This paper is the first to study the features of the synovial infiltrate of PsA in comparison with rheumatoid arthritis, taking into account disease duration and use of drug, using sophisticated digital image analysis. Interestingly, the only marked difference detected between the two groups in this study was a lower T cell count in the synovium with PsA. This is consistent with observations in two previous studies,11,13
and is perhaps remarkable because psoriasis and PsA are considered to be T cell‐driven diseases. The lower number of T cells in the synovium with PsA does not mean, however, that these cells are not important in pathogenesis: a subset of specific T cells might be sufficient to promote the inflammatory process, and regulatory T cells may have anti‐inflammatory effects. A trend towards a higher number of plasma cells in the synovium with rheumatoid arthritis was observed, but this difference was not significant. Only one earlier study10
showed a considerably higher number of plasma cells in the synovium in rheumatoid arthritis compared with that in spondyloarthropathy, but this could not be confirmed in a larger study by the same group.12
The most striking feature in both rheumatoid arthritis and PsA is the abundant overexpression of proinflammatory cytokines, especially TNFα, which was equally high in both groups. No other major differences between PsA and rheumatoid arthritis were found in synovial cell infiltrate, or in the expression of MMPs, adhesion molecules or vascularity.
A few previous studies have examined the features of the synovium in PsA with variable results.
Some studies suggested that the synovium in PsA is characterised by less pronounced lining layer in the hyperplasia and fewer monocytes/macrophages in the synovium,6,11
but neither finding could be confirmed in another study that analysed different forms of spondyloarthropathies together.10
One group found fewer T and B cells in the case of spondyloarthropathy synovium,10
but this was not found in the other studies.6,11
The fact that the synovial tissue was collected in different ways and the use of antirheumatic treatment may account for some of the observed differences.6,10,11
Interestingly, recent studies suggested that the presence of major histocompatibility complex–human cartilage gp39 peptide complexes in the synovium could be specific for rheumatoid arthritis12
and that the presence of a p53 mutation was higher in the case of rheumatoid arthritis than in the case of PsA synovium.13
These data suggest that the aetiology may be distinct between rheumatoid arthritis and PsA, although different processes may lead to the activation of common final pathways and similarities in the synovial infiltrate in established disease.
Increased vascularity has been reported in both psoriatic skin lesions and synovial tissue. The dermis of psoriatic skin has an abundance of dilated and tortuous blood vessels.31
This increased dermal vascularity is believed to be mediated by angiogenetic factors.32
Several authors have reported that the synovium in PsA is characterised by an increase in macroscopically tortuous blood vessels, and this is more pronounced—but not exclusive—in PsA than in rheumatoid arthritis.6,7,8,33
Consistent with the vascular abnormalities, overexpression of VEGF, which is involved in angiogenesis, has been reported in both psoriatic skin34
and synovial tissue in PsA.8,9
However, the increased vascularity in PsA compared with rheumatoid arthritis was not confirmed in all studies.11
In the present study, hypervascularity could be detected in both PsA and rheumatoid arthritis. There were trends toward increased numbers of blood vessels and expression of VEGF in PsA, but the difference from rheumatoid arthritis did not reach statistical significance, possibly because of the relatively small number of patients.
Blood vessels in psoriatic skin and PsA synovium express a variety of adhesion molecules such as ICAM‐1, VCAM‐1 and E‐selectin.6,35
These adhesion molecules are involved in leucocyte adhesion and penetration through the endothelium. TNFα has been shown to promote the expression of adhesion molecules and angiogenesis,36
whereas blockade of TNFα resulted in a decrease in the expression of angiogenetic factors and adhesion molecules in psoriatic skin22
and the synovium in PsA.22,23,37
In this study, abundant expression of adhesion molecules was found equally in rheumatoid arthritis and PsA.
The degradation of cartilage and bone, resulting in structural (radiological) damage in inflammatory arthropathies, is believed to be mediated in part by MMPs. MMPs have been shown to be abundantly present in both rheumatoid arthritis29,38
It has been suggested that high MMP expression is associated with more destructive disease.39,40
In the present study, there was high expression especially of MMP3, which was comparable for rheumatoid arthritis and PsA. This is in line with recent clinical studies, which showed that joint destruction in PsA is progressive in almost 50% of patients from an early arthritis clinic, showing radiological damage 2 years after first presentation,1
and that the degree of radiological damage in PsA is comparable to that in rheumatoid arthritis.41
Proinflammatory cytokines are important mediators of systemic and local inflammation, and abundant expression of IL1 and TNFα has been shown in psoriatic skin lesions,42
as well as in the synovial tissue of both patients with rheumatoid arthritis and PsA.11,39,43
The success of several TNFα blocking treatments in psoriasis and PsA44,45,46,47,48,49
and in rheumatoid arthritis50,51,52,53
has confirmed the importance of TNFα in these inflammatory diseases. In this study, there was equally high expression of TNFα in rheumatoid arthritis and PsA synovium. High expression of IL6, IL1β and, to a lesser extent, IL18 in rheumatoid arthritis and PsA has also been found in the present study. These data support the view that blockade of not only TNFα but also IL1β, IL6 and IL18 might be effective in PsA.
Consistent with previous reports, there were large differences in synovial infiltrate between individual patients within both groups. This may be caused by heterogeneity of what we diagnose clinically as being rheumatoid arthritis or PsA, and may point to the presence of certain disease subsets or pathophysiological differences, as has recently been suggested for rheumatoid arthritis.54
There were no clear‐cut differences between patients who used MTX and those who did not, which is in line with a previous cross‐sectional study.12
These data show that the lack of clinical response to MTX is reflected by persistent synovial inflammation.
In conclusion, although rheumatoid arthritis and PsA are clinically separate diseases, with a different aetiology, the present study showed mainly similarities in the synovial infiltrate of two well‐matched cohorts of patients with rheumatoid arthritis and PsA. This may be explained by the fact that different pathophysiological processes may lead to the activation of final common pathways. This study shows increased proinflammatory cytokine production in PsA compared with results obtained in rheumatoid arthritis. These data support the view that, in addition to TNFα blockade, targeted treatments against other proinflammatory cytokines might be effective in PsA as well.