Claudia Bracaglia

Ospedale Pediatrico Bambino Gesù | Bambino Gesù · Department of Pediatric Medicine

Background: Childhood systemic lupus erythematosus (cSLE) has been considered as a polygenic autoimmune disease; however, a monogenic lupus-like phenotype is emerging with the recent recognition of several related novel high-penetrance genetic variants. RASopathies, a group of disorders caused by mutations in the RAS/MAPK pathway, have been recentl...

Introduction Haemophagocytic lymphohistiocytosis is a rare and life-threatening condition caused by uncontrolled immune activation leading to excessive inflammation and tissue destruction. It could either be due to a primary genetic defect or be triggered by secondary causes such as infections, autoimmune diseases, rheumatological diseases or post-...

Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which leads to inflammation and organ damage caused by immune complex deposition. Classically, childhood SLE has been considered as a polygenic autoimmune disease; however, a pediatric monogenic lupus-like phenotype (LL) is emerging due to the recent recognition of sever...

Background Chronic parenchymal lung disease (LD) is a new emerging severe life-threatening complication of sJIA. The number of sJIA patients with LD is apparently increasing and interestingly they are reported more frequently in North America. Data regarding frequency and features of sJIA-LD in Europe are not available. Objectives To evaluate the...

Background Systemic juvenile idiopathic arthritis (sJIA) is a rare autoinflammatory disease of unknown etiology. Several uncontrolled studies showed that early treatment with anakinra is associated with a better outcome, according to the “window of opportunity” hypothesis. However, very limited scientific evidence is available on withdrawal strateg...

Background Macrophage Activation Syndrome (MAS) and Secondary Hemophagocytic Lymphohistiocytosis (sHLH) are hyperinflammatory conditions, in which IFNγ plays a pivotal role. Prompt recognition and early treatment are essential to improve the outcome and the mortality rate. Objectives This is a retrospective multicenter study. We correlated traditi...

Background Pediatric Sjögren’s syndrome (pSS) is a rare disorder that is often diagnosed late due to the lack of validated diagnostic criteria and validated biomarkers. The pathogenesis is largely unknown, but there is evidence of involvement of both the innate and adaptive branch of the immune system. Immunological overactivity is central in the p...

Background MAS, a form of secondary hemophagocytic lymphohistiocytosis (sHLH), is a severe, life-threatening complication of rheumatic diseases that occurs most frequently in patients (pts) with sJIA and adult-onset Still’s disease (AOSD). MAS is characterized by hyperinflammation and overproduction of interferon γ (IFNγ). Treatment with emapalumab...

Background Macrophage activation syndrome (MAS) is a life-threatening complication of different rheumatic diseases, particularly of systemic juvenile idiopathic arthritis (sJIA). Objectives We report the case of 17-year-old girl with sJIA complicated by recurrent severe MAS episodes. Methods Patient received emapalumab (anti-IFNg antibody) in two...

Background Systemic Lupus Erythematosus (SLE) is an autoimmune disease affecting different organs and causing significant morbidity and mortality. Pulmonary arterial hypertension (PAH) is a rare manifestation of SLE. The prevalence of PAH in patients with SLE varies between 0.5 to 5% [1]. No screening algorithms have been developed in patients with...

Background Pediatric Antiphospolipid Syndrome (APS) is an autoimmune disease characterized by venous and/or arterial thrombotic events (TE) associated with 2 consecutive positive determinations (at least 12 weeks apart) of antiphospholipid antibodies (aPL), IgG/IgM anticardiolipin (aCL), IgG/IgM β2-glycoprotein I (aβ2GPI) and/or lupus anticoagulant...

Background Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of antinuclear antibodies (ANA). Monitoring of anti-DNA antibody levels may reflect disease activity, by contrast a single anti-RBP antibody determination is thought to suffice for clinical purposes. Recent data suggests that ANA levels may decrease...

Background Systemic lupus erythematosus (SLE) is an autoimmune disease causing significant morbidity and mortality. B cells play a central role in SLE pathogenesis. T-bet, is a transcription factor promoting T helper-1 development. B cells expressing T-bet are expanded in aging, chronically infected individuals, and murine models of autoimmunity [1...

Systemic lupus erythematosus (SLE) is an autoimmune disease causing significant morbidity and mortality, despite important improvements in its management in the last decades. The objective of this work is to investigate the role of IFN‐γ in the pathogenesis of childhood‐onset systemic lupus erythematosus (cSLE), evaluating the crosstalk between IFN...

Objectives: Macrophage activation syndrome (MAS) is a severe, life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD). The objective of this study was to confirm the adequacy of an emapalumab dosing regimen in relation to interferon-γ (IFNγ) activity by assessing efficacy and safety. Th...

Objectives: The 2016 ACR-EULAR Response Criteria for juvenile dermatomyositis (JDM) was developed as a composite measure with differential weights of six core set measures (CSMs) to calculate a Total Improvement Score (TIS). We assessed the contribution of each CSM, representation of muscle-related and patient-reported CSMs towards improvement, an...

Objectives Polymorphism in a coding region of Deoxyribonuclease I-like III (DNASE1L3), causing amino acid substitution of Arg-206 to Cys (R206C), is a robustly replicated heritable risk factor for systemic sclerosis (SSc) and other autoimmune diseases. DNASE1L3 is secreted into the circulation, where it can digest genomic DNA (gDNA) in apoptosis-de...

Objectives Macrophage activation syndrome (MAS) is a severe, life threatening complication of systemic juvenile idiopathic arthritis (sJIA) and adult onset Still s disease (AOSD). The objective of this study was to confirm the adequacy of an emapalumab dosing regimen in relation to interferon-gamma (IFNgamma) activity by assessing efficacy and safe...

Background To report baseline characteristics, patient reported outcomes and treatment of children with Juvenile Dermatomyositis (JDM) in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods Children newly diagnosed with JDM were enrolled in the CARRA Registry from 41 pediatric rheumatology centers. Baseline patient...

Background Children with juvenile idiopathic arthritis (JIA) who achieve a drug free remission often experience a flare of their disease requiring either intraarticular steroids (IAS) or systemic treatment with disease modifying anti-rheumatic drugs (DMARDs). IAS offer an opportunity to recapture disease control and avoid exposure to side effects f...

Background Following the Coronavirus Disease-19 (COVID-19) pandemic outbreaks, the hyperinflammatory condition termed Multisystem Inflammatory Syndrome in Children (MIS-C) became a healthcare issue worldwide. Since December 2020 the mRNA vaccine against SARS-CoV-2 has become available with a good safety profile. However, evidence regarding safety a...

Purpose to identify the presence of variants in gene related to monogenic lupus and their relationship with clinical manifestations in childhood-onset systemic lupus erythematosus (cSLE) or lupus-like phenotype. Methods a descriptive, observational, cross-sectional study was carried out in children with a diagnosis of cSLE or with lupus-like. The...

Purpose Interferonopathies are conditions characterized by excessive production of type 1 interferon. Several diseases, autoinflammatory or autoimmune, are classified as type1 interferonopathies such as Aicardi-Goutieres, Sting associated vasculopathy with onset in Infancy, monogenic Systemic lupus erythematosus (SLE) and Dermatomyositis. The aim o...

Purpose to investigate the trend of antinuclear antibodies (ANA) and anti-dsDNA autoantibodies titers over time in children with a diagnosis of systemic lupus erythematosus (SLE). Methods We enrolled 15 children with a diagnosis of SLE, fulfilling the SLICC criteria. For all patients included in the study ANA and anti-dsDNA antibodies testing was...

Objective: The goal was to characterize short-term kidney status and describe variation in early care utilization in a multicenter cohort of patients with childhood-onset systemic lupus erythematosus (cSLE) and nephritis. Methods: We analyzed previously collected prospective data from North American patients with cSLE with kidney biopsy-proven n...

The hyper‐inflammatory response, also known as multisystem inflammatory syndrome in children (MIS‐C), represents a major concern in children with SARS‐CoV‐2 infection. We report bone marrow features of three patients with MIS‐C who were diagnosed during the first wave of the SARS‐CoV‐2 pandemic. A bone marrow evaluation was performed at onset of th...

Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniasis. The auricle is an extremely rare site for CL in the Old World. Auricular CL may be mistaken for other entities, such as relapsing polychondritis (RP). Here we report a pediatric case of Old World auricular CL mimicking RP in a child successfully treated with intralesional lipo...

Background MAS is a severe, life-threatening complication of rheumatic diseases that occurs most frequently in patients with sJIA. The mainstay of treatment for MAS is high dose glucocorticoids (GCs); however, GCs do not provide adequate control in all patients. Additional treatments are used without a standardized approach; however, morbidity and...

Background Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic events (TEs) and/or pregnancy morbidity, in association with two consecutive positive determinations (at least 12 weeks apart) of antiphospholipid antibodies (aPLs). Several manifestations which are not considered clinical criteria of APS have been ident...

CD8+ T-cell activation has been demonstrated to distinguish patients with primary and infection-associated hemophagocytic lymphohistiocytosis (pHLH and iaHLH) from patients with early sepsis. We evaluated the activation profile of CD8+ T cells in patients with various forms of secondary HLH (sHLH), including macrophage activation syndrome (MAS). Fl...

Background Social determinants of health (SDH) greatly influence outcomes during the first year of treatment in rheumatoid arthritis, a disease similar to polyarticular juvenile idiopathic arthritis (pJIA). We investigated the correlation of community poverty level and other SDH with the persistence of moderate to severe disease activity and functi...

The paper describes the case of a 1-year-old Caucasian boy with a 1-month history of fever and splenomegaly. Laboratory findings showed pancytopenia, hypertriglyceridemia and hyperferritinemia. Secondary haemophagocytic lymphohistiocytosis was suspected on the basis of clinical and laboratory features. Bone marrow aspirate revealed active haemophag...

Objective To determine the dose-response relationship of tumor necrosis factor (TNF) inhibition in the treatment of juvenile idiopathic arthritis (JIA). Methods Participants of the Childhood Arthritis and Rheumatology Research Alliance Registry were eligible for inclusion in the analyses if they started TNF inhibition for JIA. The primary treatmen...

Objective. To assess the safety, tolerability, pharmacokinetics, and efficacy of rituximab (RTX) in pediatric patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Methods. The Pediatric Polyangiitis Rituximab Study was a phase IIa, international, open-label, single-arm study. During the initial 6-month remission-i...

Background Italy was the first Western country to be hit by the SARS-CoV-2 epidemic. There is now mounting evidence that a minority of children infected with SARS-CoV2 may experience a severe multisystem inflammatory syndrome, called Multisystem inflammatory Syndrome associated with Coronavirus Disease 2019 (MIS-C). To date no universally agreed ap...

Background There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its rel...

Background The impact of social determinants of health on children with polyarticular juvenile idiopathic arthritis (pJIA) is poorly understood. Prompt initiation of treatment for pJIA is important to prevent disease morbidity; however, a potential barrier to early treatment of pJIAs is delayed presentation to a pediatric rheumatologist. We examine...

Background We aimed to characterize etanercept (ETN) use in juvenile idiopathic arthritis (JIA) patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods The CARRA Registry is a convenience cohort of patients with paediatric onset rheumatic diseases, including JIA. JIA patients treated with ETN for w...

Introduction: MAS is a severe, life-threatening complication of rheumatic diseases that occurs most frequently in patients with sJIA. The mainstay of treatment for MAS is high dose glucocorticoids (GCs); however, GCs do not always provide adequate control in all patients. Additional treatments are used without a standardized approach; however, morb...

Background Antibodies to double-stranded DNA are prevalent and pathogenic in systemic lupus erythematosus (SLE), particularly in patients with lupus nephritis. However, the physical nature and regulation of cell-free DNA (cfDNA) that becomes antigenic in SLE is poorly understood. Null mutations in the secreted DNase DNASE1L3 cause human monogenic S...

Interferon-γ (IFNγ) is a pleiotropic cytokine with multiple effects on the inflammatory response and on innate and adaptive immunity. Overproduction of IFNγ underlies several, potentially fatal, hyperinflammatory or immune-mediated diseases. Several data from animal models and/or from translational research in patients point to a role of IFNγ in hy...

Background Pleural effusion in systemic lupus erythematous (SLE) is a common symptom, and recent studies demonstrated that IL-6 has a pivotal role in its pathogenesis. Case presentation We report a case of a 15 years old Caucasian boy with a history of persistent pleural effusion without lung involvement or fever. Microbiological and neoplastic ae...

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by a state of hyperinflammation. Blood purification techniques can blunt the inflammatory process with a rapidly relevant nonselective effect on the cytokine storm, thus potentially translating into survival benefit for these patients. In this cohort, we evaluate...

Objective To evaluate in real-life the effectiveness and safety of canakinumab in Italian patients with systemic juvenile idiopathic arthritis (sJIA). Methods A retrospective multicentre study of children with sJIA was performed. Clinical features, laboratory parameters and adverse events were collected at baseline, after 6 and 12 months from star...

Objective To assess safety, tolerability, pharmacokinetics, and efficacy of rituximab in pediatric patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Methods PePRS (Pediatric Polyangiitis Rituximab Study) was a Phase IIa, international, open-label, single-arm study. During the initial 6-month remission inductio...

Background and objectives. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is extremely rare in children. We report the clinico-pathological features, long-term outcomes, and prognostic factors of a large paediatric cohort of patients with ANCA-associated kidney vasculitis. Design, setting, participants, and measurements. This ret...

Background: Cytokine storm syndromes are life-threatening complications which can occur in children with rheumatic conditions (macrophage activation syndrome, MAS), inherited cytotoxicity defects (primary haemophagocytic lymphohistiocytosis, pHLH) or in course of infection or malignancies (secondary HLH, sHLH). To adequately steer subsequent treatm...

Objective To describe the clinical characteristics, treatment, and outcomes of a multinational cohort of patients with macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). Study design International pediatric rheumatologists were asked to collect retrospectively the data of patients with the co-occurrence of MAS and TMA. Clin...

Antibodies to double-stranded DNA (dsDNA) are prevalent in systemic lupus erythematosus (SLE), particularly in patients with lupus nephritis, yet the nature and regulation of antigenic cell-free DNA (cfDNA) are poorly understood. Null mutations in the secreted DNase DNASE1L3 cause human monogenic SLE with anti-dsDNA autoreactivity. We report that >...

Objective To investigate the activation of the IFNγ signaling pathway in monocytes of patients with secondary hemophagocytic lymphohistiocytosis (sHLH)/macrophage activation syndrome (MAS) and to evaluate whether levels of phosphorylated STAT1 represent a biomarker for the identification of patients at early stages of the disease. Methods Fresh wh...

Objective To describe characteristics of children with enthesitis‐related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods All children with ERA and JPsA were identified. Demographics, clinical characteristics, and treatments were described. Tho...

Objective To evaluate the impact of early treatment and IL1RN genetic variants on the response to anakinra in systemic juvenile idiopathic arthritis (sJIA). Methods Response to anakinra was defined as clinically inactive disease (CID) at 6 months, without glucocorticoids treatment. Demographic, clinical and laboratory characteristics of 56 patient...

Objective Sjögren syndrome in children is a poorly understood autoimmune disease. We aimed to describe the clinical and diagnostic features of children diagnosed with Sjögren syndrome and explore how the 2016 ACR/EULAR classification criteria apply to this population. Methods An international workgroup retrospectively collected cases of Sjögren sy...

Objective To develop and test shortened versions of Manual Muscle Testing-8 (MMT-8) in juvenile dermatomyositis (JDM). Methods Construction of reduced tools was based on retrospective analysis of individual scores of MMT-8 muscle groups in three multinational datasets. The 4 and 6 most frequently impaired muscle groups were included in MMT-4 and M...

Background: There is mounting evidence on the existence of a Pediatric Multi-inflammatory Syndrome related to SARS-CoV-2 (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining...

Background: Children with systemic lupus erythematosus (SLE) frequently have kidney involvement. Lupus nephritis sometimes presents alone, without systemic SLE features, representing the so-called full-house nephropathy (FHN). Distinguishing patients with SLE or FHN has therapeutic and prognostic implications. Methods: In this retrospective obse...

We describe a 2 year old boy with two previously undescribed frameshift mutations in the interferon (IFN)α/β receptor 2 (IFNAR2) gene presenting with hemophagocytic lymphohistiocytosis (HLH) following measles-mumps-rubella vaccination. Functional analyses show the absence of response to type I IFN in the patient’s cells, as revealed by the lack of...

Objective. To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. Methods. The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Valida...

Background MAS is a severe complication of rheumatic diseases and occurs most frequently in patients with sJIA. Data from animal models and from observational studies in patients suggest that interferon gamma (IFNy) is a driver of the hyperinflammation and hypercytokinemia observed in MAS. Objectives To assess the pharmacokinetics, efficacy, and s...

Objectives: The aim of the study is to evaluate the compliance rate to secondary prophylaxis and the presence of rheumatic heart disease (RHD) in a cohort of Italian patients with acute rheumatic fever (ARF). Methods: This is a multicentre retrospective study. The patients were divided into two groups by the presence or absence at last follow-up...

Aim of this study was to investigate the activation of the IFNγ pathway in the affected liver and in the blood of patients with secondary hemophagocytic lymphohistiocytosis (sHLH). To this purpose, the mRNA expression levels of IFNG and IFNγ-inducible genes as well as Tyrosine (701)-phosphorylated signal transducer and activator of transcription 1...

Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematolog...

Background Use of NGS in patients with unclassifiable disease lies a possible approach to the identification of novel disease causing genes. Objectives We report a patient with an early onset inflammatory bowel disease with granulomatous lesions and recurrent HLH episodes carrying a missense mutation in the WNT6 gene. Methods A trio based Whole E...

Background Systemic juvenile idiopathic arthritis (sJIA) accounts for 10-20% of all patients with JIA. The prominent systemic clinical features, the marked elevation of inflammatory markers and the absence of autoantibodies make this disease different from other JIA forms. sJIA should be considered as a polygenic autoinflammatory disease. Interleuk...

Background Systemic juvenile idiopathic arthritis (sJIA) is a polygenic autoinflammatory disease. Innate immune mechanisms appear to play a central role in the pathogenesis of the disease. Nevertheless, a better understanding of the pathophysiology of sJIA is still needed to identify patients responsive to IL-1 or IL-6 targeted therapies. Objectiv...

Background The NLRC4 inflammasome activation is essential in host defence, particularly against enteric pathogens. Gain-of-function mutations in NLRC4 are associated with a distinct autoinflammatory syndrome characterized by enterocolitis and recurrent HLH. Objectives To report safety and efficacy of faecal microbiota transplantation (FMT) in a pa...

Background Recurrent pericarditis affects 15-30% of patients with acute pericarditis. The etiology is poorly understood, with about 80% being idiopathic. Several treatment options are available for recurrences, including NSAIDs, colchicine, glucocorticoids and IL-1 inhibitors (i.e. Anakinra). Standardized guidelines for the management of these pati...

Background Juvenile Arthritis Disease Activity Score (JADAS) has gained increasing popularity for the measurement of the level of disease activity in patients with juvenile idiopathic arthritis (JIA). However, so far the JADAS has been validated only in children with the non-systemic categories of JIA. Objectives To develop and validate the system...

Background Paediatric systemic lupus erythematosus (pSLE) is an autoimmune disorder of childhood characterized by the production of autoantibodies against nuclear antigens. In the last decade, several studies showed an up-regulation of genes induced by type I interferons (IFNα) in peripheral blood and tissues of pSLE patients². It has been reported...

Background Macrophage Activation Syndrome (MAS) is a severe, life-threatening, complication of rheumatic diseases in childhood, particularly of systemic Juvenile Idiopathic Arthritis (sJIA), occurring in approximately 25% of the patients with sJIA. A score that identifies sJIA patients who are at high risk to develop MAS would be useful in clinical...

Background Hyperzincaemia and hypercalprotectinemia (HandH) syndrome has been described as a new rare entity characterized by recurrent infections, dermatological involvement, increased inflammatory markers, hepatosplenomegalia and anemia. Little is known about its heterogeneous presentation, pathophysiology and treatment. Objectives To describe t...

Background Macrophage activation syndrome (MAS) is a severe complication of rheumatologic conditions, mainly systemic juvenile idiopathic arthritis (sJIA), and is classified as a secondary form of hemophagocytic lymphohistiocytosis (HLH). Thrombotic microangiopathy (TMA) is a heterogeneous group of potentially fatal diseases characterized by microa...

Background In the last years, an expanding group of complex genetic disorders characterized by disturbance of the homeostatic control of IFN-mediated immune responses, have been identified, so called type I interferonopathies. An increased expression of type I IFN regulated genes, IFN signature (IS), is described in these conditions. IS represent a...