Expert Review of Clinical Immunology

INTRODUCTION: Psoriatic arthritis (PsA) is a rheumatic disorder that may be responsible for relevant articular impairment. The recently licensed Janus Kinase (JaK) inhibitors represent a new opportunity to improve PsA treatment. This review deals with the clinical usefulness of the selective JaK-1 inhibitor upadacitinib (UPA) in patients with PsA. COVERED AREAS: Two phase-III studies are available: SELECT-PsA 1, performed in patients with an inadequate response to non-biological therapies, and SELECT-PsA 2, conducted in biologic-experienced patients...

INTRODUCTION: Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1,000,000 children. Currently there is only one consensus treatment guideline concerning skin, pulmonary and vascular involvement for jSSc, the jSSc SHARE (Single Hub and Access point for pediatric Rheumatology in Europe) initiative, which was based on data procured up to 2014. Therefore, an update of these guidelines, with a more recent literature and expert experience, and extension of the guidance to more aspects of the disease is needed...

INTRODUCTION: Metabolic-associated liver diseases have emerged pandemically across the globe and are clinically related to metabolic disorders such as obesity and type 2 diabetes. The new nomenclature and definition (i.e. metabolic dysfunction-associated steatotic liver disease - MASLD; metabolic dysfunction-associated steatohepatitis - MASH) reflect the nature of these complex systemic disorders, which are characterized by inflammation, gut dysbiosis and metabolic dysregulation. In this review, we summarize recent advantages in understanding the pathophysiology of MASLD, which we parallel to emerging therapeutic concepts...

INTRODUCTION: Allergic contact dermatitis (ACD) is a common cutaneous inflammatory skin disorder that is diagnosed via epicutaneous patch testing (PT). ACD may also coexist with other systemic inflammatory conditions such as atopic dermatitis and psoriasis. Many of the treatments used to manage severe ACD, along with other systemic conditions, interact with and suppress the immune system, thereby potentially interfering with the mechanism of PT. There is uncertainty in the literature regarding the effects of immunosuppression on the results of PT...

INTRODUCTION: Familial Mediterranean Fever (FMF) is the most common autoinflammatory disease that has mainly been treated with colchicine since 1972. A significant portion of patients do not respond to colchicine and require further treatment, mainly IL-1β antagonists such as anakinra, canakinumab and rilonacept as IL-1β has a crucial role in pathogenesis of FMF. This review summarizes the current approach to treating FMF and discovers the pharmacological and clinical utility of IL-1 blocking agents based on accumulated evidence with a focus on anakinra...

INTRODUCTION: Hidradenitis suppurativa (HS) is an autoinflammatory skin disease with a high unmet need for effective medical management. Clinically, it is characterized by inflammatory nodules that may progress into abscesses, draining tunnels and extensive scarring, mainly affecting apocrine gland-bearing areas. AREAS COVERED: Treatment options include topical and systemic medications and a variety of surgical procedures. The anti-TNF-α antibody adalimumab and the anti-IL-17 secukinumab are the only two approved biologics for HS, showing moderate efficacy...

INTRODUCTION: Plaque psoriasis, a chronic immune-mediated skin disorder, is characterized by well-demarcated erythematous plaques with silvery scales. This condition stems from complex interactions between genetic predisposition, immune dysregulation, and environmental triggers. Tapinarof downregulates the cytokine IL-17, diminishes the inflammatory infiltrate, and provides antioxidant properties while enhancing the expression of skin barrier proteins. AREAS COVERED: This review begins by assessing tapinarof's mechanism in treating plaque psoriasis...

BACKGROUND: The only causal treatment for allergic rhinitis (AR) is allergen immunotherapy (AIT) including personalized liquid sublingual AIT (SLIT). We present the methodology for establishing the EfficAPSI cohort to further evaluate the real-life effectiveness and use of SLIT liquid. RESEARCH DESIGN AND METHODS: The EfficAPSI cohort was constituted by deterministic linkage of Stallergenes Greer dispensing and nationwide French healthcare insurance system (SNDS) databases...

INTRODUCTION: Hydroxychloroquine (HCQ) and glucocorticoids (GCs) constitute the oldest and more used drugs in the treatment of systemic lupus erythematosus (SLE). Despite this long experience, both are still subject to a number of uncertainties regarding the dose. AREAS COVERED: We review the main mechanisms of action, the clinical and toxic effects of HCQ and GCs and analyze the recommendations for the use of both in guidelines published since 2018. We offer a set of recommendations based on the pharmacology, mechanisms of action and clinical evidence...

OBJECTIVES: Innate and adaptive immunity play different roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, previous studies on the relationship between immune cells and COPD reported inconsistent results. METHODS: The causal connection between 731 immune cells and COPD was established using a two-sample Mendelian randomization (MR) analysis through publicly accessible genetic data. The heterogeneity and horizontal pleiotropism of the findings were confirmed using sensitivity analysis...

INTRODUCTION: Large granular lymphocytic (LGL) leukemia is a rare lymphoproliferative disorder characterized by an expansion of clonal T or NK lymphocytes. Neutropenia-related infections represent the main clinical manifestation. Even if the disease follows an indolent course, most patients will ultimately need treatment in their lifetime. Interestingly, LGL leukemia is characterized by a high frequency of autoimmune disorders with rheumatoid arthritis being the most frequent. AREAS COVERED: This review covers the pathophysiology, clinic-biological features and the advances made in the treatment of LGL leukemia...

INTRODUCTION: SARS-CoV-2 infection is a potentially life-threatening infection in immunocompromised pediatric patients and its management has rapidly evolved during the pandemic. For the control of SARS-CoV-2 infection, over time, the scenario changed for the better with the introduction of specific treatments such as antiviral drugs, vaccines and monoclonal antibodies together with drugs blocking the inflammatory cytokine cascade and improvements of supportive care. AREAS COVERED: the paper discusses the therapeutic strategies to apply for patients affected by COVID-19 in the pediatric population, with a focus on the immunocompromised patients...

INTRODUCTION: Despite the high rate of cure in classical Hodgkin Lymphoma (cHL), some patients experienced a refractory disease, sometimes, hardly curable. In the pathogenesis of cHL, Reed Sternberg Cells (HRSC), which represent only less than 1% of tumor cells, are not the only protagonist; infact, the role of tumor microenvironment is essential in survival, tumor growth and progression of the disease due to the interaction between immune cells, chemokines, and cytokines. AREAS COVERED: In this review the current significant literature was discussed...

INTRODUCTION: The 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) rely on clinical and routine immunological items. The criteria have anti-nuclear antibodies (ANA) as an obligatory entry criterion; items are weighted and ordered in domains. While demonstrating good sensitivity and specificity, the lack of a more molecular approach to some came as a disappointment. AREAS COVERED: Based on a non-systematic literature search, this review covers items investigated in the EULAR/ACR classification criteria project, but not included in the set of criteria...

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a significant health-care burden worldwide. While medical therapy aims to induce and maintain remission, optimal management of mild to moderate UC remains challenging due to heterogeneity in severity classifications and non-standardized approaches. This comprehensive review summarizes current evidence and knowledge gaps to optimize clinical decision-making in patients with mild to moderate UC. AREAS COVERED: After an extensive literature search of PubMed, Medline, and Embase through August 2023, we provide an overview of definitions utilized to characterize mild to moderate UC severity and established therapeutic targets...

INTRODUCTION: Atopic dermatitis is a prevalent skin condition causing dry, pruritic, inflammatory skin lesions that can result in patient distress. Various emerging classes of therapy, including biologics and Janus kinase inhibitors, have been developed in recent years. AREAS COVERED: A literature search of PubMed was conducted to explore existing literature and clinical trials. Treatment options and adverse effects were summarized by class and severity. JAK inhibitors and biologics are efficacious options for adults with severe atopic dermatitis...

BACKGROUND: The pharmacokinetics and pharmacodynamics of biosimilar infliximab (IFX-BioS) in pediatric inflammatory bowel disease (IBD) are poorly investigated. The aim of this study was to investigate factors predicting IFX-BioS trough levels (TLs). RESEARCH DESIGN AND METHODS: IBD children with an indication to start IFX-BioS were included in this prospective observational study (January 2021-June 2022). TLs were measured at the 4th and 6th infusions and correlated with several covariates...

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INTRODUCTION: Atopic dermatitis (AD) is a chronic, intensely pruritic disease associated with significant patient burden. Recent advancements in AD pathogenesis have expanded its therapeutics pipeline. Tralokinumab is a fully human monoclonal antibody that binds specifically Interleukin (IL)-13, inhibiting the downstream IL-13 signaling. Phase 3 clinical trials and some real-world studies showed that tralokinumab, as monotherapy or in combination with topical corticosteroids, is efficacious and safe in adult patients with moderate-to-severe AD...

INTRODUCTION: Non-radiographic axial spondyloarthritis (nr-axSpA) is a chronic inflammatory condition with axial and peripheral musculoskeletal involvement, fulfilling criteria of axSpA in the absence of advanced radiographic sacroiliitis. While appropriate treatment is required for chronic pain and disability resulting from disease progression, the limited availability of treatment options becomes evident. Upadacitinib, an oral selective Janus kinase1 inhibitor, was approved in Europe, the United States, and other countries for management of nr-axSpA with inadequate response to existing therapies...