Clinical and Ultrasound Concordance of Joint Damages in Rheumatoid Arthritis in a Resource-Limited Country ()
1. Introduction
Rheumatoid arthritis (RA) is an immune-mediated chronic inflammatory joint disease in which synovial proliferation, pannus formation and bone erosions are histologic lesions [1]. It affects around 1% of the adult population of all sexes [2]. In Benin, its frequency is 0.8% [3] [4]. The European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) in 2010 established criteria for the early diagnosis of RA. These criteria are essentially based on clinical and biology, eliminating often late radiographic criteria [1].
In recent years, modern imaging including Magnetic Resonance Imaging (MRI) and ultrasound have proven to be more sensitive than standard X-rays for early detection of synovitis and bone erosions for the early diagnosis of RA [5]. Ultrasound has become increasingly important in the early diagnosis and monitoring under treatment of RA [6] given its accessibility, its non-irradiating nature, its multi-site explorability and the reasonable cost compared to MRI. Osteoarticular ultrasound, increasingly practiced by specialists (radiologists and rheumatologists) therefore appears to be a good diagnostic alternative complementary to clinical examination in developing countries. The reinforcement of the medical staff by specialists in osteoarticular imaging at the Benin referral hospital made it possible to carry out this work. Our objective was to assess the clinical and ultrasound concordance of joint lesions in rheumatoid arthritis at the National University Hospital Center-Hubert Koutoukou Maga (CNHU-HKM) Cotonou in the Republic of Benin.
2. Patients and Methods
This was a descriptive and analytical cross-sectional study carried out from October to December 2018 in the medical imaging and rheumatology departments of the CNHU-HKM in Cotonou.
This was a convenience sampling by an exhaustive census of patients followed in the rheumatology department meeting the following criteria:
- To be followed for at least 6 months.
- Have a diagnosis of RA selected on the basis of EULAR ACR 2010 criteria.
- Have performed an ultrasound of the wrists, hands and feet.
- Have given informed consent.
Patients with another rheumatic pathology associated with RA or in whom ultrasound could not be performed because of joint deformities were excluded.
All the patients underwent a clinical osteoarticular examination carried out by a rheumatologist during which he tried as possible to collect socio-demographic (age, sex), clinical and biological data and the DAS 28 activity score (Disease Activity Score Index 28) of the disease. Each patient received after that, frontal X-rays of both hands taking the wrists and both forefoots, then an osteoarticular ultrasound of the 32 articulated joints (the 2 wrists, the 10 MCP and PPI of the hands and the 10 MTP). The ultrasound was performed according to the daily practice protocol proposed by Guerini [7].
In addition, the X-rays were interpreted and the ultrasounds carried out by two (02) radiologists and when discrepancy, the opinion of the most experienced was retained. X-rays and ultrasound were subsidized by the hospital.
The clinical, radiological and ultrasound diagnostic criteria for lesions observed in RA have been summarized in Table 1 [8].
The data entry was carried out with Epi data 3.1 French version software. SPSS version 24.0 software enabled data analysis with a significance level “<5%” defined for a p-value.
Quantitative variables were described by the mean with the standard deviation (normal distribution) or the median followed by extremes. Cohen’s non-parametric Kappa (k) test was used to estimate the rate of concordance or concordance between the results obtained on ultrasound and in the clinic, on the one hand, then between the results of the ultrasound and those of radiography on the other hand. The Landis and Koch classification was used to qualitatively assess the rate of agreement between observations [9]. The concordance between clinical and ultrasound was assessed using “synovitis” which is the characteristic lesion of RA. The concordance between the X-ray and the ultrasound was assessed on bone erosions. The observations were judged to be concordant when the Kappa coefficient was statistically different from 0. The concordance was either very weak (k = 0 - 0.20), weak (k = 0.21 - 0.40), moderate (k = 0.41 - 0.60), strong (k = 0.61 - 0.80) or nearly perfect (k = 0.81 - 1).
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Table 1. Diagnostic criteria for rheumatoid arthritis lesions at clinic, radiography and ultrasound [8].
3. Results
A total of fifty-three (53) female subjects are eligible to the study’s criteria inclusion within a total of 102 RA patients collected during the period. The average age was 55 ± 13 years with extremes of 11 and 58 years.
3.1. Clinical and Biological Manifestations
A family history of RA was found in 21 (39.6%) patients. The mean age of patients at onset was 41.5 ± 13.9 years.
Clinical and biological characteristics of the participants are summarized in Table 2.
The joint most frequently affected by synovitis in the patients was the metacarpo-phalangeal with a frequency of 79.2%. Figure 1 shows the distribution of patients according to the joints involved in RA.
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Table 2. Clinical and biological manifestations.
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Figure 1. Distribution of patients according to joints affected during RA, Rheumatology Department of CNHU-HKM in 2018 (N = 53).
3.2. Radiographic Lesions
46 of the 53 patients who were investigated (86.8%) presented lesions on the X-ray. Bone erosion was the most common radiographic lesion in 43 of them, 81.1% (Table 3). These bone erosions were bilateral in 39 (90.7%) patients.
3.3. Ultrasound Lesions
The ultrasound revealed lesions in all patients, unlike the X-ray. Ten types of lesions were observed; the most frequent were synovitis in 52 patients (98.1%) and bone erosions in 47 (88.7%) cases (Table 4).
Inactive synovitis (Figure 2) was more frequently observed in metatarsophalangeal and metacarpophalangeal with the same prevalence of 94.2% at these two sites.
3.4. Clinico-Ultrasound Concordance
Table 5 summarizes the clinical and ultrasound concordance of synovitis in the different groups of joints. Active synovitis (Figure 3) was observed in 20.8% of patients at the clinic and in 17% of patients on ultrasound.
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Table 3. Main radiographic lesions in patients followed for rheumatoid arthritis, Rheumatology Department of the CNHU-HKM in 2018 (N = 53).
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Table 4. Main ultrasound lesions in patients followed for rheumatoid arthritis, Rheumatology Department of the CNHU-HKM in 2018 (N = 53).
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Table 5. Clinical and ultrasound concordance of synovitis (active or not) in patients followed for RA according to the different groups of joints, Rheumatology department of the CNHU-HKM in 2018 (N = 53).
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Figure 2. Inactive synovitis of a right MTP1 and inactive synovitis with erosion of a right MTP2 in mode B in a 37-year-old patient followed for RA for 1 year.
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Figure 3. Active grade 2 synovitis of a right radiocarpal joint in B-mode with power doppler in a 40-year-old patient followed for RA for 2 years.
Concordance between clinic and ultrasound (Table 6) regarding the diagnosis of active synovitis was very low (k = 0.16).
3.4.1. Comparison between Radiography and Ultrasound
This comparison was made on the basis of the presence of bone erosions in the distal joints affected by RA (wrist, MCP, PPI, MTP) (Table 7). There is a weak concordance between ultrasound erosions and radiographic erosions (k between 0.022 and 0.22). Nevertheless, the ultrasound seems to detect more lesion than the radiography; with 21 times more erosions objectified for MCP and 30 times more for PPIs.
3.4.2. Factors Associated with Ultrasound Lesions
After multivariate analysis, Table 8 and Table 9 present the factors associated with bone erosions and active synovitis.
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Table 6. Clinical and ultrasound concordance of active synovitis in patients followed for RA, Rheumatology department of the CNHU-HKM in 2018 (N = 53).
SA: Active Synovitis.
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Table 7. Concomitant search for bone erosions according to the different groups of joints by ultrasound and radiography in patients followed for RA, Department of Rheumatology of the CNHU-HKM in 2018 (N = 53).
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Table 8. Association between bone erosions and clinical and biological data.
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Table 9. Association between age and active synovitis.
4. Discussion
This preliminary work experienced one main difficulty during its completion, namely the presence of joint deformities in the patients, which made ultrasound examination difficult and sometimes impossible. The limits of this work also lie in the small number of our only female sample, the absence of control cases and the non-updating of certain biological assessments at the time of the study. Furthermore, the study did not isolate patients who were naïve to disease-modifying treatment for RA, from patients already on treatment because of the reduced number of the cohort. This should not impact on the internal and external validity of this work, the results of which have given rise to the following discussion.
Ultrasound lesions were present in all of our patients. This high frequency of RA-related ultrasound lesions is explained by the long time from beginning to diagnosis and also by the recognized performance of ultrasound which detects lesions even in the absence of clinical signs [10] [11]. Ultrasound synovitis was the most observed lesion (98.1%). Naredo in 2013 and Vreju in 2016 [12] [13] found respectively 87.8% and 94.8% of ultrasound synovitis, unlike Harman H. et al. who found 3 times fewer cases of ultrasound synovitis (36%) [14]. This difference is explained by the fact that the cohort of Harman consisted mainly of patients in clinical remission for at least 6 months, whereas our study and others contained very few patients in complete remission. In addition, the too long diagnostic delay in our work and in Zomalheto et al.’s in patients with RA (>1 year) could also explain this high proportion of ultrasound synovitis [4]. Doppler activity was found in 17% of our patients compared to 29% in Harman et al. [14] despite the fact that the entire population is in complete remission. Synovial inflammation may therefore persist in RA patients who experience clinical remission [10]. Several authors had also found active synovitis in patients suffering from RA in remission (DAS ≤ 2.6) with frequencies of 36%, 46% and 57.4% [12] [15]. All this proves the performance of ultrasound in detecting subclinical synovitis in patients with RA in clinical remission. This subclinical synovitis could be linked to neoangiogenesis which persists for many months and which has been explored in numerous works such as those of Kamishima et al. [16].
We found bone erosions in 47 patients (88.7%). Naredo in Spain, Vreju in Romania and Tanaka in France recorded 59%, 21.7% and 36.8% bone erosion, respectively [12] [13] [17]. The long diagnostic delay in the patients in the present study would explain the high frequency of erosions on ultrasound. Apart from synovitis and bone erosions mainly present and studied in RA, our patients presented numerous other ultrasound lesions. These were joint effusion in 34% of patients, tenosynovitis (20.8%), de Quervain tendinitis (7.5%) and overlapping and angulation-type deformities (60.4% and 7.5%). Tenosynovitis has also been described in studies as an ultrasound sign of RA in rheumatoid arthritis. In fact, apart from the articular tropism, the periarticular structures constitute a bed for rheumatoid disease [7] [18].
There was no match between clinical examination and ultrasound, for wrists, MCPs and MTPs. On the other hand, the concordance was very low at the level of the PPIs (k = 0.03). Garrigues et al. found a very low concordance for MTPs (k = 0.01 - 0.03) and wrists (0.23 to 0.30) and moderate concordance for MCP (k = 0.47 - 0.51), and PPIs (0.55) [19]. Garrigues et al. suggest that ultrasound assessment of RA patients might focus only on PTMs and wrists but also on shoulders and that other joint sites should be assessed by physical examination.
There was poor concordance between ultrasound and radiographic erosions at wrists, MCP, PPI, and MTP (k between 0.022 and 0.22). Backhaus and Naredo found in their study, a similar concordance at the level of the distal joints [12] [20]. The use of small compact golf club type probes would facilitate exploration of the metacarpophalangeal joints, compared to linear probes. According to some authors, detecting bone erosions on ultrasound is especially useful in the first few months of the disease [21]. After one year of development, X-rays are just as effective, except for new erosions which will be detected earlier on MRI [21]. X-rays should be used as the initial imaging technique to detect joint damage. Ultrasound or MRI may be considered when X-rays do not show a lesion [21]. Ultrasound may be a valid and reproducible technique for detecting synovitis in the joints of the wrist and fingers. It may be considered for routine use as part of standard diagnostic tools in RA [7] [21] especially in developing countries like ours.
Age, positive RA factor, and biologic inflammatory syndrome were all significantly associated with ultrasound erosions. Comparable results have been reported in the literature in rheumatoid patients in clinical remission [22] [23]. As for active synovitis, only age was significantly associated. Vreju et al. found a significant association of active ultrasound synovitis with strong anti CCP antibody positivity, disease activity, as well as a significant correlation with serum levels of vascular endothelial growth factor (VEGF) and active synovitis on ultrasound [13].
Ultrasound abnormalities such as synovitis and bone erosions, however, are not specific to RA and can be seen in other chronic inflammatory rheumatism. The clinical context, the topography of the lesions as well as the biological assessment remain the best means of differentiating an incipient rheumatoid arthritis from other chronic inflammatory rheumatism.
5. Conclusions
Rheumatoid arthritis was found to be more common in Beninese women and affected the middle-aged population. Radiologically, RA was very destructive in our population. Synovitis and bone erosion are the most frequent Ultrasound manifestations. The main factor associated with these ultrasound lesions was age.
There is no concordance between ultrasound and clinical examination for wrists, PCMs and MTPs, but it was very weak for PPIs. There is a weak concordance between ultrasound erosions and radiographic erosions. The ultrasound seems, however, to detect more lesions than the radiography with 10 times and 30 times more erosions objectified respectively for MCP and PPI.
Ultrasound is by far a good complementary alternative to clinical examination and diagnostic radiography in the early diagnosis of RA in the absence of MRI, which remains a luxury in our developing countries.
Acknowledgements
The authors acknowledge all the patients followed for rheumatoid arthritis who agreed to collaborate in this study.