VEXAS and Myelodysplastic Syndrome: An Interdisciplinary Challenge.

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.

Dual-Energy Computed Tomography Collagen Density Mapping of the Cranio-Cervical Ligaments-A Retrospective Feasibility Study.

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.

Unexpected Sex Differences in the Relationship of Sacroiliac Joint and Lumbar Spine Degeneration.

The relationship between degenerative changes of the sacroiliac joints and the lumbar spine on CT has not been studied yet. The aim of this analysis is to determine the nature of their association as well as the influence of fixed anatomical spinopelvic parameters on sacroiliac joint degeneration. For this institutional review-board-approved investigation, imaging datasets as well as electronic medical records of 719 patients without back pain from the clinical routine of our department of radiology were included. Age, sex, weight category (slim, normal, obese), parity in women and indication for imaging were noted for all patients. The presence of degenerative lesions of the lumbar spine (disc degeneration, endplate degeneration, spondylophytes, and facet joint osteoarthritis) was noted separately at each lumbar segment (L1 to L5). Sacroiliac joints were assessed for sclerosis and osteophytes. Fixed anatomical spinopelvic parameters were measured: pelvic radius = PR; pelvic incidence = PI; sacral table angle = STA. Correlation as well as regression analyses were performed; data were analyzed for males and females separately. PI increased significantly with age in both women and men, while STA decreased and PR remained constant; neither of them was associated with SIJ degeneration. SIJ degeneration correlated with disc degeneration (tau = 0.331; p < 0.001), spondylophytes (tau = 0.397; p < 0.001), and facet joint degeneration (tau = 0.310; p < 0.001) in men, but with no parameter of spinal degeneration in women. Lumbar spinal degeneration increased the risk of sacroiliac joint degeneration in men significantly (OR 7.2; 95%CI 2.8-19.0), but it was not a significant covariable in women. Fixed spinopelvic parameters have little impact on sacroiliac joint degeneration. The degeneration of the sacroiliac joints and the lumbar spine appear to be parallel processes in men, but are largely unrelated in women.

What amount of structural damage defines sacroiliitis: a CT study.

OBJECTIVES: To propose a data-driven definition for structural changes of sacroiliac (SI) joints in the context of axial spondyloarthritis (axSpA) imaging on a large collective of CT datasets. METHODS: 546 individuals (102 axSpA, 80 non-axSpA low back pain and 364 controls without back pain) with SI joint CTs were evaluated for erosions, sclerosis and ankylosis using a structured scoring system. Lesion frequencies and spatial distribution were compared between groups. Diagnostic performance (sensitivity (SE), specificity (SP), positive predictive values, negative predictive values and positive and negative likelihood ratios) was calculated for different combinations of imaging findings. Clinical diagnosis served as standard of reference. RESULTS: Ankylosis and/or erosions of the middle and dorsal joint portions yielded the best diagnostic performance with SE 67.6% and SP 96.3%. Inclusion of ventral erosions and sclerosis resulted in lower diagnostic performance with SE 71.2%/SP 92.5% and SE 70.6%/SP 90.0%, respectively. CONCLUSIONS: Sclerosis and ventrally located erosions of SI joints have lower specificity on CT of the SI joint in the context of axSpA imaging. Ankylosis and/or erosions of the middle and dorsal joint portions show a strong diagnostic performance and are appropriate markers of a positive SI joint by CT.

Joint anatomy in axial spondyloarthritis: strong associations between sacroiliac joint form variation and symptomatic disease.

OBJECTIVES: The aim of this investigation was to determine the prevalence of variant SI joint forms in symptomatic patients with mechanical joint disease (MJD) and axial SpA (axSpA) compared with control patients. METHOD: A total of 973 patients were included in this cross-sectional study (95 axSpA; 61 MJD; 817 controls); clinical diagnosis, age and gender were noted. An established scoring system was used to classify joint forms on CT scans of the pelvis. Frequencies of joint forms were compared between groups (axSpA; MJD; controls). RESULTS: Patients with MJD exhibited the highest proportion of atypical joints (80.3% in MJD vs 44.1% in axSpA and 37.5% in controls; P < 0.001). Overall, females had a significantly higher proportion of atypical joints than men (65.0 vs 17.8%; P < 0.001); proportions of atypical joints were significantly higher in males with symptomatic joint disease than in male controls: 32.2% in axSpA, 55.0% in MJD and 13.9% in controls; P ≤ 0.001. Two specific joint forms were significantly more prevalent in symptomatic patients than in controls: the iliosacral complex (16.2 vs 4.2%; P < 0.001) and the crescent-shaped ilium (9.1 vs 2.8%; P < 0.05). CONCLUSIONS: Our data demonstrate a strong association between atypical joint forms and symptomatic joint disease.

Impact of age, sex, and joint form on degenerative lesions of the sacroiliac joints on CT in the normal population.

Degeneration of the sacroiliac joints (SIJs) is a common finding, while its underlying cause and development remain incompletely understood. The aim of this investigation was to describe the spatial distribution of degenerative SIJ changes across age groups and to investigate for the first time their relationship to anatomical form and sex. For this IRB-approved investigation, demographic data of 818 patients without SIJ disease were retrieved from electronic patient records. High-resolution computed tomography (CT) datasets of all patients were analysed retrospectively for seven predefined age groups (ten-year increments, from < 25 to ≥ 75). A structured scoring system was applied to assess sclerosis, osteophytes, joint space alterations, and anatomical form. Chi-square tests were used to compare frequencies of degenerative lesions, and logistic regression analyses were performed to investigate associations between demographic data, anatomical form, and the presence of structural lesions. Sclerosis and osteophytes were common findings, with an overall prevalence of 45.7% and 46.8%, respectively. Female sex had an odds ratio (OR) of 0.15 (95% CI: 0.08-0.27) for the presence of ventral osteophytes and of 4.42 (95% CI: 2.77-7.04) for dorsal osteophytes. Atypical joint forms were significantly more prevalent in women with 62.1% vs. 14.1% in men (p < 0.001). Accessory joints increased the likelihood of dorsal sclerosis (OR 2.735; 95% CI 1.376-5.436) while a typical joint form decreased its likelihood (OR 0.174; 95% CI 0.104-0.293). Sex and anatomical joint form have a major impact on the development of degenerative lesions of the SIJs and their spatial distribution.

Asymptomatic secondary hyperparathyroidism can mimic sacroiliitis on computed tomography.

Secondary hyperparathyroidism (sHPT) as a result of chronic kidney disease (CKD) is a common health problem and has been reported to manifest at the sacroiliac joints (SIJ). The aim of this investigation was to systematically assess sacroiliac joint changes in asymptomatic sHPT as detected by high-resolution CT. Included in this IRB-approved retrospective case-control study were 56 patients with asymptomatic sHPT as well as 259 matched controls without SIJ disease. Demographic data were retrieved from electronic patient records. High-resolution computed tomography datasets of all patients were subjected to a structured scoring, including erosions, sclerosis, osteophytes, joint space alterations and intraarticular calcifications. Chi2 tests were used to compare frequencies of lesions. Erosions were significantly more prevalent in patients with sHPT, and were found mainly in the ventral (28.6% vs. 13.9%; p = 0.016) and middle (17.9% vs. 7.7%; p = 0.040) iliac portions of the SIJ. Partial ankylosis was rare in both cohorts (3.6% vs. 5.0%; p > 0.999); complete ankylosis was not observed. Neither extent not prevalence of sclerosis or calcifications differed significantly between groups. Joint lesions reminiscent of sacroiliitis can be found in a substantial portion of asymptomatic patients with secondary hyperparathyroidism. Further investigations into the clinical significance of these findings are warranted.