We aimed to compare the efficacy of steroids alone or associated with immunosuppressive drugs for the prevention of relapse in cardiac sarcoidosis (CS).
In this monocentric multidisciplinary ...retrospective single center study, all consecutive patients with histologically proven sarcoidosis hospitalized from January 2012 to December 2016 were considered. All patients with symptomatic CS were studied. Patients received steroids or steroids plus immunosuppressive drugs (IS) for CS treatment at diagnosis. The efficacy of each treatment strategy (steroids vs steroids + IS) was assessed by the cardiac relapse rate over follow up.
326 consecutive patients with histologically proven sarcoidosis were screened. Among them, 36 (11%) had symptomatic CS (20 (55.5%) men, median age at diagnosis 48.5 22.8–76). Twenty-four patients received steroids and 12 received steroids + IS (azathioprine n = 5, methotrexate n = 5, cyclophosphamide n = 2) at CS diagnosis. Over a median follow up of 3.6 1–15.2 years, 13 (36.1%) patients suffered a cardiac relapse including reduced left ventricular ejection fraction (LVEF, n = 4), third degree heart block (n = 2), atrio-ventricular (n = 1) or ventricular (n = 1) tachycardia and sudden cardiac death (n = 1). Except for a higher frequency of black patients in patients receiving IS, CS features at diagnosis and median time to relapse did not significantly differ between patients who did or did not receive IS. Relapse rate was 45.8% in the steroids group versus 16.7% in the steroids + IS group (p = 0.048).
In cardiac sarcoidosis, the combination of steroids with immunosuppressive drugs might reduce the risk of cardiac relapse, as compared to steroids alone.
•Heart involvement is the leading cause of death in sarcoidosis•Evidence-based data regarding cardiac sarcoidosis treatment are poor•Steroids and immunosuppressive drugs may be more effective than steroids alone in preventing cardiac sarcoidosis relapse.
In systemic lupus erythematosus (SLE), autoantibody production can lead to kidney damage and failure, known as lupus nephritis. Basophils amplify the synthesis of autoantibodies by accumulating in ...secondary lymphoid organs. Here, we show a role for prostaglandin D2 (PGD2) in the pathophysiology of SLE. Patients with SLE have increased expression of PGD2 receptors (PTGDR) on blood basophils and increased concentration of PGD2 metabolites in plasma. Through an autocrine mechanism dependent on both PTGDRs, PGD2 induces the externalization of CXCR4 on basophils, both in humans and mice, driving accumulation in secondary lymphoid organs. Although PGD2 can accelerate basophil-dependent disease, antagonizing PTGDRs in mice reduces lupus-like disease in spontaneous and induced mouse models. Our study identifies the PGD2/PTGDR axis as a ready-to-use therapeutic modality in SLE.
Abstract
IFNα and anti-IFNα autoantibodies have been implicated in susceptibility both for systemic lupus erythematosus (SLE) and viral infection. We aimed to analyze the SLE disease phenotype and ...risk for infection associated with anti-IFN-α IgG autoantibodies in SLE patients In this multidisciplinary retrospective single referral center study, all consecutive patients with SLE admitted between January 1st and November 30th 2020 were considered. All subjects fulfilled the ACR/EULAR 2019 criteria for SLE. Anti-IFNα IgG autoantibodies were quantified at admission by ELISA. Demographic, medical history, laboratory, treatment, and outcome data were extracted from electronic medical records using a standardized data collection form. 180 patients female 87.2%, median age of 44.4 (34–54.2) years were included. The median disease duration was 10 years 4–20 with a median SLEDAI score of 2 0–4 at study time. Fifty-four (30%) patients had a past-history of lupus nephritis. One hundred and forty-four (80%) had received long-term glucocorticoids and 99 (55%) immunosuppressive drugs. Overall, 127 infections—mostly bacterial and viral—were reported in 95 (52.8%) patients. Twenty SLE patients (11.1%) had positive anti-IFNα IgG autoantibodies with a titer ranging from 10 to 103 UA/mL. Age, sex, SLE phenotype and treatment did not significantly differ between SLE patients with or without anti-IFNα. Infection rate was similar in both groups except for tuberculosis which was more frequent in patients with anti-IFNα (20% vs. 3.1%,
p
= 0.01). The prevalence of autoantibodies against IFNα is high in SLE and associated with a higher frequency of tuberculosis.
Abstract Objectives Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory syndrome that can occur during systemic lupus erythematosus (SLE). Data on MAS in adult SLE patients ...are very limited. The aim of this study is to describe the clinical characteristics, laboratory findings, treatments, and outcomes of a large series of SLE-associated MAS. Methods. We conducted a retrospective study that included 103 episodes of MAS in 89 adult patients with SLE. Results 103 episodes in 89 adult patients were analyzed. Median age at first MAS episode was 32 (18–80) years. MAS was inaugural in 41 patients (46%).Thirteen patients relapsed. Patients had the following features: fever (100% episodes), increased serum levels of AST (94.7%), LDH (92.3%), CRP (84.5%), ferritin (96%), procalcitonin (41/49 cases). Complications included myocarditis ( n = 22), acute lung injury ( n = 15) and seizures ( n = 11). In 33 episodes, patients required hospitalization in an ICU and 5 died. Thrombocytopenia and high CRP levels were associated independently with an increased risk for ICU admission. High dose steroids alone as first line therapy induced remission in 37/57 cases (64%). Additional medications as first or second line therapies included IV immunoglobulins ( n = 22), cyclophosphamide ( n = 23), etoposide ( n = 11), rituximab ( n = 3). Etoposide and cyclophosphamide-based regimens had the best efficacy. Conclusion MAS is a severe complication and is often inaugural. High fever and high levels of AST, LDH, CRP, ferritin and PCT should be considered as red flags for early diagnosis. High dose steroids lead to remission in two third of cases. Cyclophosphamide or etoposide should be used for uncontrolled/severe forms.
Shiga toxin-producing
-associated hemolytic uremic syndrome (STEC-HUS) is a form of thrombotic microangiopathy secondary to an infection by an enterohemorrhagic
. Historically considered a pediatric ...disease, its presentation has been described as typical, with bloody diarrhea at the forefront. However, in adults, the clinical presentation is more diverse and makes the early diagnosis hazardous. In this review, we review the epidemiology, most important outbreaks, physiopathology, clinical presentation and prognosis of STEC-HUS, focusing on the differential features between pediatric and adult disease. We show that the clinical presentation of STEC-HUS in adults is far from typical and marked by the prevalence of neurological symptoms and a poorer prognosis. Of note, we highlight knowledge gaps and the need for studies dedicated to adult patients. The differences between pediatric and adult patients have implications for the treatment of this disease, which remains a public health threat and lack a specific treatment.
The emergence of rituximab biosimilars offers the prospect of significant savings to the healthcare system. However, these drugs have never been evaluated for treating immune thrombocytopenia (ITP). ...This was an observational, matched study. We included adults who received a rituximab biosimilar for ITP. Each rituximab-naïve biosimilar patient was matched with two controls from the historic ITP-ritux registry. For non-naïve patients, we compared the response to the biosimilar with that observed with the reference product. Response status was defined according to international criteria. We included 107 patients; 55 receiving Rixathon™ and 52 Truxima™. Three months after the first infusion of rituximab biosimilars, the overall response rate was 47/74 (63.5%) versus 76/142 (53.5%) for the matched controls receiving the reference product (p = .13). The 3-month overall response rate was 76.5% for Rixathon™ versus 51.5% for the matched control group (p = .01) and 21/40 (52.5%) for Truxima™ versus 41/74 (55.4%) for the matched controls (p = .81). For non-naïve patients, the response pattern was similar to that observed previously with the reference product. Safety was analogous to that observed with the reference product. Rituximab biosimilars seemed safe and effective for ITP treatment.
What is the context?
Immune thrombocytopenia (ITP) is an autoimmune disease defined by a low platelet count without any other cause of thrombocytopenia. Patients with ITP may experience severe bleedings.
Rituximab, a biotechnological therapy, is a valid second-line treatment option for ITP.
Biotechnological therapies are expensive. Because the patent expiratory date of the reference product of Rituximab expired, highly similar drugs called biosimilars have been developed and used in ITP treatment without any direct evaluation in this particular disease.
What is new?
In this study, we evaluate the efficacy and safety of rituximab biosimilars versus the reference product for treating adult ITP
We included adults who received a rituximab biosimilar for ITP. Each rituximab-naïve biosimilar patient was matched with two controls from a historic registry that included ITP patients treated by the reference product. For non-naïve patients, we compared the response to the biosimilar with that observed with the reference product.
For naïve and non-naïve patients, the response pattern was similar to that observed previously with the reference product. Safety was analogous to that observed with the reference product.
What is the impact?
This study provides further evidence that rituximab biosimilars are safe and effective for immune thrombocytopenia treatment.
Cardiovascular disease (CVD) is the main cause of death in systemic lupus erythematous (SLE) patients. The Framingham score underestimates the risk for CVD in this population. Our study aimed to ...determine whether serum high-sensitivity cardiac troponin T (HS-cTnT) might help to identify SLE patients at risk for CVD.
The presence of carotid plaques was prospectively assessed by ultrasound in 63 consecutive SLE patients asymptomatic for CVD and 18 controls. Serum HS-cTnT concentration was measured using the electrochemiluminescence method. Factors associated with carotid plaques were identified and multivariate analysis was performed.
Framingham score was low in both SLE patients (median 1 (range 1-18%)) and controls (1 (1-13%)). Nevertheless, 23 (36.5%) SLE patients, but only 2 (11.1%) controls (p = 0.039), had carotid plaque detected by vascular ultrasound. In the multivariate analysis, only age (p = 0.006) and SLE status (p = 0.017) were independently associated with carotid plaques. Serum HS-cTnT concentration was detectable (i.e. >3 ng/L) in 37 (58.7%) SLE patients and 6 (33.3%) controls (p = 0.057). Interestingly, 87% of SLE patients with carotid plaques, but only 42.5% of SLE patients without plaques (p < 0.001), had detectable HS-cTnT. Conversely, 54.5% of SLE patients with detectable HS-cTnT, but only 11.5% with undetectable HS-cTnT (p < 0.001), had a carotid plaque. In the multivariate analysis, only body mass index (p = 0.006) and HS-cTnT (p = 0.033) were statistically associated with carotid plaques in SLE patients. Overall, the risk of having a carotid plaque was increased by 9 (odds ratio 9.26, 95% confidence interval 1.55-90.07) in SLE patients in whom HS-cTnT was detectable in serum.
Serum HS-cTnT level is high and associated with carotid plaques in SLE patients who are at an apparently low risk for CVD according to the Framingham score. HS-cTnT may be a useful biomarker for SLE-associated atherosclerosis.
We conducted a retrospective study on hemolytic uremic syndrome caused by Shiga toxin–producing Escherichia coli (STEC) in 96 adults enrolled in the cohort of the National Reference Center for ...Thrombotic Microangiopathies network in France during 2009–2017. Most infections were caused by STEC strains not belonging to the O157 or O104 serogroups. Thirty (31.3%) patients had multiple risk factors for thrombotic microangiopathy. In total, 61 (63.5%) patients required dialysis, 50 (52.1%) had a serious neurologic complication, 34 (35.4%) required mechanical ventilation, and 19 (19.8%) died during hospitalization. We used multivariate analysis to determine that the greatest risk factors for death were underlying immunodeficiency (hazard ratio 3.54) and severe neurologic events (hazard ratio 3.40). According to multivariate analysis and propensity score-matching, eculizumab treatment was not associated with survival. We found that underlying conditions, especially immunodeficiency, are strongly associated with decreased survival in adults who have hemolytic uremic syndrome caused by STEC.
Black people are at increased risk of thrombotic thrombocytopenic purpura (TTP). Whether clinical presentation of TTP in Black patients has specific features is unknown. We assessed here differences ...in TTP presentation and outcome between Black and White patients. Clinical presentation was comparable between both ethnic groups. However, prognosis differed with a lower death rate in Black patients than in White patients (2.7% versus 11.6%, respectively, P = .04). Ethnicity, increasing age and neurologic involvement were retained as risk factors for death in a multivariable model (P < .05 all). Sixty-day overall survival estimated by the Kaplan-Meier curves and compared with the Log-Rank test confirmed that Black patients had a better survival than White patients (P = .03). Salvage therapies were similarly performed between both groups, suggesting that disease severity was comparable. The comparison of HLA-DRB1*11, -DRB1*04 and -DQB1*03 allele frequencies between Black patients and healthy Black individuals revealed no significant difference. However, the protective allele against TTP, HLA-DRB1*04, was dramatically decreased in Black individuals in comparison with White individuals. Black people with TTP may have a better survival than White patients despite a comparable disease severity. A low natural frequency of HLA-DRB1*04 in Black ethnicity may account for the greater risk of TTP in this population.
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