Rheumatoid arthritis (RA) is a chronic inflammatory disease where the contribution of T cells is now supported by clinical results. Among the cytokines produced by T cells, interleukin (IL)-17A ...(previously known as IL-17) and IL-17F constitute the signature cytokines of the newly described Th17 T helper cell subset. While the effects of IL-17A on RA synoviocytes been well described, those of IL-17F remain less studied. The present review describes the effects of IL-17A and IL-17F on synoviocytes and their contribution to RA pathogenesis. Although IL-17F is less active than IL-17A when used alone, IL-17A and IL-17F induce in synoviocytes a rather similar expression pattern in the presence of tumour necrosis factor α. They enhance their response by stabilising mRNA of cytokines and enhancing receptor expression. They increase the migration, chemokine gene expression and invasiveness of synoviocytes. They contribute to disease chronicity by inhibiting synoviocyte apoptosis. Finally, they enhance metalloprotease secretion leading to cartilage damage. These properties support the combined inhibition of IL-17A and -F to control RA inflammation and joint destruction.
Conventional treatment of eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss) with glucocorticoids, with or without additional immunosuppressive drugs, is limited by partial ...efficacy, frequent toxicity and a high relapse rate. Rituximab is a licensed treatment for granulomatosis with polyangiitis and microscopic polyangiitis and is of potential benefit to patients with EGPA.
Patients with EGPA who received rituximab as single or repeated courses were identified from four vasculitis centres. Standardised data collection was performed, including disease activity status and adverse events, at the time of initial treatment and after 6 and 12 months. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and partial response as a ≥50% reduction in BVAS compared with baseline.
41 patients (21 women) with EGPA treated with rituximab between 2003 and 2013 were identified. 15 (37%) had refractory, 21 (51%) relapsing and 5 (12%) new onset disease. 19 received a single course and 22 received repeat-dose rituximab to prevent relapse. By 6 months, 83% improved with remission in 34% and partial response in 49%, and by 12 months 49% were in remission and 39% had a partial response. Prednisolone doses decreased in all patients by 6 and 12 months. Antineutrophil cytoplasmic antibody positivity at baseline was associated with a higher remission rate at 12 months. Adverse events included 15 infections (6 were severe).
The treatment of EGPA with rituximab resulted in high rates of improvement and reduced requirement of prednisolone. Rituximab may be considered for the treatment of EGPA.
Patients with systemic lupus erythematosus (SLE) are at risk of cytomegalovirus (CMV) infection, due to the disease itself or to drug-induced immunosuppression. Also, active CMV infection may trigger ...or worsen SLE flare-up.
In this retrospective single-centre cohort study, we reported all adult inpatients with a diagnosis of SLE, presenting with active and confirmed CMV infection. The goal was to describe their characteristics and outcomes (evolution of CMV infection, secondary infections and SLE flare-up), and to review the existing literature.
We identified 400 patients with confirmed SLE, including 12 who presented with active CMV infection. Severe CMV manifestations were present in 7 patients treated with immunosuppressive regimen out of 10, and in one patient out of two without immunosuppressive therapy. Six patients developed other infections, and 3 showed characterised SLE flare-up over the 3-month follow-up. All patients were alive at end of follow-up.
Among patients with SLE, CMV infection affected more frequently those treated with immunosuppressive drugs, but treatment-free patients were sometimes severely affected. CMV infection was associated with an increased incidence of SLE flare-up and infectious complications. Our results suggest that early anti-viral chemotherapy may be beneficial in these patients.
The Coronavirus Disease 2019 (COVID-19) epidemic especially worries people with chronic diseases the entire world. In this study, the frequency, and clinical course of COVID-19 infection in patients ...with Celiac disease (CD) were investigated. CD patients' adherence to purchasing gluten free products (GFPs), the strict diet, and how patients' anxiety affects CD symptoms during the COVID-19 outbreak were also examined.
A detailed questionnaire was administered by telephone and emailed to the CD patients to determine the status of these patients in obtaining GFPs, and dietary compliance during the COVID-19 pandemic. State and trait anxiety levels of patients were evaluated using the State-trait Anxiety Inventory (STAI) scale. Additionally, whether patients with CD were diagnosed with COVID-19, and if diagnosed, their clinical course of the disease were investigated.
One hundred and one patients were included in the study. The total number of patients who could obtain GFPs decreased significantly in the pandemic than before the pandemic. The patients' state anxiety index was 40.7±7.9, and the trait anxiety index was 44.5±8.5, and all patients were evaluated as mildly anxious. During the pandemic, two female patients were diagnosed with COVID-19.
CD patients did not have any additional risk compared to other individuals in terms of becoming infected with COVID-19 for patients under gluten free diet, and these patients will have a similar clinical course as individuals without CD.
To describe the outcome and tolerance in patients treated with anti-TNFα in severe and refractory major vessel disease in Behçet's disease (BD).
A multicenter study evaluating 18 refractory BD ...patients with major vessel involvement pulmonary artery (n = 4), aorta (n = 4) or peripheral artery aneurysm (n = 1) and/or pulmonary artery (n = 7), inferior vena cava (n = 5), or intra-cardiac (n = 3) thrombosis or Budd Chiari Syndrome (n = 2) treated with anti-TNFα agents.
Vascular remission was achieved in 16 (89%) patients. The 9 months risk of relapse was significantly higher with conventional immunosuppressants used prior anti-TNFα agents as compared to anti-TNFα therapy OR = 8.7 (1.42–62.6), p = 0.03. The median daily dose of corticosteroids significantly decreased at 12 months. Side effects included infection (n = 4) and pulmonary edema (n = 1).
TNFα-antagonists are safe and might be associated with a decreased risk of relapse at 9 months compared to conventional immunosuppressants in BD patients with major vessels disease.
•Anti-TNFα agents represent an effective and safe therapeutic approach for BD patients with major vessel involvement.•However, relapses can been observed after anti-TNFα withdrawal.•The risk of relapse at 9 months under anti-TNF seems to be decreased compared to that of conventional immunosuppressants.
Objective
Management of nonviral cryoglobulinemia vasculitis has yet to be defined. Rituximab has emerged as a novel and promising therapeutic alternative, but data are scarce. Our objective was to ...evaluate the safety and efficacy of rituximab in nonviral cryoglobulinemia vasculitis in off‐trial real‐life patients.
Methods
Prospective data from the French AutoImmunity and Rituximab (AIR) registry, which includes data on patients with autoimmune disorders treated with rituximab in off‐label conditions, were analyzed.
Results
Twenty‐three patients received treatment with rituximab for cryoglobulinemia vasculitis. Tolerance was marked by the occurrence of side effects in almost half of the patients, including severe infections in 6 (26%) of 23, with a rate of 14.1 per 100 patient‐years. These infections occurred in a particular subset of patients ages >70 years, with essential type II mixed cryoglobulinemia and renal failure with a glomerular filtration rate of <60 ml/minute, and receiving high‐dose corticosteroids. Three of these patients died. In contrast, clinical and immunologic efficacy was noted in all evaluable patients. Clinical relapses occurred in half of the patients after a median time of 13.5 months following rituximab administration, and were more frequent in patients refractory to previous immunosuppressive therapy than in previously untreated patients.
Conclusion
Data from the AIR registry show a dramatic efficacy and a steroid‐sparing effect of rituximab, but also show the occurrence of severe infections in elderly patients with renal failure and high‐dose steroids. The role of rituximab in nonviral cryoglobulinemia vasculitis remains to be defined in well‐designed randomized controlled trials.
Summary
Background
Studies on sarcoidosis in elderly patients are scarce and none have specifically evaluated patients aged ≥75 at onset.
Aim
We aimed to analyse the characteristics of patients with ...sarcoidosis diagnosed after 75 and to compare them with those of younger patients.
Design
Multicenter case–control study comparing elderly-onset sarcoidosis (EOS) with young-onset sarcoidosis (YOS) seen at Lyon University Hospitals between 2006 and 2018.
Methods
Using our institutional database, we included 34 patients in the EOS group and compared them with 102 controls from the YOS group in a 1:3 ratio. Demographic characteristics, medical history, clinical presentation, laboratory and imaging findings, sites of biopsies, histological analyses, treatments and outcomes were recorded using a comprehensive questionnaire.
Results
There were more Caucasians in the EOS group (94.1% vs. 59.8%; P < 0.001), who had significantly more comorbidities (mean, 3.1 ± 2 vs. 1.1 ± 1.6; P < 0.001). In the EOS group, there was less pulmonary involvement (26.5% vs. 49%; P = 0.022), less lymphadenopathy (2.9% vs. 16.7%; P = 0.041), no erythema nodosum (0% vs. 12.8%; P = 0.029) and no arthralgia (0% vs. 25.5%; P = 0.001). Conversely, uveitis was more common in the EOS group (55.9% vs. 20.6%; P < 0.001). Pathological confirmation was obtained significantly less frequently in the EOS group (67.7% vs. 85.3%; P = 0.023). Corticosteroid-related side effects were significantly more common in the EOS group (100% vs. 75.9%; P = 0.030).
Conclusion
Epidemiology and clinical presentation of EOS differs from YOS, including more comorbidities and more uveitis. Elderly patients are more prone to corticosteroid side effects.
Abstract
Background
Renal and splenic infarctions are close entities, with few data concerning their clinical, biological and radiological features.
Aim
The aim of this study was to compare the ...clinical presentations, etiologies and outcomes of acute renal infarctions (RI) and splenic infarctions (SI).
Design
A retrospective multicentric cohort study included patients of the 6 university hospitals in Lyon with RI, SI, or associated RI-SI infarctions was conducted.
Methods
All consecutive cases diagnosed by CT imaging, between January 2013 and October 2016, were included. The exclusion criteria were causes of infarction that did not require additional investigations.
Results
A total of 161 patients were selected for analysis: 34 patients with RI, 104 patients with SI and 23 patients with both RI-SI. Mean ± SD age of patients was 63.2 ± 16.6 years; 59.6% were male. Only 5/161 (3.1%) were healthy prior to the event. The main symptoms were diffuse abdominal pain (26.4%), followed by nausea/vomiting (18.3%) and fever (16.4%).The causes of RI or SI varied significantly within the three groups. Hypercoagulable state was associated with SI, and embolic disease and arterial injury were associated with RI. Extensive (i.e.>2/3 of organ volume) (OR 6.22, 95%CI 2.0119.22) and bilateral infarctions (OR 15.05, 95%CI 1.79–126.78) were significantly associated with hemodynamic shocks. The survival at 1 month follow-up did not significantly differ between the three groups.
Conclusion
Acute RI and SI are heterogenous entities in regards to their clinical presentation, etiology, associated venous or arterial thrombosis, but prognoses were not different at short term follow-up.
The aim of this study was to compare the effects of interleukin (IL)-17A and IL-17F on gene expression and signalling in human rheumatoid arthritis (RA) synoviocytes.
IL-17A- and IL-17F-induced mRNA ...expression was analysed using Affymetrix microarrays. IL-6 and IL-8 secretion was evaluated by ELISA. Inhibition of two receptors (IL-17RA and IL-17RC) was achieved by small interfering RNA (saran). The effects on mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1) and nuclear factor κB (NF-κB) expression and activation were evaluated by western blotting, qRT-PCR and DNA binding assay.
IL-17A and IL-17F induced a molecular pattern characterised by 27 inflammation-related genes for IL-17F and 165 for IL-17A. Virtually all IL-17A and IL-17F inducible genes were dependent on NF-κB activation, whereas a small number were modulated by p38. IL-17A induced activation of all three MAPKs (ERK, p38 and JNK) and downstream transcription factors AP-1 and p65 NF-κB. IL-17F was less potent but induced activation of p50 NF-κB. IL-17A was more potent at inducing IL-6 secretion than IL-17F, which was inactive alone. IL-17A and, to a lesser extent, IL-17F induced TRAF6 but not MyD88. Inhibition of either IL-17RA or IL-17RC expression via siRNA led to near complete abrogation of IL-6 expression mediated by IL-17A and the combination of IL-17F and tumour necrosis factor α.
Like IL-17A, IL-17F regulates proinflammatory gene expression by a very similar but not identical signalling pathway involving IL-17RA and IL-17RC.
Recurrent FUO (fever of unknown origin) is a rare subtype of FUO for which diagnostic procedures are ill-defined and outcome data are lacking.
We performed a retrospective multicentre study of ...patients with recurrent FUO between 1995 and 2018. By multivariate analysis, we identified epidemiological, clinical and prognostic variables independently associated with final diagnosis and mortality.
Of 170 patients, 74 (44%) had a final diagnosis. Being ≥ 65 years of age (OR = 5.2; p < 0.001), contributory history (OR = 10.4; p < 0.001), and abnormal clinical examination (OR = 4.0; p = 0.015) independently increased the likelihood of reaching a diagnosis, whereas lymph node and/or spleen enlargement decreased it (OR = 0.2; p = 0.004). The overall prognosis was good; 58% of patients recovered (70% of those with a diagnosis). Twelve (7%) patients died; patients without a diagnosis had a fatality rate of 2%. Being ≥ 65 years of age (OR = 41.3; p < 0.001) and presence of skin signs (OR = 9.5; p = 0.005) significantly increased the risk of death.
This study extends the known yield of recurrent FUO and highlights the importance of repeated complete clinical examinations to discover potential diagnostic clues during follow-up. Moreover, their overall prognosis is excellent.
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