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Objective To assess concordance among criteria for inactive disease (ID) and low disease activity (LDA) in juvenile idiopathic arthritis (JIA) and to seek factors driving discordance. Methods The frequency of fulfillment of existing criteria was evaluated in information on 10,186 patients extracted from 3 cross-sectional data sets. Patients were divided up according to the functional phenotypes of oligoarthritis and polyarthritis. Concordance between criteria was examined using weighted Venn diagrams. The role of each individual component in explaining discordance between criteria was assessed by calculating the absolute number and percentage of instances in which the component was responsible for discrepancy between definitions. Results Criteria for ID were met by 28.6–41.1% of patients with oligoarthritis and by 24.0–33.4% of patients with polyarthritis. Criteria for LDA were met by 44.8–62.4% of patients with oligoarthritis and by 44.6–50.4% of patients with polyarthritis. There was a 57.9–62.3% overlap between criteria for ID and a 67.9–85% overlap between criteria for LDA. Parent and physician global assessments and acute-phase reactants were responsible for the majority of instances of discordance among criteria for ID (8.7–15.5%, 10.0–12.3%, and 10.8–17.3%, respectively). Conclusion We found fair concordance between criteria for ID and LDA in JIA, with the main drivers of discordance for ID being physician and parent global assessments and acute-phase reactants. This observation highlights the need for further studies aimed to evaluate the impact of subjective physician and parent perception of disease remission and of laboratory measures of inflammatory activity on the definition of ID.

Osteoid osteoma is a primary benign bone tumor that consists of a central area (nidus), surrounded by sclerotic bone. The most relevant symptom is pain that increases during the night and improves after salicylates or nonsteroidal anti-inflammatory drug administration. Osteoid osteoma is frequently misdiagnosed because it mimics juvenile idiopathic arthritis, bone infection, or malignancy. A 14-year-old girl presented to our department with a history of chronic pain in her left ankle. Juvenile idiopathic arthritis was diagnosed and anti-inflammatory treatment was prescribed. Because of persistence of ankle pain, the patient underwent further examinations, in particular, bone scintigraphy and computed tomography. As a result, osteoid osteoma of the talar neck was diagnosed. The patient underwent surgical treatment and her condition improved. Osteoid osteoma should also be considered in patients with chronic ankle pain to avoid misdiagnosis and start adequate treatment. This condition should be suspected in a patient with chronic bone pain and normal complete blood count and inflammatory parameters.

Objective.To investigate the effect of morning stiffness (MS) on parent disease perception in children with juvenile idiopathic arthritis (JIA) with clinically inactive disease (CID).Methods.We examined 652 visits in which patients fulfilled 2004 or 2011 Wallace criteria for CID. Parent-reported outcomes were compared among patients with no MS or with MS < or ≥ 15 min.Results.Among 652 visits with CID by 2004 criteria, no MS was reported in 554 visits (85%), MS < 15 min in 53 (8%), and MS ≥ 15 min in 45 (7%). The frequency of altered physical function, health-related quality of life and well-being, pain, and disease activity visual analog scales was proportionally greater in patients without MS than those with longer MS. The frequency of parent subjective rating of disease state as remission was 87.7%, 58%, and 26.7% among patients with no MS, MS < 15 min, and MS ≥ 15 min, respectively.Conclusion.Our results suggest that a change in 2011 CID criteria to require absence of MS should be considered.

Background: Pandemics are states of disease that occur worldwide and sharply increase in populations. It causes life events which trigger anxiety, depression, anger, sleep deprivation, emotional distress and stress. World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic on March 11, pointing to the over 118,000 cases in over 110 countries. Many healthcare workers became ill during the pandemic and some among them died. In this study, we aimed to evaluate and compare level of stress against COVID-19 pandemic among doctors from Turkey and Italy. Methods: This research is a cross-sectional study in which Perceived Stress Scale (PSS-10) and Secondary Traumatic Stress Scale (STSS) are administered online via social networks. All data collection tools were delivered to individuals between 1 and 15 June 2020 and filled in online with Google Forms application. In total, 618 individuals were included in this study and all of them were medical doctors. Results: Higher PS and STS levels were found related to female gender, being married, working in pandemic hospital and older ages. Stress levels were found statistically higher in Turkish doctors when compared to Italian doctors for both stress scales (Turkish/Italian PSS:20.18±7.90/ 19.35±6.71, STSS: 44.19±13.29/ 38.83±13.74). Conclusion: The number of doctors per 1000 of population is lower and per capita visits to a physician are higher in Turkey when compared to Italy. Besides pandemic, these heavier working conditions, increased weekly working hours can cause stress for Turkish doctors. Reporting information such this study is important and international collaborations are essential to plan future prevention strategies. We need to strengthen international ties and build more international collaborations rather than staying within our national silos. Additionally, interventions to promote mental well-being in health care professionals exposed to COVID-19 need to be immediately implemented.

We evaluated chronic kidney disease (CKD) (proteinuria or estimated glomerular filtration rate < 60 mL/min/1.73 m2) or hypertension prevalence in 110 children with juvenile idiopathic arthritis (JIA). CKD and hypertension were clustered under the umbrella term of "renal injury". Median age at the last visit was 14 years. Nine out of 110 (8.1%) patients showed renal injury (8 hypertension, 1 proteinuria). Patients with renal injury presented higher age at last visit, longer duration of active JIA, shorter intervals free from JIA relapses, longer duration of non-steroidal anti-inflammatory drugs (NSAIDs) treatment but with similar cumulative NSAIDs dose and higher rate of methotrexate (MTX) prescription, longer time of MTX administration, and higher cumulative MTX dose compared to patients without renal injury. At the last visit, patients with and without renal injury presented similar prevalence of active disease. The cumulative proportion of patients free from renal injury at 240 months since JIA onset was 40.72% for all population; while the cumulative proportion was 23.7% for patients undergoing NSAIDs+MTX treatment and 100% for those undergoing NSAIDs (p = 0.039) treatment.Conclusion:About 8% of the children with JIA develop hypertension or CKD. The main risk factor was longer exposure to both NSAIDs and MTX due to a more severe form of the disease. What is Known •Anecdotal reports showed that rarely juvenile idiopathic arthritis (JIA) could present renal involvement due to prolonged and uncontrolled inflammation (renal amyloidosis) or to long exposure to anti-rheumatic drugs. •No cohort studies investigated renal health in children with JIA. What is new •About 8% of the children with JIA developed hypertension or chronic kidney disease. •The main risk factor was long exposure to non-steroidal anti-inflammatory drugs and methotrexate for patients suffering from a more severe form of the disease. •In JIA patients, periodic evaluation of renal function, blood pressure and proteinuria should be warranted.

Background : Henoch Schonlein purpura (HSP) is an acute small vessel vasculitis. It is the most common vasculitis in children. Although the cause is unknown, IgA seems to play a central role in the pathogenesis of Henoch Schonlein purpura. The major clinical features include a palpable purpuric rash on the lower extremities, abdominal pain or renal involvement, and arthritis. Cutaneous manifestations are the essential elements in the diagnosis of Henoch Schonlein purpura. The palpable purpura is characteristically 2 to 10mm in diameter and is usually present on the lower extremities. There are no specific diagnostic tests available for diagnosing this condition. Laboratory studies are useful to exclude other conditions that may mimic Henoch Schonlein purpura. In majority of the cases, the disease is self-limited. Relapsing can occur, in particular during the first year of the disease. There is no consensus on a specific treatment. Corticosteroids are effective in rapid resolution of renal and abdominal manifestations. Immunosuppressive drugs, such as Mycophenolate Mofetil may be a better treatment choice in case of renal involvement.Case report : We report a case of a 14 years old girl affected from recurrent Henoch Schonlein Purpura. From the age of nine years patient presented three episodes of purpura with gastrointestinal involvement, in particular hematemesis, abdominal pain and diarrhoea. Each episode was treated with high doses of corticosteroids (methylprednisolone in vein or prednisone per os). Patient came to our Department during the third episode of Purpura. In consideration of the recurrence of the Henoch Schonlein Purpura and the gastrointestinal involvement we decided to start Mycophenolate Mofetil treatment. Patient’s conditions improved thanks to Mycophenolate Mofetil treatment. Conclusion: In our case of recurrent HSP Mycophenolate Mofetil treatment has been very effective, avoiding the adverse events of a prolonged steroid treatment. This experience teaches us that immunosuppressive agents may be very useful to induce and maintain remission not only in renal involvement, but in all cases of persistence, recurrence or complicated forms of Henoch Schonlein purpura in children.

Introduction: Cryopyrin associated periodic syndromes (CAPS) are rare autoinflammatory disorders associated with dominantly gain-offunction mutations in the NLRP3 gene that result in overactivation of the inflammasome, increased secretion of interleukin (IL)-1beta and IL-18, and systemic inflammation. It has been reported that oligomeric particles of the adaptor ASC (apoptosis-associated Speck-like protein with a caspase-recruitment domain) are released together with IL-1beta and active caspase-1 subunits after activation of the inflammosome complex and that patients with CAPS show an increased serum concentration of ASC+ particles. Objectives: The diagnosis of CAPS is a critical factor due to both the lack of specific laboratory results and the sharing of similar clinical manifestations with other autoinflammatory diseases, our aim is to develop a simple assay to evaluate the levels of ASC particles in the serum of CAPS patients to provide novel biomarkers facilitating early disease diagnosis and able to monitor treatment responses. Methods: We developed an ELISA for the quantification of ASC particles in serum and plasma of normal and pathological subjects. We analysed samples from CAPS patients and from patients with autoimmune disorders (Multiple Sclerosis (MS), Type 1 Diabetes (T1D) and juvenile idiopathic arthritis), to confirm that ASC presence in the serum is not due to other chronic inflammatory processes characterizing autoimmunity. In addition, we also evaluated the concentration of ASC in the sera of TNF receptor–associated periodic syndrome (TRAPS) patients to reinforce the concept of specificity of this biomarker in CAPS patients and not in individuals suffering from others inflammatory disorders. Results: We observed that untreated CAPS patients are characterized by the presence of a significant higher amount of ASC particles when compared with healthy controls (HS) and with patients suffering from MS and T1D. This tendency was also evident in patients with arthritis and TRAPS even if the difference was not statistically significant due to the small number of samples. In addition there is a tendency through a reduction of ASC levels in CAPS patients after pharmacological treatment, which require future investigations. Conclusion: These data suggest that ELISA quantitation of ASC protein could represent a novel and additional strategy for the diagnosis and monitoring of CAPS.

Congenital diabetes mellitus is a rare disorder characterized by hyperglycemia that occurs shortly after birth. We define "Diabetes of Infancy" if hyperglycemia onset before 6 months of life. From the clinical point of view, we distinguish two main types of diabetes of infancy: transient (TNDM), which remits spontaneously, and permanent (PNDM), which requires lifelong treatment. TNDM may relapse later in life. About 50% of cases are transient (TNDM) and 50% permanent. Clinical manifestations include severe intrauterine growth retardation, hyperglycemia and dehydration. A wide range of different associated clinical signs including facial dysmorphism, deafness and neurological, cardiac, kidney or urinary tract anomalies are reported. Developmental delay and learning difficulties may also be observed. In this paper we review all the causes of congenital diabetes and all genes and syndromes involved in this pathology. The discovery of the pathogenesis of most forms of congenital diabetes has made it possible to adapt the therapy to the diagnosis and in the forms of alteration of the potassium channels of the pancreatic Beta cells the switch from insulin to glibenclamide per os has greatly improved the quality of life. Congenital diabetes, although it is a very rare form, has been at the must of research in recent years especially for pathogenesis and pharmacogenetics. The most striking difference compared to the more frequent autoimmune diabetes in children (type 1 diabetes) is the possibility of treatment with hypoglycemic agents and the apparent lower frequency of chronic complications.

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. Morning stiffness is a major symptom of JIA, and is usually associated with active disease. The 2004 preliminary criteria for inactive disease (ID) in JIA did not include the assessment of morning stiffness, whereas the 2011 revision of the criteria has allowed the presence of morning stiffness (MS) lasting ≤ 15 minutes. MS was included in 2011 revision based on the consideration that MS of a short duration (i.e., ≤ 15 minutes) can represent residua of previously active disease without current active disease. However, it is unclear whether the disease status of children with ID who have or do not have morning stiffness is comparable. Objectives: To compare the disease status of children with JIA who met the 2004 and 2011 revised criteria for ID in relation to the presence or absence morning stiffness. Methods: A database of 1208 Italian children included in 2 multicenter studies (1,2) who underwent a total of 3380 visits was examined to identify all visits in which the patients fulfilled the 2004 or 2011 criteria for ID. In case a patient met the ID criteria in more than 1 visit, only the first visit was retained. For each visit with ID, the duration of morning stiffness was categorized as ≤ 15 min or > 15 min. Clinical assessments included demographic features and parent-reported outcomes Results: A total of 668 visits in which patients met the criteria for ID were identified. Absence of morning stiffness was reported in 564 (84.4%) visits, whereas in 104 visits (15.5%) there was morning stiffness. Among the visits with morning stiffness, in 55 (8.2%) duration was ≤15 min, and in 49 (7.3%) duration was > 15 min. The table shows the comparison of disease duration and parent-reported outcomes between patients with absence or presence of morning stiffness. MS: morning stiffness; IQR: interquartile range, *above the mean of healthy children (2) Conclusion: Among patients who met the 2011 criteria for ID, those with morning stiffness ≤15 min had worse parent-reported outcomes than those without morning stiffness. This finding suggests that parents may not perceive their child’s disease state as true remission when lower degrees of morning stiffness are present. Notably, a sizeable proportion (7,3%) of children meeting the 2004 ID criteria had morning stiffness lasting > 15 min. The removal of the criterion “Duration of morning stiffness of ≤ 15 minutes” to “Absence of morning stiffness” in the definition for ID should be considered. References [1] Filocamo, et al. A new approach to clinical care of juvenile idiopathic arthritis: the Juvenile Arthritis Multidimensional Assessment Report. J Reumatol 2011 [2] Verazza, et al. Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept. PROJ 2016 Disclosure of Interests: Maria Francesca Gicchino: None declared, Gabriella Giancane: None declared, Alessandra Alongi: None declared, Silvia Rosina: None declared, Jessica Tibaldi: None declared, Marta Mazzoni: None declared, Angelo Ravelli Grant/research support from: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Consultant for: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Speakers bureau: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Alessandro Consolaro Grant/research support from: AbbVie, Pfizer

Background The choice of an appropriate definition of inactive disease (ID) is important because ID has been identified as the ideal therapeutic goal in the treat-to-target strategy in juvenile idiopathic arthritis (JIA).1 Several criteria for ID in JIA have been proposed, including Wallace 2004 and 2011 criteria and JADAS10 and clinical JADAS10 (cJADAS10) criteria. However, a recent study2 has shown that these criteria do not always identify the same group of patients. In addition, it is unknown whether and to what extent the formal definitions of ID agree with the subjective perception of disease remission by the physician and the parent.3 Objectives To investigate the concordance between current criteria for ID and subjective judgment of disease remission by physicians and parents in children with JIA. Methods We evaluated the clinical data of the last visits made in 669 children with JIA from March 2007 to December 2010 to identify all visits in which the caring physician and a parent judged subjectively and independently the child’s disease state as remission or non-remission and the parent declared whether he/she was satisfied or non-satisfied with current illness state (i.e. Parent Acceptable Symptom State, PASS).4 All visits judged subjectively by the physician and the parent as remission or judged in PASS by the parent were examined to identify those which met the Wallace 2004 and 2011 criteria and the JADAS10 and cJADAS10 criteria for ID. Visits which met both subjective and objective definitions were defined as concordant. Results Of the 246 visits in which the physician judged subjectively the disease state as remission, 34.6% and 27.6% met the 2004 and 2011 Wallace criteria, respectively, and 38.6% and 54.5% met the JADAS10 and cJADAS10 criteria for ID, respectively.(Figure 1) Of the 338 visits in which the parent judged subjectively the disease state as remission, 19.8% and 18% met the 2004 and 2011 Wallace criteria, respectively, and 34.9% and 48.8% met the JADAS10 and cJADAS10 criteria for ID, respectively.(Figure 2) In 76.4% of visits judged as remission by the physician, the parent provided the same evaluation. In 55.6% of visits judged as remission by the parent, the physician provided the same evaluation.(Figure 1-2) Of 467 visits judged in PASS by the parent, 17.6% and 14.8% met the 2004 and 2011 Wallace criteria, respectively, and 26.6% and 37.5% met the JADAS10 and cJADAS10 criteria for ID, respectively. Conclusion The JADAS10 and cJADAS10 criteria for ID were more concordant with physician’s and parent’s subjective judgment of remission and with parent’s satisfaction with current illness state than Wallace criteria. The cJADAS10, which lacks the acute phase reactant, revealed the best concordance with both physician’s and parent’s subjective assessments. Physician-parent agreement was greater for remission judged by the physician than for remission judged by the parent. References [1] Ravelli A, et al. Ann Rheum Dis. 2018;77:819-828; 2. Shoop-Whorral SJW, et al. Ann Rheum Dis. 2017;76:1381-1388; 3. Giancane G, et al. Nat Rev Rheumatol. 2017;13:460-461. 4. Filocamo G, et al. J Rheumatol. 2012;39:856-63. Disclosure of Interests Gabriella Giancane: None declared, Maria Francesca Gicchino: None declared, Alessandra Alongi: None declared, Chiara Campone: None declared, Alessandro Consolaro Grant/research support from: AbbVie, Pfizer, Angelo Ravelli Grant/research support from: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & johnson, novartis, pfizer, reckitt benkiser, and roche, consultant for: angelini, abbvie, bristol-myers squibb, johnson & johnson, novartis, pfizer, reckitt benkiser, and roche, speakers bureau: angelini, abbvie, bristol-myers squibb, johnson & johnson, novartis, pfizer, reckitt benkiser, and roche

Rationale: Henoch–Schönlein Purpura (HSP) is an acute small vessel vasculitis. It is the most common vasculitis in children. In majority of the cases, the disease is self-limited. Relapses can occur, in particular during the first year of the disease. There is no consensus on a specific treatment. The efficacy and safety of steroidal treatment in treating HSP is still controversial. Immunosuppressive treatment of HSP nephritis is used in patients with severe renal involvement (nephrotic range proteinuria and/or progressive renal impairment). The literature on immunosuppressive treatment of severe HSP without kidney involvement is scanty. Patients concerns: We report 2 case reports of 2 adolescents affected from Henoch–Schönlein Purpura and severe gastrointestinal involvement. Both patients presented a poor response to steroids treatment. Diagnoses: The diagnosis of HSP was made according to the diagnostic criteria published by European League against Rheumatism and Pediatric Rheumatology European Society in 2006 Interventions: In consideration of the recurrence of the Henoch Schönlein Purpura and the gastrointestinal involvement, we decided to start Mycophenolate Mofetil treatment. Outcomes: In both patients all clinical manifestations resolved in few days. Lessons: In our cases of HSP with gastrointestinal involvement Mycophenolate Mofetil treatment has been very effective. This experience teaches us that immunosuppressive agents may be very useful to induce and maintain remission not only in renal involvement, but in all cases of persistent, recurrent, or complicated Henoch Schönlein Purpura in children.

Background: Dominantly gain-of-function mutations in the NLRP3 gene lead to Cryopyrin associated periodic syndromes (CAPS) characterized by constitutive activation of the inflammasome, increased secretion of interleukin (IL)-1beta and IL-18, and systemic inflammation. IL-1beta and active caspase-1 subunits are released in the serum together with the oligomeric particles of the adaptor ASC (apoptosis-associated Speck-like protein with a caspase-recruitment domain) after activation of the inflammosome complex and, as a consequence, patients with CAPS show an increased serum concentration of ASC+ particles. Objectives: Patients suffering from CAPS are characterized by clinical manifestation similar to other autoinflammatory diseases. This phenomenon together with the lack of specific laboratory tests makes difficult the diagnosis of CAPS. In this context the development of a test for the evaluation of serum ASC levels could provide novel biomarkers facilitating early disease diagnosis and able to monitor treatment responses. Methods: We analysed, with a novel ELISA assay, the levels of ASC particles in serum and plasma of normal subjects, CAPS patients and patients with autoimmune disorders (Multiple Sclerosis (MS), Type 1 Diabetes (T1D) and juvenile idiopathic arthritis), to confirm that ASC presence in the serum is not due to other chronic inflammatory processes characterizing autoimmunity. To evaluate the specificity of this biomarker in CAPS patients and not in individuals suffering from others inflammatory disorders, we also analysed sera from TNF receptor–associated periodic syndrome (TRAPS) patients. Results: ASC particles were higher in untreated CAPS patients with respect to healthy controls and patients suffering from MS and T1D. This tendency was also evident in patients with arthritis and TRAPS even if the difference was not statistically significant due to the small number of samples. In addition after pharmacological treatment there is a tendency to be confirmed through a reduction of ASC levels in CAPS patients. Conclusion: These data suggest that ELISA quantitation of ASC protein could represent a novel and additional strategy for the diagnosis and monitoring of CAPS. Disclosure of Interests:: Fortunata Carbone: None declared, Teresa Micillo: None declared, Luca Cantarini: None declared, Maria Alessio: None declared, Alma Nunzia Olivieri: None declared, Maria Francesca Gicchino: None declared, Antonella Insalaco: None declared, Maria Cristina Maggio: None declared, Orso Maria Lucherini: None declared, Roberto Scarpioni: None declared, Matteo Piga: None declared, Maria Maddalena Angioni: None declared, Laura Obici: None declared, Antonella Simpatico: None declared, Pietro Leccese: None declared, Rita Consolini: None declared, Raffaele Manna: None declared, Paolo Sfriso: None declared, Sara Bindoli: None declared, Paola Galozzi: None declared, Ida Orlando: None declared, Sabrina Chiesa: None declared, Marco Gattorno Grant/research support from: MG has received unrestricted grants from Sobi and Novartis, Giuseppe Matarese Grant/research support from: Matarese reports research grants from Merck-Serono, Biogen Idec, Novartis and IBSA.

Background Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic nonbacterial osteomyelitis, is a rare, noninfectious inflammatory disorder that causes multifocal bone lesions with swelling and pain. Lytic and sclerotic bone lesions could be found on X-ray. Short tau inversion recovery magnetic resonance imaging (STIR MRI) shows bone marrow oedema, bone expansion, lytic areas and periosteal reaction. CRMO is characterized by periodic exacerbations and remissions of unclear/unknown pathogenesis. Case presentation A 10 years old girl, suffering from pain in her right shoulder since the age of 9 years presented to our Department. Thanks to clinical data, laboratoristic and radiological findings and bone biopsy CRMO was diagnosed. So patient started anti-inflammatory treatment and her conditions improved. Conclusions In a child with bone pain should be considered also rare condition as CRMO to perform a correct diagnosis and start an adequate treatment avoiding complications such as bone damage. This condition should be suspected in a child with recurrent bone pain, modest increase of inflammatory indices, lytic or sclerotic bone lesion on X Ray. Typical CRMO localizations are metaphyses of long bones, pelvis, clavicle, vertebral column, sternum, ribs, jaw, but any bone can be involved. The most common CRMO differential diagnosis is represented by infections, malignant bone tumors, Langerhans Cells Histiocytosis (LCH).

Introduction: Methotrexate (MTX) is widely adopted as a first line treatment in moderate to severe forms of juvenile idiopathic arthritis (JIA), when NSAIDs and intra-articular corticosteroid injections are not sufficient to control joint disease. MTX is generally prescribed at 10-15 mg/m2 weekly and its administration can be either oral or parenteral (subcutaneous (SC) or intramuscular). Contrasting evidence is available in the literature about the difference in efficacy and safety of MTX, according to the route of administration. Objectives: Aim of the study is to compare the efficacy of oral versus SC MTX in inducing sustained disease remission in children with oligoarticular JIA enrolled in two prospective cohorts. Methods: Children with oligoarthritis included in 3 prospective studies were considered for inclusion: a) the TRIMECA trial (1), b) the MD-Paedigree study (2), c) the PharmaChild registry. Patient evaluated at the IRCCS Istituto Giannina Gaslini and at the Ospedale Pediatrico Bambino Gesù were included if they had received methotrexate treatment as a first line systemic medication within 6 months after disease onset and if a follow up of at least 12 month after treatment initiation was available. Patients were then grouped according to the route of MTX administration. Baseline demographic and disease features were compared between the 2 groups. Efficacy was assessed by comparing the rate of inactive disease (ID) and clinical remission on medication (CRM) at 12 months, the rate of patients changing the route of MTX administration or requiring a biologic medication due to treatment failure. Safety was assessed by comparing the frequency of treatment interruption due to side effects of MTX. Results: 79 patients were included in the study: 43 received oral MTX, 36 received SC MTX. At treatment initiation, disease duration was not different in the two groups; children receiving SC MTX were older at baseline (4.6 yrs vs. 2.5 yrs) and at disease onset (4.2 yrs vs. 2.3 yrs). Disease activity was comparable in the 2 groups, with a median of 2 active joints in both groups. Median MTX dose was 14.4 mg/m2 for oral MTX group and 15.2 mg/m2 for SC MTX (Mann-Whitney U test, p

Introduction: Erythema nodosum (EN)is the most common panniculitis in childhood. The lesions of EN are localized at the lower limbs, in particular in the pretibial region, while upper limbs and trunk are rarely involved. Erythema nodosum can be associated with general symptoms such as fever, weakness, and severe pain, but skin lesions resolve without skin damage. Objectives: To describe five cases of Erythema nodosum in childhood Methods: R.G. f. 3 years old came to our department for a two week history of fever (up to 38 °C) and skin lesions. Physical examination revealed pharyngeal hyperemia and multiple erythematous nodules on the extensor surface of the lower extremities. Laboratory tests showed an elevation of ESR(35 mm/h) and CRP, (1,06 mg/dL) and high levels of Chlamydia Pneumoniae IgM.Throat swab was negative for group A beta-hemolytic Streptococcus (GAS) and her chest X-ray was negative. So antibiotic therapy was prescribed and symptomatology improved. A.N. m. 8 years old was hospitalized for fever up to 39 °C and skin lesions in the lower limbs. Patient suffered from recurrent abdominal pain and diarrhea. Physical examination revealed abdominal pain and erythematous and painful nodules in pretibial region of both lower limbs. Blood tests showed increase of ESR (40 mm/h) and CRP (1,3 mg/dL). Blood examinations for celiac disease were negative. Fecal calprotectin was high (500 mg/kg). Abdomen ultrasound revealed terminal ileum bowel wall thickening. Crohn’s Disease (CD)was suspected and confirmed with an endoscopy including biopsies. A.N. f. 5 years old was admitted to our department for fever (38 °C) and skin lesions that started two weeks ago. The patient also had 1 month history of cough. Physical examination revealed: pharyngeal hyperemia, cervical and axillary lymphadenopathy and skin lesions suggestive of erythema nodosum on the extensor parts of both lower limbs. Inflammatory tests were increased (ERS 28 mm/h, CRP 1,5 mg/dL). Her chest X-ray was negative. Mantoux test was positive with an induration of 15 millimeters (mm) after 48 hours and 18 mm after 72 hours, also a Quantiferon test was positive. L.B. f. 12 years old had an history of fever, headache, fatigue, joint pain and skin lesions.The objective examination revealed: malar rash, arthritis of the right knee, erythematous nodules on the extensor surface of the lower limbs. Blood tests showed anemia (Hb,5 g/dL), thrombocytopenia (PLT 75.000/mm3), ERS increased (30 mm/h) positive ANA, antiDNA. Systemic Lupus Erythematous was diagnosed according to ACR criteria I.L. f. 8 months old had a two months history of recurrent fever and skin lesions. On admission the patient was febrile (TC 38 °C). Physical examination revealed pharyngeal hyperemia, splenomegaly and erythematous nodules on the extensor surface of the lower limbs.Inflammatory tests were increased (ERS 33 mm/h, CRP 2 mg/dL). Antibodies anti CMV, EBV, Chlamydia and Mycoplasma Pneumoniae were negative. Biopsy of a lesion showed a condition compatible with panarteritis nodosa. Results: EN is a skin inflammatory reaction. EN could be associated with infectious diseases (GAS, Chlamydia Pneumoniae, Mycoplasma Pneumoniae, Epstein-Barr virus, Mycobacterium Tuberculosis), drugs, inflammatory bowel diseases, rheumatologic diseases, malignant tumor. Conclusion: The presented cases show that erythema nodosum can be secondary to different diseases.In the diagnostic process associated symptomatology and laboratory tests should be considered to diagnose the disease and to start specific treatment

A 17-year-old female patient affected by systemic lupus erythematosus (SLE) (who had been taking 300 mg/die of hydroxychloroquine for 3 years), Graves' disease (treated with 10 mg/die of tapazole), and celiac disease came to our attention for urticarial vasculitis. She had been taking prednisone (25 mg/die) for 3 days, and her blood tests showed high levels of Mycoplasma pneumoniae IgM and IgG antibodies. The association between urticaria and M. pneumoniae infections can be present in up to 7% of the cases and, to the best of our knowledge, only two reports of urticarial vasculitis and M. pneumoniae in adults are available in the literature. Urticarial vasculitis can also be a rare cutaneous manifestation of SLE (affecting 2% of the patients), and our case is the first in the literature describing the coexistence of M. pneumoniae infection, SLE, and urticarial vasculitis in a pediatric patient, a case that rises an important differential diagnosis issue about the origin of urticarial vasculitis: SLE reactivation or urticarial vasculitis due to M. pneumoniae infection?

Objectives: To investigate whether the functional variant Q63R of the cannabinoid 2 (CB2) receptor is associated with susceptibility to oligo/poly-articular juvenile idiopathic arthritis (JIA) and with its clinical features. Method: A total of 171 Italian children with oligoarticular/rheumatoid factor negative poly-articular JIA and 600 healthy controls were enrolled in the study and genotyped. Results: A significant difference in genotype distribution of the CB2 Q63R variant (CNR2 rs35761398) between oligo/poly-articular JIA patients and controls was found (p = 0.001). The R63 variant was associated with increased rates of relapse (p = 0.0001). Conclusions: This study indicates that the CB2 receptor contributes to susceptibility to oligo/polyarticular JIA and to the severity of its clinical course.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease of unknown etiology. Clinically, the disease is characterized by the insidious onset of local pain and swelling in affected bones. Its course is one of intermittent periods of exacerbation and remission with successive bones affected.CRMO most commonly affects the metaphysis of long bones, especially the tibia, femur, and clavicle. The spine, pelvis, ribs, sternum, and mandible may also be affected. Although lesions are mostly multiple, patients may present with a single symptomatic focus. Treatment in CRMO is empiric, since placebo controlled randomized trials have not been performed.

Acute Rheumatic fever is still a challenge for physicians, it is often not diagnosed at onset and adequately treated.

Lameness is a symptom very common in childhood, it depends on inflammatory, neoplastic, infective, orthopedic diseases.

Type 1 diabetes mellitus may be associated with many autoimmune diseases with the common autoimmune pathogenesis. We describe the case of a girl suffering from Type 1 diabetes mellitus and autoimmune Hashimoto's thyroiditis since the childhood and, due to the onset of Juvenile Idiopathic Arthritis during adolescence, for three years practiced therapy with an anti-TNF drug, etanercept . Currently her inflammatory markers are normal, arthritis is inactive and diabetes is well controlled. During the treatment with anti-TNF drug we observed a significative reduction of insulin dose, probably due to an increased tissue sensitivity secondary to the suppression of the activity of TNF-alpha. Several clinical trials that have evaluated the effect of immunomodulatory agents in diabetic patients, especially in those with recent onset of disease, were already performed but further studies of longer duration on a larger population are needed to assess the role of biologic drugs and immunotherapy in this group of patients.

Juvenile Idiopathic Arthritis(JIA) is an inflammatory chronic disease concerning joints and others structures. According to International League of Association for Rheumatology (ILAR) seven subtypes of arthritis can be defined in relation with the number of joints and the extra-articular involvement occurring in the first six months of disease. Although JIA pathogenesis is not completely clear is known that T-cell activation is a feature of oligoarticular and polyarticular JIA. The endocannabinoid system is involved in immune regulation by reducing cells activation, modulating Th1 and Th2 balance, inhibiting proinflammatory cytokine production. T-cell and other cellular components of immune system express cannabinoid receptor 1 and 2 (CB1-CB2).

S-JIA has the worst long-term prognosis compared to other types of JIA. Corticosteroids, methotrexate and anti - tumor necrosis factor (TNF) are the most commonly used drugs for it. Recently, newer biologic agents targeting IL-1 and IL-6 have proven their effectiveness in treating s-JIA and in minimizing corticosteroid exposure.