Large vessel vasculitis: which imaging method?

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IMAGING AND SEROLOGICAL PROFILING OF PATIENTS WITH POLYMYALGIA RHEUMATICA AND GIANT CELL ARTERITIS

Background: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are two inflammatory conditions affecting people aged over 50 years. PMR is characterized by pain and stiffness in the shoulder and hip girdles. GCA, a large vessel vasculitis, is the most common form of primary systemic vasculitis. About 40-60% of patients with GCA present with concomitant PMR, and histologic features consistent with GCA can be detected on temporal artery biopsy of about 16% to 21% of patients with PMR. It is still debated whether PMR and GCA are different conditions or represent different clinical manifestations across the spectrum of a single disease. The aim of this research project was to profile immunological and imaging aspects of these two conditions to better characterize their similarities and differences. Patients and methods: A cohort of unselected, consecutive patients with PMR, GCA or both was studied. PMR was diagnosed according to Bird et al. criteria, whereas patients with cranial (C)-GCA were diagnosed according to the 1990 ACR classification criteria; a subset of these patients underwent temporal artery biopsy. Five further patients with fever of unknown origin (FUO) and imaging evidence of large vessel vasculitis (LVV) were included. All patients underwent a detailed and standardized clinical examination and, subsequently, a 18F- Fluorodeoxyglucose (FDG) positron emission tomography (PET) scan.. Joint and vascular uptake were evaluated by a qualitative visual score, using the liver uptake as a reference, and with semi-quantitative mean standardized uptake value (SUV). Each value of the qualitative joint and vascular scores of every region were summed up to obtain a total joint score (TJS) and a total vascular score (TVS). In a subgroup of patients, serum samples were collected just before the injection of FDG on the same day of the PET scan. The soluble (s) immune checkpoints cytotoxic T-lymphocyte antigen-4 (CTLA-4), soluble programmed death-1 (sPD-1) and programmed death-ligand 1 and 2 (PD-L1 and PD-L2) were measured in this subgroup. The serum of fifty healthy controls were studied for comparison. Results: One hundred and thirty-one patients underwent FDG-PET/CT scanning, including 89 females and 42 males, with a median age of 74 years (range 47-92). Ninety-seven patients were diagnosed as PMR, 13 as C-GCA, 16 with both PMR and C-GCA and five patients presented with FUO. Soluble CTLA-4, sPD1, sPD-L1, and sPD-L2, evaluated in 40 patients (32 with PMR and 8 with PMR+C-GCA), were increased in comparison with controls (p<0.001 for all the comparisons), although no statistically significant difference between patients with PMR+C-GCA and those with isolated PMR was found. Conclusions: Patients with PMR and GCA share many immunological and imaging abnormalities. Results from this study demonstrate that available and evaluated biomarkers are unable to precisely differentiate these two conditions

Imaging studies of crystalline arthritides

Gout, calcium pyrophosphate dihydrate (CPPD) deposition disease, and calcium hydroxyapatite deposition disease (HADD) are the three most common crystal-induced arthropathies. Multimodality imaging may help in their diagnosis, and is useful for a precise and comprehensive assessment and grading of the related osteoarticular damage. Plain film radiography, due to its low cost and wide availability, is the first imaging technique to be used in crystal deposition diseases, providing well-known and specific findings for CPPD deposition disease and HADD, while it may undergrade the early osteoarticular lesions in gouty patients. Ultrasonography (US) is a radiation-free approach that accurately depicts crystal deposits in cartilage, peri- and intra-articular soft tissues, but it does not give a panoramic view of the affected joints. Cross-sectional imaging techniques can examine crystal deposits in the spine and axial joints. CT has the potential to distinguish monosodium urate (MSU) crystals from calcium containing crystals, due to their different attenuation values. MRI may demonstrate synovitis, erosions and bone marrow edema in gouty patients and it may differentiate tophi from other soft tissue nodules due to its high contrast resolution and power of tissue characterization

Subclinical giant cell arteritis in new onset polymyalgia rheumatica:A systematic review and meta-analysis of individual patient data

Objectives: To determine the prevalence and predictors of subclinical giant cell arteritis (GCA) in patients with newly diagnosed polymyalgia rheumatica (PMR). Methods: PubMed, Embase, and Web of Science Core Collection were systematically searched (date of last search July 14, 2021) for any published information on any consecutively recruited cohort reporting the prevalence of GCA in steroid-naïve patients with PMR without cranial or ischemic symptoms. We combined prevalences across populations in a random-effect meta-analysis. Potential predictors of subclinical GCA were identified by mixed-effect logistic regression using individual patient data (IPD) from cohorts screened with PET/(CT). Results: We included 13 cohorts with 566 patients from studies published between 1965 to 2020. Subclinical GCA was diagnosed by temporal artery biopsy in three studies, ultrasound in three studies, and PET/(CT) in seven studies. The pooled prevalence of subclinical GCA across all studies was 23% (95% CI 14%-36%, I2=84%) for any screening method and 29% in the studies using PET/(CT) (95% CI 13%-53%, I2=85%) (n=266 patients). For seven cohorts we obtained IPD for 243 patients screened with PET/(CT). Inflammatory back pain (OR 2.73, 1.32-5.64), absence of lower limb pain (OR 2.35, 1.05-5.26), female sex (OR 2.31, 1.17-4.58), temperature >37° (OR 1.83, 0.90-3.71), weight loss (OR 1.83, 0.96-3.51), thrombocyte count (OR 1.51, 1.05-2.18), and haemoglobin level (OR 0.80, 0.64-1.00) were most strongly associated with subclinical GCA in the univariable analysis but not C-reactive protein (OR 1.00, 1.00-1.01) or erythrocyte sedimentation rate (OR 1.01, 1.00-1.02). A prediction model calculated from these variables had an area under the curve of 0.66 (95% CI 0.55-0.75). Conclusion: More than a quarter of patients with PMR may have subclinical GCA. The prediction model from the most extensive IPD set has only modest diagnostic accuracy. Hence, a paradigm shift in the assessment of PMR patients in favour of implementing imaging studies should be discussed

Associations between polymyalgia rheumatica and giant cell arteritis and twelve cardiovascular diseases

Objectives: Evidence of the association of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) with the full range of cardiovascular diseases (CVDs) is limited. We examined their relationship with the first clinical presentation of the 12 most common CVDs in an unselected population-based cohort of men and women. Methods: We analysed CALIBER data, which links primary care, hospital and mortality data in England, from 1997-2010. We assembled a cohort of men and women initially free from CVD at baseline and included all patients with PMR and/or GCA (PMR/GCA) diagnosis, matched by age, sex and general practice with up to ten individuals without PMR/GCA. Random effects Poisson regression analysis was used to study the association between PMR/GCA and the initial presentation of 12 types of CVDs. Results: The analysis included 9,776 patients with PMR only, 1,164 with GCA only, 627 with PMR and GCA, and 105,504 patients without either condition. During a median of 3.14 years of follow-up 2,787 (24.1%) individuals with PMR/GCA and 21,559 (20.4%) without PMR/GCA developed CVDs. Patients with PMR/GCA had lower rates of unheralded coronary death (3.18 vs. 3.61/1000 person-years; adjusted incidence ratio 0.79, 95%CI 0.66-0.95), transient ischemic attack (5.11 vs. 5.61/1000 person-years; 0.67, 95%CI 0.54-0.84) and coronary and death composite (24.17 vs. 25.80/1000 person-years; 0.90, 0.82-0.98). No associations were observed for other cardiovascular or cerebrovascular diseases, and in patients with only PMR or GCA. No evidence of interaction by age or sex was found. Estimates decreased with longer PMR/GCA duration and findings were robust to multiple sensitivity analyses. Conclusion: In this large contemporary population-based cohort the presence of PMR and/or GCA was not associated with an increased risk of cardiovascular or cerebrovascular diseases regardless of PMR/GCA duration

2015 recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients'and clinicians'values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR