Psoriatic arthritis RMD Open: first published as 10.1136/rmdopen-2018-000656 on 13 August 2018. Downloaded from REVIEW Distinguishing rheumatoid arthritis from psoriatic arthritis Joseph F Merola,1 Luis R Espinoza,2 Roy Fleischmann3 To cite: Merola JF, Espinoza LR, ABSTRACT Key messages Fleischmann R. Distinguishing Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) rheumatoid arthritis from have key differences in clinical presentation, radiographic What is already known about this subject? psoriatic arthritis. RMD Open findings, comorbidities and pathogenesis to distinguish Rheumatoid arthritis (RA) and psoriatic arthritis 2018;4:e000656. doi:10.1136/ between these common forms of chronic inflammatory ► rmdopen-2018-000656 (PsA) are both common chronic inflammatory dis- arthritis. Joint involvement is typically, but not always, eases, and differentiation of these conditions can be asymmetric in PsA, while it is predominantly symmetric in challenging. ► Prepublication history for RA. Bone erosions, without new bone growth, and cervical this paper is available online. spine involvement are distinctive of RA, while axial spine To view these files, please visit What does this study add? involvement, psoriasis and nail dystrophy are distinctive ► We review key differences in clinical, serological, ra- the journal online (http://dx. doi. of PsA. Patients with PsA typically have seronegative test org/ 10. 1136/ rmdopen- 2018- diographic and pathogenic features of RA and PsA, findings for rheumatoid factor (RF) and cyclic citrullinated 000656). and provide practical guidance for achieving a cor- peptide (CCP) antibodies, while approximately 80% of rect diagnosis. Received 31 January 2018 patients with RA have positive findings for RF and CCP Revised 25 May 2018 antibodies. Although there is overlap in the pathogenesis How might this impact on clinical practice? Accepted 25 May 2018 of PsA and RA, differences are also present that affect ► Accurate diagnosis of RA and PsA is important be- the efficacy of treatment. In PsA, levels of interleukin cause differences in underlying pathogenesis and (IL)-1β, IL-6, IL-17, IL-22, IL-23, interferon-γ and tumour response to therapy translate into substantially dif- necrosis factor-α (TNF-α) are elevated, and in RA, levels ferent clinical outcomes. of IL-1, IL-6, IL-22, IL-33, TNF-α, chemokine ligand 11 and chemokine C-X-C motif ligand 13 are elevated. Differences in the pathogenesis of RA and PsA translate disease processes that drive inflammation into some variances in the specificity and efficacy of and joint damage in RA and PsA. However, http://rmdopen.bmj.com/ therapies. depending on the molecule, therapeutic selection is complicated by variable efficacy between patients with RA and the manifes- tations of psoriatic disease (eg, enthesitis or INTRODUCTION skin psoriasis). Rheumatoid arthritis (RA) and psoriatic To help practitioners determine an accurate arthritis (PsA) are common chronic inflam- diagnosis, key differences in clinical, serolog- matory diseases; both are characterised ical, radiographic and pathogenic features of on September 30, 2021 by guest. Protected copyright. by pain and swelling in the joints and have RA and PsA are reviewed. The different ther- significant systemic manifestations.1–3 If not apeutic classes that can be of benefit in each diagnosed and treated early, both can lead to 1 disease are discussed in depth. Department of Dermatology, joint destruction with loss of function. For this Medicine and Rheumatology, reason, early diagnosis is important to deter- Brigham and Women’s Hospital mine therapeutic strategies that will optimise DIFFERENCES OF RA AND PSA and Harvard Medical School, 4 Boston, Massachusetts, USA clinical and radiographic outcomes. Differ- RA is an autoimmune systemic inflamma- 2Section of Rheumatology, LSU entiating between RA and PsA can be clini- tory disease characterised by synovitis, bony Health Sciences Center at New cally challenging because there are many erosions and cartilage damage.9 PsA is a heter- Orleans, New Orleans, Louisiana, similarities in their clinical presentation and ogeneous autoimmune systemic disease with USA 3 manifestations. Both also have similarities diverse clinical and radiographic manifesta- Department of Medicine, 5 9 University of Texas Southwestern with other inflammatory diseases and associ- tions. The presence of psoriasis precedes the Medical Center, Metroplex ation with coprevalent forms of arthritis, such development of PsA in 85% of patients, and Clinical Research Center, Dallas, as gout and secondary osteoarthritis.6–8 PsA typically develops about 10 years after the Texas, USA In the last 20 years, biologic disease- onset of psoriasis.10 Other common clinical Correspondence to modifying antirheumatic drugs, many with features of PsA include synovitis with subse- Dr Joseph F Merola; differing mechanisms of action, have become quent osteolysis and/or joint fusion of periph- jfmerola@ bwh. harvard. edu available. These medications target the eral joints, axial involvement, sacroiliitis, and Merola JF, et al. RMD Open 2018;4:e000656. doi:10.1136/rmdopen-2018-000656 1 RMD Open RMD Open: first published as 10.1136/rmdopen-2018-000656 on 13 August 2018. Downloaded from Epidemiological characteristics of RA and PsA Table 1 Clinical, serological and radiographic characteristics of PsA and RA RA is more common than PsA, affecting more than 1 million in the USA.11 PsA affects roughly half a million Characteristic PsA RA people in the USA12 and approximately 30% of patients Clinical with psoriasis.13 Worldwide prevalence estimates for RA Psoriasis +++ − and PsA are variable. In many populations, RA preva- Symmetric joint involvement + +++ lence is estimated to be 0.5%–1.0%; however, prevalence Asymmetric joint involvement ++ + is much higher in Native American Indian populations Polyarthritis ++ +++ (~5% to 7%) but lower in China and Japan (~0.2% to Oligoarthritis/monarthritis + + 0.3%).14–19 PsA prevalence estimates in the USA and Distal interphalangeal joint involvement +++ − Europe range from 0.1% to 0.4%, whereas in Japan, PsA 12 20 21 Metacarpophalangeal and wrist involvement +++ +++ prevalence is lower. This variability in prevalence Metatarsophalangeal joint involvement +++ +++ suggests that both environmental and genetic factors Axial spine involvement +++ − affect risk for disease. Cervical spine involvement + +++ Enthesitis +++ − Pathogenesis of RA and PsA Dactylitis +++ + A combination of genetic factors and environmental Synovitis ++ +++ triggers is thought to elicit autoimmune inflammatory Tenosynovitis ++ +++ responses in both RA and PsA. The pathogenesis of RA Nail dystrophy +++ − and PsA is not completely understood. In addition to Arthritis mutilans + − the known association with human leucocyte antigen Interstitial lung disease − ++ (HLA)-DR4 in RA, one theory is the development of Serological lung inflammation, typically prior to joint symptoms, with production of antibodies to citrullinated protein Rheumatoid factor − +++ antigens that mediate pathogenesis.22 23 Gut dysbiosis has Cyclic citrullinated peptide antibodies −* +++ been linked with the pathogenesis of PsA.24 While there C reactive protein ++ +++ is some overlap in the development of inflammation in Erythr ocyte sedimentation rate ++ +++ PsA and RA, some important differences are evident.25 Th17 cell upregulation ++ − For example, in both PsA and RA, HLA alleles have TNF-α-driven +++ +++ been shown to affect disease susceptibility and severity; IL-17A-driven +++ − however, the primary genotypes associated with each IL-12/23-driven +++ − disease are different. In PsA, HLA-B27 is associated with http://rmdopen.bmj.com/ IL-6-driven − +++ the development of enthesitis and symmetric sacroiliitis, Imaging and HLA-B08 is associated with joint fusion, asymmetric 26 Pencil-in-cup deformity ++ − sacroiliitis and dactylitis. In RA, HLA-DRB1 alleles Ankylosis ++ − are associated with disease susceptibility and severity in Subluxation ++ ++ patients who have positive findings for rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibodies.27 Bone proliferation +++ − In both PsA and RA, inflammatory responses are char- Number of erosions + +++ acterised by the increased production of proinflamma- on September 30, 2021 by guest. Protected copyright. Bone erosion + +++ tory molecules that act in synergy to propagate chronic Synovitis ++ +++ inflammation (figure 1).25 28 29 In PsA, activated T cells Tenosynovitis ++ +++ and macrophages induce production of inflamma- Distal interphalangeal joint involvement +++ − tory chemokines and cytokines, including interleukin Genetic (IL)-17, IL-23, IL-22, IL-1β, IL-6, interferon-γ and tumour 29 30 HLA-B27 alleles ++ − necrosis factor-α (TNF-α). Specifically, elevated levels HLA-DRB1 alleles − ++ of IL-17 + CD8+ T cells have been observed in the joints 31 The greater number of symbols (+, ++, +++) indicates a more common characteristic. of patients with PsA but not in those with RA. In addi- The dash (–) indicates the characteristic is not common. tion, recent studies have implicated increased expres- *Approximately 5% of patients with PsA have seropositive findings for anticyclic citrullinated peptide antibodies.71 sion of IL-9 and its receptor (IL-9R) in the promotion of HLA, human leucocyte antigen; IL, interleukin; PsA, psoriatic arthritis; RA, rheumatoid pathological T-cell growth and subclinical gut inflamma- arthritis; Th17, T helper 17; TNF, tumournecrosis factor. tion.32 33