Juvenile idiopathic arthritis-associated uveitis

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, with JIA-associated uveitis its most common extra-articular manifestation. JIA-associated uveitis is a potentially sight-threatening condition and thus carries a considerable risk of morbidity. The aetiology of the condition is autoimmune in nature with the predominant involvement of CD4(+) T cells. However, the underlying pathogenic mechanisms remain unclear, particularly regarding interplay between genetic and environmental factors. JIA-associated uveitis comes in several forms, but the most common presentation is of the chronic anterior uveitis type. This condition is usually asymptomatic and thus screening for JIA-associated uveitis in at-risk patients is paramount. Early detection and treatment aims to stop inflammation and prevent the development of complications leading to visual loss, which can occur due to both active disease and burden of disease treatment. Visually disabling complications of JIA-associated uveitis include cataracts, glaucoma, band keratopathy and macular oedema. There is a growing body of evidence for the early introduction of systemic immunosuppressive therapies in order to reduce topical and systemic glucocorticoid use. This includes more traditional treatments, such as methotrexate, as well as newer biological therapies. This review highlights the epidemiology of JIA-associated uveitis, the underlying pathogenesis and how affected patients may present. The current guidelines and criteria for screening, diagnosis and monitoring are discussed along with approaches to management

Diagnosing haemophagocytic syndrome

Haemophagocytic syndrome, or haemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory disorder characterised by uncontrolled activation of the immune system. It can result from mutations in multiple genes involved in cytotoxicity or occur secondary to a range of infections, malignancies or autoimmune rheumatic diseases. In the latter case, it is also known as macrophage activation syndrome (MAS). Characteristic features are persistent fever, hepatosplenomegaly, petechial/purpuric rash, progressive cytopenias, coagulopathy, transaminitis, raised C reactive protein, falling erythrocyte sedimentation rate, hypertriglyceridaemia, hypofibrinogenaemia and extreme hyperferritinaemia often associated with multi-organ impairment. Distinguishing HLH from systemic sepsis can present a major challenge. Criteria for diagnosis and classification of HLH and MAS are available and a serum ferritin &gt;10 000 µg/L is strongly supportive of HLH. Without early recognition and appropriate treatment, HLH is almost universally fatal. However, with prompt referral and advancements in treatment over the past two decades, outcomes have greatly improved.</jats:p

Chronic Recurrent Multifocal Osteomyelitis (CRMO):advancing the diagnosis

BackgroundChronic recurrent multifocal osteomyelitis (CRMO) is a little known inflammatory bone disease occurring primarily in children and adolescents. Delays in referral and diagnosis may lead to prolonged courses of antibiotics with in-patient care, unnecessary radiation exposure from multiple plain radiographs or bone scans and repeated surgery including bone biopsies.Children (aged &lt; 18 years) diagnosed with CRMO between January 2005 and December 2012, reviewed at Bristol Royal Hospital for Children were included and all available data collected. Information regarding CRMO was sent to all orthopaedic surgeons in the region in 2009.The aim of the study was to examine the features of the cohort, to examine the length of time to diagnosis and to explore the criteria used for diagnosis with and without biopsy.FindingsOver an 8 year period, 41 patients were diagnosed with CRMO. Symptom onset occurred at a median of 9 years of age and time to diagnosis had a median of 15 months (range 0 - 92). Correlation coefficient analysis for time to diagnosis by year showed statistical significance with a decreasing trend. From the cohort data, diagnostic criteria were developed; applied retrospectively, 34 (83%) children may have been diagnosed using the criteria, without a biopsy.ConclusionsThe data suggest that increasing knowledge of this condition may shorten time to diagnosis. Use of the Bristol diagnostic criteria by an experienced clinician may obviate the need for biopsy in some patients

Big data and stratified medicine:what does it mean for children?

Stratified medicine in paediatrics is increasingly becoming a reality, as our understanding of disease pathogenesis improves and novel treatment targets emerge. We have already seen some success in paediatrics in targeted therapies such as cystic fibrosis for specific cystic fibrosis transmembrane conductance regulator variants. With the increased speed and decreased cost of processing and analysing data from rare disease registries, we are increasingly able to use a systems biology approach (including ‘-omics’) to screen across populations for molecules and genes of interest. Improving our understanding of the molecular mechanisms underlying disease, and how to classify patients according to these will lead the way for targeted therapies for individual patients. This review article will summarise how ‘big data’ and the ‘omics’ are being used and developed, and taking examples from paediatric renal medicine and rheumatology, demonstrate progress being made towards stratified medicine for children