Analysis of treatment outcomes in patients with antineutrophil cytoplasmic antibody-associated vasculitis on rituximab therapy.

Objectives: This study aimed to analyze a group of patients with severe and refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) managed with rituximab and to report on treatment outcomes. Patients and methods: A total of 78 patients (41 females, 37 males; mean age: 50.1±13.4 years; range, 18 to 76 years) with AAV on rituximab treatment were included in the single-center, retrospective study conducted between 2009 and 2018. The diagnosis was established based on the 1990 classification criteria of the American College of Rheumatology and the definitions of vasculitis of Chapel Hill Consensus Conference. Laboratory and immunological tests were conducted. Disease activity was determined through the Birmingham Vasculitis Activity Score. Results: Rituximab was preferred over cyclophosphamide in 37 patients and used as a second-line therapy after cyclophosphamide in 41 cases. Rituximab treatment showed favorable outcomes with regard to serum creatinine levels, proteinuria, and hematuria, as well as in cases of isolated lung involvement. Nearly half of patients with pulmonary renal syndrome also improved, with 22.2% achieving remission. ANCAs were positive in 85.9% of patients at the onset of rituximab treatment and became negative in 82% of the positive cases. Adverse events were rare and included infusion reactions (one case of reactivation of a herpes zoster infection and one case of allergic reaction). Conclusion: Rituximab is an efficient and safe therapeutic option in patients with AAV who are difficult to treat, have insufficient response, or have not tolerated other treatments.

Exploring the Novel Dimension of Immune Interactions in Pain: JAK Inhibitors' Pleiotropic Potential.

This review explores the link between immune interactions and chronic pain, offering new perspectives on treatment. It focuses on Janus kinase (JAK) inhibitors' potential in pain management. Immune cells' communication with neurons shapes neuroinflammatory responses, and JAK inhibitors' effects on pain pathways are discussed, including cytokine suppression and microglial modulation. This review integrates studies from rheumatoid arthritis (RA) pain and central sensitization to highlight connections between immune interactions and pain. Studies on RA joint pain reveal the shift from cytokines to sensitization. Neurobiological investigations into central sensitization uncover shared pathways in chronic pain. Clinical evidence supports JAK inhibitors' efficacy on pain-related outcomes and their effects on neurons and immune cells. Challenges and future directions are outlined, including interdisciplinary collaboration and dosing optimization. Overall, this review highlights JAK inhibitors' potential to target immune-mediated pain pathways, underscoring the need for more research on immune-pain connections.

Alterations of serum levels of plasminogen, TNF-α, and IDO in granulomatosis with polyangiitis patients.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a representative of vasculitides associated with anti-neutrophil cytoplasmic autoantibodies. "Classical" antibodies directed against proteinase 3 are involved in the pathogenesis and are part of the GPA diagnosis at the same time. Along with them, however, antibodies against Lysosomal-Associated Membrane Protein-2 (LAMP-2) and antibodies directed against plasminogen have been described in GPA.Objectives and methodology: We performed a cross-sectional study enrolling 34 patients diagnosed with GPA. Our study was aimed at looking for correlations between serum levels of LAMP-2 and plasminogen and the clinical manifestations of the GPA. Furthermore, we examined serum levels of tumor necrosis factor-alpha (TNF-α) and its associated indoleamine-pyrrole 2,3-dioxygenase (IDO), as well as we looked for a correlation between these cytokines and the clinical manifestations of GPA. RESULTS: The results showed that in GPA, serum plasminogen levels were negatively associated with renal involvement (receiver operating characteristic (ROC) area under the curve (AUC) of 0.78) (95% CI 0.53-0.91), p = 0.035, and the extent of proteinuria, Spearman's Rho = -0.4, p = 0.015. Increased levels of TNF-α and IDO correlated with disease activity, Spearman's Rho =0.62, p = 0.001 and Spearman's Rho = 0.4, p = 0.022, respectively, whereas only TNF-α was increased in severe forms of GPA with lung involvement (ROC AUC of 0.8) (95% CI 0.66-0.94), p = 0.005. CONCLUSIONS: In this study, we demonstrate the alteration of soluble factors, which play an important role in the pathogenesis of GPA and their relationship with the clinical manifestations of the disease. Our main results confirm the associations of increased secretory TNF-α and some clinical manifestations, and we describe for the first time decreased serum plasminogen levels and their association with renal involvement.

Two clinical cases of granulomatosis with polyangiitis with isolated otitis media and mastoiditis.

Granulomatosis with polyangiitis (GPA) is characterised by granulomatous necrotising inflammatory lesions of the upper and lower respiratory tract, often associated with pauci-immune glomerulonephritis. The diagnosis of granulomatosis with polyangiitis is made according to the classification criteria of the ACR criteria for granulomatosis with polyangiitis. We present two cases of granulomatosis with polyangiitis limited/localised form. The common feature between two clinical cases were not sufficient criteria for a definite diagnosis at the beginning. In both cases the clinical presence was otitis media with acute mastoiditis, peripheral facial nerve palsy, and severe headache. Early diagnosis and treatment of patients with granulomatosis with polyangiitis define favourable prognosis. On the other hand, the treatment of granulomatosis with polyangiitis (corticosteroids and immunosuppressive therapy) has various side effects, and the "ex juvantibus" therapy is hazardous.

Denosumab improves bone mineral density and microarchitecture and reduces bone pain in women with osteoporosis with and without glucocorticoid treatment.

Osteoporosis is a key health problem in postmenopausal women with high social and economic impact. Decreased bone mineral density (BMD) and deterioration of bone microarchitecture may occur also as a result of long-term glucocorticoid treatment (GCT) of autoimmune or inflammatory conditions. Denosumab specifically inhibits the binding of the receptor activator of nuclear factor-κB to its ligand, thus preventing osteoclast activation and bone resorption. The efficacy and safety of denosumab, administered subcutaneously as 60 mg, once every six months for 12 months, were evaluated in 60 patients with postmenopausal osteoporosis (PMO) divided into two groups. The GCT group included 30 patients receiving concomitant glucocorticoid therapy and the non-GCT group included 30 patients that did not receive GCT. In the non-GCT group, the 12-month treatment with denosumab resulted in BMD increase of 6.1% and 2.8% in lumbar spine and hip, respectively. T-score increased by 13.1% and 5.6% in both, the lumbar spine and hip. A slight rise in the Trabecular Bone Score (TBS) of 0.3% was observed. Bone pain was markedly reduced by 56.2%. In the GCT group, denosumab therapy increased BMD with 5.8% and 2.3% in lumbar spine and hip, respectively. T-score of lumbar spine and hip significantly increased by 14.0% and 4.4%, and the TBS rose by 5%. Bone pain was reduced by 53.6%. These data confirm the available knowledge on denosumab efficacy and safety in women with PMO and also provide new insights into its therapeutic potential in patients with osteoporosis related to a long-term corticosteroid treatment.