Search

VEXAS syndrome is a newly described autoinflammatory entity characterized by somatic mutations in the UBA1 X-linked gene in hematopoietic progenitor cells. Several studies have demonstrated that the presence of vacuoles in progenitor cells from bone marrow aspirates is a hallmark finding for this syndrome. Therefore, this study aimed to characterize leukocytes from VEXAS patients versus patients with ANCA-associated vasculitis (AAV), familial Mediterranean fever (FMF), and healthy donors (HD) to define a specific cytological pattern that can support VEXAS diagnosis. Twelve VEXAS patients were included in the study. Blood samples from FMF (n = 16), AAV (n = 16) and HDs (n = 20) acted as controls. May-Grünwald Giemsa (MGG) staining was used for studying cellular morphology, including cytoplasm, granules, and vacuoles and to perform a cytogenic evaluation of leucocytes. Plasma IL-1b, IL-1a, TNFa, IL-18 and IL-8 were measured using ELISA assay. The cytological analysis from blood smears confirmed the presence of immature neutrophils in VEXAS patients. We found a greater number of vacuoles in VEXAS patients vs. FMF, AAV and HD. Micronuclei (MNi) and cell death rate were higher in VEXAS patients vs. HD. Cell death correlated with IL-1b and IL-8 levels. MNi were positively associated with IL-8 and IL-1b levels, and with the percentage of immature neutrophils and vacuoles. In conclusion, our findings suggested that cytological test may be supportive for VEXAS diagnosis, despite genetical analysis is mandatory for confirming the disease. Finally, we identified several cytological hallmarks that may distinguish the VEXAS “cytotype” not only from HD but also from other inflammatory diseases. [ABSTRACT FROM AUTHOR]

The topic of fertility in women with spondyloarthritis (SpA) has been scarcely investigated to date. Recent systematic reviews and registry studies have brought renewed attention to the plight of women of childbearing age with rheumatic diseases, in particular SpA. Fertility may be impacted by physical impairment, hormonal imbalances and psychological distress. Several studies observed a reduction in anti-Müllerian hormone in women with SpA, reflecting a reduced ovarian reserve (OR). Furthermore, disease activity and the use of certain therapies can alter fertility, and this is reflected in a prolonged time-topregnancy (TTP), a validated outcome measure that can evaluate the status of subfertility. The employment of glucocorticoids or non-steroidal antiinflammatory drugs has also been linked to reduced fertility, whereas the use of biologics, especially tumour necrosis factor inhibitors (TNFi), is not associated with a prolonged TTP. In all women of childbearing age with rheumatic diseases, preconception counselling is paramount, and a referral to a reproductive specialist should be considered in the presence of multiple factors that may influence fertility. A comprehensive evaluation involving a multidisciplinary team of rheumatologists, gynaecologists, and often psychologists is warranted. In this narrative review, we collected the currently available literature focusing on fertility issues in women affected by SpA, providing data on fertility outcomes, hormonal imbalance, and therapeutic concerns. [ABSTRACT FROM AUTHOR]

Objective: To assess if patients affected by systemic autoinflammatory diseases (SAIDs) present an increased risk of osteoporosis (OP). Methods: Forty adults patients referred to the Rheumatology Unit of Padova University Hospital affected by Familial Mediterranean Fever (FMF), TNF-Receptor Associated Periodic Syndrome (TRAPS), and Mevalonate Kinase Deficiency (MKD) and 40 healthy subjects were enrolled. Blood and urine samples were collected in order to define phosphocalcic metabolism, including Receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG), and among inflammatory markers serum amyloid A (SAA). Femur and lumbar dual-energy X-ray absorptiometry (DXA) scans were performed and Trabecular Bone Score (TBS) was calculated on DXA lumbar images. Results: We did not observe a statistically significant difference between Bone Mineral Density (BMD) and TBS of patients compared to controls. Also, the values of phosphocalcic metabolites in patients did not statistically differ from those in controls. However, SAA and OPG levels were significantly higher in patients compared to healthy subjects (p = 0.0244 and p = 0.0064, respectively). Conclusion: Patients of our cohort affected by FMF, TRAPS, and MKD do not present an increased risk of OP compared to the healthy controls. TBS and BMD are similar between the two groups underlining a preserved bone quality in patients. High OPG levels could suggest a protective role and a bone re-balancing action in response to an inflammatory background. Finally, it should be taken into account a modulatory role played by a pro-inflammatory cytokine such as SAA on bone homeostasis. [ABSTRACT FROM AUTHOR]