Current Opinion in Allergy and Clinical Immunology最新文献

Purpose of review: Liver disease has emerged as a major risk factor for increased mortality in patients with common variable immunodeficiency (CVID). This is mostly due to presinusoidal portal hypertension (PHTN) frequently secondary to nodular regenerative hyperplasia (NRH). Its pathogenesis is still poorly understood and treatment strategies for its various stages are often guided by trial and error. This review summarizes the most recent findings in the light of previous literature.

Recent findings: In the last 2 years, different groups have addressed pathology, diagnostics, treatment, and liver transplantation. Histological examinations seem to support the pathogenetic sequence of T-cell mediated infiltration and damage of the sinusoidal space with secondary development of NRH, pericellular fibrosis, and the manifestation of PHTN. While markers of the early phase - beyond slight elevation of cholestatic enzymes - are still missing, elevated liver stiffness and splenomegaly above 16 cm longitudinal diameter have been suggested as warning signs for PHTN in CVID patients. Data on immunosuppressive treatment of this manifestation is still very heterogeneous, but a recent report on liver transplantation was encouraging for end stage liver disease.

Summary: Liver disease deserves higher attention in the management of CVID. More studies are needed to understand its pathogenesis and optimal treatment.

Purpose of review: The identification of STAT1 gain-of-function (GOF) in 2011 and STAT3 GOF in 2014 has advanced our understanding of the host immunity along the JAK/STAT pathway and allowed targeted treatment approaches. We review the clinical features and pathogenesis of STAT1 and STAT3 GOF and how this has shaped new approaches to therapy.

Recent findings: STAT1 GOF, initially described in patients with chronic mucocutaneous candidiasis (CMC) and autoimmune thyroid disease, is now recognized to cause early-onset multisystem autoimmunity and a range of infections. STAT3 GOF comprises mostly lymphoproliferation and autoimmunity but also with varying severity, including some with life threatening organ dysfunction. Treatment has evolved along with the understanding of the pathogenesis, with patients now receiving JAK inhibition to block upstream of the STAT defect with good response in autoimmunity and CMC in STAT1 GOF. Blockade of IL-6 signaling has also been used in STAT3 GOF. Hematopoietic cell transplantation had initial poor outcomes, but outcomes are now improving with focus on the control of inflammation pretransplant.

Summary: Understanding the pathogenesis of STAT1 and STAT3 GOF has allowed great recent advancements in therapy, but many questions remain as to the best approach to therapy for each patient's clinical presentation as well as the durability of these therapies.

Purpose of review: The full understanding of the long-term effectiveness and safety of allergen immunotherapy (AIT) for allergic respiratory diseases cannot be achieved through randomized controlled trials (RCTs) alone. However, real-world studies designed as registries can complement RCTs.

Recent findings: The significance of registries is highlighted by their potential to reassess contraindications and collect data on adult and pediatric patients with multiple comorbidities who are often excluded from RCTs.

Summary: AIT is the sole disease-modifying therapeutic approach capable of inducing tolerance and offering a long-term response to allergens. AIT has been shown to play a role in arresting the 'allergic march' in young people, which reduces the risk of developing asthmatic clinical manifestations. Although RCTs are considered the gold standard for evaluating the efficacy and safety of AIT, their duration is usually too short (seldom lasting more than 1 year) to assess the long-term effects of AIT. Several long-term studies show that AIT's effect depends strongly on its use duration.

Purpose of review: For decades, treatment options for hereditary angioedema (HAE) were limited by major adverse effects, insufficient efficacy, and difficult routes of administration. However, the growing body of knowledge regarding HAE pathophysiology has led to the development of innovative drugs for self-administered, on-demand therapy and for short- and long-term prophylaxis. This review provides a comprehensive overview of the approved drugs and the development of HAE treatments.

Recent findings: The implementation of new therapies will improve the application of individualized action plans based on the key goals of minimizing the number of attacks and meeting the complex needs of patients.

Summary: HAE is a rare genetic disease with a high impact on patients' quality of life due to the unpredictability and variable severity of attacks. Advances in HAE research have allowed optimization of attack management and individualization of therapeutic approaches.

Purpose of review: This review explores the relevance of eHealth technologies to address unmet needs in pediatric respiratory allergies, particularly allergic rhinitis (AR) and asthma. Given the increasing burden of these conditions, there is a pressing need for effective solutions to enhance disease surveillance, diagnosis, and management.

Recent findings: Recent literature highlights the potential of eHealth tools to transform pediatric respiratory allergy care. The use of digital data for infodemiology, application of machine learning models to improve diagnostic sensitivity, smartphone apps with digital patient reported outcome measure (PROMs) and embedded sensors to monitor disease, healthcare professional dashboards with real-time data monitoring and clinical decision support systems (CDSS) are advances emerging to optimize pediatric respiratory allergy care.

Summary: Integrating eHealth technologies into the pediatric respiratory allergy care pathway is a potential solution for current healthcare challenges to better meet the needs of children with AR and asthma. However, while the potential of eHealth is evident, its widespread implementation in real-world practice requires continued research, collaboration, and efforts to overcome existing barriers.

Purpose of review: Allergic rhinitis is a relevant and global health problem affecting up to 5-50% of the general population and its prevalence is increasing due to climate change and pollution among other factors and counts among the 10 most frequent reasons for medical consultation, generating an important economic impact. Allergen immunotherapy (AIT) is the only allergy-disease-modifying treatment and there is plenty of evidence of its effectiveness with regards subcutaneous and oral routes of AIT.This narrative review article examines published literature in the last 24 months regarding the pharmacoeconomics of AIT versus standard of care treatment (SOC) for the treatment of allergic rhinitis and asthma.

Recent findings: Farraia et al. assessed in 2022 subcutaneous immunotherapy (SCIT, _438/$500.28) and sublingual immunotherapy (SLIT) (_1021/$1116.19) plus symptomatic treatment versus SOC treatment in children with HDM-driven allergic asthma, measuring QALYs, decrease of medication, decrease of exacerbations and symptoms. They used the cost-effective threshold: _18 482.80 ($21 110.14), finding that AIT is cost-effective.Also, SCIT and SLIT plus symptomatic treatment was assessed versus SOC treatment in children with grass pollen allergic rhinitis. The authors concluded that SCIT (_933/$1065.67) and SLIT (_1408/ $1608.22) seem cost-effective, particularly SCIT.

Summary: Allergen immunotherapy is cost-effective in the management of allergic rhinitis and asthma as compared with SOC alone. As most studies consider only during-treatment costs and no long-term benefits or preventive effects are being assessed, the real cost-effectiveness of allergen immunotherapy could be even higher.

Purpose of review: Common variable immunodeficiency enteropathy (CVID-E) is a noninfectious complication of CVID caused by chronic inflammation of the gastrointestinal (GI) tract. Based on literature, a paucity or lack of plasma cells, although not obligatory for diagnosis, is a pathognomonic feature of CVID and more frequent in CVID-E. However, there is no consensus on standardized histopathological analysis of this feature in biopsies. In this systematic review, we highlight methods of reproducible plasma cell quantification of biopsies in CVID and describe the plasma cell counts and classes as presented in the literature.

Recent findings: Reduced plasma cell counts are commonly found over the entire GI tract, except for in the oesophagus. Immunoglobulin A+ (IgA+) plasma cells appear to be the most commonly reduced plasma cell class in CVID, yet there is scarce literature on the predictive value of low IgA+ plasma cell counts in CVID-E.

Summary: We propose two optimized methodologies of quantification using a cut-of value of <10 plasma cells per HPF at 40× magnification, or a proportion of ≥1-5% of total mononuclear cells, recorded over ≥3 sections, and in ≥2 biopsies, as the most conservative agreeable definitions for a paucity of plasma cells to be used in diagnostics and further research.

Purpose of review: C1q deficiency is a rare inborn error of immunity characterized by susceptibility to severe infections and profound immune dysregulation, with a systemic lupus erythematosus-like phenotype. The management of patients with C1q deficiency is challenged by the rarity of this condition and the wide clinical variability. This review aims to emphasize the importance of a thorough immunological and clinical characterization to help guide a personalized and comprehensive approach to patients.

Recent findings: We focus on the concept of C1q deficiency as a bridge between the monogenic form of systemic lupus erythematosus and the Mendelian type I interferonopathies. Moreover, we explore the role of new treatment strategies such as Janus-associated kinase (JAK) inhibitors and allogeneic stem cell transplantation.

Summary: In this narrative review, we provide a systematic overview of C1q deficiency, starting with the description of the pathophysiological background and the variable clinical phenotype, and then exploring the different prognoses, the consequent treatment strategies and future directions.