We report a case of a 62‐year‐old man who developed cerebral venous sinus thrombosis with subarachnoid hemorrhage and concomitant thrombocytopenia, which occurred 13 days after ChAdOx1 nCov‐19 ...injection. The patient died in the intensive care unit after heparin infusion and platelet transfusion. The key clinical purpose of this case report is to better understand how to confirm vaccine‐induced immune thrombotic thrombocytopenia VITT). VITT diagnosis was made using 14C‐serotonin release and flow cytometry evaluating activation and platelet microvesicles on washed platelets. Four control patients were examined: a patient with heparin‐induced thrombocytopenia (HIT), two patients with thrombotic events without thrombocytopenia after ChAdOx1 nCov‐19 or BNT162b2, and a patient with suspected HIT and an excluded diagnosis. We evidenced in the VITT case a high level of IgG anti–platelet factor 4–heparin antibodies associated with a high level of platelet activation in the absence of heparin. Conversely, the functional assays were negative in the patients with thrombosis without thrombocytopenia.
Stratifying the risk of death in SSc-related interstitial lung disease (SSc-ILD) is a challenging issue. The extent of lung fibrosis on high-resolution CT (HRCT) is often assessed by a visual ...semiquantitative method that lacks reliability. We aimed to assess the potential prognostic value of a deep-learning-based algorithm enabling automated quantification of ILD on HRCT in patients with SSc.
We correlated the extent of ILD with the occurrence of death during follow-up, and evaluated the additional value of ILD extent in predicting death based on a prognostic model including well-known risk factors in SSc.
We included 318 patients with SSc, among whom 196 had ILD; the median follow-up was 94 months (interquartile range 73-111). The mortality rate was 1.6% at 2 years and 26.3% at 10 years. For each 1% increase in the baseline ILD extent (up to 30% of the lung), the risk of death at 10 years was increased by 4% (hazard ratio 1.04, 95% CI 1.01, 1.07, P = 0.004). We constructed a risk prediction model that showed good discrimination for 10-year mortality (c index 0.789). Adding the automated quantification of ILD significantly improved the model for 10-year survival prediction (P = 0.007). Its discrimination was only marginally improved, but it improved prediction of 2-year mortality (difference in time-dependent area under the curve 0.043, 95% CI 0.002, 0.084, P = 0.040).
The deep-learning-based, computer-aided quantification of ILD extent on HRCT provides an effective tool for risk stratification in SSc. It might help identify patients at short-term risk of death.
To assess the association of gender with clinical expression, health-related quality of life (HRQoL), disability, and self-reported symptoms of depression and anxiety in patients with systemic ...sclerosis (SSc).
SSc patients fulfilling the American College of Rheumatology and/or the Leroy and Medsger criteria were assessed for clinical symptoms, disability, HRQoL, self-reported symptoms of depression and anxiety by specific measurement scales.
Overall, 381 SSc patients (62 males) were included. Mean age and disease duration at the time of evaluation were 55.9 (13.3) and 9.5 (7.8) years, respectively. One-hundred-and-forty-nine (40.4%) patients had diffuse cutaneous SSc (dcSSc). On bivariate analysis, differences were observed between males and females for clinical symptoms and self-reported symptoms of depression and anxiety, however without reaching statistical significance. Indeed, a trend was found for higher body mass index (BMI) (25.0 4.1 vs 23.0 4.5, p = 0.013), more frequent dcSSc, echocardiography systolic pulmonary artery pressure >35 mmHg and interstitial lung disease in males than females (54.8% vs 37.2%, p = 0.010; 24.2% vs 10.5%, p = 0.003; and 54.8% vs 41.2%, p = 0.048, respectively), whereas calcinosis and self-reported anxiety symptoms tended to be more frequent in females than males (36.0% vs 21.4%, p = 0.036, and 62.3% vs 43.5%, p = 0.006, respectively). On multivariate analysis, BMI, echocardiography PAP>35 mmHg, and anxiety were the variables most closely associated with gender.
In SSc patients, male gender tends to be associated with diffuse disease and female gender with calcinosis and self-reported symptoms of anxiety. Disease-associated disability and HRQoL were similar in both groups.
Anti-endothelial cell antibodies (AECAs) have been identified in patients with systemic sclerosis (SSc) with and without pulmonary arterial hypertension (PAH) and in patients with idiopathic ...pulmonary arterial hypertension (iPAH). However, their target antigens remain poorly identified. Sera from 24 patients with SSc without PAH, 20 patients with SSc with PAH, 30 with iPAH and 12 healthy controls were collected. Target antigens were identified by two-dimensional electrophoresis and immunoblotting in protein extracts of human umbilical vein endothelial cells. Targeted antigens were identified by mass spectrometry. Serum immunoglobulin G from patients with SSc with or without PAH and patients with iPAH specifically recognised 110, 82 and 37 protein spots, respectively. Among others, target antigens of AECAs included lamin A/C, tubulin β-chain and vinculin. One-dimension immunoblotting experiments confirmed the identification of lamin A/C and tubulin β-chain. In conclusion, our results confirm the presence of AECA in patients with systemic sclerosis with and without pulmonary arterial hypertension and in those with idiopathic pulmonary arterial hypertension, and provide evidence for the identification of target antigens of these autoantibodies including lamin A/C and tubulin β-chain.
Abstract Objectives Ischemic digital ulcers (DU) represent a major complication of systemic sclerosis (SSc). We investigated the impact of controlling the ulcerative disease on disability, pain, and ...quality of life in SSc patients receiving bosentan. Methods ECLIPSE (Study AC-052-517) is a 2-year prospective, multicenter, and observational study. Patients with SSc who experienced at least 1 DU in the previous year and received bosentan were included between October 2009 and March 2011. Disability scores Cochin Hand Function Scale (CHFS) and Health Assessment Questionnaire Disability Index (HAQ-DI), pain scores (visual analog scale), and quality-of-life scores (SF-36) were collected at inclusion and 1 year later (primary endpoint). A controlled ulcerative disease was defined by the absence of ongoing/new DU episode between inclusion and 1-year follow-up. Results Data were available at 1 year for 120 patients out of 190 included. During follow-up, 46 (38.3%) patients experienced a new DU episode. The number of DU per patient decreased from 1.4 ± 1.8 at inclusion to 0.6 ± 1.6 ( p < 0.0001) at 1 year. Disability scores decreased from 1.0 ± 0.7 to 0.9 ± 0.7 ( p = 0.04) for the HAQ-DI and from 29 ± 20 to 25 ± 20 ( p = 0.005) for the CHFS; the pain score decreased from 4.3 ± 3.1 to 2.9 ± 2.8 ( p < 0.0001). This improvement was attributed to patients with a controlled ulcerative disease (48.3%), who significantly improved HAQ-DI ( p = 0.04), CHFS ( p = 0.04), and pain score ( p = 0.046). Conclusions In patients with SSc, control of the ulcerative disease for 1 year was associated with significant attenuation of hand disability.
Age at onset of large-vessel vasculitis (LVV) is commonly used to distinguish giant cell arteritis (GCA) and Takayasu arteritis (TA). However, LVV between age 50 and 60 years may be difficult to ...classify.
We conducted a retrospective study including LVV aged between 50 and 60 years at onset (LVV50–60, cases) and compared them to LVV aged over 60 years (LVV>60, controls). LVV was defined histologically and/or morphologically. Controls fulfilled ACR 1990 criteria for GCA or presented isolated aortitis.
We included 183 LVV50–60 and 183 gender-matched LVV>60. LVV50–60 had more frequent peripheral limb manifestations (23 vs. 5%), and less frequent cephalic (73 vs. 90%) and ocular signs (17 vs. 27%) than LVV>60. Compared to LVV>60, CT angiography and PET/CT scan were more frequently abnormal in LVV50–60 (74 vs. 38%, and 90 vs. 72%, respectively), with aorta being more frequently involved (78 vs. 47%). By multivariate analysis, absence of cephalic symptoms, presence of peripheral limb ischemia and aorta involvement, and increased CRP level were significantly associated with LVV50–60 presentation compared to LVV>60. At last follow-up, compared to LVV>60, LVV50–60 received significantly more lines of treatment (2 vs. 1), more frequent biologics (12 vs. 3%), had more surgery (10 vs. 0%), and had higher prednisone dose (8.8 vs. 6.5 mg/d) at last follow-up,
LVV onset between 50 and 60 years identifies a subset of patients with more frequent aorta and peripheral vascular involvement and more refractory disease compared to patients with LVV onset after 60.
•LVV50-60 have more frequent aorta and peripheral limb involvement.•LVV50-60 have more refractory disease.•LVV50-60 should be probably treated more aggressively and monitored for aortic complications.
To evaluate the effects and safety of 6-month intravenous cyclophosphamide (CYC) followed by 18-month oral azathioprine (AZA) therapy in patients with systemic sclerosis (SSc) and worsening ...interstitial lung disease (ILD).
All patients presented with ILD and worsened forced vital capacity (FVC) and/or total lung capacity of more than 10% and/or DLCO of more than 15% during the previous year. Treatment was 6 monthly pulses of 0.6 g/m(2) CYC followed by oral AZA for 18 months on disease stabilization or improvement. The endpoint was the rate of percentage change in pulmonary function tests (PFT) after 6 and 24 months.
Twenty-seven patients with SSc (20 females) were recruited. Age and disease duration before CYC therapy were (mean +/- SD) 49.4 +/- 15 years and 75.5 +/- 87.8 months, respectively. Mean baseline FVC was 67% +/- 19% of predicted value. At 6 months, in 7 (26%) patients disease was improved, in 12 (44%) stabilized, and in 8 (30%) worsened. Among the 19 (70%) responders, 15 received AZA and 4 declined. Twenty-three completed 2-year followup, 3 died, and one dropped out. Six (22.2%) had improved, 8 (29.6.%) were stable, and 13 (48.2%) had worsened. Evolution of the slope of FVC (in % per year) varied from -15.5 prior to treatment to +3 (p = 0.004) at 6 months and to +1 (p < 5 x 10(-5)) at 24 months.
Intravenous CYC followed by oral maintenance immunosuppressive therapy for worsening ILD was well tolerated and was associated with stable or improved PFT in 70% and 51.8% of SSc patients at 6 months and 2 years, respectively.
Background
Granulomatous disease (GD) will develop in a subset of patients with common variable immunodeficiency (CVID). Little is known about the efficacy of therapeutic agents used for treating ...this disorder.
Objective
To evaluate the efficacy of immunosuppressive drugs with the help of a set of clinical, biological and radiological criteria.
Method
Clinical and laboratory features of CVID patients were collected from the French DEFI cohort, a prospective study on adults with hypogammaglobulinemia. The medical charts of 55 patients (93 %) of the GD cohort were reviewed.
Results
Among 436 subjects with CVID, 59 patients (13.5 %) were diagnosed with GD. Of the 55 patients in whom medical charts were available, 32 patients received treatment for the granulomatous disease. Corticosteroids were the most frequently used drug. Complete response to treatment was infrequent. It was achieved with corticosteroids, cyclophosphamide, hydroxychloroquine, rituximab and methotrexate. Azathioprine, cyclosporine, mycophenolate mofetil, sirolimus, infliximab and thalidomide led to partial or absence of response. Complete and partial responses were observed in lymph nodes, lungs, liver, skin, bone marrow and central nervous system. Absent of response for gastrointestinal tract granulomas was noted in all cases of treatment attempt.
Conclusion
CVID patients with GD exhibit a particular biological phenotype. Treatment should be considered in any symptomatic patient or if there is evidence of organ dysfunction. Corticosteroids are the drug of choice in most instances but response to treatment is often unsatisfactory.
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