The effect of prednisolone and a short-term prednisolone discontinuation for the diagnostic accuracy of FDG-PET/CT in polymyalgia rheumatica-a prospective study of 101 patients.

PURPOSE: 2-[18F]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been suggested as an imaging modality to diagnose polymyalgia rheumatica (PMR). However, the applicability of FDG-PET/CT remains unclear, especially following glucocorticoid administration. This study aimed to investigate the diagnostic accuracy of FDG-PET/CT before and during prednisolone treatment, as well as following short-term prednisolone discontinuation. METHODS: Treatment naïve suspected PMR patients were clinically diagnosed at baseline and subsequently had an FDG-PET/CT performed. Patients diagnosed with PMR were administered prednisolone following the first FDG-PET/CT and had a second FDG-PET/CT performed after 8 weeks of treatment. Subsequently, prednisolone was tapered with short-term discontinuation at week 9 followed by a third FDG-PET/CT at week 10. An FDG-PET/CT classification of PMR/non-PMR was applied, utilizing both the validated Leuven score and a dichotomous PMR score. The final diagnosis was based on clinical follow-up after 1 year. RESULTS: A total of 68 and 27 patients received a final clinical diagnosis of PMR or non-PMR. A baseline FDG-PET/CT classified the patients as having PMR with a sensitivity/specificity of 86%/63% (Leuven score) and 82%/70% (dichotomous score). Comparing the subgroup of non-PMR with inflammatory diseases to the PMR group demonstrated a specificity of 39%/54% (Leuven/dichotomous score). After 8 weeks of prednisolone treatment, the sensitivity of FDG-PET/CT decreased to 36%/41% (Leuven/dichotomous score), while a short-term prednisolone discontinuation increased the sensitivity to 66%/60%. CONCLUSION: FDG-PET/CT has limited diagnostic accuracy for differentiating PMR from other inflammatory diseases. If FDG-PET/CT is intended for diagnostic purposes, prednisolone should be discontinued to enhance diagnostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04519580). Registered 17th of August 2020.

Recommendations for early referral of individuals with suspected polymyalgia rheumatica: an initiative from the international giant cell arteritis and polymyalgia rheumatica study group.

OBJECTIVE: To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR). METHODS: A task force including 29 rheumatologists/internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1-5 scale) and agreement (LOA) (0-10 scale) were evaluated. RESULTS: Two overarching principles and five recommendations were developed. LOE was 4-5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care. CONCLUSIONS: These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR.

Concurrent baseline diagnosis of giant cell arteritis and polymyalgia rheumatica - A systematic review and meta-analysis.

INTRODUCTION: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) can be concurrent diseases. We aimed to estimate the point-prevalence of concurrent GCA and PMR. Additionally, an incidence rate (IR) of GCA presenting after PMR diagnosis in patients was estimated. METHODS: Two authors performed a systematic literature search, data extraction and risk of bias assessment independently. Studies assessing cohorts of patients presenting with both GCA and PMR were included. The outcomes were point-prevalence of concurrent GCA and PMR and IR for development of GCA after PMR diagnosis. A meta-analysis was performed to calculate a pooled prevalence of concurrent PMR and GCA. RESULTS: We identified 29 studies investigating concurrent GCA and PMR. Only two studies applied imaging systematically to diagnose GCA and none to diagnose PMR. GCA presenting after PMR diagnosis was assessed in 12 studies but imaging was not applied systematically. The point-prevalence of concurrent GCA present at PMR diagnosis ranged from 6%-66%. The pooled estimate of the point-prevalence from the meta-analysis was 22%. The point-prevalence of PMR present at GCA diagnosis ranged from 16%-65%. The pooled estimate of the point-prevalence from the meta-analysis was 42%. The IR ranged between 2-78 cases of GCA presenting after PMR per 1000 person-years. CONCLUSION: This review and meta-analysis support that concurrent GCA and PMR is frequently present at the time of diagnosis. Additionally, we present the current evidence of GCA presenting in patients after PMR diagnosis. These results emphasize the need for studies applying imaging modalities to diagnose GCA.

Histomorphometric case-control study of subarticular osteophytes in patients with osteoarthritis of the hip.

OBJECTIVE: The objective of this cross-sectional case-control study was to determine the prevalence and size of marginal and subarticular osteophytes in patients with osteoarthritis (OA), and to compare these to that of a control group. DESIGN: We investigated femoral heads from 25 patients with OA following hip replacement surgery, and 25 femoral heads from a control group obtained post-mortem. The area and boundary length of the femoral head, marginal osteophytes, and subarticular osteophytes were determined with histomorphometry. Marginal osteophytes were defined histologically as bony projections at the peripheral margin of the femoral head, while subarticular osteophytes were defined as areas of bone that expanded from the normal curvature of the femoral head into the articular cartilage. RESULTS: The prevalence of OA patients with marginal- and subarticular osteophytes were 100 and 84%, respectively. Whereas the prevalence of the participants in the control group with marginal- and subarticular osteophytes were 56 and 28%, respectively. The area and boundary length of marginal osteophytes was (median (Interquartile range)) 165.3mm2 (121.4-254.0) mm2 and 75.1 mm (50.8-99.3) mm for patients with OA compared to 0 mm2 (0-0.5) mm2 and 0 mm (0-0.5) mm for the control group (P <  0.001). For the subarticular osteophytes, the area and boundary length was 1.0 mm2 (0-4.4) mm2 and 1.4 mm (0-6.5) mm for patients with OA compared to 0 mm2 (0-0.5) mm2 and 0 mm (0-0.5) mm for the control group (P <  0.001). CONCLUSION: As expected, both marginal- and subarticular osteophytes at the femoral head, were more frequent and larger in patients with OA than in the control group. However, in the control group, subarticular osteophytes were more prevalent than expected from the minor osteophytic changes at the femoral head margin, which may suggest that subarticular osteophytes are an early degenerative phenomenon that ultimately might develop into clinical osteoarthritis.

Age-related histological changes in calcified cartilage and subchondral bone in femoral heads from healthy humans.

OBJECTIVE: Age is the most important risk factor for osteoarthritis (OA). It is suggested that changes in subchondral bone and calcified cartilage may occur in early OA. Therefore, the aim was to investigate age-related changes in the femoral head composition. We hypothesise that the thickness of the subchondral bone plate decreases with age, while the thickness of the calcified cartilage increases with age as seen in early-stage OA. METHODS: Femoral heads from 29 women (20-74 years) and 32 men (23-78 years), who had died suddenly and unexpectedly, were obtained at autopsy. Individuals with bone or joint diseases or macroscopic abnormal cartilage were excluded. Using design-based stereology, femoral head volume as well as thickness and volume of the calcified cartilage and subchondral bone plate were estimated and correlated to sex and age. RESULTS: The thickness and volume of the subchondral bone plate were not correlated with age. Calcified cartilage thickness and volume correlated positively with age in women, while the femoral head volume was correlated positively with age in men. CONCLUSION: In human femoral heads obtained from a cross-sectional population without macroscopic OA changes, the thickness of the subchondral bone plate did not change with age, which differs from the thinning seen in early OA. Surprisingly, the age-related changes of the volume and thickness of the calcified cartilage and of the volume of the femoral head were different for women and men. This indicate that cartilage and bone metabolism is sex-specific, which may influence ageing of the hip joint.

Thickness of the bone-cartilage unit in relation to osteoarthritis severity in the human hip joint.

OBJECTIVE: Bone formation is a hallmark of osteoarthritis (OA). It has been speculated that bone formation may occur because of ossification at the bone-cartilage unit, that is, bone formation directly involving the calcified cartilage (CC). This study aimed to investigate the thickness of the CC and subchondral bone (SCB) in relation to the severity of the overlying articular cartilage (AC) degeneration. DESIGN: We investigated femoral heads from 20 patients with OA and 15 healthy subjects with design-based stereology using systematic uniform random sampling of the entire joint surface. This was combined with the Osteoarthritis Research Society International (OARSI) OA cartilage histopathology assessment system, thus obtaining focal OARSI grades paired with thickness measurements of AC, CC and the SCB. RESULTS: The patients with OA had thicker CC (mean 159; 95% CI 144 to 177 µm) compared with the healthy subjects (mean 132; 95% CI 113 to 1550 µm; p=0.036), and this difference was even higher in areas without loss of AC thickness (OARSI grade ≤3); 187 (95% CI 164 to 214) µm vs 132 (95% CI 113 to 155) µm (p=0.001). In the patients with OA, a thicker SCB was observed in areas with loss of AC thickness (OARSI grade ≥4), but not in areas without loss of AC thickness (OARSI grade ≤3). CONCLUSION: The study showed that thicker CC is present in early stages of OA, suggesting that bone formation by endochondral ossification is an early phenomenon of OA. Thickening of the SCB was present, but only in areas with denuded bone. Suggesting that also appositional bone growth occurs and that it may be a consequence of changed biomechanics.