Department of Rheumatology, St. Vincent's University Hospital, Dublin 4, Ireland.
Correspondence to:
D. Kane, Centre for Rheumatic Diseases, Glasgow Royal Infirmary, Glasgow G31 2ER, Scotland. E-mail: dk44a{at}clinmed.gla.ac.uk
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Abstract |
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Methods. A total of 129 patients presenting with PsA to an Irish early synovitis clinic were assessed at presentation and at 1- and 2-yr follow-up. The Veale criteria were used for PsA classification and the Sharp score of hands and feet was used to quantify radiological outcome.
Results. At presentation, 52 (40%) had oligoarticular PsA and 77 (60%) had polyarticular PsA. Patients with polyarticular PsA were administered disease-modifying anti-rheumatic drugs (DMARDs) more frequently than patients with oligoarticular PsA and this resulted in a significant number of polyarticular PsA patients being reclassified as oligoarticular PsA at 1- [27/70 (39%)] and 2-yr [26/53 (49%)] follow-up. Fewer patients initially classified with oligoarticular PsA were reclassified as polyarticular PsA. More patients with oligoarticular PsA at baseline were in DMARD-free remission and there was less radiological damage at 2-yr follow-up. DIP disease was associated with other classic seronegative disease featuresenthesopathy and nail dystrophybut did not influence clinical or radiological outcome and the separation of DIP disease as a distinct subgroup in classification criteria was not supported. Synovitisacnepustulosishyperostosis (SAPHO) syndrome was not observed as a separate subgroup.
Conclusion. This study confirms that the application of classification criteria of PsA based on the pattern and number of involved joints may be confounded in established PsA by the effects of DMARDs. The application of classification criteria based on disease pattern prior to treatment may be more useful in studies of pathogenesis and long-term outcome in PsA.
KEY WORDS: Psoriatic arthritis, Distal interphalangeal joint, DMARDs, Classification criteria.
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Introduction |
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The principal areas of contention centre on the number of joints involved (oligoarticular or polyarticular), the symmetry or asymmetry of joint involvement and the presence or absence of spinal or distal interphalangeal (DIP) joint involvement. Some studies have found that the largest PsA subgroup is the polyarticular subgroup [8, 9] while other studies have found that the oligoarticular subgroup is the largest [6, 10]. A retrospective evaluation of the presenting pattern of articular disease in 100 patients with a mean disease duration of 12.1 yr found that 64% of patients had changed from their initial presenting pattern [10]. In particular, 41/63 (65%) patients with oligoarticular/monoarticular disease had evolved to a polyarticular pattern, while only 2/25 (8%) of patients with polyarticular disease had evolved to an oligoarticular pattern. The degree of symmetry of joint involvement has also been used for classification criteria though it is likely that this is principally a function of the number of joints involved [11]. DIP joint predominant was one of the original five separate patterns of PsA described [2], but Torre Alonso et al. [12] found that DIP joint involvement was not a separate category but existed equally in all PsA subgroups. In 1994, Veale et al. [6] also suggested that DIP predominant was not a separate category and a simplified PsA classification into just three patternsoligoarthritis (predominantly asymmetrical), polyarthritis (predominantly symmetrical) and predominant spondylitiswas proposed.
All of these classification systems, based on the pattern and number of involved joints in patients with long-standing PsA, are likely to be confounded by the effects of pre-existing joint damage and of the higher prevalence of disease-modifying anti-rheumatic drug (DMARD) and corticosteroid treatment in established PsA. Examination of the pattern of disease in early PsAwith little or no DMARD treatment to influence the pattern of articular diseasemay be more informative. Published studies of early PsA have not yet addressed this issue [13, 14] and it is not known if classification of PsA influences clinical outcome. The detailed characterization of the classification and outcome of a large inception cohort of PsA early in the course of disease would allow these issues to be addressed.
This study examined a cohort of 129 patients presenting with PsA to an early inflammatory arthritis clinic in order to examine the pattern of joint involvement early in the course of PsA. Most patients were not taking DMARDs or corticosteroids at presentation; those who were on DMARDs had commenced it for a few weeks only. The Veale criteria were applied to evaluate the evolution of oligoarticular and polyarticular patterns at 1- and 2-yr follow-up and to determine the influence of initial disease pattern on clinical and radiological outcome. The influence of DIP joint involvement on the presentation, classification and evolution of early PsA was also examined.
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Patients and methods |
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Clinical assessment
Full demographic details and history of skin and joint disease and previous and current medications were recorded for each patient at the time of initial assessment. Clinical examination of all joints was carefully performed recording the pattern of peripheral and axial joint disease in addition to the presence of skin and nail disease. Patients were reassessed at 3-monthly intervals for the first year and at yearly intervals thereafter. Clinical assessment was performed for tenderness and swelling of each peripheral joint. The Ritchie Articular Index [15] and the European League Against Rheumatism (EULAR) swollen joint count (maximum of 44 includes metacarpophalangeal, proximal interphalangeal, wrist, elbow, glenohumeral, acromioclavicular, sternoclavicular, knee, ankle and metatarsophalangeal joints) were calculated. Patients were asked to determine the duration of generalized joint stiffness present on awakening in the morning according to the following four categories: (a) <10 min, (b) 1030 min, (c) 30120 min, or (d) >120 min. They were asked to record the degree of joint pain they had experienced over the preceding week on a 10-point visual analogue scale (VAS), ranging from 0 (no pain) to 10 (worst pain ever). Patients were asked to complete the pain and disability sections of the modified version of the Health Assessment Questionnaire (HAQ) [16]. They were questioned about the degree of impairment of self-care, work-related activities and leisure-related activities and were categorized according to the American College of Rheumatology (ACR) functional class [17].
Laboratory investigations
Erythrocyte sedimentation rate (ESR) was measured by standard Westergren method (in mm/h). C-reactive protein (CRP) levels were measured by standard nephelometry (in mg/l). Rheumatoid factor (RF) was measured by the rheumatoid arthritis particle agglutination method and results are expressed in titres of 1/40 and higher. Antinuclear antibody (ANA) was measured using Hep-2 substrate and results are expressed in titres of 1/40 and higher. RF and ANA were measured using commercial standardized kits in a hospital diagnostic laboratory.
Radiological assessment
Plain radiographs of the hands and feet were performed at the initial visit and were scheduled at annual intervals. Radiographs of other affected joints including knees and sacroiliac joints were obtained at baseline and follow-up visits when clinically indicated. The radiographs were evaluated by two trained observers in agreement using the Sharp method [18] modified to include the DIP joints. Radiographs were analysed in chronological order of dates with the observers blinded to the patient identity. In the Sharp method, erosions (05) and joint space narrowing (04) were graded separately. The DIP, proximal interphalangeal (PIP), metacarpophalangeal (MCP) and wrist joints were scored in the hands. The wrist was scored for erosions in seven areas and for joint space narrowing in eight areas. The MTP joints were scored in the feet. Using this method the maximum score for erosions in the hands is 210 and the maximum score for erosions in the feet is 50; the maximum scores for joint space narrowing in the hands and feet are 168 and 40, respectively. Periostitis of the hands and feet was also recorded when present.
Sacroiliitis was determined from anteroposterior radiographs of the sacroiliac joints by two observers scoring in agreement. The New York radiological criteria for sacroiliitis were applied [19].
Classification and clinical subgroups
Patients were classified according to the Veale criteria [6]. This classification defines patient groups according to joint involvement regardless of DIP disease. Patients were classified as follows: (1) an oligoarthritis, frequently asymmetrical with few erosions, infrequent deformity and good preservation of function; (2) a polyarthritis (4 or more joints), frequently symmetrical and erosive, but rheumatoid factor negative; or (3) predominant spondylitis. Remission was defined as absence of fatigue, <10 min of morning stiffness, no joint pain (including inflammatory back pain), no joint swelling (including dactylitis and enthesitis) and ESR <20 mm/h (males) or <30 mm/h (females) [20].
Serum amyloid A (SAA) measurement
Serum was obtained from all subjects at the time of assessment and stored at 70°C until analysed. Acute SAA (A-SAA) was measured using an enzyme-linked immunosorbent assay (ELISA) technique specific for A-SAA and with no cross-reactivity for its constitutive counterpart C-SAA (Biotrin Ltd, Dublin, Ireland). The assay was calibrated against the National Institute for Biological Standards and Control and the World Health Organization standard for SAA and performed as already described [21, 22]. All samples were assayed in duplicate and repeated if there was a discrepancy in the paired results. The detection limit of the assay is 2.25 µg/l. The normal range for the assay has been previously reported as 1.215.2 mg/l in 20 healthy volunteers. An A-SAA of >20 mg/l was considered elevated.
Statistical analysis
All values are given as mean (median) ± standard deviation. Analysis of the data was performed using non-parametric analysis in StatviewTM software. The MannWhitney U-test was performed to compare the medians of groups. Simple regression and Spearman correlation coefficient was used to test for correlation of variables.
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Results |
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Frequency of joint involvement in PsA
Joints were assessed separately for tenderness and swelling and the results are presented in Fig. 1. The small joints of the hands and feet were the most frequently involved joints in this cohort. The most frequently involved large joint was the knee, being present in 67 (52%) patients, with DIP involvement being present in 50 (39%) patients. Hip joint involvement was infrequent in early PsA. Temporomandibular (5%), sternoclavicular (2%) and acromioclavicular (2%) involvement were usually detected by the presence of joint tenderness. No patient had synovitisacnepustulosishyperostosis (SAPHO) syndrome.
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Classification of PsA
Using the Veale classification, 52 (40%) had oligoarthritis and 77 (60%) had polyarthritis at presentation. As referral to the early synovitis clinic required the presence of peripheral synovitis, no patient had predominant spondylitis at presentation. Of 129 patients, 119 (97%) were assessed 1 yr after presentation; 31 (26%) patients were in complete remission of disease, 53 (45%) had oligoarthritis, 33 (28%) had polyarthritis and 2 (2%) had predominant spondylitis. Of 129 patients, 97 (75%) were assessed 2 yr after presentation; 20 (21%) patients were in complete remission of disease, 47 (48%) had oligoarthritis, 28 (29%) had polyarthritis and 2 (2%) had predominant spondylitis.
Evolution of disease subsets
At 1 yr, 49/52 patients classified as oligoarticular at presentation were reassessed (Fig. 2a); 5 (10%) were now classified as polyarticular, 26 (53%) remained classified as oligoarticular and 18 (37%) were in remission. At 2 yr, 39/52 patients classified as oligoarticular at presentation were reassessed; 9/39 (23%) were now classified as polyarticular and 21/39 (54%) remained classified as oligoarticular (Fig. 2b).
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The effect of DMARDs on classification of PsA is detailed in Fig. 2. A greater percentage of patients classified with oligoarticular disease at baseline were in DMARD-free disease remission at 2 yr (75 vs 42%); 73% of patients classified as polyarticular disease at baseline who were subsequently classified as oligoarticular disease at 2 yr were taking a DMARD (Fig. 2d).
Comparison of clinical and radiological features of oligoarticular and polyarticular PsA
Clinical features and radiological outcome were compared between patients presenting with oligoarticular and polyarticular disease (Table 1). Polyarticular PsA was significantly associated with an older age of arthritis (P = 0.001) and psoriasis (P = 0.002) onset. At the initial assessment, articular disease indices, acute-phase indices and functional and radiological scores were siginificantly higher in polyarticular disease than in oligoarticular disease. There was a significantly higher use of DMARDs at 1- (P = 0.02) and 2-yr (P = 0.003) follow-up in polyarticular disease compared with oligoarticular disease. Oral corticosteroid prescription did not differ significantly between PsA subgroups, being most frequent in patients with polyarticular disease (9% of patients at 1 and 2 yr). Nineteen per cent (11/58) of patients with polyarticular disease and 13% (5/39) of patients with oligoarticular disease were ACR functional class III or IV at 2-yr follow-up (P = 0.86). There was no difference in the overall frequency of clinical remission in oligoarticular or polyarticular PsA, though DMARD-free remission was more frequent in oligoarticular disease.
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Comparison of PsA subgroups based on the presence or absence of DIP involvement at presentation
DIP joint involvement occurred in 50 (39%) patients at the initial assessment. A comparison of the features of the DIP involvement and no DIP involvement subgroups is given in Table 2. Patients with DIP involvement had increased articular indices and acute-phase indices, though only the ESR reached statistical significance. Both subgroups of patients had similar Sharp scores at baseline and follow-up. Periostitis was more frequent in patients with DIP joint involvement, but this did not reach statistical significance (P = 0.05). Nail dystrophy, enthesopathy and dactylitis were significantly more frequent in patients with DIP joint involvement. Radiological sacroiliitis was present in 17% of patients in both subgroups.
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Discussion |
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The median number of swollen or tender joints was four and is lower than reported in the other two early PsA cohorts reported, though Harrison et al. [13] specifically examined patients with PsA polyarthritis. The most frequently involved joints were the small joints of the hands and feet. In the lower limb, knee and ankle involvement was frequent, while hip, talocalcaneal and mid-talar joint involvement was uncommon. In the upper limb, wrist involvement was frequent with a lower frequency of elbow and shoulder involvement. Sternoclavicular joint involvement was noted in 2% of patients, though none of the patients had SAPHO syndrome. This provides further evidence that the rarity of SAPHO makes its separate classification difficult to justify [6].
In applying the Veale criteria for PsA classification, polyarthritis was the most common group in early PsA. With increasing DMARD treatment rates the oligoarticular group increased in size. The majority of previous studies have found that polyarticular disease is the most common subgroup [8, 9] while others find that oligoarticular disease is the most common [6, 10]. This is the first study to look at classification in a large cohort of early PsA patients before the effects of DMARD treatment. Patients initially classified as having oligoarticular disease were less frequently reclassified as having polyarticular disease and were more likely to achieve DMARD-free disease remission. Patients initially classified as having polyarticular disease were frequently reclassified as having oligoarticular disease and the majority of these patients were taking DMARDs, which would be expected to reduce the number of inflamed joints. This suggests that the pattern of joint involvement at initial assessment gives a more accurate representation of PsA subgroups than at a later stage.
It has been recently postulated that the enthesis may be the initial site of joint inflammation in SpA [24, 25] and a classification of PsA has been proposed based on the pattern of synovial or entheseal inflammation [7]. In this PsA cohort, peripheral enthesopathy was noted in 38% of patients at presentation, being most frequently present as dactylitis. Dactylitis and enthesopathy were also significantly more frequent in patients with DIP disease, but were equally distributed in the polyarticular and oligoarticular subgroups. As enthesopathy may be subclinical and only detectable by MRI [25] or ultrasonography [2628], the frequency of enthesopathy may be underestimated by clinical examination. Detailed imaging studies of large numbers of patients with PsA are still required to clarify if PsA subgroups can be readily classified according to the pattern of involvement of articular tissues.
The polyarticular group had increased clinical, laboratory, functional and radiological markers of arthritis, probably as a function of the greater number of inflamed joints. Comparison of oligoarticular and polyarticular disease also showed that the polyarticular group were likely to have an older age of arthritis and psoriasis onset, which may be a reflection of the association of elderly onset PsA (EoPsA) with more severe inflammatory joint disease [14]. In the enthesitis/synovitis model of PsA it has been proposed that polyarthritis in PsA may represent seronegative rheumatoid arthritis (RA) in patients with psoriasis. The age and sex characteristics of the polyarticular PsA subgroup are more in keeping with PsA cohorts than with RA, particularly the increased number of males in the polyarthritis group. Similarly, DIP involvementa feature not seen in RAwas more frequent in polyarticular disease and equal rates of specific seronegative features such as enthesopathy and dactylitis were observed in both oligoarticular and polyarticular groups.
DIP joint involvement and nail dystrophy are distinctive clinical features of PsA that have been reported to be topographically associated, possibly by a common local inflammatory mechanism [10]. In our study, DIP involvement at presentation was associated with enthesopathy and nail dystrophy providing further evidence of this mechanism. This may be due to the close anatomical proximity of the nail bed and the ligamentous capsule of the DIP joint [7]. It is not known if the primary abnormality occurs in the enthesis of the DIP joint or the nail bed. Patients with DIP involvement were more frequent in the polyarticular PsA group and had significantly higher articular inflammatory indices and a higher acute-phase response. However, DIP involvement was not associated with a significantly different clinical outcome in terms of radiological scores, though there was an increase in periostitis in the DIP group that approached significance. Initial classification systems of PsA proposed a subgroup of DIP predominant, though subsequent studies have argued that this is not useful, as it does not exist as a separate entity [6, 12]. This study concludes that DIP joint involvement is not a separate entity in early PsA and that its presence does not significantly affect disease outcome measures.
In conclusion, this study confirms that the application of the Veale or other classification criteria of PsA based on the pattern and number of involved joints is confounded in established PsA by the effects of therapy. Polyarticular PsA was the commonest subgroup of peripheral joint disease in early PsA at presentation. This subgroup was administered DMARDs more frequently than patients with oligoarticular PsA resulting in a significant number of polyarticular PsA patients being reclassified as oligoarticular. Fewer patients initially classified with oligoarticular PsA were reclassified as polyarticular PsA, and oligoarticular PsA demonstrated trends to more DMARD-free remission and less radiological damage, though this did not reach statistical significance at 2-yr follow-up. These findings support previous studies that have shown that polyarthritis [29] or a high ESR [30] are associated with a poor prognosis, while a lower number of inflamed joints at presentation is associated with remission [31]. Predicting outcome based on the classification of PsA may be more usefully applied when based on the initial pattern of disease. DIP disease was associated with other classic seronegative disease featuresenthesopathy and nail dystrophybut did not influence clinical or radiological outcome and the separation of DIP disease as a distinct subgroup in classification criteria was not supported.
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References |
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