title: Clinical course and therapeutic approach to varicella zoster virus infection in children with rheumatic autoimmune diseases under immunosuppression.
abstract: BACKGROUND
  To analyze the clinical presentation and complications of varicella zoster virus (VZV) infection in children with rheumatic diseases treated with immunosuppressive medication such as biological disease-modifying antirheumatic drugs (bDMARDs) and/or conventional disease-modifying antirheumatic drugs (cDMARDs), and to analyze the therapeutic approach to VZV infections with respect to the concomitant immunosuppressive treatment.
  
  
  METHODS
  Retrospective multicenter study using the Swiss Pediatric Rheumatology registry. Children with rheumatic diseases followed in a Swiss center for pediatric rheumatology and treated with cDMARD and/or bDMARD with a clinical diagnosis of varicella or herpes zoster between January 2004 and December 2013 were included.
  
  
  RESULTS
  Twenty-two patients were identified, of whom 20 were treated for juvenile idiopathic arthritis, 1 for a polyglandular autoimmune syndrome type III, and 1 for uveitis. Of these 22 patients, 16 had varicella and 6 had herpes zoster. Median age at VZV disease was 7.6 years (range 2 to 17 years), with 6.3 years (range 2 to 17 years) for those with varicella and 11.6 years (range 5 to 16 years) for those with herpes zoster. The median interval between start of immunosuppression and VZV disease was 14.1 months (range 1 to 63 months). Two patients had received varicella vaccine (1 dose each) prior to start of immunosuppression. Concomitant immunosuppressive therapy was methotrexate (MTX) monotherapy (n = 9) or bDMARD monotherapy (n = 2), or a combination of bDMARD with prednisone, MTX or Leflunomide (n = 11). Four patients experienced VZV related complications: cellulitis in 1 patient treated with MTX, and cellulitis, sepsis and cerebellitis in 3 patients treated with biological agents and MTX combination therapy. Six children were admitted to hospital (range of duration: 4 to 9 days) and 12 were treated with valaciclovir or aciclovir.
  
  
  CONCLUSIONS
  The clinical course of varicella and herpes zoster in children under immunosuppression is variable, with 4 (18 %) of 22 children showing a complicated course. Thorough assessment of VZV disease and vaccination history and correct VZV vaccination according to national guidelines at diagnosis of a rheumatic autoimmune disease is essential to minimize VZV complications during a later immunosuppressive treatment.
authors.affiliation: University of Basel Medical School, Basel, Switzerland.|Pediatric Rheumatology, University of Basel Children's Hospital, Spitalstrasse 33, CH - 4031, Basel, Switzerland.
authors.forename: Raphael
authors.initials: R
authors.lastname: Leuvenink
authors.affiliation: University Children's Hospital, Zürich, Switzerland.
authors.forename: Florence
authors.initials: F
authors.lastname: Aeschlimann
authors.affiliation: Department of Pediatrics, Hospital of Chur, Chur, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Baer
authors.affiliation: Department of Pediatrics, Hospital of Aarau, Aarau, Switzerland.
authors.forename: Gerald
authors.initials: G
authors.lastname: Berthet
authors.affiliation: University Children's Hospital, Zürich, Switzerland.
authors.forename: Elvira
authors.initials: E
authors.lastname: Cannizzaro
authors.affiliation: Unité romande de rhumatologie pédiatrique, CHUV, University of Lausanne and HUG, Geneva, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Hofer
authors.affiliation: Department of Pediatrics, Hospital of Lucerne, Lucerne, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kaiser
authors.affiliation: University Children's Hospital, Zürich, Switzerland.
authors.forename: Silke
authors.initials: S
authors.lastname: Schroeder
authors.affiliation: Pediatric Rheumatology, University of Basel Children's Hospital, Spitalstrasse 33, CH - 4031, Basel, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Heininger
authors.affiliation: Pediatric Rheumatology, University of Basel Children's Hospital, Spitalstrasse 33, CH - 4031, Basel, Switzerland. andreas.woerner@ukbb.ch.
authors.forename: Andreas
authors.initials: A
authors.lastname: Woerner
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D000293:Adolescent; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000150:complications* / Q000188:drug therapy; D002644:Chickenpox / Q000150:complications* / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D006562:Herpes Zoster / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007555:Isoxazoles / Q000627:therapeutic use; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D000077339:Leflunomide; D014633:Valine; D000077483:Valacyclovir; D000068800:Etanercept; D000212:Acyclovir; D008727:Methotrexate
keywords: Immunosuppression; Pediatric; Rheumatic autoimmune disease; Varicella zoster virus