Innate immune system represents the ancestral defense against infectious agents preserved along the evolution and species; it is phylogenetically older than the adaptive immune system, which exists ...only in the vertebrates. Cells with phagocytic activity such as neutrophils, macrophages, and natural killer (NK) cells play a key role in innate immunity. In 1999 Kastner et al. first introduced the term “autoinflammation” describing two diseases characterized by recurrent episodes of systemic inflammation without any identifiable infectious trigger: Familial Mediterranean Fever (FMF) and TNF Receptor Associated Periodic Syndrome (TRAPS). Autoinflammatory diseases (AIDs) are caused by self-directed inflammation due to an alteration of innate immunity leading to systemic inflammatory attacks typically in an on/off mode. In addition to inflammasomopathies, nuclear factor (NF)-κB-mediated disorders (also known as Rhelopathies) and type 1 interferonopathies are subjects of more recent studies.
This review aims to provide an overview of the field with the most recent updates (see “Most recent developments in..” paragraphs) and a description of the newly identified AIDs.
•Autoinflammatory diseases are caused by self-directed inflammation.•Alteration of innate immunity leads to systemic inflammation attacks.•The autoinflammatory field is exponentially expanding.•The advances in AIDs have led to new insights into immune system understanding.•Autoimmunity and autoinflammation features may be simultaneously present.
Respiratory tract infections (RTIs) are the most common infectious syndromes, primarily caused by viruses. The primary objective was to compare the illness courses between historical RTIs and recent ...SARS-CoV-2 infections. The study cohort consisted of RTI cases evaluated at the Pediatric Emergency Departments of Padua and Bologna, discharged or admitted with microbiologically confirmed viral RTI between 1 November 2018 and 30 April 2019 (historical period) and 1 March 2020 and 30 April 2021 (recent period). We evaluated the risk of oxygen or respiratory support, hospitalization, antibiotic therapy, and complications among different viral infections. The odds ratio (OR) and the 95% confidence intervals (CIs) were estimated through mixed-effect logistic regression models, including a random intercept on the individual and hospital. We identified 767 RTIs: 359 in the historical period compared with 408 SARS-CoV-2 infections. Infections of SARS-CoV-2 had a lower risk of being admitted (OR 0.04, 95% CI 0.03-0.07), receiving respiratory support (OR 0.19, 95% CI 0.06-0.58), needing antibiotic therapy (OR 0.35, 95% CI 0.22-0.56) and developing complications (OR 0.27, 95% CI 0.14-0.51) compared to all other viral RTIs. COVID-19 in children is clinically similar to other viral RTIs but is associated with a less severe infection course. Thus, most prevention strategies implemented for SARS-CoV-2 should still be considered during RSV and Influenza epidemics.
Currently, monoarticular Juvenile Idiopathic Arthritis (monoJIA) is included in the ILAR classification as oligoarticular subtype although various aspects, from clinical practice, suggest it as a ...separate entity.
To describe the clinical characteristics of persistent monoJIA.
Patients with oligoJIA and with at least two years follow-up entered the study. Those with monoarticular onset and persistent monoarticular course were compared with those with oligoJIA. Variables considered were: sex, age at onset, presence of benign joint hypermobility (BJH), ANA, uveitis, therapy and outcome. Patients who had not undergone clinical follow-up for more than 12 months were contacted by structured telephone interview.
Of 347 patients with oligoJIA, 196 with monoarticular onset entered the study and 118 (60.2%), identified as persistent monoJIA, were compared with 229 oligoJIA. The mean follow-up was 11.4 years. The switch from monoarticular onset to oligoarticular course of 78 patients (38.8%) occurred by the first three years from onset. In comparison with oligoJIA, the most significant features of monoJIA were later age at onset (6.1 vs. 4.7 years), lower female prevalence (70.3 vs. 83.4%), higher frequency of BJH (61.9 vs. 46.3%), lower frequency of uveitis (14.4 vs. 34.1%) and ANA+ (68.6 vs. 89.5%) and better long-term outcome.
MonoJIA, defined as persistent arthritis of unknown origin of a single joint for at least three years, seems to be a separate clinical entity from oligoJIA. This evidence may be taken into consideration for its possible inclusion into the new classification criteria for JIA and open new therapeutic perspectives.
There is evidence that obesity could be a risk factor for the severity and response to treatment in adult patients with rheumatoid arthritis (RA) due both to the mechanical effect of overweight and ...to the potential pro-inflammatory effects of cytokines produced by adipose tissue.
To evaluate the role of overweight and obesity in a cohort of young patients with juvenile idiopathic arthritis (JIA) in terms of incidence, disease activity, outcome, and response to treatments.
This single-center retrospective cohort study evaluated 110 children affected by JIA under treatment with conventional disease-modifying antirheumatic drugs (DMARDs) and biologic agents. Body mass index (BMI) categories of 5-84th (normal weight), 85-94th (overweight), and ≥95th (obese) percentile were used. Patients with systemic JIA, uveitis, chronic comorbidities, or under other potentially confounding systemic treatments were excluded. Uni- and multivariate analyses were performed.
One hundred and ten JIA patients (polyarticular
= 50, oligoarticular
= 38, psoriatic
= 12, enthesitis-related arthritis
= 8, undifferentiated
= 2) were enrolled in the study, 75% girls and 25% boys. The mean age at treatment onset was 6.09 years. Baseline BMI was ≥5th and ≤84th percentile in 80 patients, 85-94th in 27, and ≥95th in 3. We did not observe a significant association between BMI and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or number of active joints at baseline, while involvement of the joints of lower limbs was significantly greater (
= 0.025) in overweight/obese patients. However, a trend toward lower remission rates and higher number of relapses, both after DMARDs and biologics, in patients with higher BMI was observed.
This study focuses on the relationship between overweight/obesity and JIA. A significant correlation between obesity and a greater involvement of the joints of the lower limbs at baseline was demonstrated. Furthermore, our data suggest that obesity could negatively influence the course of the disease as well as treatment response.
Multisystem inflammatory syndrome in children (MIS-C) is a serious condition triggered by SARS-COV-2 infection, characterized by persistent fever, multiorgan dysfunction, and increased inflammatory ...markers. It requires hospitalization and prompt treatment, with nearly 60% of the cases needing intensive care and 2% fatality rate. A wide spectrum of clinical characteristics and therapeutic approaches has been reported in MIS-C. We describe a series of four patients with MIS-C, defined according to the current case definitions, with a self-limiting course and no need for immunomodulatory treatment ("self-limiting MIS-C"). Few data about self-limiting MIS-C are available to date and no information on medium- and long-term outcome of this subset of patients has been reported. Although limited in size, our experience provides new insights into the MIS-C syndrome, highlighting an underestimated aspect of the disease that may have significant therapeutic implications.
Kidney involvement has been poorly investigated in SARS-CoV-2 Multisystem Inflammatory Syndrome in Children (MIS-C). To analyze the spectrum of renal involvement in MIS-C, we performed a ...single-center retrospective observational study including all MIS-C patients diagnosed at our Pediatric Department between April 2020 and May 2022. Demographic, clinical, pediatric intensive care unit (PICU) admission’s need and laboratory data were collected at onset and after 6 months. Among 55 MIS-C patients enrolled in the study, kidney involvement was present in 20 (36.4%): 13 with acute kidney injury (AKI) and 7 with isolated tubular dysfunction (TD). In eight patients, concomitant AKI and TD was present (AKI-TD). AKI patients needed higher levels of intensive care (PICU: 61.5%, p < 0.001; inotropes: 46.2%, p = 0.002; second-line immuno-therapy: 53.8%, p < 0.001) and showed lower levels of HCO3- (p = 0.012), higher inflammatory markers neutrophils (p = 0.092), PCT (p = 0.04), IL-6 (p = 0.007) as compared to no-AKI. TD markers showed that isolated TD presented higher levels of HCO3- and lower inflammatory markers than AKI-TD. Our results indicate a combination of both pre-renal and inflammatory damage in the pathogenesis of kidney injury in MIS-C syndrome. We highlight, for the first time, the presence of tubular involvement in MIS-C, providing new insights in the evaluation of kidney involvement and its management in this condition.
Juvenile psoriatic arthritis (JPsA) is a relatively rare condition in childhood as it represents approximately 5% of the whole Juvenile Idiopathic Arthritis (JIA) population. According to ...International League of Associations of Rheumatology (ILAR) classification, JPsA is defined by the association of arthritis and psoriasis or, in the absence of typical psoriatic lesions, with at least two of the following: dactylitis, nail pitting, onycholysis or family history of psoriasis in a first-degree relative. However, recent studies have shown that this classification system could conceal more homogeneous subgroups of patients differing by age of onset, clinical characteristics and prognosis. Little is known about genetic factors and pathogenetic mechanisms which distinguish JPsA from other JIA subtypes or from isolated psoriasis without joint involvement, especially in the pediatric population. Specific clinical trials testing the efficacy of biological agents are lacking for JPsA, while in recent years novel therapeutic agents are emerging in adults. In this review, we summarize the clinical features and the current evidence on pathogenesis and therapeutic options for JPsA in order to provide a comprehensive overview on the clinical management of this complex and overlapping entity in childhood.
Background
Euthyroid sick syndrome (ESS) is characterized by low serum levels of free triiodothyronine (fT3) with normal or low levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) ...and is reported in different acute clinical situations, such as sepsis, diabetic ketoacidosis and after cardiac surgery. Our aim was to evaluate the predicting role of ESS for disease severity in patients with Multisystem Inflammatory Syndrome in children (MIS-C).
Methods
A single-centre observational study on consecutive patients with MIS-C. Before treatment clinical, and laboratory data were collected and, in a subset of patients, thyroid function tests were repeated 4 weeks later. Variables distribution was analyzed by Mann-Whitney
U
-test and correlations between different parameters were calculated by Spearman's Rho coefficient.
Results
Forty-two patients were included and 36 (85.7%) presented ESS. fT3 values were significantly lower in patients requiring intensive care, a strong direct correlation was shown between fT3 and Hb, platelet count and ejection fraction values. A significant inverse correlation was retrieved between fT3 levels and C-reactive protein, brain natriuretic peptide, IL-2 soluble receptor and S-100 protein. Subjects with severe myocardial depression (EF < 45%) had lower fT3 values than subjects with higher EF. The thyroid function tests spontaneously normalized in all subjects who repeated measurement 4 weeks after admission.
Conclusion
ESS is a frequent and transient condition in acute phase of MIS-C. A severe reduction of fT3 must be considered as important prognostic factor for severe disease course, with subsequent relevant clinical impact in the management of these patients.
Due to the growing evidence of the efficacy of intravenous (IV) cefazolin with an early switch to oral cefalexin in uncomplicated pediatric osteomyelitis (OM) and septic arthritis (SA) in children, ...we changed our guidelines for empiric antibiotic therapy in these conditions. This study aims at evaluating the impact of the guidelines' implementation in reducing broad-spectrum antibiotic prescriptions, duration of IV antibiotic treatment and hospital stay, treatment failure and recurrence.
This is a retrospective, observational, quasi-experimental study. The four years pre-intervention were compared to the six years, ten months post-intervention (January 2012, through December 2015; January 2016, through October 31st, 2022). All patients aged 3 months to 18 years with OM or SA were evaluated for inclusion. Each population was divided into three groups: pre-intervention, post-intervention not following the guidelines, and post-intervention following the guidelines. Differences in antibiotic prescriptions such as Days of Therapy (DOT), activity spectrum and Length of Therapy (LOT), length of hospital stay (LOS), broad-spectrum antibiotics duration (bsDOT), treatment failure and relapse at six months were analyzed as outcomes.
Of 87 included patients, 48 were diagnosed with OM (8 pre-intervention, 9 post-intervention not following the guidelines and 31 post-intervention following the guidelines) and 39 with SA (9 pre-intervention, 12 post-intervention not following the guidelines and 18 post-intervention following the guidelines). In OM patients, IV DOT, DOT/LOT ratio, and bsDOT were significantly lower in the guidelines group, with also the lowest proportion of patients discharged on IV treatment. Notably, significantly fewer cases required surgery in the post-intervention groups. Considering SA, LOS, IV DOT, DOT/LOT ratio, and bsDOT were significantly lower in the guidelines group. The treatment failure rate was comparable among all groups for both OM and SA. There were no relapse cases. The overall adherence was between 72 and 100%.
The implementation of guidelines was effective in decreasing the extensive use of broad-spectrum antibiotics and combination therapy for both OM and SA. Our results show the applicability, safety, and efficacy of a narrow-spectrum IV empirical antibiotic regimen with cefazolin, followed by oral monotherapy with first/second-generation cephalosporins, which was non-inferior to broad-spectrum regimens.
Treatment in Juvenile Scleroderma Zulian, Francesco; Tirelli, Francesca
Current rheumatology reports,
08/2020, Volume:
22, Issue:
8
Journal Article
Peer reviewed
Purpose of Review
Treatment of scleroderma in children is challenging since little is known about its pathogenesis. Herein, we review the most recent evidence regarding the treatment of juvenile ...scleroderma.
Recent Findings
According to the recent recommendations for Pediatric Rheumatology in Europe (SHARE), systemic treatment in localized scleroderma is needed when there is a risk for disability, such as in generalized or pansclerotic morphea and progressive linear scleroderma. In juvenile systemic sclerosis, the introduction of the severity score, J4S, has standardized the assessment of the patients in the daily practice and allowed a more tailored therapeutic approach. Since, to date, no clinical trial is available in JSSc, due to its rarity, the treatment is based on adults’ experience.
Summary
The recent recommendations for juvenile scleroderma represent an important instrument to standardize the treatment approach, confirm the role of methotrexate, and open new windows for effective experimental treatments, such as mycophenolate mofetil and biological agents, for severe or refractory cases.
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