Low remission rates and high incidence of adverse events in a prospective VEXAS syndrome registry.

OBJECTIVE: We aimed to gather real-world clinical evidence of detailed disease activity, treatments, remission rates, and adverse events (AEs) associated with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome in a prospective study. METHODS: Patients in Japan suspected of having VEXAS syndrome were enrolled in a registry study. A novel disease activity measure (VEXASCAF) assessing 11 symptoms associated with VEXAS syndrome was evaluated at enrolment and after 3 months. AEs, survival, CRP levels, and treatments were also recorded at enrolment and 3 months after enrolment. All exons of UBA1 were sequenced using a next-generation sequencer to determine the variant allele frequencies of pathogenic variants in the peripheral blood of all patients. RESULTS: Of the 55 registered patients, 30 patients were confirmed to have pathogenic variants of UBA1. All patients were male, with a median age of 73.5 years. VEXASCAF and CRP levels decreased significantly at 3 months post-enrolment, but the oral prednisolone dose did not change. Only two patients achieved complete remission according to FRENVEX at 3 months after enrolment. During the observation period of 6 months, 28 AEs were observed, including 3 deaths, 4 malignancies from two cases, 2 thromboses, and 13 infections (including 4 mycobacterial infections). Inflammation of the lung and cervical region (i.e. parotid and submandibular gland swelling, tonsillitis, cervical swelling, and pain) were the most common AEs. CONCLUSIONS: Patients with VEXAS syndrome required high-dose glucocorticoids to achieve remission, and complications-such as malignancy, thrombosis, and infection-occurred frequently within a short observation period.

Differences and similarities in cytokine profiles of macrophage activation syndrome in systemic lupus erythematosus and adult-onset Still's disease.

To clarify the differences and similarities in the cytokine profiles of macrophage activating syndrome (MAS) between systemic lupus erythematosus (SLE) and adult-onset Still's disease (AOSD). The study participants included 9 patients with MAS-SLE, 22 with non-MAS-SLE, 9 with MAS-AOSD, and 13 with non-MAS-AOSD. Serum cytokine levels were measured using a multiplex bead assay. Cytokine levels were compared between patients with SLE and AOSD with/without MAS. Moreover, cytokine patterns were examined using principal component analysis (PCA) and cluster analysis. IL-6, IL-8, IL-18, and TNF-α levels were elevated in patients with SLE and AOSD. IFN-α levels were elevated in SLE, whereas IL-1ß and IL-18 levels were elevated in AOSD. In SLE, IFN-α and IL-10 levels were higher in MAS than in non-MAS and controls. PCA revealed distinctive cytokine patterns in SLE and AOSD, SLE with IFN-α and IP-10, AOSD with IL-1ß, IL-6, and IL-18, and enhanced cytokine production in MAS. PCA and cluster analysis showed no differences in cytokine patterns between the MAS and non-MAS groups. However, serum ferritin levels were correlated with IFN-α levels in SLE. Cytokine profiles differed between SLE and AOSD but not between MAS and non-MAS. MAS is induced by the enhancement of underlying cytokine abnormalities rather than by MAS-specific cytokine profiles. Type I IFN may be involved in MAS development in patients with SLE.

Changing patterns of pulmonary abnormalities in rheumatoid arthritis.

BACKGROUND: As a first step in identifying the developmental pathways of pulmonary abnormalities in rheumatoid arthritis (RA), we sought to determine the existing and changing patterns of pulmonary abnormalities. METHODS: We conducted a retrospective cohort study of consecutive patients with RA who underwent high-resolution computed tomography before and during biologic therapy. The presence of 20 pulmonary abnormalities and the changes in those abnormalities were recorded. Patterns of pre-existing and changing abnormalities were examined via cluster analysis, and their relationship was also assessed using the Kaplan-Meier method and log-rank test. RESULTS: A total of 208 subjects were included. Pulmonary abnormalities were observed in 70% of patients: 39% had interstitial lung disease, and 55% had airway disease (AD). Several different pulmonary abnormalities were commonly found to co-exist in several patterns in the same patient. In most patients with pulmonary abnormalities, AD was present alone or in combination with other abnormalities. During the observation period (mean 3.2 years), 172 pulmonary abnormalities had changed in 91 patients: 115 pulmonary abnormalities newly emerged, whereas 42 worsened and 25 demonstrated improvement. Pulmonary abnormalities changed in several patterns. Correlations were observed between pre-existing and new/worsening abnormalities at individual and regional levels, such as new ground-glass opacity (GGO) and pre-existing AD, small nodular patterns, and honeycombing. AD was a possible initial abnormality. CONCLUSIONS: Pulmonary abnormalities occurred and changed in several patterns, which suggests the existence of developmental pathways of pulmonary abnormalities. AD may play an important role in the development of these abnormalities, including GGO.