title: Infection-Related Death among Persons with Refractory Juvenile Idiopathic Arthritis.
abstract: Severe infections are emerging as major risk factors for death among children with juvenile idiopathic arthritis (JIA). In particular, children with refractory JIA treated with long-term, multiple, and often combined immunosuppressive and antiinflammatory agents, including the new biological disease-modifying antirheumatic drugs (DMARDs), are at increased risk for severe infections and death. We investigated 4 persons with JIA who died during 1994-2013, three of overwhelming central venous catheter-related bacterial sepsis caused by coagulase-negative Staphylococus or α-hemolytic Streptococcus infection and 1 of disseminated adenovirus and Epstein-Barr virus infection). All 4 had active JIA refractory to long-term therapy with multiple and combined conventional and biological DMARDs. Two died while receiving high-dose systemic corticosteroids, methotrexate, and after recent exposure to anti-tumor necrosis factor-α biological DMARDs, and 2 during hematopoietic stem cell transplantation procedure. Reporting all cases of severe infections and especially deaths in these children is of paramount importance for accurate surveillance.
authors.forename: Mario
authors.initials: M
authors.lastname: Abinun
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Lane
authors.forename: Mark
authors.initials: M
authors.lastname: Wood
authors.forename: Mark
authors.initials: M
authors.lastname: Friswell
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Flood
authors.forename: Helen E
authors.initials: HE
authors.lastname: Foster
mesh_terms: D000258:Adenovirus Infections, Human / Q000209:etiology; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D016470:Bacteremia / Q000209:etiology / Q000401:mortality; D055499:Catheter-Related Infections / Q000209:etiology*; D062905:Central Venous Catheters / Q000009:adverse effects*; D002648:Child; D020031:Epstein-Barr Virus Infections / Q000209:etiology; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D009102:Multiple Organ Failure / Q000209:etiology; D018805:Sepsis / Q000209:etiology*; D013203:Staphylococcal Infections / Q000209:etiology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014766:Viremia / Q000209:etiology
chemical_list: D000305:Adrenal Cortex Hormones; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate
keywords: Juvenile idiopathic arthritis; TNF-α blocking agents; United Kingdom; anti–TNF-α; bacteria; biological disease-modifying drugs; central venous catheter bacteria; children; combined immunosuppressive and antiinflammatory therapy; immunosuppression; sepsis