Beeldvorming – Inflammatie
Uitgangsvraag
Welke beeldvormende modaliteiten die inflammatie aantonen, kunnen worden ingezet bij patiënten die zich presenteren met artralgie om reumatoïde artritis (on)waarschijnlijk te maken?
Aanbeveling
Gebruik van:
- Echografie
- MRI
- Botscan en FDG-PET/CT
Wordt afgeraden bij patiënten met verdenking op RA om de kans op ontwikkelen van RA in te schatten gezien gebrek aan bewijs.
Overwegingen
Voor- en nadelen van de interventie en de kwaliteit van het bewijs
Beeldvorming bij verdenking op RA wordt enkel ingezet wanneer anamnese en lichamelijk onderzoek en eventueel laboratoriumonderzoek onvoldoende klinische aanwijzingen geven richting een diagnose.
In totaal zijn er vijf studies (d.w.z. 1 SR en 4 individuele studies) beschreven die de plaats van echografie, MRI, botscan of PET/CT voor het stellen van de diagnose RA en/of aantonen van inflammatie op basis van beeldvorming vergelijken met het stellen van de diagnose op basis van RA classificatie criteria of klinische praktijkervaring, bij patiënten met ‘clinically suspect arthralgia’ (CSA).
Over het algemeen berusten de DTA (diagnostic test assessment) studies op retrospectieve data, worden ze uitgevoerd in verschillende populaties, varieert de prevalentie (pre-test kans) van het ontwikkelen van de artritis of de diagnose ‘RA’, is het aantal patiënten per studie relatief klein, en is de beeldvormende diagnostiek door verschillende personen uitgevoerd. Daarnaast wordt de meerwaarde van beeldvorming boven baseline predictie model niet bepaald of gemeld, op de studie van van Steenbergen (2016) na, waar deze meerwaarde laag blijkt. Een ander aandachtspunt is het aantal (en welke) gewrichten dat wordt beoordeeld. De studie van Boer (2020) geeft zowel de diagnostische waardes van inflammatie op MRI voor voeten, handen als de combinatie. De diagnostische waardes van alleen handen en de combi (handen en voeten) verschillen niet sterk. Deze resultaten suggereren dat de additionele waarde van het detecteren van inflammatie in voeten waarschijnlijk afwezig is.
Mede door deze factoren variëren de diagnostische waardes. De bewijskracht voor de uitkomstmaten wordt gegradeerd met GRADE zeer laag. De bewijskracht voor de cruciale uitkomstmaten ‘positieve – en negatieve voorspellende waarde’ komt overeen met de bewijskracht voor de belangrijke uitkomstmaten.
Voor de modaliteit FDG-PET/CT scan zijn geen resultaten gerapporteerd ten aanzien van de diagnostische waardes.
Zoals eerder benoemd, wordt beeldvorming alleen ingezet wanneer anamnese, lichamelijk onderzoek en eventueel laboratoriumonderzoek onvoldoende klinische aanwijzingen geven richting een diagnose. In de studie van van Steenbergen (2018) was de kans op progressie naar artritis bij ACPA-positieve patiënten voor de test 63%. De studie laat zien dat na de MRI dit veranderde (na de test) naar 71% bij een positieve MRI en 40% bij een negatieve MRI. Bij ACPA-negatieve patiënten veranderde het risico voor de test (9%) naar (na de test) 18% bij een positieve MRI en 3% bij een negatieve MRI. De meerwaarde van de MRI op verandering van pretest naar posttest kans is derhalve beperkt.
Er is behoefte aan prospectief en geblindeerd DTA onderzoek naar het gebruik van m.n. echografie bij CSA bij het inschatten van de kans op het ontwikkelen van de diagnose klinische artritis en/of RA, waarbij voor de laatste de ACR 2010 classificatie criteria als referentietest gebruikt wordt. Bij voorkeur is de studieomvang groot (N > 200 patiënten), en worden ook meerdere testen (echografie, MRI, nucleaire modaliteiten) vergeleken in hetzelfde onderzoek. Tenslotte is het optimaal om ook de toegevoegde waarde te bepalen van de test, door deze toe te voegen aan een model met een uitgangs-ROC-AUC curve gebaseerd op anamnese, lichamelijk onderzoek en laboratoriumtests (waaronder BSE/CRP, RF/CCP).
De verschillende beeldvormende technieken hebben diverse voor- en nadelen, zie tabel 1.
Tabel 1. Overzicht voor- en nadelen verschillende beeldvormende technieken
|
|
Echografie |
MRI |
Botscan |
PET/CT-scan |
|
Voordelen |
Niet invasief
Tijd: 10 min.
Zithouding (afhankelijk welk gewricht onderzocht wordt)
Makkelijk beschikbaar.
Toegankelijk voor nagenoeg iedereen.
Geen schadelijke effecten van het onderzoek zelf.
|
Tijd: 15 min.
Nauwelijks schadelijke effecten van het onderzoek zelf, zeker wanneer er geen contrast toegediend wordt. |
Gehele skelet kan eenvoudig worden afgebeeld voor totaalbeeld.
|
Gehele skelet kan eenvoudig worden afgebeeld voor totaalbeeld.
|
|
Nadelen |
Relatief subjectief, afhankelijk van de expertise van de uitvoerder.
Gericht onderzoek op 1 lichaamsdeel
|
Contra-indicaties (metaal, claustrofobie)
Soms iv injectie nodig.
Gericht onderzoek op 1 lichaamsdeel.
Liggende positie in een tunnel dat als ongemakkelijk zou kunnen worden ervaren.
Het maakt veel kabaal.
Uitvoerend personeel is schaars en er is gemiddeld een wachttijd van meerdere weken/maanden |
Stralenbelasting.
Altijd iv injectie, incubatie = 4 uur
Tijd: 4 uur.
|
Stralenbelasting.
Altijd iv injectie, incubatie = 1 uur
|
|
Aandachtspunten |
Diversiteit aan gewrichten. Verschillen in kwaliteit van de apparatuur. Afhankelijk van uitvoerder.
|
Grote diversiteit aan onderzochte gewrichten. Verschillende wijze van uitvoering van de scans, protocollen, type scanners, veldsterktes, soort spoelen en of er intraveneus contrast gebruikt is.
|
Indien indicatie handen hiervan separate opnamen maken, dit kan voor de handen in zittende houding met handen op de detectoren.
Bij voorkeur gebruik maken van specifiek mallen voor handen en voeten. |
Liggen, indien indicatie handen dan met handen uitgestoken boven het hoofd
Bij voorkeur gebruik maken van specifieke mallen of steunen voor handen en voeten.
|
|
Kosten |
€ |
€€ |
€€ |
€€€ |
Literatuur voormalige richtlijn RA diagnostiek
Echografie
De conclusies uit de voormalige richtlijn komen overeen met de huidige bevindingen. Er bestaat weinig wetenschappelijk bewijs voor het gebruik van echografie voor het stellen van de diagnose RA bij patiënten met artralgie en een klinische verdenking op RA. Verschillende studies laten wel zien dat wanneer inflammatie is vastgesteld middels echografie, er een hogere kans is op het ontstaan van RA.
MRI
De conclusies uit de voormalige richtlijn komen overeen met de huidige bevindingen. Er bestaat weinig wetenschappelijk bewijs voor het gebruik van MRI voor het stellen van de diagnose RA bij patiënten met artralgie en een klinische verdenking op RA.
Nucleaire beeldvorming
De conclusies uit de voormalige richtlijn komen overeen met de huidige bevindingen. Er bestaat weinig wetenschappelijk bewijs voor het gebruik van nucleaire beeldvorming voor het stellen van de diagnose RA bij patiënten met artralgie en een klinische verdenking op RA.
Overige literatuur
Gezien deze gerichte vraagstelling bij de PICO, waarbij gekeken is naar CSA, is het artikel van Boylan (2011), over de rol van echo bij het diagnosticeren van vermoedelijke RA niet meegenomen in de samenvatting van de literatuur, omdat de doelgroepen in de verschillende studies sterk uiteenlopen. Dit artikel geeft echter wel een overzicht over de waarde van echografie bij het diagnosticeren van vroege RA. Op basis van meerdere studies wordt geconcludeerd dat echografie sensitief en specifiek is voor het diagnosticeren van RA. Daarnaast is de balans tussen voor-/nadelen van deze modaliteit gunstig.
De meerwaarde van nucleair geneeskundig onderzoek bij deze specifieke groep van patiënten met CSA is in de literatuur vooralsnog niet aangetoond.
Hoewel FDG-PET/CT actieve inflammatie afbeeldt (van neutrofielen, lymfocyten, monocyten, macrofagen), wordt de specificiteit in belangrijke mate beperkt door aspecifieke uptake in onder andere fibroblasten (Jamar, 2023). Voor afbeelding van de botombouw middels botscan (inclusief SPECT/CT) of natrium-fluoride PET/CT geldt dat toegevoegde waarde en kosteneffectiviteit voor de diagnostiek naar RA in patiënten met nieuwe artritis of artralgie met een klinische verdenking op RA onvoldoende zijn vastgesteld (Behesti, 2015; van den Wyngaert, 2016). Een nieuwe techniek voor het in kaart brengen van fibroblastactivatie en weefselremodellering bij RA betreft FAPI-PET/CT. De werkgroep doet geen uitspraak over het gebruik van deze techniek, vanwege onvoldoende bewijs.
In aanvulling op bovenstaande studies is tijdens ontwikkeling van de module en na het uitvoeren van de literatuursearch, een EULAR/ACR artikel verschenen waarin een risico-stratificatie methode is ontwikkeld voor patiënten met artralgie (van Steenbergen, 2025). Hierbij is, na exclusie van patiënten die reeds met DMARD’s werden behandeld, data uit acht verschillende cohorten (n = 2293) geanalyseerd m.b.t. risicofactoren en uitkomstdata voor het ontstaan van RA. Bij 730 patiënten was hierbij MRI-data beschikbaar en bij 835 patiënten US-data. Inflammatoire artritis (IA) ontwikkelde zich binnen één jaar bij 389 personen (17%).
De studie liet geen aanvullende waarde zien van US en een beperkte meerwaarde van MRI in de diagnose IA t.o.v. alleen klinische en serologische factoren (AUC bij aanvullende MRI: 0.87 (95%CI: 0.82-0.90) versus AUC bij klinische/serologische factoren: 0.80 (0.77-0.83).
In de toekomst zullen mogelijk meer studies volgen die de aanvullende diagnostische waarde van beeldvorming t.o.v. klinische en serologische factoren bij patiënten met artralgie onderzoeken. De werkgroep is vooralsnog echter terughoudend in het adviseren van MRI bij de diagnostiek van RA bij patiënten met artralgie. Hoewel de bovenstaande studie een meerwaarde van MRI laat zien, zijn er diverse aanvullende overwegingen. Zo is de methodiek voor de MRI verschillend in de diverse cohorten en daarmee niet (altijd) conform de radiologische praktijk in Nederland. Ook is er vooralsnog geen test-treat-trial verricht, waardoor de behandelconsequentie en de aanvullende klinische waarde voor de patiënt onduidelijk blijft. Tenslotte spelen ook kosten en belasting voor de patiënt (zij het beperkt, zie verderop) een rol.
Waarden en voorkeuren van patiënten (en evt. hun verzorgers)
Genoemde radiologische en nucleair geneeskundige onderzoeken zijn non-invasief of beperkt invasief (iv injectie) en beschikbaar in de meeste ziekenhuizen met relatief lage belastbaarheid voor de patiënt, hoewel houding en duur van een onderzoek een patiënt wel ongemak kunnen geven. Echo en MRI geven geen stralingsbelasting en de stralingsbelasting van FDG-PET/CT (6 – 8 mSv) en botscan (3 – 4 mSv) zijn dermate laag dat dit bij gepast (niet vaak herhaald) gebruik onder volwassenen geen punt van zorg is. Met steeds gevoeligere PET/CT-scanners zal de stralingsbelasting in de toekomst daarnaast verder afnemen.
De beoordeling kan van wisselende kwaliteit zijn en is (erg) afhankelijk van de beoordelaar (radioloog, gesubspecialiseerde radioloog of reumatoloog of nucleair geneeskundige).
Het is belangrijk om patiënten goed te informeren over het te verrichten onderzoek.
Kosten (middelenbeslag)
Van de beeldvorming is echografie het goedkoopst, MRI en botscan zijn ongeveer even duur, FDG-PET/CT is aanzienlijk duurder. Daartegenover staan niet-materiële en materiële kosten bij het niet uitvoeren van deze onderzoeken, waaronder onzekerheid voor patiënt, mogelijk progressie nog niet gediagnostiseerde ziekte en het onterecht starten of juist uitstellen van een behandeling.
Aanvaardbaarheid, haalbaarheid en implementatie
De haalbaarheid en beschikbaarheid van echografie, MRI en nucleair geneeskundige onderzoeken is goed. Het aantal patiënten met nieuwe CSA in Nederland is per jaar beperkt (enkele duizenden), en de huidige capaciteit aan echo door reumatologen en radiologen, en MRI en nucleaire imaging modaliteiten is (op moment van schrijven van de richtlijn) ruim voldoende voor deze vraag. Echter er zijn weinig laboranten.
Aangezien het advies is deze beeldvorming niet routinematig in te zetten, omdat er te weinig ondersteunende evidence is, zijn er geen verdere praktische, morele of ethische bezwaren.
Rationale van de aanbeveling:
Slechts enkele studies bestudeerden de waarde van echografie of MRI in opeenvolgende patiënten met artralgie die klinisch verdacht waren om RA te ontwikkelen. De aanwezige studies vonden enige associatie tussen echografie (met name een positief power doppler signaal), en voor MRI (met name synovitis handen en/of voeten) en de latere ontwikkeling van RA. Er zijn echter vrijwel geen onderzoeken die de aanvullende waarde bepalen boven alles wat al bekend is met anamnese, lichamelijk onderzoek, en standaard laboratoriumtesten. Ook is er nog geen goede behandeling om progressie van CSA naar RA te voorkomen. In de klinische praktijk worden patiënten met CSA ook niet of nauwelijks met een DMARD behandeld. Er bestaat weinig wetenschappelijk bewijs voor het gebruik van botscan en FDG-PET/CT of andere nucleaire beeldvorming voor het routinematig inzetten voor de diagnostiek naar RA in patiënten met nieuwe artritis of artralgie met een klinische verdenking op RA.
Eindoordeel:
Sterke aanbeveling voor niet doen.
Onderbouwing
Achtergrond
People may present with complaints of arthralgia (painful joints) which could be a sign of subclinical arthritis, and/or precursor to arthritis (inflammation of the joints) at a later stage. It may be important to diagnose this timely and correctly, to conceptually prevent both over- and undertreatment, resulting in better clinical outcomes for patients in the long run. However, making the diagnosis is complicated. The findings on physical examination are not evident in the case of arthralgia alone, making it challenging to distinguish which arthralgia will develop into arthritis and which will not. This may be because the arthritis is still subclinical, developing, or occurs in attacks and is absent at the time of presentation. Symptoms of arthralgia as precursor or arthritis include morning stiffness and nocturnal pain. The overarching term for these complaints is clinically suspected arthralgia (CSA; van Steenbergen, 2017). Since the history and physical examination are not accurate enough in detecting arthritis in this presentation of complaints it may be important to use diagnostic imaging which is suitable for detecting active inflammation (ultrasound, MRI, bone scintigraphy, PET/CT) to determine whether there is subclinical arthritis. Some people with CSA will develop arthritis, and eventually chronic arthritis consistent with RA. Research into CSA may therefore have undifferentiated arthritis and/or RA as outcome.
Important issues which need to be considered regarding use of diagnostics in CSA:
- There is not yet an effective treatment to prevent CSA from progressing to arthritis and ultimately RA. However, the trials that have been conducted show that the complaints can decrease during treatment and that diagnosis of RA can be postponed (Krijbolder, 2022; Gerlag, 2019; Cop, 2024; Rech, 2024).
- There are methodological challenges in research into imaging for CSA to predict arthritis. The reference standard for research into imaging in CSA for predicting clinical arthritis and subsequent possible RA is difficult. Most studies also do not report the added value of imaging added to a model with history, physical examination, CRP and CCP/RF, and do not report the numbers needed to test/diagnose.
Conclusies / Summary of Findings
Ultrasound vs. classification criteria
|
Very low GRADE
No GRADE |
The negative predictive value of MSUS for the risk of developing inflammatory arthritis in patients with clinically suspect arthralgia ranges from 75% to 93%, using the diagnosis of the treating rheumatologist as reference, and compared to a pretest chance of developing inflammatory arthritis of 79%.
No evidence was found regarding the sensitivity, specificity, and positive predictive value of MSUS compared to the RA classification criteria in patients with clinically suspect arthralgia to assess inflammation.
Source: (Rogier, 2022) |
MRI vs. classification criteria
|
Very Low GRADE |
The evidence is very uncertain about the diagnostic values of MRI, when compared to the RA classification criteria, in patients with clinically suspect arthralgia to assess any inflammation.
The sensitivity of MRI (any inflammation hands and feet) to assess inflammation in patients with clinically suspect arthralgia ranges from 78% to 84% using the RA 2010 classification criteria as reference.
The specificity of MRI (any inflammation hands and feet) to assess inflammation in patients with clinically suspect arthralgia ranges from 43% to 63% using the RA classification criteria as reference.
The positive predictive value of MRI (any inflammation hands and feet) to assess inflammation patients with clinically suspect arthralgia ranges from 18% to 31% using the RA classification criteria as reference.
The negative predictive value of MRI (any inflammation hands and feet) to assess inflammation in patients with clinically suspect arthralgia ranges from 60% to 98% using the RA classification criteria as reference.
The accuracy of MRI (any inflammation hands and feet) to assess inflammation in patients with clinically suspect arthralgia was 62% using the RA classification criteria as reference.
The AUC of MRI (any inflammation hands and feet) to assess inflammation in patients with clinically suspect arthralgia range from 0.63 to 0.72 using the RA classification criteria as reference.
Sources: (Boer, 2020; van Steenbergen, 2016) |
SPECT/CT vs. classification criteria
|
Very low GRADE |
The evidence is very uncertain about the diagnostic values of bone scintigraphy, when compared to the RA classification criteria, in patients with clinically suspect arthralgia to assess inflammation.
The sensitivity of bone scintigraphy (planar bone scintigraphy in mineralization phase and with blood pool) for the diagnosis of RA in patients with clinically suspect arthralgia ranges from 76% to 84%, using the RA classification criteria as reference.
The specificity of bone scintigraphy (mineralization phase and with blood pool) for the diagnosis of RA in patients with clinically suspect arthralgia ranges from 83% to 87%, using the RA classification criteria as reference.
The positive predicted value of bone scintigraphy (mineralization phase and with blood pool) for the diagnosis of RA in patients with clinically suspect arthralgia ranges from 76% to 79%, using the RA classification criteria as reference.
The negative predicted value of bone scintigraphy (mineralization phase and with blood pool) for the diagnosis of RA in patients with clinically suspect arthralgia ranges from 85% to 89%, using the RA classification criteria as reference.
Source: (Kim, 2016) |
FDG-PET/CT vs. classification criteria
|
No GRADE |
No evidence was found regarding the diagnostic values of FDG-PET/CT when compared to the RA classification criteria in patients with clinically suspect arthralgia to assess inflammation.
Source: (Dos Anjos, 2014) |
Samenvatting literatuur
Description of studies
Description of systematic review
Dos Anjos (2014) performed a systematic review to assess the role of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (18F-FDG) in patients with (suspected) RA. A systematic literature search was performed of the databases Medline, Cochrane Library, Lilacs, Pubmed and Scopus up to 2012. Original articles and case reports that addressed the role of PET in RA were included. Review articles, letters to the editor and editorials were excluded. More details are available in the evidence tables. A total of 12 studies were included. Of them two studies evaluated the role of PET regarding the diagnosis of RA, which were relevant for the current summary of literature (Okabe, 2011; Elzinga, 2007). A limitation of the current review is that only two studies met the criteria for the current PICO.
Description of additional studies
Kim (2016) performed a retrospective cohort study to investigate the diagnostic performance of bone scintigraphy with additional blood pool phase compared with conventional bone scintigraphy (CBS) in patients with arthralgia, using the RA 1987 classification criteria as reference standard.
Patients visiting their rheumatology department for arthralgia and undergoing bloodpool phase and mineralisation phase bone scintigraphy (BSBP) were included. Patients were excluded if their images field of blood pool phase were inappropriate, see also evidence tables for further information. In all cohorts, a bilateral MSUS examination was performed of the wrists, MCP joints 2–5, PIP joints 2–5 and MTP joints 2–5 (in cohort 3, MTP joint 4 was not examined). Subclinical synovitis was defined as greyscale (GS) ≥2 and/or power Doppler >0. In total 242 patients were included. The prevalence of RA (according to ACR 1987 criteria) was 39% (95/242). The mean age was 48 (SD 12) years and 199/242 (82%) were female. The study is limited by the fact that the prevalence of RA was relatively high, and outdated classification criteria were used as reference standard (1987 vs. 2010). In addition, the reference standard was based on the classification criteria as well as on other medical information e.g., laboratory test and radiographic findings.
Rogier (2022) performed a study (based on four cohorts) to investigate the diagnostic performance of negative musculoskeletal US (MSUS) for subclinical synovitis/tenosynovitis in excluding inflammatory arthritis development in patients with arthralgia.
Patients visiting their rheumatology department for arthralgia and undergoing MSUS were included. In total patients from four different cohorts were included, in which n=166, n=162, n= 40, and n=43 patients were included, respectively. The prevalence of developing inflammatory arthritis after 1 year ranged from 18 to 38%. The mean age was 45 years in three cohorts and 51 years in one cohort (= cohort 2). The disease duration was longer in cohort 2, compared to the other cohorts.
The study is limited by the fact that different US machines were used and different sonographers performed MSUS, no stratification was performed for ACPA, and the follow-up was limited to 1 year. In addition, the reference standard was based on the treating rheumatologist at physical examination. Besides, the study is limited by the fact that the OMERACT-RAMRIS criteria used were not developed for diagnostic purposes.
Boer (2020) performed a cohort study to investigate the diagnostic performance of MRI (feet, hands, or both) for prediction of RA in patients with arthralgia.
Patients visiting their rheumatology department for arthralgia and undergoing MRI were included. In total 357 patients were included in the analysis. The prevalence of developing RA was 38/357 (11%) after 1 year. The mean age was 44 (SD 12), and 280/357 (78%) were female.
The study is limited by the fact that the OMERACT-RAMRIS criteria used were not developed for diagnostic purposes.
Van Steenbergen (2016) performed a cohort study to investigate the progression to clinically detectable arthritis in terms of clinical and serological factors and the association with MRI inflammation. A total of 150 patients with clinically suspected arthralgia were included from the Leiden cohort in the Netherlands. Patients were included if having arthralgia of the small joints <1 year, suspected to progress to RA over time, according to clinical expertise of a rheumatologist. The prevalence of developing RA was 23/150 (15%) after a median follow-up of 75 weeks. The mean age of the study population was 43.2 years (SD12.9); 27% were male. For this literature summary, only the results regarding MRI were considered. For MRI, synovitis, bone marrow oedema (BME) and tenosynovitis were assessed in the MCP joints 2-5 and MTP joints 1-5 of the most painful side or dominant side in cases of equally severe symptoms. The study is limited by the fact that the OMERACT-RAMRIS criteria used were not developed for diagnostic purposes. Besides, the reported diagnostic values corresponded to progression to arthritis and not specifically RA.
Results
Outcomes for diagnostic values are summarized per intervention (i.e., Ultrasound, MRI, planar bone scintigraphy, SPECT/CT, FDG-PET/CT) and outcome measure.
1. Ultrasound (any joint)
The study of Rogier (2022) reported outcomes regarding the diagnostic values of MSUS using “not developing clinical arthritis based on the treating rheumatologist” as reference in patients with CSA, in 4 cohorts. No comparison was made with other tests (US, MRI) and no added value over already known variables (history taking, physical examination, CRP, RF/CCP) was calculated.
Negative predictive values were calculated (i.e., prior risk of not developing inflammatory arthritis.
In cohort 1, the prior risk of not developing inflammatory arthritis was 78% after 1 year. This resulted in a negative predictive value of 78% (95%CI 71% to 83%).
In cohort 2, the prior risk of not developing inflammatory arthritis was 82% after 1 year. This resulted in a negative predictive value of 82% (95%CI 75% to 87%).
In cohort 3, the prior risk of not developing inflammatory arthritis was 77% after 1 year. This resulted in a negative predictive value of 77% (95%CI 62% to 86%).
In cohort 4, the prior risk of not developing inflammatory arthritis was 72% after 1 year. This resulted in a negative predictive value of 72% (95%CI 57% to 83%).
The pooled prevalence of absence of inflammatory arthritis was 79% (95%CI 75% to 83%).
The pooled NPV was 86% (95%CI 81% to 89%). This means that of all negative diagnostic tests performed, 86% are correctly interpreted implying no development of RA within 1 year. Stratified by ACPA status, the pooled NPV was 67% (95%CI 57% to 77%) for ACPA-positive patients with CSA and 85% (95%CI 78% to 93%) for ACPA-negative patients with CSA.
2. MRI (any joint)
The study of Boer (2020) reported outcomes regarding the diagnostic values of MRI using the ACR 2010 criteria for RA as reference in patients with CSA, in 4 cohorts. No comparison was made with other tests (e.g., US,) and no added value over already known variables (history taking, physical examination, CRP, RF/CCP) was calculated.
In total 357 patients with arthralgia were included. Of them 38 (11%) were diagnosed with RA after 1 year.
Subclinical inflammation was assessed with MRI. The following diagnostic values (with 95%CI) were presented for detecting subclinical inflammation on MRI with development of RA as reference:
Feet - any inflammation
- Sensitivity: 47% (95%CI 31 to 64).
- Specificity: 88% (95%CI 84 to 91).
- Positive predictive value: 28% (95%CI 18 to 42).
- Negative predictive value: 94% (95%CI 91 to 96).
- Accuracy: 85% (95%CI 80 to 88)
- AUC: 0.68
Hands - any inflammation
- Sensitivity: 84% (95%CI 68 to 93).
- Specificity: 64% (95%CI 59 to 69).
- Positive predictive value: 19% (95%CI 13 to 26).
- Negative predictive value: 98% (95%CI 95 to 99).
- Accuracy: 66% (95%CI 61 to 77)
- AUC: 0.74
Hands and feet - any inflammation
- Sensitivity: 84% (95%CI 68 to 93).
- Specificity: 60% (95%CI 55 to 65).
- Positive predictive value: 17% (95%CI 12 to 24).
- Negative predictive value: 98% (95%CI 94 to 99).
- Accuracy: 62% (95%CI 57 to 67)
- AUC: 0.72
Van Steenbergen (2016) reported outcomes regarding the diagnostic value of MRI for arthritis development, not for RA. In total 150 patients with CSA were included, with a prevalence of RA after follow-up (median 75 weeks, IQR 41-106) of 23/150 patients (15%).
Subclinical inflammation (synovitis, BME and tenosynovitis) was assessed with MRI. The following diagnostic values (with 95%CI) were presented with development of arthritis as reference:
Hand and feet – any inflammation (all patients)
- Sensitivity: 81% (95%CI 74 to 88).
- Specificity: 63% (95%CI 55 to 72).
- Positive predictive value: 31% (95%CI 23 to 40).
- Negative predictive value: 94% (95%CI 90 to 98).
- AUC: 0.72 (95%CI 0.61 to 0.84).
Hand and feet – any inflammation (ACPA-positive patients)
- Sensitivity: 83% (95%CI 67 to 100).
- Specificity: 43% (95%CI 21 to 65).
- Positive predictive value: 71% (95%CI 51 to 92).
- Negative predictive value: 60% (95%CI 38 to 82).
- AUC: 0.63 (95%CI 0.36 to 0.90).
Hand and feet – any inflammation (ACPA-negative patients)
- Sensitivity: 78% (95%CI 70 to 68).
- Specificity: 65% (95%CI 56 to 74).
- Positive predictive value: 18% (95%CI 10 to 25).
- Negative predictive value: 97% (95%CI 93 to 100).
- AUC: 0.71 (95%CI 0.54 to 0.88).
3. Bone scintigraphy
The retrospective cohort study of Kim (2016) reported outcomes regarding the diagnostic values of planar bone scintigraphy (i.e., bloodpool phase and mineralisation phase) using 1987 ACR classification criteria (together with other medical data) as reference in patients with CSA. No comparison was made with other tests (US, MRI) and no added value over already known variables (history taking, physical examination, CRP, RF/CCP) was calculated.
Planar bone scintigraphy, mineralisation phase
In total 242 patients with arthralgia were included. Of them, after physical examination, 95 (39%) were diagnosed with RA based on the classification criteria.
In total 72 patients were correctly diagnosed, and 128 were correctly classified as non-RA.
This resulted in the following diagnostic values (with 95%CI):
- Sensitivity: 76% (66 to 84%).
- Specificity: 87% (81 to 92%).
- Positive predictive value: 79% (71 to 85%).
- Negative predictive value: 85% (80 to 89%).
Planar bone scintigraphy, including blood pool phase
In total 242 patients with arthralgia were included. Of them, after physical examination, 95 (39%) were diagnosed with RA based on the classification criteria.
In total 80 patients were correctly diagnosed, and 122 were correctly classified as non-RA.
This resulted in the following diagnostic values (with 95%CI):
- Sensitivity: 84% (75 to 91%).
- Specificity: 83% (76 to 89%).
- Positive predictive value: 76% (69 to 82%).
- Negative predictive value: 89% (84 to 93%).
Bloodpool phase aids the scintigraphic study to sensitively depict inflammation, without adding radiation burden to the procedure. The late phase of the study is aimed at sensitively reflecting bone remodeling, in these patients in reaction to (microscopic) bone erosion as a result of inflammation or osteoarthritis.
4. FDG-PET/CT
In the systematic review of dos Anjos (2014), two of the included studies reported outcomes regarding the role of FDG-PET/CT on detecting inflammation, and the possibility of arthritis. Only descriptive results were reported.
Both studies concluded that the degree of F-18 FDG uptake within joints may reflect active synovitis, as the uptake was higher in inflamed joints. Although both studies concluded as well that more specific evaluation is needed.
Level of evidence of the literature
The level of evidence (GRADE method) is determined per comparison and diagnostic outcome measure and is based on results from diagnostic accuracy studies and therefore starts at level “high”. Subsequently, the level of evidence was downgraded if there were relevant shortcomings in one of the several GRADE domains: risk of bias, inconsistency, indirectness, imprecision, and publication bias.
Ultrasound vs. classification criteria
The level of evidence regarding the outcome measure “negative predicted values” started as high, because results were from diagnostic accuracy studies. The level of evidence was downgraded by three levels because of risk of bias (i.e., reference standard was based on decision of threating physical; -1), indirectness (variety in study populations/definitions; -1), and imprecision (less than 1,000 patients screened; -1). The level of evidence for the outcome ‘negative predictive value’ is very low.
MRI vs. classification criteria
The level of evidence regarding the outcome measures sensitivity, specificity, positive predictive value, negative predictive value, accuracy and AUC started as high, because results were from diagnostic accuracy studies. The level of evidence was downgraded by three levels because of indirectness (aim of both studies was the development of (inflammatory) arthritis, which is not in line with the PICO, although subanalyses were performed for development of RA; -1), and imprecision (less than 1,000 patients screened in both studies; wide 95% CI; -2). The level of evidence for all diagnostic values is very low.
SPECT/CT vs. classification criteria
The level of evidence regarding the outcome measures sensitivity, specificity, positive predicted value, negative predicted value started as high, because results were from diagnostic accuracy studies. The level of evidence was downgraded by three levels because of risk of bias (i.e., only one study included in the analysis; -1), indirectness (reference standard was not only based on classification criteria; -1), and imprecision (less than 1,000 patients screened; -1). The level of evidence for the outcome ‘sensitivity, specificity, positive predictive value, negative predictive value’ is very low.
FDG-PET/CT vs. classification criteria
Not applicable as no diagnostic values were presented.
Zoeken en selecteren
A systematic review of the literature was performed to answer the following question:
What is the (comparative) diagnostic value of performing imaging techniques (ultrasound, MRI, nuclear modalities) in patients with clinically suspected arthralgia to assess the presence or future risk of arthritis?
This search is focused on diagnostic test accuracy studies (DTA), because the expectation was that formal test-treat trials (TT) would not be available. The following PICRO is therefore tailored for use in DTA studies, not TT studies.
| P: | Clinically suspect arthralgia |
| I: | Ultrasound, MRI (focus on detection of inflammation), or nuclear modalities (SPECT/CT, FDG-PET/CT) |
| C: | (when available): ultrasound, MRI (focus on detection of inflammation), or nuclear modalities (bone scintigraphy, SPECT/CT, FDG-PET/CT) |
| R: | Diagnosis of arthritis based on clinical judgement, or diagnosis of RA (classification criteria), both within 2 years after I |
| O: | Diagnostic test characteristics |
| T/S: | Secondary care, within 2 years from testing (I or C) |
Relevant outcome measures
The guideline development group considered positive predictive value and negative predictive value as a critical outcome measure for decision making; and sensitivity and specificity as an important outcome measure for decision making.
In addition, numbers needed to diagnose can be calculated when deemed of value.
The working group didn’t define a priori outcome measures, but used the definition as defined in the studies. No a priori cut off values for relevance of the outcomes have been established.
The working group defined the following boundaries for a minimal clinically important difference (MCID) both for mutual comparisons between tests and for tests in themselves:
1. The working group defined a MCID of 10% in sensitivity, specificity, PPV and NPV as a minimal clinically (patient) important difference.
2. The working group defined an area under the ROC of 0.80 (with relevant pretest chance ≈10 patients to screen for 1 confirmed diagnosis) as a MCID.
|
Outcome |
Consequence |
Consequence relevant for patient |
Importance (1-10) |
|
TP |
Confirmation of diagnosis |
Start treatment |
8 |
|
TN |
Ruling out diagnosis |
Continuing diagnostic proces |
10 |
|
FP |
Wrong diagnosis |
Possibly incorrect treatment |
8 |
|
FN |
Missing diagnosis |
Delayed start of treatment |
10 |
|
Inconclusive to interpret results |
Diagnosis remains unclear |
Possibly incorrect or delayed treatment |
7 |
|
TP= true positives, TN= true negatives, FP= false positives, FN= false negatives |
|||
Search and select (Methods)
The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms from 2010 until June 2024. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 201 systematic reviews (SR) and 2001 observational studies. Studies were selected based on the following criteria: PICO, adult patients, articles in English, no animal research. First, systematic reviews were selected for inclusion. Fifteen systematic reviews were selected based on title and abstract. After reading the full text, fourteen studies were excluded (see the table with reasons for exclusion under the tab Methods), and one SR was included. Additionally, observational studies from the same search were selected after the search period of the included SR. A total of three additional observational studies were included for the modality MRI (n=1), US (n=1), and SPECT/CT (n=1). In addition to the search of June 2024, an extra search was performed on 13 February 2025 without diagnostic filter (see tab Search strategy). This systematic literature search resulted in 456 systematic reviews (SR) and 3,518 observational studies. From this search, three studies were initially selected based on title/abstract screening (in addition to the first search). One extra observational study was included (van Steenbergen, 2016).
Results
One systematic review and four additional studies were included in the analysis of the literature. Important study characteristics and results are summarized in the evidence tables. The assessment of the risk of bias is summarized in the risk of bias tables.
Referenties
- Beheshti, Mohsen & Mottaghy, Felix & Payche, F & Behrendt, F & Wyngaert, T & Fogelman, I & Strobel, Klaus & Celli, Monica & Fanti, Stefano & Giammarile, Francesco & Krause, B & Langsteger, Werner. (2015). 18F-NaF PET/CT: EANM procedure guidelines for bone imaging. European journal of nuclear medicine and molecular imaging. 42. 10.1007/s00259-015-3138-y.
- Boer AC, Wouters F, Dakkak YJ, Niemantsverdriet E, van der Helm-van Mil AHM. Improving the feasibility of MRI in clinically suspect arthralgia for prediction of rheumatoid arthritis by omitting scanning of the feet. Rheumatology (Oxford). 2020 Jun 1;59(6):1247-1252. doi: 10.1093/rheumatology/kez436. PMID: 31566238; PMCID: PMC7244779.
- Boylan M. Should ultrasound be used routinely in the diagnosis of rheumatoid arthritis? Ir J Med Sci. 2020 May;189(2):735-748. doi: 10.1007/s11845-019-02096-3. Epub 2019 Oct 23. PMID: 31646431.
- Cope AP, Jasenecova M, Vasconcelos JC, Filer A, Raza K, Qureshi S, D'Agostino MA, McInnes IB, Isaacs JD, Pratt AG, Fisher BA, Buckley CD, Emery P, Ho P, Buch MH, Ciurtin C, van Schaardenburg D, Huizinga T, Toes R, Georgiou E, Kelly J, Murphy C, Prevost AT; APIPPRA study investigators. Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial. Lancet. 2024 Mar 2;403(10429):838-849. doi: 10.1016/S0140-6736(23)02649-1. Epub 2024 Feb 13. PMID: 38364839.
- Dale J, Stirling A, Zhang R, Purves D, Foley J, Sambrook M, Conaghan PG, van der Heijde D, McConnachie A, McInnes IB, Porter D. Targeting ultrasound remission in early rheumatoid arthritis: the results of the TaSER study, a randomised clinical trial. Ann Rheum Dis. 2016 Jun;75(6):1043-50. doi: 10.1136/annrheumdis-2015-208941. Epub 2016 Mar 29. PMID: 27026689.
- Diekhoff T, Ulas ST. Current and future role of CT and advanced CT applications in inflammatory arthritis in the clinic and trials. Skeletal Radiol. 2025 Apr 16. doi: 10.1007/s00256-025-04931-4. Epub ahead of print. PMID: 40234331.
- dos Anjos DA, da Mota LM. Tomografia por emissão de pósitrons com FDG-(18)F na avaliação de pacientes com artrite reumatoide--revisão sistemática [Positron emission tomography with (18)F-FDG in the evaluation of patients with rheumatoid arthritis--a systematic review]. Rev Bras Reumatol. 2014 Nov-Dec;54(6):474-82. Portuguese. doi: 10.1016/j.rbr.2014.07.002. Epub 2014 Sep 28. PMID: 25458029.
- Elzinga EH, van der Laken CJ, Comans EF, Lammertsma AA, Dijkmans BA, Voskuyl AE. 2-Deoxy-2-[F-18]fluoro-D-glucose joint uptake on positron emission tomography images: rheumatoid arthritis versus osteoarthritis. Mol Imaging Biol. 2007 Nov-Dec;9(6):357-60. doi: 10.1007/s11307-007-0113-4. PMID: 17902022; PMCID: PMC2040173.
- Gerlag DM, Safy M, Maijer KI, Tang MW, Tas SW, Starmans-Kool MJF, van Tubergen A, Janssen M, de Hair M, Hansson M, de Vries N, Zwinderman AH, Tak PP. Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study. Ann Rheum Dis. 2019 Feb;78(2):179-185. doi: 10.1136/annrheumdis-2017-212763. Epub 2018 Dec 1. PMID: 30504445; PMCID: PMC6352407.
- Haavardsholm EA, Aga AB, Olsen IC, Lillegraven S, Hammer HB, Uhlig T, Fremstad H, Madland TM, Lexberg ÅS, Haukeland H, Rødevand E, Høili C, Stray H, Noraas A, Hansen IJ, Bakland G, Nordberg LB, van der Heijde D, Kvien TK. Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial. BMJ. 2016 Aug 16;354:i4205. doi: 10.1136/bmj.i4205. PMID: 27530741; PMCID: PMC4986519.
- Jamar F, van der Laken CJ, Panagiotidis E, Steinz MM, van der Geest KSM, Graham RNJ, Gheysens O. Update on Imaging of Inflammatory Arthritis and Related Disorders. Semin Nucl Med. 2023 Mar;53(2):287-300. doi: 10.1053/j.semnuclmed.2022.08.010. Epub 2022 Sep 23. PMID: 36155690.
- Kim JY, Choi YY, Kim CW, Sung YK, Yoo DH. Bone Scintigraphy in the Diagnosis of Rheumatoid Arthritis: Is There Additional Value of Bone Scintigraphy with Blood Pool Phase over Conventional Bone Scintigraphy? J Korean Med Sci. 2016 Apr;31(4):502-9. doi: 10.3346/jkms.2016.31.4.502. Epub 2016 Feb 22. PMID: 27051232; PMCID: PMC4810331.
- Krijbolder DI, Verstappen M, van Dijk BT, Dakkak YJ, Burgers LE, Boer AC, Park YJ, de Witt-Luth ME, Visser K, Kok MR, Molenaar ETH, de Jong PHP, Böhringer S, Huizinga TWJ, Allaart CF, Niemantsverdriet E, van der Helm-van Mil AHM. Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): a randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet. 2022 Jul 23;400(10348):283-294. doi: 10.1016/S0140-6736(22)01193-X. PMID: 35871815.
- Møller-Bisgaard S, Hørslev-Petersen K, Ejbjerg B, Hetland ML, Ørnbjerg LM, Glinatsi D, Møller J, Boesen M, Christensen R, Stengaard-Pedersen K, Madsen OR, Jensen B, Villadsen JA, Hauge EM, Bennett P, Hendricks O, Asmussen K, Kowalski M, Lindegaard H, Nielsen SM, Bliddal H, Krogh NS, Ellingsen T, Nielsen AH, Balding L, Jurik AG, Thomsen HS, Østergaard M. Effect of Magnetic Resonance Imaging vs Conventional Treat-to-Target Strategies on Disease Activity Remission and Radiographic Progression in Rheumatoid Arthritis: The IMAGINE-RA Randomized Clinical Trial. JAMA. 2019 Feb 5;321(5):461-472. doi: 10.1001/jama.2018.21362. PMID: 30721294; PMCID: PMC6440221.
- Okabe T, Shibata H, Shizukuishi K, Yoneyama T, Inoue T, Tateishi U. F-18 FDG uptake patterns and disease activity of collagen vascular diseases-associated arthritis. Clin Nucl Med. 2011 May;36(5):350-4. doi: 10.1097/RLU.0b013e318212c858. PMID: 21467850.
- Rech J, Tascilar K, Hagen M, Kleyer A, Manger B, Schoenau V, Hueber AJ, Kleinert S, Baraliakos X, Braun J, Kiltz U, Fleck M, Rubbert-Roth A, Kofler DM, Behrens F, Feuchtenberger M, Zaenker M, Voll R, Venhoff N, Thiel J, Glaser C, Feist E, Burmester GR, Karberg K, Strunk J, Cañete JD, Senolt L, Filkova M, Naredo E, Largo R, Krönke G, D'Agostino MA, Østergaard M, Schett G. Abatacept inhibits inflammation and onset of rheumatoid arthritis in individuals at high risk (ARIAA): a randomised, international, multicentre, double-blind, placebo-controlled trial. Lancet. 2024 Mar 2;403(10429):850-859. doi: 10.1016/S0140-6736(23)02650-8. Epub 2024 Feb 13. PMID: 38364841.
- Rogier C, Frazzei G, Kortekaas MC, Verstappen M, Ohrndorf S, van Mulligen E, van Vollenhoven RF, van Schaardenburg D, de Jong PHP, van der Helm-van Mil AHM. An ultrasound negative for subclinical synovitis in arthralgia patients: is it helpful in identifying those not developing arthritis? Rheumatology (Oxford). 2022 Nov 28;61(12):4892-4897. doi: 10.1093/rheumatology/keac239. PMID: 35416958; PMCID: PMC9707035.
- van Steenbergen HW, Aletaha D, Beaart-van de Voorde LJ, Brouwer E, Codreanu C, Combe B, Fonseca JE, Hetland ML, Humby F, Kvien TK, Niedermann K, Nuño L, Oliver S, Rantapää-Dahlqvist S, Raza K, van Schaardenburg D, Schett G, De Smet L, Szücs G, Vencovský J, Wiland P, de Wit M, Landewé RL, van der Helm-van Mil AH. EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis. Ann Rheum Dis. 2017 Mar;76(3):491-496. doi: 10.1136/annrheumdis-2016-209846. Epub 2016 Oct 6. PMID: 27991858.
- van Steenbergen HW, Mangnus L, Reijnierse M, Huizinga TW, van der Helm-van Mil AH. Clinical factors, anticitrullinated peptide antibodies and MRI-detected subclinical inflammation in relation to progression from clinically suspect arthralgia to arthritis. Ann Rheum Dis. 2016 Oct;75(10):1824-30. doi: 10.1136/annrheumdis-2015-208138. Epub 2015 Nov 27. PMID: 26613769.
- Van den Wyngaert T, Strobel K, Kampen WU, Kuwert T, van der Bruggen W, Mohan HK, Gnanasegaran G, Delgado-Bolton R, Weber WA, Beheshti M, Langsteger W, Giammarile F, Mottaghy FM, Paycha F; EANM Bone & Joint Committee and the Oncology Committee. The EANM practice guidelines for bone scintigraphy. Eur J Nucl Med Mol Imaging. 2016 Aug;43(9):1723-38. doi: 10.1007/s00259-016-3415-4. Epub 2016 Jun 4. PMID: 27262701; PMCID: PMC493.
Evidence tabellen
Evidence table for systematic reviews of diagnostic test accuracy studies
|
Study reference |
Study characteristics |
Patient characteristics
|
Index test (test of interest) |
Reference test
|
Follow-up |
Outcome measures and effect size |
Comments |
|
Dos Anjos, (2014)
|
SR and meta-analysis
Literature search up to 2012
Diagnose RA A: Okabe, 2011 B: Elzinga, 2007
Study design: A: retrospective cohort study B: Clinical cross over study
Setting and Country: A: Japan B: Netherlands
Source of funding and conflicts of interest: No conflict of interest. |
Inclusion criteria
Only 2 studies for diagnosis.
Important patient characteristics:
N, mean age A: 72, 63y B: 25 (14 RA), 57y (RA) ….
Sex: Female (n, %) A: 47, 65% B: 21, 84% (10/14 RA, 72%)
|
Describe index and interpretation
A: PET Imaging or PET with CT. B: PET Imaging
|
Describe reference test: follow-up; prevalence (RA and other diagnose)
A: RA according to criteria (n=30/72)
B: RA according to criteria
|
See under reference test |
Outcome measures and effect size (include 95%CI and p-value if available):
No diagnostic values only descriptive for diagnosis. A: Seventy patients with arthritis, 30 with RA, were included in a study with the aim to establish a pat-tern of distribution of18F-FDG. Ninety percent of patients with RA exhibited polyarticular hypermetabolism. However, other diseases also demonstrated this pattern of polyarticular hypermetabolism, such as mixed connective tissue disease systemic sclerosis and RS3PE syndrome (Remitting Seronegative Symmetrical Synovitis with Pitting Edema syndrome).The atlantoaxial involvement was unique to patients with RA. Some sites of hypermetabolism were characteristic of other diseases, such as sacroiliac joint uptake in patients with ankylosing spondylitis; liver, spleen and bone marrow increased uptake in patients with adult Still’s disease; and arterial hyper-metabolism in patients with polymyalgia rheumatica. It should be noted that sites of extra-articular activity of AR may also exhibit hypermetabolism, such as lymph nodes and subcutaneous nodules17,18and this subject was not addressed by Okabe et al.;16this could have contributed to the differentiation of arthritides
B: As might be expected, patients with fibromyalgia showed no areas of articular hypermetabolism. The number of hyper-metabolic joints in patients with RA (88) was significantly higher than in patients with osteoarthritis (12) (P < 0.001). How-ever, uptake intensity was not statistically different between the two groups. This indicates that PET does not work adequately as a tool for the differential diagnosis of these diseases.
|
Conclusion:
Although the actual role of this new technique in the investigation of RA is not yet established,18F-FDG PET is a promising tool for the determination of disease activity and in the assessment and prediction of treatment response inpatients with RA. It might be that in the future,18F-FDGPET will play a more important role in the diagnosis and assessment of disease activity.
Limitations: Only two studies relevant for PICO. |
*comparator test equals the C of the PICO; two or more index/ comparator tests may be compared; note that a comparator test is not the same as a reference test
Evidence table for diagnostic test accuracy studies
|
Study reference |
Study characteristics |
Patient characteristics
|
Index test (test of interest) |
Reference test
|
Follow-up |
Outcome measures and effect size |
Comments |
|
Kim, 2016 |
Type of study[1]: retrospective cohort study
Setting and country: Hospital, South-Korea
Funding and conflicts of interest: None. |
Inclusion criteria:
Exclusion criteria: Inappropriate imaging
N= 242
Prevalence: 95/242 (39%)
Mean age ± SD: 48 (12)
Sex: 18% M (43)/ 82% F (199)
Other important characteristics:
At baseline, patients with RA were significant different compared non-RA patients for joint count, CRP/ESR, RF, anti ccp
|
Describe index test 1: Scintigraphy diagnostic performance bone scintigraphy with additional blood pool phase (BSBP)
Cut-off point(s): See method part
Describe index test 2: Scintigraphic diagnostic performance conventional bone scintigraphy (CBS)
Cut-off point(s): See method part
|
Describe reference test[2]: Reference standard diagnoses of RA were made by the experienced rheumatologist based on the 1987 American College of Rheumatology (ACR) classification criteria (11) together with detailed history taking and physical examination, laboratory
Cut-off point(s): See method part
|
Time between the index test en reference test: Unknow, but assessors were not aware of clinical data.
For how many participants were no complete outcome data available? N.a. à retrospective cohort study.
Reasons for incomplete outcome data described? n.a. |
Outcome measures and effect size (include 95%CI and p-value if available)4:
CBS
With arthralgia (n= 242) Diagnostic values for diagnose RA (n=95) Sensi= 75.8 (72/95) Speci = 87.1 (128/147) PPV= 79.1 (72/91) NPV= 84.8 (128/151)
With arthritis (n=128) Diagnostic values for diagnose RA (n=87) Sensi= 80.5 (70/87) Speci= 70.7 (29/41) PPV= 85.4 (70/82) NPV= 63.0 (29/46)
BSBP
With arthralgia (n= 242) Diagnostic values for diagnose RA (n=95) Sensi= 84.2 (80/95) Speci = 83.0 (122/147) PPV= 76.2 (80/105) NPV= 89.1 (122/137)
With arthritis (n=128) Diagnostic values for diagnose RA (n=87) Sensi= 87.4 (76/87) Speci= 63.4 (26/41) PPV= 83.5 (76/91) NPV= 70.3 (26/37) |
BSBP higher sensitivity compared to CBS, but lower specificity
Prevalence seems to be higher in study population compared to general population.
In conclusion, both BSBP and CBS appear to provide acceptable accuracy and comparable diagnostic performance for diagnosing of RA among patients with arthralgia and/or arthritis. However, in the patients with arthralgia, BSBP was found to be more sensitive than CBS and more accurate when interpreted with the result of anti-CCP antibody. This could help physicians diagnose RA in daily clinical practice.
|
|
Boer, 2020 |
Type of study[3]: Cohort study
Setting and country: Hospital, the Netherlands
Funding and conflicts of interest:
The research leading to these results has received funding from the Dutch Arthritis Foundation and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Starting grant, agreement No. 714312). No consequences for study.
The authors have declared no conflicts of interest. |
Inclusion criteria: CSA cohort that had 51 year followup (to allow time for IA development)
Exclusion criteria: Patients without MRI or included in trial as well.
N=357
Prevalence: AI 63/357= 18%
RA 38/357=11%
Mean age= 44 years
Sex: 22% M / 78% F
Other important characteristics: Any subclinical MRI-detected inflammation in hands or feet was present in 43%; hands and feet, 29% only in hands, and 3% only in feet.
|
Describe index test: MRI
Cut-off point(s): Inflammation based on OMERACT RAMIS, see methods part
|
Describe reference test[4]: Development of AI
And
Development of RA
Cut-off point(s): joint swelling at physical examination by a rheumatologist.
The secondary outcome, fulfilment of the 2010 criteria,was also assessed. |
Time between the index test en reference test: Within 1 year.
For how many participants were no complete outcome data available? N (%)
N.a.
|
Outcome measures and effect size (include 95%CI and p-value if available)4:
Outcome of interest regarding development of RA
Diagnostic values for subclinical inflammation and RA development within the first year.
Feet – any inflammation Speci= 88 (84-91) PPV= 28 (18-42) NPV= 94 (91-96) Accuracy= 85 (80-88)
Hands– any inflammation Speci = 64 (59-69) PPV= 19 (13-26) NPV= 98 (95-99) Accuracy= 66 (61-71)
Hands and feet – any inflammation Speci= 60 (55-65) PPV= 17 (12-24) NPV= 98 (94-99) Accuracy= 62 (57-67)
Outcome also present for tenosynovitis, synovitis, bone marrow oedema in supplement. |
Conclusion: In conclusion, the current study showed the prognostic value of MRI-detected tenosynovitis of the feet in patients with arthralgia at risk for RA. Further, although MRI-detected tenosynovitis was associated with IA development, addition of foot MRI to hand MRI did not increase the predictive accuracy. Therefore, in light of time management and cost efficiency, MRI of the feet can be omitted
limitations: OMERACT RAMIS was used, but these values were not developed for diagnostic purpose. |
|
Van Steenbergen, 2016 |
Type of study[5]: Cohort study
Setting and country: Hospital, the Netherlands
Funding and conflicts of interest: Non-commercial funding and no conflicts of interest reported. |
Inclusion criteria: Patients with CSA of the small joints for <1 year that was, according to the clinical expertise of the rheumatologist, suspected to progress to RA over time. Follow-upduration of >6 months.
Exclusion criteria: -
N=150
Prevalence of arthritis: 30/150 (20%)
Prevalence of RA: 23/150 (15%)
Mean age= 43.2 years
Sex: 27% male
|
Describe index test: MRI
Cut-off point(s): Inflammation based on OMERACT RAMIS, see methods part
|
Describe reference test[6]: Development of arthritis and RA
Cut-off point(s): Joint s at physical examination by a rheumatologist.
|
Time between the index test en reference test: Within 1 year.
For how many participants were no complete outcome data available? N=28.
|
Outcome measures and effect size (include 95%CI and p-value if available)4:
Outcome of interest regarding development of RA
Diagnostic values for subclinical inflammation and arthritis development within the first year.
Hand and feet – any inflammation (all patients) - Sensitivity: 81% (95%CI 74 to 88).
Hand and feet – any inflammation (ACPA-positive patients) - Sensitivity: 83% (95%CI 67 to 100). - Specificity: 43% (95%CI 21 to 65).
Hand and feet – any inflammation (ACPA-negative patients) - Sensitivity: 78% (95%CI 70 to 68). - Specificity: 65% (95%CI 56 to 74). |
Patients with incomplete data were patients with no data for both ACPA status and MRI at 1-year follow-up. Two patients developed arthritis after the first year and were classified as non-arthritis in the analyses. Further limitations: OMERACT RAMIS was used, but these values were not developed for diagnostic purpose. |
|
Rogier, 2022 |
Type of study: Cohort
Setting and country: Hospital, the Netherlands
Funding and conflicts of interest: received funding from: Dutch Arthritis Foundation (SONAR cohort, clinically suspect arthralgia Leiden cohort, Amsterdam cohort, clinically suspect arthralgia Rotterdam), The European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (starting grant, agreement no. 714312) (clinically suspect arthralgia Leiden cohort).
Some authors have disclosures, see article |
Inclusion criteria: arthralgia patients at risk for inflammatory arthritis development in four independent Dutch arthralgia cohorts. All patients underwent MSUS at baseline and were followed for inflammatory arthritis development for 1 year.
Exclusion criteria: Not mentioned in article, only when patients were included.
N= 1 = 166 2 = 162 3= 40 4 = 43
Prevalence of development clinical arthritis: 1= 37 (22%) 2= 29 (18%) 3= 9 (23%) 4= 12 (38%)
Mean age ± SD: 1 = 45 (12) 2 = 51 (11) 3 = 45 (11) 4 = 45 (13)
Sex: n, % F 1 = 136 (82) 3 = 28 (70) 4 = 34 (81)
Other important characteristics: Disease duration in cohort 2 longer compared to other cohorts. |
Describe index test: US
Cut-off point(s): Negative MSUS, no subclinical synovitis
Comparator test:
Cut-off point(s):
|
Describe reference test: Not developing inflammatory arthritis
Cut-off point(s): All cohorts had inflammatory arthritis development after 1 year as outcome, which had to be detected by the treating rheumatologist at physical examination. Importantly, no DMARD treatment (including glucocorticoid injections) was allowed in the arthralgia phase before inflammatory arthritis development.
|
Time between the index test en reference test: Within 1 year
For how many participants were no complete outcome data available? N (%) N.a.
Reasons for incomplete outcome data described? |
Outcome measures and effect size (include 95%CI and p-value if available):
Prior risk of not developing inflammatory arthritis. = NPV
1 78 (71 to 83) 2 82 (75 to 87) 3 77 (62 to 86) 4 72 (57-83)
Combined
|
Conclusion result contributed <10%, performing MSUS might therefore not be necessary for the purpose of ruling out future inflammatory arthritis development.
Limitation - different machines and sonographers were used for MSUS
Remark: Purpose is not developing |
Risk of Bias tabellen
Table of quality assessment for systematic reviews of diagnostic studies
Based on AMSTAR checklist (Shea et al.; 2007, BMC Methodol 7: 10; doi:10.1186/1471-2288-7-10) and PRISMA checklist (Moher et al 2009, PLoS Med 6: e1000097; doi:10.1371/journal.pmed1000097)
|
Study
First author, year |
Appropriate and clearly focused question?1
Yes/no/unclear |
Comprehensive and systematic literature search?2
Yes/no/unclear |
Description of included and excluded studies?3
Yes/no/unclear |
Description of relevant characteristics of included studies?4
Yes/no/unclear |
Assessment of scientific quality of included studies?5
Yes/no/unclear |
Enough similarities between studies to make combining them reasonable?6
Yes/no/unclear |
Potential risk of publication bias taken into account?7
Yes/no/unclear |
Potential conflicts of interest reported?8
Yes/no/unclear |
|
Dos Anjos, 2014 |
Unlcear, only purpose |
Yes, described in method part |
Yes, described in method part |
Unclear, not all relevant characteristics are described. |
No, not described. |
No, no detailed information. Outcomes not pooled. |
Unclear, publication bias is not mentioned in the publication. |
Unclear, mentioned for the SR but not for the individual studies. |
1. Research question (PICO) and inclusion criteria should be appropriate (in relation to the research question to be answered in the clinical guideline) and predefined
2. Search period and strategy should be described; at least Medline searched
3. Potentially relevant studies that are excluded at final selection (after reading the full text) should be referenced with reasons
4. Characteristics of individual studies relevant to the research question (PICO) should be reported
5. Quality of individual studies should be assessed using a quality scoring tool or checklist (preferably QUADAS-2; COSMIN checklist for measuring instruments) and taken into account in the evidence synthesis
6. Clinical and statistical heterogeneity should be assessed; clinical: enough similarities in patient characteristics, diagnostic tests (strategy) to allow pooling? For pooled data: at least 5 studies available for pooling; assessment of statistical heterogeneity and, more importantly (see Note), assessment of the reasons for heterogeneity (if present)? Note: sensitivity and specificity depend on the situation in which the test is being used and the thresholds that have been set, and sensitivity and specificity are correlated; therefore, the use of heterogeneity statistics (p-values; I2) is problematic, and rather than testing whether heterogeneity is present, heterogeneity should be assessed by eye-balling (degree of overlap of confidence intervals in Forest plot), and the reasons for heterogeneity should be examined.
7. There is no clear evidence for publication bias in diagnostic studies, and an ongoing discussion on which statistical method should be used. Tests to identify publication bias are likely to give false-positive results, among available tests, Deeks’ test is most valid. Irrespective of the use of statistical methods, you may score “Yes” if the authors discuss the potential risk of publication bias.
8. Sources of support (including commercial co-authorship) should be reported in both the systematic review and the included studies. Note: To get a “yes,” source of funding or support must be indicated for the systematic review AND for each of the included studies.
Risk of bias assessment diagnostic accuracy studies (QUADAS II, 2011)
|
Study reference |
Patient selection
|
Index test |
Reference standard |
Flow and timing |
Comments with respect to applicability |
|
Kim, 2016 |
Was a consecutive or random sample of patients enrolled? Yes, All consecutive patients who first visited our rheumatology department from January 2010 to December 2010 for arthralgia (pain, tenderness, or swelling) and underwent BSBP were retrospectively accessed.
Was a case-control design avoided? Yes, retrospective cohort
Did the study avoid inappropriate exclusions? Yes, only data with inappropriate imaging were excluded.
|
Were the index test results interpreted without knowledge of the results of the reference standard? Yes, Two board-certified nuclear medicine physicians with 15 years and 3 years of experience, respectively, who were not aware of the clinical data, results of laboratory tests, and other imaging studies, evaluated the bone scintigraphy in consensus
If a threshold was used, was it pre-specified? Yes, see method part.
|
Is the reference standard likely to correctly classify the target condition? Yes, reference standard diagnoses of RA were made by the experienced rheumatologist based on the 1987 American College of Rheumatology (ACR) classification criteria (11) together with detailed history taking and physical examination, laboratory tests, and radiographic findings for symptomatic joints.
Were the reference standard results interpreted without knowledge of the results of the index test? Yes, see under index test.
|
Was there an appropriate interval between index test(s) and reference standard? Unclear, not mentioned in text
Did all patients receive a reference standard? Yes, inclusion criteria
Did patients receive the same reference standard? Yes, inclusion criteria
Were all patients included in the analysis? Yes, retrospective cohort study
|
Are there concerns that the included patients do not match the review question? Yes, in the paper is stated that the prevalence is higher compared to the general population
Are there concerns that the index test, its conduct, or interpretation differ from the review question? No, question about diagnostic value. Values are present.
Are there concerns that the target condition as defined by the reference standard does not match the review question? Unclear, diagnosis of RA in the study is based on old classification criteria as reference standard (1987 vs. 2010). In addition, the reference standard was based on the classification criteria as well as on other medical information e.g., laboratory test and radiographic findingsThe research question fot this guideline focussed on classification criteria only. |
|
CONCLUSION: Could the selection of patients have introduced bias?
RISK: LOW |
CONCLUSION: Could the conduct or interpretation of the index test have introduced bias?
RISK: LOW
|
CONCLUSION: Could the reference standard, its conduct, or its interpretation have introduced bias?
RISK: LOW |
CONCLUSION Could the patient flow have introduced bias?
RISK: low |
|
|
|
Boer, 2020 |
Was a consecutive or random sample of patients enrolled? Yes
Was a case-control design avoided? Yes
Did the study avoid inappropriate exclusions? Yes
|
Were the index test results interpreted without knowledge of the results of the reference standard? Yes
If a threshold was used, was it pre-specified? Yes, OMERACT
|
Is the reference standard likely to correctly classify the target condition? Yes
Were the reference standard results interpreted without knowledge of the results of the index test? Yes, within 1 year
|
Was there an appropriate interval between index test(s) and reference standard? Yes
Did all patients receive a reference standard? Yes
Did patients receive the same reference standard? Yes
Were all patients included in the analysis? No |
Are there concerns that the included patients do not match the review question? Yes, diagnostic values are reported for arthritis instead of RA.
Are there concerns that the index test, its conduct, or interpretation differ from the review question? No
Are there concerns that the target condition as defined by the reference standard does not match the review question? No |
|
CONCLUSION: Could the selection of patients have introduced bias?
RISK: LOW |
CONCLUSION: Could the conduct or interpretation of the index test have introduced bias?
RISK: SOME CONCERNS. OMERACT not developed for diagnostic purpose
|
CONCLUSION: Could the reference standard, its conduct, or its interpretation have introduced bias?
RISK: LOW |
CONCLUSION Could the patient flow have introduced bias?
RISK: LOW |
|
|
|
Van Steenbergen (2016) |
Was a consecutive or random sample of patients enrolled? Yes
Was a case-control design avoided? Yes
Did the study avoid inappropriate exclusions? Yes
|
Were the index test results interpreted without knowledge of the results of the reference standard? Yes
If a threshold was used, was it pre-specified? Yes, OMERACT
|
Is the reference standard likely to correctly classify the target condition? Yes
Were the reference standard results interpreted without knowledge of the results of the index test? Yes, within 1 year
|
Was there an appropriate interval between index test(s) and reference standard? Yes
Did all patients receive a reference standard? Yes
Did patients receive the same reference standard? Yes
Were all patients included in the analysis? No, 28 patients were excluded due to missing data on ACPA status and/or MRI
|
Are there concerns that the included patients do not match the review question? Yes, diagnostic values are reported for arthritis instead of RA.
Are there concerns that the index test, its conduct, or interpretation differ from the review question? No
Are there concerns that the target condition as defined by the reference standard does not match the review question? No
|
|
CONCLUSION: Could the selection of patients have introduced bias?
RISK: LOW |
CONCLUSION: Could the conduct or interpretation of the index test have introduced bias?
RISK: SOME CONCERNS. OMERACT not developed for diagnostic purpose
|
CONCLUSION: Could the reference standard, its conduct, or its interpretation have introduced bias?
RISK: LOW |
CONCLUSION Could the patient flow have introduced bias?
RISK: HIGH Two patients who developed arthritis after one year were classified in non-arthritis group. |
||
|
Rogier, 2022 |
Was a consecutive or random sample of patients enrolled? Yes
Was a case-control design avoided? Yes
Did the study avoid inappropriate exclusions? Yes
|
Were the index test results interpreted without knowledge of the results of the reference standard? Yes
If a threshold was used, was it pre-specified? Yes
|
Is the reference standard likely to correctly classify the target condition? Yes
Were the reference standard results interpreted without knowledge of the results of the index test? Yes
|
Was there an appropriate interval between index test(s) and reference standard? Yes
Did all patients receive a reference standard? Yes
Did patients receive the same reference standard? Yes
Were all patients included in the analysis? Unclear |
Are there concerns that the included patients do not match the review question? no
Are there concerns that the index test, its conduct, or interpretation differ from the review question? no
Are there concerns that the target condition as defined by the reference standard does not match the review question? No, but the rq is not completely according to PICO
|
|
|
CONCLUSION: Could the selection of patients have introduced bias?
RISK: LOW |
CONCLUSION: Could the conduct or interpretation of the index test have introduced bias?
RISK: LOW |
CONCLUSION: Could the reference standard, its conduct, or its interpretation have introduced bias?
RISK: low/unclear, although ref is not completely according to PICO |
CONCLUSION Could the patient flow have introduced bias?
RISK: unclear |
|
Judgments on risk of bias are dependent on the research question: some items are more likely to introduce bias than others, and may be given more weight in the final conclusion on the overall risk of bias per domain:
Patient selection:
- Consecutive or random sample has a low risk to introduce bias.
- A case control design is very likely to overestimate accuracy and thus introduce bias.
- Inappropriate exclusion is likely to introduce bias.
Index test:
- This item is similar to “blinding” in intervention studies. The potential for bias is related to the subjectivity of index test interpretation and the order of testing.
- Selecting the test threshold to optimise sensitivity and/or specificity may lead to overoptimistic estimates of test performance and introduce bias.
Reference standard:
- When the reference standard is not 100% sensitive and 100% specific, disagreements between the index test and reference standard may be incorrect, which increases the risk of bias.
- This item is similar to “blinding” in intervention studies. The potential for bias is related to the subjectivity of index test interpretation and the order of testing.
Flow and timing:
- If there is a delay or if treatment is started between index test and reference standard, misclassification may occur due to recovery or deterioration of the condition, which increases the risk of bias.
- If the results of the index test influence the decision on whether to perform the reference standard or which reference standard is used, estimated diagnostic accuracy may be biased.
- All patients who were recruited into the study should be included in the analysis, if not, the risk of bias is increased.
Judgement on applicability:
Patient selection: there may be concerns regarding applicability if patients included in the study differ from those targeted by the review question, in terms of severity of the target condition, demographic features, presence of differential diagnosis or co-morbidity, setting of the study and previous testing protocols.
Index test: if index tests methods differ from those specified in the review question there may be concerns regarding applicability.
Reference standard: the reference standard may be free of bias but the target condition that it defines may differ from the target condition specified in the review question.
Table of excluded studies
|
Referentie |
Reden voor exclusie |
|
de Pablo P, Dinnes J, Berhane S, Osman A, Lim Z, Coombe A, Raza K, Filer A, Deeks JJ. Systematic review of imaging tests to predict the development of rheumatoid arthritis in people with unclassified arthritis. Semin Arthritis Rheum. 2022 Feb;52:151919. doi: 10.1016/j.semarthrit.2021.10.003. Epub 2021 Oct 24. PMID: 34782180. |
Patient population not according to PICO |
|
Lage-Hansen PR, Lindegaard H, Chrysidis S, Terslev L. The role of ultrasound in diagnosing rheumatoid arthritis, what do we know? An updated review. Rheumatol Int. 2017 Feb;37(2):179-187. doi: 10.1007/s00296-016-3587-z. Epub 2016 Nov 1. PMID: 27803965. |
No diagnostic values reported |
|
Rogier C, Frazzei G, Kortekaas MC, Verstappen M, Ohrndorf S, van Mulligen E, van Vollenhoven RF, van Schaardenburg D, de Jong PHP, van der Helm-van Mil AHM. An ultrasound negative for subclinical synovitis in arthralgia patients: is it helpful in identifying those not developing arthritis? Rheumatology (Oxford). 2022 Nov 28;61(12):4892-4897. doi: 10.1093/rheumatology/keac239. PMID: 35416958; PMCID: PMC9707035. |
Not according to PICO |
|
Suter LG, Fraenkel L, Braithwaite RS. Role of magnetic resonance imaging in the diagnosis and prognosis of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2011 May;63(5):675-88. doi: 10.1002/acr.20409. PMID: 21557523; PMCID: PMC3135707. |
More recent review included |
|
van den Berg R, Ohrndorf S, Kortekaas MC, van der Helm-van Mil AHM. What is the value of musculoskeletal ultrasound in patients presenting with arthralgia to predict inflammatory arthritis development? A systematic literature review. Arthritis Res Ther. 2018 Oct 11;20(1):228. doi: 10.1186/s13075-018-1715-8. PMID: 30305156; PMCID: PMC6235211. |
No diagnostic values reported |
|
Aleo E, Barbieri F, Sconfienza L, Zampogna G, Garlaschi G, Cimmino MA. Ultrasound versus low-field magnetic resonance imaging in rheumatic diseases: a systematic literature review. Clin Exp Rheumatol. 2014 Jan-Feb;32(1 Suppl 80):S91-8. Epub 2014 Feb 17. PMID: 24528870. |
Patient population not according to PICO |
|
Colebatch AN, Edwards CJ, Østergaard M, van der Heijde D, Balint PV, D'Agostino MA, Forslind K, Grassi W, Haavardsholm EA, Haugeberg G, Jurik AG, Landewé RB, Naredo E, O'Connor PJ, Ostendorf B, Potocki K, Schmidt WA, Smolen JS, Sokolovic S, Watt I, Conaghan PG. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013 Jun;72(6):804-14. doi: 10.1136/annrheumdis-2012-203158. Epub 2013 Mar 21. PMID: 23520036. |
More recent review included |
|
Ten Cate DF, Luime JJ, Swen N, Gerards AH, De Jager MH, Basoski NM, Hazes JM, Haagsma CJ, Jacobs JW. Role of ultrasonography in diagnosing early rheumatoid arthritis and remission of rheumatoid arthritis--a systematic review of the literature. Arthritis Res Ther. 2013 Jan 8;15(1):R4. doi: 10.1186/ar4132. PMID: 23298444; PMCID: PMC3672772. |
No diagnostic values reported |
|
Zhao CY, Jiang YX, Li JC, Xu ZH, Zhang Q, Su N, Yang M. Role of Contrast-enhanced Ultrasound in the Evaluation of Inflammatory Arthritis. Chin Med J (Engl). 2017 Jul 20;130(14):1722-1730. doi: 10.4103/0366-6999.209885. PMID: 28685724; PMCID: PMC5520561. |
More recent review included |
|
Boylan M. Should ultrasound be used routinely in the diagnosis of rheumatoid arthritis? Ir J Med Sci. 2020 May;189(2):735-748. doi: 10.1007/s11845-019-02096-3. Epub 2019 Oct 23. PMID: 31646431. |
Not according to PICO |
|
Bruijnen ST, Gent YY, Voskuyl AE, Hoekstra OS, van der Laken CJ. Present role of positron emission tomography in the diagnosis and monitoring of peripheral inflammatory arthritis: a systematic review. Arthritis Care Res (Hoboken). 2014 Jan;66(1):120-30. doi: 10.1002/acr.22184. PMID: 24124027. |
No diagnostic values reported |
|
Machado PM, Koevoets R, Bombardier C, van der Heijde DM. The value of magnetic resonance imaging and ultrasound in undifferentiated arthritis: a systematic review. J Rheumatol Suppl. 2011 Mar;87:31-7. doi: 10.3899/jrheum.101072. PMID: 21364054. |
More recent review included |
|
Sakellariou G, Scirè CA, Adinolfi A, Batticciotto A, Bortoluzzi A, Delle Sedie A, De Lucia O, Dejaco C, Epis OM, Filippucci E, Idolazzi L, Picchianti Diamanti A, Zabotti A, Iagnocco A, Filippou G. Differential Diagnosis of Inflammatory Arthropathies by Musculoskeletal Ultrasonography: A Systematic Literature Review. Front Med (Lausanne). 2020 May 7;7:141. doi: 10.3389/fmed.2020.00141. PMID: 32457913; PMCID: PMC7221062. |
More recent review included |
|
Woodworth TG, Morgacheva O, Pimienta OL, Troum OM, Ranganath VK, Furst DE. Examining the validity of the rheumatoid arthritis magnetic resonance imaging score according to the OMERACT filter-a systematic literature review. Rheumatology (Oxford). 2017 Jul 1;56(7):1177-1188. doi: 10.1093/rheumatology/kew445. PMID: 28398508; PMCID: PMC5850856. |
Not accoding to PICO |
|
den Hollander NK, Verstappen M, Sidhu N, van Mulligen E, Reijnierse M, van der Helm-van Mil AHM. Hand and foot MRI in contemporary undifferentiated arthritis: in which patients is MRI valuable to detect rheumatoid arthritis early? A large prospective study. Rheumatology (Oxford). 2022 Oct 6;61(10):3963-3973. doi: 10.1093/rheumatology/keac017. PMID: 35022703; PMCID: PMC9536782. |
Focus on UA |
|
Tamai M, Grundeken V, Arima K, Brinck RT, Mil AHMVH, Ohki N, Uetani M, Kawakami A. Predictive Value of Magnetic Resonance Imaging-detected Tenosynovitis of the Metacarpophalangeal and Wrist Joints for the Development of Rheumatoid Arthritis among Patients with Undifferentiated Arthritis. Intern Med. 2023 Aug 15;62(16):2329-2334. doi: 10.2169/internalmedicine.0077-22. Epub 2023 Jan 12. PMID: 36631087; PMCID: PMC10484776. |
Focus on UA |
Verantwoording
Beoordelingsdatum en geldigheid
Publicatiedatum : 13-04-2026
Beoordeeld op geldigheid : 13-04-2026
Algemene gegevens
De ontwikkeling/herziening van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd door de Stichting Kwaliteitsgelden Medisch Specialisten (SKMS). Patiëntenparticipatie bij deze richtlijn werd medegefinancierd uit de Kwaliteitsgelden Patiënten Consumenten (SKPC) binnen het programma Kwaliteit, Inzicht en Doelmatigheid in de medisch specialistische Zorg (KIDZ). De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.
Samenstelling werkgroep
Voor het ontwikkelen van de richtlijnmodule is in 2023 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor patiënten met een inflammatoire (reumatische) aandoening.
Werkgroep
- Dr. S.M. van der Kooij (voorzitter), reumatoloog, werkzaam in HagaZiekenhuis, NVR.
- Dr. A.A. den Broeder, reumatoloog en klinisch epidemioloog, werkzaam in Sint Maartensklinkiek en Radboud Universitair Medische Centrum, NVR.
- Prof. Dr. D. van der Woude, reumatoloog, werkzaam in Leids Universitair Medisch Centrum, NVR.
- Drs. T. de Mooij, AIOS reumatologie, werkzaam in Erasmus Medisch Centrum, NVR.
- Drs. Z. Kerami, reumatoloog, werkzaam in Dijklander Ziekenhuis, NVR (tot december 2024, vanaf mei 2025 werkzaam als reumatoloog bij NHS Lothian).
- Dr. M.A. Korteweg, radioloog, Reade, NVvR.
- Dr. W. van der Bruggen, nucleair geneeskundige, werkzaam in Slingeland Ziekenhuis en Streekziekenhuis Koningin Beatrix, NVNG.
- Dr. M.C.F.J. de Rotte, klinisch chemicus, werkzaam in Amsterdam Universitair Medisch Centrum, NVKC.
- MSc. J. Postma, verpleegkundig specialist reumatologie, werkzaam in Martini Ziekenhuis, V&VN.
- Drs. H. Koning, patiëntvertegenwoordiger, Nationale Vereniging ReumaZorg Nederland.
Klankbordgroep
- P. Borsje, ervaringsdeskundige en beleidsmedewerker Patiëntenparticipatie en Communicatie, Nationale Vereniging ReumaZorg Nederland, Nationale Vereniging ReumaZorg Nederland.
Met ondersteuning van
- Dr. L. Küpers , adviseur, Kennisinstituut van de Federatie Medisch Specialisten.
- Dr. M.M.A. Verhoeven, adviseur, Kennisinstituut van de Federatie Medisch Specialisten tot april 2025.
- Drs. J.M.H. van der Hart MSc, adviseur, Kennisinstituut van de Federatie Medisch Specialisten vanaf april 2025.
- Drs. F.A. Pepping MSc, junior adviseur, Kennisinstituut van de Federatie Medisch Specialisten.
Belangenverklaringen
Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten via secretariaat@kennisinstituut.nl.
Tabel Gemelde (neven)functies en belangen werkgroep
|
Werkgroeplid |
Functie |
Nevenfuncties |
Gemelde belangen |
Ondernomen actie |
|
Dr S.M. van der Klooij (voorzitter), NVR |
Reumatoloog |
- |
- |
Geen
|
|
Dr. A.A. den Broeder, NVR |
Reumatoloog en epidemioloog |
- Expert advisering ZIN - Associate editor Rheumatology |
Extern gefinancierd onderzoek door o.a. ZonMw, Abbvie, Galapagos en Novartis. Geen raakvlakken met richtlijnmodules. |
Geen |
|
Prof. Dr. D. van der Woude, NVR |
Reumatoloog |
- Docent Antonius Academy Nieuwegein - Hoofdredacteur Nederlands Tijdschrift voor Reumatologie - Advisory board Galapagos (gebruik van JAK-remmers, 2019 en 2020) |
Onderzoek gefinancierd door ZonMw, NWO en FOREUM. Geen raakvlakken met richtlijnmodules. |
Geen |
|
Drs. T. de Mooij, NVR |
AIOS reumatologie |
- |
- |
Geen |
|
Drs. Z. Kerami, NVR |
Reumatoloog |
- |
- |
Geen |
|
Dr. M.A. Korteweg, NVvR |
Radioloog |
- Radioloog waarnemer Bovenij ziekenhuis, Acibadem,in Kralendijk Bonaire -PI ESSR uniform grading CT scans of SIjoints -reviewer ECR |
- |
Geen |
|
Dr. W. van der Bruggen, NVNG |
Nucleair geneeskundige |
- |
- |
Geen |
|
Dr. M.C.F.J. de Rotte, NVKC |
Klinisch chemicus |
Vakspecialist-auditor Raad voor accredatie |
Meerdere onderzoeksproejcten in personalized medicine of methotrexaat bij RA (niet extern gefinancierd, geen raakvlakken met richtlijn). |
Geen |
|
MSc. J. Postma, V&VN |
Verpleegkundig specialist reumatologie |
Deelname ontwikkeling ‘ziektekaarten in beeld’ ReumaZorg Nederland |
Online sessie ‘patient journey’ reumapatienten Pfizer (eenmalig, geen raakvlakken met richtlijn) |
Geen |
|
Drs. H. Koning, ReumaZorg Nederland |
Patiëntvertegenwoordiger |
- Referent Patientenfederatie Nederland |
- |
Geen |
Inbreng patiëntenperspectief
De werkgroep besteedde aandacht aan het patiëntenperspectief door een afgevaardigde van de patiëntenvereniging Nationale Vereniging ReumaZorg Nederland. De conceptrichtlijn is tevens voor commentaar voorgelegd aan deze patiëntenvereniging en de eventueel aangeleverde commentaren zijn bekeken en verwerkt.
Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz
Bij de richtlijnmodule voerde de werkgroep conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uit om te beoordelen of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling is de richtlijnmodule op verschillende domeinen getoetst (zie het stroomschema bij Werkwijze).
|
Module |
Uitkomst raming |
Toelichting |
|
Beeldvorming - Inflammatie |
Geen financiële gevolgen |
Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (5.000-40.000 patiënten per jaar), volgt ook uit de toetsing dat het overgrote deel van de zorgaanbieders en zorgverleners al aan de norm voldoet. Er worden daarom geen substantiële financiële gevolgen verwacht. |
Werkwijze
Voor meer details over de gebruikte richtlijnmethodologie verwijzen wij u naar de Werkwijze. Relevante informatie voor de ontwikkeling/herziening van deze richtlijnmodule is hieronder weergegeven.
Zoekverantwoording
Algemene informatie
|
Cluster/richtlijn: Diagnostiek bij verdenking reumatoïde artritis - UV7 Beeldvorming - artralgie - inflammatie – V2 |
|
|
Uitgangsvraag/modules: Welke (nucleaire) beeldvormende modaliteiten moeten worden meegenomen in de diagnostiek van reumatoïde artritis bij presentatie artralgie met een focus op aantonen/ uitsluiten van artritis ? |
|
|
Database(s): Embase.com, Ovid/Medline |
Datum: 13 februari 2025 |
|
Periode: vanaf 2010 |
Talen: geen restrictie |
|
Literatuurspecialist: Esther van der Bijl |
Rayyan review: https://rayyan.ai/reviews/1075268 |
|
BMI-zoekblokken: voor verschillende opdrachten wordt (deels) gebruik gemaakt van de zoekblokken van BMI-Online https://blocks.bmi-online.nl/ Deduplication: voor het ontdubbelen is gebruik gemaakt van http://dedupendnote.nl:9777/ |
|
|
Toelichting: Voor deze vraag is gezocht op de elementen (artralgie OF reumatoïde artritis) EN (echo OF MRI OF CT OF nucleaire modaliteiten) EN inflammatie.
Zoals afgesproken is gezocht met een extra zoekblok: inflammatie. Voor de tweede versie is gezocht zonder sensitiviteit/ specificiteitfilter.
De sleutelartikelen worden gevonden met deze search. |
|
|
Te gebruiken voor richtlijntekst: In de databases Embase.com en Ovid/Medline is, in aanvulling op de search van 25 juni 2024, op 13 februari 2025 systematisch gezocht naar systematische reviews en observationele studies over beeldvormende modaliteiten in de diagnostiek van reumatoïde artritis bij presentatie artralgie met een focus op aantonen/ uitsluiten van artritis. De literatuurzoekactie leverde 3974 nieuwe unieke treffers op. |
|
Zoekopbrengst - 13 februari 2025
|
|
EMBASE |
OVID/MEDLINE |
Ontdubbeld |
|
SR |
581 |
275 |
456 |
|
Observationele studies |
4905 |
2750 |
3518 |
|
Rayyan 25 juni 2024 |
|
|
2202 |
|
Totaal |
5486 |
3025 |
3974* |
*in Rayyan
Zoekopbrengst - 25 juni 2024
|
|
EMBASE |
OVID/MEDLINE |
Ontdubbeld |
|
SR |
182 |
104 |
201 |
|
Observationele studies |
1735 |
1093 |
2001 |
|
Totaal |
1917 |
1197 |
2202* |
*in Rayyan
Zoekstrategie - 13 februari 2025
Embase.com
|
No. |
Query |
Results |
|
#1 |
'rheumatoid arthritis'/exp OR 'arthralgia'/exp OR (((rheuma* OR reuma* OR revma*) NEAR/3 (arthrit* OR artrit* OR diseas* OR condition* OR nodule*)):ti,ab,kw) OR ((inflammat* NEAR/3 (arthrit* OR artrit* OR joint*)):ti,ab,kw) OR ((('auto immun*' OR autoimmun* OR deform* OR persistent) NEAR/3 (arthrit* OR artrit*)):ti,ab,kw) OR ((felty* NEAR/2 syndrome*):ti,ab,kw) OR ((caplan* NEAR/2 syndrome*):ti,ab,kw) OR (((ach* OR pain*) NEAR/3 (joint* OR articular*)):ti,ab,kw) OR arthralgia*:ti,ab,kw OR arthrodynia*:ti,ab,kw OR polyarthralgia*:ti,ab,kw OR 'acpa positive*':ti,ab,kw OR 'positive* acpa':ti,ab,kw |
455214 |
|
#2 |
'nuclear magnetic resonance imaging'/exp OR 'mri scanner'/exp OR ('magnetic resonance':ab,ti AND (image:ab,ti OR images:ab,ti OR imaging:ab,ti)) OR mri:ab,ti OR mris:ab,ti OR nmr:ab,ti OR mra:ab,ti OR mras:ab,ti OR zeugmatograph*:ab,ti OR 'mr tomography':ab,ti OR 'mr tomographies':ab,ti OR 'mr tomographic':ab,ti OR 'mr imag*':ti,ab,kw OR 'proton spin':ab,ti OR ((magneti*:ab,ti OR 'chemical shift':ab,ti) AND imaging:ab,ti) OR fmri:ab,ti OR fmris:ab,ti OR rsfmri:ti,ab,kw |
1713763 |
|
#3 |
'computer assisted tomography'/exp OR 'cat scan*':ti,ab,kw OR ((compute* NEAR/3 tomograph*):ti,ab,kw) OR ct:ti,ab,kw |
1892570 |
|
#4 |
'ultrasound'/exp OR 'ultrasound scanner'/exp OR 'echography'/exp OR 'endoscopic ultrasonography'/exp OR ultraso*:ti,ab,kw OR sonograph*:ti,ab,kw OR echograph*:ti,ab,kw OR sonogram*:ti,ab,kw |
1570611 |
|
#5 |
'positron emission tomography'/exp OR 'pet scanner'/exp OR 'single photon emission computed tomography'/exp OR 'fluorodeoxyglucose f 18'/exp OR 'sodium fluoride f 18'/exp OR 'bone scintiscanning'/exp OR 'technetium 99m'/exp OR 'fluorodeoxyglucose'/exp OR 'fibroblast activation protein inhibitor'/exp OR ((pet NEAR/3 scan*):ti,ab,kw) OR 'p.e.t.':ti,ab,kw OR 'positron emission tomograph*':ti,ab,kw OR 'positron tomograph':ti,ab,kw OR 'positron emission compute* tomograph*':ti,ab,kw OR 'single photon emission compute* tomograph*':ti,ab,kw OR 'single photon emission computer tomograph*':ti,ab,kw OR '18f fdg':ti,ab,kw OR '18f fluorodeoxyglucose':ti,ab,kw OR 'fludeoxyglucose f18':ti,ab,kw OR 'fludeoxyglucose f 18':ti,ab,kw OR 'fluoride sodium f 18':ti,ab,kw OR 'fluoride sodium f18':ti,ab,kw OR 'sodium fluoride f 18':ti,ab,kw OR 'sodium fluoride f18':ti,ab,kw OR 'bone scan*':ti,ab,kw OR 'bone scinti*':ti,ab,kw OR 'osteoscintigraph*':ti,ab,kw OR 'skelet* scintigraph*':ti,ab,kw OR 'skeleton scinti*':ti,ab,kw OR 'spect':ti,ab,kw OR '99m tc':ti,ab,kw OR '99mtc':ti,ab,kw OR 'tc 99 m':ti,ab,kw OR 'tc 99m':ti,ab,kw OR 'tc99m':ti,ab,kw OR 'technetium 99 m':ti,ab,kw OR 'technetium 99m':ti,ab,kw OR 'technetium tc 99':ti,ab,kw OR 'technetium tc 99m':ti,ab,kw OR 'technetium tc99':ti,ab,kw OR 'fluorodeoxyglucose':ti,ab,kw OR 'fibroblast activation protein inhibitor*':ti,ab,kw OR fapi:ti,ab,kw |
458424 |
|
#6 |
#2 OR #3 OR #4 OR #5 |
4319999 |
|
#7 |
'synovitis'/exp OR (((arthriti* OR joint* OR disease*) NEAR/3 activ*):ti,ab,kw) OR 'inflammat*':ti,ab,kw OR 'synoviti*':ti,ab,kw OR tenosynoviti*:ti,ab,kw |
2116251 |
|
#8 |
#1 AND #6 AND #7 |
25807 |
|
#9 |
#8 AND [2010-2024]/py NOT ('conference abstract'/it OR 'editorial'/it OR 'letter'/it OR 'note'/it) NOT (('animal'/exp OR 'animal experiment'/exp OR 'animal model'/exp OR 'nonhuman'/exp) NOT 'human'/exp) |
10610 |
|
#10 |
'meta analysis'/exp OR 'meta analysis (topic)'/exp OR metaanaly*:ti,ab OR 'meta analy*':ti,ab OR metanaly*:ti,ab OR 'systematic review'/de OR 'cochrane database of systematic reviews'/jt OR prisma:ti,ab OR prospero:ti,ab OR (((systemati* OR scoping OR umbrella OR 'structured literature') NEAR/3 (review* OR overview*)):ti,ab) OR ((systemic* NEAR/1 review*):ti,ab) OR (((systemati* OR literature OR database* OR 'data base*') NEAR/10 search*):ti,ab) OR (((structured OR comprehensive* OR systemic*) NEAR/3 search*):ti,ab) OR (((literature NEAR/3 review*):ti,ab) AND (search*:ti,ab OR database*:ti,ab OR 'data base*':ti,ab)) OR (('data extraction':ti,ab OR 'data source*':ti,ab) AND 'study selection':ti,ab) OR ('search strategy':ti,ab AND 'selection criteria':ti,ab) OR ('data source*':ti,ab AND 'data synthesis':ti,ab) OR medline:ab OR pubmed:ab OR embase:ab OR cochrane:ab OR (((critical OR rapid) NEAR/2 (review* OR overview* OR synthes*)):ti) OR ((((critical* OR rapid*) NEAR/3 (review* OR overview* OR synthes*)):ab) AND (search*:ab OR database*:ab OR 'data base*':ab)) OR metasynthes*:ti,ab OR 'meta synthes*':ti,ab |
1104324 |
|
#11 |
'major clinical study'/de OR 'clinical study'/de OR 'case control study'/de OR 'family study'/de OR 'longitudinal study'/de OR 'retrospective study'/de OR 'prospective study'/de OR 'comparative study'/de OR 'cohort analysis'/de OR ((cohort NEAR/1 (study OR studies)):ab,ti) OR (('case control' NEAR/1 (study OR studies)):ab,ti) OR (('follow up' NEAR/1 (study OR studies)):ab,ti) OR (observational NEAR/1 (study OR studies)) OR ((epidemiologic NEAR/1 (study OR studies)):ab,ti) OR (('cross sectional' NEAR/1 (study OR studies)):ab,ti) |
8647868 |
|
#12 |
'case control study'/de OR 'comparative study'/exp OR 'control group'/de OR 'controlled study'/de OR 'controlled clinical trial'/de OR 'crossover procedure'/de OR 'double blind procedure'/de OR 'phase 2 clinical trial'/de OR 'phase 3 clinical trial'/de OR 'phase 4 clinical trial'/de OR 'pretest posttest design'/de OR 'pretest posttest control group design'/de OR 'quasi experimental study'/de OR 'single blind procedure'/de OR 'triple blind procedure'/de OR (((control OR controlled) NEAR/6 trial):ti,ab,kw) OR (((control OR controlled) NEAR/6 (study OR studies)):ti,ab,kw) OR (((control OR controlled) NEAR/1 active):ti,ab,kw) OR 'open label*':ti,ab,kw OR (((double OR two OR three OR multi OR trial) NEAR/1 (arm OR arms)):ti,ab,kw) OR ((allocat* NEAR/10 (arm OR arms)):ti,ab,kw) OR placebo*:ti,ab,kw OR 'sham-control*':ti,ab,kw OR (((single OR double OR triple OR assessor) NEAR/1 (blind* OR masked)):ti,ab,kw) OR nonrandom*:ti,ab,kw OR 'non-random*':ti,ab,kw OR 'quasi-experiment*':ti,ab,kw OR crossover:ti,ab,kw OR 'cross over':ti,ab,kw OR 'parallel group*':ti,ab,kw OR 'factorial trial':ti,ab,kw OR ((phase NEAR/5 (study OR trial)):ti,ab,kw) OR ((case* NEAR/6 (matched OR control*)):ti,ab,kw) OR ((match* NEAR/6 (pair OR pairs OR cohort* OR control* OR group* OR healthy OR age OR sex OR gender OR patient* OR subject* OR participant*)):ti,ab,kw) OR ((propensity NEAR/6 (scor* OR match*)):ti,ab,kw) OR versus:ti OR vs:ti OR compar*:ti OR ((compar* NEAR/1 study):ti,ab,kw) OR (('major clinical study'/de OR 'clinical study'/de OR 'cohort analysis'/de OR 'observational study'/de OR 'cross-sectional study'/de OR 'multicenter study'/de OR 'correlational study'/de OR 'follow up'/de OR cohort*:ti,ab,kw OR 'follow up':ti,ab,kw OR followup:ti,ab,kw OR longitudinal*:ti,ab,kw OR prospective*:ti,ab,kw OR retrospective*:ti,ab,kw OR observational*:ti,ab,kw OR 'cross sectional*':ti,ab,kw OR cross?ectional*:ti,ab,kw OR multicent*:ti,ab,kw OR 'multi-cent*':ti,ab,kw OR consecutive*:ti,ab,kw) AND (group:ti,ab,kw OR groups:ti,ab,kw OR subgroup*:ti,ab,kw OR versus:ti,ab,kw OR vs:ti,ab,kw OR compar*:ti,ab,kw OR 'odds ratio*':ab OR 'relative odds':ab OR 'risk ratio*':ab OR 'relative risk*':ab OR 'rate ratio':ab OR aor:ab OR arr:ab OR rrr:ab OR ((('or' OR 'rr') NEAR/6 ci):ab))) |
15798093 |
|
#13 |
#9 AND #10 - SR |
581 |
|
#14 |
#9 AND (#11 OR #12) NOT #13 - Observationeel |
4905 |
|
#15 |
#13 OR #14 - Totaal |
5486 |
Ovid/Medline
|
# |
Searches |
Results |
|
1 |
exp Arthritis, Rheumatoid/ or exp Arthralgia/ or ((rheuma* or reuma* or revma*) adj3 (arthrit* or artrit* or diseas* or condition* or nodule*)).ti,ab,kf. or (inflammat* adj3 (arthrit* or artrit* or joint*)).ti,ab,kf. or ((auto immun* or autoimmun* or deform* or persistent) adj3 (arthrit* or artrit*)).ti,ab,kf. or (felty* adj2 syndrome*).ti,ab,kf. or (caplan* adj2 syndrome*).ti,ab,kf. or ((ach* or pain*) adj3 (joint* or articular*)).ti,ab,kf. or arthralgia*.ti,ab,kf. or arthrodynia*.ti,ab,kf. or polyarthralgia*.ti,ab,kf. or acpa positive*.ti,ab,kf. or positive* acpa.ti,ab,kf. |
258410 |
|
2 |
exp magnetic resonance imaging/ or ("magnetic resonance" and (image or images or imaging)).ti,ab,kf. or mri.ti,ab,kf. or mris.ti,ab,kf. or nmr.ti,ab,kf. or mra.ti,ab,kf. or mras.ti,ab,kf. or zeugmatograph*.ti,ab,kf. or "mr tomography".ti,ab,kf. or "mr tomographies".ti,ab,kf. or "mr tomographic".ti,ab,kf. or 'mr imag*'.ti,ab,kf. or "proton spin".ti,ab,kf. or ((magneti* or "chemical shift") and imaging).ti,ab,kf. or fmri.ti,ab,kf. or fmris.ti,ab,kf. or rsfmri.ti,ab,kf. |
1035223 |
|
3 |
exp Tomography, X-Ray Computed/ or computed tomograph*.ti,ab,kf. or ct.ti,ab,kf. or cts.ti,ab,kf. or cat scan*.ti,ab,kf. or computer assisted tomograph*.ti,ab,kf. or computerized tomograph*.ti,ab,kf. or computerised tomograph*.ti,ab,kf. or computed x ray tomograph*.ti,ab,kf. or computed xray tomograph*.ti,ab,kf. |
919861 |
|
4 |
exp Ultrasonography/ or exp Ultrasonics/ or exp Endosonography/ or ultraso*.ti,ab,kf. or sonograph*.ti,ab,kf. or echograph*.ti,ab,kf. or sonogram*.ti,ab,kf. |
802727 |
|
5 |
exp Positron-Emission Tomography/ or exp Positron Emission Tomography Computed Tomography/ or exp Fluorodeoxyglucose F18/ or exp Radionuclide Imaging/ or exp Technetium/ or exp Fluorodeoxyglucose F18/ or (pet adj3 scan*).ti,ab,kf. or positron emission tomograph*.ti,ab,kf. or positron tomograph.ti,ab,kf. or positron emission compute* tomograph*.ti,ab,kf. or single photon emission compute* tomograph*.ti,ab,kf. or single photon emission computer tomograph*.ti,ab,kf. or 18f fdg.ti,ab,kf. or 18f fluorodeoxyglucose.ti,ab,kf. or fludeoxyglucose f18.ti,ab,kf. or fludeoxyglucose f 18.ti,ab,kf. or fluoride sodium f 18.ti,ab,kf. or fluoride sodium f18.ti,ab,kf. or sodium fluoride f 18.ti,ab,kf. or sodium fluoride f18.ti,ab,kf. or bone scan*.ti,ab,kf. or bone scinti*.ti,ab,kf. or osteoscintigraph*.ti,ab,kf. or skelet* scintigraph*.ti,ab,kf. or skeleton scinti*.ti,ab,kf. or spect.ti,ab,kf. or 99m tc.ti,ab,kf. or 99mtc.ti,ab,kf. or tc 99 m.ti,ab,kf. or tc 99m.ti,ab,kf. or tc99m.ti,ab,kf. or technetium 99 m.ti,ab,kf. or technetium 99m.ti,ab,kf. or technetium tc 99.ti,ab,kf. or technetium tc 99m.ti,ab,kf. or technetium tc99.ti,ab,kf. or fluorodeoxyglucose.ti,ab,kf. or fibroblast activation protein inhibitor*.ti,ab,kf. or fapi.ti,ab,kf. |
309250 |
|
6 |
2 or 3 or 4 or 5 |
2596845 |
|
7 |
exp Synovitis/ or ((arthriti* or joint* or disease*) adj3 activ*).ti,ab,kf. or inflammat*.ti,ab,kf. or synoviti*.ti,ab,kf. or tenosynoviti*.ti,ab,kf. |
1458435 |
|
8 |
1 and 6 and 7 |
9159 |
|
9 |
limit 8 to yr="2010 -Current" |
6752 |
|
10 |
9 not (comment/ or editorial/ or letter/) not ((exp animals/ or exp models, animal/) not humans/) |
6211 |
|
11 |
meta-analysis/ or meta-analysis as topic/ or (metaanaly* or meta-analy* or metanaly*).ti,ab,kf. or systematic review/ or cochrane.jw. or (prisma or prospero).ti,ab,kf. or ((systemati* or scoping or umbrella or "structured literature") adj3 (review* or overview*)).ti,ab,kf. or (systemic* adj1 review*).ti,ab,kf. or ((systemati* or literature or database* or data-base*) adj10 search*).ti,ab,kf. or ((structured or comprehensive* or systemic*) adj3 search*).ti,ab,kf. or ((literature adj3 review*) and (search* or database* or data-base*)).ti,ab,kf. or (("data extraction" or "data source*") and "study selection").ti,ab,kf. or ("search strategy" and "selection criteria").ti,ab,kf. or ("data source*" and "data synthesis").ti,ab,kf. or (medline or pubmed or embase or cochrane).ab. or ((critical or rapid) adj2 (review* or overview* or synthes*)).ti. or (((critical* or rapid*) adj3 (review* or overview* or synthes*)) and (search* or database* or data-base*)).ab. or (metasynthes* or meta-synthes*).ti,ab,kf. |
808271 |
|
12 |
Epidemiologic studies/ or case control studies/ or exp cohort studies/ or Controlled Before-After Studies/ or Case control.tw. or cohort.tw. or Cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Longitudinal.tw. or Retrospective*.tw. or prospective*.tw. or consecutive*.tw. or Cross sectional.tw. or Cross-sectional studies/ or historically controlled study/ or interrupted time series analysis/ [Onder exp cohort studies vallen ook longitudinale, prospectieve en retrospectieve studies] |
4957854 |
|
13 |
Case-control Studies/ or clinical trial, phase ii/ or clinical trial, phase iii/ or clinical trial, phase iv/ or comparative study/ or control groups/ or controlled before-after studies/ or controlled clinical trial/ or double-blind method/ or historically controlled study/ or matched-pair analysis/ or single-blind method/ or (((control or controlled) adj6 (study or studies or trial)) or (compar* adj (study or studies)) or ((control or controlled) adj1 active) or "open label*" or ((double or two or three or multi or trial) adj (arm or arms)) or (allocat* adj10 (arm or arms)) or placebo* or "sham-control*" or ((single or double or triple or assessor) adj1 (blind* or masked)) or nonrandom* or "non-random*" or "quasi-experiment*" or "parallel group*" or "factorial trial" or "pretest posttest" or (phase adj5 (study or trial)) or (case* adj6 (matched or control*)) or (match* adj6 (pair or pairs or cohort* or control* or group* or healthy or age or sex or gender or patient* or subject* or participant*)) or (propensity adj6 (scor* or match*))).ti,ab,kf. or (confounding adj6 adjust*).ti,ab. or (versus or vs or compar*).ti. or ((exp cohort studies/ or epidemiologic studies/ or multicenter study/ or observational study/ or seroepidemiologic studies/ or (cohort* or 'follow up' or followup or longitudinal* or prospective* or retrospective* or observational* or multicent* or 'multi-cent*' or consecutive*).ti,ab,kf.) and ((group or groups or subgroup* or versus or vs or compar*).ti,ab,kf. or ('odds ratio*' or 'relative odds' or 'risk ratio*' or 'relative risk*' or aor or arr or rrr).ab. or (("OR" or "RR") adj6 CI).ab.)) |
5904765 |
|
14 |
10 and 11 - SR |
275 |
|
15 |
(10 and (12 or 13)) not 14 - Observationeel |
2750 |
|
16 |
14 or 15 - Totaal |
3025 |