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1.
Pediatr Int ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33567119

RESUMO

BACKGROUND: Whole Body Magnetic Resonance Imaging (WBMRI) is a multiregional imaging technique suitable to investigate the extent of multisystemic diseases without exposure to radiation, with a high sensitivity to bone alterations. The aim of our study was to evaluate the role of WBMRI in the workup of children with non-specific musculoskeletal features, and non-indicative laboratory and instrumental data, suspected to have a rheumatologic disease. METHODS: We retrospectively analysed medical records, including laboratory tests and radiological data of 34 children who have been evaluated due to non-specific musculoskeletal manifestations, for which a WBMRI was prescribed. RESULTS: We included 34 children, 19 females and 15 males, mean age 10 years (range 2-16 years), with the following clinical features: diffuse arthralgia (12 children), persistent fever (2 children), persistent fever and diffuse arthralgia (20 children). Serologic inflammatory markers resulted increased in 29/34 patients. Twenty-five children had already performed X-Ray and/or ultrasound before WBMRI, with a negative/uninformative result. WBMRI was performed 3-6 weeks (median, 3.5 weeks) after the initial presentation of symptoms. In 22/34 (65%) children WBMRI revealed some abnormalities that supported the final diagnosis. Twelve out of 34 children (34%) resulted to be affected by chronic recurrent multifocal osteomyelitis (CRMO). CONCLUSIONS: WBMRI is helpful in paediatric rheumatology in the differential diagnosis of undefined inflammatory conditions. It appears to be a promising tool especially in the detection of multifocal bone lesions. The diagnosis that mainly benefits from WBMRI was CRMO. WBMRI can also help in excluding neoplastic diseases.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33261821

RESUMO

OBJECTIVE: Sjogren's syndrome (SS) is a chronic autoimmune disease with a highly variable presentation. This study aims to describe childhood SS (cSS) features to help guide clinicians in their consideration of and workup for cSS. METHODS: We retrospectively reviewed medical records of patients with cSS referred to three Italian pediatric rheumatology centers from 2015 to 2019 and we conducted a literature review of cSS. Statistical analysis was performed to detect associations between clinical/laboratory features. RESULTS: We reviewed 12 cases (9 female) followed in 3 Italian centers and 240 cases (191 female) in the published literature reporting individual information. The median age at disease onset was 10 years for both cohorts. The most frequently reported clinical SS-specific feature was parotitis in both cohorts (67% each). Extraglandular manifestations were very common and joint involvement was the most frequent. In the cluster analysis, we identified a significant association between parotitis and younger patients (< 11 years). We verified the presence of the main SS features (exocrine gland inflammation, exocrine gland dysfunction, and presence of autoantibodies) in the Italian cohort and the literature review-based cohort: 92% and 80% of the cohorts, respectively, had at least 2/3 main characteristics. CONCLUSION: We described cSS features with relative frequencies and we found that parotid involvement was related to cSS in younger patients. The majority of patients showed various combinations of exocrine gland inflammation, exocrine gland dysfunction, and presence of autoantibodies giving a theoretical basis for future research to pave the way for the development of cSS specific diagnostic criteria.

3.
Ital J Pediatr ; 46(1): 169, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33187546

RESUMO

BACKGROUND: SAPHO (synovitis, acne, pustolosis, hyperostosis and osteitis) syndrome is a rare autoinflammatory chronic disorder, presenting with non-infectious osteitis, sterile joint inflammation and skin manifestations including palmoplantar pustolosis and severe acne. It could be often misdiagnosed for its heterogeneous clinical presentation. Treatment is challenging and, due to the rarity of this syndrome, no randomized controlled clinical trials have been conducted. Empirical treatments, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibiotics and bisphosphonates and disease-modifying anti-rheumatic drugs (DMARDs) could be quite effective. Anti-tumor necrosis factor-alpha (anti-TNF-α) agents and interleukin-1 (IL-1) antagonists have shown promising results in refractory patients. Isotretinoin, commonly used for severe acne, has been rarely described as possible trigger of osteo-articular manifestations, in particular sacroiliitis. CASE PRESENTATION: The case of a boy, affected by acne fulminans and depression, who presented with sacroiliitis after a 10-week treatment with isotretinoin is presented. After SAPHO diagnosis, NSAIDs therapy was started but the onset of bilateral gluteal hidradenitis suppurativa required the switch to a TNF-α antagonist (Adalimumab) with the achievement of a good control of the disease. Despite specific therapy with sertraline, the patient continued to complains severe depression. CONCLUSIONS: Our case reports a temporal association between the onset of osteo-articular symptoms and the introduction of isotretinoin, as previously described. However, this timeline is not sufficient to establish a causal role of this drug into the pathogenesis of sacroiliitis. At this regard, further studies are required. The occurrence of hidradenitis suppurativa during SAPHO course supported the introduction of TNF-α blockers with a favourable result, as reported in a few cases in literature. The association between SAPHO syndrome and depressive mood disorders is already reported. Our patient experienced severe depression whose trend seems to be independent from the course of the main disease. Currently, it is not clarified if depression could be considered reactive to the underling disease or if it forms an integral part of the autoinflammatory disorder.

4.
Paediatr Drugs ; 22(6): 645-652, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32885390

RESUMO

Kawasaki disease (KD) is one of the most common vasculitides of childhood and the main cause of acquired heart disease in developed countries. Intravenous immunoglobulin (IVIG) in association with aspirin represents the main treatment for KD. However, 10-20% of patients fail to respond to standard treatment and have an increased risk of cardiac complications. There is currently no accepted protocol for treatment of resistant cases. Several authors highlighted the role of interleukin-1 (IL-1) as a mediator of inflammation in KD and suggested the possibility of using IL-1 or its receptor as a target of therapy. The use of IL-1 inhibitors in patients with KD has been reported in the scientific literature, but data are largely limited to individual case reports and small case series. We summarized the scientific literature related to the use of anakinra, analyzing preclinical and clinical data. Thirty-eight patients have been described so far, most of them with KD-related complications. Twenty-two were described in case reports and case series, while 16 were patients from the completed KAWAKINRA phase IIa study. Almost all patients received clinical benefit, and no relevant side effects were noted. Based on this evidence, in our opinion, anakinra may be considered as an option after the failure of the first IVIG infusion, especially in patients with coronary involvement.

5.
J Transl Autoimmun ; 3: 100031, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32743516

RESUMO

Innate immune system represents the ancestral defense against infectious agents preserved along the evolution and species; it is phylogenetically older than the adaptive immune system, which exists only in the vertebrates. Cells with phagocytic activity such as neutrophils, macrophages, and natural killer (NK) cells play a key role in innate immunity. In 1999 Kastner et al. first introduced the term "autoinflammation" describing two diseases characterized by recurrent episodes of systemic inflammation without any identifiable infectious trigger: Familial Mediterranean Fever (FMF) and TNF Receptor Associated Periodic Syndrome (TRAPS). Autoinflammatory diseases (AIDs) are caused by self-directed inflammation due to an alteration of innate immunity leading to systemic inflammatory attacks typically in an on/off mode. In addition to inflammasomopathies, nuclear factor (NF)-κB-mediated disorders (also known as Rhelopathies) and type 1 interferonopathies are subjects of more recent studies. This review aims to provide an overview of the field with the most recent updates (see "Most recent developments in.." paragraphs) and a description of the newly identified AIDs.

6.
Clin Exp Rheumatol ; 38(6): 1255-1262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32828142

RESUMO

OBJECTIVES: Chronic non-bacterial osteomyelitis (CNO) is a rare non-infectious bone inflammatory disorder; when multifocal, it is referred to as Chronic Recurrent Multifocal Osteomyelitis (CRMO). This study evaluates the demographic, clinical and radiological characteristics of a multi-centre cohort of patients with CNO/CRMO. METHODS: Demographic and clinical data of patients with an established diagnosis of CNO/CRMO followed at paediatric rheumatology centres across Europe (Italy, France, Slovenia) and India were retrospectively collected. RESULTS: There were no demographic differences across countries, but time to diagnosis was significantly longer in India (p=0.041). Pain was almost invariably present at disease onset; functional impairment was more frequent among Italian and Slovenian patients (p=0.001). The number of sites of bone involvement was similar between genders and countries, with long bone metaphises being the most common site. Raised acute phase reactants, detected in >50% of patients, were not associated with clinical manifestations or response to treatment. Comorbidities, evinced in 37% of patients, were equally distributed between genders and nationalities. Imaging approach was similar across countries, without any association between radiological findings and clinical manifestations. NSAIDs were almost invariably used as first-line treatment, but response rate was significantly lower in Italy (p=0.02). Methotrexate was used in 28% of case, with an overall rate of response of 82%. Health conditions and rate of permanent deformities were similar across different countries. CONCLUSIONS: The differences in clinical presentation, radiological features and response to treatment described in this multinational cohort of CNO/CRMO might provide novel insights into this still elusive disease.

7.
Expert Opin Pharmacother ; 21(17): 2161-2168, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32726179

RESUMO

INTRODUCTION: Spondyloarthropathies (SpA) represent a heterogeneous group of inflammatory arthritides with autoimmune pathogenesis that can affect both adults and children with peculiar features such as enthesitis, sacroiliac joint, and axial involvement. Since juvenile onset of SpA (JSpA) is not well codified by the current juvenile idiopathic arthritis classification, studies in this field are restricted to single categories and therefore cannot be exhaustive. This review aims to report recent advances in the treatment of JSpA. AREAS COVERED: In order to assess the available therapies for JSpA, the authors have analyzed data obtained from retrospective and prospective studies, case reports, and case series, as well as from controlled trials. EXPERT OPINION: Given the challenging classification of JSpA, research in this field has been restricted to single subcategories. Little is known of which patients are more likely to develop axial involvement leading to severe spinal damage. Whether TNF inhibitors are capable to prevent or stop disease progression, once started, is yet to be ascertained with structural damage still a matter for research. Therefore, trials on the efficacy of TNF inhibitors in JSpA are strongly advocated since they may help to elucidate their place as a treatment option.

8.
Eur J Immunol ; 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32691428

RESUMO

How T-helper (Th) lymphocyte subpopulations identified in synovial fluid from patients with juvenile idiopathic arthritis (JIA) (Th17, classic Th1, or nonclassic Th1) drive joint damage is of great interest for the possible use of biological drugs that inhibit the specific cytokines. Our objective was to clarify the role of such Th subpopulations in the pathogenesis of articular cartilage destruction by synovial fibroblasts (SFbs), and the effect of Th17 blockage in an animal model. SFbs were isolated from healthy subjects and patients with JIA, and peripheral blood Th lymphocytes subsets were obtained from healthy subjects. Fragments of human cartilage from healthy subjects in a collagen matrix containing JIA or normal SFbs grafted underskin in SCID mice were used to measure cartilage degradation under the effects of Th supernatants. JIA SFbs overexpress MMP9 and MMP2 and Th17 induce both MMPs in normal SFbs, while nonclassic Th1 upregulate urokinase plasminogen activator (uPA) activity. In vitro invasive phenotype of normal SFbs is stimulated with conditioned medium of Th17 and nonclassic-Th1. In the in vivo "inverse wrap" model, normal SFbs stimulated with supernatants of Th17-lymphocytes and nonclassic Th1 produced a cartilage invasion and degradation similar to JIA SFbs. Secukinumab inhibits the cartilage damage triggered by factors produced by Th17.

9.
Pediatr Rheumatol Online J ; 18(1): 42, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493352

RESUMO

BACKGROUND: Arthritis is often an underestimated extraintestinal manifestation in pediatric inflammatory bowel disease (IBD), including sacroiliitis, whose early signs are well detectable at magnetic resonance imaging (MRI). Magnetic resonance enterography (MRE) is an accurate imaging modality for pediatric IBD assessment. We studied the possibility to detect signs of sacroiliac inflammation in a group of children with IBD who underwent MRE for gastrointestinal disease evaluation. METHODS: We retrospectively reviewed MRE scans performed in pediatric patients with IBD. We looked for signs of sacroiliitis taking the ASAS (Assessment of SpondyloArthritis international Society) criteria as a model. Presence of bone marrow edema (using T2W sequences with fat suppression), diffusion restriction in Diffusion Weighted Imaging (DWI) or Diffusion Weighted Imaging with Background Suppression (DWIBS), and dynamic contrast enhancement were evaluated. Each SI joint was divided into 4 quadrants: upper iliac, lower iliac, upper sacral, and lower sacral. Two blinded observers with experience in pediatric and skeletal imaging independently evaluated the images. Cases upon which there was a disagreement were evaluated by the two reviewing radiologists and a third radiologist with similar experience together. RESULTS: We enrolled 34 patients (24 males and 10 females, with mean age at scanning 14.3 years, median 15.3 years; 2 affected by ulcerative colitis, 32 by Crohn's disease) for a total of 59 examinations performed at the time of their first diagnosis or at symptom exacerbations. No patient complained of musculoskeletal symptoms, neither had pathological findings at articular examination. At the time of MRE 25 patients were under treatment for their IBD. Five patients had radiological signs of SI inflammation at MRE, albeit of mild degree. All patients with SI joint edema also had a restricted diffusion in DWIBS or DWI and almost everyone had contrast media uptake. CONCLUSIONS: Sacroiliitis is one of the extraintestinal manifestation associated with IBD; it is often asymptomatic and clinically underdetected, with an unrelated progression with respect to the underlying IBD. MRE offers the possibility to study SI joints in young patients with IBD who undergo MRE for the investigation of their intestinal condition. Furthermore, we observed that gadolinium enhancement does not improve diagnostic specificity in sacroiliiitis detection.

10.
Pediatr Rheumatol Online J ; 18(1): 35, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321540

RESUMO

On March 11th, 2020 the World Health Organization declared COVID-19 a global pandemic. The infection, transmitted by 2019 novel coronavirus (2019-nCov), was first discovered in December 2019, in Wuhan, Hubei Province, and then rapidly spread worldwide. Italy was early and severely involved, with a critical spread of the infection and a very high number of victims. Person-to-person spread mainly occurs via respiratory droplets and contact. The median incubation period is 5 days. The spectrum of respiratory symptoms may range from mild to severe, strictly depending on the age of the patient and the underlying comorbidities.In children COVID-19 related disease is less frequent and less aggressive. In Italy 1% of positive cases are under 18 years of age, and no deaths have been recorded before 29 years of age. For patients affected by rheumatic disease, despite the concerns related to the imbalance of their immune response and the effect of immunosuppressive treatments, there are still few data to understand the real consequences of this infection. Major scientific societies have issued recommendations to help rheumatologists in caring their patients. Interestingly, some of the drugs mostly used by rheumatologists appear to be promising in critical COVID-19 infected patients, where the hyperinflammation and cytokine storm seem to drive to the multiorgan failure.Pediatric rheumatologists are expected to play a supporting role in this new front of COVID-19 pandemic, both as general pediatricians treating infected children, and as rheumatologists taking care of their rheumatic patients, as well as offering their experience in the possible alternative use of immunomodulatory drugs.


Assuntos
Antirreumáticos/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Pediatras , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Doenças Reumáticas/complicações , Doenças Reumáticas/virologia , Reumatologistas , Adolescente , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Juvenil/complicações , Artrite Juvenil/virologia , Betacoronavirus , Criança , Pré-Escolar , Cloroquina/uso terapêutico , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Humanos , Hidroxicloroquina/uso terapêutico , Lactente , Interleucina-6/antagonistas & inibidores , Itália/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia
12.
J Pediatr ; 218: 228-230.e1, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31748120

RESUMO

We describe 10 children with Alagille syndrome and inflammatory arthritis. In our centers, the prevalence of chronic arthritis in patients with Alagille syndrome is approximately 50 times higher compared with the general population. Arthritis was refractory to most treatment. Patients with Alagille syndrome should routinely be screened for musculoskeletal symptoms.


Assuntos
Síndrome de Alagille/complicações , Síndrome de Alagille/diagnóstico , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Adolescente , Síndrome de Alagille/epidemiologia , Artrite Juvenil/epidemiologia , Criança , Pré-Escolar , Doença Crônica , Meios de Contraste , Feminino , Humanos , Inflamação , Transplante de Fígado , Imagem por Ressonância Magnética , Masculino , Pediatria , Estudos Retrospectivos , Reumatologia , Inquéritos e Questionários , Punho/diagnóstico por imagem
13.
Int J Rheum Dis ; 23(3): 448-453, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31858744

RESUMO

BACKGROUND: Granulomatous diseases are a heterogeneous group of conditions characterized by an inflammatory infiltrate with a core of macrophages, epithelioid, giant cells and a corona of fibroblasts and lymphocytes. They are associated with a wide range of disorders such as mycobacterial and fungal infections, neoplasms, immunodeficiencies and systemic inflammatory disorders as sarcoidosis. CASE REPORT: We report the case of a previously healthy 9-year-old male child who presented with persistent cough, diffuse lymphadenopathy, enlargement of liver and spleen and protracted fever. Anemia, lymphopenia and reduced platelet count was reported, with an increase of inflammatory markers. High levels of Angiotensin-converting enzyme and chitotriosidases were noted. A PET-CT scan showed increased uptake of 18 F-FDG glucose in multiple lymph nodes in thorax and abdomen and in the spleen. Biopsy of inguinal and bronchial nodes showed nodal granulomatous inflammation. The child was diagnosed with sarcoidosis and treated with corticosteroids with only transient efficacy. Further tests reported panhypogammaglobulinaemia and a reduced pool of B-memory lymphocytes. Thus, the diagnosis was revised to common variable immunodeficiency (CVID). CONCLUSION: Common variable immunodeficiency is a heterogeneous condition with a highly variable clinical phenotype and a strong association with autoimmune disorders. The presence of noncaseating granuloma and pulmonary lesions, along with extrapulmonary features required a step by step approach to differentiate between CVID and sarcoidosis. This enables early introduction of immunoglobulin replacement therapy and decreases the morbidity and mortality of CVID.

14.
Clin Rheumatol ; 39(4): 1341-1345, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31838640

RESUMO

The association of different autoimmune diseases in the same subject is not uncommon, also in the pediatric age. The coexistence of morphea and juvenile idiopathic arthritis (JIA) is however exceptional. We report four such cases. Unlike the few other reported cases, in 3/4 of our patients, morphea appeared well after the onset of JIA, when the articular disease was in full clinical remission. Based on the epidemiology of pediatric morphea in the general population, this association is unlikely to be fortuitous. Pediatric rheumatologists should be aware of this possible association, and follow clinically patients who achieve long-term clinical remission. Key Points ⦁ Morphea is an unusual occurrence in the context of JIA. These conditions have a common autoimmune background, but are very rarely reported together. ⦁ It is important to follow JIA patients even during long-term remission since other autoimmune phenomena can occur.

15.
Curr Opin Rheumatol ; 32(1): 15-20, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31599798

RESUMO

PURPOSE OF REVIEW: Kawasaki disease is a childhood vasculitis of unknown origin, whose major complication is the development of coronary artery aneurysms (CAA). The purpose of this review is to provide an overview on the most recent evidence on the pathogenesis, diagnosis and treatment options of Kawasaki disease summarizing the most relevant studies published in the last year. RECENT FINDINGS: Several genetic polymorphisms leading to Kawasaki disease susceptibility have been identified, mostly related to immune system regulation; potential external triggers are being investigated by environmental epidemiology studies. A new diagnostic test based on trascriptomics has been tested with promising preliminary results. With regards to first-line treatments, the real effectiveness of high-dose aspirin remains a matter of debate. For refractory cases, the ones at the highest risk for developing CAA, promising results come from the use of biologic agents, especially TNF and IL-1 blockers. SUMMARY: Recent literature has provided interesting insights on the various factors involved in the complex scenario behind the pathogenesis of Kawasaki disease, especially genetic ones. Novel diagnostic tests and new evidence on the use of biologic agents in Kawasaki disease are emerging, but further evidence is needed to permit early diagnosis and effective treatment of this condition.

17.
Front Pediatr ; 7: 419, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681717

RESUMO

Recurrent pericarditis (RP) is a clinical syndrome characterized by recurrent attacks of acute pericardial inflammation. Prognosis quoad vitam is good, although morbidity might be significant, especially in children and adolescents. Multiple potential etiologies result in RP, in the vast majority of cases through autoimmune or autoinflammatory mechanisms. Idiopathic RP is one of the most frequent diagnoses, that requires the exclusion of all known etiologies. Therapeutic advances in the last decade have been significant with the recognition of the effectiveness of anti IL1 therapy, but a correct diagnostic and therapeutic algorithm is of key importance. Unfortunately, most of evidence comes from studies in adult patients. Here we review the etiopathogenesis, diagnosis and management of RP in pediatric patients.

18.
Isr Med Assoc J ; 21(7): 475-479, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507124

RESUMO

BACKGROUND: Uveitis is an inflammatory disorder of the uveal tract of the eye that can affect both adults and children. Non-infectious uveitis can be an expression of a systemic autoimmune condition, or it can be idiopathic. It is a serious disease, associated with possible severe complications leading to visual impairment and blindness. For this reason, a prompt diagnosis and assessment of an appropriate treatment, with the collaboration of specialists such as ophthalmologists and rheumatologists, are extremely important. Many treatment options may be associated to side effects; therefore, clinicians should follow a stepladder approach starting with the least aggressive treatments to induce remission of inflammation. In this review, we reported the current evidence-based treatments for non-infectious uveitis in pediatric and adult patients with particular attention to the biologic response modifier treatment options. Important multicenter studies have demonstrated the efficacy of adalimumab, both in adults (VISUAL I, VISUAL II, VISUAL III) and in children (SYCAMORE, ADJUVITE), while for other agents data are still scarce.


Assuntos
Adalimumab/administração & dosagem , Fatores Imunológicos/administração & dosagem , Uveíte/tratamento farmacológico , Adulto , Criança , Comportamento Cooperativo , Medicina Baseada em Evidências , Humanos , Inflamação/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/patologia
20.
Autoimmun Rev ; 18(8): 761-766, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31181328

RESUMO

Numerous proteases produced by synovial cells of arthritic joints, chondrocytes, macrophages and polymorphonuclear cells have been identified as responsible for the joint damage in rheumatoid arthritis. There are few scientific contributions aimed to identify similar mechanisms in the joints of patients with juvenile idiopathic arthritis. Recently, some mechanisms emerged, triggered by the TH17 and TH1/TH17 lymphocytes, which could shed new light on unexpected pathogenic pathways of joint damage in the JIA, mainly regarding the RANK-RANKL pathway. Other novelties are linked to the mechanisms of acidification of the synovial fluid, which create a microenvironment suitable for the extracellular activity of lysosomal enzymes. Some biological drugs currently used in the therapy of JIA can interfere with these mechanisms.


Assuntos
Artrite Juvenil/enzimologia , Peptídeo Hidrolases/metabolismo , Adolescente , Artrite Juvenil/sangue , Artrite Juvenil/patologia , Osso e Ossos/química , Osso e Ossos/patologia , Cartilagem Articular/química , Cartilagem Articular/patologia , Criança , Humanos
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