title: Hyperferritinemia as the diagnostic clue in life-threatening hemophagocytic lymphohistiocytosis.
abstract: We report on a seventeen year old girl with persistent fever of unknown origin. An initial episode of abdominal pain led to laparotomy and appendectomy, which did not reveal any pathological findings. In the course of the next 3 weeks, the girl's general condition progressively deteriorated. Despite extensive diagnostics, no explanation was found. In summary, the girl was cared for by five different departments in two hospitals before she was admitted to our Children's Hospital. We too were initially misguided by the clinical picture of an infectious disease and treated the girl unsuccessfully with antibiotics. The clue in this case was the finding of a markedly elevated level of serum ferritin. While a normal upper value of less than 400 microg/l is reported, our patient displayed levels above 60,000 microg/l. Such extreme elevations of serum ferritin have been almost exclusively reported for hemophagocytic syndromes, as hemophagocytic lymphohistiocytosis (HLH). In HLH, impaired cytolytic function of T cells and natural killer cells leads to a state of hyperinflammation. We treated our patient with immunoglobulins and corticosteroids. Simultaneously, we started immunomodulatory therapy with oral cyclosporine A. The clinical response to this treatment was remarkable. The child's general condition stabilized quickly and the fever vanished. Additionally, the recovery was accompanied by a normalization of laboratory findings. In conclusion, HLH is a potentially life-threatening disease, which has to be considered in cases with fever of unknown origin. In our case, the diagnostic clue was an extreme elevation of ferritin.
authors.affiliation: Department of Pediatrics, Philipps-University Marburg, Germany. kerzel@med.uni-marburg.de
authors.forename: S
authors.initials: S
authors.lastname: Kerzel
authors.forename: M
authors.initials: M
authors.lastname: Zemlin
authors.forename: M
authors.initials: M
authors.lastname: Kömhoff
authors.forename: G
authors.initials: G
authors.lastname: Klaus
authors.forename: R F
authors.initials: RF
authors.lastname: Maier
mesh_terms: D015746:Abdominal Pain / Q000209:etiology / Q000601:surgery; D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002210:Caprylates / Q000627:therapeutic use; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000627:therapeutic use; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015278:Intensive Care Units, Pediatric; D007694:Killer Cells, Natural / Q000276:immunology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D008775:Methylprednisolone / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D019564:Unnecessary Procedures
chemical_list: D000893:Anti-Inflammatory Agents; D002210:Caprylates; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D005293:Ferritins; D008775:Methylprednisolone