Athimalaipet V Ramanan

Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies

Background: Coeliac disease (CD) is a disorder that may depend on genetic, immunological, and environmental factors. Recent observational studies suggest that breast feeding may prevent the development of CD. Aim: To evaluate articles that compared effects of breast feeding on risk of CD. Methods: Systematic review and meta-analysis of observational studies published between 1966 and June 2004 that examined the association between breast feeding and the development of CD. Results: Six case-control studies met the inclusion criteria. With the exception of one small study, all the included studies found an association between increasing duration of breast feeding and decreased risk of developing CD. Meta-analysis showed that the risk of CD was significantly reduced in infants who were breast feeding at the time of gluten introduction (pooled odds ratio 0.48, 95% CI 0.40 to 0.59) compared with infants who were not breast feeding during this period. Conclusions: Breast feeding may offer protection against the development of CD. Breast feeding during the introduction of dietary gluten, and increasing duration of breast feeding were associated with reduced risk of developing CD. It is, however, not clear from the primary studies whether breast feeding delays the onset of symptoms or provides a permanent protection against the disease. Long term prospective cohort studies are required to investigate further the relation between breast feeding and CD.

Autoantibodies to a 140‐kd protein in juvenile dermatomyositis are associated with calcinosis

Objective The identification of novel autoantibodies in juvenile dermatomyositis (DM) may have etiologic and clinical implications. The aim of this study was to describe autoantibodies to a 140-kd protein in children recruited to the Juvenile DM National Registry and Repository for UK and Ireland. Methods Clinical data and sera were collected from children with juvenile myositis. Sera that recognized a 140-kd protein by immunoprecipitation were identified. The identity of the p140 autoantigen was investigated by immunoprecipitation/immunodepletion, using commercial monoclonal antibodies to NXP-2, reference anti-p140, and anti-p155/140, the other autoantibody recently described in juvenile DM. DNA samples from 100 Caucasian children with myositis were genotyped for HLA class II haplotype associations and compared with those from 864 randomly selected UK Caucasian control subjects. Results Sera from 37 (23%) of 162 patients with juvenile myositis were positive for anti-p140 autoantibodies, which were detected exclusively in patients with juvenile DM and not in patients with juvenile DM–overlap syndrome or control subjects. No anti-p140 antibody–positive patients were positive for other recognized autoantibodies. Immunodepletion suggested that the identity of p140 was consistent with NXP-2 (the previously identified MJ autoantigen). In children with anti-p140 antibodies, the association with calcinosis was significant compared with the rest of the cohort (corrected P < 0.005, odds ratio 7.0, 95% confidence interval 3.0–16.1). The clinical features of patients with anti-p140 autoantibodies were different from those of children with anti-p155/140 autoantibodies. The presence of HLA–DRB1*08 was a possible risk factor for anti-p140 autoantibody positivity. Conclusion This study has established that anti-p140 autoantibodies represent a major autoantibody subset in juvenile DM. This specificity may identify a further immunogenetic and clinical phenotype within the juvenile myositis spectrum that includes an association with calcinosis.

Clinical features and outcomes of juvenile dermatomyositis and other childhood onset myositis syndromes

The childhood myositis syndromes, primarily JDM, are relatively homogeneous diseases that have a good outcome in most cases, but are chronic, with poor outcomes, in a substantial number of cases. Because of the rarity of childhood myositis, and because there has not yet been a unified evidence-based approach to therapy, optimal treatment remains unknown. In clinic-based series the disease seems to be homogeneous but there are patients with rare clinical features, (e.g., cardiac, pulmonary, and neurologic disease), that impact prognosis. Racial, genetic, and other factors may lead to geographic variations in clinical presentations and outcomes, and perhaps further exploration of these influences will lead to a better understanding of the clinical features and outcomes seen in children. Our treatments are based on accumulated experience, but proper clinical trials have not been done. Ongoing registry studies, development of validated activity and damage assessment tools, large clinical trials, and continued investigation into the pathogenesis of the childhood myositis syndromes should lead to improved understanding and better treatments.

A case of macrophage activation syndrome successfully treated with anakinra

Background A 13-year-old girl presented with features typical of systemic juvenile idiopathic arthritis, including fever, rash and arthritis. Her past medical history was unremarkable.Investigations Routine investigations, including CBC, serological tests for urea and electrolyte levels, tests of liver function and clotting, measurement of erythrocyte sedimentation rate, cultures of blood, urine and throat swabs, abdominal ultrasonography, echocardiography, bone marrow aspiration, and determination of laboratory parameters, including presence of anti-streptolysin O antibody and levels of C-reactive protein, lactate dehydrogenase, serum ferritin, D-dimer, fibrinogen and ciclosporin. Specialized investigations included measurement of serum levels of interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor and soluble CD25.Diagnosis Systemic juvenile idiopathic arthritis complicated by macrophage activation syndrome.Management The disease remained active following treatment with intravenous steroid, immunoglobulin and ciclosporin. The patients disease was successfully controlled following the introduction of anakinra.

Recognition and management of macrophage activation syndrome in juvenile arthritis.

Purpose of reviewMacrophage activation syndrome is a life-threatening complication seen predominantly in children with systemic onset juvenile idiopathic arthritis. It accounts for a significant amount of the morbidity and mortality seen with systemic onset juvenile idiopathic arthritis. Recent findingsIn this article, we will look at the new developments in the diagnosis, classification, pathogenesis and management of macrophage activation syndrome in systemic onset juvenile idiopathic arthritis patients. SummaryMore work is needed to further elucidate the pathophysiology of macrophage activation syndrome in systemic onset juvenile idiopathic arthritis. This would be the key to early diagnosis using more sensitive criteria and better management.

Review of haemophagocytic lymphohistiocytosis

Haemophagocytic lymphohistiocytosis (HLH) describes a clinical syndrome of hyperinflammation resulting in an uncontrolled and ineffective immune response. It may develop subsequent to a number of recognised genetic mutations or in association with infection, malignancy, autoinflammatory or metabolic conditions. Even with the published diagnostic criteria it can be difficult to make the diagnosis of HLH. Patients presenting acutely to the general paediatrician or paediatric intensivist with a clinical picture of likely sepsis, ie fever, laboratory evidence of inflammatory response, coagulopathy and thrombocytopaenia should be appropriately investigated and managed for sepsis, but the possible diagnosis of HLH should be borne in mind, particularly in the child who deteriorates despite maximal therapy. This review discusses current knowledge on the classification, diagnosis and management of primary and secondary HLH, and suggests a pathway of investigation for the paediatrician faced with a potential case.

Successful treatment of severe or methotrexate-resistant juvenile localized scleroderma with mycophenolate mofetil

OBJECTIVE To evaluate the efficacy of mycophenolate mofetil (MMF) in the treatment of severe refractory juvenile localized scleroderma (JLS). METHODS A retrospective chart review was performed in patients with JLS who had been treated with MMF after the failure of a combination of MTX and corticosteroids for at least 4 months, or whose JLS had concomitant severe extracutaneous manifestations. Outcome was assessed through clinical examination and thermography. Adverse events were recorded. RESULTS Ten patients (six females and four males) were enrolled in the study. JLS clinical subtypes were deep morphoea (two patients with disabling pansclerotic morphoea), generalized morphoea (three patients), linear scleroderma (five patients) affecting the limbs in two and face in three patients (en coup de sabre). The age at onset of disease was 8 (range 2-16) years, and the disease duration at the time of treatment with MMF was 18 (range 8-62) months. All MMF-treated patients experienced clinical improvement that allowed withdrawal or reduction of doses of corticosteroids and MTX. Over a follow-up of 27 (range 6-36) months, mild abdominal discomfort was reported in only one patient. CONCLUSIONS MMF appears to be effective in arresting disease progression in severe or MTX-refractory JLS and is generally well tolerated. Further controlled studies are needed to confirm these data.

2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative

To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA).

2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis

To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA—associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ=0.76). We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies.

Use of infliximab in juvenile onset rheumatological disease-associated refractory uveitis: efficacy in joint and ocular disease

There is an identified disparity between the efficacy of tumour necrosis factor (TNF) inhibition in the treatment of uveitis in paediatric onset inflammatory arthritis and that of joint disease.1–5 We retrospectively reviewed the case notes of six patients with aggressive, refractory joint and ocular paediatric-onset disease treated with infliximab in a multidisciplinary clinic. Our report uses the Standardised Uveitis Nomenclature (SUN) grading system6 for uveitis and steroid dose as an outcome measure. All patients received weekly infliximab infusions at 0, 2, 6 and 8 weeks. Patients were maintained on low dose immunosuppression with methotrexate while receiving treatment. Five of six patients had previously been treated with another anti-TNF agent (three …