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

Luna Dillemans; Youri Bekhuis; Albrecht Betrains; Karen Yu; Maarten van Hemelen; Noëmie Pörtner; Lien De Somer; Patrick Matthys; Jeroen Breckpot; Thomas Tousseyn; Marijke Peetermans; Paul Proost; Carine Wouters; Steven Vanderschueren

doi:10.1016/j.clim.2023.109815

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

Clin Immunol. 2023 Dec:257:109815. doi: 10.1016/j.clim.2023.109815. Epub 2023 Oct 26.

Authors

Affiliations

¹ Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Belgium.
² Laboratory of Cardiology, Department of Cardiovascular Sciences, KU Leuven, Belgium; Department of Cardiovascular Diseases, University Hospitals Leuven, Belgium.
³ 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.
⁴ Medical Intensive Care Unit, Department of General Internal Medicine, University Hospitals Leuven, Belgium.
⁵ 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.
⁶ Laboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Belgium.
⁷ Department of Human Genetics, KU Leuven, Belgium.
⁸ Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Belgium.
⁹ 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.
¹⁰ Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Belgium. Electronic address: [email protected].
¹¹ 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.

PMID: 37898413
DOI: 10.1016/j.clim.2023.109815

Abstract

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).

Keywords: Adult-onset Still's disease; Atypical hemolytic uremic syndrome; Autoinflammation; Macrophage activation syndrome.

Publication types

Case Reports

MeSH terms

Adult
Atypical Hemolytic Uremic Syndrome* / genetics
Cyclosporine / therapeutic use
Female
Humans
Lymphohistiocytosis, Hemophagocytic* / genetics
Macrophage Activation Syndrome* / genetics
Still's Disease, Adult-Onset* / complications
Still's Disease, Adult-Onset* / genetics
Young Adult

Substances

Cyclosporine