New treatment strategies in the treatment of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood with an incidence of 10-19/100.000 children below the age of 16 years, and it is also one of the major causes of acquired disability and impairment of quality of life in childhood. Early and aggressive control of arthritis is essential to prevent long-term disability. Methotrexate (MTX) provides clinical benefits in JIA with an acceptable profile of toxic effects. Nevertheless, in many cases, inefficacy, especially in patients with polyarticular and systemic-onset form of JIA (SOJIA) or intolerance to MTX, has led investigators to try other therapeutic options. Biologic agents have been designed to target key cytokines implicated in JIA including tumor necrosis factor-α (TNF-α), Interleukin-1 (IL-1), IL-6 as well as signaling molecules involved in the regulation of T-cell and B-cell lympocyte responses. Up to now, the U.S. Food and Drug Administration (FDA) has approved three biologic agents for use in moderate to severe polyarticular JIA: etanercept, adalimumab and abatacept. In general, TNF-α inhibitors are more beneficial for children with polyarticular disease, and the biological agents that target IL-1 and IL-6 activity appear to be successful also in treating patients with SOJIA. The T-cell costimulation modulator, abatacept, was shown to be effective for the treatment of patients with moderate to severe polyarticular JIA. Autologous stem cell transplantation has also been used in patients with refractory JIA; however, the procedure carries the risk of treatment-related high morbidity and mortality. The purpose of this review is to summarise the recent advances in the treatment of JIA. © 2011 Turkish League Against Rheumatism. All rights reserved

Musculoskeletal ultrasound in pediatric rheumatology

Although musculoskeletal ultrasound (MSUS) has emerged as an indispensible tool among physicians involved in musculoskeletal medicine in the last two decades, only recently has it become more attractive to pediatric rheumatologists. Thereafter, the use of MSUS in pediatric rheumatology has started to increase. Yet, an ever-growing body of literature shows parity and even superiority of MSUS when compared to physical examination and other imaging modalities

Musculoskeletal ultrasound in pediatric rheumatology

Although musculoskeletal ultrasound (MSUS) has emerged as an indispensible tool among physicians involved in musculoskeletal medicine in the last two decades, only recently has it become more attractive to pediatric rheumatologists. Thereafter, the use of MSUS in pediatric rheumatology has started to increase. Yet, an evergrowing body of literature shows parity and even superiority of MSUS when compared to physical examination and other imaging modalities. MSUS is suitable for examination of children of all ages and it has certain advantages over other imaging modalities; as it is cheaper, mobile, instantly accessible bedside, easy to combine with clinical assessment (interactivity) and non-invasive. It does not require sedation, which facilitates repetitive examinations. Assessment of multiple locations is possible during the same session. Agitation is rarely a problem and small children can be seated in their parents\u27 lap or they can even play while being examined. © 2011 Tok et al; licensee BioMed Central Ltd

Protracted Febrile Myalgia in a Child as the Presenting Sign of Familial Mediterranean Fever: Case Report and Review of the Literature

Protracted febrile myalgia (PFM) is a rare form of vasculitic disease which is an uncommon dramatic manifestation of familial Mediterranean fever (FMF), characterized by severe crippling myalgia and high fever. We describe a 14-year-old boy who presented with fever, abdominal pain and severe myalgia in all his muscles for 5 days. The diagnosis of PFM was considered based on the presence of fever, paralyzing myalgia with normal CPK, elevated CRP and ESR. Thus, we started prednisolone treatment and his symptoms disappeared and acute-phase reactants declined rapidly. Mutational analysis of the MEFV gene demonstrated homozygote M694V mutation. Thus, he was diagnosed as PFM and FMF. In this report, we present a child with PFM as the sole feature preceding the diagnosis of FMF, and draw attention to the PFM for the diagnosis of FMF even the patient does not fulfi ll the criteria for the clinical diagnosis. © Trakya University Faculty of Medicine

New Horizons in the Genetic Etiology of Systemic Lupus Erythematosus and Lupus-Like Disease: Monogenic Lupus and Beyond

Systemic lupus erythematosus (SLE) is a clinically and genetically heterogeneous autoimmune disease. The etiology of lupus and the contribution of genetic, environmental, infectious and hormonal factors to this phenotype have yet to be elucidated. The most straightforward approach to unravel the molecular pathogenesis of lupus may rely on studies of patients who present with early-onset severe phenotypes. Typically, they have at least one of the following clinical features: childhood onset of severe disease (\u3c5 \u3eyears), parental consanguinity, and presence of family history for autoimmune diseases in a first-degree relative. These patients account for a small proportion of patients with lupus but they inform considerable knowledge about cellular pathways contributing to this inflammatory phenotype. In recent years with the aid of new sequencing technologies, novel or rare pathogenic variants have been reported in over 30 genes predisposing to SLE and SLE-like diseases. Future studies will likely discover many more genes with private variants associated to lupus-like phenotypes. In addition, genome-wide association studies (GWAS) have identified a number of common alleles (SNPs), which increase the risk of developing lupus in adult age. Discovery of a possible shared immune pathway in SLE patients, either with rare or common variants, can provide important clues to better understand this complex disorder, it\u27s prognosis and can help guide new therapeutic approaches. The aim of this review is to summarize the current knowledge of the clinical presentation, genetic diagnosis and mechanisms of disease in patents with lupus and lupus-related phenotypes

Time to focus on outcome assessment tools for childhood vasculitis

Childhood systemic vasculitides are a group of rare diseases with multi-organ involvement and potentially devastating consequences. After establishment of new classification criteria (Ankara consensus conference in 2008), it is now time to establish measures for proper definition of activity and damage in childhood primary vasculitis. By comparison to adult vasculitis, there is no consensus for indices of activity and damage assessment in childhood vasculitis. Assessment of disease activity is likely to become a major area of interest in pediatric rheumatology in the near future. After defining the classification criteria for primary systemic childhood vasculitis, the next step was to perform a validation study using the original Birmingham vasculitis activity score as well as the disease extent index to measure disease activity in childhood vasculitis. Presently, there are efforts in place to develop a pediatric vasculitis activity score. This paper reviews the current understanding about the assessment tools (i.e., clinical features, laboratory tests, radiologic assessments, etc.) widely used for evaluation of the disease activity and damage status of the children with vasculitis. © 2011 Demirkaya et al; licensee BioMed Central Ltd

Paediatric Behcet's Disease: A Comprehensive Review with an Emphasis on Monogenic Mimics

Behçet’s disease (BD) is a polygenic condition with a complex immunopathogenetic background and challenging diagnostic and therapeutic concepts. Advances in genomic medicine have provided intriguing insights into disease pathogenesis over the last decade, especially into monogenic mimics of BD. Although a rare condition, paediatric BD should be considered an important differential diagnosis, especially in cases with similar phenotypes. Emerging reports of monogenic mimics have indicated the importance of genetic testing, particularly for those with early-onset, atypical features and familial aggregation. Treatment options ought to be evaluated in a multidisciplinary setting, given the complexity and diverse organ involvement. Owing to the rarity of the condition, there is a paucity of paediatric trials; thus, international collaboration is warranted to provide consensus recommendations for the management of children and young people. Herein, we summarise the current knowledge of the clinical presentation, immunopathogenetic associations and disease mechanisms in patients with paediatric BD and BD-related phenotypes, with particular emphasis on recently identified monogenic mimics

Current State of Precision Medicine in Primary Systemic Vasculitides

Precision medicine (PM) is an emerging data-driven health care approach that integrates phenotypic, genomic, epigenetic, and environmental factors unique to an individual. The goal of PM is to facilitate diagnosis, predict effective therapy, and avoid adverse reactions specific for each patient. The forefront of PM is in oncology; nonetheless, it is developing in other fields of medicine, including rheumatology. Recent studies on elucidating the genetic architecture of polygenic and monogenic rheumatological diseases have made PM possible by enabling physicians to customize medical treatment through the incorporation of clinical features and genetic data. For complex inflammatory disorders, the prevailing paradigm is that disease susceptibility is due to additive effects of common reduced-penetrance gene variants and environmental factors. Efforts have been made to calculate cumulative genetic risk score (GRS) and to relate specific susceptibility alleles for use of target therapies. The discovery of rare patients with single-gene high-penetrance mutations informed our understanding of pathways driving systemic inflammation. Here, we review the advances in practicing PM in patients with primary systemic vasculitides (PSVs). We summarize recent genetic studies and discuss current knowledge on the contribution of epigenetic factors and extracellular vesicles (EVs) in disease progression and treatment response. Implementation of PM in PSVs is a developing field that will require analysis of a large cohort of patients to validate data from genomics, transcriptomics, metabolomics, proteomics, and epigenomics studies for accurate disease profiling. This multi-omics approach to study disease pathogeneses should ultimately provide a powerful tool for stratification of patients to receive tailored optimal therapies and for monitoring their disease activity