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COVID-19 was declared a pandemic on 11 March 2020 and unprecedented containment measures were taken to limit its spreading. These exceptional measures may have an impact on the mental health of the population.We hypothesize that children with the rheumatological chronic disease might be a population at higher risk of psychological distress.This study evaluated the psychological effect of social distancing in pediatric rheumatological patients and its possible correlation with disease relapse.Pediatric patients diagnosed with juvenile idiopathic arthritis (JIA) were included in the study.They completed the Multidimensional Anxiety Scale for Children (MASC-2) to assess anxious symptoms, the Children Depression Inventory Self Report (CDI-2 SR) for depression symptoms and a semi-structured questionnaire to collect their activities. Their parents completed the Children Depression Inventory 2 Parent (CDI-2 P).The MASC-2 test showed high values in anxiety factors. The CDI-2 SR test showed high values for Ineffectiveness and Functional Problems. The CDI-2 P showed high values for Emotional Problems factor. All the patients with high level of depression were females. The result is that those who take therapy were younger, have reduced values in Functional Problems and in Social Anxiety. 47% of the sample had disease relapse.During the COVID-19 period of isolation, in patients with JIA, there was an increase in anxious and depressive symptoms in female adolescents, a tendency to disease relapse, despite generally good compliance to therapy. Those under treatment were younger and showed reduced values in Functional Problems, Social Anxiety, and Humiliation/Rejection.Limited number of patients to whom questionnaires could be distributed.

Severe Acute Respiratory Syndrome – Coronavirus – 2 (SARS-CoV-2) and its related Coronavirus Disease – 19 (COVID-19) has become a health emergency worldwide. The medical community has been concerned since the beginning of the outbreak about the potential impact of COVID-19 in children, especially in those with underlying chronic diseases. Fortunately, COVID-19 has been reported to be less severe in children than in adults. However, epidemiologic and clinical data are scarce. Children show unique features of SARS-CoV-2 involvement that may account for the low rate of infection and death in this age group. The purpose of this review is to summarize the most relevant evidence of COVID-19 in children highlighting similarities and differences with adults.

SARS-CoV2 infection may present at onset with cutaneous manifestations as chilblains, pernio-like lesions characterized by rapid onset, itching, pain and tenderness and quick improvement with re-warming as similarly observed in primary acrocyanosis. The purpose of the present study was to detect in a single institution series of pediatric patients, during COVID-19 pandemic, the prevalence of acrocyanosis compared to previous period and an eventual correlation with SARS-Cov2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection or other secondary etiologies of this disorder.We retrospectively analyzed the prevalence of pediatric patients with acrocyanosis between January 2020 and July 2021, compared to the same period of previous year. All patients were investigated with capillaroscopies, clinical and laboratory texts. Those patients referred to our Institution, during the Covid-19 pandemic were also examined for SARS-CoV2 serologies to find out an eventual specific correlation with this secondary potential etiology.During the first wave of Covid-19 pandemic we observed an increased prevalence of this manifestation. The analysis showed that the higher prevalence of patients with acrocyanosis, in this period, was not related to SARS-Cov2 infection.The acrocyanosis in pediatric patients is rarely associated with rheumatological diseases, being more frequently a primary disorder and strictly related to a sedentary lifestyle.

The overwhelming success of tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML) patients has opened a discussion among medical practitioners and the lay public on the real possibility of pregnancy and conception in females and males with CML. In the past 10 years this subject has acquired growing interest in the scientific community and specific knowledge has been obtained “from bench to bedside”. Embryological, pharmacological, and pathophysiological studies have merged with worldwide patient databases to provide a roadmap to a successful pregnancy and birth in CML patients. Male conception does not seem to be affected by TKI therapy, since this class of drugs is neither genotoxic nor mutagenic, however, caution should be used specially with newer drugs for which little or no data are available. In contrast, female patients should avoid TKI therapy specifically during the embryonic stage of organogenesis (5–12 weeks) because TKIs can be teratogenic. In the last 15 years, 41 pregnancies have been followed in our center. A total of 11 male conceptions and 30 female pregnancies are described. TKI treatment was generally terminated as soon as the pregnancy was discovered (3–5 weeks), to avoid exposure during embryonic period and to reduce the risk of needing treatment in the first trimester. Eleven pregnancies were treated with interferon, imatinib or nilotinib during gestation. Nilotinib plasma levels in cord blood and maternal blood at delivery were studied in 2 patients and reduced or absent placental crossing of nilotinib was observed. All of the patients were managed by a multidisciplinary team of physicians with obligatory hematological and obgyn consultations. This work provides an update on the state of the art and detailed description of pregnancy management and outcomes in CML patients.

Objectives Auto-inflammatory Diseases (AIDs) are a group of diseases with a strong genetic component, inducing an inappropriate activation of innate immunity. The patients with pediatric onset will face the transitional care (TC) from a pediatrician to an adult care setting, during the critical phase of the adolescence. That implies a risk of failure and drop out, due to the different approach of pediatrician compared to the adult doctor. To describe the model of TC for AIDs from a paediatric to adult centre of two hospitals in Rome, and to pointing out the different steps emerged from specific experiences. Methods In November 2020, a Board of paediatricians and internists discussed their experience to identify “hot topics” for a successful management of TC. Results The Board agreed on the optimal time for the transition (12–18 years). Specific elements to be considered are the reached level of emotional and intellectual maturity, and the clinical stability of the disease. Conclusions The TC of patients with chronic AIDs, requires a strong cooperation to define the adequate follow-up, and to guarantee the compliance to the treatment. This model allows us to investigate AIDs complex cases, requiring a long period of observations.

The primary aim of this study was to assess the impact of an education intervention on knowledge regarding medication use in hospitalized children and adolescents.A pre-post multicentre study was conducted in pediatric wards of the hospitals in Lazio Region between July 2019-March 2021. An in-person education intervention was provided to hospitalized patients aged 6-15 years, able to understand spoken and written Italian language. Topics included: correct intake and management of medications at home. Prior and after the education intervention, we evaluated patient knowledge with a self-administered test.One-hundred-and-four (n = 104) patients participated in the study. In the pre-education period, 79.8% of the patients answered correctly to at least 60% of the questions of the test; the lowest number of correct answers concerned medication intake (36.5%; 33.6%), food-drug interactions (44.2%), appropriate indication to use of antibiotics (36.5%) and antibiotic resistance (55.8%). After the education intervention, 100% of the patients completed the test correctly.The education intervention increased knowledge on several areas of interest, in children of different age-groups and including patients with chronic diseases.Children's education is essential to encourage gradual transfer of responsibility for medication use, in ways that respect parental responsibilities and the health status and capabilities of the child.

In Italy, during the second epidemic wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapid antigenic (Ag) test at point-of-care (POCT) station were employed to quickly evaluate large numbers of swabs. We collected data of all children who underwent the Ag test in our hospital. All positive patients were recalled to perform reverse transcription polymerase chain reaction. A total of 2133 tests were collected over 1 month. Clinical data of 1941 children (median age = 3.7 years) were analyzed: 1343 (69.2%) patients complained of symptoms, 594 (30.6%) had a history of close contact with SARS-CoV-2-positive individuals. Among symptoms reported, acute rhinitis was the most frequent (67.9%), followed by cough (42.6%) and fever (31.5%). Among all tests, 95.8% resulted negative, 4.2% positive: 37/89 were confirmed. In confirmed cases, fever (56.2% vs 32.2%; P = .041) and gastrointestinal symptoms (18.8% vs 6.25%; P = .041) were significantly more frequent compared with negative children. The use of POCT for Ag test seems appropriate for SARS-CoV-2 screening in the pediatric population. In children, fever and gastrointestinal symptoms may constitute red flags of SARS-CoV-2.

Aim of these revised recommendations for the general management of Kawasaki disease is to encourage its prompter recognition and warrant the most appropriate therapy, based on ascertained scientific data, raising awareness of the complications related to misdiagnosis or delayed treatment. A set of 20 synthetic operative statements is herein provided, including the definition of Kawasaki disease, its protean presentations, clinical course and seminal treatment modalities of all disease phases. The application of these recommendations should improve prognosis of Kawasaki disease and prevent the progression to permanent vascular abnormalities, thereby diminishing morbidity and mortality.

Background: Although epidemic, novel coronavirus (SARS-CoV-2) infection rarely affects pediatric population. However, in the last months an increasing number of Italian pediatricians has reported the occurrence of erythema pernio-like in children following a flu-like syndrome, after the outbreak of SARS-CoV-2 infection. Objective: To report cutaneous manifestation of SARS-CoV-2 infection in 4 adolescents. Methods: Observational study reporting 4 adolescents with skin lesions, 2 weeks after the occurrence of a flu-like syndrome. Results: Fourteen days after a flu-like syndrome, adolescents exhibited skin lesions to toes and feet. These lesions were rounded, with blurred limits, with a 5-15 mm diameter, red-violaceous- bluish colored, sometimes resulting in bullous lesions in correspondence of the central or apical portion, which tended to be covered with blackish crusts after evolution. Lesions were also accompanied by pain of variable intensity and evolved within two or three weeks to self-resolution without particular sequelae. In two patients, pharyngeal and nasal swabs were negative for SARSCoV- 2 infection, at the presentation of skin lesions. After 2 months from clinical manifestations, patients were tested positive for SARS-CoV-2 antibodies. Conclusions: In pediatric and adolescent population, the occurrence of an erythema pernio-like after a flu-like syndrome could be associated to SARS-CoV-2 infection.

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Italian language.The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents.The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity).A total of 1296 JIA patients (7.2% systemic, 59.5% oligoarticular, 21.4% RF negative polyarthritis, 11.9% other categories) and 100 healthy children, were enrolled in 18 centres. The JAMAR components discriminated well healthy subjects from JIA patients except for the Health Related Quality of Life (HRQoL) Psychosocial Health (PsH) subscales. All JAMAR components revealed good psychometric performances.In conclusion, the Italian version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Acute mastoiditis (AM) is the most common complication of acute otitis media (AOM) and is one of the most severe acute bacterial diseases in infants and children. In some geographic areas, the incidence of AM is increasing, and the causative role of some bacterial pathogens could be greater than previously thought. In this paper, the results of a study that evaluated the epidemiology and microbial etiology of paediatric AM in Umbria, which is a region of central Italy, are reported. This is a retrospective study of patients aged 0&ndash, 14 years with AM admitted to the pediatric wards of the hospitals of Umbria, Italy, between June 1 and September 30 in four consecutive years (2015&ndash, 2018). A total of 108 children were enrolled. The prevalence of AM in males during the four years of analysis was significantly higher than that in females at 63% (95% confidence intervals [CI]: 0.54&ndash, 0.72). The most frequently affected age groups were 5&ndash, 9 years (45.4%) and 10&ndash, 14 years (31.5%), with statistically significant differences in comparison with children aged &lt, 1 year (5.6%, 95% CI: 0.01&ndash, 0.10) and 1&ndash, 4 years (17.6%, 95% CI: 0.10&ndash, 0.25). In most cases (64, 59.3%), AM was associated with spontaneous tympanic membrane perforation (STP). The culture of the middle ear fluid revealed the presence of Pseudomonas aeruginosa in 56 cases (51.6%). The mean incidence rates of pediatric AM in Umbria during the study increased significantly with time, as it was 18.18/100,000 children/year in 2015&ndash, 2016 and 29.24/100,000 children/year in 2017&ndash, 2018 (CI difference: +2.5 &ndash, +19.9, p &lt, 0.05). The incidence rates of Pseudomonas aeruginosa detection in pediatric AM associated with STP significantly increased with time. The incidence was 6.06/100,000 children/year in 2015&ndash, 2016 and 18.61/100,000 children/year in 2017&ndash, 2018 (CI difference: +6.1 &ndash, +19.0, p &lt, 0.001). This study demonstrated the high and increasing incidence of AM in the Umbria region during the summer months and the frequent detection of P. aeruginosa as an etiologic agent of the disease in the presence of STP. Confirmation of these results with a larger study population, in different settings, and throughout the whole year is needed to define the first-line approach of AM with STP in pediatrics.

Questo articolo presenta una metodologia socio-costruttivista usata nella realizzazione di un libretto destinato a bambini e ragazzi con Artrite Idiopatica Giovanile, da usare come mediatore della relazione medico paziente al momento della comunicazione della diagnosi e durante il successivo processo di cura. Tale metodologia ha coinvolto attivamente alcuni bambini e ragazzi con questa patologia e si e svolta attraverso fasi diverse che hanno compreso: (1) la creazione di un libretto operativo basato su fumetti; (2) lo svolgimento di un laboratorio didattico-creativo con bambini malati e gia consapevoli della diagnosi; (3) la raccolta e l’organizzazione delle narrazioni prodotte dai bambini in un libretto finale; (4) La revisione di quanto prodotto dai bambini da parte di genitori e personale sanitario. Ciascuna fase di lavoro ha contribuito alla costruzione del libretto finale. L’approccio socio-costruttivista adottato e il clima accogliente creato durante il workshop hanno facilitato i partecipanti nell’espressione dei loro vissuti e nell’ascolto dei loro coetanei. Il personale pediatrico consultato ha fornito indicazioni scientifiche per far si che i contenuti trasmessi fossero corretti e aggiornati dal punto di vista medico-terapeutico. Il presente progetto dimostra come sia possibile fornire informazioni scritte che riguardano la malattia e la sua gestione terapeutica a bambini con AIG. Le narrazioni di altri bambini affetti da questa patologia hanno fornito informazioni che altrimenti sarebbero probabilmente rimaste trascurate da adulti e personale sanitario. La metodologia presentata in questo lavoro puo essere testata e verificata in futuro con pazienti affetti da altre patologie per valutarne l’efficacia e l’estendibilita.

This study aimed to create a book to explain juvenile arthritis to newly diagnosed children, starting with the narratives of currently ill children. The development of the book followed a socio-constructivist approach and occurred over several stages, including: design of a comic-based workbook; conducting a workshop with ill children to listen to their experiences; collecting and organising the narratives into a children's book; adding physician explanations; consulting with parents and medical practitioners; and design of the final product. All stages led to meaningful enhancements to the book. The socio-constructivist approach and the workshop's open and friendly climate allowed children to express their conception of the illness, and to listen to and understand their peers’ points of view. Paediatric practitioners contributed to the project, providing clarity to the book and ensuring it would be scientifically sound and usable within the paediatric setting. In conclusion, written material addr...

The primary purpose of these practical guidelines related to Kawasaki disease (KD) is to contribute to prompt diagnosis and appropriate treatment on the basis of different specialists’ contributions in the field. A set of 40 recommendations is provided, divided in two parts: the first describes the definition of KD, its epidemiology, etiopathogenetic hints, presentation, clinical course and general management, including treatment of the acute phase, through specific 23 recommendations. Their application is aimed at improving the rate of treatment with intravenous immunoglobulin and the overall potential development of coronary artery abnormalities in KD. Guidelines, however, should not be considered a norm that limits treatment options of pediatricians and practitioners, as treatment modalities other than those recommended may be required as a result of peculiar medical circumstances, patient’s condition, and disease severity or complications.

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Italian language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, test–retest reliability, and construct validity (convergent and discriminant validity). A total of 1296 JIA patients (7.2% systemic, 59.5% oligoarticular, 21.4% RF negative polyarthritis, 11.9% other categories) and 100 healthy children, were enrolled in 18 centres. The JAMAR components discriminated well healthy subjects from JIA patients except for the Health Related Quality of Life (HRQoL) Psychosocial Health (PsH) subscales. All JAMAR components revealed good psychometric performances. In conclusion, the Italian version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Incidence rates for varicella and herpes zoster were similar in patients with juvenile idiopathic arthritis receiving etanercept/methotrexate (n = 85, 184.9 patient-years [PY]) or methotrexate alone (n = 71, 199.4 PY); no complicated varicella or herpes zoster cases were reported; herpes labialis incidence was higher in patients receiving etanercept/methotrexate versus methotrexate alone (0.38 vs. 0.24 PY).

A tutt’oggi non esiste un test diagnostico per le diverse malattie reumatologiche, ma gli esami di laboratorio possono fornire un valido supporto per la gestione della malattia e della terapia. Solo nel forte sospetto clinico sostenuto da solidi dati anamnestici vanno richiesti esami ematochimici, che altrimenti possono risultare fuor- vianti. E opportuno iniziare sempre con esami di primo livello (emo- cromo, indici di flogosi, enzimi muscolari ed esame delle urine) che, se correttamente interpretati, possono indicarci la necessita di ese- guire a scopo diagnostico esami di secondo livello (titolo anti-strep- tolisinico, complemento, ferritina e pannello auto-anticorpale). Tuttavia, in reumatologia, le indagini di laboratorio servono soprattutto per monitorare l’attivita della malattia e gli effetti collaterali della terapia, consentendo una miglior definizione in termini prognostici e terapeutici.

Objective.To evaluate safety, tolerability, and efficacy of etanercept in a cohort of patients with juvenile idiopathic arthritis (JIA) under 4 years of age.Methods.Data were collected at every visit during treatment with etanercept in 25 children who began treatment at a mean age of 3 years (range 18–48 months). Safety endpoints included the incidence of any adverse events. Efficacy endpoints included the American College of Rheumatology (ACR) Pediatric 30, 50, and 70 criteria for improvement.Results.Data from 25 patients with JIA treated with etanercept for a mean period of 23 months were analyzed. All patients received concomitant medications: 24 methotrexate, 3 cyclosporin A, and 10 corticosteroids. After the first 6 months of treatment, 15 (71.4%) patients achieved an ACR Pedi30 response and at the last observation 20 (80%) achieved ACR Pedi30. ACR Pedi50 and 70 responses were, respectively, 62% and 43% at 6 months and 72% and 64% at the last followup. Five patients (20%) discontinued etanercept for lack of efficacy. Two (8%) developed adverse events, both primary varicella zoster virus (VZV) infections (both not vaccinated). One was hospitalized because of a necrotizing fasciitis secondary to VZV infection. No cases of tuberculosis, opportunistic infections, or malignancies were reported.Conclusion.In our cohort of patients etanercept proved to be safe and efficacious in the majority of children. The response in toddlers was similar to that in older children. We observed only 1 case of severe infection that required hospitalization and stopped treatment temporarily.

Background: High levels of cytokines in juvenile idiopathic arthritis (JIA) can alter target cell sensitivity to growth hormone (GH) leading to short stature in adulthood. We hypothesized that the down-regulation of GH receptor (GHR) gene expression could be involved in growth failure of children with JIA. Methods: In 18 (12 F and 6 M) prepubertal JIA patients and 13 age- and sex-matched healthy children, we evaluated serum growth-promoting factors and inflammatory indexes. We also measured GHR gene expression, by real-time PCR, in lymphocytes of patients and controls. All parameters were evaluated in patients before and after treatment of JIA. Results: The most interesting (p = 0.007) result was the increase in GHR mRNA expression in all JIA patients. Moreover, we observed a significant (p = 0.0156) decrease in IL-6 levels in JIA patients after 2 years of therapy (19.37 ± 41.01) with respect to basal values (90.84 ± 124.71). On the contrary, IGF-I significantly (p = 0.0005) increased to a mean SDS value of 0 (range -1.69 to +1.70 SDS) with respect to values at disease onset (-0.64 SDS). Conclusions: Our preliminary data suggest that the restoration of both GHR gene expression and IGF-I secretion correlate with inactive disease in JIA children.

To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA). Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome. Among 46 patients meeting inclusion criteria, anakinra monotherapy was used in 10 patients (22%), while 67% received corticosteroids and 33% received additional DMARDs. Outcomes were evaluated at a median followup interval of 14.5 months. Fever and rash resolved within 1 month in >95% of patients, while C-reactive protein and ferritin normalized within this interval in >80% of patients. Active arthritis persisted at 1 month in 39% of patients, at 3 months in 27%, and at >6 months of followup in 11%. Approximately 60% of patients, including 8 of 10 receiving anakinra monotherapy, attained a complete response without escalation of therapy. Disease characteristics and treatment were similar in partial and complete responders, except that partial responders were markedly younger at onset (median age 5.2 years versus 10.2 years; P = 0.004). Associated adverse events included documented bacterial infection in 2 patients and hepatitis in 1 patient. Tachyphylaxis was not observed. Anakinra as first-line therapy for systemic JIA was associated with rapid resolution of systemic symptoms and prevention of refractory arthritis in almost 90% of patients during the interval examined. These results justify further study of IL-1 inhibition as first-line, rather than rescue, therapy in systemic JIA

Objectives. Toll-like receptor 9 (TLR9), which recognizes hypomethylated DNA [cytosine-phosphate-guanine (CpG)], plays a role in the maintenance of serological memory and has been recently implicated in the pathogenesis of SLE. We previously reported that in vitro TLR9 triggers memory B-cell differentiation into antibody-producing cells, and that the MyD88-inhibitor ST2825 blocks TLR9-induced plasma cell (PC) generation. Here, we investigated whether memory B cells produce autoantibodies in SLE patients with active disease or in clinical remission, and whether ST2825 could inhibit PC generation in SLE patients. Methods. Peripheral blood mononuclear cells from 10 SLE patients in clinical remission and 2 with active SLE were cultured in the presence of CpG with or without ST2825. Phenotypical analysis of CpG-stimulated cells was performed by flow cytometry. Supernatants were collected to measure antibody production by ELISA and to detect autoantibodies by IF. Results. CpG-induced TLR9 stimulation caused autoantibody secretion in patients with active disease and in the majority of patients in clinical remission. Inhibition of MyD88 completely blocked the de novo generation of PCs and the secretion of autoantibodies. Conclusions. Autoreactive B cells persist in SLE patients during disease remission in the circulating B-cell memory pool. TLR9-dependent activation of memory B cells by pathogens could be one of the mechanisms triggering relapses in SLE. Compounds targeting the TLR/MyD88 pathway may be used as novel therapeutic tools to treat acute disease and to prevent relapses in SLE patients.

Kawasaki disease (KD) is a rare and often undiagnosed disease, at least in the western countries. It is characterized by an inflammatory acute febrile vasculitis of medium sized arteries with a propensity to damage the coronary arteries. It normally occurs in the early childhood and the diagnosis is based on clinical symptoms. During the progression of the disease thrombocytosis is usually detected. This can exert a pathogenetic role in the cardiovascular complications occurring in KD. In the present work peripheral blood plasma and platelets from twelve naïve patients with KD were analyzed in order to detect possible pathogenetic determinants or progression markers. Morphological, biochemical and flow cytometrical methods have been used. With respect to age-matched healthy donors, we found an increase of platelet activation markers, i.e. degranulation, phosphatidylserine (PS) externalization and leukocyte-red cell-platelet aggregates. Some significant alterations that could represent suitable diagnostic determinants have also been detected in patient plasma: (i) decreased antioxidant power, (ii) decreased levels of asymmetric dymethylarginine (ADMA), a naturally occurring chemical interfering with the production of nitric oxide, and (iii) increased levels of soluble P-Selectin and soluble annexin V. Since PS externalizing platelets are known to exert a pro-coagulant activity, our data suggest the hypothesis that increased risk of vascular complications in KD could depend on platelet stimulation and defective apoptosis probably related to nitrosative stress.

OBJECTIVES: To analyze whether there were clinical differences between genetically positive and negative patients fulfilling periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome criteria and to test the accuracy of the Gaslini diagnostic score for identifying patients with PFAPA syndrome with higher probabilities of carrying relevant mutations in genes associated with periodic fevers. METHODS: Complete clinical and genetic information was available for 393 children with periodic fever; 82 had positive genetic test results, 75 had incomplete genetic test results, and 236 had negative results for MVK, TNFRSF1A, and MEFV mutations. Current diagnostic criteria for PFAPA syndrome were applied. RESULTS: Of 393 children, 210 satisfied PFAPA syndrome criteria; 43 carried diagnostic mutations (mevalonate kinase deficiency: n = 33; tumor necrosis factor receptor-associated periodic syndrome: n = 3; familial Mediterranean fever: n = 7), 37 displayed low-penetrance mutations or incomplete genotypes, and 130 demonstrated negative genetic testing results. Genetically positive patients had higher frequencies of abdominal pain and diarrhea (P < .001), vomiting (P = .006), and cutaneous rash and arthralgia (P = .01). Genetically negative patients had a higher frequency of exudative pharyngitis (P = .010). Genetically undetermined patients showed the same pattern of symptom frequency as genetically negative patients. The Gaslini diagnostic score was able to identify 91% of genetically positive patients correctly, with a global accuracy of 66%. CONCLUSION: The Gaslini diagnostic score represents a useful tool to identify patients meeting PFAPA syndrome criteria and at low risk of carrying relevant mutations in genes associated with periodic fevers.

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.

To examine the change in health-related quality of life (HRQOL) and its determinants in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX).Patients were extracted from the PRINTO clinical trial which aimed to evaluate the efficacy and safety profile of MTX administered in standard, intermediate or higher doses (10, 15 and 30 mg/m(2)/week respectively). Children with polyarticular-course JIA, who were less than 18 years and had a complete HRQOL assessment were included.A total of 521 children were included. At baseline, patients with JIA showed poorer HRQOL (p0.01) than healthy children. In 207/412 (50%) and 63 (15%) children, HRQOL values were 2 standard deviations below the mean of healthy controls in the physical and psychosocial summary scale, respectively. After 6 months of treatment with standard dose MTX, there was a statistically significant improvement in all HRQOL health concepts, particularly the physical ones. Similar improvements were observed in those who did not respond to a standard dose of MTX and were subsequently randomised to a higher dose. The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with standard dose MTX. Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation, pain intensity and an antinuclear-antibody-negative status.MTX treatment produces a significant improvement across a wide range of HRQOL components, particularly in the physical domains, in patients with JIA.

Vasculitis are a heterogeneous group of disorders characterized by inflammation of the blood vessels of different caliber and sometimes fibrinoid necrosis with vessel wall destruction [1]. Vasculitis are divided into cutaneous and systemic forms, primary and secondary to hypertension, immunosuppression therapy, metabolic complications. The classification is based on the affected vessel size (Table ​(Table1).1). They may have neurological manifestations at the onset and during the desease development. These are more common in systemic forms such as SLE and Nodose Polyarteritis (PAN). Table 1 Vasculitis: classification (Adapted from EULAR/PReS endorsed criteria for the classification of childhood vasculitis) 2006; 65:936-41 The Schonlein-Henoch purpura and Kawasaki disease, the most frequent vasculitisin childhood, rarely can have neurological disorders. There are forms of mild to moderate intensity like headache, irritability, mood disorders and behavioral and forms of severe as seizures and sensory disturbance up to coma. In the course of SLE, neuropsychiatric manifestations, headache and chorea are common, with an incidence of 20-40% (also 80% with cognitive disorders and asymptomatic alterations RMN). The neuropsychiatric manifestations involve 40-56% of children; headache the 22-64%; convulsions the 20-31%; chorea 4-10%; peripheral neuropathy 5-6%; myelopathy 1%. Heterogeneity in their neurological symptoms are important for prognostic purposes. In antiphospholipid syndrome, primary or secondary, the following are common: transient cerebral ischemia and ischemic stroke, memory loss, chorea, seizures, vision problems [2]. The PAN is a necrotizing vasculitis histo-pathological examination, rarely aneurysm, stenosis or occlusion (not caused by fibro-muscular dysplasia, or by other causes not inflammatory) artery of small and medium caliber. In addition, at least one of the following signs/symptoms: skin involvement (livedo, nodules or heart attacks); myalgia; hypertension; peripheral neuropathy (sensory or motor); renal involvement (proteinuria, haematuria, renal impairment). The primary central nervous system vasculitis is a brain vessels inflammation not associated with vasculitis of other organs. The classification is based on the vessel size: small (with normal angiography) and medium-large (progressive and non-progressive). This form, responsible for 40-60% of arterial ischemic stroke, affects 3-8/100.000 children/year. Symptoms are characterized by acute severe headache (80%), focal neurological deficit (78%), motor deficit (62%), cognitive disorders (54%), cranial nerve involvement (59%), seizures (small vessel vasculitis). Peripheral neuropathies are characteristic of the Churg-Strauss disease. The clinical diagnosis is often difficult (Table ​(Table22). Table 2 Vasculitis: diagnosis Neurological complications are diagnosed early because the treatment must be immediate and aggressive.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2014-02-26T17:25:12Z No. of bitstreams: 1 WOS000238172900004.pdf: 103404 bytes, checksum: 52ca85593f8181517f9ab1e237d2d561 (MD5) Made available in DSpace on 2014-02-26T17:25:13Z (GMT). No. of bitstreams: 1 WOS000238172900004.pdf: 103404 bytes, checksum: 52ca85593f8181517f9ab1e237d2d561 (MD5) Previous issue date: 2006-06-15 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:20:26Z No. of bitstreams: 1 WOS000238172900004.pdf: 103404 bytes, checksum: 52ca85593f8181517f9ab1e237d2d561 (MD5) Made available in DSpace on 2014-05-20T15:20:26Z (GMT). No. of bitstreams: 1 WOS000238172900004.pdf: 103404 bytes, checksum: 52ca85593f8181517f9ab1e237d2d561 (MD5) Previous issue date: 2006-06-15 Objective. To use the Pediatric Rheumatology International Trials Organization (PRINTO) core set of outcome measures to develop a validated definition of improvement for the evaluation of response to therapy in juvenile systemic lupus erythematosus (SLE).Methods. Thirty-seven experienced pediatric rheumatologists from 27 countries, each of whom had specific experience in the assessment of juvenile SLE patients, achieved consensus on 128 patient profiles as being clinically improved or not improved. Using the physicians' consensus ratings as the gold standard measure, the chi-square, sensitivity, specificity, false-positive and false-negative rates, area under the receiver operating characteristic curve, and kappa level of agreement for 597 candidate definitions of improvement were calculated. Only definitions with a kappa value greater than 0.7 were retained. The top definitions were selected based on the product of the content validity score multiplied by its kappa statistic.Results. The definition of improvement with the highest final score was at least 50% improvement from baseline in any 2 of the 5 core set measures, with no more than 1 of the remaining worsening by more than 30%.Conclusion. PRINTO proposes a valid and reproducible definition of improvement that reflects well the consensus rating of experienced clinicians and that incorporates clinically meaningful change in core set measures in a composite end point for the evaluation of global response to therapy in patients with juvenile SLE. The definition is now proposed for use in juvenile SLE clinical trials and may help physicians to decide whether a child with SLE responded adequately to therapy. Univ Genoa, Pediat Rheumatol Int Trials Org, IRCCS G Gaslini, I-16147 Genoa, Italy Inst Puericultura & Pediat Martagao Gesteira, Rio de Janeiro, Brazil Univ Naples Federico II, Naples, Italy Childrens Univ Hosp, Sofia, Bulgaria Mother & Child Hlth Inst Serbia, Belgrade, Serbia Monteneg Univ Catolica, Cordoba, Argentina Hosp Gen Mexico City, Mexico City, DF, Mexico Aristotle Univ Thessaloniki, Ippokrat Gen Hosp, Thessaloniki, Greece Hosp Dr Exequiel Gonzalez Cortes, Santiago, Chile Clin Pediat 2 de Marchi, Milan, Italy Ist Gaetano Pini, Milan, Italy Karolinska Univ Hosp, Stockholm, Sweden Sanjay Gandhi Inst Med Sci, Lucknow, Uttar Pradesh, India Fac Med 1, Prague, Czech Republic Gen Fac Hosp, Prague, Czech Republic Univ Estadual Paulista, Fac Med Botucatu, Botucatu, SP, Brazil Hanyang Univ, Med Ctr, Hosp Rheumat Dis, Seoul 133791, South Korea Univ Hosp, Kosice, Slovakia Univ Med Ctr, Ljubljana, Slovenia Royal Victoria Infirm, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England Ctr Nacl Rehabil, Mexico City, DF, Mexico Skejby Sygehus Univ Hosp, Aarhus, Denmark Univ Klin & Poliklin Kinder & Jugendmed, Halle, Germany Univ Trieste, Trieste, Italy Emma Childrens Hosp, AMC, Amsterdam, Netherlands IRCCS G Gaslini, Serv Epidemiol & Biostat, Genoa, Italy Ryhovs Cty Hosp, Jonkoping, Sweden Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA Univ Estadual Paulista, Fac Med Botucatu, Botucatu, SP, Brazil

We report a family with pyogenic sterile arthritis, pyoderna and acne syndrome (PAPA). The proband presented several episodes of sterile pyogenic arthritis and became unresponsive to glucocorticoids. After treatment with the tumor necrosis factor inhibitor etanercept, the disease underwent rapid and sustained clinical remission. Production of tumor necrosis factor-α by mononuclear cells of the proband and of the affected relatives was abnormally elevated.

Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are characterized by chronic inflammation, synovial cell proliferation and progressive joint damage. It has been speculated that T cells play an important role in the pathogenesis of RA and JRA in the early stage of the disease. Previous studies have demonstrated discrepant results regarding the significance of T-cell clonality in RA or JRA lesions. It can be postulated that the heterogeneity of these data may be linked to the stage of the disease, as the relative importance of selective immunological events is different during the time from onset to established disease. To avoid this problem, we conducted the present study in nine children affected by JRA at the onset of the disease and before treatment. We analysed the T-cell receptor beta chain variable (TCRBV) of CD4+ and CD8+ lymphocytes in peripheral blood (PBL) and synovial fluid (SFL), by a panel of monoclonal antibodies (MoAbs). Furthermore, to assess the clonotypic pattern of T-cell repertoire, the CDR3 length distribution was evaluated by spectratyping analysis. Our results showed no significant expansion of distinct TCRBV subset in either synovial or peripheral compartments. Conversely, when we studied the CDR3 length distribution, an oligoclonal pattern was found in the SFL of six patients, suggesting the presence of a clonotypic restriction of T cells in SFL, which is not detectable in PBL. These findings are consistent with an antigen driven T-cell expansion sequestered at the inflammatory site.

The NLRP12 related autoinflammatory disorder (NLRP12-RD) is a rare autosomal dominant disease,caused by mutations in the NLRP12 gene.Clinical manifestations are extremely heterogeneous.At present,only few cases have been described.Patients occasionally required treatment with steroids and NSAIDS for short periods.Treatment with Anakinra induced an initial good response,that appears to decrease over time.

Polyarteritis or panarteritis nodosa (PAN) is a necrotizing, focal segmental vasculitis that affects predominantly medium-sized arteries in many different organ systems. It is extremely rare in childhood. Involvement of the oral mucosa at diagnosis is uncommon in PAN. Here, we report a case of a pediatric patient with tongue necrosis.

Takayasu arteritis (TA) is a chronic vasculitis of unknown etiology. Experience with anti-tumor necrosis factor alpha (anti-TNF) agents in difficult-to-treat patients with TA is limited and refers to adult patients. Here, we present two cases of pediatric TA treated with infliximab, in which clinical remission was observed. Anti-TNF treatment represents a useful therapy in pediatric Takayasu arteritis too, especially to avoid the risk of long-term corticosteroids toxicity.

Results New patients had higher baseline disease activity compared to flared patients, but initiated corticosteroids at similar doses. Cyclophosphamide was the most common (41.2%; 99/240) immunosuppressive medication, followed by azathioprine (25%; 60/240). Mycophenolate mofetil and azathioprine were more commonly used in flared patients. Patients from Latin America received more pulses and higher doses of steroids when compared to Western Europe. The use of cyclophosphamide was similar in all 4 regions. In the “as observed” analysis 78% (103/132) of new compared to 57.4% (58/101) of flared JSLE patients (p=0.0007) reached at least PRINTO/ACR 70 level of response at 6 months, which increased to 87.1% in new and 77.2% in flared patients at month 24 (p=0.12). Corresponding figures for the ITT analysis were similar and 80% (68/85) of new vs 73.7% (42/57) of flared patients were able to maintain the initial assigned therapy over 24 months (p=0.38). Corticosteroids were discontinued in 28.6% (20/143).

Made available in DSpace on 2013-08-12T19:10:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-01-15 Made available in DSpace on 2013-09-30T19:20:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-01-15 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:33:16Z No. of bitstreams: 0 Made available in DSpace on 2014-05-20T15:33:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-01-15 Myositis Association European Union Objective. To investigate the long-term outcome and prognostic factors of juvenile dermatomyositis (DM) through a multinational, multicenter study.Methods. Patients consisted of inception cohorts seen between 1980 and 2004 in 27 centers in Europe and Latin America. Predictor variables were sex, continent, ethnicity, onset year, onset age, onset type, onset manifestations, course type, disease duration, and active disease duration. Outcomes were muscle strength/endurance, continued disease activity, cumulative damage, muscle damage, cutaneous damage, calcinosis, lipodystrophy, physical function, and health-related quality of life (HRQOL).Results. A total of 490 patients with a mean disease duration of 7.7 years were included. At the cross-sectional visit, 41.2-52.8% of patients, depending on the instrument used, had reduced muscle strength/endurance, but less than 10% had severe impairment. Persistently active disease was recorded in 41.2-60.5% of the patients, depending on the activity measure used. Sixty-nine percent of the patients had cumulative damage. The frequency of calcinosis and lipodystrophy was 23.6% and 9.7%, respectively. A total of 40.7% of the patients had decreased functional ability, but only 6.5% had major impairment. Only a small fraction had decreased HRQOL. A chronic course, either polycyclic or continuous, consistently predicted a poorer outcome. Mortality rate was 3.1%.Conclusion. This study confirms the marked improvement in functional outcome of juvenile DM when compared with earlier literature. However, many patients had continued disease activity and cumulative damage at followup. A chronic course was the strongest predictor of poor prognosis. These findings highlight the need for treatment strategies that enable a better control of disease activity over time and the reduction of nonreversible damage. Ist Ricovero & Cura Carattere Sci G Gaslini, Genoa, Italy Univ Genoa, Genoa, Italy Great Ormond St Hosp Sick Children, London WC1N 3JH, England UCL, Inst Child Hlth, London, England Univ Fed Rio de Janeiro, Rio de Janeiro, Brazil Universidade do Estado do Rio de Janeiro (UERJ), BR-20550011 Rio de Janeiro, Brazil Hosp Gen Ninos Pedro de Elizalde, Buenos Aires, DF, Argentina Fdn IRCCS Policlin, Milan, Italy Hosp Pediat Juan P Garrahan, Buenos Aires, DF, Argentina Univ São Paulo, Fac Med Ribeirao Preto, Hosp Clin, Ribeirao Preto, Brazil Hosp Gen Mexico City, Mexico City, DF, Mexico Fdn Ist Ricovero & Cura Carattere Sci Policlin S, Pavia, Italy Ctr Med Natl La Raza, Mexico City, DF, Mexico Hosp Pequeno Principe, Curitiba, Parana, Brazil Clin Pediat 1, Padua, Italy Ctr Med Nacl Siglo XXI, Mexico City, DF, Mexico Osped Pediat Bambino Gesu, Rome, Italy Osped Villa Monna Tessa, Florence, Italy Univ Naples Federico 2, Naples, Italy Ist Ortoped Gaetano Pini, Milan, Italy Univ estadual Paulista, Botucatu, SP, Brazil II Clin Pediat, Cagliari, Italy Univ São Paulo, São Paulo, Brazil Ist Ricovero & Cura Carattere Sci Burlo Garofalo, Trieste, Italy Univ estadual Paulista, Botucatu, SP, Brazil EU: AML/B7-311/970666/II-0246-FI

Objectives The aim of the study is to assess the rate of atypical manifestations at onset in pediatric systemic lupus erythematosus (SLE) and to evaluate their effect on disease outcome. Study design This is a multicenter retrospective cohort study. A manifestation was considered atypical if it was not included in the American College Rheumatology classification criteria for SLE but was reported in literature as associated with SLE. Unfavorable outcome was considered presence of organ damage in the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index at the last available evaluation. Results One hundred patients were enrolled in the study; 24% presented atypical clinical features at onset. Univariate analysis showed a significant association of worse outcome variables with the presence of atypical manifestations at onset ( P = .004), as well as renal involvement ( P = .027). A multivariate logistic regression analysis showed that atypical manifestations at onset ( P = .018), renal involvement at onset or during follow up ( P = .024), and central nervous system disease involvement during follow up ( P = .021) were independent predictors of poor prognosis. Conclusions Our data support a relatively high rate of atypical onset in pediatric SLE. Presence of atypical manifestations at presentation and early kidney disease correlate with poor outcome. Similarly, during follow-up, kidney and central nervous system diseases are associated with worse outcome.

Objective Macrophage activation syndrome (MAS) in systemic onset juvenile idiopathic arthritis (SoJIA) is considered to be an acquired form of familial haemophagocytic lymphohistiocytosis (fHLH). FHLH is an autosomal recessive disorder, characterized by diminished NK cell function and caused by mutations in the perforin gene (PRF1) in 20-50% of patients. Interestingly, SoJIA patients display decreased levels of perforin in NK cells and diminished NK cell function as well. Here, we analysed PRF1 and its putative promoter in SoJIA patients with or without a history of MAS. Methods DNA of 56 SoJIA patients (41 Italian and 15 Dutch) was isolated. Of these, 15 (27%) had a confirmed history of MAS. We sequenced PRF1 and 1.5 kb of the 5'-upstream region. DNA sequence variations in the promoter region were functionally tested in transfection experiments using a human NK cell line. Results We detected a previously undescribed sequence variation (-499 C > T) in the promoter of PRF1 in 18% of the SoJIA patients. However, transfection experiments did not show functional implications of this variation. Secondly, we found that 11 of 56 (20%) SoJIA patients were heterozygous for missense mutations in PRF1. In particular, we found a high prevalence of the Ala91Val mutation, a variant known to result in defective function of perforin. Interestingly, the prevalence of Ala91Val in SoJIA patients with a history of MAS (20%) was increased compared with SoJIA patients without MAS (9.8%). One SoJIA patient, heterozygous for Ala91Val, showed profound decreased perforin levels at the time of MAS. Conclusions These findings suggest that PRF1 mutations play a role in the development of MAS in SoJIA patients.

Relapsing polychondritis (RP) is a rare disease of unknown etiology characterized by recurrent episodes of inflammation resulting in the destruction of cartilaginous tissues. We describe a young girl with RP unresponsive to conventional therapy.

Address: 1Institute for Maternal and Child Health – IRCCS Burlo Garofolo, Trieste, Italy, 2Division of Rheumatology A.I. duPont Hospital for Children, Department of Pediatrics, Thomas Jefferson University, Wilmington/DE, USA, 3Division of Rheumatology, Department of Pediatric Medicine, IRCCS Ospedale Pediatrico Bambino Gesu, Rome, Italy and 4Department of Pediatric Sciences, Universita Cattolica Sacro Cuore, Rome, Italy * Corresponding author

Background MAS is a life-threatening complication seen predominantly in children with SoJIA, often difficult to recognize because specific diagnostic criteria for MAS have not yet been devised. MAS is characterized by an overwhelming inflammatory reaction driven by excessive T cell expansion and hemophagocytic macrophages. Preliminary studies suggest that high sIL-2R α serum levels and sCD163 might be useful as diagnostic markers for MAS. This study assesses the expression of CD163 and CD68 in bone marrow cells of patients with MAS and especially in those with SoJIA who developed MAS.

Open Access Oral presentation 3.5 Comparison of functional ability in juvenile idiopathic arthritis, juvenile dermatomyositis, juvenile systemic lupus erythematosus and healthy controls. An analysis of the PRINTO database G Filocamo*, S Meiorin*, C Saad-Magalhaes, A Pistorio, A Ravelli, E Cortis, D Mihaylova, M Alessio, O Arguedas, S Garay, A Martini, N Ruperto and for the Paediatric Rheumatology International Trials Organisation (PRINTO)