consensus. Results: Pulmonary manifestations in IEI encompass a wide spectrum of conditions. Infectious complications include recurrent bacterial pneumonias, bronchitis, and opportunistic infections, frequently resulting in irreversible lung damage such as bronchiectasis. Noninfectious complications, including granulomatous–lymphocytic interstitial lung disease (GLILD) and interstitial lung disease (ILD), are common in disorders such as common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA). Early diagnosis using high-resolution computed tomography (HRCT) and immunological testing, combined with the timely initiation of immunoglobulin replacement therapy and anti-biotic prophylaxis, significantly improves prognosis. Conclusions: Pulmonary complications are key clinical indicators of IEI and often precede systemic manifestations. Early, integrated, and interdisciplinary diagnostic and therapeutic management are crucial for preventing irreversible lung damage and improving patient outcomes. Regular monitoring and individualized therapy, including immunoglobulin replacement, targeted immunosuppression, and vaccination, are the cornerstones of effective long-term care in IEI. Full article

Procellariiformes are among the most threatened seabirds globally, yet viral pathogens affecting this group remain poorly understood. Herpesviruses are widespread in birds and capable of establishing latency, reactivating under immunosuppression, and causing severe disease, particularly in cross-species transmission. We surveyed herpesvirus in 50 individuals (12 species) that stranded along the southeastern Brazilian coast (2017–2023). A nested pan-PCR protocol targeting the DNA polymerase gene detected herpesvirus DNA in 24% (12/50) of the birds. Seven distinct herpesvirus sequence types were identified, all clustering within the genus Mardivirus, including two previously known variants and novel lineages. To our best knowledge, this represents the first herpesvirus report in the Black-browed Albatross (Thalassarche melanophris), Cape Verde Shearwater (Calonectris edwardsii), Manx Shearwater (Puffinus puffinus), and Southern Giant-Petrel (Macronectes giganteus), as well as new host reports for the Yellow-nosed Albatross (T. chlororhynchos) and Cory’s Shearwater (C. borealis). No associated lesions were observed in histopathology. Our findings expand the known host range of herpesviruses in Procellariiformes and reveal possible circulation among colonies and non-breeding areas across the Southern and Northern hemispheres. Our results underscore the need for integrative ecological-, virological-, and population-based studies to clarify how seabird ecology influences herpesvirus transmission dynamics and long-term persistence in this group. Full article

Background: The development of anti-drug antibodies (ADAs) and resulting immune complexes are key mechanisms behind the secondary loss of response to adalimumab in Crohn’s disease (CD). Despite their clinical importance, routine immunogenicity assays are limited, underscoring the need for alternative predictive approaches. Objective: This study aimed to develop interpretable artificial neural network (ANN) models to predict immune complex formation and estimate serum adalimumab levels using routinely available clinical and laboratory data from CD patients. Methods: A prospective analysis was performed on 58 CD patients on maintenance adalimumab. Immune complexes and serum adalimumab were measured via ELISA and lateral flow assays. ANN and ensemble regression models were trained on demographic, clinical, and inflammatory data, with performance evaluated by five-fold cross-validation. Interpretability was enhanced using Garson’s algorithm and permutation importance. Results: The ANN-based classification model accurately predicted ADA immune complex formation, achieving an accuracy of 77.47% and an area under the curve (AUC) of 82.63%. The main predictive variables included extraintestinal manifestations, perianal disease, disease behavior, and age at diagnosis. For estimating serum adalimumab levels measured by ELISA, the model performed modestly (accuracy 59.89%, AUC 79.72%), incorporating factors such as Montreal classification, perianal disease, C-reactive protein, immunosuppressant use, and disease duration. Conclusions: Interpretable ANN models robustly predict anti-adalimumab immune complexes and, to a lesser extent, serum adalimumab, using clinically available data, including perianal disease. This proof-of-concept study is limited by the relatively small, single-center dataset (n = 58), which may affect model generalizability and increase the risk of overfitting. External validation in larger and multicenter cohorts is required before clinical implementation. Full article

Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by the destruction of insulin-producing pancreatic β-cells by autoreactive T cells. Current treatments, including insulin replacement therapy and various immunotherapies, often modulate but fail to permanently halt the underlying autoimmune process or restore β-cell function. In this review, we examine T cell receptor (TCR)-based treatment strategies for T1DM. We focus on two main approaches: selective elimination of pathogenic autoreactive T cell clones and induction of immune tolerance using TCR-modified regulatory T cells (TCR-Tregs). We describe key islet autoantigens, including post-translationally modified neoantigens such as fusion insulin peptides, which are crucial for identifying pathogenic TCRs. Next, we will review methodologies for TCR detection and TCR-Treg generation, highlighting their mechanisms of action and impact on various immune cells, including dendritic cells, B cells, and macrophages. We will also examine the potential of CD8⁺T cell regulatory cells (CD8⁺Tregs). Finally, we will discuss the future of TCR-based therapy, emphasizing the need to optimize TCR affinity, ensure Tregs’ stability, and develop combination therapies. TCR-based therapy represents a revolutionary approach to restoring immune tolerance in T1DM, providing high specificity and reducing the risk of systemic immuno-suppression compared to traditional treatments. Full article

Atopic dermatitis is the most prevalent chronic inflammatory skin disease, posing a significant individual and healthcare burden. Traditionally managed with topical agents and broad immunosuppressants, the treatment landscape has shifted significantly in recent years. This review explores the transition from immunopathogenic understanding to personalized treatment strategies through advanced systemic therapies. We provide a thorough description of the current therapeutic arsenal, including approved monoclonal antibodies and Janus kinase (JAK) inhibitors, as well as experimental agents under clinical investigation. Key cytokines and receptors implicated in type 2 inflammation are explored alongside relevant intracellular signaling pathways. Special attention has been given to literature published from 2015 onwards. By synthesizing the latest scientific and clinical knowledge, this review aims to provide clinicians with practical guidance for navigating the evolving landscape of atopic dermatitis management and improving patient outcomes. Full article

Beta-arrestin 1 (ARRB1) is a multifunctional adaptor protein that regulates diverse signaling pathways beyond its canonical role in G-protein-coupled receptor desensitization. While ARRB1 has been implicated in cancer progression, its role in modulating host immunity against multiple myeloma (MM) remains unexplored. Here, we demonstrate that host ARRB1 deficiency significantly enhances anti-myeloma immunity and prolongs survival in a syngeneic murine MM model. Using Vk*MYC myeloma cells transplanted into wild-type and ARRB1 knockout mice, we show that ARRB1 deficiency in the host microenvironment promotes robust T cell infiltration and activation while reducing immunosuppressive myeloid populations. Notably, ARRB1 knockout mice exhibited markedly decreased programmed cell death protein-1 (PD-1) expression on both T cells and myeloid-derived suppressor cells, indicating reduced immune exhaustion. Furthermore, ARRB1 deficiency conferred protection against myeloma-induced bone disease, suggesting a dual role in immune regulation and bone homeostasis. These findings establish ARRB1 as a critical negative regulator of host anti-myeloma immunity and identify it as a potential therapeutic target for enhancing immunotherapy efficacy in MM. Full article

Birt–Hogg–Dubé Syndrome (BHDS) is a rare autosomal dominant disorder associated with mutations in the Foliculin gene (FLCN), characterized by skin lesions, renal tumors (often malignant or leading to malignancy), and lung cysts, often leading to spontaneous pneumothorax. Lung function is generally preserved in these patients, which is why lung transplantation (LTx) has not been performed in this population to date. Below, we present the case of a 15-year-old boy with BHDS, with extensive cystic lung disease, complicated by recurrent pneumothorax (requiring pleurodesis) and, in his case, progressive respiratory failure, who ultimately underwent double sequential lung transplantation (DLTx). Postoperative management included treatment of humoral rejection and treatment of SARS-CoV-2 infection, in addition to typical immunosuppression. To our knowledge, this is the first DLTx for BHDS reported worldwide. The patient underwent a double lung transplant due to a life-threatening recurrent pneumothorax. This case highlights the importance of multidisciplinary care and demonstrates the feasibility of transplantation in advanced cases of BHDS (despite prior pleurodesis). Full article

Background/Objectives: The rising global prevalence of inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, has resulted in an increase in the number of affected patients requiring dental care. The heightened risk of Clostridioides difficile infection (CDI) in IBD patients, particularly when exposed to commonly used dental antibiotics, is attributable to their altered gut microbiota and frequent immunosuppressive therapy. The objective of this review is to evaluate current antibiotic strategies for dental management in IBD and to identify safe and effective alternatives that minimise CDI risk. Methods: A narrative review was conducted in accordance with the SANRA guidelines. A comprehensive analysis of literature sourced from PubMed, Embase, Scopus, and Google Scholar was conducted. Results: The available evidence suggests that first- and second-line dental antibiotics—amoxicillin, ampicillin, and clindamycin—carry the highest risk of CDI. In contrast, metronidazole, which exhibits a comparable antimicrobial spectrum, has been shown to possess significantly reduced CDI potential and minimal disruption of gut microbiota. The utilisation of emerging local delivery systems, such as platelet-rich fibrin (PRF), has the potential to further reduce systemic antibiotic exposure. The adjunctive use of probiotics, prebiotics and synbiotics has been demonstrated to have the capacity to maintain microbial balance during therapy. Conclusions: Tailored, microbiome-conscious antibiotic strategies are essential in dental management of IBD patients. Further clinical research is needed to develop evidence-based guidelines and validate promising adjunctive approaches. Full article

We present a case report of invasive fungal infection in an immunocompromised host, which required a multidisciplinary approach. Mucormycosis is a mold infection caused by a fungi belonging to the order Mucorales. Various forms of the disease have been described, and rhino-orbital-cerebral infection is the most common manifestation. Diabetes, corticosteroid use, malignancy, and a recent history of COVID-19 are well-established immunosuppressive factors that predispose individuals to mucormycosis. Our patient was a forty-five-year-old man with chronic pancreatitis and untreated diabetes mellitus. He presented with sinusitis extending into the right orbit and complicated by central retinal artery occlusion. On admission, the patient complained of three weeks of right-sided headache and eye pain followed by sudden vision loss. He was in good general condition, was alert, oriented, and afebrile. Endoscopic examination revealed the nasal cavity completely filled with pathological tissue displaying fungal morphology. Computed tomography and magnetic resonance imaging revealed a massive orbit infiltration with extraocular muscles and optic nerve invasion. The patient underwent urgent endoscopic debridement. Histopathological examination of the specimens confirmed fungal infiltration. Significant growth of Rhizopus arrhizus was obtained from tissue samples. The surgical procedure was followed by a prolonged antifungal therapy with intensive diabetes management. Full article

Background: Psoriasis is a chronic inflammatory skin disease driven by keratinocyte hyperproliferation and immune dysregulation. Despite the availability of biologics and immunosuppressants, recurrence and adverse effects remain major limitations. Myricetin (Myr), a natural flavonoid with well-documented anti-inflammatory and immunomodulatory properties, has shown promise in inflammatory disorders; however, its efficacy and mechanisms in psoriasis have not been fully elucidated. Methods: The therapeutic effects of topical Myr (0.5–2%) were evaluated in an imiquimod (IMQ)-induced psoriatic mouse model. Network pharmacology and molecular docking were employed to predict potential targets, followed by validation using histological analysis, cytokine profiling, qPCR, and Western blotting. Results: Network analysis identified 52 overlapping targets between Myr and psoriasis, including TNF, PTGS2, MMP9, and EGFR, with enrichment in TNF, IL-17, and PI3K/AKT signaling pathways. Myr treatment significantly alleviated IMQ-induced erythema, scaling, and epidermal thickening, improved skin-barrier function, and reduced the expression of IL-6, IL-17A, and TNF-α. Molecular docking showed strong binding affinities of Myr with TNF, PTGS2, MMP9, and EGFR. Western blotting confirmed that Myr suppressed EGFR and AKT phosphorylation and downregulated Mmp9, Ptgs2, and Tnf expression. Conclusions: Myr exerts multi-target anti-psoriatic effects by inhibiting the EGFR/AKT axis and inflammatory mediators, highlighting its potential as a safe and effective natural therapeutic agent for psoriasis. Full article

Background: Aspergillus endocarditis is a rare but life-threatening form of infective endocarditis that typically occurs in patients with a history of cardiac surgery, prosthetic valve implantation, or profound immunosuppression. Native valve involvement in non-traditional hosts remains exceptionally rare and is diagnostically challenging. Case presentation: We describe a 56-year-old woman with CREST syndrome and advanced liver disease awaiting transplantation who developed native aortic valve endocarditis. Blood cultures and serum biomarkers (galactomannan and β-d-glucan) were also negative. Transthoracic echocardiography revealed vegetation on the aortic valve. Valve replacement was performed, and Aspergillus fumigatus was isolated from two valve cultures. Liposomal amphotericin B was initiated; however, the patient died of multiorgan failure two weeks later. Systematic review: To contextualise this case, we conducted a systematic review of the literature following the PRISMA guidelines. We included microbiologically confirmed cases of native valve Aspergillus endocarditis based on valve or embolic tissue analysis. Forty-three studies met the inclusion criteria, comprising 45 patients in total. Data were independently extracted by two reviewers and narratively synthesised due to clinical heterogeneity. Conclusions: This case illustrates the diagnostic and therapeutic challenges of native-valve Aspergillus endocarditis in patients without classical risk factors for the disease. Early imaging and a high index of suspicion are crucial for diagnosis. Combined surgical and antifungal therapy remains the cornerstone of management, although the mortality rate remains high. Full article

Diagnosis and treatment of acute exacerbation of interstitial lung disease (AE-ILD) continue to be challenging. The annual incidence of AE in idiopathic pulmonary fibrosis (IPF) is 5% to 15%, with an in-hospital mortality exceeding 50%. Similar annual incidence and mortality rates have been documented in other ILDs. The pathogenic mechanisms underlying AE are not entirely clear, although they could involve an acute injury or inflammatory process in previously affected lung tissue, with histological features of diffuse alveolar damage, similar to acute respiratory distress syndrome. AE-ILD is defined based on the following criteria: acute respiratory worsening within 30 days in a patient with a previous or concurrent diagnosis of ILD accompanied by new bilateral ground-glass abnormalities and/or consolidation on high-resolution computed tomography after ruling out heart failure or fluid overload. Pharmacologic treatments such as corticosteroids, antibiotics, and immunosuppressants have been and continue to be used despite scarce evidence from randomized placebo-controlled clinical trials. Oxygen therapy and ventilatory support are key elements of treatment of AE-ILD. The aim of our article is to provide an updated review on the diagnosis and treatment of AE-ILD and to propose practical algorithms for management. Full article