Which undifferentiated arthritis progresses to RA?

*Only for medical professionals to read and reference Nature sub-journals are "speaking"! On January 12, 2022, a large prospective study was published in Rheumatology (Oxford) reporting which patients with undifferentiated arthritis (UA) had MRI of the hands and feet for their progression to rheumatoid arthritis (RA)
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Meanwhile, the study was published in Nature Reviews Rheumatology in February
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"Medical Rheumatism Immunity Channel" specially invited Deng Xuerong, Chief Physician of the Department of Rheumatism and Immunity, Peking University First Hospital, to share this research and bring dry goods with clinical value to the readers
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Swipe up for background on the study abstract: Identifying UA in RA patients remains a clinical challenge
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This study aims to report the predictive value of MRI for RA progression in current UA patients [UA patients are defined as patients who do not meet the RA classification criteria (either the 1987 ACR criteria or the 2010 ACR/EULAR criteria) nor other diagnoses
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] Methods: The study included two types of UA patients: UA diagnosed based on the above classification criteria (n=405) and UA based on the empirical diagnosis of rheumatologists (n=564)
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All patients underwent contrast-enhanced MRI of the hands and feet at baseline with MRI scores for osteitis, synovitis, and tenosynovitis, and the patients were followed up for 1 year
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 RESULTS: Among UA patients diagnosed based on classification criteria (n=405), 21% developed RA
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MRI-detected synovitis and tenosynovitis predict the progression of RA
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Tenosynovitis was independently associated with RA progression (OR 2.
79; 95%CI 1.
40-5.
58), especially in patients with UA who were anti-cyclic citrullinated peptide antibody (ACPA)-negative (OR 2.
91; 95%CI 1.
42-5.
96)
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The ex ante risk of developing RA in UA patients with monoarthritis, oligoarthritis, and polyarthritis was 3%, 19%, and 46%, respectively
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MRI findings had the greatest impact on this risk in the oligoarthritis subgroup: a positive predictive value of 27% and a negative predictive value of 93%
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Similar results were found in UA empirically diagnosed based on expert opinion (n = 564)
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 Conclusions: This large prospective study suggests that MRI is most valuable in ACPA-negative UA patients with oligoarthritis; MRI-negative (without osteitis, synovitis, or tenosynovitis) helps prevent overtreatment
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According to local conditions, the treatment methods are different for different situations.
Q: UA is a group of inflammatory arthritis that cannot be clearly classified and diagnosed.
According to epidemiological data, about 30% of UA patients will develop RA.
What is the status of the diagnosis and treatment? Professor Deng Xuerong: UA may have several different outcomes: some patients will spontaneously remission; some patients will develop RA and become persistent chronic arthritis; some patients may maintain the status quo for a long time, neither progress nor ease
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Due to the lack of evidence-based medical evidence and guidelines in this area, the current status of diagnosis and treatment is not very uniform, and the differences between clinicians will be relatively large
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 In some cases, we will give patients symptomatic treatment, mainly non-steroidal analgesics and anti-inflammatory drugs (NSAIDs), to help patients relieve clinical symptoms as soon as possible
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 The following conditions are treated more aggressively, and disease-modifying anti-rheumatic drugs (DMARDs) are used.
For example, patients with more risk factors for progression to RA (such as increased number of swollen joints, less spontaneous remission, joint increased duration of inflammatory episodes); the patient's rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies turned from negative to positive, or had increasing titers; and the patient's imaging studies showed evidence of severe joint damage
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In addition to NSAIDs, glucocorticoids can help patients (especially those with monoarthritis) relieve symptoms quickly
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 In China, drug treatment may be the mainstay, and less attention is paid to non-drug treatment methods
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However, the guidelines issued by EULAR emphasize that for early inflammatory arthritis, there are some non-drug treatment methods: such as smoking cessation, weight loss, oral hygiene management, vaccination, control of other comorbidities,
etc.

Standard VS experience, not a clear distinction Q medical community: There are two definitions of UA in this study, one is UA based on classification criteria, and the other is UA based on empirical diagnosis of rheumatologists.
What is the clinical application? Professor Deng Xuerong: I think the definition of UA in this study is relatively rigorous
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In actual clinical work, doctors in most cases still diagnose UA based on personal experience
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Due to feasibility issues, it is rare to define UA strictly according to the above classification criteria
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  In clinical research, the definition is more stringent
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In this study, UA was defined as neither the 1987 nor the 2010 ACR/EULAR classification criteria for RA, and the enrolled patients were patients with inflammation of at least one joint for a duration of <2 years, and other diagnoses were excluded, So I think this definition is more rigorous
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Neglected Tenosynovitis in MRI Q medical community: This study examined the importance of three inflammatory MRI findings, osteitis, synovitis, and tenosynovitis, respectively, to examine their importance in predicting RA, where MRI-detected tenosynovitis was The strongest independent predictor, what do you think is the implication for clinical diagnosis and treatment? Professor Deng Xuerong: This study gives clinicians a very big hint that our current understanding of RA is based on its pathological mechanism, that is, invasive synovitis
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Therefore, in the process of diagnosis and follow-up, everyone pays more attention to the performance of synovitis, and does not pay enough attention to tenosynovitis
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 The reasons for this situation are: 1.
The feasibility of MRI
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Conditions vary from center to center, and contrast agents are required for contrast-enhanced MRI to identify synovitis, tenosynovitis, etc.
, limiting the use of MRI
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 2, the clinician's cognitive reasons
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Too much focus on synovitis, not too much emphasis on the performance of tenosynovitis
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Tenosynovitis has received relatively little attention from both radiologists and rheumatologists
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3.
Tenosynovitis was not included in the RAMRIS score of MRI for RA
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 4.
Usually domestic more rely on ultrasound to check tenosynovitis
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This may be the reason why clinicians pay less attention to tenosynovitis detected by MRI
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 This study points out that the tenosynovitis detected by MRI has a very high predictive value for the progression of UA to RA, which can make us pay more attention to the performance of tenosynovitis in MRI in future clinical work, and help us to diagnose RA patients faster, so as to start earlier.
DMARDs treatment
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 Moreover, the results also suggest that tenosynovitis detected by MRI is more meaningful for patients with negative rheumatoid factor and anti-CCP antibodies, especially for patients with oligoarthritis
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Therefore, for these patients, if tenosynovitis is detected on MRI, it is of great significance for a clear diagnosis
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The high detection value of MRI does not mean that ultrasound is inferior to the medical community Q: From the conclusions of the article, it can be seen that MRI is the most valuable in ACPA-negative UA patients with oligoarthritis
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UA patients with negative MRI can almost rule out the possibility of developing RA.
From the perspective of clinical diagnosis, what do you think of this conclusion? Professor Deng Xuerong: Because the positive MRI in the study refers to osteitis, synovitis and tenosynovitis, so this The results of the study are actually quite plausible
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 It is mentioned in the article that for these seronegative UAs, using the 2010 standard, it may put forward higher requirements on the number of joint involvements, for example, more than ten joints are required to pass the classification criteria and the score will be very high
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Therefore, diagnosis can be more difficult in seronegative patients such as rheumatoid factor or anti-CCP antibodies
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Therefore, if we see the inflammatory manifestations of these patients on imaging, it can prompt us to pay more attention to these patients because they are more likely to develop RA
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  In fact, as early as the 2016 EULAR recommendation on the management of early arthritis, some predictors of the development of RA in these patients were mentioned: such as the number of swollen joints, high acute phase reactants, positive serological or imaging results
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  The conclusion of this article has two meaningful points: 1.
It suggests which inflammatory manifestations we should pay attention to in MRI of the hands and feet of patients with UA
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2.
Prompt us in which patients should pay more attention to the performance of MRI, that is, patients with negative ACPA and oligoarthritis
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Moreover, in the inflammatory manifestations of MRI, tenosynovitis should be paid special attention
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Although synovitis is the most characteristic manifestation and is very sensitive, it is not specific for UA and can also be seen in other arthritis
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In addition, the sensitivity of osteitis manifestations is also low
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Therefore, the conclusions of this article can help clinicians to use MRI for diagnosis more quickly
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However, in China, due to the cost-effectiveness of MRI and the need to use contrast agents, its clinical application may be limited
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 The final conclusion of the article mentions the problems of ultrasound: First, the frequency of ultrasound is currently higher than that of MRI
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However, the tenosynovitis detected by MRI is of particular interest because no similar studies have been performed using ultrasound in UA patients
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Second, the sensitivity of ultrasound to detect tenosynovitis is worse than that of MRI (19%-50%)
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On this point, I have other opinions.
I don't think ultrasound is less sensitive than MRI.
In fact, our domestic rheumatology department uses ultrasound more
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With the improvement of ultrasound technology and training level, our ability to recognize tenosynovitis will also improve, which can be strengthened through training
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So I don't think ultrasound will be less valuable than MRI
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UA, defined by standard and clinical experience, is actually the same goal in the medical community: In this study, although the trials were divided into two groups according to 2 different definitions, the findings were similar, what do you think this has to do with clinical Guiding significance? Professor Deng Xuerong: The article divides UA into two groups, one group is patients who do not meet the RA classification criteria
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The other group consisted of patients diagnosed based on expert opinion
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The conclusions of the two groups are very similar, which means that the heterogeneity of the two groups of patients is not large
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Even this class of UAs, as judged by expert opinion, may be very close in nature to another group of UAs diagnosed based on classification criteria
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  That is to say, although clinicians diagnose UA based on personal experience and do not strictly follow the criteria to compare items one by one, personal experience is very consistent with the items included in the classification criteria
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  UA judged according to expert opinion is also judged from the number of affected joints, acute phase reactants and serological antibodies, so these two groups of patients are essentially close
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In fact, a lot of expert opinions were also included in the formulation of this standard, so this conclusion makes sense, that is, the two groups of patients are relatively similar
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  Therefore, clinically, we do not need to spend a lot of time to compare the standards, especially in the rheumatology centers of large tertiary hospitals, the UA diagnosed empirically by the doctor and the UA judged by the classification standard will not be too different
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References: [1] Hollander N, Verstappen M, Sidhu N, et al.
Hand and foot MRI in contemporary undifferentiated arthritis: in which patients is MRI valuable to detect rheumatoid arthritis early? – a large prospective study[J].
Rheumatology, 2022.
Expert Profile Chief Physician Deng Xuerong graduated from Peking University School of Medicine, MD, currently Chief Physician of the Department of Rheumatology and Immunology, Peking University First Hospital, Deputy Head of the Imaging Group of the Rheumatology and Immunology Branch of the Chinese Medical Doctor Association Member and secretary of the imaging group of the committee.
The main research directions are various arthritic diseases and musculoskeletal ultrasound.
The EULAR-certified musculoskeletal ultrasound training teachers have successively served as visiting scholars at Queen Mary Hospital of the University of Hong Kong and the Rheumatology and Musculoskeletal Medicine Center of the University of Leeds, UK.
Received the Travel Scholar Award from the Japanese Society of Rheumatology