title: Invasive fungal infections in pediatric patients treated with tumor necrosis alpha (TNF-α) inhibitors.
abstract: Macromolecular immunosuppressive monoclonal antibodies and fusion proteins directed against molecules or cells involved in inflammation and immunity represent a recent and important addition to our therapeutic armamentarium. Tumor necrosis alpha (TNFα) is a cytokine involved in systemic inflammation and clinical utilization of its antagonists has revolutionized treatment of juvenile rheumatoid and psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, and plaque psoriasis. Clinical utility has also been demonstrated for use against steroid-refractory graft-vs-host disease and other immune-mediated conditions. Currently, five anti-TNFα agents are approved by the European Medicines Agency (EMA), including the monoclonal anti-TNF antibodies infliximab, adalimumab, golimumab and certolizumab pegol along with etanercept, a TNFα-receptor/IgG-Fc fusion protein. Theoretical considerations related to their mode of action and clinical observations suggest that opportunistic infectious complications should be seriously considered as possible adverse events of macromolecular immunosuppressants. The purpose of this review is to critically analyze the literature on invasive fungal infections (IFIs) occurring in association with TNFα inhibitors alone or in combination with other immunosuppressive agents, with a focus on pediatric patients, and to provide a framework of evaluating the risk for IFIs in this population.
authors.affiliation: Second Department of Pediatrics, AHEPA University General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Athanasios
authors.identifier: http://orcid.org/0000-0003-4294-2605
authors.initials: A
authors.lastname: Tragiannidis
authors.affiliation: Second Department of Pediatrics, AHEPA University General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Ioannis
authors.identifier: http://orcid.org/0000-0002-8153-9643
authors.initials: I
authors.lastname: Kyriakidis
authors.affiliation: Institute of Pharmaceutical Biology, Goethe-University of Frankfurt, Frankfurt am Main, Germany.
authors.forename: Ilse
authors.initials: I
authors.lastname: Zündorf
authors.affiliation: Department of Pediatric Hematology and Oncology, Center for Bone Marrow Transplantation, Infectious Disease Research Program, University Childrens Hospital, Muenster, Germany.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Groll
mesh_terms: D000068879:Adalimumab / Q000009:adverse effects / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000068582:Certolizumab Pegol / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003879:Dermatologic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000068800:Etanercept / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D000069285:Infliximab / Q000009:adverse effects / Q000627:therapeutic use; D000072742:Invasive Fungal Infections / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D011565:Psoriasis / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D003879:Dermatologic Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; C529000:golimumab; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D000068582:Certolizumab Pegol
keywords: 
  Pneumocystis
  ; adalimumab; anti-TNF agents; etanercept; infliximab; monoclonal antibodies