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Katherine Anne B MarzanDivision of Rheumatology, Children's Hospital Los Angeles, Los Angeles, CA, USAAbstract: Treatment of children and adolescents with juvenile idiopathic arthritis and other pediatric rheumatic diseases has evolved. Where once there was only a limited arsenal of medications, with significant side effects and inadequate efficacy, today, with an increased understanding of the pathogenesis of these diseases, there is a wider variety of more targeted and effective treatments. TNF-α is a cytokine involved in a number of inflammatory pathways in pediatric rheumatic diseases. The emergence of biologic modifiers that target TNF-α has been pivotal in providing the ability to deliver early and aggressive treatment. Adalimumab, a recombinant monoclonal antibody to TNF-α, is an important therapeutic option, which affords children and adolescents with chronic illnesses an improved quality of life.Keywords: adalimumab, juvenile idiopathic arthritis, TNF-α, pediatric, rheumatic diseases, treatment

Objectives: This study aimed to characterise the burden of illness of patients with inadequately controlled hereditary periodic fevers (HPFs), during and outside of flares. It was focused on the burden to the patients and also considered the wider impact on their caregivers and families., Methods: The target population was patients or caregivers of patients with clinically/genetically confirmed colchicine resistant FMF (crFMF), mevalonate kinase deficiency/hyperimmunoglobinaemia D with periodic fever syndrome (MKD/HIDS) or TRAPS, who were expected to flare at least once in a 6-month period based on patient history. Disease burden was captured during and between flares using an electronic diary (e-diary) with questions on patient functioning, emotional/social well-being and pain, using validated instruments., Results: HPF-related symptoms such as fever, joint, muscle or bone pain and tiredness and fatigue were reported by patients both during and outside of a flare. The SF-10 Health Survey (SF-10v2) (paediatric patients) and SF-12 Health Survey (SF-12v2) (adult patients) showed that flares negatively impacted patients' psychosocial and physical health. Negative effect of on-flare status on health utility index score assessed by the Short-Form Six-Dimension (SF-6D) was significant only for crFMF patients. Furthermore, the Sheehan Disability Score (SDSv3) showing the on-flare status resulted in significant functional impairment in all 3 disease cohorts through assessment of impact on work/school, social and family life., Conclusions: crFMF, MKD/HIDS and TRAPS negatively affected the quality of life (QoL) of adult and paediatric patients, including their physical, mental, psychosocial health, and social functioning. There remains, however, a high number of unmet needs for these patients to reduce their disease burden.

Objective: To describe the first reported case of pneumatosis intestinalis (PI) in a pediatric patient with granulomatosis with polyangiitis (GPA) and multiple other risk factors and review the literature for PI in adult and pediatric rheumatologic conditions., Methods: A PubMed search was completed using the search phrase "pneumatosis intestinalis." Searches were limited to humans and the English language, and remaining articles involving patients with rheumatologic diagnoses were identified and included in our discussion., Results: This is the first reported of case of PI in a patient with underlying GPA or antineutrophil cytoplasmic antibody-associated vasculitides. Out of 90 previously reported cases of PI in patients with rheumatologic conditions, 79 cases were in adults and 11 in children. There were 30 patients with systemic sclerosis, 18 with MCTD/overlap syndrome, 18 with dermatomyositis or polymyositis, 16 with SLE, and 8 with other diagnoses. Overall, 81% of the patients were on corticosteroids or other immunosuppressants prior to development of PI. The most common presenting symptom was abdominal pain, and 51% of patients had associated pneumoperitoneum., Conclusions: PI can be associated with a broad spectrum of rheumatic diseases, including GPA, and should be included in the differential diagnosis of patients with rheumatologic conditions and nonspecific gastrointestinal symptoms., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Pediatric Takayasu arteritis (pTA) is difficult to treat and can lead to significant morbidity and mortality., Objectives: The objective of this study was to describe clinical characteristics for pTA and determine the safety and efficacy of cyclophosphamide (CYC) and infliximab (IFX) in pTA., Methods: This was a retrospective analysis of 23 pTA patients seen at Children's Hospital Los Angeles and Universidade Federal de São Paulo-Brazil from 1990 to 2011. All patients fulfilled the 1990 American College of Rheumatology criteria for Takayasu arteritis. Disease activity was assessed using a modified National Institutes of Health score., Results: Twenty-three patients (14 female and 9 male patients), mean age of 15.7 ± 6.0 years, were included. Cyclophosphamide was used before IFX treatment in 17 of 23 and IFX before CYC in 2 of 23 patients. The average time from disease onset to treatment initiation was 2.6 ± 2.4 years for CYC and 4.1 ± 2.4 years for IFX. Nine (60%) of 15 patients failed CYC, and of these 6 were changed to IFX with subsequent clinical stabilization in 5 (83%) of 6. Two patients initially treated with IFX were switched to CYC because of lack of appropriate response: 1 patient later worsened, and the other was lost to follow-up. Five opportunistic infections requiring hospitalization occurred in the CYC group, whereas none were observed in the IFX group. Patients in the IFX group were more likely to decrease or stop their corticosteroids when compared with the CYC patients., Conclusions: Cyclophosphamide is often used as initial treatment but has many adverse effects. In this retrospective case series, IFX was equivalent to CYC with fewer adverse effects, making IFX an alternative therapeutic option for pTA.

Progress in the diagnosis and management of pediatric rheumatic disease has improved complications from underlying disease and the survival of children. However, as a consequence, infection has now become one of the leading causes of morbidity and mortality. Differentiating between infections and disease flares in children with rheumatic conditions can often pose diagnostic quandaries. Children with rheumatic diseases are at risk of infection, not only because of the use of immune-modulating medications but also because of underlying immune dysfunction associated with their disease. Although bacterial infections are the most common, any organism can potentially be a causative agent and, at times, more invasive measures of diagnosis, for example bronchoscopy and tissue biopsies may be necessary. Maintaining a high index of suspicion of infection with prompt diagnosis and treatment are important to further improve patient outcomes.

Objective: This study describes the 15-yr experience of a large urban tertiary care children's hospital in treating critically ill patients with pediatric rheumatic diseases., Design: Retrospective case series., Setting: Children's Hospital Los Angeles, a large urban tertiary care children's hospital., Patients: All patients with pediatric rheumatic diseases admitted to the Children's Hospital Los Angeles pediatric intensive care unit from January 1995 to July 2009., Interventions: None., Measurements and Main Results: An internal database and medical records were reviewed for demographics, diagnoses, treatments, organ dysfunction, interventions, infections, and outcomes. Standardized mortality ratio was calculated based on Pediatric Risk of Mortality III estimated mortality. Factors associated with mortality were identified by univariate analyses.Ninety patients with 122 total admissions were identified. The majority of patients were Hispanic (63%), female (73%), and had systemic lupus erythematosus (62%). Pediatric rheumatic disease-related complications (50%) were the most common reason for admission; 32% of admissions involved multiorgan dysfunction. Eighteen admissions (15%) resulted in mortality. Deaths were most commonly attributed to combined infection and active rheumatic disease (50%), infection only (22%), rheumatic disease only (11%), or other causes (17%). In 30 (25%) admissions, a new rheumatologic diagnosis was established. Standardized mortality ratio was 0.72 (95% confidence interval 0.38-1.25) for pediatric rheumatic disease patients compared to 0.87 (95% confidence interval 0.79-0.96) for all pediatric intensive care unit patients. Factors associated with mortality included use of mechanical ventilation, vasopressors, and renal replacement (continuous venovenous hemodialysis) (all p < .05)., Conclusions: Pediatric rheumatic disease-related complications were the principal cause of pediatric intensive care unit admission. Deaths occurred most often from severe infections in patients with active rheumatic disease. Pediatric rheumatology patients admitted to the pediatric intensive care unit had outcomes similar to the global pediatric intensive care unit population when adjusted for severity of illness.

Early juvenile idiopathic arthritis (JIA) is important to recognize as timely diagnosis and treatment improves prognosis. It is a misconception that complications of JIA arise only from long-standing disease and that children will outgrow it. Early aggressive treatment is the paradigm as early disease activity has long-term consequences. There are predictors of persistent disease and joint erosions that may identify patients at higher risk. Control of disease activity within the first 6 months of onset confers improved clinical course and outcomes. The treatment perspective is thus one of early aggressive treatment for induction of disease control and ultimately remission., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We present the case of a 16-year-old patient with systemic lupus erythematosus who presented with altered mental status and regressive behaviour. She was worked up and empirically treated for common and opportunistic infectious agents. All work-up was negative and after an extensive course of antibiotics she was treated for neuropsychiatric lupus with cytoxan. She initially responded, but this was short-lived and she eventually became comatose and passed away. On brain biopsy she was found to have numerous trophozoites with round nucleus, prominent nucleolus and thin nuclear membrane. Methenamine silver stain showed encysted amoeba, corresponding with a diagnosis of acanthamoeba meningoencephalitis. Making the diagnosis of acanthamoeba meningoencephalitis requires a high degree of suspicion. Specific serum antibodies may not be a reliable measure in immunocompromised patients and trophozoites in CSF can be confused with monocytes. Brain biopsy may be required to make a definitive diagnosis. It is important for clinicians treating immunocompromised patients to keep this agent in mind in an immunocompromised patient with neurological manifestations. Acanthamoeba infections have only been reported in a small handful of patients and, to our knowledge, this is the first reported case in the United States.

Chronic arthritis in childhood is the most common pediatric rheumatic disease and can lead to significant short- and long-term disability. TNF-a is a cytokine involved in joint inflammation and destruction. It has been suggested that early and aggressive treatment leads to improved outcomes by ameliorating clinical signs and symptoms, inhibiting joint destruction and improving functional disability. The early and aggressive use of disease-modifying antirheumatic drugs and biologic response modifiers are key to achieving this goal. Anti-TNF agents are effective biologic modifiers that have had a major impact on the clinical course of arthritis. Adalimumab, a recombinant monoclonal antibody to TNF-alpha, is emerging as a valuable new therapy for juvenile arthritis.

The etiology of Behr syndrome remains uncertain. A 6-year-old girl with a progressive syndrome of optic atrophy, ataxia, myoclonic epilepsy, urinary incontinence, and pyramidal tract degeneration suggestive of Behr syndrome is described. Diffuse, symmetric white matter abnormalities were demonstrated by magnetic resonance imaging suggesting that Behr syndrome may represent a disorder of white matter associated with an unknown biochemical abnormality.