title: Previously undiagnosed fatal familial haemophagocytic lymphohistiocytosis in a 24-year-old woman.
abstract: We present a case of a 24-year-old woman with previously undiagnosed familial haemophagocytic lymphohistiocytosis (HLH). The patient presented with fevers and cough and was found to have pancytopaenia. She underwent an extensive work up and initially met only 3 of 8 criteria for HLH. Owing to high clinical suspicion, soluble CD25 level was sent and HLH2004 protocol initiated. The soluble CD25 level returned elevated with other laboratory work and the patient met criteria for diagnosis of HLH. Genetic studies revealed a homozygous mutation in PRF1 with absent perforin in cytotoxic cells, consistent with familial HLH. The patient expired before intrathecal chemotherapy could be initiated. This case illustrates the potential for familial HLH to present at an older age, and highlights the importance of early recognition and initiation of treatment of HLH, as patients may not initially fulfil the diagnostic criteria for HLH, and mortality is high if left untreated.
authors.affiliation: Department of Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Barmettler
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Nowak
authors.affiliation: Section of Hematology-Oncology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Terri
authors.initials: T
authors.lastname: Parker
authors.affiliation: Section of Allergy and Clinical Immunology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Price
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging*; D017809:Fatal Outcome; D005260:Female; D006720:Homozygote; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood*; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging* / Q000235:genetics; D008279:Magnetic Resonance Imaging; D009154:Mutation; D054353:Perforin / Q000235:genetics*; D012640:Seizures / Q000209:etiology; D055815:Young Adult
chemical_list: C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; C510468:PRF1 protein, human; D054353:Perforin