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Discovery of the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome demonstrates that somatic mutations in haematological precursor cells can cause adult-onset, complex inflammatory disease. Unlike germline mutations, somatic mutations occur throughout the lifespan, are restricted to specific tissue types, and may play a causal role in non-heritable rheumatological diseases, especially conditions that start in later life. Improvements in sequencing technology have enabled researchers and clinicians to detect somatic mutations in various tissue types, especially blood. Understanding the relationships between cell-specific acquired mutations and inflammation is likely to yield key insights into causal factors that underlie many rheumatological diseases. The objective of this review is to detail how somatic mutations are likely to be relevant to clinicians who care for patients with rheumatological diseases, with particular focus on the pathogenetic mechanisms of the VEXAS syndrome. [ABSTRACT FROM AUTHOR]

Objectives Relapsing polychondritis (RP) is a rare, heterogeneous, systemic inflammatory disease that targets cartilage. Patient-reported outcome measures may differ from physician assessment. This study compared patient global assessment (PtGA) and physician global assessment (PhGA) scores in a prospective cohort of patients with RP. Methods Adult patients with RP underwent a standardized comprehensive evaluation at ∼6 month intervals. At each visit, three physicians scored PhGA by consensus. The patient independently completed four patient-reported outcomes: PtGA, 36-item Short Form Health Survey (SF-36), Brief Illness Perception Questionnaire (BIPQ) and Multidimensional Fatigue Inventory (MFI). Patient–physician discordance was defined as a difference between PtGA and PhGA of ≥3 on a 0–10 scale. Results A total of 76 patients were evaluated over 154 visits. The median PhGA was 3 [interquartile range (IQR) 2–3] and the median PtGA was 5 (IQR 4–7). PtGA and PhGA were concordant in 66 visits (42.9%) and patients scored disease severity ≥3 points higher than physicians scored disease activity (positive discordance) in 84 visits (54.5%). Compared with visits with concordance, visits with positive discordance were associated with significantly worse scores on the MFI, BIPQ, SF-36 physical component score and SF-36 mental component score. Conclusion Patients with RP typically self-report high PtGA that does not align with PhGA. Discordance is likely driven by the high physical and psychological burden of illness experienced by patients. Multifaceted treatment approaches that address the burden of disease in RP from the patient perspective are needed. [ABSTRACT FROM AUTHOR]

Objectives This study describes the spectrum and initial impact of pulmonary manifestations in the primary systemic vasculitides. Methods Description and comparison of pulmonary manifestations in adults with Takayasu's arteritis (TAK), GCA, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic GPA (EGPA), polyarteritis nodosa (PAN) and IgA vasculitis (IgAV), using data collected within the Diagnostic and Classification Criteria in Vasculitis study. Results Data from 1952 patients with primary vasculitides were included: 170 TAK, 657 GCA, 555 GPA, 223 MPA, 146 EGPA, 153 IgAV and 48 PAN. Pulmonary manifestations were observed in patients with TAK (21.8%), GCA (15.8%), GPA (64.5%), MPA (65.9%), EGPA (89.0%), PAN (27.1%) and IgAV (5.9%). Dyspnoea occurred in patients with TAK (14.7%), GCA (7.8%), GPA (41.8%), MPA (43.5%), EGPA (65.8%), PAN (18.8%) and IgAV (2.6%). Cough was reported in TAK (7.6%), GCA (9.3%), GPA (34.8%), MPA (37.7%), EGPA (55.5%), PAN (16.7%) and IgAV (3.3%). Haemoptysis occurred mainly in patients with ANCA-associated vasculitis (AAV). Fibrosis on imaging at diagnosis was documented in GPA (1.9%), MPA (24.9%) and EGPA (6.3%). Only patients with AAV (GPA 2.7%, MPA 2.7% and EGPA 3.4%) required mechanical ventilation. At 6 months, the presence of at least one pulmonary item in the Vasculitis Damage Index was observed in TAK (4.1%), GCA (3.3%), GPA (15.4%), MPA (28.7%), EGPA (52.7%), PAN (6.2%) and IgAV (1.3%). Conclusion Pulmonary manifestations can occur in all primary systemic vasculitides, but are more frequent and more often associated with permanent damage in AAV. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the time-dependent effects of tocilizumab on vascular inflammation as measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in GCA. Methods Patients with GCA treated with tocilizumab were selected from a prospective, observational cohort. Patients underwent FDG-PET at the baseline visit prior to initiation of tocilizumab and at subsequent follow-up visits performed at 6-month intervals. All imaging findings were interpreted blinded to clinical data. The PET vascular activity score (PETVAS) was used to quantify arterial FDG uptake. Wilcoxon signed rank test was used to compare change in PETVAS between visits. Linear regression was used to determine change in PETVAS over multiple timepoints. Results Twenty-five patients with GCA were included. All patients had physician-determined active vasculitis at the baseline visit by clinical assessment and FDG-PET interpretation. PETVAS was significantly reduced in association with tocilizumab treatment from the baseline to the most recent follow-up visit [24.0 (IQR 22.3–27.0) vs 18.5 (IQR 15.3–23.8); P  <0.01]. A significant reduction in PETVAS was observed over a two-year treatment period (P  <0.01 for linear trend), with a similar degree of improvement in both the first and second years of treatment. Repeat FDG-PET scans after tocilizumab discontinuation showed worsening PET activity in five out of six patients, with two patients subsequently experiencing clinical relapse. Conclusion Treatment of patients with GCA with tocilizumab was associated with both clinical improvement and reduction of vascular inflammation as measured by serial FDG-PET. Future clinical trials in GCA should study direct treatment effect on vascular inflammation as an outcome measure. [ABSTRACT FROM AUTHOR]

Objectives To describe the clinical profile of Asian Indian patients with Takayasu's arteritis (TAK) and to compare clinical features and outcome of childhood-onset Takayasu's arteritis (cTAK) with adult-onset TAK (aTAK). Methods Data related to clinical features and response to treatment of patients with cTAK (age of onset <16 years) and aTAK from a large observational cohort in our tertiary care teaching hospital were noted and compared. Results Altogether, 602 patients (cTAK = 119; aTAK = 483) were studied. Patients with cTAK had a blunted female: male ratio; but fever, elevated acute phase reactants, involvement of abdominal aorta or its branches, hypertension, abdominal pain, elevated serum creatinine and cardiomyopathy were more common in cTAK as compared with aTAK. Patients with aTAK were more likely to have aortic-arch disease and claudication than cTAK. During follow-up, complete remission was more common in cTAK (87% vs 66%; P < 0.01), but subsequent relapses were equally common (30% vs 27%; P = 0.63). Independent associations of disease duration at presentation with disease extent [Disease Extent Index in TAK (DEI.Tak)] and damage [TAK Damage Score (TADS)] were observed (P ≤ 0.01). Moreover, 54% of patients with symptom duration of >5 years at presentation still continued to have elevated CRP suggesting continued and active inflammation warranting escalation or inititation of immunosuppression. Conclusion Patients with cTAK are more likely to have arterial disease below the diaphragm, systemic inflammation and achieve remission. Disease of the aortic arch is more common in patients with aTAK. Longer duration of symptoms prior to initiation of immunosuppression, thereby leading to extensive disease and damage, reflects ongoing disease activity as the rule rather than exception in untreated TAK. [ABSTRACT FROM AUTHOR]

The article presents a pilot research which reviewed the results of the Diagnostic and Classification Criteria for Vasculitis (DCVAS) Study to develop diagnostic criteria and update the classification criteria for primary systemic vasculitides.