Review One year in review 2018: ultrasonography in rheumatoid arthritis and psoriatic arthritis
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Review
One year in review 2018: ultrasonography in
rheumatoid arthritis and psoriatic arthritis
A. Zabotti1, P. Mandl2, G. Zampogna3, C. Dejaco3,4, A. Iagnocco5
1
Department of Medical and Biological ABSTRACT monitoring of disease activity and dam-
Sciences, Rheumatology Clinic, Ultrasound is playing an increasingly age in RA and peripheral PsA.
University of Udine, Italy; important role in the differential diag-
2
Department of Rheumatology,
nosis and monitoring of rheumatoid Ultrasonographic imaging
Medical University of Vienna, Austria;
3
Department of Rheumatology, arthritis (RA) and psoriatic arthritis of rheumatoid arthritis
Hospital of Bruneck, Italy; (PsA). This technique is more sensitive Role of US in predicting progression
4
Department of Rheumatology and specific than clinical examination to RA from clinically suspected
and Immunology, Medical University to detect active synovitis, and the iden- arthralgia or undifferentiated arthritis
Graz, Austria; tification of specific synovitis patterns Early treatment is the cornerstone of
5
Academic Rheumatology Center, enable differentiation of PsA from RA the management of early arthritis, fa-
Università degli Studi di Torino, Italy.
and other entities. Ultrasound verified vouring a higher rate of remission
Alen Zabotti, MD inflammation changes along with clin- and a lower disability. Currently, the
Peter Mandl, MD, PhD
ical improvement during therapy, and preclinical phases of RA include two
Giuseppe Zampogna, MD
Christian Dejaco, MD ultrasound was shown to predict future possible clinical entities: clinically
Annamaria Iagnocco, MD clinical and structural suspected arthralgia (CSA) and undif-
Please address correspondence to: outcomes thus complementing the clin- ferentiated arthritis (UA); predictive
Prof. Annamaria Iagnocco, ical risk assessment of patients. In the algorithms for RA progression have
Dipartimento di Scienze present review, we summarised the sci- been recently implemented with the
Cliniche e Biologiche, entific evidence published in 2017 fo- aim to stratify patients and improve
Università degli Studi di Torino, cussing on the use of ultrasonography outcome (e.g. even prevent RA de-
Regione Gonzole 10, for clinically relevant and pragmatic velopment) (4). Data on the role of US
10043 Orbassano (TO), Italy.
E-mail: annamaria.iagnocco1@gmail.com
aspects of diagnosis and management in the earlier phases of RA in patients
of RA and PsA. with CSA without clinical synovitis are
Received on April 26, 2018; accepted in
revised form on May 7, 2018.
emerging and of high interest. Nam
Introduction et al. found that in anti-CCP-positive
Clin Exp Rheumatol 2018; 36: 519-525
Ultrasonography (US) has shown to be patients without clinical synovitis, the
© Copyright Clinical and
of particular help in the management detection of US synovitis, particularly
Experimental Rheumatology 2018.
of chronic arthritis (1, 2), from its pre- the presence of power Doppler (PD)
clinical phases to established disease, could predict progression to inflamma-
from early diagnosis to evaluation of tory arthritis (IA) (5). The importance
damage progression. US integrated into of synovial PD signal, as a risk factor
clinical examination could improve the to develop IA was confirmed one year
outcome of patient with arthritis. How- later in another cohort of CSA patients
ever, this requires the pragmatic use (6). Furthermore, given the high nega-
of US in clinical practice (3). For this tive predictive value of US, the same
purpose, this review focuses on the use authors suggested that US has added
of US for clinically relevant aspects of value to identify which patients (i.e.
the management of the two most com- patients without US synovitis) would
mon inflammatory arthritides, namely not develop into IA. In patients with
rheumatoid arthritis (RA) and psoriatic UA (i.e. clinical synovitis without ful-
arthritis (PsA). We performed a Med- filment of classification criteria for RA
line search of English language articles or other chronic arthritis), US could be
published in the PubMed database from useful not only for differential diag-
January 2017 to April 2018. All the arti- nosis, but also to predict RA develop-
cles were critically analysed in order to ment or reclassify UA as RA, detecting
select the most relevant contributions subclinical synovitis or bone erosions
Competing interests: none declared. with regard to diagnosis, prognosis and (7). Recently, Horton et al. showed
Clinical and Experimental Rheumatology 2018 519Ultrasonography in chronic arthritis / A. Zabotti et al. that the degree of grey-scale (GS) syn- cible technique for detecting synovitis ly disease. When combined with the ovitis appeared to be a sensitive indi- in the wrist and finger joints and may DAS28 or HAQ, reduced sonographic cator of disease progression to RA in be considered for routine use as part of scores (i.e. the US 7-joint inflamma- early UA patients: the presence of at the standard diagnostic armamentar- tion PD and GS synovitis sum-scores) least two joints with GS synovitis ≥2 ium in RA (15). were predictive of the change in HAQ was clinically relevant to the starting score over one year (21). Regarding of methotrexate while five joints with Role of US in predicting outcome treatment response, poor improvement GS synovitis ≥2 discriminated between in RA of GS and PD scores at three months low and high risk to develop RA (8). Subclinical disease activity detected by had good predictive value for non-re- Furthermore, Sahbudin et al. suggested imaging methods such as US or MRI sponders at six months (p
Ultrasonography in chronic arthritis / A. Zabotti et al. as well as in patients with prominent was supplemented with the most symp- no swollen joints, and non-progression subcutaneous swelling, sensitivity of tomatic joint outside this set, resulting of radiographic joint damage at 16, 20 PD might be limited, yet US may still in a higher sensitivity to detect active and 24 months whereas use of biologic- be more objective to assess synovitis synovitis (39). Tan et al. suggested to al agents was higher in the US group. than clinical examination (32). US re- even replace traditional 7- and 12-joint The study, however, had some limita- sults may improve along with clinical scores with the selection of the 7 and tions such as the absence of blinding or amelioration after the implementation 12 most affected joints either by US or the fact that the outcome (DAS44 re- of effective therapy (7). A rapid reduc- based on a combined US and clinical mission) was part of the intervention in tion of joint synovitis and tenosynovi- assessment. The individualised scores the conventional group. Besides, there tis has been observed in a prospective performed better than the traditional was a trend toward a better radiological study on 157 RA patients undergoing scores, however, they might be limited outcome in the US group. A post-hoc biological treatment (33). In patients by feasibility in clinical practice and analysis of the ARCTIC trial revealed treated with adalimumab and tocil- by the open question, whether results that intra-articular infiltration was most izumab, a similar reduction of US obtained with these scores are compar- effective in joints with moderate PD scores of inflammation has been ob- able across different patients and stud- activity regardless of clinical swell- served while clinical composite indices ies (40). A study on 100 RA patients in ing and irrespective of whether an US (containing acute phase reactants) were clinical remission reported that a six- -guided or palpation-guided injection lower in the tocilizumab as compared joint score (bilateral MCP 2, 3, wrist) procedure was used (44). In TASER, to the adalimumab group (34). The au- had moderate sensitivity (75%) to de- 111 patients with early RA or undif- thors suggested that US might be more tect subclinical activity (that had been ferentiated arthritis were randomised. precise for the objective evaluation of found in 60% of cases using a 38-joint In the intervention group, US was con- inflammation in patients treated with US joint count). The authors conclud- ducted in patients with DAS28
Ultrasonography in chronic arthritis / A. Zabotti et al. Ultrasonographic imaging sign and it showed that GUESS scores PsA with prevalent hands involvement of psoriatic arthritis of patients with Pso who developed from RA (56, 60). Furthermore, US Role of US in predicting progression PsA, compared with those who did not could be useful to support the diagnosis to PsA in patients with psoriasis develop PsA, did not statistically differ of inflammatory and non-inflammatory Imaging studies have found that a sig- but in the logistic regression analysis, disease (e.g. fibromyalgia). Recently, it nificant proportion of patients with baseline thickness of the quadriceps has been proposed that there is a PsA psoriasis (Pso) without musculoskel- tendon was found to be an independent subgroup suffering mostly from en- etal symptoms have subclinical signs predictor of the development of PsA thesitis, without association of evident of synovitis and enthesitis, supporting (54). These data strongly suggest that clinically swollen joints and increase of the concept of psoriatic disease with US is a useful tool to detect subclinic- acute phase reactants. In this scenario, various degrees of activity in various al involvement, but prospective studies pain could be localised at one or a few domains and different clinical expres- are needed to consider it as a biomarker entheseal sites, but could involve the siveness. Currently, the majority of of arthritis development. whole body, resulting in chronic wide- US studies in psoriatic patients with- spread syndrome, mimicking fibro- out musculoskeletal complaints have a Role of US in making a diagnosis myalgia (61). In this case, the sono- cross-sectional design, with the aim to of PsA graphic detection of entheseal inflam- identify subclinical articular inflamma- The 2016 EULAR recommendations matory changes, particularly PD signal, tory involvement compared to healthy for the management of early arthritis could be useful to discriminate between controls: lower limbs enthesis were recognise US as a supportive tool for PsA and fibromyalgia (62, 63). frequently evaluated showing an in- the detection of synovitis (2), as several crease of subclinical enthesitis (49). At controlled studies suggested a greater Role of US in detecting disease present, only one US study focalised sensitivity of US than clinical examin- activity and damage on extra-entheseal structures showing ation. Furthermore, enthesitis has been US could be useful to monitor disease a significant increase in subclinical identified as an important clinical entity activity (both for synovial and entheseal synovitis (50). Up to now, little infor- in diagnosing and classifying PsA in involvement) and therefore to support mation exists about preclinical phases accordance with the CASPAR criteria clinical assessment of PsA patients and of PsA and, considering that in many (55). Currently, no study evaluated the for this purpose the use of high-sensi- cases the psoriatic skin lesions precede overall performance of US in addition tivity PD signal is essential. Recently, the onset of arthritis by several years, to clinical findings to diagnose PsA in patients with chronic arthritis (in- psoriasis gives us a unique opportun- (49). Nevertheless, the ability of US to cluding PsA), Najm et al. demonstrat- ity to study a defined pool of patients detect elementary lesions, which may ed that US examination of the knee at risk of developing arthritis (51). Re- support the diagnosis of PsA has been with both B-mode and PD, reflected cently, Eder et al. demonstrated that demonstrated in a number of studies, accurately histological inflammation prior to the diagnosis of PsA, a pre- particularly those focusing on entheses and vascularisation (26); previously, clinical phase exists, and it is charac- of the lower limbs. The use of high fre- in the unique US study in PsA patients terised by nonspecific musculoskeletal quency probes gives us the opportunity using histopathology as gold standard, symptoms (i.e. joint pain, fatigue and not only to detect the presence of joint the amount of PD was not significantly stiffness) (52). In this scenario, imaging inflammation, but also to describe the associated with the histopathological could be useful not only to identify sub- type of involvement (e.g. prominent inflammatory score (64). Further stud- clinical inflammatory lesions but also to synovial vs. prominent extra-synovial) ies on correlations between US activity identify, if any, a possible imaging bio- (56, 57). In this regard, the involvement and histology are needed to clarify the marker for the prediction of PsA. For of the synovio-entheseal complex (SEC) role of US as an imaging biomarker this purpose, imaging studies, focusing and enthesis-related inflammation have for activity. Furthermore, US provides not only on enthesis but also on syn- a pivotal role: functional or classical the clinician a more accurate picture ovial and soft tissue abnormalities and enthesitis with or without associated of inflamed joints demonstrating US with a prospective design, are needed. synovitis could support and assist in synovitis in clinically silent areas, in Recently, Faustini et al. in a MRI pro- the differential diagnosis of early PsA certain cases leading to the reclassifica- spective study, showed that subclinical or peripheral spondylarthritis (SpA), tion of PsA patients from oligoarthritis inflammation appears to substantial- especially in case of clinically undiffer- to polyarthritis, which may therefore ly influence the risk of patients with entiated forms (58, 59). For example, improve their follow up. Interestingly, psoriasis to progress to PsA, but the the sonographic detection of functional US enthesitis seems to have no correla- small sample size and high proportion enthesitis (namely peritenonitis of the tion with clinical examination in PsA of arthritis development at one year of extensor digitorum tendons at the level patients (65). Recently, Michelsen et follow up, due to the inclusion also of of the MCP joints as well as thickening al. reported that Achilles enthesitis, de- patients with arthralgia, could influence of the pulleys and soft tissue oedema) tected by US, was not significantly as- the results of the study (53). Among US has been demonstrated to be specific for sociated with clinical enthesitis in their studies, only one had a longitudinal de- PsA, which may be used to differentiate PsA population and that the percentage 522 Clinical and Experimental Rheumatology 2018
Ultrasonography in chronic arthritis / A. Zabotti et al.
of patients with inflammation and/or Table I. Research agenda on ultrasonography in rheumatoid arthritis: items that need to be
structural damage was similar for the prioritised.
groups with and without entheseal pal-
1. To conduct clinical studies using US-based parameters as outcomes
patory tenderness, suggesting a limited 2. To investigate how US can guide management decisions in clinical practice
value of clinical examination compared 3. To study the role of US in predicting patient reported outcomes
with US evaluation (66). As a damage 4. To investigate the prognostic role of US in identifying CSA or UA patient at risk to develop RA
biomarker, US can easily depict struc-
CSA: clinically suspect arthralgia; RA: rheumatoid arthritis; UA: undifferentiated arthritis; US: ultrasound.
tural lesions of bones (e.g. erosions,
bony spurs and enthesophytes) and
Table II. Research agenda on ultrasonography in psoriatic arthritis: items that need to be
tendon (e.g. thickening of the tendon prioritised.
and tendinous lesions). These damage
lesions are useful not only to evaluate 1. To investigate the integration of US in clinical practice in order to improve the clinical diagnosis
reversible versus irreversible features, 2. To investigate which US elementary lesions could be highly specific for PsA
3. To investigate the prognostic role of US in identifying Pso patient at risk to develop PsA
but they could improve the differen-
4. To identify US predictors of treatment response in order to stratify treatment regimen (i.e. better
tial diagnosis since a large component selection of patients with poorer outcome)
of the structural changes is driven by
entheseal inflammation which is a hall- Pso: psoriasis; PsA: psoriatic arthritis; US: ultrasound.
mark of SpA (67).
was associated with a lower chance to still needed. Whether US should be
Role of US in predicting outcome achieve MDA, supporting the superior- part of management strategies has in
in PsA ity of US. Polacheck et al. found that a part been answered by ARCTIC and
Establishing the prognosis of a patient higher MAdrid Sonographic Enthesitis TASER studies in RA. US plus clinic-
with PsA is important to define the Index (MASEI) score was associated al remission seems not to be superior
treatment strategy. Currently, observa- with severity of peripheral radiographic to strict clinical remission concerning
tional and prospective cohort studies joint damage (e.g. erosions, ankylosis) clinical disease activity as the primary
have identified some prognostic fac- (70). However, these clinical and US outcome. In clinical practice, however,
tors correlating with the achievement results need to be validated in a larger US is probably more relevant for the as-
of therapeutic response. Recently, Eder cohort. Moving to clinical remission, sessment of patients with high clinical
et al. demonstrated that overweight and active synovitis, defined as PD grade composite scores due to accompanying
obesity, female gender, old age and ≥1, was found to be a strong predictor osteoarthritis or fibromyalgia. In these
a longer duration of the disease were of flare during short-term follow up in patients, US might enable a more ob-
associated with a lower probability of PsA patients, and similar findings were jective evaluation of disease activity
achieving sustained Minimal Disease recently confirmed also in juvenile idio- and exclude active inflammation de-
Activity (MDA) (68). Furthermore, in pathic arthritis (71). spite high levels of pain. Whether an
accordance with the criterion of “the US-based management strategy in these
sooner the better” in the Swedish Early Conclusion patients might result in better outcomes
PsA register, a shorter delay between In 2017, significant progress was made and a more adequate use of resources
the onset of symptoms and diagno- in the development of US for diagno- are questions that only future research
sis was a predictor for MDA (69). To sis, monitoring and outcome prediction will clarify.
date, in PsA, US predictors of poorer of RA and PsA. While the role of US
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