Publications by authors named "Luciana Breda"

58 Publications

Bone Health in Children with Rheumatic Disorders: Focus on Molecular Mechanisms, Diagnosis, and Management.

Int J Mol Sci 2022 May 20;23(10). Epub 2022 May 20.

Department of Pediatrics, University of Chieti, 66100 Chieti, Italy.

Bone is an extremely dynamic and adaptive tissue, whose metabolism and homeostasis is influenced by many different hormonal, mechanical, nutritional, immunological and pharmacological stimuli. Genetic factors significantly affect bone health, through their influence on bone cells function, cartilage quality, calcium and vitamin D homeostasis, sex hormone metabolism and pubertal timing. In addition, optimal nutrition and physical activity contribute to bone mass acquisition in the growing age. All these factors influence the attainment of peak bone mass, a critical determinant of bone health and fracture risk in adulthood. Secondary osteoporosis is an important issue of clinical care in children with acute and chronic diseases. Systemic autoimmune disorders, like juvenile idiopathic arthritis, can affect the skeletal system, causing reduced bone mineral density and high risk of fragility fractures during childhood. In these patients, multiple factors contribute to reduce bone strength, including systemic inflammation with elevated cytokines, reduced physical activity, malabsorption and nutritional deficiency, inadequate daily calcium and vitamin D intake, use of glucocorticoids, poor growth and pubertal delay. In juvenile arthritis, osteoporosis is more prominent at the femoral neck and radius compared to the lumbar spine. Nevertheless, vertebral fractures are an important, often asymptomatic manifestation, especially in glucocorticoid-treated patients. A standardized diagnostic approach to the musculoskeletal system, including prophylaxis, therapy and follow up, is therefore mandatory in at risk children. Here we discuss the molecular mechanisms involved in skeletal homeostasis and the influence of inflammation and chronic disease on bone metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms23105725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143357PMC
May 2022

Epidemiological and clinical aspects of immunoglobulin A vasculitis in childhood: a retrospective cohort study.

Ital J Pediatr 2021 Dec 15;47(1):237. Epub 2021 Dec 15.

Department of Paediatrics, University of Perugia, Piazza dell'Università 1, Perugia, Italy.

Background: A retrospective study was conducted in order to investigate and describe the characteristics of Immunoglobulin A vasculitis (IgAV), previously known as Henoch-Schӧnlein purpura, in the paediatric population of a community-based healthcare delivery system in the Italian region of Abruzzo.

Methods: This is a population-based retrospective chart review of the diagnosis of IgAV in children ages 0 to 18, admitted to the Department of Paediatrics of Chieti and Pescara between 1 January 2000 and 31 December 2016. All children enrolled presented with clinical symptoms and laboratory findings and met the EULAR/PRINTO/PRES 2008 criteria.

Results: Two-hundred-eight children met the criteria for IgAV, with the highest incidence reported among children below 7-years of age. A correlation with recent infections was found in 64% of the cohort; the onset was more frequently during the winter and fall. Purpura had a diffuse distribution in the majority of patients; joint impairment was the second most frequent symptom (43%), whereas the gastrointestinal tract was involved in 28% of patients.

Conclusions: Hereby, we confirm the relative benignity of IgAV in a cohort of Italian children; with regards to renal involvement, we report a better outcome compared to other studies. However, despite the low rate of renal disease, we observed a wide use of corticosteroids, especially for the treatment of persistent purpura.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13052-021-01182-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672591PMC
December 2021

Intra-articular osteoid osteoma mimicking juvenile psoriatic dactylitis.

Clin Exp Rheumatol 2022 05 3;40(5):1058. Epub 2021 Nov 3.

Department of Paediatrics, University of Chieti-Pescara, Chieti, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.55563/clinexprheumatol/a55rk0DOI Listing
May 2022

Serum Calprotectin a Potential Biomarker in Juvenile Idiopathic Arthritis: A Meta-Analysis.

J Clin Med 2021 Oct 22;10(21). Epub 2021 Oct 22.

Department of Pediatrics, Pediatric Rheumatology Unit, G. D'Annunzio University, 66100 Chieti, Italy.

Juvenile idiopathic arthritis (JIA) is the most common inflammatory chronic disease affecting children and adolescents. Today, there are no specific biomarkers of inflammation. Therefore, it is important to identify new markers as predictors of disease activity. Recently, some researchers have directed their interest toward a protein, calprotectin (CLP), as a potential biomarker. The primary objective of our systematic review and meta-analysis was to analyze the possible role of CLP in JIA.

Method: A literature search was conducted using PubMed, EMBASE, Scopus, Science Direct on 10 August 2021. The selection of studies was made using the PRISMA 2020 guidelines. Cohen's d with 95% CI and -value were used as a measure of effect size. The random effects model was used to account for different sources of variation among studies. Heterogeneity was assessed using Q statistics and I. The publication bias was analyzed and represented by a funnel plot, and funnel plot symmetry was assessed with Egger's test.

Results: Our results at follow-up showed a statistically significant difference between patients with active disease compared to patients with inactive disease: 0.39 (0.16; 0.62), = 0.001; without statistical heterogeneity. Another important aspect that emerged were the differences between the systemic disease form and any form of inactive disease showing a different concentration of calprotectin: 0.74 (0.40; 1.08), < 0.001; without statistical heterogeneity. On the other hand, meta-regression analyses performed on gender, age, duration of disease, percentage of patients with ANA+ or RF+, medium value of ESR or CRP were not statistically significant. A statistically significant difference in serum calprotectin concentration between patients with JIA and healthy controls were observed. In fact, it presented lower values in the control group.

Conclusions: The use of serum CLP could represent, in the future, a useful tool in JIA in order to stratify disease activity more accurately and may aid a more tailored approach to drug of choice in children with JIA. Further studies are needed to evaluate CLP as a predictor of flare in combination with other potential biomarkers of subclinical disease activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10214861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584429PMC
October 2021

Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives.

Int J Mol Sci 2021 Jun 14;22(12). Epub 2021 Jun 14.

Department of Pediatrics, University of Chieti, 66100 Chieti, Italy.

Systemic autoinflammatory diseases are a heterogeneous family of disorders characterized by a dysregulation of the innate immune system, in which sterile inflammation primarily develops through antigen-independent hyperactivation of immune pathways. In most cases, they have a strong genetic background, with mutations in single genes involved in inflammation. Therefore, they can derive from different pathogenic mechanisms at any level, such as dysregulated inflammasome-mediated production of cytokines, intracellular stress, defective regulatory pathways, altered protein folding, enhanced NF-kappaB signalling, ubiquitination disorders, interferon pathway upregulation and complement activation. Since the discover of pathogenic mutations of the pyrin-encoding gene MEFV in Familial Mediterranean Fever, more than 50 monogenic autoinflammatory diseases have been discovered thanks to the advances in genetic sequencing: the advent of new genetic analysis techniques and the discovery of genes involved in autoinflammatory diseases have allowed a better understanding of the underlying innate immunologic pathways and pathogenetic mechanisms, thus opening new perspectives in targeted therapies. Moreover, this field of research has become of great interest, since more than a hundred clinical trials for autoinflammatory diseases are currently active or recently concluded, allowing us to hope for considerable acquisitions for the next few years. General paediatricians need to be aware of the importance of this group of diseases and they should consider autoinflammatory diseases in patients with clinical hallmarks, in order to guide further examinations and refer the patient to a specialist rheumatologist. Here we resume the pathogenesis, clinical aspects and diagnosis of the most important autoinflammatory diseases in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22126360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232320PMC
June 2021

Type I Interferonopathies in Children: An Overview.

Front Pediatr 2021 31;9:631329. Epub 2021 Mar 31.

Department of Pediatrics, University of Chieti, Chieti, Italy.

Notable advances in gene sequencing methods in recent years have permitted enormous progress in the phenotypic and genotypic characterization of autoinflammatory syndromes. Interferonopathies are a recent group of inherited autoinflammatory diseases, characterized by a dysregulation of the interferon pathway, leading to constitutive upregulation of its activation mechanisms or downregulation of negative regulatory systems. They are clinically heterogeneous, but some peculiar clinical features may lead to suspicion: a familial "idiopathic" juvenile arthritis resistant to conventional treatments, an early necrotizing vasculitis, a non-infectious interstitial lung disease, and a panniculitis associated or not with a lipodystrophy may represent the "interferon alarm bells." The awareness of this group of diseases represents a challenge for pediatricians because, despite being rare, a differential diagnosis with the most common childhood rheumatological and immunological disorders is mandatory. Furthermore, the characterization of interferonopathy molecular pathogenetic mechanisms is allowing important steps forward in other immune dysregulation diseases, such as systemic lupus erythematosus and inflammatory myositis, implementing the opportunity of a more effective target therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2021.631329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044321PMC
March 2021

Growth and puberty in children with juvenile idiopathic arthritis.

Pediatr Rheumatol Online J 2021 Mar 12;19(1):28. Epub 2021 Mar 12.

Department of Pediatrics, University of Chieti, Chieti, Italy.

Juvenile Idiopathic Arthritis is one of the most prevalent chronic diseases in children, with an annual incidence of 2-20 cases per 100,000 and a prevalence of 16-150 per 100,000. It is associated with several complications that can cause short-term or long-term disability and reduce the quality of life. Among these, growth and pubertal disorders play an important role. Chronic inflammatory conditions are often associated with growth failure ranging from slight decrease in height velocity to severe forms of short stature. The prevalence of short stature in JIA varies from 10.4% in children with polyarticular disease to 41% of patients with the systemic form, while oligoarthritis is mostly associated with localized excessive bone growth of the affected limb, leading to limb dissymmetry. The pathogenesis of growth disorders is multifactorial and includes the role of chronic inflammation, long-term use of corticosteroids, undernutrition, altered body composition, delay of pubertal onset or slow pubertal progression. These factors can exert a systemic effect on the GH/IGF-1 axis and on the GnRH-gonadotropin-gonadic axis, or a local influence on the growth plate homeostasis and function. Although new therapeutic options are available to control inflammation, there are still 10-20% of patients with severe forms of the disease who show continuous growth impairment, ending in a short final stature. Moreover, delayed puberty is associated with a reduction in the peak bone mass with the possibility of concomitant or future bone fragility. Monitoring of puberty and bone health is essential for a complete health assessment of adolescents with JIA. In these patients, an assessment of the pubertal stage every 6 months from the age of 9 years is recommended. Also, linear growth should be always evaluated considering the patient's bone age. The impact of rhGH therapy in children with JIA is still unclear, but it has been shown that if rhGH is added at high dose in a low-inflammatory condition, post steroids and on biologic therapy, it is able to favor a prepubertal growth acceleration, comparable with the catch-up growth response in GH-deficient patients. Here we provide a comprehensive review of the pathogenesis of puberty and growth disorders in children with JIA, which can help the pediatrician to properly and timely assess the presence of growth and pubertal disorders in JIA patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12969-021-00521-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953722PMC
March 2021

Epilepsy in systemic lupus erythematosus.

Clin Exp Rheumatol 2021 May-Jun;39(3):651-659. Epub 2020 Sep 4.

Department of Paediatrics, University of L'Aquila, Italy.

Systemic lupus erythematosus (SLE) is an autoimmune systemic disease characterised by a broad spectrum of clinical manifestations that may also affect the central nervous system. Among the neurological symptoms, seizures were included in the criteria for the classification of SLE published by EULAR/ACR in 2019. Several studies have been undertaken to explore the role of SLE antibodies in the onset of seizures, however, their complex relation is still a matter of debate. The most common seizure type reported is generalised tonic-clonic. EEG and MRI findings are usually non-specific; background slowing, brain atrophy and hyper-intense lesions on the white matter are the most common finding. Prognosis is overall favourable, with a good response to antiepileptic drugs and immunosuppressive therapy. The purpose of this review is to summarise the most relevant literature contributions published over the years on the epidemiology, aetiopathogenesis, clinical aspects, diagnosis and treatment of seizures in the context of SLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2021

Factor XIII as a potential predictor of severe gastrointestinal involvement in Henoch Schoenlein purpura: A case study research.

J Paediatr Child Health 2020 11 15;56(11):1821-1823. Epub 2020 Apr 15.

Pediatric Rheumatology Unit, SS Annunziata Hospital, Chieti, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpc.14886DOI Listing
November 2020

Pediatrician's approach to diagnosis and management of group A streptococcal pharyngitis.

Eur J Clin Microbiol Infect Dis 2020 Jun 27;39(6):1103-1107. Epub 2020 Jan 27.

Department of Life, Health and Environmental Sciences, Epidemiology Unit, University of Aquila, L'Aquila, Italy.

Group A streptococcal (GAS) pharyngitis is responsible for 20-30% of pharyngitis cases in children (Shulman et al. Clin Infect Dis 55(10):e86-e102, 2012). Recommendations for the diagnosis and treatment of GAS pharyngitis have been published by the Italian National Institute of Health guidelines in 2012 (ESCMID Sore Throat Guideline Group et al. Clin Microbiol Infect 18(Suppl 1):1-28, 2012). Adherence to such guidance is relevant for primary prevention of complications of GAS pharyngitis, above all rheumatic fever (RF). The aim of our study was to evaluate the application of Italian guidelines by the family pediatricians from the Abruzzo region. A validated questionnaire was completed by the family pediatricians and used for data collection. The 154 family pediatricians from Abruzzo (88% of the total number of family pediatricians) participated in the study. Out of the 1232 answers, 455 (37%) were wrong. Only 8% of the participants answered correctly all the questions, whereas 0.6% missed all the questions. Through the Spearman's correlation, our study found an inverse significant correlation between the questions regarding primary prophylaxis (Score B) and the work experience of pediatricians (Rho = - 0.276, p = 0.048). The majority of the family pediatricians from the Abruzzo region, in line with studies from other countries, have significant knowledge gaps about the diagnosis and treatment of GAS pharyngitis. Therefore, strategies to increase the pediatricians' awareness of the guidelines are needed, in order to reduce the RF incidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10096-020-03821-yDOI Listing
June 2020

Acute rheumatic fever prophylaxis in high-income countries: clinical observations from an Italian multicentre, retrospective study.

Clin Exp Rheumatol 2020 Sep-Oct;38(5):1016-1020. Epub 2020 Jan 20.

University of Trieste and Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.

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 of RHD. Clinical features, ARF recurrences and the rate of compliance to secondary prophylaxis were evaluated.

Results: Two-hundred and ninety patients were enrolled (137 females; 153 males). Carditis at onset was present in 244 patients (84.7%). At the end of follow-up, 173 patients manifested RHD. Adherence to secondary prophylaxis was low in 26% of patients. The presence of RHD at follow-up was associated with the presence of carditis and its severity at onset (p=0.001), but it was not related to secondary prophylaxis adherence (p=NS). No association between prophylaxis adherence and ARF recurrence was found (p=NS) nor between ARF recurrence and RHD at the end of follow-up (p=NS).

Conclusions: Poor adherence to secondary prophylaxis does not seem to be associated with increased risk of RHD in developed countries. Further studies are needed to confirm our data in a larger population.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2020

Transitional care of young people with juvenile idiopathic arthritis in Italy: results of a Delphi consensus survey.

Clin Exp Rheumatol 2019 Nov-Dec;37(6):1084-1091. Epub 2019 Jul 25.

UOC Reumatologia, IRCCS Fondazione Policlinico San Matteo and Università degli Studi di Pavia, Italy.

Objectives: To present the results of a Delphi consensus survey among Italian paediatric and adult rheumatologists on transitional care (TC) of young people (YP) with juvenile idiopathic arthritis (JIA).

Methods: A taskforce of 27 paediatric and adult rheumatologists evaluated the applicability of the 2016 EULAR/PReS recommendations for TC to the Italian rheumatology practice and healthcare system and formulated additional country-specific statements aimed to increase their suitability. After a two-round discussion, applicability of EULAR/PReS recommendations and agreement with newly-proposed statements were voted on a 0-10 scale (where 0 = no applicability/agreement and 10 = total applicability/agreement). A mean level of agreement ≥8 was deemed acceptable.

Results: The consensus threshold was reached for only 4 of the 12 EULAR/PReS recommendations and for 25 of the 27 country-specific statements. Poor agreement with EULAR/PReS recommendations was mostly explained by paucity of centres in Italy that possess both paediatric and adult rheumatologists, disagreement about optimal time of transition start and de nition of transition coordinator, diversity between paediatric and adult clinimetric assessments, and lack of administrative and financial support.

Conclusions: This consensus initiative represents an important step forward toward the establishment of a nationwide TC network for YP with JIA in Italy. The main goals established for the future are the identification of adult rheumatology centres that are willing to participate in the TC process, the education of adult rheumatology teams on childhood-onset rheumatic diseases and transition issues, and the increased awareness of public healthcare authorities and other stakeholders about the importance of good-quality TC.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2019

Etanercept treatment for extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, or psoriatic arthritis: 6-year efficacy and safety data from an open-label trial.

Arthritis Res Ther 2019 05 23;21(1):125. Epub 2019 May 23.

Clinica Pediatrica e Reumatologia, IRCCS Istituto Giannina Gaslini, EULAR Centre of Excellence in Rheumatology 2008-2023, Paediatric Rheumatology International Trials Organisation (PRINTO), Via Gaslini, 5, 16147, Genoa, Italy.

Background: To describe the 6-year safety and efficacy of etanercept (ETN) in children with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), and psoriatic arthritis (PsA) METHODS: Patients who completed the 2-year, open-label, phase III CLinical Study In Pediatric Patients of Etanercept for Treatment of ERA, PsA, and Extended Oligoarthritis (CLIPPER) were allowed to enroll in its 8-year long-term extension (CLIPPER2). Children received ETN at a once-weekly dose of 0.8 mg/kg, up to a maximum dose of 50 mg/week. Efficacy assessments included the JIA core set of outcomes, the JIA American College of Rheumatology response criteria (JIA-ACR), and the Juvenile Arthritis Disease Activity Score (JADAS). Efficacy data are reported as responder analyses using a hybrid method for missing data imputation and as observed cases. Safety assessments included treatment-emergent adverse events (TEAEs).

Results: Out of 127 patients originally enrolled in CLIPPER, 109 (86%) entered CLIPPER2. After 6 years of trial participation (2 years in CLIPPER and 4 years in CLIPPER2), 41 (32%) patients were still taking ETN, 13 (11%) entered the treatment withdrawal phase after achieving low/inactive disease (of whom 7 had to restart ETN), 36 (28%) discontinued treatment for other reasons but are still being observed, and 37 (29%) discontinued treatment permanently. According to the hybrid imputation analysis, proportions of patients achieving JIA ACR90, JIA ACR100, and JADAS inactive disease after the initial 2 years of treatment were 58%, 48%, and 32%, respectively. After the additional 4 years, those proportions in patients who remained in the trial were 46%, 35%, and 24%. Most frequently reported TEAEs [n (%), events per 100 patient-years] were headache [28 (22%), 5.3], arthralgia [24 (19%), 4.6], and pyrexia [20 (16%), 3.8]. Number and frequency of TEAEs, excluding infections and injection site reactions, decreased over the 6-year period from 193 and 173.8, respectively, during year 1 to 37 and 61.3 during year 6. A single case of malignancy (Hodgkin's lymphoma) and no cases of active tuberculosis, demyelinating disorders, or deaths were reported.

Conclusions: Open-label etanercept treatment for up to 6 years was safe, well tolerated, and effective in patients with eoJIA, ERA, and PsA.

Trial Registration: ClinicalTrials.gov: CLIPPER, NCT00962741 , registered 20 August, 2009, CLIPPER2, NCT01421069 , registered 22 August, 2011.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-019-1916-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533709PMC
May 2019

Lung function in children with juvenile idiopathic arthritis: A cross-sectional analysis.

Pediatr Pulmonol 2019 08 17;54(8):1242-1249. Epub 2019 May 17.

Department of Pediatrics, University of Chieti, Chieti, Italy.

Aim: We measured respiratory parameters in children with juvenile idiopathic arthritis (JIA) without clinical signs of respiratory involvement and assessed the influence of methotrexate (MTX) treatment and disease activity on lung function.

Methods: In 49 JIA children and 70 controls lung volumes by spirometry and body plethysmography, and lung diffusion for carbon monoxide (DLCO) with single-breath technique were evaluated.

Results: DLCO was significantly different between JIA children and controls (P = .01), whereas no differences were found in flow expiratory volume in 1 second (FEV ), forced vital capacity (FVC), forced expiratory flow at 25% to 75% of FVC (FEF ), peak expiratory flow, total lung capacity, and residual volume. After dividing study JIA patients according to MTX treatment, a significant difference in DLCO was found among JIA patients treated with MTX and those treated with other drugs and controls (P < .001). A significant difference in DLCO was also found among JIA patients with active disease and those with inactive disease and controls (P = .003). Analysis of covariance showed a weak independent effect of MTX therapy on DLCO after adjusting for sex and height (P = .04). Furthermore, a negative correlation of DLCO with MTX cumulative dose and MTX treatment duration (r = -.58, P = .006; r = -.68, P = .001, respectively) was found, whereas there was no correlation between DLCO and disease activity (r = -.10; P = .51).

Conclusions: In JIA children MTX treatment seems to have a dose-dependent effect on lung function. For this reason in these patients, a regular assessment of lung function, especially with DLCO evaluation, is recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ppul.24360DOI Listing
August 2019

Asymptomatic Multiple Liver Granulomas in a Child.

J Paediatr Child Health 2019 Jan;55(1):119-120

Pediatric Rheumatology Unit, SS Annunziata Hospital, Chieti, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpc.14326DOI Listing
January 2019

Kerion celsi caused by Trichophyton tonsurans in a child.

Lancet Infect Dis 2018 07;18(7):812

Department of Paediatrics, University of Chieti, Chieti, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(18)30105-1DOI Listing
July 2018

90K immunostimulatory glycoprotein in children with juvenile idiopathic arthritis.

Mod Rheumatol 2018 Jul 20;28(4):637-641. Epub 2017 Nov 20.

a Department of Pediatrics , University of Chieti , Chieti , Italy.

Objectives: To assess whether circulating levels of 90K glycoprotein are increased in children with juvenile idiopathic arthritis (JIA) at different stages of the disease, compared to healthy controls and to evaluate potential over time changes in its concentrations following treatment with the antitumor-necrosis factor (TNF) drug etanercept.

Methods: 90K glycoprotein, C-reactive protein, erythrocyte sedimentation rate, TNF, antinuclear antibodies, rheumatoid factor and the Juvenile Arthritis Disease Activity Score were assessed in 71 children: 23 with newly diagnosed JIA, 23 with established and active JIA and 25 healthy controls. Patients, eligible for anti-TNF treatment, underwent a similar clinical/laboratory assessment after 6- and 12-month etanercept therapy.

Results: At baseline, significant differences were found in 90K levels between the three study groups: JIA at onset (157.7 [131.4-241.5] μg/ml), JIA on treatment (90.0 [68.8-120.2] μg/ml) and control group (58.0 [44.5-79.0] μg/ml), (p for trend <.001), with the JIA at onset group showing the highest values. In the JIA on treatment group, following one-year etanercept treatment, a significant reduction in 90K was detected already at 6 months (74.3 [56.0-104.1] μg/ml p = .001) and a further decline was observed at 12 months (49.3 [46.0-67.6] μg/ml p < .001).

Conclusion: Our study showed that 90K glycoprotein levels are increased in JIA children compared to healthy controls, suggesting a potential pathogenetic role in the JIA. Besides, 12 months of therapy with etanercept can reduce 90K levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14397595.2017.1397895DOI Listing
July 2018

Macrophage activation syndrome in Still's disease: analysis of clinical characteristics and survival in paediatric and adult patients.

Clin Rheumatol 2017 Dec 15;36(12):2839-2845. Epub 2017 Sep 15.

Division of Rheumatology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.

Macrophage activation syndrome (MAS) is a reactive form of hemophagocytic lymphohistiocytosis, complicating Still's disease, both in paediatric and adult patients. In this work, we aimed to investigate clinical picture and outcome of Still's disease patients developing MAS. We performed a retrospective analysis of patients, both paediatrics and adults, affected by Still's disease attending our department. During the follow-up, each patient was investigated for MAS occurrence and possible predictors, clinical and laboratory factors, were analysed. We evaluated 50 patients affected by Still's disease, 21 paediatric and 29 adult patients. Ten patients experienced MAS (five adult and five paediatric patients) and its development significantly reduced the survival rate when compared with patients without this complication (p < 0.0001). The analysis of possible predictors showed that high-value systemic score (p = 0.03) and high levels of serum ferritin (p = 0.002) were independently associated with an increased likelihood of MAS. MAS occurrence significantly reduced survival rate in both paediatric and adult patients affected by Still's disease. The high levels of serum ferritin and an elevated systemic score, at the time of diagnosis, were significantly associated with MAS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-017-3830-3DOI Listing
December 2017

MBL2 and FCN2 gene polymorphisms in a cohort of Italian children with rheumatic fever: A case-control study.

Semin Arthritis Rheum 2017 10 27;47(2):264-268. Epub 2017 Apr 27.

Department of Paediatrics, "G. d'Annunzio" University, Chieti-Pescara, Italy. Electronic address:

Background: Mannose-binding lectins and human ficolins are pattern-recognition proteins involved in innate immunity. A role for MBL2 and FCN2 gene polymorphisms in the pathogenesis of recurrent severe streptococcal infections and rheumatic carditis has been suggested.

Objectives: The aim of this study is to evaluate the presence of MBL2 and FCN2 gene polymorphisms (SNPs) in children with a history of rheumatic fever (RF) and to investigate their possible role in RF clinical presentation and disease course.

Methods: A total of 50 Caucasian patients with RF were recruited with a control group of 52 healthy children. DNA was extracted for analysis of MBL2 gene (exon 1, codons: 52, 54, and 57) and FCN2 gene (promoter region at position -986, -602, and -4).

Results: The FCN2 AG genotype at the -986 position was more frequently observed in patients, as compared to healthy subjects (p = 0.006); furthermore, the A allele was identified as a possible risk factor for the development of RF (OR = 7.14, CI: 2.439-20.89). Conversely, the GG genotype at the same position was observed more frequently in the control group and can be considered a protective factor for the development of the disease (p = 0.001, OR = 8.37, 95% CI: 2.763-25.33). In addition, the FCN2 GG and AG genotypes in the -4 position were also found to be protective factors for the development of RF and for carditis respectively (OR = 3.32, CI: 1.066-10.364; OR = 0.15, 95% CI: 0.037-0.566). Finally, the AA genotype in the -602 position was associated with a late onset of RF (p = 0.006). The analysis of the MBL2 gene only resulted in a higher frequency of the AA genotype on position 57 in controls as compared to patients (p = 0.025).

Conclusions: This is the first study evaluating the FCN2 gene polymorphisms in patients with RF and rheumatic carditis finding a protective effect of -986 GG and -4 GG genotypes in the development of RF and the -4 AG genotype for the development of carditis. Our data do not support a possible role for MBL2 polymorphisms in the pathogenesis and in the clinical manifestations of RF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.semarthrit.2017.04.006DOI Listing
October 2017

Protein-losing enteropathy in an infant with rotavirus infection.

Paediatr Int Child Health 2018 05 6;38(2):154-157. Epub 2017 Mar 6.

a Department of Paediatrics , University of Chieti , Chieti , Italy.

Protein-losing enteropathy (PLE) is a rare gastro-intestinal complication characterised by intestinal loss of proteins with consequent hypoproteinaemia and generalised oedema. Rotavirus infection associated with PLE in children has rarely been reported. A 6-month-old girl presented with diarrhoea, fever and generalised oedema. Total serum proteins were 34 g/L (61-79) and plasma albumin 16.8 g/L (40-50), serum sodium was 126 mmol/L and there was mild metabolic alkalosis (pH 7.46). Stool for alpha-1 antitrypsin was >1.2 mg/g (<0.6) which supported the diagnosis of PLE. Stool examination demonstrated the presence of rotavirus antigen by the rapid immunochromatographic test. Abdominal ultrasound showed bowel distension and intestinal wall thickening with a small amount of ascites. Echocardiography excluded pericardial effusion. Two albumin infusions (1 g/kg) were required to sustain normal serum albumin levels. Over the next 2 weeks, there was gradual normalisation of stools and progressive reduction of oedema. In children with acute and symptomatic PLE, rotavirus should be considered in the differential diagnosis. The availability of the rapid immunochromatographic test facilitates the diagnosis. In most cases, supportive care alone is sufficient, but albumin infusions may be required in more severely affected children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/20469047.2017.1295011DOI Listing
May 2018

Intra-articular corticosteroids versus intra-articular corticosteroids plus methotrexate in oligoarticular juvenile idiopathic arthritis: a multicentre, prospective, randomised, open-label trial.

Lancet 2017 03 3;389(10072):909-916. Epub 2017 Feb 3.

Istituto Giannina Gaslini, Genoa, Italy; Università degli Studi di Genova, Genoa, Italy.

Background: Little evidence-based information is available to guide the treatment of oligoarticular juvenile idiopathic arthritis. We aimed to investigate whether oral methotrexate increases the efficacy of intra-articular corticosteroid therapy.

Methods: We did this prospective, open-label, randomised trial at ten hospitals in Italy. Using a concealed computer-generated list, children younger than 18 years with oligoarticular-onset disease were randomly assigned (1:1) to intra-articular corticosteroids alone or in combination with oral methotrexate (15 mg/m; maximum 20 mg). Corticosteroids used were triamcinolone hexacetonide (shoulder, elbow, wrist, knee, and tibiotalar joints) or methylprednisolone acetate (ie, subtalar and tarsal joints). We did not mask patients or investigators to treatment assignments. Our primary outcome was the proportion of patients in the intention-to-treat population who had remission of arthritis in all injected joints at 12 months. This trial is registered with European Union Clinical Trials Register, EudraCT number 2008-006741-70.

Findings: Between July 7, 2009, and March 31, 2013, we screened 226 participants and randomly assigned 102 to intra-articular corticosteroids alone and 105 to intra-articular corticosteroids plus methotrexate. 33 (32%) patients assigned to intra-articular corticosteroids alone and 39 (37%) assigned to intra-articular corticosteroids and methotrexate therapy had remission of arthritis in all injected joints (p=0·48). Adverse events were recorded for 20 (17%) patients who received methotrexate, which led to permanent treatment discontinuation in two patients (one due to increased liver transaminases and one due to gastrointestinal discomfort). No patient had a serious adverse event.

Interpretation: Concomitant administration of methotrexate did not augment the effectiveness of intra-articular corticosteroid therapy. Future studies are needed to define the optimal therapeutic strategies for oligoarticular juvenile idiopathic arthritis.

Funding: Italian Agency of Drug Evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(17)30065-XDOI Listing
March 2017

Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept.

Pediatr Rheumatol Online J 2016 Dec 20;14(1):68. Epub 2016 Dec 20.

Policlinico Universitario A. Gemelli, Roma, Italy.

Background: Data from routine clinical practice are needed to further define the efficacy and safety of biologic medications in children with juvenile idiopathic arthritis (JIA). The aim of this analysis was to investigate the disease status, reasons for discontinuation and adverse events in Italian JIA patients treated with etanercept (ETN).

Methods: In 2013, all centers of the Italian Pediatric Rheumatology Study Group were asked to make a census of patients given ETN after January 2000. Patients were classified in three groups: group 1 = patients still taking ETN; group 2 = patients discontinued from ETN for any reasons; group 3 = patients lost to follow-up while receiving ETN. All three groups received a retrospective assessment; patients in group 1 also underwent a cross-sectional assessment.

Results: 1038 patients were enrolled by 23 centers: 422 (40.7%) were in group 1, 462 (44.5%) in group 2, and 154 (14.8%) in group 3. Median duration of ETN therapy was 2.5 years. At cross-sectional assessment, 41.8% to 48.6% of patients in group 1 met formal criteria for inactive disease, whereas 52.4% of patients in group 2 and 55.8% of patients in group 3 were judged in clinical remission by their caring physician at last visit. A relatively greater proportion of patients with systemic arthritis were discontinued or lost to follow-up. Parent evaluations at cross-sectional visit in group 1 showed that 52.4% of patients had normal physical function, very few had impairment in quality of life, 51.2% had no pain, 76% had no morning stiffness, and 82.7% of parents were satisfied with their child's illness outcome. Clinically significant adverse events were reported for 27.8% of patients and ETN was discontinued for side effects in 9.5%. The most common adverse events were new onset or recurrent uveitis (10.2%), infections (6.6%), injection site reactions (4.4%), and neuropsychiatric (3.1%), gastrointestinal (2.4%), and hematological disorders (2.1%). Ten patients developed an inflammatory bowel disease and 2 had a malignancy. One patient died of a fulminant streptococcal sepsis.

Conclusions: Around half of the patients achieved complete disease quiescence under treatment with ETN. The medication was overall well tolerated, as only one quarter of patients experienced clinically significant adverse events and less than 10% had treatment discontinued for toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12969-016-0126-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170898PMC
December 2016

Autoimmune sensorineural hearing loss as presenting manifestation of paediatric Behçet disease responding to adalimumab: a case report.

Ital J Pediatr 2016 Sep 6;42(1):81. Epub 2016 Sep 6.

Department of Pediatrics, University of Chieti, Via dei Vestini 5, Chieti, 66100, Italy.

Background: Autoimmune sensorineural hearing loss, also known as autoimmune inner ear disease (AIED) is a rare clinical entity characterized by progressive and bilateral sensorineural hearing loss often accompanied by vestibular symptoms. Diagnosis is essential as a consistent number of patients show a positive response to steroids alone or in association with other immunosuppressive drugs. AIED is defined as primary when the disease is limited to the ear, whereas in up to a third of cases it is associated to other systemic autoimmune diseases such as Behçet disease (BD). BD is a rare multisystem vasculitis characterized by recurrent oral and genital aphtosis, uveitis, skin lesions, neurological and vascular manifestations. Clinical presentation is variable thus making the diagnosis difficult in many instances. The choice of therapy is also limited by the scarceness of high-quality therapy studies.

Case Presentation: We present a 15-year-old-boy with six months of history of fever, dizziness, tinnitus and ataxia. He had a final diagnosis of AIED associated to BD and was successfully treated with the anti-tumor necrosis factor (TNF)-α adalimumab.

Conclusions: This case report points out to the diagnostic and therapeutic challenges of BD especially when unusual symptoms are the prominent manifestations of the disease. It also suggests that adalimumab is a good therapeutic option in children with BD and audiovestibular symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13052-016-0291-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011950PMC
September 2016

Neonatal-Onset Urticaria and Fever.

J Pediatr 2016 Oct 8;177:329-329.e1. Epub 2016 Aug 8.

UO Pediatria II G. Gaslini Scientific Institute Genova, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2016.07.004DOI Listing
October 2016

Recurrent pericarditis in children and adolescents: a multicentre cohort study.

J Cardiovasc Med (Hagerstown) 2016 Sep;17(9):707-12

aCardiology Department, Maria Vittoria Hospital and University of Torino, Torino bInternal Medicine, Ospedale Papa Giovanni XXIII, Bergamo, Italy cMaastricht University, Faculty of Medicine, Maastricht, the Netherlands dPediatrics Department, University of Chieti, Chieti eRheumatology Department, University of Siena, Siena fMeyer Children Hospital, Firenze gUOS Reumatologia Pediatrica - Fondazione IRCCS Ca' Granda Milan, Milan, Italy hDivision of Rheumatology, Department of Paediatric Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome iCardiology Department, Monaldi Hospital, Second University of Naples, Naples jUniversity of Genoa and Pediatria II Istituto Gianna Gaslini, Genova, Italy kDivisions of Emergency Medicine and Clinical Pharmacology and Toxicology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada *Drs. Finkelstein and Martini are cosenior authors.

Objective: Limited data are available about recurrent pericarditis in children. We sought to explore contemporary causes, characteristics, therapies and outcomes of recurrent pericarditis in paediatric patients.

Methods: A multicentre (eight sites) cohort study of 110 consecutive cases of paediatric patients with at least two recurrences of pericarditis over an 11-year period (2000-2010) [median 13 years, interquartile range (IQR) 5, 69 boys].

Results: Recurrences were idiopathic or viral in 89.1% of cases, followed by postpericardiotomy syndrome (9.1%) and familial Mediterranean fever (0.9%). Recurrent pericarditis was treated with nonsteroidal anti-inflammatory drugs (NSAIDs) in 80.9% of cases, corticosteroids in 64.8% and colchicine was added in 61.8%. Immunosuppressive therapies were administered in 15.5% of patients after subsequent recurrences. After a median follow-up of 60th months, 528 subsequent recurrences were recorded (median 3, range 2-25). Corticosteroid-treated patients experienced more recurrences (standardized risk of recurrence per 100 person-years was 93.2 for patients treated with corticosteroids and 45.2 for those without), side effects and disease-related hospitalizations (for all P < 0.05). Adjuvant therapy with colchicine was associated with a decrease in the risk of recurrence from 3.74 per year before initiation of colchicine to 1.37 per year after (P < 0.05). Anakinra therapy (n = 12) was associated with a drop in the number of recurrences from 4.29 per year before to 0.14 per year after (P < 0.05). Transient constrictive pericarditis developed in 2.7% of patients.

Conclusion: Recurrent pericarditis has an overall favourable prognosis in children, although it may require frequent readmissions and seriously affect the quality of life, especially in patients treated with corticosteroids. Colchicine or anakinra therapies were associated with significant decrease in the risk of recurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2459/JCM.0000000000000300DOI Listing
September 2016

Chronic nonbacterial osteomyelitis may be associated with renal disease and bisphosphonates are a good option for the majority of patients.

Acta Paediatr 2016 Jul 24;105(7):e328-33. Epub 2016 Apr 24.

University of Trieste, Trieste, Italy.

Aim: The aim of this Italian study was to describe the clinical features, treatment options and outcomes of a cohort of patients with chronic nonbacterial osteomyelitis (CNO).

Methods: This was a retrospective cohort study. Laboratory data, diagnostic imaging, histological features and clinical course are reported.

Results: We enrolled 47 patients diagnosed with CNO. Bone pain was the leading symptom, and multifocal disease was present in 87% of the patients. The majority of the bone lesions were located in the appendicular skeleton (58%). Extraosseous manifestations were present in 34% of the patients, and renal involvement was detected in four patients. Inflammatory indices were increased in 80%, and bone x-rays were negative in 15% of the patients. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the first therapy for all patients, achieving clinical remission in 27%. A good response to NSAIDs was significantly associated with a better prognosis. Bisphosphonates were used in 26 patients, with remission in 73%. Only six patients (13%), all with spine involvement, developed sequelae.

Conclusion: We found a possible association between CNO and renal disease. Bisphosphonates were more likely to lead to clinical remission when NSAIDs and corticosteroids had failed. Vertebral localisation was the only risk factor for potential sequelae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apa.13420DOI Listing
July 2016

Escherichia coli Urinary Infection as a Cause of Acute Hemorrhagic Edema in Infancy.

Pediatr Dermatol 2015 Nov-Dec;32(6):e309-11. Epub 2015 Oct 8.

Department of Pediatrics, University of Chieti, Chieti, Italy.

Acute hemorrhagic edema of infancy (AHEI) is a benign leukocytoclastic small-vessel vasculitis that affects infants, presenting with a classic clinical triad. Because of the self-limited progression, conservative management is the most common approach. We describe a case of AHEI apparently triggered by an Escherichia coli urinary tract infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pde.12690DOI Listing
September 2016

Dissecting the heterogeneity of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.

J Rheumatol 2015 Jun 15;42(6):994-1001. Epub 2015 Apr 15.

From the Istituto Giannina Gaslini, Genoa, Italy; Karolinska University Hospital Solna, Stockholm, Sweden; Gulhane Military Medical Faculty, Ankara, Turkey; Royal Children's Hospital, Melbourne, Australia; Bakırkoy Maternity and Children Education and Research Hospital, Istanbul, Turkey; King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Policlinico Università di Catania, Catania, Italy; Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil; Universitaetsklinik fuer Kinderheilkunde, Inselspital, Berne, Switzerland; Ospedale Policlinico, Chieti, Italy; Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico; University of Messina, Messina, Italy; Carolinas HealthCare System, Charlotte, North Carolina; Women and Children's Hospital, Buffalo, New York, USA; Zentrum fuer Allgemeine Paediatrie und Neonatologie, Sankt Augustin, Germany; Stanford School of Medicine, Palo Alto, California, USA; Department for Immunology and Rheumatology, Children's Hospital of Zagreb, Zagreb, Croatia; Steven and Alexandra Cohen Children's Hospital of New York, New York, New York, USA; IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy; University of Latvia, Riga, Latvia; Hospital das Clínicas, Botucatu, Brazil; King Fahad National Guard Hospital, Riyadh, Saudi Arabia; Arkansas Children's Hospital, Little Rock, Arkansas, USA; Kyriakou Children's Hospital of Athens, Athens, Greece; The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Children's University Hospital, Riga, Latvia; Hospital Universitario 12 de Octubre, Madrid, Spain; M. Iashvili Children's Central Clinic, Tbilisi, Georgia; Azienda Ospedaliera Universitaria Ospedali Riuniti, Ancona, Italy; Gazi University, Ankara, Turkey; Università degli Studi di Genova, Genoa, Italy; University of Alabama at Birmingham, Birmingham, Alabama, USA.F. Minoia, MD; S. Davì, MD, Istituto Giannina Gaslini; A. Horne, M

Objective: To seek insights into the heterogeneity of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA) through the analysis of a large patient sample collected in a multinational survey.

Methods: International pediatric rheumatologists and hemato-oncologists entered their patient data, collected retrospectively, in a Web-based database. The demographic, clinical, laboratory, histopathologic, therapeutic, and outcome data were analyzed in relation to (1) geographic location of caring hospital, (2) subspecialty of attending physician, (3) demonstration of hemophagocytosis, and (4) severity of clinical course.

Results: A total of 362 patients were included by 95 investigators from 33 countries. Demographic, clinical, laboratory, and histopathologic features were comparable among patients seen in diverse geographic areas or by different pediatric specialists. Patients seen in North America were given biologics more frequently. Patients entered by pediatric hemato-oncologists were treated more commonly with biologics and etoposide, whereas patients seen by pediatric rheumatologists more frequently received cyclosporine. Patients with demonstration of hemophagocytosis had shorter duration of sJIA at MAS onset, higher prevalence of hepatosplenomegaly, lower levels of platelets and fibrinogen, and were more frequently administered cyclosporine, intravenous immunoglobulin (IVIG), and etoposide. Patients with severe course were older, had longer duration of sJIA at MAS onset, had more full-blown clinical picture, and were more commonly given cyclosporine, IVIG, and etoposide.

Conclusion: The clinical spectrum of MAS is comparable across patients seen in different geographic settings or by diverse pediatric subspecialists. There was a disparity in the therapeutic choices among physicians that underscores the need to establish uniform therapeutic protocols.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.141261DOI Listing
June 2015
-->