title: Therapeutic role of anakinra, an interleukin-1 receptor antagonist, in the management of secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction/macrophage activating syndrome in critically ill children*.
abstract: OBJECTIVE
  Secondary hemophagocytic lymphohistiocytosis, macrophage activating syndrome, and sepsis share the same inflammatory phenotype leading often to multiple organ dysfunction syndrome needing intensive care. The goal of this article is to describe our experience with anakinra (Kineret), a recombinant interleukin-1 receptor antagonist, in decreasing the systemic inflammation.
  
  
  METHODS
  Retrospective case series.
  
  
  METHODS
  The PICU at the Helen DeVos Children's Hospital (Grand Rapids, MI).
  
  
  METHODS
  The records of eight critically ill children presumed to have secondary hemophagocytic lymphohistiocytosis at our institution between January 1, 2011, and July 31, 2012, were reviewed.
  
  
  METHODS
  All of the patients were treated with anakinra (Kineret) and in some cases systemic corticosteroids as first-line therapy for secondary hemophagocytic lymphohistiocytosis.
  
  
  RESULTS
  Patients had a median age of 14 years and a median Pediatric Risk of Mortality score of 11.5. Four were previously healthy and four had underlying diseases that could have made them susceptible to secondary hemophagocytic lymphohistiocytosis. Indications for PICU transfer were respiratory distress 50% (4 of 8), cardiovascular instability 37.5% (3 of 8), and chest pain (1 of 8). Five of the patients (62.5%) were mechanically ventilated and 62.5% (5 of 8) received vasoactive infusions. Inflammatory markers were assessed linearly at the start of therapy and 7 days later. Baseline C-reactive protein was 206 ± 50 mg/L (mean ± SEM) at the start of anakinra and decreased by 67.1% to 68 ± 36 mg/L (p = 0.03). Ferritin decreased by 63.8% to 3,210 ± 1,178 ng/mL (p = 0.30), and fibrinogen decreased by 42% to 158 ± 41 mg/dL (p = 0.03). Absolute neutrophil count (p = 0.38) and absolute lymphocyte count (p = 0.69) did not change significantly. No infections were attributed to anakinra therapy. One patient died long after treatment with anakinra while receiving pre-hematopoietic stem cell transplant chemotherapy.
  
  
  CONCLUSIONS
  Anakinra could represent a promising therapeutic approach in these life-threatening disorders that are likely underdiagnosed and often difficult to treat.
authors.affiliation: 1Pediatric Critical Care Medicine, Helen DeVos Children's Hospital. Grand Rapids, MI. 2Grand Rapids Medical Education Partners, Grand Rapids, MI. 3Department of Rheumatology, Helen DeVos Children's Hospital. Grand Rapids, MI.
authors.forename: Surender
authors.initials: S
authors.lastname: Rajasekaran
authors.forename: Katherine
authors.initials: K
authors.lastname: Kruse
authors.forename: Karen
authors.initials: K
authors.lastname: Kovey
authors.forename: Alan T
authors.initials: AT
authors.lastname: Davis
authors.forename: Nabil E
authors.initials: NE
authors.lastname: Hassan
authors.forename: Akunne N
authors.initials: AN
authors.lastname: Ndika
authors.forename: Sandra
authors.initials: S
authors.lastname: Zuiderveen
authors.forename: James
authors.initials: J
authors.lastname: Birmingham
mesh_terms: D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D003422:Critical Care; D005260:Female; D005293:Ferritins / Q000097:blood; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008214:Lymphocytes; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood / Q000188:drug therapy*; D055501:Macrophage Activation Syndrome / Q000188:drug therapy; D008297:Male; D009102:Multiple Organ Failure / Q000188:drug therapy; D009504:Neutrophils; D012189:Retrospective Studies; D018805:Sepsis / Q000188:drug therapy; D013256:Steroids / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D053590:Interleukin 1 Receptor Antagonist Protein; D013256:Steroids; D005340:Fibrinogen; D002097:C-Reactive Protein; D005293:Ferritins