Association between vascular FDG uptake during follow-up and the development of thoracic aortic aneurysms in giant cell arteritis.

Background: A positive PET scan at diagnosis was associated with a greater yearly increase in ascending and descending aortic diameter and thoracic aortic volume in patients with giant cell arteritis (GCA). Radiologic and histopathologic vascular abnormalities persist in a subset of treated patients despite clinical remission. The aim of this study was to evaluate the association between vascular FDG uptake during follow-up and the development of thoracic aortic aneurysms. Methods: We recently performed a prospective cohort study of 106 GCA patients, who underwent FDG PET and CT imaging at diagnosis and CT imaging yearly for a maximum of 10 years. In this post hoc analysis, GCA patients who also have had FDG PET imaging during follow-up were included. PET scans were visually scored (0-3) at 7 vascular areas. PET scans were considered positive in case of FDG uptake ≥grade 2 in any large vessel. Results: Eighty-eight repeat PET scans were performed in 52 out of 106 GCA patients, who were included in the original prospective cohort. Fifty-five (63%) PET scans were done at the time of a relapse and 33 (38%) were done while in remission. Nine out of ten patients with an incident thoracic aortic aneurysm had both a positive PET scan at diagnosis and during follow-up. Conclusion: In addition to the intensity and extent of the initial vascular inflammation, ongoing aortic inflammation may contribute to the development of thoracic aortic aneurysms in GCA. However, this hypothesis should be confirmed in a large prospective trial with repeat PET scans at predefined time points during follow-up.

Prevalence, characteristics, and outcome of subclinical vasculitis in polymyalgia rheumatica: a retrospective cohort study.

OBJECTIVES: Two recent meta-analyses reported subclinical vasculitis in 22-23% of patients with polymyalgia rheumatica (PMR). We aimed to evaluate the prevalence, characteristics, and outcome of subclinical vasculitis among our PMR patients. METHODS: Consecutive patients with GCA/PMR spectrum disease with isolated PMR symptoms who underwent FDG PET imaging between 2003-2020 and who were followed for ≥6 months, were included retrospectively. Vasculitis was defined as FDG uptake ≥ grade 2 in any vessel. RESULTS: We included 337 patients, of whom 31 (9%) with subclinical vasculitis. Among those with subclinical vasculitis, 21 (58%) had isolated large vessel vasculitis, 3 (10%) had isolated cranial vasculitis and 7 (23%) had both cranial and large vessel vasculitis. The glucocorticoid (GC) starting dose and GC doses during follow-up were higher in those with subclinical vasculitis until 12 months after diagnosis (p< 0.001). There was no difference in the duration of GC treatment (25 vs 20 months, p= 0.187). Cox proportional hazard regression analyses showed no difference in the proportion of patients able to stop GC (HR 0.78 [95% CI 0.49-1.25], p= 0.303) and in the proportion of patients with relapse (HR 0.82 [95%CI 0.50-1.36], p= 0.441). CONCLUSION: Only 9% of our PMR patients had subclinical vasculitis with a predilection for large vessel vasculitis. There were no differences in relapse rate and duration of GC treatment, however those with subclinical vasculitis received higher GC doses until 12 months after diagnosis. Prospective interventional trials are needed to evaluate the outcome of PMR patients with and without subclinical vasculitis treated with similar GC protocol.

Comparison of diagnostic spectrum between inflammation of unknown origin and fever of unknown origin: A systematic review and meta-analysis.

BACKGROUND: Patients with inflammation of unknown origin (IUO) and fever of unknown origin (FUO) are commonly considered a single population. Differences in underlying causes between both groups may steer the diagnostic work-up. METHODS: PubMed, Embase, Web of Science, and ClinicalTrials.gov were searched from July 2009 through December 2023. Studies including both FUO and IUO patients with a sample size of ≥20 were considered. The primary outcome was the difference in the rate of patients affected by predefined diagnostic categories according to meeting FUO or IUO criteria. Data were pooled using random-effects models. RESULTS: A total of 8 studies met criteria for inclusion, with a total of 1452 patients (466 with IUO and 986 with FUO). The median rate of IUO patients among the included studies was 32 % (range 25-39 %). Patients with IUO had a lower likelihood of infection (OR 0.59 [95 % CI; 0.36-0.95]; I2 0 %). There were no significant differences in the rate of noninfectious inflammatory disorders, malignancies, miscellaneous disorders, or remaining undiagnosed. Comparison of diagnostic subgroups revealed that IUO patients were less likely to have systemic autoinflammatory disorders (OR 0.17 [95 % CI, 0.05-0.58]; I2 42 %) and more likely to have vasculitis (OR 2.04 [95 % CI, 1.23-3.38]; I2 21 %) and rheumatoid arthritis or spondylarthritis (OR 3.52 [95 % CI, 1.16-10.69]; I2 0 %). CONCLUSION: Based on our findings, there is little reason to assume that FUO and IUO patients would benefit from a different initial diagnostic approach.

Association Between Vascular 18F-Fluorodeoxyglucose Uptake at Diagnosis and Change in Aortic Dimensions in Giant Cell Arteritis : A Cohort Study.

BACKGROUND: Previous studies have shown that patients with giant cell arteritis (GCA) who have vascular 18F-fluorodeoxyglucose (FDG) uptake at diagnosis are at increased risk for thoracic aortic complications. OBJECTIVE: To measure the association between vascular FDG uptake at diagnosis and the change in aortic dimensions. DESIGN: Prospective cohort study. SETTING: University Hospitals Leuven. PATIENTS: 106 patients with GCA and FDG positron emission tomography (PET) imaging 3 days or less after initiation of glucocorticoids. MEASUREMENTS: Patients had PET and computed tomography (CT) imaging at diagnosis and CT imaging yearly for a maximum of 10 years. The PET scans were scored 0 to 3 in 7 vascular areas and summed to a total vascular score (TVS). The PET scan results were positive when FDG uptake was grade 2 or greater in any large vessel. The association between vascular FDG uptake and aortic dimensions was estimated by linear mixed-effects models with random intercept and slope. RESULTS: When compared with patients with a negative PET scan result, those with a positive scan result had a greater increase in the diameter of the ascending aorta (difference in 5-year progression, 1.58 mm [95% CI, 0.41 to 2.74 mm]), the diameter of the descending aorta (1.32 mm [CI, 0.38 to 2.26 mm]), and the volume of the thoracic aorta (20.5 cm³ [CI, 4.5 to 36.5 cm³]). These thoracic aortic dimensions were also positively associated with TVS. Patients with a positive PET scan result had a higher risk for thoracic aortic aneurysms (adjusted hazard ratio, 10.21 [CI, 1.25 to 83.3]). LIMITATION: The lengthy inclusion and follow-up period resulted in missing data and the use of different PET machines. CONCLUSION: Higher TVS was associated with greater yearly increase in thoracic aortic dimensions. Performing PET imaging at diagnosis may help to estimate the risk for aortic aneurysm formation. PRIMARY FUNDING SOURCE: None.

Diagnostic yield of combined cranial and large vessel PET/CT, ultrasound and MRI in giant cell arteritis: A systematic review and meta-analysis.

OBJECTIVES: To estimate the diagnostic accuracy of combined cranial and large vessel imaging by PET/CT, ultrasound and MRI for giant cell arteritis (GCA). METHODS: PubMed, Embase, Cochrane and Web of Science databases were searched from inception till August 31, 2022. Studies were included if they involved patients with suspected GCA and assessed the diagnostic accuracy of combined cranial and large vessel imaging by PET/CT, ultrasound or MRI with the final clinical diagnosis as reference standard. RESULTS: Eleven (1578 patients), 3 (149 patients) and 0 studies were included for the diagnostic accuracy of ultrasound, PET/CT and MRI, respectively. Combined cranial and large vessel ultrasound had a sensitivity of 86% (76-92%) and specificity of 96% (92-98%). PET/CT of both cranial and large vessels yielded a sensitivity of 82% (61-93%) and specificity of 79% (60-90%). No studies assessed both PET/CT and ultrasound, which precluded head-to-head comparison. Addition of large vessel ultrasound to ultrasound of the temporal arteries (7 studies) significantly increased sensitivity (91% versus 80%, p < 0.001) without decrease in specificity (96% versus 95%, p = 0.57). Evaluating cranial arteries in addition to large vessels on PET/CT (3 studies) tended to increase the sensitivity (82% versus 68%, p = 0.07) without decrease in specificity (81% versus 79%, p = 0.70). CONCLUSION: Combined cranial and large vessel ultrasound and PET/CT provided excellent accuracy for the diagnosis of GCA. Either PET/CT or ultrasound may be preferred depending on setting, expertise and clinical presentation. The diagnostic accuracy of combined cranial and large vessel MRI needs to be determined in future studies.

Higher diagnostic yield of 18F-FDG PET in inflammation of unknown origin compared to fever of unknown origin.

OBJECTIVE: 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is an important imaging technique in the workup of fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Studies comparing the diagnostic yield of 18F-FDG PET between both entities are lacking. METHODS: Retrospective analysis of FUO/IUO patients who underwent 18F-FDG PET between 2000 and 2019 in the University Hospitals of Leuven (Belgium). 18F-FDG PET images were assessed for accuracy and contribution towards the final diagnosis. Logistic regression was performed to evaluate the association between meeting FUO or IUO criteria and diagnostic contribution of 18F-FDG PET with and without adjustment for confounders. RESULTS: Out of 604 patients, 439 (73%, mean age 56 years, 43% female) underwent 18F-FDG PET imaging, including 349 (79%) classified as FUO and 90 (21%) as IUO. Noninfectious inflammatory disorders were significantly more frequent in the IUO group (37% versus 25%; P = 0.03). 18F-FDG PET imaging had a sensitivity of 93% (89-96%), a specificity of 35% (29-42%), and made a positive contribution to the final diagnosis in 25% (21-29%) of cases. IUO was significantly associated with contributive 18F-FDG PET imaging compared to FUO (aOR 2.21 [95% CI 1.31-3.72]; P = 0.003). Among those with contributive 18F-FDG PET imaging, giant cell arteritis (IUO 25% versus FUO 12%) and polymyalgia rheumatica (IUO 17% versus FUO 1%) were numerically more frequent in the IUO group. CONCLUSION: The diagnostic contribution of 18F-FDG PET was higher among those with IUO, most likely due to differences in diagnostic spectrum.

Epidemiology and predictors of relapse in giant cell arteritis: A systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to estimate the timing of relapse, the prevalence of multiple relapses and the predictors of relapse in patients with giant cell arteritis (GCA). METHODS: PubMed, Embase and Cochrane databases were searched from inception till November, 30 2021. Outcome measures include cumulative relapse rate (CRR) of first relapse at year 1, 2, and 5 after treatment initiation, CRR of second and third relapse and predictors of relapse. RESULTS: Thirty studies (2595 patients) were included for timing of relapse, 16 studies (1947 patients) for prevalence of multiple relapses and 40 studies (4213 patients) for predictors of relapse. One-year, 2-year and 5-year CRRs were 32% [95% confidence interval (CI) 22-43%], 44% [95% CI 31-59%], and 47% [95% CI 27-67%], respectively. The duration of scheduled glucocorticoid therapy was negatively associated with the 1-year CRR (P=0.03). CRR of second and third relapse were 30% [95% CI 21-40] and 17% [95% CI 8-33%], respectively. Female sex (OR 1.43) and large vessel involvement (OR 2.04) were predictors of relapse. CONCLUSION: Relapse occurred in almost half of GCA patients mainly during the first two years after diagnosis. One in three patients had multiple relapses. The optimal glucocorticoid tapering schedule, which seeks a balance between the lowest relapse risk and the shortest glucocorticoid duration, needs to be determined in future studies. Longer scheduled glucocorticoid therapy or early introduction of glucocorticoid-sparing agents may be warranted in female patients and patients with large vessel involvement.

Duration of Treatment With Glucocorticoids in Giant Cell Arteritis: A Systematic Review and Meta-analysis.

ABSTRACT: The aim of this meta-analysis was to estimate the mean duration of glucocorticoid (GC) treatment in patients with giant cell arteritis. PubMed, EMBASE, and Cochrane databases were searched from inception until November 30, 2021. The outcome measures were the proportion of patients on GCs at years 1, 2, and 5 after diagnosis and the mean GC dose (in the entire cohort and expressed in prednisone equivalents) at these time points. Twenty-two studies involving a total of 1786 patients were included. The pooled proportions of patients taking GCs at years 1, 2, and 5 were 89.7% (95% confidence interval [CI], 83.2%-93.9%), 75.2% (95% CI, 58.7%-86.6%), and 44.3% (95% CI, 15.2%-77.6%), respectively. The pooled GC dose at years 1 and 2 was 9.1 mg/d (95% CI, 2.8-15.5 mg/d) and 7.8 mg/d (95% CI, 1.4-14.1 mg/d), respectively. The proportion of patients taking GCs at year 1 was lower in multicenter studies ( p = 0.003), in randomized controlled trials ( p = 0.01), and in studies using a GC-tapering schedule ( p = 0.01). There were no significant differences in the proportion of patients taking GCs at years 1 and 2 according to study design (retrospective vs. prospective), initial GC dose, use of pulse GCs, publication year, enrolment period, duration of follow-up, age, and sex. This meta-analysis showed that giant cell arteritis is a chronic disease that requires substantial and prolonged GC treatment in a considerable proportion of patients. A predefined GC-tapering schedule may help to avoid inadequately long GC treatment.

Diagnostic accuracy and validation of 18F-fluorodeoxyglucose positron emission tomography scores in a large cohort of patients with polymyalgia rheumatica.

Background: Several studies have shown that 18F-FDG PET may contribute to the diagnosis of polymyalgia rheumatica (PMR). Previously, we developed a composite PET score called the Leuven score, which was recently adapted to the more concise Leuven/Groningen score by van der Geest et al. The aim of this study is to validate and compare the diagnostic accuracy and cut-off points of both scores in a large cohort of PMR patients. Methods: Patients with a possible clinical diagnosis of PMR and a PET scan prior to the initiation of glucocorticoids between 2003 and 2020 were included retrospectively. The gold standard for the diagnosis of PMR was the judgment of two experienced clinicians after a follow-up of at least 6 months. FDG uptake was scored visually in 12 articular regions (scores 0-2) and a total skeletal score was calculated by summing the individual scores (maximum of 24 for the Leuven score and 14 for the Leuven/Groningen score). Receiver operating characteristic (ROC) analysis and the Youden index were used to determine the diagnostic accuracy and optimal cut-off points. Results: A total of 162 patients with PMR and 83 control patients were included. Both PET scores showed high diagnostic accuracy in the ROC analysis (area under the curve 0.986 and 0.980, respectively). The Leuven Score provided a sensitivity of 91.4%, specificity of 97.6% and accuracy of 93.5% at its predefined cut-off point of 16. With the newly determined cut-off point of 12 the sensitivity was 98.8%, the specificity 95.2% and the accuracy 97.6%. The Leuven/Groningen score had a sensitivity, specificity and accuracy of 93.2%, 95.2%, and 93.9%, respectively, with the pre-specified cut-off point of 8, and 96.9%, 92.8%, and 95.5% with the optimal cut-off point of 7. Conclusion: The original Leuven score and the simplified Leuven/Groningen score both had excellent diagnostic accuracy. The latter may be easier to apply in clinical practice.

Undiagnosed adult congenital heart disease presenting with postpartum dyspnoea: a case report.

Patients with adult congenital heart disease are born with structural heart defects who survived into adulthood. Occasionally, complex lesions remain undiagnosed, potentially causing substantial cardiovascular health problems at young age. Here, the case is presented of a patient with subacute heart failure 1 week postpartum, revealing the diagnosis of aortic coarctation (CoA) with patent ductus arteriosus (PDA). A 34-year-old woman presented to the emergency department with severe hypertension and exercise-related dyspnoea 1 week postpartum. An initial diagnosis of pulmonary embolism was made after detection of a solitary opacity in the pulmonary artery (PA) on CT pulmonary angiography. Symptoms persisted despite anticoagulant treatment. Thorough clinical and echocardiographic reassessment unmasked the diagnosis of severe CoA with PDA, which was treated with percutaneous dilatation and stenting. Follow-up consultation 4 weeks later showed an asymptomatic patient with normalized blood pressure. The puerperium is a high-risk period to develop hypertensive heart failure for mothers with pre-existing heart disease, due to mobilization of extracellular fluid to the intravascular compartment. Undiagnosed CoA should always be ruled out in case of unexplained postpartum hypertension. When detecting a solitary opacity in the PA, a PDA with associated heart defects should be excluded by further investigations. This opacity is located at the orifice of the PDA in the PA and is probably a flow effect, which results from the mix of contrast-free with contrast-rich blood.

High flow nasal cannula as respiratory support in treating infant bronchiolitis: a systematic review.

Bronchiolitis is a common respiratory illness in early childhood, often leading to hospitalization and associated healthcare costs. Low flow 100% oxygen through nasal prongs is the standard therapy for infants with bronchiolitis and hypoxemia. Nasal continuous positive airway pressure (nCPAP) or invasive ventilation is used in case of progressive respiratory failure. High flow heated and humidified oxygen therapy with delivery of an air-oxygen mixture up to 2 L/min/kg body weight via nasal prongs (referred to as high flow nasal cannula or HFNC) is a newer method for respiratory support. Initial data from retrospective studies were promising but should be interpreted with caution. A limited number of prospective randomized controlled trials (RCT) have now compared HFNC with either standard oxygen therapy (SOT) or nCPAP. In this review, we critically summarize the data from these RCTs with the aim to provide advice on how to position HFNC in clinical practice.Conclusion: HFNC is a safe mode of respiratory support that can be positioned between SOT and nCPAP as rescue therapy for children not adequately supported by SOT. It does not seem to shorten the duration of oxygen need nor the duration of hospital admission.What is Known:• HFNC is being used increasingly in the context of infant bronchiolitis. However, evidence on efficacy and safety are limited. Different published studies involve different disease severities and different pediatric settings.What is New:• In this review, we summarize data only from prospective RCTs with the aim to provide guidance on how to use HFNC.