Progression of peripheral joint disease in psoriatic arthritis: a 5-yr prospective study

N. J. McHugh, C. Balachrishnan and S. M. Jones

Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL, UK


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Objective. To assess the evolution of disease subgroups and the frequency of progression of peripheral joint disease in a prospectively studied cohort of patients with psoriatic arthritis (PsA).

Methods. The cohort was identified as the first consecutive 100 patients attending a psoriatic arthritis clinic and who had been the subject of a previously published cross-sectional retrospective study. Nine of the 100 patients had died, three declined follow-up and one could not be traced. The remaining 87 patients (49 females, 38 males) completed the study proforma at a median follow-up interval of 65 months (range 39–90). An analysis of initial plasma viscosity compared with rates of progression of joint score was performed.

Results. Eighteen patients changed subgroup; 11 had an increase in the number of joints involved, six a decrease, and one changed from an oligoarticular pattern to predominant spondylitis. Within the polyarticular group 37/51 patients had an increase in the number of joints involved. For the whole population, there were significant increases in the number of joints involved (median 6 vs 11, P < 0.001 Wilcoxon signed rank) and Health Assessment Questionnaire scores (median 0.375 vs 0.5, P < 0.001). The median rate of joint progression was 0.42 peripheral joints per year (range 0–7.2). However, the rate of peripheral joint involvement was highest in the first year of arthritis (median 4.0 joints/yr) as measured in 13 patients who had onset within 12 months of baseline assessment. There were no significant differences in skin and nail scores although nine more patients had developed nail disease. There was a significant correlation between the initial viscosity and rate of progression of joint damage (Spearman correlation, P < 0.011).

Conclusions. Peripheral joint disease is progressive in the majority of patients with PsA and reinforces the need for effective monitoring and treatment.

KEY WORDS: Psoriasis, Psoriatic arthritis, Mortality, Outcome, Spondylarthropathy.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Psoriatic arthritis (PsA) is a distinctive inflammatory form of arthritis with a predilection for early involvement of the enthesis [1] and an estimated incidence rate of 6.1 to 6.59 per 100 000 [2, 3]. The concept of PsA being a relatively benign inflammatory joint disorder is controversial. Community-based studies of inflammatory arthropathy suggest that the presence of psoriasis does not confer a poor outcome [3, 4]. However, the presence of psoriasis may indicate a worse short-term outcome in patients with spondylarthropathy attending an early arthritis clinic [5]. Furthermore, patients reaching a referral centre for arthritis are likely to have progressive spinal and peripheral joint disease [69]. Relatively few centres have studied the rate of arthritis progression prospectively, or factors that may predict prognosis. With the advent of biological therapies that offer much potential for preventing disease progression in PsA [10], more precise information is needed on the rate and pattern of joint damage.

The consistency of the classic subgroups of PsA described in the early studies by Moll and Wright [11] is less obvious when patients are studied over time. For instance, in a more recent longitudinal study only two subgroups comprising peripheral compared with axial disease could be discerned [12]. The concept of an asymmetrical pattern of disease being characteristic of psoriatic arthritis has also been challenged with a recent study demonstrating no difference in symmetry between PsA and rheumatoid arthritis (RA) after adjusting for the number of peripheral joints involved [13]. Previously we reported findings in a cross-sectional cohort of patients where clinical subgroups appeared to change over time, and the mode of onset did not predict outcome [7]. That study was limited by its retrospective design and the wide variation in disease duration. In the current study we have had the opportunity of re-studying our previously documented cohort of patients with PsA with a rigorous protocol over a more clearly defined time interval in order to obtain more precise information on the pattern and rate of progression of joint involvement.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Patients
Eighty-seven patients from our previous cross-sectional study were available for follow-up. Ninety per cent of these patients came from Bath and surrounding areas. The majority of patients constituting the baseline cohort were recruited from other rheumatology clinics at the Royal National Hospital for Rheumatic Diseases in Bath, about 25% were new referrals from general practice and less than 10 per cent were from a dermatology clinic. All patients had baseline information recorded sometime between October 1987 and March 1990. These patients were followed-up at a median of 65 months (range 39–90). Fifty of these 87 patients were still attending the psoriatic arthritis clinic or other general rheumatology clinics in Bath; the remaining 37 patients were contacted by letter or telephone and asked to attend a follow-up appointment.

Of the remaining 13 patients, nine had died, one could not be traced and three declined follow-up. The cause of death of the nine patients who died was ascertained by obtaining the contemporary medical records or general practitioner's notes; where these were incomplete or unhelpful, the general practitioner was contacted by telephone.

Clinical and radiological documentation
A proforma identical to that completed in the cross-sectional study was completed for all patients [7]. The proforma included a standardized examination of peripheral joint and axial involvement, skin psoriasis score using the Psoriasis Area and Severity Index (PASI) [14], nail score [7] and functional assessment using the Stanford Health Assessment Questionnaire (HAQ) Score [15]. Seventy-five patients had standard anteroposterior radiographs of hands and feet taken at baseline and follow-up. Other radiographs were performed when clinically indicated.

Patient subgroups
Patients were divided into subgroups based on objective clinical and/or radiological evidence of joint involvement at follow-up. The subgroup distinctions employed in the cross-sectional study were used as follows: monoarthritis; oligoarthritis (<5 peripheral joints involved); distal interphalangeal (DIP) joint disease only; polyarthritis (>4 joints involved); arthritis mutilans and predominant spondylitis. Arthritis mutilans was defined as a severe deforming polyarthritis causing widespread radiographic osteolysis. Symmetry was defined by number of joints involved as symmetric pairs/total number of peripheral joints involved >=0.5 [13].

Peripheral joint score
The peripheral joint score ranged from 0–70 joints involved, with one point scored for each involved joint. Joint involvement was defined as the presence of either synovial swelling or joint deformity or radiological abnormality not solely attributable to osteoarthritis. The joints included were DIP, interphalangeal (IP) of the thumbs, proximal interphalangeal (PIP), metacarpophalangeal (MCP), wrist, elbow, shoulder, temporomandibular, sternoclavicular, acromioclavicular, hip, knee, tibiotalar, talocalcaneal, midtarsal, metatarsophalangeal (MTP), IP of the first toe and the remaining toes (each toe counting as one). The spine was excluded from this score although involvement of the cervical and lumbar spine was noted. Rate of progression of joint score was calculated by dividing the joint score (at baseline and follow-up) by the duration of arthritis in years (to baseline and follow-up, respectively) and by subtracting joint score at baseline from joint score at follow-up, dividing by the months of follow-up and reported as joint progression per year.

Laboratory tests
A full blood count, rheumatoid factor and plasma viscosity were obtained from all patients at baseline and follow-up. C-reactive protein levels were only available for patients at follow-up.

Data analysis
All data were stored in a Microsoft Excel database and analysed using Statworks and Multistat software packages on an Apple Macintosh computer. The distribution of the various data sets was assessed first and a descriptive comparison of the data at baseline and follow-up was made. Differences between non-parametric data sets were analysed using Wilcoxon signed rank test. Correlation between initial plasma viscosity and the rate of joint progression was made using Spearman's test.

Ethical approval
The study had full ethical approval of the Bath District local regional ethical committee.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Demographic data and mortality
The demographic data for the 87 patients are shown in Table 1Go. Nine patients had died since the original study. Five of the deaths were related to coronary artery disease, but one death was attributed to immobility and general debility associated with psoriatic arthritis mutilans. All of the patients who died were elderly.


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TABLE 1. Demographic data and mortality

 

Medications at baseline and follow-up
With the exception of methotrexate there was a decrease in the frequency of all oral medications used to treat arthritis at follow-up compared with baseline. At follow-up 15% of patients were taking methotrexate compared with 12% at baseline. In comparison there was less use of non-steroidal anti-inflammatory agents (95 to 66%), sodium aurothiomalate (19 to 4%), sulphasalazine (14 to 4%), D-penicillamine (10 to 1%), azathioprine (7 to 3%), hydroxyurea (5 to 0%), hydroxychloroquine (5 to 0%) and auranofin (3 to 0%).

Evolution of joint disease and functional outcome
Clinical subgroups at baseline and follow-up are shown in Table 2Go. In total, 18 patients (21%) changed pattern, 12 of whom had an increase in the number of joints involved and six of whom had decreased joint involvement. The most notable change in subgroup was from oligoarthritis to polyarthritis, with 10 of 23 patients with oligoarthritis switching to polyarthritis. One patient who had peripheral joint involvement with four joints involved developed predominant spondyloarthritis. Four patients with predominant spondyloarthropathy also developed peripheral joint disease. The polyarthritis in one patient evolved to arthritis mutilans. Four patients (three with monoarthritis at baseline and one with oligoarthritis at baseline) had no clinical evidence of joint disease at follow-up. One male patient continued to have evidence of distal joint disease exclusively.


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TABLE 2. Clinical subgroups at baseline and follow-up

 
There was a significant increase in peripheral joint disease in the group as a whole. The median number of peripheral joints involved increased from 6 at baseline to 11 at follow-up (P < 0.001) (Table 3Go). The median rate of joint progression was 0.42 peripheral joints per year (range 0–7.2). Joint involvement in the patients with polyarthritis at baseline increased in 37 out of 51 patients. The progression of peripheral joint disease was also accompanied by a significant increase in disability as measured by the median HAQ score (0.375 at baseline and 0.5 at follow-up; P < 0.001).


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TABLE 3. Median rates of joint progression according to age of onset or stage of arthritis (interquartile ranges are given in parentheses)

 
Seventy-five patients had radiographs of hands and feet at both baseline and follow-up. Forty of 75 patients (53%) had erosions of hand or wrist at baseline and 51 of 75 (68%) had erosions at follow-up. Twenty-eight of 75 patients (37%) had foot erosions at baseline and 35 of 75 (44%) had foot erosions at follow-up.

The rate of progression of joint score was also investigated separately for 10 patients who had a young age of onset of arthritis (<=20 yr) and five patients who had an older age of onset (>=60 yr) (Table 3Go). There did not appear to be any marked differences in the rate of joint progression in either of these two subgroups, although the numbers of patients were small.

There were 13 patients who had arthritis of less than 12 months duration at the baseline assessment. The rate of peripheral joint progression was significantly higher in this group up to baseline assessment compared with the rate of the joint progression in the same patients over subsequent years until follow-up (4.0 vs 0.32; P=0.003)

Pattern of joint disease
The distribution of peripheral joint disease at baseline and follow-up is shown in Table 4Go. There was an increase in the involvement of all peripheral joint groups with the largest change for the shoulder (increase from 23 to 43.7%) and the smallest change for the subtalar joint (increase from 17.2 to 18.4%). Of interest, involvement of DIP joints of the hand (46% at follow-up) or IP involvement of the feet (47.1% at follow-up) was common, emphasizing their potential value in differentiating PsA from RA, where involvement of these joints is less common.


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TABLE 4. Pattern of peripheral joint involvement in 87 patients at baseline and follow-up (frequencies in parentheses)

 
The percentage of patients with symmetrical joint disease in the polyarthritis group was high both at baseline (81%) and at follow-up (73%). While four of 23 (18%) in the oligoarthritis group had symmetrical joint disease at baseline, a further five had symmetrical disease by the time of follow-up. Of the 10 patients who evolved from oligoarthritis to polyarthritis, seven had asymmetrical polyarthritis at follow-up and three had symmetrical polyarthritis.

Laboratory markers
Fifty patients (57%) had elevated plasma viscosities at baseline compared with 45 (52%) patients at follow-up. There was no significant difference between plasma viscosity levels at baseline (median 1.74) and follow-up (median 1.76). Twenty patients at follow-up had elevated C-reactive protein levels (greater than 0.01 g/l). There was a significant correlation between initial plasma viscosity and the rate of progression of joint damage (Spearman, P < 0.011). One patient was positive for rheumatoid factor at baseline (>80 units by nephelometry). Three patients became seropositive for rheumatoid factor by the time of follow-up. All four patients with rheumatoid factor had polyarthritis.

Nail and skin disease
There were no significant differences between skin and nail scores at baseline and follow-up. The types of psoriasis did not change between baseline and follow-up and there was no association between subgroups of joint disease or type of psoriasis or severity of psoriasis based on the PASI score. Eleven further patients had developed nail disease, so a total of 68/87 (78%) had nail disease. Twenty-three of the 87 patients reported simultaneous exacerbations of their skin and peripheral joint disease. The temporal relationship between joint, skin and nail disease was studied prospectively in more detail in a cohort of 24 patients and will be reported separately.


    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
In contrast to early studies that suggested oligoarthritis was the predominant pattern seen in individuals with psoriatic arthritis [11], it is now apparent that polyarthritis is at least as common [9] and usually more common in those with established disease [7, 12]. In the current study only 14% of patients had oligoarthritis by the time of follow-up, with 10 of 23 patients changing from oligoarthritis at baseline to polyarthritis at follow-up. Marsal et al. [12] reported only 6.8% patients had oligoarthritis in a similar-sized cohort followed for a median of 8 yr. Arthritis mutilans and DIP joint disease alone are also uncommon, accounting for less than 5% of patients in our cohort. Other studies have also argued against exclusive DIP joint disease being a useful subgroup [9, 12, 16]. However, the frequency of either DIP joint involvement of the hands or IP joint involvement of the feet was relatively common overall, and certainly may be a useful feature for differentiating PsA from other inflammatory arthritides, especially RA. Otherwise, we would support the concept of there being at most two subgroups of psoriatic arthritis [12], even then allowing for a degree of overlap, based on axial vs peripheral joint involvement.

The majority of patients in our cohort had progressive peripheral joint disease. Gladman et al. [6] reported that the proportion of patients with at least 5 damaged joints doubled from 19 to 41% in 126 patients followed for at least 5 yr. The rate of progression of joint damage, calculated by the ratio of the number of damaged joints to the duration of arthritis in years, decreased during follow-up from 1.97 to 0.5/yr. Our findings are very similar, although we measured clinical or radiological joint involvement rather than joint damage. The rate of progression was 0.4 peripheral joints/yr. The rate was remarkably similar across age groups of onset. Punzi et al. [17] reported a higher rate of disease progression in elderly-onset psoriatic arthritis (disease onset at 60 yr or over), findings not supported in the current study although the number of patients in our older age of onset was small. The highest rate of peripheral joint involvement appeared to be within 12 months of disease onset, which together with the data from Gladman et al. [6], suggests that treatment targeted to early intervention is likely to be the most effective.

Erosive joint disease was common in our cohort and similar to that reported by Marsal et al. [12]. The latter study reported erosive disease in 52/73 patients (71%). In a Finnish study, 46% of patients who had radiographs of the hands had hand erosions, and an identical rate was reported for the feet [2]. In our study the percentage of patients with erosions in hand or wrist increased from 53 to 68% and erosive foot disease increased from 37 to 44%. In a community-based study, development of erosions in hands and feet was reported as 8% for hands and 3% for feet over an average length of follow-up of 7.2 yr [3]. The higher rate of erosion in our study is likely to reflect the more severe end of the spectrum of arthritis seen in a referral centre compared with that managed in the community.

Gladman's group have published extensively concerning factors that may predict poor prognosis in psoriatic arthritis [1820]. Number of effusions, elevated erythrocyte sedimentation rate and past medication were proposed as the best clinical predictors of damage progression [18], to which genetic factors [19] and time varying indicators [20] were later added. In the current study we found baseline plasma viscosity correlated well with subsequent rate of peripheral joint progression, supporting the notion that evidence of active inflammatory disease is a good prognostic marker for progressive joint disease. More than 50% of patients had an elevated plasma viscosity at either baseline or follow-up with no difference in the median level between the two intervals, suggesting that there is much scope for improving our current disease treatment interventions. Only four of 87 patients in our cohort had no clinical or radiological evidence of disease at follow-up. A relatively small rate of remission has been reported in the Toronto cohort (17.6%) with half of these patients having further disease flares [21], emphasizing the usually persistent and relentless course of PsA.

Quality-of-life status has also been the subject of studies within PsA [22, 23] and in comparison with RA [24, 25]. The mean global HAQ score in our group increased significantly from baseline (0.375) to follow-up (0.5), at which time it appeared to be similar to the Toronto cohort (0.55) [23]. In a comparison of hospital patients with PsA vs RA matched for disease duration, functional status including HAQ score was similar despite patients with RA having greater radiological damage [25]. The impact of skin psoriasis may play an additional role, yet there was no difference in PASI score in our patients despite an increase in HAQ score with time. Features such as pain and tenderness are likely to contribute to quality-of-life measurements in addition to joint damage [22].

Nine of our baseline cohort of 100 patients had died by the time of follow-up. There have been relatively few studies of mortality in PsA. Roberts et al. [26] reported 18 deaths in 168 patients followed from 1 to 10 yr, nine of which were due to complications of atherosclerosis. We have previously reported an atherogenic profile in PsA [27] that may possibly contribute to increased cardiovascular deaths. Wong et al. [28] found an increased standard mortality ratio in both men and woman (1.65 and 1.59, respectively) in the Toronto group compared with the general population. In the latter study there was an increase in death from respiratory disease that was not obvious in our cohort. However, we are in the process of completing a 15-yr follow-up of our baseline cohort that will allow us to investigate whether there is a similar excess in mortality as reported in Canada.

In conclusion, although a disproportionately high number of peripheral joints are involved in the first 12 months following disease onset, there is a steady progression of peripheral joint involvement in patients with PsA who are referred to a hospital clinic. High inflammatory markers such as plasma viscosity, rather than age of onset of disease, are associated with greater disease progression as measured by the number of peripheral joints involved. Knowledge of expected rates of joint progression will facilitate planning of therapeutic studies using potential disease-remitting agents that should aim at early intervention.


    Acknowledgments
 
The authors are grateful for the support of the Jules Thorn Charitable Trust and Remedi UK.


    Notes
 
Correspondence to: N. J. McHugh. E-mail: N.J.McHugh{at}bath.ac.uk Back


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

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Submitted 22 July 2002; Accepted 28 November 2002