Psoriatic Arthritis: Overcoming Challenges of Differential Diagnosis

Editor’s Note: This article was originally posted on Rheumatology Advisor on 07/01/2021.

Approximately 1.5 million Americans have psoriatic arthritis (PsA), the most common comorbidity of psoriasis. Of the 8 million Americans with psoriasis, 30% to 33% are reported to also have PsA.^1-3 The reported global prevalence of PsA varies widely, depending on the population studied, and rates as high as 41% have been reported in patients with psoriasis.^4,5 In general, the age distribution of PsA parallels that of psoriasis: the highest incidence is in adults 50 to 59 years of age (Figure 1), although even young children can be affected.^4,5

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Psoriatic arthritis is a complex inflammatory disease with multiple interrelated pathologies, including synovitis, enthesitis, tendinopathy, and dactylitis. Inflammation results in pain, tenderness, and swelling, which can be localized around a joint or more diffuse and along an entire digit (dactylitis). Disease progression has a high psychosocial burden; fusion of the vertebrae can result in significant functional limitation, work disability, and reduced quality of life.^6-8 Several comorbidities can emerge, including depression, ophthalmic disease, chronic obstructive pulmonary disease, nonalcoholic fatty liver disease, cardiovascular disease, diabetes, inflammatory bowel disease, and osteoarthritis.^9,10

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Factors for Delayed Diagnosis and Misdiagnosis of PsA

With the increasing availability of biologic therapies that target specific disease pathogenesis, early differentiation of inflammatory arthritis and prompt treatment can improve patient outcomes by reducing disease activity and preventing joint damage. The progressive nature of psoriasis to PsA suggests that early diagnosis and appropriate intervention can improve clinical outcomes. Delayed diagnosis and underdiagnosis of PsA in patients with psoriasis increase the risk of joint damage.¹⁰

Although prompt differential diagnosis is critical for optimal PsA management, diagnostic delay and misdiagnosis are prevalent. PsA diagnostic delays of more than 2 years have been reported, especially among younger patients, those who are obese, and those with enthesitis.^10,11 Undiagnosed PsA has been reported in 9% of patients with psoriasis.¹²
 
Several factors contribute to PsA diagnostic delays or failure to diagnose PsA. Patient-related factors include reluctance to seek immediate medical intervention on initial symptom presentation and barriers to diagnostic assessment. Lack of awareness of the progressive nature of psoriasis can also contribute to poor medical care-seeking behavior — particularly for nonspecific arthritis symptoms. Those symptoms can precede PsA and can develop soon after the onset of psoriasis, with progression, and accumulating risk over time.

Insight into the diagnostic experiences of patients with PsA was revealed in a real-world study that monitored self-reported PsA diagnosis among US patients through an online patient research registry and social media outreach. Among the 203 respondents, 172 (84.7%) were women.¹⁰ Common initial symptoms that triggered seeking medical attention were joint pain and stiffness. Most respondents sought care from a general practitioner (79.8%) or rheumatologist (66.5%); however, the time between seeking medical attention and receiving a diagnosis ranged from 6 months to 4 years for 68 (33.5%) respondents, and was more than 5 years for 66 (32.5%) respondents.¹⁰ The most common misdiagnoses prior to receiving a diagnosis of PsA were psychosomatic disorder (26.6%), osteoarthritis (21.7%), anxiety or depression (18.2%), and orthopedic problems (18.2%) (Figure 2).¹⁰ In general, fewer than 50% of patients who have psoriasis and concomitant PsA consult a rheumatologist,¹ suggesting a high risk of poor outcomes among patients with psoriasis who experience progression to PsA.
 
Clinician-related factors that contribute to diagnostic delay include a lack of clinical experience for the heterogeneous nature of PsA and the lack of autoimmune diagnostic markers, both of which make the differential diagnosis challenging. Indeed, differential diagnosis can be challenging because the symptoms of PsA, particularly at early disease stages, can mimic other diseases, including osteoarthritis, rheumatoid arthritis, gout, ankylosing spondylitis, reactive arthritis, and plantar fasciitis.¹³ Furthermore, although psoriasis precedes the onset of PsA in most cases, a small population of patients manifest PsA before skin signs and symptoms emerge; in some, skin signs and symptoms never develop.¹⁰ 

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Challenges to Early PsA Diagnosis

There are no definitive tests for PsA. Unlike rheumatoid arthritis or other spondyloarthropathies, such as ankylosing spondylitis for which biomarkers are available, there are no biomarkers for identifying early PsA. Elevation of acute-phase markers, such as C-reactive protein, have limited diagnostic value in early PsA because an elevated level occurs in approximately half of patients and, when psoriasis is absent, often results in misdiagnosis of undifferentiated arthritis.¹⁴ 

Consequently, the diagnosis of PsA depends on identification of specific features identified during routine clinical evaluation, laboratory testing, and radiographs based on the clinical expertise of the clinician.¹⁴ While such evaluations are typically sufficient to differentiate between established inflammatory (such as PsA) and noninflammatory arthritis (such as osteoarthritis), the evaluations cannot accurately differentiate early-stage disease. Although imaging techniques, in particular ultrasound, are increasingly used in the diagnosis of early inflammatory arthritis, currently studies are limited on clinical application.¹⁶ Consequently, the differential diagnosis of early PsA can be challenging for rheumatologists. For many patients, functional limitations are already manifesting at diagnosis, and patients are often highly distressed and anxious by the time they receive their diagnosis.¹⁷

Psoriasis Comorbidities and Serologic Markers for Early PsA Diagnosis

The progression to PsA in approximately 30% of patients with psoriasis^1-3 suggests that early identification of those who are at risk for progression to PsA will enable earlier initiation of treatment. The challenge, however, is to identify psoriasis patients who are at risk of progression based on clinical serologic study. A study demonstrated that antinuclear antibodies were seen more often in the serum of PsA patients than in the serum of individuals without PsA. However, that study involved patients with established, rather than early, PsA, and the specificity of the antibodies for PsA remains to be further evaluated.¹⁷ 

A potential serologic marker for the identification and differentiation of early PsA was explored in a study that retrospectively analyzed the relationships between comorbid disease and serologic markers in 629 patients with psoriasis, 102 of whom had PsA.¹⁸ The study found that comorbid hyperlipidemia, gout, and allergic rhinitis were significantly more prevalent in patients with PsA than in patients with psoriasis (P <.05 for hyperlipidemia and gout; P <.01 for allergic rhinitis).¹⁸ Plasma microRNA (hs-miR-210-3p) provided a serologic distinction between PsA and psoriasis. Statistically higher levels of hs-miR-210-3p were seen in patients with psoriasis than in patients with PsA (P =.04); furthermore, treatment of PsA with anti-tumor necrosis factor-α biologic agents increased hs-miR-210-3p to levels seen in patients with psoriasis.¹⁸
 
These results suggest that comorbid diseases in patients with psoriasis — gout, hyperlipidemia, and allergic rhinitis — might be an early indicator of risk of progression to PsA. Rheumatologists should therefore raise their index of suspicion for PsA to initiate early evaluation and diagnosis of PsA in patients with psoriasis and the identified comorbidities. If the plasma microRNA diagnostic test is made available to clinicians, hs-miR-210-3p could be a marker that differentiates psoriasis and PSA.¹⁸ Using this diagnostic approach, the only challenge would be patients with PsA who do not have an initial presentation of psoriasis.

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Summary

PsA is a common comorbidity in patients with psoriasis. The clinical presentation of PsA overlaps with several inflammatory and noninflammatory diseases. In the absence of diagnostic biomarkers, and without specific diagnostic tools, early differential diagnosis of PsA can be challenging. Misdiagnosis and delayed diagnosis are common and can lead to disease progression and poor patient outcomes. 

Recognition that specific comorbid diseases, including gout, hyperlipidemia, and allergic rhinitis, are prevalent in patients with psoriasis who experience progression to PsA might offer rheumatologists an early indicator of risk of PsA in their patients with psoriasis. Furthermore, plasma microRNA testing, if made available, may be an early diagnostic marker that can differentiate psoriasis and PsA.

References

1. Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80(4):1073-1113. doi:10.1016/j.jaad.2018.11.058
2. Psoriasis statistics. National Psoriasis Foundation. Accessed May 31, 2021. www.psoriasis.org/psoriasis-statistics
3. Psoriatic arthritis. Johns Hopkins Arthritis Center. Accessed May 31, 2021. www.hopkinsarthritis.org/arthritis-info/psoriatic-arthritis/
4. Rech J, Sticherling M, Stoessel D, Biermann MHC, Häberle BM, Reinhardt M. Psoriatic arthritis epidemiology, comorbid disease profiles and risk factors: results from a claims database analysis. Rheumatol Adv Pract. 2020;4(2):rkaa033. doi:10.1093/rap/rkaa033
5. Liu J-T, Yeh H-M, Liu S-Y, Chen K-T. Psoriatic arthritis: epidemiology, diagnosis, and treatment. World J Orthop. 2014;5(4):537-543. doi:10.5312/wjo.v5.i4.537
6. Gottlieb AB, Merola JF. Axial psoriatic arthritis: an update for dermatologists. J Am Acad Dermatol. 2021;84(1):92-101. doi:10.1016/j.jaad.2020.05.089
7. Spondylitis Association of America. In psoriatic arthritis, axial involvement is associated with more severe psoriasis. August 2018. Accessed May 31, 2021. https://spondylitis.org/research-new/in-psoriatic-arthritis-axial-involvement-is-associated-with-more-severe-psoriasis/
8. Truong B, Rich-Garg N, Ehst BD, et al. Demographics, clinical disease characteristics, and quality of life in a large cohort of psoriasis patients with and without psoriatic arthritis. Clin Cosmet Investig Dermatol. 2015;8:563-569. doi:10.2147/CCID.S90270
9. Puig L. Cardiometabolic comorbidities in psoriasis and psoriatic arthritis. Int J Mol Sci. 2017;19(1):58. doi:10.3390/ijms19010058
10. Ogdie A, Nowell WB, Applegate E, et al. Patient perspectives on the pathway to psoriatic arthritis diagnosis: results from a web-based survey of patients in the United States. BMC Rheumatol. 2020;4:2. doi:10.1186/s41927-019-0102-7
11. Karmacharya P, Wright K, Achenbach SJ, et al. Diagnostic delay in psoriatic arthritis: a population-based study. J Rheumatol. Published online February 15, 2021. doi:10.3899/jrheum.201199
12. Spelman L, Su JC, Fernandez-Peñas P, et al. Frequency of undiagnosed psoriatic arthritis among psoriasis patients in Australian dermatology practice. J Eur Acad Dermatol Venereol. 2015;29(11):2184-2191. doi:10.1111/jdv.13210
13. Coates LC, Helliwell PS. Psoriatic arthritis: state of the art review. Clin Med (Lond). 2017;17(1):65-70. doi:10.7861/clinmedicine.17-1-65
14. Dubash SR, De Marco G, Wakefield RJ, Tan AL, McGonagle D, Marzo-Ortega H. Ultrasound imaging in psoriatic arthritis: what have we learnt in the last five years? Front Med (Lausanne). 2020;7:487. doi:10.3389/fmed.2020.00487
15. Kaeley GS, Bakewell C, Deodhar A. The importance of ultrasound in identifying and differentiating patients with early inflammatory arthritis: a narrative review. Arthritis Res Ther. 2020;22(1):1. doi:10.1186/s13075-019-2050-4
16. Dures E, Bowen C, Brooke M, et al. Diagnosis and initial management in psoriatic arthritis: a qualitative study with patients. Rheumatol Adv Pract. 2019;3(2):rkz022. doi:10.1093/rap/rkz022
17. Silvy F, Bertin D, Bardin N, et al. Antinuclear antibodies in patients with psoriatic arthritis treated or not with biologics. PLoS One. 2015;10(7):e0134218. doi:10.1371/journal.pone.0134218
18. Su Y-J. Early diagnosis of psoriatic arthritis among psoriasis patients: clinical experience sharing. Clin Rheumatol. 2020;39(12):3677-3684. doi:10.1007/s10067-020-05132-1

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Reviewed May 2022