Choosing Wisely: The Canadian Rheumatology Association Pediatric Committee's List of Items Physicians and Patients Should Question.

OBJECTIVE: To develop a list of tests or treatments frequently used in pediatric rheumatology practice that may be unnecessary based on existing evidence. METHODS: A Choosing Wisely (CW) working group composed of 16 pediatric rheumatologists, 1 allied health professional, 1 parent, and 1 patient used the Delphi method to generate, rank, and refine a list of tests and treatments that may be unnecessary or harmful. The items with the highest content agreement and perceived impact were presented in a survey to all Canadian Rheumatology Association (CRA) physicians who practice pediatric rheumatology. Respondents were asked to rate their agreement and impact, and to rank the items. Five items with the highest composite scores and 2 additional items selected by the CW working group were put forward for literature review. RESULTS: The initial Delphi procedure generated 80 items. After 3 rounds, the list was narrowed to 13 items. The survey was completed by 41/81 (51%) CRA pediatric members across Canada. Respondent characteristics were similar to those of the CRA pediatric membership for self-reported gender, geographical location, and career stage. The highest composite score items were antinuclear antibody testing, drug toxicity monitoring, HLA-B27 testing, rheumatoid factor/anticyclic citrullinated peptide testing, and Lyme serology testing. Two additional items (numerous or repeated intraarticular corticosteroid injections, and autoinflammatory diseases genetic testing) were also selected. Literature review was performed for these 7 highest priority items. CONCLUSION: We have identified areas for quality improvement in the evaluation and treatment of rheumatic diseases in Canadian children.

Approach to recurrent fever in childhood.

OBJECTIVE: To provide an approach to recurrent fever in childhood, explain when infections, malignancies, and immunodeficiencies can be excluded, and describe the features of periodic fever and other autoinflammatory syndromes. SOURCES OF INFORMATION: PubMed was searched for relevant articles regarding the pathogenesis, clinical findings, diagnosis, prognosis, and treatment of periodic fever and autoinflammatory syndromes. MAIN MESSAGE: Fever is a common sign of illness in children and is most frequently due to infection. However, when acute and chronic infections have been excluded and when the fever pattern becomes recurrent or periodic, the expanding spectrum of autoinflammatory diseases, including periodic fever syndromes, should be considered. Familial Mediterranean fever is the most common inherited monogenic autoinflammatory syndrome, and early recognition and treatment can prevent its life-threatening complication, systemic amyloidosis. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome is the most common periodic fever syndrome in childhood; however, its underlying genetic basis remains unknown. CONCLUSION: Periodic fever syndromes and other autoinflammatory diseases are increasingly recognized in children and adults, especially as causes of recurrent fevers. Individually they are rare, but a thorough history and physical examination can lead to their early recognition, diagnosis, and appropriate treatment.

Approche à la fièvre récurrente de l'enfant.

OBJECTIF: Fournir une approche à la fièvre récurrente de l'enfant, expliquer quand les infections, les affections malignes et les immunodéficiences peuvent être exclues, et décrire les caractéristiques de la fièvre périodique et des autres syndromes auto-inflammatoires. SOURCES DE L'INFORMATION: Une recherche d'articles pertinents sur la pathogenèse, les observations cliniques, le diagnostic, le pronostic et le traitement de la fièvre périodique et des syndromes auto-inflammatoires a été effectuée sur PubMed. MESSAGE PRINCIPAL: La fièvre est un signe courant de maladie chez les enfants, et elle est le plus souvent causée par une infection. Mais lorsque les infections aiguës et chroniques ont été exclues et que la fièvre devient récurrente ou périodique, le spectre croissant des maladies auto-inflammatoires, y compris les syndromes de fièvre périodique, doit être envisagé. La fièvre méditerranéenne familiale est le syndrome auto-inflammatoire monogénique héréditaire le plus fréquent, et sa reconnaissance et son traitement précoces peuvent prévenir l'amylose systémique, sa complication menaçant le pronostic vital. Le syndrome de fièvre périodique accompagnée d'une stomatite aphteuse, d'une pharyngite et d'une adénite cervicale est le syndrome de fièvre périodique le plus souvent observé chez l'enfant, mais son fondement génétique sous-jacent est toujours inconnu. CONCLUSION: Les syndromes de fièvre périodique et autres maladies auto-inflammatoires sont de plus en plus dépistés chez les enfants et les adultes, surtout comme causes de la fièvre récurrente. Sur le plan individuel, ils sont rares, mais une anamnèse et un examen physique détaillés peuvent mener au dépistage précoce, au diagnostic et au traitement approprié.

Recurrence and outcomes of Stevens-Johnson syndrome and toxic epidermal necrolysis in children.

OBJECTIVES: To report clinical course, etiology, management, and long-term outcomes of children suffering from Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). METHODS: We conducted a study of all pediatric patients with SJS or TEN admitted between 2000 and 2007 to the Hospital for Sick Children and Children's Hospital Boston, and particular attention was paid to clinical manifestations, etiology, mortality, and long-term outcomes. RESULTS: We identified 55 cases of SJS (n = 47), TEN (n = 5), or SJS/TEN overlap syndrome (n = 3). Drugs were identified as the most likely etiologic agent in 29 children (53%); antiepileptic drugs were the most common agents (n = 16), followed by sulfonamide antibiotics (n = 7) and chemotherapy drugs (n = 2). Acute Mycoplasma pneumoniae infection was confirmed in 12 children (22%), and herpes simplex virus was confirmed in 5 children (9%). Treatment regimens differed significantly between participating sites and included systemic antimicrobial agents (67%), systemic corticosteroids (40%), and antiviral drugs (31%). Intravenous immunoglobulin was administered to 21 children (38%), of whom 8 received concomitant systemic corticosteroids. Ten children (18%) had recurrence of SJS up to 7 years after the index episode, and 3 experienced multiple recurrences. Twenty-six children (47%) suffered long-term sequelae that mostly involved the skin and eyes. CONCLUSIONS: Mortality rate in children was lower than that reported in adults, but half of affected children suffered long-term complications. The recurrence rate of SJS was high (1 in 5), which suggests vulnerability and potential genetic predisposition. In the absence of standardized management guidelines for these conditions, treatment regimens differed significantly between participating institutions.

Community-based case-control study of childhood chronic abdominal pain: role of selected laboratory investigations.

OBJECTIVE: To compare laboratory investigation results in children with chronic abdominal pain and in healthy control children. Our hypothesis was that parasitic infection was not a causal factor for chronic abdominal pain and that there would be no difference in leukocyte count, hemoglobin level, or erythrocyte sedimentation rate (ESR) between the 2 groups. PATIENTS AND METHODS: Children with chronic abdominal pain and healthy control children (5-15 years) were recruited from the practices of 6 primary care pediatricians in Toronto, Canada. Stool samples were analyzed for ova and parasites, and serum samples were used to estimate leukocyte count, hemoglobin, and ESR. A standardized questionnaire was used to gather social, demographic, and clinical information. RESULTS: A total of 157/200 children (79%) provided samples. Children with chronic abdominal pain were more likely to be female than were control children. Stool samples were positive for parasitic infection in 15 children, with no difference in prevalence between children with chronic abdominal pain (6/87; 7%) and healthy control children (9/70; 13%); P = 0.28). The mean (standard deviation) leukocyte count in children with chronic abdominal pain was 7.4 x 10(9)/L (2.03), compared with 8.3 x 10(9)/L (1.82) in healthy control children. No child had a leukocyte count above 20 x 10(9)/L. The mean (SD) hemoglobin in children with chronic abdominal pain was 131 g/L (8.4), compared with 130 g/L (9.2) in healthy control children. Last, the median ESR in children with chronic abdominal pain was 5 mm/hour, compared with 3 mm/hour in control children. CONCLUSIONS: The study findings suggest that in the absence of alarming symptoms and signs, parasitic infection is not a causal factor for chronic abdominal pain and that routine screening tests (leukocyte count, hemoglobin, ESR) are not useful.

Amino-terminal determinants of U-type inactivation of voltage-gated K+ channels.

The T1 domain is a cytosolic NH2-terminal domain present in all Kv (voltage-dependent potassium) channels, and is highly conserved between Kv channel subfamilies. Our characterization of a truncated form of Kv1.5 (Kv1.5deltaN209) expressed in myocardium demonstrated that deletion of the NH2 terminus of Kv1.5 imparts a U-shaped inactivation-voltage relationship to the channel, and prompted us to investigate the NH2 terminus as a regulatory site for slow inactivation of Kv channels. We examined the macroscopic inactivation properties of several NH2-terminal deletion mutants of Kv1.5 expressed in HEK 293 cells, demonstrating that deletion of residues up to the T1 boundary (Kv1.5deltaN19, Kv1.5deltaN91, and Kv1.5deltaN119) did not alter Kv1.5 inactivation, however, deletion mutants that disrupted the T1 structure consistently exhibited inactivation phenotypes resembling Kv1.5deltaN209. Chimeric constructs between Kv1.5 and the NH2 termini of Kv1.1 and Kv1.3 preserved the inactivation kinetics observed in full-length Kv1.5, again suggesting that the Kv1 T1 domain influences slow inactivation. Furthermore, disruption of intersubunit T1 contacts by mutation of residues Glu(131) and Thr(132) to alanines resulted in channels exhibiting a U-shaped inactivation-voltage relationship. Fusion of the NH2 terminus of Kv2.1 to the transmembrane segments of Kv1.5 imparted a U-shaped inactivation-voltage relationship to Kv1.5, whereas fusion of the NH2 terminus of Kv1.5 to the transmembrane core of Kv2.1 decelerated Kv2.1 inactivation and abolished the U-shaped voltage dependence of inactivation normally observed in Kv2.1. These data suggest that intersubunit T1 domain interactions influence U-type inactivation in Kv1 channels, and suggest a generalized influence of the T1 domain on U-type inactivation between Kv channel subfamilies.