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.

The provisional OMERACT ultrasonography score for giant cell arteritis.

OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.

An international survey of current management practices for polymyalgia rheumatica by general practitioners and rheumatologists.

OBJECTIVES: To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment. METHODS: An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group. RESULTS: In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials. CONCLUSION: This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.

Diagnostic accuracy of high-resolution peripheral quantitative computed tomography and X-ray for classifying erosive rheumatoid arthritis.

OBJECTIVE: To investigate whether high-resolution peripheral quantitative CT (HR-pQCT) of two metacarpophalangeal (MCP) joints can more accurately classify patients as having erosive RA compared with conventional radiography (CR) of 44 joints in the hands, wrists and feet. METHODS: In this single-centre cross-sectional study, patients with established RA (disease duration ≥5 years) were investigated by HR-pQCT and CR. The second and third MCP joints of the dominant hand were assessed for erosions by HR-pQCT. CR of the hands, wrists and feet were scored according to the Sharp-van der Heijde (SHS) method. RESULTS: In total, 353 patients were included; 66 (18.7%) patients were classified as having non-erosive RA, and 287 (81.3%) had erosive RA by CR. The sensitivity and specificity (95% CI) of HR-pQCT for classifying patients as having erosive RA when standard CR of hands, wrists and feet was used as the reference was 89% (84, 92%) and 30% (20, 43%), respectively. Using HR-pQCT as the reference, the sensitivity and specificity of CR for classifying patients having erosive RA were 85% (80, 89%) and 38% (25, 52%), respectively. McNemar's χ2 test showed no significant difference between the sensitivities of patients classified as having erosive RA by HR-pQCT or by CR (2.14, P = 0.177). CONCLUSION: The diagnostic accuracy of HR-pQCT scanning of only two MCP joints and CR of 44 joints suggests the two modalities were comparable for classifying patients with established RA as having erosive disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03429426).

Diagnostic accuracy of ultrasound for detecting large-vessel giant cell arteritis using FDG PET/CT as the reference.

OBJECTIVES: The diagnostic accuracy of axillary artery US in the diagnosis of large-vessel (LV)-GCA using 18F-fluorodeoxyglucose (FDG) PET/CT as reference standard was prospectively evaluated in GCA-suspected patients. As an exploratory analysis, the diagnostic accuracy of cranial artery FDG PET/CT was evaluated. METHODS: Briefly, the inclusion criteria were age ≥50 years, raised inflammatory markers and potential GCA symptoms. Patients in immunosuppressive therapy or with a previous diagnosis of GCA or PMR were excluded. Examinations were performed pre-treatment. LV-GCA reference diagnosis was a clinical diagnosis of GCA and PET-proven LV inflammation. GCA patients fulfilling ACR criteria were considered as cranial-GCA (c-GCA). Patients without GCA were considered controls. Receiver operating characteristic curve analysis of the US-measured axillary intima-media thickness was performed. FDG uptake in temporal, maxillary and vertebral arteries was also assessed. RESULTS: Forty-six patients were diagnosed with LV-GCA, 10 with isolated c-GCA, and in 34 patients GCA was dismissed. Axillary US yielded a sensitivity of 76% and a specificity of 100% for LV-GCA. An axillary intima-media thickness cut-off of 1.0 mm yielded a sensitivity of 74% and a specificity of 92%. Adding LV US to temporal assessment increased sensitivity from 71% to 97% (all GCA patients). Cranial artery PET showed a diagnostic sensitivity of 78% and specificity of 100% for c-GCA. CONCLUSION: Axillary artery US shows high accuracy for the LV-GCA diagnosis. Building upon the recent EULAR recommendations, we propose a diagnostic algorithm with US as the first-line confirmatory test, not only in c-GCA-suspected patients, but in all patients suspected of 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.

PR3-ANCA-associated vasculitis is associated with a specific motif in the peptide-binding cleft of HLA-DP molecules.

OBJECTIVES: This study aimed to characterize the association between HLA alleles and ANCA-associated vasculitis (AAV) in a genetically homogeneous population, and to analyse the contribution of specific HLA molecule amino acid sequences to the risk of AAV. METHODS: We included 187 Danish patients with AAV and 1070 healthy controls. All were HLA typed at two-field resolution. The association of HLA alleles to PR3- or MPO-AAV was analysed. The contribution of the dominant molecular motifs of the HLA-DPB1 molecule to the risk of AAV was investigated by association studies that included specific amino acid sequences of the hypervariable regions in exon 2. RESULTS: Ninety-four percent of patients with PR3-AAV were carriers of HLA-DPB1*04:01 while all patients with PR3-AAV were carriers of an HLA-DPB1*04 allele, and 85% were homozygous. This was significantly more than in the control group (P < 0.0001). The association was even stronger when HLA-DPB1*04:02 and -DPB1*23:01 were included. HLA-DPB1*04:01, -DPB1*04:02 and -DPB1*23:01 share amino acids in positions 8-9, 69, 76 and 84-87 within the hypervariable regions, but only positions 69 and 84-87 contributed significantly to the disease risk. HLA-DRB1*15 was associated with an increased risk of developing PR3-AAV, while HLA-DRB1*04, -DRB1*07 and -DQB1*03 were associated with a reduced risk of kidney involvement in PR3-AAV. MPO-AAV was only weakly associated with HLA class I alleles. CONCLUSION: PR3-AAV is strongly associated with the HLA-DPB1 alleles HLA-DPB1*04:01, -DPB1*04:02 and -DPB1*23:01, which share amino acid sequences crucial for the peptide-binding groove.

Simple dichotomous assessment of cranial artery inflammation by conventional 18F-FDG PET/CT shows high accuracy for the diagnosis of giant cell arteritis: a case-control study.

PURPOSE: To estimate the diagnostic accuracy of conventional 18F-FDG PET/CT of cranial arteries in the diagnosis of giant cell arteritis (GCA). METHODS: The study was a retrospective case-control study. The reference diagnosis was fulfillment of the 1990 ACR criteria for GCA. All patients had new-onset GCA. Conventional 18F-FDG PET/CT was performed before glucocorticoid treatment. Controls were age- and sex-matched patients with a previous history of malignant melanoma (MM) undergoing surveillance PET/CT >6 months after MM resection. PET images were evenly cropped to include only head and neck and were assessed in random order by four nuclear medicine physicians blinded to reference diagnosis. Temporal (TA), maxillary (MA) and vertebral (VA) arteries were visually rated for 18F-FDG uptake. Interreader agreement was evaluated by Fleiss kappa. RESULTS: A total of 44 patients and 44 controls were identified. In both groups, the mean age was 69 years (p = 0.45) and 25/44 were women. 35/41 GCA patients were temporal artery biopsy positive (TAB). Considering only FDG uptake in TA and/or MA, diagnostic sensitivity and specificity was 64 and 100%. Including VA, sensitivity increased to 82% and specificity remained 100%. Interreader agreement was 91% and Fleiss kappa 0.82 for the PET diagnosis based on the cranial arteries. CONCLUSION: Conventional 18F-FDG PET/CT is an accurate and reliable tool to diagnose cranial arteritis in glucocorticoid-naïve GCA patients. The high diagnostic specificity suggests that TAB can be omitted in patients with 18F-FDG uptake in cranial arteries. 18F-FDG PET/CT performed in patients with suspected vasculitis should always include the head and neck.

Acetylcholinesterase-associated inflammation in patients with giant cell arteritis. Evaluation by histology and 11C-donepezil PET/CT.

OBJECTIVES: To investigate the in-situ expression of acetylcholinesterase (AChE) in the inflamed vessel wall of patients with biopsy-positive giant cell arteritis (GCA) as compared to biopsy-negative non-GCA patients, and to evaluate the in-vivo expression of AChE in patients with large-vessel GCA (LVGCA) by 11C-donepezil (AChE inhibitor) positron emission tomography/computed tomography (PET/CT). METHODS: Twenty-four biopsy-positive GCA and 44 biopsy-negative non-GCA patients were included for AChE histology. Immunohistochemical methods were used to determine the AChE expression. The histological inflammation and the AChE expression were assessed by an experienced pathologist on a 3-point scale. Two patients with newly diagnosed 18F-fluorodeoxyglucose (18F-FDG) PET/CT verified LVGCA were included for 11C-donepezil PET/CT. PET images were assessed by an experienced nuclear medicine physician. RESULTS: AChE was expressed in all 24 positive temporal artery biopsies, 10/24 showed high AChE expression (grade 2) and 14/24 showed moderate AChE expression (grade 1). No AChE expression was observed outside the media smooth muscle cells (grade 0) in any of the biopsy-negative non-GCA patients. The AChE expression was in 86% agreement with the histological inflammation. The AChE expression was not associated with any clinical or biochemical findings. In both LV-GCA patients, PET/CT revealed extensive vascular FDG uptake but no 11C-donepezil uptake. CONCLUSIONS: AChE is highly expressed in the inflamed vessel wall of patients with GCA. Although, 11C-donepezil PET/CT showed no vascular uptake in the FDG PET/CT verified LV-GCA patients, histological findings raise the possibility that AChE can be used in the development of new diagnostic and disease monitoring tools for GCA.

Three days of high-dose glucocorticoid treatment attenuates large-vessel 18F-FDG uptake in large-vessel giant cell arteritis but with a limited impact on diagnostic accuracy.

PURPOSE: To evaluate the in-treatment diagnostic accuracy of FDG PET/CT in large-vessel giant cell arteritis (LV-GCA) by serial scans before and after a short course of high-dose glucocorticoid treatment. METHODS: Twenty-four glucocorticoid-naïve patients with new-onset PET/CT verified LV-GCA (pre-treatment baseline PET) were prospectively included. Excluded were patients with a previous history of GCA or polymyalgia rheumatica, LV-GCA-mimicking conditions and patients on immunosuppressive therapy. All patients were treated with 60 mg of oral prednisolone daily and assigned for in-treatment FDG PET/CT after either 3 (PET3) or 10 days (PET10). Two experienced nuclear medicine physicians, blinded to patients' clinical data, reviewed the FDG PET/CT images. A visual semi-quantitative approach was used. Segmental and homogenous FDG uptake in the wall of the aorta and/or supra-aortic branches with higher uptake intensity than liver was considered consistent with vasculitis. Inter-reader reliability was evaluated. RESULTS: Although glucocorticoid treatment attenuated FDG uptake in large vessels, LV-GCA was accurately diagnosed in 10/10 patients after 3 days of treatment, but only in 5/14 patients after 10 days of treatment (p < 0.001). Interrater reliability was substantial (agreement 87%, Cohen's weighted kappa 0.70). No correlation between CRP and FDG uptake was found. CONCLUSIONS: Within 3 days of high-dose glucocorticoid treatment, FDG PET/CT can diagnose LV-GCA with high sensitivity. This window of opportunity ensures that prompt glucocorticoid treatment can be initiated to avoid debilitating GCA complications with a limited effect on diagnostic accuracy. After 10 days of treatment, FDG PET/CT sensitivity decreases significantly.

Prolonged risk of specific malignancies following cyclophosphamide therapy among patients with granulomatosis with polyangiitis.

OBJECTIVE: The long-term cancer risk for patients treated for granulomatosis with polyangiitis (GPA) is not well characterized. We assessed the risk of early and late-occurring cancers among 293 patients diagnosed with GPA from 1973 to 1999 and followed throughout 2010. METHODS: Cancer incidence in the cohort was determined by linkage with the Danish Cancer Registry and compared with that in the general population by calculation of standardized incidence ratios (SIRs). RESULTS: The median duration of follow-up was 9.7 years (range 0-36). Seventy-three cancers occurred, of which 30 were non-melanoma skin cancers (NMSCs) and 11 were bladder carcinomas. A high occurrence of NMSC was observed from the second year of follow-up onwards, with a SIR of 7.0 (95% CI 2.3, 16) for cases diagnosed ≥20 years after GPA. The incidence of bladder cancer increased after 5-9, 10-14 and 15-19 years of follow-up, with SIR estimates for these latency periods of 5.3 (95% CI 1.1, 15), 14.4 (95% CI 5.3, 31) and 10.5 (95% CI 1.2, 38), respectively. The incidence of myeloid leukaemia was significantly increased during years 5-9 [SIR 23.9 (95% CI 2.7, 86)]. Increased incidence of NMSC, bladder cancer and myeloid leukaemia was observed among patients exposed to cumulative CYC doses >36 g, while the only malignancy type observed in excess among those treated with lower CYC doses was NMSC. The cancer risk among CYC-naive patients was not significantly increased. CONCLUSION: GPA patients experience a greater than expected number of specific malignancies following conventional therapies. Our analyses demonstrate a substantially increased risk of very late-occurring NMSC and bladder cancer in this patient group.

Bony proliferations in rheumatoid arthritis, psoriatic arthritis and osteoarthritis using high-resolution peripheral quantitative computed tomography-A systematic literature review.

PURPOSE: Osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PsA) can all lead to the formation of bony proliferations (BP). This systematic review aimed to examine the characteristics of BPs in patients with RA, PsA, OA, and healthy controls (HC) using high-resolution peripheral quantitative computed tomography (HR-pQCT). Secondarily, we examined any treatment-related effect on BP number and size. METHODS: A systematic literature search was conducted in PubMed and Embase, and a total of 15 studies were included. RESULTS: Seven studies demonstrated a disease-specific variation in BP location. One study showed no difference in the number of BPs between patients with PsA and OA. The number of BPs was greater in patients with PsA compared to RA in one study, and to HC in another study, while one study documented no difference in the number of BPs between patients with RA and HC. Five studies showed larger BPs in patients with PsA compared to HC, and one study larger BPs in patients with PsA compared to RA. One study showed no difference in BP size between patients with PsA and OA. Secukinumab may have a potential effect on arresting BP progression. Otherwise, no other treatment was reported to influence BP size and progression. No standard definitions or measurement techniques for BPs using HR-pQCT have been identified. CONCLUSION: BPs showed disease-specific variations in location, size, and number. Results regarding treatment-related effects are sparse. An agreement on the definition and measurement technique for BPs using HR-pQCT is warranted for diagnostic accuracy, disease comparability, and monitoring potential.

SKG arthritis as a model for evaluating therapies in rheumatoid arthritis with special focus on bone changes.

The aim was to further characterize the SKG model of rheumatoid arthritis (RA) and its potential for studying intervention treatments, with special focus on bone targeting therapies. Three individual studies were conducted, using a total of 71 SKG mice, comparing arthritis induction with mannan versus zymosan A, female versus male mice, and the effect of dexamethasone intervention treatment initiated at different time points after arthritis induction. Hind paws were embedded undecalcified in methyl methacrylate, and sections were stained with Masson-Goldner trichrome. Areal Bone Mineral Density (aBMD) of the femora was determined with pDXA. RNA was extracted from the hind paws followed by the quantification by reverse transcriptase PCR. SKG mice stimulated with mannan presented a higher arthritis score than mice stimulated with zymosan A. Female SKG mice developed a more severe arthritis than male SKG mice. Dexamethasone inhibited arthritis clinically as well as histologically when the treatment was initiated prophylactically or within the first week of arthritis. Femoral aBMD was lower in animals with arthritis than in control animals. The RANKL RNA expression was elevated in arthritic mice, whereas OPG RNA expression was unchanged. The results suggest mannan as arthritis inductor and female instead of male mice in experiments as well as an optimal time window for the initiation of treatment. Systemic bone loss as well as local up regulation of RANKL was present early in SKG arthritis. These results demonstrate that SKG arthritis is a suitable new model for evaluating therapies in RA.

High-resolution peripheral quantitative computed tomography for the evaluation of bone erosions of metatarsophalangeal joints in patients with rheumatoid arthritis.

OBJECTIVES: To compare if the 4th and 5th metatarsophalangeal (MTP) joints evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT) could classify more patients with erosive rheumatoid arthritis (RA) compared with conventional radiography (CR) of the hands, wrists, and feet. Furthermore, we characterize and quantify bone erosions in the two MTP joints by HR-pQCT. METHODS: This single-center cross-sectional study included patients with established RA (disease duration ≥5 years). Blinded to patient data, the number and volume of erosions in the 4th and 5th MTP joints were measured by HR-pQCT, whereas the erosive scores by CR of 44 joints in the hands, wrists, and feet were assessed according to the Sharp/van der Heijde method. RESULTS: Among 42 participants, 30 patients were classified with erosive RA and 12 with non-erosive RA by CR. HR-pQCT of two MTP joints could classify more patients with erosive RA compared with CR of 44 joints (p = .03). The optimal cut-off value for the number and volume of erosions per patient in the 4th and 5th MTP joints by HR-pQCT was 7.5 erosions and 11.7 mm3 , respectively, for detecting erosive disease by CR. Erosions in the two MTP joints by HR-pQCT were found most frequently and were largest at the lateral quadrant of the 5th metatarsal head. CONCLUSION: The superiority of HR-pQCT of the 4th and 5th MTP joints compared with CR of 44 joints for classifying erosive RA provides a basis for larger studies evaluating if HR-pQCT could be used for diagnosing erosive RA in the future.

The Minimal Erosive Volume Needed for Radiographic Identification of Erosions in the Metacarpophalangeal Joints in Patients With Rheumatoid Arthritis.

OBJECTIVE: To compare in images, obtained by high-resolution peripheral quantitative computed tomography (HR-pQCT) and conventional radiography (CR) of the second and third metacarpophalangeal (MCP) joints, the minimal erosive cortical break needed to differentiate between pathological and physiological cortical breaks. METHODS: In this single-center cross-sectional study, patients with established rheumatoid arthritis (disease duration ≥ 5 yrs) had their second and third MCP joints of the dominant hand investigated by HR-pQCT and CR. Empirical estimation was used to find the optimal cut-off value for the number of erosions and total erosive volume, which were detectable between patients with and without erosions in the second and third MCP joints according to CR. RESULTS: The total erosive volume in the second and third MCP joints by HR-pQCT for CR-detected erosive disease was estimated to be 56.4 mm3 (95% CI 3.5-109.3). The sensitivity and specificity at this cutpoint were 78% and 83%, respectively, with an area under the receiver-operating characteristic curve (AUC) of 0.81. The optimal cut-off value for the number of erosions by HR-pQCT was 8.5 (95% CI 5.9-11.1) for CR-detected erosive disease in the second and third MCP joints. The sensitivity and specificity at this cutpoint were 74% and 88%, respectively, with an AUC of 0.81. CONCLUSION: Erosions by HR-pQCT were larger in patients with erosive damage in the second and third MCP joints by CR. We found that CR had poor sensitivity for detecting erosive disease when the erosive volume was < 56.4 mm3 or the number of erosions was < 8.5.

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.

Acceptance and image quality of high-resolution peripheral quantitative computed tomography of the metacarpophalangeal joints in rheumatoid arthritis.

OBJECTIVE: High-resolution peripheral quantitative computed tomography (HR-pQCT) requires longer immobilization time than conventional radiography, which challenges patient acceptance and image quality. Therefore, the aim was to investigate the acceptance of HR-pQCT in patients with rheumatoid arthritis (RA), and secondly the effect of an inflatable hand immobilization device on motion artefacts of the metacarpophalangeal (MCP) joints. METHODS: Fifty patients with established RA and a median (interquartile range) age of 64.3 (55.0-71.2) years had their MCP joints scanned by HR-pQCT with the hand positioned with and without an inflatable immobilization device followed by a full radiographic examination and a questionnaire on the imaging experience. The comparability of the erosion measures was investigated with and without the immobilization device using Bland-Altman plot and intrareader repeatability by intraclass correlation coefficient. The motion artefacts were graded for each acquisition, and intrareader repeatability was investigated by Cohen's kappa coefficient. RESULTS: Forty percent of the patients preferred HR-pQCT imaging, only 6% preferred conventional X-ray. Seventy-four percent reported it was not difficult to keep their fingers steady during the scan. Sixty percent of the patients reported the immobilization device helped keep their fingers steady. However, as motion artefacts were sparse, no clinically relevant difference was observed concerning the effect of the immobilization device on readability. The intrareader repeatability and comparability for the erosion measures were excellent. CONCLUSION: The high patient acceptance adds to the feasibility of HR-pQCT imaging of MCP joints in RA. The inflatable immobilization device did not reduce motion-induced image degradation.

Vasculitis therapy refines vasculitis mechanistic classification.

The primary vasculitides constitute a heterogeneous group of immune mediated diseases of incompletely understood pathogenesis currently classified by the size of blood vessels affected (Chapel Hill classification). In recent years, several drugs with well-characterized immunological targets have been tested in clinical trials in large vessel vasculitis and small vessel vasculitis. Such trials provide "reverse translational" or bedside to bench information about underlying pathogenic mechanisms. Therefore, the aim of this systematic literature review was to examine the evidence base for a more refined mechanistic immunological classification of vasculitis. A total of 40 studies (20 randomized controlled trials (RCTs), 16 prospective studies, 1 retrospective cohort study and 3 case series) were included for full qualitative assessment. RCTs concerning biologic therapy for large vessel vasculitis mainly supports interleukin 6 receptor inhibition (tocilizumab). RCTs concerning biologic therapy for granulomatosis with polyangiitis and microscopic polyangiitis mainly support anti-CD20 treatment (rituximab) and complement inhibition with a small molecule C5a receptor antagonist (avacopan) is an emerging treatment option. The biologic treatment of eosinophilic granulomatosis with polyangiitis is centered around interleukin 5 inhibition (mepolizumab). Studies on tumor necrosis factor alpha inhibition (adalimumab, infliximab, and etanercept) showed negative results in giant cell arteritis but some effect in Takayasu arteritis. Taken together, clinical studies with cytokine and cell specific drugs are dissecting the heterogeneous immunopathogenic mechanisms of vasculitis and support a mechanistic immunological classification. Especially, cytokine antagonism is pointing towards immunological distinctions between eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis/microscopic polyangiitis and differences between giant cell arteritis and Takayasu arteritis.