Biallelic mutations in the CFHR genes underlying atypical hemolytic uremic syndrome in a patient with catastrophic adult-onset Still's disease and recurrent macrophage activation syndrome: A case report.

Adult-onset Still's disease Atypical hemolytic uremic syndrome Autoinflammation Macrophage activation syndrome

Journal

Clinical immunology (Orlando, Fla.)
ISSN: 1521-7035
Titre abrégé: Clin Immunol
Pays: United States
ID NLM: 100883537

Informations de publication

Date de publication:
Dec 2023
Historique:
received: 28 04 2023
revised: 02 10 2023
accepted: 24 10 2023
pubmed: 29 10 2023
medline: 29 10 2023
entrez: 28 10 2023
Statut: ppublish

Résumé

We report the fatal case of a 20-year-old woman with refractory adult-onset Still's disease (AOSD) accompanied by fulminant macrophage activation syndrome (MAS) and atypical hemolytic uremic syndrome (aHUS). Anakinra and tocilizumab temporarily controlled AOSD. In 2021, she presented to ICU with generalized tonic-clonic seizure, lymphocytic aseptic meningitis, and acute kidney injury. Despite hemodialysis and methylprednisolone, she developed another seizure, MAS, and disseminated intravascular coagulation (DIC). Following brief control, MAS flares -reflected by increased plasma CXCL9 and CXCL10- re-emerged and were controlled through dexamethasone, etoposide, cyclosporin and tofacitinib. No mutations were detected in haemophagocytic lymphohistiocytosis (HLH)-associated genes, nor in genes associated with periodic fever syndromes. Post-mortem genetic testing revealed loss-of-function biallelic deletions in complement factor H-related proteins (CFHR) genes, predisposing aHUS. This case underscores the importance of prompt genetic assessment of complement-encoding alleles, in addition to HLH-related genes, in patients with severe AOSD with recurrent MAS and features of thrombotic microangiopathy (TMA).

Identifiants

DOI: 10.1016/j.clim.2023.109815 PMID: 37898413
pubmed: 37898413
pii: S1521-6616(23)00578-8
doi: 10.1016/j.clim.2023.109815
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

109815

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest None.

Auteurs

Luna Dillemans (L)

Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Belgium.

Youri Bekhuis (Y)

Laboratory of Cardiology, Department of Cardiovascular Sciences, KU Leuven, Belgium; Department of Cardiovascular Diseases, University Hospitals Leuven, Belgium.

Albrecht Betrains (A)

Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium; European Reference Network for Immunodeficiency, Autoinflammatory, Autoimmune and Pediatric Rheumatic disease (ERN-RITA), University Hospitals Leuven, Belgium.

Karen Yu (K)

Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Belgium.

Maarten van Hemelen (M)

Medical Intensive Care Unit, Department of General Internal Medicine, University Hospitals Leuven, Belgium.

Noëmie Pörtner (N)

Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Belgium.

Lien De Somer (L)

European Reference Network for Immunodeficiency, Autoinflammatory, Autoimmune and Pediatric Rheumatic disease (ERN-RITA), University Hospitals Leuven, Belgium; Laboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Belgium; Department of Pediatric Rheumatology, University Hospitals Leuven, Belgium.

Patrick Matthys (P)

Laboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Belgium.

Jeroen Breckpot (J)

Department of Human Genetics, KU Leuven, Belgium.

Thomas Tousseyn (T)

Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Belgium.

Marijke Peetermans (M)

Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium; Medical Intensive Care Unit, Department of General Internal Medicine, University Hospitals Leuven, Belgium.

Paul Proost (P)

Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Belgium. Electronic address: paul.proost@kuleuven.be.

Carine Wouters (C)

European Reference Network for Immunodeficiency, Autoinflammatory, Autoimmune and Pediatric Rheumatic disease (ERN-RITA), University Hospitals Leuven, Belgium; Laboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Belgium.

Steven Vanderschueren (S)

Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium; European Reference Network for Immunodeficiency, Autoinflammatory, Autoimmune and Pediatric Rheumatic disease (ERN-RITA), University Hospitals Leuven, Belgium.

Classifications MeSH