|Year : 2017 | Volume
| Issue : 2 | Page : 81-85
Erosive arthritis and anti-cyclic citrullinated peptide antibodies in systemic sclerosis
A Abdessemed1, N Khaldoun1, A Tahiat2, R Djidjik2, Y Mellal2, I Allam2, S Slimani3, A Haddouche4, N Brahimi1, M Ghaffor2, A Ladjouze Rezig1
1 Department of Rheumatology, Ben Aknoun Hospital, Algiers, Algeria
2 Department of Immunology, Beni Messous Hospital, Algiers, Algeria
3 Department of Rheumatology, CHU Batna, Algeria
4 Department of Rheumatology, EPH Blida, Algeria
|Date of Web Publication||26-May-2017|
Department of Rheumatology, Ben Aknoun Hospital, Route Des Deux Bassins, Algiers
Source of Support: None, Conflict of Interest: None
Background: The frequency and characteristics of erosive arthritis in systemic sclerosis (SSc) remains unclear. The aim of the study was to determine the prevalence and characteristics of erosive arthritis and to define the role of anti-CCP antibodies in the differential diagnosis of joint involvement in SSc.
Methods: One hundred and fifty patients who met the 1980 American College of Rheumatology (ACR) criteria and/or Leroy and Medsger criteria for SSc were assessed.
Results: Among the 150 SSc patients, 139 were women. Their median age was 45.12 ± 13.59 years and disease duration ( first non-Raynaud symptom) of 9.7 years. Of these patients, 5 patients were classified as having limited SSc, 103 as limited cutaneous SSc and 42 as diffuse cutaneous SSc. Joint involvement was characterized as arthralgia in 95 (63%) patients, arthritis in 60 (40%) patients, erosive arthritis in 21 (14%) and systemic sclerosis (SSc)-rheumatoid arthritis (RA) overlap syndrome in 7 patients. The prevalence of diffuse cutaneous involvement (50%) (P = 0.01), digital ulcers (81%) (P = 0.009), interstitial lung disease (81%) (P = 0.009) and anti-topoisomerase I antibodies (P = 0.01) was higher in patients with erosive arthritis. Anti-CCP antibodies were found in 14 of the 150 (9.4%) cases. A statistically significant association between the presence of anti-CCP antibodies and the presence of arthritis (P = 0.01), erosive arthritis (P = 0.01) and SSc-RA overlap syndrome (P < 0.05) was noted. High titers of anti-CCP antibodies were found in patients with SSc-RA overlap syndrome.
Conclusion: Erosive arthritis is not rare in SSc, and it might be a marker of severe disease. Anti-CCP antibodies can be present in patients with SSc, and high titers of anti-CCP antibodies may be indicative of SSc-RA overlap syndrome.
Keywords: Anti-CCP, erosive arthritis, systemic sclerosis
|How to cite this article:|
Abdessemed A, Khaldoun N, Tahiat A, Djidjik R, Mellal Y, Allam I, Slimani S, Haddouche A, Brahimi N, Ghaffor M, Rezig A L. Erosive arthritis and anti-cyclic citrullinated peptide antibodies in systemic sclerosis. Indian J Rheumatol 2017;12:81-5
|How to cite this URL:|
Abdessemed A, Khaldoun N, Tahiat A, Djidjik R, Mellal Y, Allam I, Slimani S, Haddouche A, Brahimi N, Ghaffor M, Rezig A L. Erosive arthritis and anti-cyclic citrullinated peptide antibodies in systemic sclerosis. Indian J Rheumatol [serial online] 2017 [cited 2021 Jan 19];12:81-5. Available from: https://www.indianjrheumatol.com/text.asp?2017/12/2/81/203089
| Introduction|| |
Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular involvement and fibrotic changes in the skin and internal organs. Musculoskeletal involvement is common in SSc and joint pain is the most common manifestation. Joint-related symptoms have been noted in 12%–66% of patients at the time of diagnosis, and in 24%–97% of patients during the course of the illness. In the clinical context, arthralgia is considered to have a higher prevalence rate than arthritis. Arthritis mostly occurs in the hand joints, particularly, the metacarpophalangeal and proximal interphalangeal joints, and less frequently in the knees and elbows. If synovitis is present, it may be indicative of an overlap with rheumatoid arthritis (RA) or the existence of primary arthropathy specific to systemic sclerosis. The prevalence of radiographic erosive arthritis has been reported to be around 18%. Moreover, the prevalence of SSc-RA overlap syndrome seems to be close to 1–5%.,
The main objective of our study was to determine the prevalence and characteristics of erosive arthritis and to define the role of anti-CCP antibodies in the differential diagnosis of joint involvement in SSc.
| Methods|| |
Patients and assessments
Patients who met the 1980 American College of Rheumatology criteria and/or Leroy and Medsger criteria for SSc participated in this two-year cross-sectional study, which was conducted at the Rheumatology Department of our institution., The patients were evaluated by one investigator, and they were diagnosed with limited SSc or diffuse SSc according to the classification system proposed by LeRoy et al.
Pulmonary involvement was defined by the presence of bibasilar fibrosis, as observed on a high-resolution computed tomography scan, and/or pulmonary arterial hypertension (PAH), detected by color doppler echocardiography. Oesophagus involvement was defined by the presence of gastroesophageal reflux disease (GERD). Skin involvement was assessed by the modified Rodnan skin thickness score. Joint involvement was categorized as follows: Arthralgia, arthritis (joint swelling and tenderness on physical examination or synovitis on ultrasonography [US]) and erosive arthritis (erosions and joint space narrowing on radiographs or erosions on US). Only the wrist, metacarpophalangeal and proximal interphalangeal joints were studied.
Standard hand and wrist radiographs were taken and evaluated. All radiographs were evaluated in a blinded manner, with the evaluator having no prior knowledge of the clinical or serological data of the examined patients. The presence of extra-articular (subcutaneous calcinosis and digital tuft resorption) or articular involvement (juxta-articular osteoporosis, marginal erosions and joint space narrowing) was recorded.
The French version of the Stanford Health Assessment Questionnaire disability index and the Cochin Hand Function Scale were used to evaluate functional disability.
The presence of anti-cyclic citrullinated peptide (anti-CCP2 IgG) antibodies was evaluated with an enzyme-linked immunosorbent assay (ELISA) kit. The test kit was used following the procedures of the manufacturer. The samples were classified as negative (<5 units) or positive (≥5 units). The presence of anti-nuclear antibodies in monolayers of human larynx epidermoid carcinoma cells was analyzed using a standard immunofluorescence technique. IgG antibodies against Extractable Nuclear Antigen were analyzed using an ELISA kit.
The results were analyzed using Epidata analysis. Data were expressed as the median and range or mean ± standard deviation (SD) and 95% confidence interval (95% CI), when necessary. The statistical significance of the various associations was calculated using the χ2 test. The difference was significant when the P value was < 0.05.
This study was approved by the Ethics Committee of our institution. All patients had given their informed consent prior to enrollment in this study.
| Results|| |
The study included 150 patients with SSc (139 women and 11 men) with a median age of 45.12 ± 13.59 years and a mean disease duration ( first non-Raynaud symptom) of 9.7 ± 8.47 years. Of these patients, 5 patients were classified as having limited SSc, 103 (69%) as having limited cutaneous SSc and 42 (28%) as having diffuse cutaneous SSc.
Joint involvement was characterized by arthralgia in 95 (63%) patients, arthritis in 60 (40%), and flexion contractures in 78 (52%) patients. Anti-CCP antibodies were found in the serum of 14 (9%) patients with SSc. The main demographic, clinical and laboratory characteristics of these patients are shown in [Table 1].
|Table 1: Main clinical and laboratory characteristics of systemic sclerosis patients|
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Articular and extra-articular radiographic changes were found in SSc patients. Digital tuft resorption was observed in 58 (39%) cases, and subcutaneous calcinosis was observed in 28 (19%) cases. Juxtaarticular osteoporosis was found in 79 (53%) patients, and marginal erosions and joint space narrowing were observed in 14 (9%) patients.
Erosions were found in 7 (5%) patients with normal radiographic findings.
Comparison of patients with and without arthritis
Among the 150 patients examined, 60 had arthritis. There was no significant difference between patients with and without arthritis with regard to the presence of digital ulcers, skin, lung, heart and kidney involvement. Anti-CCP antibodies were present in 10 patients with arthritis and in 4 patients without arthritis (P = 0.01). The main demographic, clinical and laboratory characteristics of these patients are shown in [Table 2].
|Table 2: Demographic, clinical and laboratory characteristics of systemic sclerosis patients with and without arthritis|
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Erosive arthritis was found in 21 (14%) of the 150 patients. Patients with erosive arthritis had more diffuse cutaneous involvement (9 [43%] vs. 6 [15%]; P = 0.01) and a higher modified Rodnan skin score (15.14 ± 10.29 vs. 8.77 ± 10.02; P = 0.02). Moreover, the incidence of digital ulcers (17 [81%] vs. 18 [46%]) (P = 0.009) and interstitial lung disease (ILD) (17 [81%] vs. 18 [46%]; P = 0.009) was higher in this group. The mean Cochin Hand Function Scale score (23.87 ± 24.44 vs. 11.82 ± 14.14; P = 0.03) and the mean Health Assessment Questionnaire disability index (0.95 ± 0.88 vs. 0.66 ± 0.81; P = 0.05) were higher in the patients with erosive arthritis. Differences between the two groups were not significant in other parameters. Anti-CCP antibody was present in 7 patients with erosive arthritis and in 3 patients without erosive arthritis (P = 0.01). Moreover, anti-topoisomerase I antibodies were present in 15/21 patients with erosive arthritis and in 6/21 patients without erosive arthritis (P = 0.01).
We also compared erosive arthritis, patients with and without features of SSc-RA overlap syndrome. Out of the 21 patients, 7 met the ACR criteria for RA and the remaining 14 had erosive arthritis but not RA. The erosive arthritis patients without RA, had a higher incidence of flexion contracture (13 [93%] vs. 3 [43%]; P = 0.01), digital ulcers (13 [93%] vs. 4 [52%]; P = 0.04), acro-osteolysis (7 [50%] vs. 1 [14%]; P = 0.04), oesophagus involvement (14 [100%] vs. 5 [71%]; P = 0.03), and ILD (13 [93%] vs. 4 [57%]; P = 0.04). [Table 3] shows a statistically significant association between the presence of anti-CCP antibodies and arthritis, erosive arthritis and SSc-RA overlap syndrome. The level of anti-CCP antibodies was 139.30 ± 124.47, 141.57 ± 125.47 and 167 ± 139.95 U/mL in the arthritis, erosive arthritis and SSc-RA overlap syndrome groups respectively.
|Table 3: Relationship between anti-CCP antibodies, arthritis, erosive arthritis and overlap syndrome SSc-RA|
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| Discussion|| |
Our data showed that joint involvement is common in SSc. This is in accordance with previous observations which indicate that joint complaints are common during the course of SSc. The presence of synovitis may be associated with SSc-RA overlap syndrome, which is a rare condition,, or with the existence of primary arthropathy specific to systemic sclerosis. In our study, joint synovitis was not associated with digital ulcers or skin and pulmonary involvement. However, the presence of joint erosions was associated with diffuse cutaneous thickening, digital ulcers, ILD, functional impairment, and anti-topoisomerase I antibodies. Our study also found that patients with erosive arthritis and no features of SSc-RA overlap syndrome had severe disease.
A search of the EUSTAR database revealed that joint synovitis was predictive of overall disease progression and worsening of the modified Rodnan skin score in patients with early SSc. However, there is no evidence of the association between erosive arthritis and clinical variables from the data in the EUSTAR database. Previous cross-sectional studies failed to demonstrate the correlation between erosive arthritis and clinical variables. For example, in one study, erosive disease had no correlation with disease duration, rheumatoid factor, antinuclear antibodies, distal tuft resorption, or the extent of scleroderma-related skin changes. Moreover, in another study no significant difference between patients with and without arthritis (n = 22/120) or erosions, (n = 25/120) in terms of disease duration (P = 0.39), cutaneous subtype (P = 0.64) and occurrence of terminal tuft resorption (P = 0.06) was found. Yet another study also did not find any significant correlation between the key radiographic findings and the severity of Raynaud's phenomenon or the extent and pattern of skin or visceral involvement.
The presence of anti-CCP antibodies is highly specific to RA., These antibodies have been reported to be present in up to 76% patients with RA. In accordance with the results of our study, several cross-sectional studies have also estimated the prevalence of anti-CCP antibodies in patients with SSc to be 1%–15%.,,,,, We also identified a statistically significant association between the presence of anti-CCP antibodies and the presence of arthritis, erosive arthritis and SSc-RA overlap syndrome. High titers of anti-CCP antibodies were reported in patients with SSc–RA overlap syndrome. A previous study found a statistically significant association between the presence of anti-CCP antibodies and the presence of arthritis and marginal erosions. Rheumatoid factor is found in up to 30% of SSc patients,, but does not distinguish between patients with and without erosive arthritis.
This study is the first North African study to evaluate the joint involvement and anti-CCP antibodies in SSc and in correlating joint erosions with the severity of systemic sclerosis. Its major limitation is being a cross-sectional study which included patients at various stages of the disease.
In this study, erosive arthritis was associated with severe disease and a high prevalence of anti-topoisomerase I antibodies. According to our findings, erosive arthritis specific to SSc is not rare, and therefore, patients should be screened for it by conventional radiography and ultrasonography. Further, anti-CCP antibodies can also be present in patients with SSc, and high levels of anti-CCP antibodies may be indicative of SSc-RA overlap syndrome.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]