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Fever and fever syndromes
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220316.pdf (Publisher’s version ) (Open Access)Radboud University, 27 augustus 2020Promotor : Netea, M.G. Co-promotores : Simon, A., Bleeker-Rovers, C.P
Immunology of chronic Q fever
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201894.pdf (Publisher’s version ) (Open Access)Radboud University, 26 april 2019Promotores : Joosten, L.A.B., Netea, M.G. Co-promotores : Deuren, M. van, Bleeker-Rovers, C.P
Challenging queries of Q fever, emphasizing Q fever fatigue syndrome
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187512.pdf (Publisher’s version ) (Open Access)Radboud University, 02 maart 2018Promotores : Meer, J.W.M. van der, Bleijenberg, G., Knoop, H. Co-promotor : Bleeker-Rovers, C.P
Positron emission tomography with fluorodeoxyglucose in fever of unknown origin and infectious and non-infectious inflammatory diseases.
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52547.pdf (Publisher’s version ) (Open Access)In management of patients with fever of unknown origin (FUO) or suspected infectious or inflammatory disease, timely identification and localization of infectious and inflammatory lesions is essential for optimal treatment. Since activated inflammatory cells take up large amounts of glucose as a result of an increased metabolic rate, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) represents a promising imaging technique in these patients. The aim of the studies presented in this thesis was to further investigate the clinical value of FDG-PET in diagnosis of FUO and several infectious and inflammatory diseases. It is shown that FDG-PET is a useful diagnostic technique as part of a structured diagnostic protocol in all patients with FUO. FDG-PET contributed to the final diagnosis in 33% of all FUO patients in whom the chance of reaching a diagnosis was only 50%. In patients with bacteremia or candidemia and a high risk of metastatic infection, FDG-PET was also able to identify metastatic infectious foci, which were, in many cases, not found by conventional diagnostic techniques. Identification of these metastatic infections led to a change of treatment in most patients. Lipodystrophy, a serious complication of antiretroviral therapy in HIV-infected patients, is accompanied by adipose tissue inflammatory activity and by mitochondrial toxicity resulting in metabolic stress. FDG-PET was able to visualize lipodystrophy in HIV-infected patients. In addition, FDG-PET showed promising results in the imaging of different types of vasculitis, including giant cell arteritis, polyarteritis nodosa, Takayasu arteritis, Churge-Strauss syndrome, and Wegener's granulomatosis. However, at present, the diagnostic value of FDG-PET is only sufficiently studied in patients with FUO to recommend its use as part of a structured diagnostic protocol in clinical practice. Although results were invariably promising, in most other cases results of larger prospective studies should be awaited before widespread clinical use can be recommendedRU Radboud Universiteit Nijmegen, 11 januari 2007Promotores : Oyen, W.J.G., Meer, J.W.M. van der, Corstens, F.H.M.209 p
Challenges in diagnosis and follow-up of chronic Q fever
Get PDFCoxiella burnetii is the causative pathogen of the zoonosis Q fever. Upon primary infection, patients can remain asymptomatic or experience the disease called acute Q fever. After primary infection, 1-5% develop chronic Q fever, which is a persistent infection with C. burnetii causing vascular (prosthesis) infection and/or endocarditis. Diagnosis of chronic Q fever is based on clinical symptoms, radiologic, and microbiological results and is further classified into proven, probable, and possible chronic Q fever, based on the likelihood of infection. Antibiotic treatment for chronic Q fever is advised for at least 18 months and can be stopped when clinical, microbiological, and radiologic criteria are met. Part one of this thesis described the diagnosis and prognosis of Q fever. The diagnostic value of C. burnetii polymerase chain reaction (PCR) on throat swabs for Q fever pneumonia is evaluated in chapter two. As a low diagnostic value was found, diagnosis of Q fever pneumonia should be based on C. burnetii serology, and not on throat swab analysis alone. Chapter three outlines methods for detecting C. burnetii in tissue samples of chronic Q fever patients. This is routinely performed with PCR and should remain so, as fluorescence in situ hybridization (FISH) for C. burnetii detection in tissue samples was inferior to it. In chapter four the long-term follow-up of Dutch chronic Q fever patients is described. Many years after the 2007-2010 Q fever outbreak patients are still being diagnosed with chronic Q fever, with an incidence of ~20 cases per year. There is a considerable diagnostic delay between acute Q fever and the diagnosis of chronic Q fever, with intervals reaching up to nine years. Performing serological follow-up after acute Q fever resulted in patients being diagnosed within a shorter interval. The prognostic value of serological titres on clinical outcome during treatment and follow-up of patients with chronic Q fever is investigated in chapter five. Serological titres were found to have no prognostic value for clinical endpoints. Treatment decisions in chronic Q fever patients should be based on other factors. Chapter six analyses the association between genetic variations in genes encoding for pattern recognition receptors, for phagolysosomal pathways components, and for matrix metalloproteinases with clinical outcomes. Two genetic variations of interest were found, but these results need to be reproduced before treatment decisions can be based upon them. In part two of this thesis, the focus lies on vascular chronic Q fever. Chapter seven reevaluated patients with vascular risk factors for chronic Q fever that were already screened after the epidemic. Still, one patient was identified as having chronic Q fever. This finding warrants clinicians to stay vigilant for chronic Q fever, especially in high risk patients, even for so many years after the epidemic. Chapter eight addresses the growing concerns of vascular complications following quinolone exposure. In a high risk study population of patients with vascular chronic Q fever, no association was found between quinolone exposure and vascular complications. Therefore, quinolone therapy should not be withheld when indicated
The use of FDG-PET/CT in patients with febrile neutropenia
No full textItem does not contain fulltextFever is a frequent complication of neutropenia induced by the treatment of various neoplasms. This is referred to as febrile neutropenia, which is considered to be a sign of a potentially life-threatening infectious complication until proven otherwise. However, most infectious foci do not have localizing signs and symptoms owing to the lack of inflammatory infiltrates during neutropenia. At the same time, recent studies also showed that febrile neutropenia is not a specific indicator for infection. An increase in C-reactive protein and fever may initially be caused by inflammation of the digestive tract mucosa due to cytotoxic treatment of hematologic malignancies. Infectious foci can be found in various organ systems, such as the respiratory tract including invasive fungal disease, septic thrombophlebitis in those patients with central venous catheters, metastatic infection including soft tissue abscesses, and the digestive tract, for example, colitis and esophagitis probably associated with mucosal barrier injury. A growing number of studies focus on the use of FDG-PET/CT to detect infection in patients with febrile neutropenia. Studies show that FDG uptake in inflammatory foci seems not to be hampered by the lack of circulating neutrophils. At the same time, the very high negative predictive value of FDG-PET/CT excluding localized infectious foci might facilitate guidance of antimicrobial treatment. However, larger prospective studies are needed before FDG-PET/CT would be embedded in diagnostic guidelines in patients with febrile neutropenia
FDG-PET in fever of unknown origin
No full textItem does not contain fulltextFever of unknown origin (FUO) is commonly defined as fever higher than 38.3 degrees C on several occasions during at least 3 weeks with uncertain diagnosis after a number of obligatory tests. FUO remains a clinical challenge as no diagnosis is reached in up to 50% of cases. In general, infection accounts for one-fourth of cases of FUO, followed by neoplasm and noninfectious inflammatory diseases. FDG-PET is a sensitive diagnostic technique for the evaluation of FUO. Especially integrated imaging combining PET and CT facilitates anatomical localization of focally increased FDG uptake, thereby guiding further diagnostic tests to achieve a final diagnosis. FDG-PET/CT appears to be a more sensitive diagnostic tool in FUO than stand-alone FDG-PET, because of the precise anatomical localization of small lesions and better differentiation between physiological and pathologic metabolic foci. With FDG-PET/CT becoming widely available, FDG-PET/CT should be a routine procedure in the workup of FUO
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