|Year : 2021 | Volume
| Issue : 4 | Page : 415-421
Absence of metacarpophalangeal synovitis by high-resolution ultrasonography distinguishes psoriatic arthritis from rheumatoid arthritis – A cross-sectional study
Ashish K Badika1, Ashish Jacob Mathew1, Shivraj Padiyar1, Avinash Suresh Buche2, John Mathew1, Anitha Barney3, Shyamkumar N Keshava4, Debashish Danda1
1 Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, India
2 Department of Medicine, Dr. Hedgewar Rugnalaya, Aurangabad, Maharashtra, India
3 Department of Clinical Genetics, Christian Medical College, Vellore, India
4 Department of Interventional Radiology, Christian Medical College, Vellore, India
|Date of Submission||06-Apr-2021|
|Date of Acceptance||31-Oct-2021|
|Date of Web Publication||22-Dec-2021|
Dr. Debashish Danda
Department of Clinical Immunology and Rheumatology, Christian Medical College and Hospital, Ida Scudder Road, Vellore - 632 004, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background: We aimed to evaluate the high-resolution ultrasonography (HRUS) findings in the hands of patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA).
Materials and Methods: This was a cross-sectional study of ultrasonography (USG) of hands in patients with PsA fulfilling the Classification criteria for psoriatic arthritis (CASPAR) in comparison with cases with RA fulfilling 1987 American College of Rheumatology classification criteria. Bilateral 1st and 2nd metacarpophalangeal (MCP) and proximal interphalangeal joints were assessed for synovitis and bone erosions, and extensor tendons at wrist for tenosynovitis by a single observer using the GE LOGIQ BOOK XP USG machine (General Electric Medical Systems) with a high-frequency 12-MHz linear array transducer. Demographic and clinical details were extracted from the electronic database of the hospital information system.
Results: A total of 62 patients (31 with RA and PsA each) were studied. Demographic and baseline features were similar, except for more male patients in PsA as compared to RA (41.9% vs. 16.1%; P = 0.02). MCP synovitis was higher in RA as compared to PsA (71% vs. 29%; P = 0.001). Multiple logistic regression analysis found that absence of MCP synovitis by HRUS (adjusted odds ratio [OR]: 5.97; P = 0.02) in spite of higher number of swollen joints (adjusted OR: 29.3; P = 0.03) favors the diagnosis of PsA as compared to RA.
Conclusion: “Our finding of fewer or no MCP synovitis by HRUS in PsA as compared to RA warrants a larger, powered validation study; if reproduced, it can be an additional tool to differentiate PsA including those without overt skin lesions from seronegative RA/early undifferentiated polyarthritis.”
Keywords: Psoriatic arthritis, rheumatoid arthritis, synovitis, ultrasound
|How to cite this article:|
Badika AK, Mathew AJ, Padiyar S, Buche AS, Mathew J, Barney A, Keshava SN, Danda D. Absence of metacarpophalangeal synovitis by high-resolution ultrasonography distinguishes psoriatic arthritis from rheumatoid arthritis – A cross-sectional study. Indian J Rheumatol 2021;16:415-21
|How to cite this URL:|
Badika AK, Mathew AJ, Padiyar S, Buche AS, Mathew J, Barney A, Keshava SN, Danda D. Absence of metacarpophalangeal synovitis by high-resolution ultrasonography distinguishes psoriatic arthritis from rheumatoid arthritis – A cross-sectional study. Indian J Rheumatol [serial online] 2021 [cited 2022 Jan 24];16:415-21. Available from: https://www.indianjrheumatol.com/text.asp?2021/16/4/415/333216
| Introduction|| |
Psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are chronic inflammatory diseases causing significant joint damage and varied systemic manifestations., RA is a common systemic autoimmune condition, with a prevalence of 0.28%–0.7% in India. PsA is an immune mediated, heterogeneous inflammatory disease with varied presentations, involving both peripheral and axial joints, along with other clinical domains including enthesitis, dactylitis, skin, and nail involvement. Early diagnosis and initiation of optimal therapy can mitigate long-term complications of these diseases. Both these entities differ in their epidemiological, clinical, and radiological features. Joint deformities, destruction, and disability are more common in patients with PsA., Differentiation of polyarticular PsA and RA can pose a clinical challenge at times, given the similarities in their presentation and involvement of joints, especially in the absence of skin lesions in PsA. Presence or absence of laboratory markers like rheumatoid factor and Anti Citrullinated Cyclic Peptide antibodies Anti citrullinated cyclic peptide antibodies (ACPA), at times in both conditions, may act as confounders.
Conventional radiography (CR), the most common imaging technique used in clinical practice lacks sensitivity in detecting early soft-tissue changes. CR features in PsA differ from RA in the distribution of affected joints and by the presence of destructive changes and bone proliferation in the same joint. Ultrasonography (USG) has gained utility as a sensitive, point-of-care technique to detect inflammatory and structural changes in the peripheral joints. USG can play a critical role in differentiating different types of inflammatory arthritis, more so during early phases of the disease and in patients with milder symptoms with no definite clinical findings. One of the earliest USG features to be noted in arthritis is synovitis, and its detection is important for diagnosis, treatment, and monitoring of disease progression.
The aim of this study was to evaluate the ability of high-resolution ultrasonography (HRUS) in detecting inflammatory and destructive changes in the small joints of hands, and the extensor tendons in the hands of patients with PsA as compared to RA.
| Materials and Methods|| |
In this retrospective arm of the cross-sectional observational study, we have retrieved prospectively documented data from the existing USG database of the unit between April 2009 and June 2010 and analyzed; the study was approved by the institutional review board (IRB No. 7269, dated August 11, 2010). One of the main objectives of this arm of the study was to generate preliminary data on prevalence, as in a pilot study, for the estimation of sample size for the prospective arm of the study.
Inclusion criteria of the study included: (1) patients fulfilling the classification criteria for PsA (CASPAR) and the 1987 American College of Rheumatology classification criteria for RA, attending the outpatient rheumatology clinics of our tertiary care teaching hospital;, (2) patients >18 years of age; (3) consecutive PsA and RA patients as per inclusion criteria one as above, who underwent ultrasound of hands by GE LOGIQ BOOK XP machine (General Electric Medical Systems) between April 2009 and June 2010 in our department as recorded in our USG database. Exclusion criteria were (1) Documented local injury/trauma to the hands over the preceding 1 month; (2) Documented hyperuricemia; (3) Documented infection of skin and soft tissue around the hands and forearm; (4) pregnant patients; (5) patients with documented renal or hepatic decompensation.
Being a preliminary and retrospective data retrieval arm, written consent was not feasible. However, a verbal informed consent was obtained by the treating doctor from all the subjects before the diagnostic procedure. Waiver of consent was obatined from IRB (IRB Min. No. 14281 [Retro] dated: August 25, 2021).
While USG data were retrieved from the prospectively documented and maintained USG database of the unit, demographic and clinical details of the verbally consented participants were extracted from the prospectively documented outpatient and inpatient electronic data base of the hospital information system.
All the included patients had undergone HRUS of both hands. The HRUS scans were performed by a single operator, blinded to the clinical diagnosis of the patients, on a GE LOGIQ BOOK XP machine (General Electric Medical Systems) using high-frequency 12-MHz linear array transducer (hockey stick probe). Bilateral 2nd and 3rd metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints were assessed for synovitis and bone erosions, and extensor digitorum tendons at wrist were assessed for tenosynovitis. The presence or absence of each parameter was noted.
Bone erosions at MCP and PIP were defined as intra-articular discontinuity of the bone surface, visible in two perpendicular planes. Synovial hypertrophy (synovitis) in the grayscale mode was defined as abnormal hypoechoic or anechoic tissue inside the joints that was not displaceable. Tenosynovitis in the grayscale mode was defined as hypoechoic or anechoic, thickened tissue with or without fluid within the tendon sheath, observed in two perpendicular planes.
Data were analyzed using SPSS V 21(License Number [Customer ID]: 200699; Vendor: SPSS South Asia Pvt Ltd. Bangalore, Karnataka, India). Normality of the data was checked by histogram. Continuous variables that were normally distributed were expressed as mean and standard deviation. For skewed continuous variables, median and interquartile range (IQR) (difference between 75th and 25th percentiles, or between upper and lower quartiles, IQR = Q3 − Q1) was used. Categorical variables were expressed as frequencies and percentages. For univariate analysis, Pearson's Chi-square or Fisher exact test was used. Two-sided P < 0.05 was taken as statistically significant, and odds ratios were calculated to determine the strength of association. Multiple logistic regression analysis was performed to adjust for confounding factors and adjusted odds ratios were obtained to ascertain the independent risk factors. Clinical diagnosis of RA/PsA was the dependent variable and the other variables such as age, gender, tender joint count, swollen joint count, extra articular manifestations, synovitis by USG in MCP, synovitis at PIP by USG, bone erosions on USG in PIP and MCP, and erythrocyte sedimentation rate (ESR) were the independent variables. Variables which were significant in the univariate analysis and clinically relevant were assessed for confounders in the regression analysis.
| Results|| |
A total of 62 patients (31 with RA and 31 with PsA) were studied. Demography, clinical details, and USG features of these patients are presented in [Table 1]. No patient in both arms was treatment naïve; all patients were on DMARDs (majority on methotrexate and sulfasalazine) and/or nonsteroidal anti-inflammatory drugs (NSAIDs) or/low dose steroids before USG.
|Table 1: Baseline characteristic and ultrasound findings in psoriatic arthritis and rheumatoid arthritis|
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USG detected MCP synovitis [Figure 1] was significantly higher in patients with RA (n = 22, 71%) as compared to PsA (n = 9, 29%; P = 0.002); whereas, PIP synovitis was comparable in both the groups (5 in RA and 8 in PsA). MCP erosions were comparable in both groups (7 in RA and 9 in PsA), and PIP erosions [Figure 2] were numerically higher in the PsA patients (n = 11, 35.5%) as compared to RA (n = 6, 19.4%), though that did not reach statistical significance. Twelve patients in RA group had tenosynovitis of extensor tendons as compared to 15 in PsA group and that was comparable too.
|Figure 1: Ultrasound detected synovitis in metacarpophalangeal joints (a) metacarpophalangeal synovitis in psoriatic arthritis (b) metacarpophalangeal synovitis in rheumatoid arthritis. Mh: metacarpal head. Pp: Proximal Phalanx|
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|Figure 2: Ultrasound detected erosions in proximal interphalangeal joints (a) proximal interphalangeal joint erosion in psoriatic arthritis (b) proximal interphalangeal joint erosion in Rheumatoid arthritis|
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The univariate analysis found that male gender (odds ratio [OR] = 3.8; 95% confidence interval [CI] [1.1–12.4]; P = 0.02) and swollen joint count (>4) (OR = 10.7; 95% CI [2.7–38.2]; P ≤ 0.001) had positive association with PsA as compared to RA, whereas MCP synovitis by USG (OR = 0.2; 95% CI [0.05–0.5]; P = 0.001) and ESR (OR = 0.33; 95% CI [0.1–0.9]; P = 0.04) had negative association with PsA [Supplementary Table 1]a.
Multivariate logistic regression analysis revealed that PsA patients had significantly lower adjusted odds ratio for having MCP synovitis by USG (Adjusted OR of 0.15 [0.03–0.78]; P = 0.02); and this negative association, i.e., significantly fewer or absence of MCP synovitis by USG in PsA was in spite of having significantly higher proportion of swollen joints in PsA as compared to RA [Table 2].
|Table 2: Multiple logistic regression analysis of clinical and ultrasonography features in psoriatic arthritis and rheumatoid arthritis|
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We then looked at comparison between polyarticular PsA patients (n = 21) versus RA (n = 31) which identified tender joint count (>5) (OR = 5.8; 95% CI [1.2–20.3]; P = 0.004), swollen joint count (>4) (OR = 28.7; 95% CI [6.3–130.2]; P ≤ 0.001) and fewer or absent MCP synovitis by USG (OR = 0.16; 95% CI [0.04–0.5]; P = 0.003) as the variables associated with polyarticular PsA [Supplementary Table 1]b.
Logistic regression revealed higher odds for having more swollen joints in polyarticular PsA as compared to RA (adjusted OR of 2.3 [95% CI 1.2–4.6); P = 0.01). There was also trend for lower odds of having MCP synovitis by USG in this subset of PsA, but P value was 0.08 possibly due to the smaller sample size for this analysis [Table 3].
|Table 3: Multiple logistic regression analysis between polyarticular psoriatic arthritis cases and rheumatoid arthritis (n=52)|
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Finally, we looked at PsA patients without overt skin lesions (n = 10; 7 of them are of polyarticular variety) versus RA and found that male gender (OR = 7.8; 95% CI [1.6–38.1]; P = 0.006), swollen joint count (>5) (OR = 15.7; 95% CI [2.8–87.2]; P = 0.001), extra articular manifestations (OR = 6.2; 95% CI [1.1–35.3]; P = 0.04), fewer or absent MCP synovitis by USG (OR = 0.1; 95% CI [0.01–0.5]; P = 0.004), bone erosions at PIP by USG (OR = 4.1; 95% CI [0.9–19.1]; P = 0.05) and lower ESR (OR = 0.2; 95% CI [0.04–0.9]; P = 0.03) were associated with this PsA subgroup in the univariate analysis [Supplementary Table 1]c.
Again the multiple logistic regression showed very low odds of having MCP synovitis by USG in this PsA subset as compared to RA (Adjusted OR of 0.05 [95% CI 0.004–0.7]; P = 0.02) in spite of significantly higher proportion of swollen joints in the former (70% vs. 12.9%, P = 0.01) [Table 4].
|Table 4: Multiple logistic regression analysis of psoriatic arthritis without overt skin lesion and rheumatoid arthritis|
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We also analyzed the diagnostic accuracy of presence or absence of MCP synovitis by USG in PsA under 3 scenarios as shown in [supplementary Table 2]a, [supplementary Table 2]b and [supplementary Table 2]c; and it revealed that ultrasonographic absence of MCP synovitis had a sensitivity, specificity, positive predictive value, and negative predictive value of 71% (95% CI = 59.6–82.4), in addition to Positive Likelihood ratio of 2.44 and negative likelihood ratio of 0.4 in diagnosing PsA as against RA [Supplementary Table 2]b.
Similarly, as a corollary, the sensitivity, specificity, positive predictive value, and negative predictive value, as well as positive and negative Likelihood ratios of presence of MCP synovitis by USG favors the diagnosis of RA as against PsA as a whole, as well as against PsA subsets as mentioned above [Supplementary Table 2]c.
Our data, therefore, suggest that the absence of ultra sonographic finding of MCP synovitis is a feature with a significantly high odd's for the diagnosis of PsA, including the subset without overt skin lesions as against RA; on the other hand, presence of MCP synovitis by USG favors the diagnosis of RA with high odd's ratio.
| Discussion|| |
This cross-sectional study demonstrated a significantly lower prevalence of synovitis at the MCP joints by USG in PsA as against its much higher prevalence in RA. USG has been shown to have better sensitivity compared to clinical examination in patients with inflammatory arthritis for some years now. With a narrow window of opportunity in both RA and PsA, early detection and differentiation with USG may guide the treating physician in choosing the appropriate therapy in a timely manner.
Probably, one of the important clinical challenges in diagnosing an inflammatory arthritis include differentiation between polyarticular PsA from RA, especially when skin lesions are not apparent; and at times, arthritis has been reported to appear years before psoriatic skin rashes become manifest. In such scenarios, clinicians may not suspect subtle nail changes nor may look for occult sites of psoriasis.
In our cohort, both tender and swollen joint counts seem to be higher in the PsA group on clinical examination. All patients with PsA, cases with polyarticular PsA and PsA cases without overt skin lesions have significantly higher swollen joint counts in our cohort (Crude and adjusted Odd ratios of 10.7 [95% CI 2.7–38.2] and 29.3 [95% CI: 1.3–623.7]; 28.7 [95% CI 6.3–130.2] and 2.3 [95% CI 1.2–4.6] and 15.7 [95% CI 2.8–87.2] and 39.9 [95% CI 1.8–873.9]1, respectively; P values of 0.03, 0.01, and 0.01, respectively), as compared to RA.
In spite of higher number of swollen joints as mentioned above, chance of USG detected synovitis at MCP joints is significantly less common in PsA as compared to RA. The crude and adjusted odd's ratios for this feature in PsA as a whole, and in PsA without skin lesions are 0.2 (95% CI 0.05–0.5) and 0.15 (95% CI 0.03–0.78), and 0.1 (95% CI 0.01–0.5) and 0.05 (95% CI 0.004–0.7), respectively; adjusted P values 0.02 and 0.02, respectively [Table 2] and [Table 4]. In polyarticular PsA, however, this low odd's ratio of MCP synovitis by USG missed statistical significance (P = 0.08), possibly because of smaller sample size [Table 3].
USG defined MCP synovitis in our study, therefore, is a unique differentiating feature between PsA and RA; while its absence or lower prevalence favors the diagnosis of PsA (including those without overt skin lesions mimicking RA), its presence favors the diagnosis of RA [Table 2] and [Table 4].
Very few earlier studies had compared USG findings in RA with that in PsA. Wiell et al. had performed USG for detecting inflammatory and destructive changes in 15 PsA and 5 RA patients; and they observed synovitis in 50% of all the imaged MCP joints in RA patients, compared to only 19% in the PsA patients. Zabotti et al. compared early RA and early PsA patients using USG of the two most clinically involved joints. Synovitis by USG was observed in 91% of RA joints as against 60% of the joints in their PsA patients. As compared to the study by Zabotti et al. in early disease and largely treatment naïve cases, the slightly lower prevalence of synovitis by USG in our present study could be because of treatment effect in our cases, as most our patients were of longer disease duration [median duration of 18 months versus 24 months in PsA vs. RA; [Table 1]] and therefore were already on conventional synthetic DMARD and/or NSAID therapy for a significant period of time.
Tenosynovitis is another feature that can aid in the differential diagnosis between PsA and RA. RA patients are noted to have tenosynovitis more frequently over the wrists, as opposed to finger flexors in PsA. Extensor carpi ulnaris tenosynovitis has been documented to be very common in RA patients. Tinazzi et al. demonstrated flexor tenosynovitis over the fingers to be more common in patients with PsA (67.6%) as compared to RA (21.3%). Examination of the extensor digitorum tendons for tenosynovitis in our study did not yield any significant difference between the RA and PsA patients, though it was numerically higher in the latter. The discrepancy of relatively higher number of clinically swollen joints including those over the MCPs in PsA, as against significantly lower MCP synovitis by USG may be possibly explained by the apparent clinical swelling over the small joints of hands due to extensor tenosynovitis (48.4% in PsA) in our study.
Although USG detected PIP erosions were also numerically higher in the PsA group, compared to the RA group in this study, a statistical significance in this difference could not be demonstrated presumably due to the small numbers of patients. There is a paucity of such studies in literature comparing USG features of hand joint erosions between RA and PsA. In the study by Wiell et al., erosions were, however, noted in only 3% of the PIP joints in RA patients, as compared to 14% of those in PsA. Zayat et al. had assessed erosions by USG in patients with RA, PsA, osteoarthritis, and gouty arthritis; they noted erosions at MCP2 and MCP5 and distal ulna to be highly specific for RA.
The findings of this study should, however, be interpreted considering its limitations. First, we had scanned limited joint areas in a relatively smaller sample size. As mentioned under the methods, the present study involved retrospective retrieval of prospectively documented ultrasound data from our unit's USG database; and the main objective of this preliminary retrospective arm of the cross-sectional study was to generate pilot data that may enable estimation of sample size for longitudinal arm of the study in future. Hence, we did not calculate a prior sample size here. However, if we go by the study of Zabotti et al. in early PsA vs. Early RA, we need just 27 patients in each arm with 80% power. In fact, going by our present findings of MCP synovitis figures and significant difference between the two arms (29% in PsA and 71% in RA), we need just 23 patients in each arm to detect this difference for a future prospective study. Hence, our sample size of 31 in each arm may be considered high enough and meaningful.
The second limitation is noninclusion of distal interphalangeal joints and IP joints of the thumb in our study, as these joints are known to be more frequently involved in PsA than RA.
Third, power Doppler USG (PDUS) mode was not employed in this study. PDUS mode is more sensitive in diagnosing the extrasynovial inflammation including tenosynovitis, which is a well-known feature of PsA.,
Fourth, flexor tendons of the fingers were not included in this study. Flexor tenosynovitis could be a critical feature to differentiate between PsA and RA.
Fifth, USG is well known to be operator-dependent, and involving a second observer could have increased the reliability of the findings in this study.
And finally, our patients were all treated with DMARDs, and therefore, the USG findings could be dampened by it. Future studies should include treatment naïve patients to document truly inflammatory features by USG.
Notwithstanding the shortcomings, this study adds to the scarce literature on USG differentiation between PsA and RA; fewer or absence of MCP synovitis by USG in our study favors the diagnosis of PsA with a sensitivity, specificity, positive, and negative predictive values of 71%. This feature may, therefore, aid in better phenotyping of undifferentiated inflammatory arthritis in the clinics. Our findings may also be a helpful feature differentiating PsA without overt skin lesions including the polyarticular ones from RA.
| Conclusion|| |
”Our finding of fewer or no MCP synovitis by HRUS in PsA as compared to RA warrants a larger, powered, and prospective validation study; if reproduced, it can be an additional tool to differentiate PsA including those without overt skin lesions, from seronegative RA/early undifferentiated polyarthritis.”
Study was approved by Institutional review board (IRB no. 7269, dated August 11, 2010). Waiver of consent was obtained from IRB (IRB Min. No. 14281 [Retro] dated: August 25, 2021).
Being the retrospective data retrieval arm of a preliminary cross-sectional study to generate pilot data for a future prospective study, written consent was not feasible. However, a verbal informed consent was obtained from all patients by the treating doctor prior to the USG procedure.
We are thankful to our patients for their co-operation and for agreeing to be part of our study.
Financial support and sponsorship
This study was funded by CMC fluid research grant.
Conflicts of interest
There are no conflicts of interest.
Supplementary Table 1: Univariate analysis
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]