Emma Jane MacDermott

Cutting Edge: Autoimmune Disease Risk Variant of STAT4 Confers Increased Sensitivity to IFN-α in Lupus Patients In Vivo

Increased IFN-α signaling is a primary pathogenic factor in systemic lupus erythematosus (SLE). STAT4 is a transcription factor that is activated by IFN-α signaling, and genetic variation of STAT4 has been associated with risk of SLE and rheumatoid arthritis. We measured serum IFN-α activity and simultaneous IFN-α-induced gene expression in PBMC in a large SLE cohort. The risk variant of STAT4 (T allele; rs7574865) was simultaneously associated with both lower serum IFN-α activity and greater IFN-α-induced gene expression in PBMC in SLE patients in vivo. Regression analyses confirmed that the risk allele of STAT4 was associated with increased sensitivity to IFN-α signaling. The IFN regulatory factor 5 SLE risk genotype was associated with higher serum IFN-α activity; however, STAT4 showed dominant influence on the sensitivity of PBMC to serum IFN-α. These data provide biologic relevance for the risk variant of STAT4 in the IFN-α pathway in vivo.

Neutral lipid storage disease with subclinical myopathy due to a retrotransposal insertion in the PNPLA2 gene

An 18-year-old girl referred to a rheumatologist with malar flush and Gottran papules was found to have a markedly elevated serum CK. She was a good student and an avid ballet dancer. A muscle biopsy showed massive triglyceride storage, which was also found in peripheral blood granulocytes (Jordan anomaly) and cultured skin fibroblasts. Assessment using computerized dynamometry and cycle ergometry showed normal strength and muscle energetics, but proton spectroscopy revealed severe triglyceride accumulation in both skeletal and cardiac muscle. Sequencing of PNPLA2, the gene responsible for neutral lipid storage disease with myopathy (NLSDM), revealed a retrotransposal insertion of about 1.8kb in exon 3 that abrogates transcription of PNPLA2. The sequences of CGI-58, the gene responsible for Chanarin-Dorfman syndrome (CDS), another multisystem triglyceride storage disease, and of two genes encoding lipid droplets-associated proteins, perilipin A and adipophilin, were normal. This case shows that NLSDM can be a transposon-associated disease and that massive lipid storage in muscle can present as asymptomatic hyperCKemia.

Pharmacotherapy of lupus nephritis in children: a recommended treatment approach.

Systemic lupus erythematosus (SLE) is a multisystem inflammatory disease of unknown aetiology, which is characterised by recurrent disease flares that may affect any organ system. Renal involvement remains one of the chief causes of morbidity and mortality in children with lupus. Nephritis occurs in approximately two-thirds of patients, ranging from mild glomerulitis to life-threatening occurrences of diffuse proliferative glomerulonephritis. As lupus nephritis is a condition of no single aetiology, there is no single cure. Corticosteroids, although still the first line of treatment, are increasingly being superseded by cytotoxic drugs, in particular cyclophosphamide and corticosteroid-sparing agents. Newer agents such as mycophenolate mofetil, although effective in the treatment of lupus in adults, are less effective in children. Standard of care for highly active lupus nephritis in children remains intravenous cyclophosphamide, although preliminary experience suggests that the addition of rituximab may allow for remission induction with a reduction in cumulative cyclophosphamide dose. Combination therapies and newer agents appear promising for the future as our understanding of the immune system and its dysregulation in SLE improves. In this review, we discuss the current standards of care, newer therapies currently in use, and emerging treatments still undergoing development and investigation. We conclude by discussing our guidelines for treatment at the present time and suggestions for the comprehensive care of children with lupus nephritis.

Takayasu arteritis presenting in the context of active tuberculosis: a pediatric case.

Takayasu arteritis (TA) is a large-vessel vasculitis, most commonly presenting in young adults and more rarely in pediatric patients. An apparent association between TA and Mycobacterium tuberculosis has been noted previously, although this potential relationship is not yet understood. We present the case of a 16-year-old Haitian girl diagnosed with TA, originally presenting in the context of active tuberculosis. Our patient has been treated with antituberculosis therapy, corticosteroids, methotrexate, and rituximab to control her continued active vasculitis. With this case report, we seek to promote further exploration of the apparent association between TA and tuberculosis, as further clarification of the nature of this relationship may lead to the development of more targeted therapies and better outcomes for TA patients.

Isolated ocular lichen planus in a child

Lichen planus (LP) is an autoimmune inflammatory condition of the skin and mucous membranes, of unknown aetiology, that infrequently involves the eye. Ocular LP has not been described in children. We present the case of an 8-year-old girl with severe, filamentous dry eyes and persistent conjunctival hyperemia with bilateral progressive conjunctival symblepharon. Her conjunctival biopsy showed heavy linear fibrinogen deposits along the basement membrane without IgG, IgA, IgM, or C3 deposition, consistent with LP. No skin or other mucosal lesions were present, suggesting a diagnosis of isolated conjunctival LP. Oral and topical cyclosporine combined with methotrexate and low-dose oral steroids led to sustained disease remission. To our knowledge, this is the first case of isolated ocular LP in a child.

Physical activity levels of children with juvenile idiopathic arthritis

Abstract Children with juvenile idiopathic arthritis (JIA) have lower levels of moderate to vigorous physical activity (MVPA) and spend longer in sedentary activities than their peers. A study to assess the physical activity levels at a tertiary Irish centre was undertaken to compare children with JIA in Ireland against the international experience. Children with JIA completed a nine-item validated questionnaire, the Physical Activity Questionnaire for Children (PAQ-C). Pain, medication use and disease subtype were recorded. PAQ-C scores were compared against UK threshold values. Estimated %MVPA and time (min/day) were calculated using a published formula. Fifty-three children with JIA (33 female, 20 male, mean 11.4 years) completed the PAQ-C. Mean PAQ-C level was 2.7 for males and 2.4 for females. One-third of children met the threshold levels for being sufficiently active (normative values 2.9 males, 2.7 females). Using estimated %MVPA, one-third did not achieve 30 min of MVPA. There was no significant difference in PAQ-C levels between children with active disease (active joint count >1, self-reported visual analogue scale pain >1 and elevated erythrocyte sedimentation rate/C-reactive protein) and those without active markers. Using both the PAQ-C and estimated MVPA, only one-third of children with JIA met the recommended 60 min of daily MVPA. This needs to be validated against objective measures, e.g. accelerometers.

Organ system-involvement in SLE and relationship with demographic factors, disease duration and health-related quality of life in childhood SLE

Organ system-involvement in SLE and relationship with demographic factors, disease duration and health-related quality of life in childhood SLE Lakshmi N Moorthy, Maria J Baratelli, Margaret GE Peterson, Afton L Hassett, Alexa B Adams, Laura V Barinstein, Emma J MacDermott, Elizabeth C Chalom, Karen Onel, Linda I Ray, Jorge Lopez-Benitez, Christina Pelajo, Kathleen A Haines, Daniel J Kingsbury, Victoria W Cartwright, Philip J Hashkes, Nora G Singer, Gina A Montealegres, Ingrid Tomanova-Soltys, Andreas O Reiff, Sandy D Hong, Thomas JA Lehman

Self-management needs of children with JIA in Ireland: a qualitative survey of families

Abstract Aim: To explore the self-management needs and coping activities of children with JIA and their parents. Families and children with JIA experience many different challenges with the diagnosis. One of the long-term therapy aims is to assist individuals to develop self-management and coping skills. Methods: Twenty-six face-to-face interviews were conducted at an outpatient tertiary hospital in Ireland using a semi-structured format. Results: Children and families were happy with sources of information about JIA and expressed confidence in the information provided. Parent of younger children felt that information about tricks or tips that other people used could be provided in anticipation of changing medications or flare-ups. Older children expressed a desire to be treated normally and that the means of expressing or illustrating the variable nature of the disease was needed to people outside of the immediate family, i.e. teachers, as this would assist with their coping skills. Discussion: All children refer to the impact of JIA in terms of loss of function and the effect on their role within their society. Families trusted information from medical sources, but there is a need for improving knowledge and skills for unexpected events and changing the perception of exercise and physical activity.

Internet access and utilisation of adolescents attending a national centre for paediatric rheumatology

With emerging interactive and communication technologies now available, the internet has become one of the top health information resources for adolescents (Stinson et al., 2010). Adolescents are typically the early adapters of new technologies, with in particular, the internet providing innovative opportunities for engaging youths. Traditional sources of health information are now becoming defunct and young people are increasingly going online for health related information.

Clinical and radiological features of down's arthropathy

The ‘Arthropathy of Down syndrome’ was first described in 1984. Three decades on we still have limited literature on the clinical and radiological features of this arthritis, despite the fact that it is thought to be 3-6 times more common than JIA in the general paediatric population. Down’s Arthropathy (DA) is rarely recognised at onset, and remains under-diagnosed and largely under-reported in this population group. Ireland has one of the highest Trisomy 21 birth rates in Europe (1/547), & therefore provides an ideal setting for such a study. Research Qs - 1. What are the clinical & radiological features of DA? 2. Is DA missed, leading to a delay in dx?