Clinical features, treatment and outcomes of Italian children with enthesitis-related arthritis and juvenile psoriatic arthritis: a cross-sectional cohort study.

OBJECTIVES: Limited information is available on the clinical features, treatment modalities and outcomes of the juvenile idiopathic arthritis (JIA) categories of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA). This study was aimed to describe the characteristics of Italian children with ERA and JPsA and to compare them with those of patients with the other categories of JIA. METHODS: Patients were part of a multinational sample included in a study aimed to investigate the prevalence of disease categories, treatment approaches, and disease status in patients from across different geographical areas (EPOCA Study). All patients underwent a retrospective assessment, based on the review of clinical chart, and a cross-sectional evaluation, which included assessment of physician- and parent-reported outcomes and laboratory tests, and recording of ongoing therapies. RESULTS: Of the 9081 children with JIA enrolled in the EPOCA Study, 1300 were recruited at 18 paediatric rheumatology centres in Italy. 45 (3.5%) had ERA and 49 (3.8%) had JPsA. Several remarkable differences in demographic features and frequency of articular and extra-articular manifestations, disease damage, impairment in physical function and health-related quality of life, school-related problems, comorbidities, and ongoing treatments were observed between ERA and JPsA and the other JIA categories. CONCLUSIONS: We described the characteristics of Italian children with ERA and JPsA and highlighted their peculiarities and their differences from the other JIA subsets. These data provide useful insights for future revisions of JIA classification and a benchmarking against which the features from other cohorts may be compared.

Insights into the clinical presentation of juvenile systemic lupus erythematosus: the PRAGMA monocentric cohort of 177 patients.

OBJECTIVES: The aim of this work is to describe the clinical manifestations at onset and during follow-up in a monocentric cohort of patients with juvenile systemic lupus erythematosus (jSLE) from the Paediatric Rheumatology group of the Milan area (PRAGMA). METHODS: Patients were retrospectively included in case of i) SLE diagnosis according to the 1997 American College of Rheumatology or the 2012 SLICC classification criteria and ii) disease onset before 18 years. RESULTS: Among the 177 recruited patients (155 females), haematologic involvement was the most common disease manifestation (75%), followed by joint and cutaneous involvements (70% and 57%, respectively). Renal disease was observed in 58 patients (32.8%), neurological complications in 26 cases (14.7%). Patients presented most commonly 3 clinical manifestations (32.8%), while 2 organ involvements were identified in 54 patients (30.5%) and 4 in 25 subjects (14.1%). The 49 patients with disease onset <10 years had less commonly articular involvement (p=0.02), while patients aged >14.8 years displayed less neurological manifestations (p=0.02). At a median follow-up of 118 month, the disease progressed in 93 patients, with a median of 2 new manifestations per patient. Low complement at diagnosis predicted new clinical manifestations (p=0.013 for C3 and p=0.0004 for C4). The median SLEDAI at diagnosis was 13; SLEDAI was substantially similar at 6 months, decreased at 12 months to remain stable at 18 months and further reduce at 24 months (p<0.0001). CONCLUSIONS: These data from a large jSLE monocentric cohort allow gaining further insights into a rare disease with a still high morbidity burden.

Evaluation of Six Years of Appropriateness Level of Blood Transfusion in a Pediatric Ward.

BACKGROUND: Blood transfusion can be considered as a life-saving treatment and is a primary health management topic. This study aims to assess the appropriateness of blood transfusion performed in a large tertiary hospital in Italy. METHODS: a multispecialist team composed oof hematologists, public health experts and pediatricians analyzed blood transfusions performed between 2018 and 2022 in the pediatric wards comparing the appropriateness with the available NHS guidelines available. Patients' characteristics, clinical features and blood component's data were collected and analyzed. RESULTS: considering 147 blood transfusions performed in 2018-2022, only eight (5.4%) were performed according to guidelines, while 98 (66.7%) were driven by clinicians' expertise, especially for anemia in genetic syndromes (30) (20.5%) and autoimmune diseases (20) (13.6%). Thirty-nine (26.5%) transfusions could be considered as inappropriate, while two (1.4%) blood packs were never been transfused after being requested. CONCLUSIONS: This analysis is one of the first performed to assess the appropriateness of blood component transfusions comparing their compliance to NHS guidelines. The importance of this analysis can be explained first by the clinical point of view and second by the economic one.

Corticosteroid Treatment in Sydenham Chorea: A 27-Year Tertiary Referral Center Experience.

OBJECTIVE: The purpose of this study was to investigate the effectiveness of corticosteroid therapy for children suffering from Sydenham chorea (SC). METHODS: The design of the study was observational, retrospective and conducted at the single center of the Rheumatology Unit of Policlinic Hospital of Milan, Italy, from May 1995 to May 2022. All data about the patients were collected from medical records. RESULTS: From a total of 59 patients enrolled in the study (44 females and 15 males; median age 9.3 years, range 7.4-10.6 years), 49 were eligible for primary outcome analysis (10 patients were excluded due to incomplete data). Overall, 75% of patients received steroid therapy, while the remaining cases were treated with symptomatic drugs, including neuroleptics and antiseizure drugs. We found that the duration of chorea was significantly shorter in patients treated with corticosteroids in comparison to those receiving symptomatic treatment (median time: 31 vs. 41 days, p = 0.023). Additionally, patients with arthritis at the onset of the disease had a longer duration of chorea than those without arthritis (median time 90.5 vs. 39 days, p = 0.02). We also found that chorea recurred in 12% of the patients and seemed to be linked to a younger age at onset (p = 0.01). CONCLUSIONS: The study suggests that corticosteroid therapy can lead to a faster resolution of SC when compared to neuroleptics and antiseizure drugs treatment.

Infection-Triggered Hyperinflammatory Syndromes in Children.

An association between infectious diseases and macrophage activation syndrome (MAS) has been reported, yet the exact role of infection in MAS development is still unclear. Here, a retrospective analysis of the clinical records of patients with rheumatic diseases complicated with MAS who were treated in a pediatric tertiary care center between 2011 and 2020 was performed. Any infection documented within the 30 days preceding the onset of MAS was reported. Out of 125 children in follow-up for systemic rheumatic diseases, 12 developed MAS, with a total of 14 episodes. One patient experienced three episodes of MAS. Clinical and/or laboratory evidence of infection preceded the onset of MAS in 12 events. Clinical features, therapeutic strategies, and patient outcomes were described. The aim of this study was to evaluate the possible role of infection as a relevant trigger for MAS development in children with rheumatic conditions. The pathogenetic pathways involved in the cross-talk between uncontrolled inflammatory activity and the immune response to infection deserve further investigation.

Development and Preliminary Validation of an Electromyography-Scoring Protocol for the Assessment and Grading of Muscle Involvement in Patients With Juvenile Idiopathic Inflammatory Myopathies.

INTRODUCTION: We performed a pilot study in order to investigate the feasibility of an electromyography (EMG)-scoring protocol for the assessment of disease activity in juvenile idiopathic inflammatory myopathies (JIIM). METHODS: Children with JIIM followed up in a tertiary-level care center underwent standardized clinical, laboratory, and EMG assessment. An EMG-scoring protocol was devised by a consensus panel including a pediatric neurophysiologist and two pediatric rheumatologists, based on a combined score obtained as the sum of (1) the presence of denervation signs (fibrillation potentials) and (2) motor unit remodeling (mixed pattern of short- and long-duration motor unit action potentials). The EMG-scoring protocol was then validated following the Outcome Measures in Rheumatoid Arthritis Clinical Trials filter for outcome measures in rheumatology and the consensus-based standards for the selection of health measurement instruments methodology. RESULTS: Thirteen children (77% females) were included in the study, with a median age of 10 years (interquartile range: 7-17 years) and median disease duration of 11.8 months (interquartile range: 2.1-44.5). A total of 39 EMG examinations were evaluated. A strong positive association between a standardized tool for muscle strength assessment and the combined score was observed. No significant associations were found with both creatine kinase and erythrocyte sedimentation rate levels. DISCUSSION: Our EMG-scoring protocol is the first standardized and reproducible tool for the neurophysiologic evaluation and grading of muscle involvement in patients with JIIM and could provide relevant additional information in the assessment and follow-up of these rare conditions.

Juvenile idiopathic arthritis in Harlequin ichthyosis, a rare combination or the clinical spectrum of the disease? Report of a child treated with etanercept and review of the literature.

BACKGROUND: Harlequin ichthyosis (HI) is the most severe phenotype of autosomal recessive congenital ichthyosis. Juvenile Idiopathic Arthritis (JIA) represents a heterogenous group of disorders all sharing the clinical manifestation of chronic arthritis. Association of HI and chronic arthritis has been reported in few cases. CASE PRESENTATION: We report the case of a child with HI who developed a severe form of chronic polyarthritis during the first years of life, treated with repeated multiple joint injections, methotrexate and etanercept with good response and without any adverse events. CONCLUSION: The reported case and the literature review highlighted the presence of a peculiar severe seronegative polyarthritis with early onset in a series of patients with HI, suggesting that polyarthritis may be a specific manifestation of HI, rather than a rare combination of two separate conditions.

Paediatric acute rheumatic fever in developed countries: Neglected or negligible disease? Results from an observational study in Lombardy (Italy).

INTRODUCTION: Acute Rheumatic Fever (ARF) is a multisystemic disease that results from an autoimmune reaction due to group A streptococcal infection. The disease affects predominantly children aged 5 to 15 years and although its incidence in developed Countries declined since the early 1900s, to date there is a paucity of data that confirm this epidemiological trend. OBJECTIVE: The study aimed to assess the burden of ARF in term of hospitalization and to describe the characteristics of acute rheumatic fever (ARF) in the paediatric population of Lombardy. STUDY DESIGN: The study was carried out by analyzing hospital discharge records of patients resident of Lombardy and aged 0-17 years old who, from 2014 to 2016, were hospitalized with the diagnosis of ARF. The following variables have been studied: age, sex, municipality of residence, date of diagnosis of each patient, hospital of admission, and presentation of the disease. RESULTS: From 2014 to 2016, 215 patients were found to meet the inclusion criteria and diagnosed as affected from Acute Rheumatic Fever. The rate of hospitalization showed a slightly increasing trend from 3.42 in 2014 to about 5.0 in 2016. Moreover, ARF presented a typical seasonal trend with lower cases in the autumn and a peak of hospitalization in the spring. CONCLUSION: To date, ARF seems to be a rare but not negligible disease in southern central European countries, and in Lombardy we estimated an annual hospitalization rate of 4.24 cases per 100,000 children. The increasing trend found in our study suggests that the burden of the disease could be reduced by involving multidisciplinary health professionals who, in addition to the paediatrician of free choice, would promote evidence based medicine management of the disease during all its clinical phases.

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis.

OBJECTIVE: Anti-TNF-α agents have significantly changed the management of juvenile idiopathic arthritis (JIA). We evaluated the safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of JIA-associated uveitis in patients treated for ≥ 2 years. METHODS: Patients with JIA-associated uveitis treated with IFX and ADA were managed by a standardized protocol and data were entered in the ORCHIDEA registry. At baseline, all patients were refractory to standard immunosuppressive treatment or were corticosteroid-dependent. Data recorded every 3 months were uveitis course, number/type of ocular flares and complications, drug-related adverse events (AE), and treatment switch or withdrawal. Data of patients treated for ≥ 2 years were analyzed by descriptive statistics. RESULTS: Up to December 2014, 154 patients with ≥ 24 months followup were included in the study. Fifty-nine patients were treated with IFX and 95 with ADA. Clinical remission, defined as the absence of flares for > 6 months on treatment, was achieved in 69 patients (44.8%), with a better remission rate for ADA (60.0%) as compared to IFX (20.3%; p < 0.001). A significant reduction of flares was observed in all patients without difference between the 2 treatment modalities. The number of new ocular complications decreased in both groups but was lower for ADA (p = 0.015). No serious AE were recorded; 16.4% of patients experienced 35 minor AE and the incidence rate was lower with ADA than with IFX. CONCLUSION: At the 2-year followup, ADA showed a better efficacy and safety profile than IFX for the treatment of refractory JIA-associated uveitis.

May biscuits contribute to iron balance? An observation in children with juvenile idiopatic arthritis.

Within an observational open study on the effects of a scheduled dosage of biscuits with iron, children with juvenile idiopathic arthritis were either supplemented with biscuits supplying iron fumarate (median 3.6 mg per day) or left to their customary dietary habits. After 4 months, supplemented children showed a more favourable percentage change of blood haemoglobin, while ferritin levels (markers of inflammation) remained stable. We conclude that the supply of iron with available dietary products may contribute to an adequate iron status in children with chronic inflammatory disorders in a stable situation.

Anti-nuclear antibodies as predictor of outcome in a multi-center cohort of Italian children and adolescents with Raynaud's phenomenon.

A retrospective multi-center data collection of clinical, laboratory, and treatment characteristics of 94 Caucasian children and adolescents with Raynaud's phenomenon (RP) started at a mean age of 12.8 ± 5 years, with variable involvement of hands, feet, and face, was performed for a period of 3 years. Collected data included nailfold videocapillaroscopy (NVC), lung function tests, and different laboratory tests finalized to characterize an eventual connective tissue disease (CTD), disclosed by RP itself. Twelve patients presented an early-scleroderma pattern at NVC, 1 a late-scleroderma pattern, and 58 a nonspecific pattern. Laboratory data results showed the positivity of anti-nuclear antibodies (ANA) in 29 % of patients. After this 3-year period of observation, 8 patients had developed a CTD. Our data examined by multivariate analysis, though limited to a multi-center cohort of pediatric patients with RP, strongly suggest that ANA positivity is a significant predictor of progression of RP towards a CTD.

Chorea, a little-known manifestation in systemic lupus erythematosus: short literature review and four case reports.

Chorea is a movement disorder that may be found in children due to several causes. Here we focus especially on Systemic Lupus Erythematosus associated chorea. First we outline its epidemiology, hypothesized pathogenesis, clinical presentation and treatment, then we report four significant clinical cases, which represent well the extreme variability of set of symptoms that may accompany lupus chorea. Our experience, according to literature, suggests that choreic movements in a child should alert the pediatrician and lead him to investigate a potential neurological involvement of Systemic Lupus Erythematosus.

Wegener's granulomatosis presenting with life-threatening lung hemorrhage in a 7-year-old child.

Wegener's granulomatosis (WG) is an idiopathic systemic disease that usually onsets in adolescence and is rare in young children. Its diagnosis is usually based on the presence of fever with arthralgia and weight loss, associated with symptoms of upper and/or lower respiratory tract involvement and renal disorders. We describe the appearance of a life-threatening lung hemorrhage in the absence of hemoptysis in a 7-year-old girl with a completely negative previous clinical history, who was subsequently diagnosed as having WG. The teaching message is that immediate bronchoscopy with bronchoalveolar lavage seems to be advisable in the presence of severe respiratory distress and bilateral lung as well as renal involvement. When a diffuse alveolar hemorrhage syndrome is demonstrated, WG should be considered among the main etiologies even in a relatively young child without a clinically suggestive history.