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We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.

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., (© 2024. The Author(s).)

Background: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome')., Objectives: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome., Methods: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded., Results: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis., Conclusions: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation., (© 2021 British Association of Dermatologists.)

Because Q fever is mostly diagnosed serologically, localizing a persistent focus of Coxiella burnetii infection can be challenging. F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) could be an interesting tool in this context.We performed a retrospective study on patients diagnosed with C burnetii infection, who had undergone F-FDG PET/CT between 2009 and 2015. When positive F-FDG PET/CT results were obtained, we tried to determine if it changed the previous diagnosis by discovering or confirming a suspected focus of C burnetii infection.One hundred sixty-seven patients benefited from F-FDG PET/CT. The most frequent clinical subgroup before F-FDG PET/CT was patients with no identified focus of infection, despite high IgG1 serological titers (34%). For 59% (n = 99) of patients, a hypermetabolic focus was identified. For 62 patients (62.6%), the positive F-FDG PET/CT allowed the diagnosis to be changed. For 24 of them, (38.7%), a previously unsuspected focus of infection was discovered. Forty-two (42%) positive patients had more than 1 hypermetabolic focus. We observed 21 valvular foci, 34 vascular foci, and a high proportion of osteoarticular localizations (n = 21). We also observed lymphadenitis (n = 27), bone marrow hypermetabolism (n = 11), and 9 pulmonary localizations.We confirmed thatF-FDG PET/CT is a central tool in the diagnosis of C burnetii focalized persistent infection. We proposed new diagnostic scores for 2 main clinical entities identified using F-FDG PET/CT: osteoarticular persistent infections and lymphadenitis.

Background: Coxiella burnetii endocarditis is considered to be a late complication of Q fever in patients with preexisting valvular heart disease (VHD). We observed a large transient aortic vegetation in a patient with acute Q fever and high levels of IgG anticardiolipin antibodies (IgG aCL). Therefore, we sought to determine how commonly acute Q fever could cause valvular vegetations associated with antiphospholipid antibody syndrome, which would be a new clinical entity., Methods: We performed a consecutive case series between January 2007 and April 2014 at the French National Referral Center for Q fever. Age, sex, history of VHD, immunosuppression, and IgG aCL assessed by enzyme-linked immunosorbent assay were tested as potential predictors., Results: Of the 759 patients with acute Q fever and available echocardiographic results, 9 (1.2%) were considered to have acute Q fever endocarditis, none of whom had a previously known VHD. After multiple adjustment, very high IgG aCL levels (>100 immunoglobulin G-type phospholipid units; relative risk [RR], 24.9 [95% confidence interval {CI}, 4.5-140.2]; P = .002) and immunosuppression (RR, 10.1 [95% CI, 3.0-32.4]; P = .002) were independently associated with acute Q fever endocarditis., Conclusions: Antiphospholipid antibody syndrome with valvular vegetations in acute Q fever is a new clinical entity. This would suggest the value of systematically testing for C. burnetii in antiphospholipid-associated cardiac valve disease, and performing early echocardiography and antiphospholipid dosages in patients with acute Q fever., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

The association between cancer and sarcoidosis is controversial. Some epidemiological studies show an increase of the incidence of cancer in patients with sarcoidosis but only few cases of sarcoidosis following cancer treatment have been reported. We conducted a retrospective case study from internal medicine and oncology departments for patients presenting sarcoidosis after solid cancer treatment. We also performed a literature review to search for patients who developed sarcoidosis after solid cancer. We describe the clinical, biological, and radiological characteristics and outcome of these patients. Twelve patients were included in our study. Various cancers were observed with a predominance of breast cancer. Development of sarcoidosis appeared in the 3 years following cancer and was asymptomatic in half of the patients. The disease was frequently identified after a follow-up positron emission tomography computerized tomography evaluation. Various manifestations were observed but all patients presented lymph node involvement. Half of the patients required systemic therapy. With a median follow-up of 73 months, no patient developed cancer relapse. Review of the literature identified 61 other patients for which the characteristics of both solid cancer and sarcoidosis were similar to those observed in our series. This report demonstrates that sarcoidosis must be considered in the differential diagnosis of patients with a history of malignancy who have developed lymphadenopathy or other lesions on positron emission tomography computerized tomography. Histological confirmation of cancer relapse is mandatory in order to avoid unjustified treatments. This association should be consider as a protective factor against cancer relapse.

Objective: In this article, we report and discuss the clinical presentation and management of idiosyncratic drug-induced agranulocytosis (neutrophil count <0.5 × 10(9)/l)., Results/conclusions: Idiosyncratic drug-induced agranulocytosis remains a potentially serious adverse event owing to the frequency of severe sepsis with severe deep tissue infections (e.g., pneumonia), septicemia and septic shock in approximately two-thirds of all hospitalized patients. However, several prognostic factors have recently been identified that may be helpful in practice to identify 'susceptible' patients. Old age (>65 years), septicemia or shock, metabolic disorders such as renal failure and a neutrophil count below 0.1 × 10(9)/l are currently consensually accepted as poor prognostic factors. In this potentially life-threatening disorder, modern management with broad-spectrum antibiotics and hematopoietic growth factors (particularly granulocyte colony-stimulating factor) is likely to improve prognosis. Thus, with appropriate management, the mortality rate from idiosyncratic drug-induced agranulocytosis is currently approximately 5%.

Microcrystalline arthritis sometimes have atypical localizations and presentations. The crowned dens syndrome, due to hydroxyapatite or calcium pyrophosphate deposits in peri-odontoid ligaments of the atlas, can provoke acute or chronic cervicalgia or misleading presentations such as meningitidis or fever of unknown origin. We present a particularly severe new case requesting urgent surgery, and a literature review to alert clinicians and prevent misdiagnosing this syndrome. Indeed, calcifications may be very discrete or just incidental and prevent a complete diagnostic approach.

Background: Nonrandom distribution of hepatitis C virus (HCV) quasispecies (compartmentalization between blood plasma and leukocytes) suggests the presence of HCV leukotropic variants. HCV compartmentalization in the setting of liver transplantation (LT) is poorly understood. To study HCV leukotropic variants, we investigated the evolution of HCV compartmentalization after immunosuppression in liver transplant recipients., Methods: Plasma and peripheral blood mononuclear cell (PBMC) samples were collected from 5 liver transplant recipients before and after LT. We used clone sequencing to analyze the hypervariable region 1 (HVR1)-E2(384-419) region, which plays a key role in HCV entry and the induction of neutralizing responses, and assessed compartmentalization through phylogenetic analyses and Mantel's test., Results: Compartmentalization was frequent in the LT setting. HCV quasispecies were more homogeneous after LT in both the plasma and PBMC compartments, with a significant decrease in quasispecies complexity (P = .003) and genetic distances (P = .004) after transplantation. Our analysis identified 8 PBMC-related amino acid residues in HVR1., Conclusions: HCV compartmentalization between plasma and PBMCs and the emergence of leukotropic variants could be potentiated by immunosuppression in liver transplant recipients. The identification of defined leukotropic variants may contribute to the understanding of virus-host interactions after transplantation.

Idiosyncratic drug-induced agranulocytosis is a potential adverse event of most drugs, rare but life-threatening. Its annual incidence does not exceed 10 cases per million population in Europe and has remained stable over the past two decades. Its pathogenesis is poorly understood. The principal drugs associated with it are antithyroid drugs, antibiotics including trimethoprim, sulfamethoxazole, and beta-lactamines, ticlopidine, sulfasalazine and dipyrone. Clinical presentation is highly variable but a severe infection is observed in more than one third of cases. Poor prognostic factors include a neutrophil count under 100/mm(3), age > 65 years, septicemia or shock, and severe comorbidity. Improvement in the management of infectious complications and the use of hematopoietic growth factors in severe cases helps explain that mortality rate has fallen to less than 5%.

Background: More than several hundred drugs, toxins, and herbs have been reported to cause blood abnormalities, and drugs account for 20 - 40% of all instances of cytopenias., Objective: In the present paper, we report and discuss the recognition and the management of drug-induced acute neutropenia or agranulocytosis (neutrophil count of < 0.5 x 10(9)/l)., Methods: A bibliographic search was performed on the PubMed database of the US National Library of Medicine for articles published from January 1990 to January 2008. Additional not published data of our cohort of drug-induced agranulocytosis in the University Hospital of Strasbourg, France were incorporated in this review., Results/conclusions: Idiosyncratic drug-induced acute neutropenia or agranulocytosis is a serious adverse event due to the frequency of severe infections (such as deep infections, septicemia and septic shock) but modern management with broad spectrum antibiotics and hematopoietic growth factors is likely to improve the prognosis. Given the increased life expectancy, increasing use of medications as a therapeutic modality and subsequent longer exposure to drugs, as well as the development of new agents, healthcare professionals should be aware of this adverse event and its management.

Introduction: This case report describes a rare situation in which a superinfected cyst of the urachus complicated initially unknown and inactive Crohn's disease., Case: A 21-year-old man presented a chronic fever finally attributed to a superinfected urachal cyst. Six months after ablation of the cyst, progressive Crohn's disease was diagnosed., Discussion: The association of Crohn's disease and a superinfected urachal cyst is extremely rare. The case reported here is original in two aspects: the slowly progressive Crohn's disease was diagnosed after its complication; the superinfection developed through local bacterial translocation (ileal loop adjacent to the urachal cyst).

In the adult, the urachus remains as a non-specific fibrous formation extended from the bladder dome to the Retzius space. This urachal remnant is commonly asymptomatic or may be revealed by a cyst. This later may also be asymptomatic or lead to local inflammation or inflammatory pseudo-tumor. We report an original observation of chronic fever revealing an urachal cyst in a 21-Year-old male.