Nadia Luca

Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Newly Recognized Inflammatory Brain Disease in Children

OBJECTIVE Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a newly recognized antineuronal antibody-mediated inflammatory brain disease that causes severe psychiatric and neurologic deficits in previously healthy children. The present study was undertaken to describe characteristic clinical features and outcomes in children diagnosed as having anti-NMDAR encephalitis. METHODS Consecutive children presenting over a 12-month period with newly acquired psychiatric and/or neurologic deficits consistent with anti-NMDAR encephalitis and evidence of central nervous system (CNS) inflammation were screened. Children were included in the study if they had confirmatory evidence of anti-NMDAR antibodies in the serum and/or cerebrospinal fluid. Features at clinical presentation and results of investigations were recorded. Type and duration of treatment and outcomes at last followup were documented. RESULTS Seven children were screened, and 3 children with anti-NMDAR encephalitis were identified. All patients presented with neurologic and/or psychiatric abnormalities, seizures, speech disorder, sleep disturbance, and fluctuating level of consciousness. The 2 older patients had more prominent psychiatric features, while the younger child had significant autonomic instability and prominent involuntary movement disorder. None had an underlying tumor. Immunosuppressive therapy resulted in near or complete recovery; however, 2 of the patients had early relapse necessitating re-treatment. CONCLUSION Anti-NMDAR encephalitis is an important cause of neuropsychiatric deficits in children, which must be included in the differential diagnosis of CNS vasculitis and other inflammatory brain diseases. Early diagnosis and treatment are essential for neurologic recovery.

Epidemiology and Management of Kawasaki Disease

Kawasaki disease (KD) is an acute systemic vasculitis affecting young children and is rising in incidence worldwide. It is most common in children <5 years of age, males and those of Asian ethnicity. It is an important cause of acquired heart disease in children. Standard treatment with high-dose aspirin (acetylsalicylic acid; ASA) and intravenous immune globulin (IVIG) has been shown to decrease the rate of coronary artery aneurysm development. Anti-coagulation has an important place in the management of KD, although guidance based on evidence is lacking. Treatment of refractory KD is an area under intense study and may include IVIG, corticosteroids and/or tumour necrosis factor (TNF)-α inhibitors among immunosuppressive agents. Acute complications of KD include myocarditis/KD shock syndrome and macrophage activation syndrome, which necessitate appropriate awareness in order to initiate proper management.

Choosing Wisely: The Canadian Rheumatology Association’s List of 5 Items Physicians and Patients Should Question

Objective. To develop a list of 5 tests or treatments used in rheumatology that have evidence indicating that they may be unnecessary and thus should be reevaluated by rheumatology healthcare providers and patients. Methods. Using the Delphi method, a committee of 16 rheumatologists from across Canada and an allied health professional generated a list of tests, procedures, or treatments in rheumatology that may be unnecessary, nonspecific, or insensitive. Items with high content agreement and perceived relevance advanced to a survey of Canadian Rheumatology Association (CRA) members. CRA members ranked these top items based on content agreement, effect, and item ranking. A methodology subcommittee discussed the items in light of their relevance to rheumatology, potential effect on patients, and the member survey results. Five candidate items selected were then subjected to a literature review. A group of patient collaborators with rheumatic diseases also reviewed these items. Results. Sixty-four unique items were proposed and after 3 Delphi rounds, this list was narrowed down to 13 items. In the member-wide survey, 172 rheumatologists responded (36% of those contacted). The respondent characteristics were similar to the membership at large in terms of sex and geographical distribution. Five topics (antinuclear antibodies testing, HLA-B27 testing, bone density testing, bone scans, and bisphosphonate use) with high ratings on agreement and effect were chosen for literature review. Conclusion. The list of 5 items has identified starting points to promote discussion about practices that should be questioned to assist rheumatology healthcare providers in delivering high-quality care.

Assessment and management of pain in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a common chronic childhood illness. Pain is the most common and distressing symptom of JIA. Pain has been found to negatively impact all aspects of functioning, including physical, social, emotional and role functions. Children with arthritis continue to experience clinically significant pain despite adequate doses of disease-modifying antirheumatic drugs and anti-inflammatory agents. The present article reviews the prevalence and nature of pain in JIA, the biopsychosocial factors that contribute to the pain experience, current approaches to assessing pain in this population, and ways of managing both acute and persistent pain using pharmacological, physical and psychological therapies. Finally, new approaches to delivering disease self-management treatment for youth with JIA using the Internet will be outlined.

Disease Activity Measures in Paediatric Rheumatic Diseases

Disease activity refers to potentially reversible aspects of a disease. Measurement of disease activity in paediatric rheumatic diseases is a critical component of patient care and clinical research. Disease activity measures are developed systematically, often involving consensus methods. To be useful, a disease activity measure must be feasible, valid, and interpretable. There are several challenges in quantifying disease activity in paediatric rheumatology; namely, the conditions are multidimensional, the level of activity must be valuated in the context of treatment being received, there is no gold standard for disease activity, and it is often difficult to incorporate the patients perspective of their disease activity. To date, core sets of response variables are defined for juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, and juvenile dermatomyositis, as well as definitions for improvement in response to therapy. Several specific absolute disease activity measures also exist for each condition. Further work is required to determine the optimal disease activity measures in paediatric rheumatology.

Anti-signal Recognition Particle-positive Juvenile Polymyositis Successfully Treated with Rituximab

To the Editor: Juvenile polymyositis (PM) is a rare form of idiopathic inflammatory myositis (IIM) in children, accounting for 2%–8% of cases1,2. In contrast to juvenile dermatomyositis (DM), the characteristic rashes are absent. Myositis-specific antibodies (MSA) can be used to further classify IIM. Anti-signal recognition particle (SRP) antibody is present almost exclusively in PM, and is usually associated with a necrotizing myopathy with a severe or fulminant course and a poor response to therapy3. A previously healthy 12-year-old girl presented with a 1-month history of increasing proximal muscle weakness, alopecia, dysphagia, and Raynaud’s phenomenon. There was no history of rash or skin changes. On examination, she had visible wasting of her shoulder muscles, manual muscle testing (MMT) of 3/5 in a proximal distribution, and a Childhood Myositis Assessment Scale (CMAS)4 score of 15/52. There were no skin findings associated with juvenile DM. Serum inflammatory markers were normal. Muscle enzymes were elevated (creatine phosphokinase 8826 U/l, lactate dehydrogenase 4305 U/l, aspartate aminotransferase 368 U/l), and electromyography demonstrated an active myopathic process. Magnetic resonance imaging (MRI) of the shoulder and hip girdles revealed symmetrically increased T2 signal in hip adductors and shoulder muscles. Pulmonary function tests demonstrated a mild chest wall restrictive pattern with normal carbon monoxide diffusion capacity. Electrocardiogram … Address correspondence to Dr. B.M. Feldman, Division of Rheumatology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. E-mail: brian.feldman{at}sickkids.ca

Paediatric rheumatic disease: Defining clinically inactive disease in juvenile dermatomyositis.

Achievement of a state of inactive disease has become a realistic goal in juvenile dermatomyositis. The development of a standardized definition of inactive disease in this disorder is a critical step in measuring outcomes, and might now be a step closer.

Validation of the Standardized Universal Pain Evaluations for Rheumatology Providers for Children and Youth (SUPER-KIDZ)

• STUDY DESIGN: Longitudinal observational clinimetric study with repeated measures. • BACKGROUND: No validated multidimensional pain measure for children and youth with juvenile idiopathic arthritis exists. • OBJECTIVE: To determine the test‐retest reliability, construct validity, and responsiveness of English and French versions of the Standardized Universal Pain Evaluations for Rheumatology Providers for Children and Youth (SUPER‐KIDZ). • METHODS: Measurement properties of the SUPER‐KIDZ (older child, younger child, and parent versions) were prospectively evaluated in patients (aged 4 to 18 years) with juvenile idiopathic arthritis at 2 centers. Internal consistency of the 3 subscales was measured using ordinal reliability alpha. Test‐retest reliability for each subscale was evaluated with intraclass correlation coefficients (ICCs) from participants assumed to have stable pain (over a 1‐week period with no change in treatment). Correlations of SUPER‐KIDZ scores with validated measures determined construct validity. Responsiveness of SUPER‐KIDZ subscales was evaluated in patients with improvement in pain, using standardized response mean and linear mixed‐model regression. • RESULTS: Seventy‐one children aged 8 to 18 years and 29 parent‐child dyads aged 4 to 7 years were included. Seventy‐four percent of participants were female, with a median of 3 active joints (interquartile range, 1–5). Internal consistency was strong (&agr; = .78‐.96) for pain characteristics, interference, and emotional functioning SUPER‐KIDZ subscales. Good test‐retest reliability (ICC≥0.80) was found for the pain characteristics subscale in older‐ and younger‐child versions. Most other subscales had satisfactory reliability coefficients (ICC≥0.70). Correlations of 0.50 or greater were found between the older‐child SUPER‐KIDZ scores and the Childhood Health Assessment Questionnaire and Patient‐Reported Outcomes Measurement Information System depressive symptoms items, as well as the younger‐child pain‐intensity item and the Faces Pain Scale‐Revised. Strong responsiveness was found for all subscales (standardized response mean, 0.63–1.54; significant linear mixed‐model regression), except for the older‐child emotional functioning subscale. • CONCLUSION: The SUPER‐KIDZ has shown good internal consistency and responsiveness, and satisfactory test‐retest reliability. Construct validity was moderate for the younger‐ and older‐child versions, but weak for the parent version.

Predictors of delayed treatment of Kawasaki disease in community and tertiary care hospitals

Methods From 1995 to 2006, all hospitals and pediatric cardiologists in Ontario were contacted to identify all children diagnosed with KD. The following data were retrieved: demographics, day of week admitted, symptoms, clinical features, and treatment. Hospital KD caseload was defined as low (<20 cases/year) or high (≥20 cases/year). The only institution with a KD program was the Hospital for Sick Children in Toronto. The primary outcome was the number of days of fever prior to treatment with intravenous immunoglobulin (IVIg). Secondary outcome was the number of days between admission and treatment with IVIg. Data analysis was performed using multivariable linear and logistic regression models. The estimate* (est) reflects the change in the outcome (days) associated with a 1 unit increment (if continuous) or the presence (if binary) of the variable. The analysis was carried with and without data from the tertiary care centre.