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.

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).

Diagnostic accuracy and validation of 18F-fluorodeoxyglucose positron emission tomography scores in a large cohort of patients with polymyalgia rheumatica.

Background: Several studies have shown that 18F-FDG PET may contribute to the diagnosis of polymyalgia rheumatica (PMR). Previously, we developed a composite PET score called the Leuven score, which was recently adapted to the more concise Leuven/Groningen score by van der Geest et al. The aim of this study is to validate and compare the diagnostic accuracy and cut-off points of both scores in a large cohort of PMR patients. Methods: Patients with a possible clinical diagnosis of PMR and a PET scan prior to the initiation of glucocorticoids between 2003 and 2020 were included retrospectively. The gold standard for the diagnosis of PMR was the judgment of two experienced clinicians after a follow-up of at least 6 months. FDG uptake was scored visually in 12 articular regions (scores 0-2) and a total skeletal score was calculated by summing the individual scores (maximum of 24 for the Leuven score and 14 for the Leuven/Groningen score). Receiver operating characteristic (ROC) analysis and the Youden index were used to determine the diagnostic accuracy and optimal cut-off points. Results: A total of 162 patients with PMR and 83 control patients were included. Both PET scores showed high diagnostic accuracy in the ROC analysis (area under the curve 0.986 and 0.980, respectively). The Leuven Score provided a sensitivity of 91.4%, specificity of 97.6% and accuracy of 93.5% at its predefined cut-off point of 16. With the newly determined cut-off point of 12 the sensitivity was 98.8%, the specificity 95.2% and the accuracy 97.6%. The Leuven/Groningen score had a sensitivity, specificity and accuracy of 93.2%, 95.2%, and 93.9%, respectively, with the pre-specified cut-off point of 8, and 96.9%, 92.8%, and 95.5% with the optimal cut-off point of 7. Conclusion: The original Leuven score and the simplified Leuven/Groningen score both had excellent diagnostic accuracy. The latter may be easier to apply in clinical practice.

Papillary thyroid carcinoma presenting with severe Guillain-Barré syndrome.

BACKGROUND: The Guillan-Barré syndrome (GBS) is the most common acute disease of the peripheral nervous system, often necessitating ICU care. Although no clear paraneoplastic syndrome has been defined, it has been known to occur together with several types of cancer. METHODS: We present the case of a 35-year-old man with acute flaccid paralysis and cervical lymphadenopathy. RESULTS: the patient was diagnosed with a severe presentation of GBS and papillary thyroid cancer. After surgical treatment for his cancer, his condition improved and he reached a nearly full recovery. CONCLUSION: our case concerns a young man in whom a severe presentation of GBS led to the diagnosis of thyroid cancer. To our knowledge, this represents the first reported case of this association.

Impact of age at diagnosis in polymyalgia rheumatica: A retrospective cohort study of 218 patients.

BACKGROUND: Polymyalgia rheumatica (PMR) is a common musculoskeletal inflammatory disease that may occur with giant-cell arteritis (GCA) or in an isolated form. While the incidence is highest in the elderly, there is a paucity of data on its presentation, clinical course and response to treatment in younger individuals. METHODS: We conducted a retrospective review of 40 patients who were diagnosed with isolated PMR under the age of 60 and 178 patients diagnosed above this age, taking into account clinical and laboratory data and treatment history. RESULTS: Patients who were diagnosed at a younger age had lower acute-phase reactant levels at diagnosis but not after initiation of treatment or at the time of relapse. The risk of relapse was lower in the group diagnosed under age 60 (35% vs 55%). Cumulative and maximal glucocorticoid doses, use of glucocorticoid-sparing agents and duration of glucocorticoid treatment, did not differ between the groups. In multivariate analysis, younger age at diagnosis was associated with cervical pain and male gender. CONCLUSION: Compared to patients diagnosed above age 60, patients diagnosed with PMR at a younger age have a lower risk of relapse, but similar long-term outcomes with regards to continued need for treatment.