To determine whether anti-Ro52 antibodies are associated with ILD in pSS.
Retrospective study based on the presence or absence of anti-Ro52 antibodies in patients with pSS. Patients underwent chest ...HRCT at the time of diagnosis or during follow-up.
Sixty-eight patients were included. Two groups were defined by the presence (n = 31) or absence (n = 37) of anti-Ro52 antibodies. ILD was significantly higher in the presence of anti-Ro52 (41.9%, n = 13) versus in the anti-Ro52-negative group (16.2%, n = 6; p = 0.019). Multivariate analysis adjusted for anti-SSA/Ro60, anti-SSB antibodies and rheumatoid factor status confirmed that anti-Ro52 antibodies positivity is a predictive factor for ILD (p = 0.01). Nonspecific interstitial pneumonia was the most common pattern of ILD (31.6%). The majority of patients were diagnosed with pSS simultaneously to ILD (52.6%). In the anti-Ro52-negative group, no patients develop ILD after 5 years of follow-up.
In pSS, the risk of developing ILD is higher in the presence of anti-Ro52 antibodies. In patients with pSS and anti-Ro52 antibodies, a clinical screening and pulmonary functional tests with DLCO is necessary during the follow-up and should comprise chest HRCT if there is a decline in the DLCO or clinical symptoms or inspiratory crackles.
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an acquired autoinflammatory monogenic disease with a poor prognosis whose determinants are not well understood. We aimed ...to describe serious infectious complications and their potential risk factors.
Retrospective multicentre study including patients with VEXAS syndrome from the French VEXAS Registry. Episodes of serious infections were described, and their risk factors were analysed using multivariable Cox proportional hazards models.
Seventy-four patients with 133 serious infections were included. The most common sites of infection were lung (59%), skin (10%) and urinary tract (9%). Microbiological confirmation was obtained in 76%: 52% bacterial, 30% viral, 15% fungal and 3% mycobacterial. Among the pulmonary infections, the main pathogens were
2 (28%),
(21%) and
(19%). Sixteen per cent of severe infections occurred without any immunosuppressive treatment and with a daily glucocorticoid dose ≤10 mg. In multivariate analysis, age >75 years (HR (95% CI) 1.81 (1.02 to 3.24)),
mutation (2.29 (1.10 to 5.10)) and arthralgia (2.14 (1.18 to 3.52)) were associated with the risk of serious infections. JAK inhibitors were most associated with serious infections (3.84 (1.89 to 7.81)) compared with biologics and azacitidine. After a median follow-up of 4.4 (2.5-7.7) years, 27 (36%) patients died, including 15 (56%) due to serious infections.
VEXAS syndrome is associated with a high incidence of serious infections, especially in older patients carrying the
mutation and treated with JAK inhibitors. The high frequency of atypical infections, especially in patients without treatment, may indicate an intrinsic immunodeficiency.
We conducted a prospective multicenter registry of 248 adult patients with immune thrombocytopenia (ITP) treated with rituximab to assess safety. We also assessed response and predictive factors of ...sustained response. In total, 173 patients received 4 infusions of 375 mg/m2 and 72 received 2 fixed 1-g infusions 2 weeks apart. The choice of the rituximab regimen was based on the physician’s preference and not patient characteristics. Overall, 38 patients showed minor intolerance to rituximab infusions; infusions had to be stopped for only 3 patients. Seven showed infection (n = 11 cases), with an incidence of 2.3 infections/100 patient-years. Three patients died of infection 12 to 14 months after rituximab infusions, but the role of rituximab was questionable. In total, 152 patients (61%) showed an overall initial response (platelet count ≥30 × 109/L and ≥2 baseline value). At a median follow-up of 24 months, 96 patients (39%) showed a lasting response. On multivariate analysis, the probability of sustained response at 1 year was significantly associated with ITP duration <1 year (P = .02) and previous transient complete response to corticosteroids (P = .05). The pattern of response was similar with the 2 rituximab regimens. With its benefit/risk ratio, rituximab used off-label may remain a valid option for treating persistent or chronic ITP in adults. This trial was registered at www.clinicaltrials.gov as #NC1101295.
•Tolerance of rituximab is acceptable in ITP, and with its benefit/risk ratio may remain a valid option for treating ITP in adults.
In this review, we summarise the current understanding of the potential link between cancer and anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with ...polyangiitis (Wegener's; GPA) and microscopic polyangiitis (MPA). As is true for many autoimmune or inflammatory rheumatic diseases, AAV diagnosis and therapy are associated with an increased risk of de novo cancer development, likely as a result of impaired immunosurveillance, direct oncogenicity of immunosuppressive agents and perhaps malignant degeneration of tissues undergoing chronic immune stimulation. Data from several studies suggest a standardised incidence ratio of cancer in AAV of 1.6–2.0 compared to the general population and a possibly higher risk in GPA than in MPA. The most prominent cancers observed in AAV include urinary tract cancer, leukaemia and non-melanoma skin cancer. The effect of individual therapeutic agents is difficult to dissect, but cyclophosphamide has emerged as a major contributor to cancer development because of its direct carcinogenic properties. Awareness of cancer risk in AAV calls for increased implementation of measures to prevent or screen for cancer and development of less carcinogenic therapies. Cancer has also been suggested as a potential trigger or cause of AAV. Although some studies found that prior or concomitant history of cancer increases the risk of AAV, available data are inconsistent and suggest that the fraction of AAV that might be attributable to cancer is at best small.
Primary humoral deficiency and secondary B-cell depletion may lead to prolonged Sars-Cov-2 infection due to a decreased viral clearance. Prolonged infection is mainly driven by the lack of ...anti-Sars-Cov-2 immunoglobulin (IVIg) especially in patients with no vaccine response. Anti-spike immunoglobulin can be provided by infusion of convalescent patients' plasma: recent studies highlighted that commercial immunoglobulin show high titers of neutralizing IgG. We conducted a single center retrospective cohort. We included 9 patients (6 males, median age 74 years old): one patient with X-linked agammaglobulinemia and 8 patients treated with rituximab (2 granulomatosis with polyangiitis, 1 neuromyelitis optica, 4 low grade B-cell lymphoma and 1 EBV post-transplant lymphoproliferative disorder). Mean serum globulin was 4 ± 1.6 g/L. 7/8 had received at least 3 doses of mRNA anti-Sars-Cov-2 vaccine (median 4) with no response (anti-Spike IgG 0 for 6 patients). In this specific population requiring oxygen therapy but no intensive care support, the administration of IVIg was well tolerated and provided a swift improvement of clinical status, a significant decrease of inflammation associated to the an improvement of radiological patterns. Our results suggest that immunoglobulin could be used as a salvage therapy as an alternative to convalescent plasma but highly stringent patient selection is required due to the worldwide shortage of IVIg.
Acquired mutations in the UBA1 gene were recently identified in patients with severe adult-onset auto-inflammatory syndrome called VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic). ...However, the precise physiological and clinical impact of these mutations remains poorly defined. Here we study a unique prospective cohort of VEXAS patients. We show that monocytes from VEXAS are quantitatively and qualitatively impaired and display features of exhaustion with aberrant expression of chemokine receptors. In peripheral blood from VEXAS patients, we identify an increase in circulating levels of many proinflammatory cytokines, including IL-1β and IL-18 which reflect inflammasome activation and markers of myeloid cells dysregulation. Gene expression analysis of whole blood confirms these findings and also reveals a significant enrichment of TNF-α and NFκB signaling pathways that can mediate cell death and inflammation. This study suggests that the control of the nflammasome activation and inflammatory cell death could be therapeutic targets in VEXAS syndrome.
Data on the prognosis of non-infectious mixed cryoglobulinaemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking.
The French multicentre and retrospective CryoVas survey ...included 242 patients with non-infectious mixed CryoVas. Causes of death and prognostic factors of survival were assessed and a prognostic score was determined to predict survival at 5 years.
After a median follow-up of 35 months, 42 patients (17%) died. Causes of death were mainly serious infections (50%) and vasculitis flare (19%). One-, 2-, 5- and 10-year overall survival rates were 91%, 89%, 79% and 65%, respectively. A prognostic score, the CryoVas score (CVS), for the prediction of survival at 5 years was devised. Pulmonary and gastrointestinal involvement, glomerular filtration rate <60 ml/min and age >65 years were independently associated with death. At 5 years the death rates were 2.6%, 13.1%, 29.6% and 38.5% for a CVS of 0, 1, 2 and ≥3, respectively. At 1 year the death rates were 0%, 3.2%, 18.5% and 30.8% for a CVS of 0, 1, 2 and ≥3, respectively. The CVS was strongly correlated with the Five Factor Score (FFS) 2009, another prognostic score validated in primary necrotising vasculitis (r=0.82; p<0.0001). The area under the curve for the CVS was 0.74 compared with 0.67 for the FFS, indicating a better performance of the CVS (p=0.052).
In patients with non-infectious mixed CryoVas, the main prognostic factors are age >65 years, pulmonary and gastrointestinal involvement and renal failure. A score including these variables is significantly associated with the prognosis.
Background
An increased risk of thrombosis has been reported in immune thrombocytopenic purpura (ITP), but the characteristics, risk factors of occurrence, recurrence and management of venous ...thromboembolic events (VTE) have been poorly investigated.
Aims
To describe VTE and ITP characteristics, distribution of VTE risk factors and their impact on VTE features and recurrence.
Methods
A retrospective study of patients with ITP and VTE registered in databases of three reference French centres of ITP.
Results
Among 49 patients, 66 VTE were recorded. The platelet count at the time of the first VTE was <100 × 109/L for 28/43 (65%) patients. In total, 19/48 (40%) patients had at least one positive antiphospholipid test result. For the 10 VTE occurring in eight patients with platelet count <50 × 109/L, ITP treatment was efficient in 7. One haemorrhagic complication associated with anticoagulant (AC) therapy was recorded. For 31/49 (63%) patients, long‐term AC therapy could have been discussed after the first VTE, but only 13 received it. A second VTE occurred in 13 (27%) patients. The risk of recurrence was increased in patients with unprovoked VTE before ITP diagnosis or active cancer.
Conclusion
VTE in ITP mainly occurred in the presence of multiple risk factors of TE. A low platelet count does not protect against VTE. Management with AC therapy despite persistently low platelet count seems possible. Risk of VTE recurrence is high, particularly with a history of unprovoked VTE or active cancer. In this setting, indefinite AC therapy could be discussed.
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