About Psoriatic Arthritis

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About Psoriatic Arthritis (PsA)

PsA: a heterogeneous disease
PsA is a heterogeneous disease involving up to six domains (see Figure 1).1 Every person with PsA is unique: each will present with a different combination of these domains and varying degrees of severity. Regardless of the individual’s combination, PsA has a substantial effect on patients’ lives.1
Image
Fig. 1 The prevalence of each of the six domains of PsA2

Expert opinion
Dr. Nicola Gullick discusses the importance of early diagnosis.
“The consequences of a delay in diagnosis would be that a patient may already have joint damage by the time they present, or they may have already lost quite a lot of function. So it’s not unusual for me to see a patient who’s had symptoms for perhaps two to three years, and they may have already lost their job by the time actually receive a diagnosis.”

Understanding PsA – dysregulation of cytokines
PsA is caused by the overproduction of pro-inflammatory cytokines; changes to inflammatory signalling pathways can affect cells in the skin and joints, causing symptoms of psoriatic disease, such as swelling and tenderness of the joints.3 Current research suggests that each domain is driven by the dysregulation of a different combination of cytokines (see Figure 2).
Image
Fig 2. Map of cytokines by each domain, from human and animal models 4-15

Expert opinion
Dr. David Crosbie discusses the guidelines and frameworks available to rheumatologists to support the management of patients with PsA.
“With the GRAPPA guidelines, effectively what you can then do is look across what domains your patient is challenged by, look which therapies feature in each of those domains, and try and make the best choice for that patient.”

Distinguishing PsA from Rheumatoid Arthritis (RA)
While there have been medical advances in this area, achieving an accurate diagnosis of PsA remains a challenge in the UK; specifically, distinguishing PsA from RA poses a particular issue.
Like PsA, RA is an autoimmune disease characterised by pain, swelling and stiffness of the joints (see Figure 3)3.
Image
Fig. 3 Prominent clinical features of PsA and RA1,16,17

Expert opinion
Dr. Antoni Chan discusses the distinguishing features of PsA and explains its impact on the daily lives of patients.
“PsA has a very significant impact on patients’ day-to-day life. Firstly, if you think of the involvement of the joints, it could reduce their mobility and their independence. The pain can also be significant, and as a result of the inflammation that goes on, people have difficulty with their fatigue, their sleep, and their work.”

 
Other key indicators of PsA
1
PsA can be associated with a negative serologic test for rheumatoid factor and is commonly asymmetric, presenting enthesitis and dactylitis, beyond the peripheral joint involvement (see Figure 3)1, 18.
2
The pattern of joint involvement and bone erosion is different in RA and PsA.3, 19, 20 Bone changes in PsA include erosion and new bone formation, whereas new bone formation does not occur in people with RA3, 19, 20.
Psoriatic arthritis bone erosion
Image
Fig. 4 PsA bone erosion19
Rheumatoid arthritis bone erosion
 Image
Fig. 5 RA bone erosion19
3
People with RA can experience primary synovitis, whereas PsA is characterised by enthesitis (inflammation of the entheses).19 Secondary synovitis can occur with enthesitis in PsA. This is different to the primary synovitis experienced by people with RA (see Figure 4 and Figure 5)19.
4
In PsA, radiographic disease progression is slower than in RA.21, 22, 23, 24, 25, 26 The Total Sharp Score (mTSS) was created to measure joint changes in RA and has now been modified to account for the clinical features of PsA.27

Expert opinion
Dr. William Tillett discusses the role of the six domains in diagnosing PsA and the consequences that a delay in diagnosis can have on patients.
“We know that, certainly in the UK setting, there’s a three-month delay between getting your first symptoms of PsA and a diagnosis, when you compare to RA. So there is this offset, and we don’t really know why that exists”

GRAPPA recommendations
The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) identified the six domains of PsA and advocate a tailored treatment approach for patients, based on domain involvement.
Recommendations suggest targeting as many active disease domains as possible and considering a patient’s prior treatment history and comorbidities.

References
1. Coates LC, et al. Arthritis Rheumatol 2016;68:1060–71.
2. Coates LC, et al. Lancet 2015;386:2489–98.
3. Ritchlin CT, et al. N Engl J Med 2017;376:957-970.
4. Lowes M, et al. J Invest Dermatol 2008;128:1207–11.
5. Lee E, et al. J Exp Med. 2004;199(1):125-130.
6. Yao Y, et al. PLoS One 2008;3:e2737.
7. Villanova F, et al. Ann Rheum Dis. 2013;72(Suppl 2):ii104-110.
8. Van Kuijk AW, Tak PP. Curr Rheumatol Rep. 2011;13(4):353-359.
9. Menon B, et al. Arthritis Rheumatol. 2014;66(5):1272-1281.
10. Celis R, et al. Arthritis Res Ther. 2012;14(2):R93
11. Siegel EL, et al. Curr Opin Rheumatol. 2015;27(2):111-117.
12. Bagel J, Schwartzman S. Am J Clin Dermatol. 2018.
13. Kyriakou A, et al. Expert Opin Biol Ther. 2013;13(12):1707- 1714.
14. Taylan A, et al. Rheumatol Int 2012;32:2511.
15. Limon-Camacho L,et al. J Rheumatol 2012;39:830–5.
16. Gottlieb J Am Acad Derm, 2008; 58:851-64.
17. Scutellari P, et al. Eur J Radiol 1998;27(suppl 1):S31–38.
18. Moll JMH and Wright V. Semin Arthritis Rheum 1973;3:55–78
19. McGonagle D, et al. Lancet 1998;352:1137–40.
20. Schett G, et al. Nat Rev Rheumatol 2017;13:731–41.
21. Ravindran J, et al. Arthritis Care Res 2010;62:86–91.
22. Gladman DD, et al. Arthritis Rheum 2007;56:476–88.
23. Kavanaugh A, et al. Arthritis Rheum 2012;64:2504–17.
24. Kavanaugh A, et al. Ann Rheum Dis 2014;73:1020–6.
25. Van der Heijde D, et al. Arthritis Rheum 2016;68:1914–21.
26. Strand V & Sharp JT. Arthritis Rheum 2003;48:21–34.
27. Van der Heijde, et al. Ann Rheum Dis 2005; 64(Suppl II):ii61–4.

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