RESUMO
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently recognized systemic autoinflammatory disease caused by somatic mutations in hematopoietic progenitor cells. This case series of four patients with VEXAS syndrome and comorbid myelodysplastic syndrome (MDS) aims to describe clinical, imaging, and hematologic disease presentations as well as response to therapy. Four patients with VEXAS syndrome and MDS are described. A detailed analysis of imaging features, hemato-oncological presentation including bone marrow microscopy and clinical-rheumatological disease features and treatment outcomes is given. All patients were male; ages ranged between 64 and 81 years; all were diagnosed with MDS. CT imaging was available for three patients, all of whom exhibited pulmonary infiltrates of varying severity, resembling COVID-19 or hypersensitivity pneumonitis without traces of scarring. Bone marrow microscopy showed maturation-disordered erythropoiesis and pathognomonic vacuolation. Somatic mutation in the UBA1 codon 41 were found in all patients by next-generation sequencing. Therapy regimes included glucocorticoids, JAK1/2-inhibitors, nucleoside analogues, as well as IL-1 and IL-6 receptor antagonists. No fatalities occurred (observation period from symptom onset: 18-68 months). Given the potential underreporting of VEXAS syndrome, we highly recommend contemporary screening for UBA1 mutations in patients presenting with ambiguous signs of systemic autoinflammatory symptoms which persist over 18 months despite treatment. The emergence of cytopenia, especially macrocytic hyperchromic anemia, should prompt early testing for UBA1 mutations. Notably conspicuous, pulmonary alterations in CT imaging of patients with therapy-resistant systemic autoinflammatory symptoms should be discussed in interdisciplinary medical teams (Rheumatology, Hematology, Radiology and further specialist departments) to facilitate timely diagnosis during the clinical course of the disease.
RESUMO
The objectives of this study were to investigate the mean collagen content of the atlanto-axial joint (AAJ) ligaments in a cohort without inflammatory disease and to analyze clinical confounders such as age, sex, and presence of ligamentous calcifications. A total of 153 patients who underwent dual-energy computed tomography (DECT) due to various reasons (e.g., suspected cancer or infection) were included in this retrospective study. Reconstruction of collagen density maps from the DECT dataset was performed. Region of interest (ROI) analysis was performed to assess densities in the following regions: ligamentum transversum atlantis (LTA), ligamenta alaria, fasciculi longitudinales, ligamentum nuchae, and retro-odontoid soft tissue (RDS). Osteoarthritis (OA) and the presence of calcifications were assessed by two experienced readers blinded to clinical data. Subgroup comparisons were performed using unpaired t-tests. The correlation of collagen density and clinical factors was investigated using Pearson's correlation coefficient. Mean LTA collagen density was 141.7 (SD 35.7). Ligamentous calcifications were rare (14.4 %). OA of the AAJ was common (91.5 %). LTA collagen density was not associated with age (Pearson's r of 0.109; p = 0.180) and was not significantly higher in patients with OA (p = 0.070). No correlations between RDS thickness, collagen density or calcifications were found. Our results show collagen density mapping of the cranio-cervical joint ligaments to be feasible; collagen densities are not significantly associated with age, sex, AAJ degeneration, or asymptomatic ligamentous calcification.