The prevalence of eosinophilic granulomatosis with polyangiitis (EGPA; previously known as Churg-Strauss syndrome) is lower than that of other antineutrophil cytoplasm antibody (ANCA)-associated ...vasculitides (AAV's), and only a few randomized controlled trials have been conducted for this rare disease. However, recent international efforts have helped delineate the best treatment approach.
At present, EGPA conventional therapy is by default similar to that of other AAVs. Limited, non-severe EGPA can initially be treated with glucocorticoids (GCs) alone. Patients with life-threatening manifestations and/or major organ involvement must receive a combination of GCs and an immunosuppressant, mainly cyclophosphamide. Remission can be achieved in >85% of patients with these first-line treatments, but vasculitis relapses occur in more than one-third of patients, and about 85% cannot stop GC treatment because of GC-dependent asthma and/or ENT manifestations. A few biologic agents, including rituximab or mepolizumab, are now under investigation after interesting preliminary results. Expert commentary: Treatment for EGPA still has several unmet needs. Several biologic agents are now under investigation in randomized controlled trials, but a few others should be considered soon. Their benefit should be demonstrated for devising more EGPA-tailored therapeutic strategies (ideally GC-free).
There is growing evidence that coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. To date, all patients reported with venous thromboembolic disease and COVID-19 have ...shown evidence of viral pneumonia. Here, we report the case of a 31-year-old patient with unexplained extensive DVT and bilateral pulmonary embolism in the absence of COVID-19 pneumonia, leading to the diagnosis of otherwise asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the context of the COVID-19 pandemic, given the high rates of otherwise asymptomatic patients, testing for SARS-CoV-2 should be performed in all patients with unexplained VTE occurring in COVID-19-endemic areas, even in the absence of other disease manifestations suggestive of SARS-CoV-2 infection.
How Can Hyponatremia and Hemolysis Be Explained? Since blood osmolarity was low (259 mosmol/L) and urine osmolarity was high (508 mosmol/L), the syndrome of inappropriate antidiuretic hormone ...secretion (SIADH) was suspected. Three weeks after the first serologies, C. pneumonia and M. pneumoniae antibodies' rates did not rise, pointing out a cross-serological reactivity with T. gondii antibodies. Since the patient was in a critical condition and despite mild g6pd deficiency, gold standard anti-toxoplasmosis treatment 1 was promptly started after the serological diagnosis of recent T. gondii infection. Physicians should systematically consider acute toxoplasmosis as a possible diagnosis for any infectious syndrome with visceral (especially lung) involvement in patients who have recently travelled to or lived in the Amazonian area. Since lethal cases have been reported and since treatment associating pyrimethamine and sulfadiazine is efficient, such treatment should be promptly started immediately after serological results, without waiting for positive PCR or parasitic isolation.
Abstract Background Immunocompromised patients are at increased risk for severe influenza and invasive pneumococcal diseases. Population-specific vaccine recommendations are thus warranted. This ...study aimed to estimate the prevalence and predictors of influenza and pneumococcal vaccine uptake in a large cohort of patients with secondary immune deficiency. Methods An anonymous online survey was submitted to the members of 11 French associations of immunocompromised patients. The questionnaire included questions concerning underlying disease, care and treatment, flu and pneumococcal vaccine uptake, attitudes and knowledge about vaccination. Factors associated with vaccine uptake were assessed by multivariate logistic regression. Results Among the 10,897 solicited patients, 3653 agreed to participate (33.5%): 75% were female, 20% aged 65+, 79% were followed for an autoimmune disease, 13% were solid organ recipients or waiting for transplantation and 8% were treated for hematological malignancies. 3109 (85%) participants were treated with immunosuppressive therapy. Self-reported vaccine uptake was 59% (95%CI 57–60) against seasonal influenza and 49% (95%CI 47–50) against pneumococcal diseases. Better knowledge of and favorable attitudes toward vaccination were positively associated with vaccine uptake while being treated with a biological therapy was negatively associated. Conclusion Despite specific recommendations regarding immunocompromised patients, influenza and pneumococcal vaccination rates do not reach recommended levels. Targeted information campaigns on vaccination toward these populations should be implemented to improve vaccine coverage and thus reduce the burden of infections.
Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe ...(requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19.
We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 death to 7 discharged from hospital) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021.
Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 20%), sarilumab 200 mg (n=159 38%), or sarilumab 400 mg (n=173 42%). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days 95% CI 9·0 to 15·0) and sarilumab 200 mg (10·0 days 9·0 to 12·0; hazard ratio HR 1·03 95% CI 0·75 to 1·40; log-rank p=0·96) or sarilumab 400 mg (10·0 days 9·0 to 13·0; HR 1·14 95% CI 0·84 to 1·54; log-rank p=0·34), or in proportions of patients alive (77 92% of 84 patients in the placebo group; 143 90% of 159 patients in the sarilumab 200 mg group; difference -1·7 -9·3 to 5·8; p=0·63 vs placebo; and 159 92% of 173 patients in the sarilumab 400 mg group; difference 0·2 -6·9 to 7·4; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% 95% CI -7·7 to 25·5; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group.
This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19.
Sanofi and Regeneron Pharmaceuticals.
IgG4-related disease (IgG4-RD) is characterized by variable tissue or organ involvements sharing common pathological findings. Orbital or orbital adnexa involvement of the disease has been reported ...in a few case series. The aim of our study was to characterize and analyze ophthalmic manifestations from a nationwide French case-series.Patients with IgG4-RD and orbital or orbital adnexa involvement included in the French multicentric IgG4-RD case-registry were identified. Only patients fulfilling "modified" comprehensive diagnostic criteria with pathological documentation were retained for the study. Clinical, biological, pathological, radiological findings and data regarding the response to treatment were retrospectively analyzed.According to our data registry, the frequency of IgG4-related ophthalmic disease (IgG4-ROD) was 17%. Mean age at diagnosis was 55.1 ± 7.1 years with a male/female ratio of 2.2. The 19 cases of IgG4-ROD consisted of lacrimal gland (68.4%), soft tissue (57.9%), extra-ocular muscles (36.8%), palpebral (21.1%), optical nerve (10.5%), orbital bone (10.5%), and mononeuritis (V1 and/or V2, 10.5%) involvements. IgG4-ROD was bilateral in 57.9% of cases. Extra-ophthalmic manifestations were reported in 78.9% of cases. All patients responded to prednisone but two-thirds of patients relapsed within a mean (SD) of 9.8 (3.5) months and 72.2% required long-term glucocorticoids and/or immunosuppressive agents. Eight patients were treated by rituximab with a favorable response in 87.5% of cases.Lacrimal involvement is the most frequent ophthalmic manifestation of IgG4-RD and is frequently associated with extra-orbital manifestations. Despite initial favorable response to steroids, the long-term management of relapsing patients needs to be improved.
Alternatives are urgently needed in patients with CD3− CD4+ lymphocytic-variant hypereosinophilic syndrome (L-HES) requiring high-level steroids or who are unresponsive and/or intolerant to ...conventional alternative therapies. We report five L-HES patients (44–66 years) with cutaneous involvement (n = 5) and persistent eosinophilia (n = 3) despite conventional therapies, who successfully received JAK inhibitors (tofacitinib n = 1, ruxolitinib n = 4). JAKi led to complete clinical remission in the first 3 months in all (with prednisone withdrawal in four). Absolute eosinophil counts normalized in cases receiving ruxolitinib, while reduction was partial under tofacitinib. After switch from tofacitinib to ruxolitinib, complete clinical response persisted despite prednisone withdrawal. The clone size remained stable in all patients. After 3–13 months of follow-up, no adverse event was reported. Prospective clinical trials are warranted to examine the use of JAKi in L-HES.
•Alternatives are urgently needed in patients with steroids-dependent lymphocytic variant hypereosinophilic syndrome•JAK inhibition with ruxolitinib led to complete clinical and hematological remission in five patients with refractory HES•Size of the clonal CD3− CD4+ population remained stable despite clinical response to ruxolitinib•Randomized controlled trials are mandatory to optimize the use of JAKi in lymphocytic variant hypereosinophilic syndrome Please incorporate and proceed
Abstract Objective To develop disease-specific recommendations for the diagnosis and management of eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome) (EGPA). Methods The EGPA ...Consensus Task Force experts comprised 8 pulmonologists, 6 internists, 4 rheumatologists, 3 nephrologists, 1 pathologist and 1 allergist from 5 European countries and the USA. Using a modified Delphi process, a list of 40 questions was elaborated by 2 members and sent to all participants prior to the meeting. Concurrently, an extensive literature search was undertaken with publications assigned with a level of evidence according to accepted criteria. Drafts of the recommendations were circulated for review to all members until final consensus was reached. Results Twenty-two recommendations concerning the diagnosis, initial evaluation, treatment and monitoring of EGPA patients were established. The relevant published information on EGPA, antineutrophil-cytoplasm antibody-associated vasculitides, hypereosinophilic syndromes and eosinophilic asthma supporting these recommendations was also reviewed. Discussion These recommendations aim to give physicians tools for effective and individual management of EGPA patients, and to provide guidance for further targeted research.
Yet, ICI therapy is associated with frequent and potentially organ or life-threatening immune-related adverse events (irAEs), generally mimicking autoimmune or inflammatory conditions.4 Rheumatic ...disorders have been reported in this setting, mainly rheumatoid arthritis, polymyalgia rheumatica and systemic lupus erythematosus.1–3 Vasculitis seems to occur more seldom, with predominantly medium-vessel to large-vessel involvement.5 Here, we report on a patient with eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) following treatment with ICI for a stage IV melanoma. ...in the context of asthma, hypereosinophilia, pulmonary infiltrates, arthritis and paranasal sinus abnormalities, the diagnosis of EGPA (formerly Churg-Strauss syndrome) was retained6 and the patient was treated with ICS/LABA and intraarticular corticosteroid injection. Moderate asymptomatic hypereosinophilia has been reported in up to 3% of patients treated with ICI.7 To our knowledge, this is the first case report of a patient with ICI-induced EGPA. Since the patient showed no evidence of genuine vasculitis, one might also classify him as having hypereosinophilic asthma with systemic manifestations.8 The pathophysiological process leading to eosinophilia remains unknown, but the high level of serum IgE strongly suggests Th2-mediated reactive hypereosinophilia induced by ICI.
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