Diagnostic Delay of Psoriatic Arthritis of More Than Six months Contributes to Poor Patient-Reported Outcome Measures in Depression, Social Ability, and Disease Impact: A Cross-sectional Study

J Clin Aesthet Dermatol. 2024;17(10):19–22.

by Melissa P. Zundell, BS; Lourdes Perez-Chada, MD, MMSc; Neel Tapryal, MD; George C. Gondo, MA; M. Elaine Husni, MD, MPH; Gretchen D. Ball, BS; Michael J. Woodbury, BS; Joseph F. Merola, MD, MMSc; and Alice B. Gottlieb, MD, PhD

Mses. Zundell and Ball and Dr. Gottlieb are with the Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York, New York. Dr. Perez-Chada, Mr. Woodbury, and Dr. Merola are with the Department of Dermatology at Brigham and Women’s Hospital at Harvard Medical School in Boston, Massachusetts. Drs. Tapryal and Husni are with the Department of Rheumatologic and Immunologic Disease at the Cleveland Clinic in Cleveland, Ohio. Mr. Gondo is with the National Psoriasis Foundation in Alexandria, Virginia.

FUNDING: Funding for this study was provided by the National Psoriasis Foundation (NPF) and the International Dermatology Outcome Measure (IDEOM).

DISCLOSURES: Dr. Perez-Chada has received research funding from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Mr. Condo is is an employee of the National Psoriasis Foundation. Dr. Merola was a consultant and/or investigator for Amgen, BMS, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Sanofi, Regeneron, Sun Pharma, Biogen, Pfizer, and Leo Pharma. Dr. Gottlieb has received honoraria as an advisory board member and consultant for Amgen, AnaptypsBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dice Therapeutics, Eli Lilly, Janssen, Novartis, Sanofi, UCB, and Xbiotech and has received research/educational grants from AnaptypsBio, Moonlake Immunotherapeutics AG, Novartis, Bristol-Myers Squibb, and UCB Pharma. 

ABSTRACT: Objective. We sought to correlate the time lag between psoriatic arthritis (PsA) symptom onset and diagnosis to the likelihood and severity of depression, social impairment, and disease impact on quality of life.

Methods. This cross-sectional study conducted by the National Psoriasis Foundation (NPF) surveyed individuals with PsA using patient-reported outcome measures.

Results. The analysis cohort comprised 2,196 patients with PsA. Likelihood of depression progressively increased when time between PsA symptom onset and diagnosis was beyond six months (28.6% <6 months; 29.6% 7–12 months; 38.1% 13–24 months; 35.4% >2 years; p<0.01). Individuals with more than six months delay reported increasingly higher rates of experiencing moderate limitation in social participation (22.9% <6 months; 29.2% 7–12 months; 34.0% 13–24 months; 35.3% >2 years; p<0.001). Unacceptable PsA symptom rates (PsAID score >4) increased with time between PsA symptom onset and diagnosis (74.7% <6 months; 76.4% 7–12 months; 80.8% 13–24 months; 81.6% >2 years; p<0.05). These relationships persisted in body mass index (BMI) and age adjusted models.

Limitations. The study only includes participants who were active members of the NPF, and all data was self-reported.

Conclusion. Our results demonstrate that delays between PsA symptom onset and diagnosis that are greater than six months lead to increased likelihoods of depression, social disengagement, and impaired quality of life, and that longer delays lead to increasingly worse outcomes in these domains.

Keywords: Psoriatic arthritis, diagnostic delay, depression, social participation, quality of life, patient-reported outcome measures, disease impact

Introduction

Psoriatic arthritis (PsA) is a chronic, progressive, inflammatory arthritis, and it is estimated to affect up to one-third of patients with psoriasis.¹ Yet, many patients suffer significant delays of greater than two years from the time of their PsA symptom onset until their PsA diagnosis is given.² There are a number of proposed factors that contribute to this delay, such as the heterogenous presentation of PsA, lack of gold standard diagnostic tests, and lack of PsA awareness.² However, diagnostic delay by as little as six months is associated with a lower treatment response, whereas early intervention is associated with better clinical and radiographic outcomes.^1,3 Thus, diagnostic delay may result in needless patient suffering.

PsA frequently leads to significant physical limitations, functional impairment, and diminished quality of life. While the physical disability patients suffer can be profound, the emotional burden of the disease may be equally debilitating. Depression is a well-known comorbidity of PsA with an estimated 20 percent of patients with PsA experiencing at least mild depression.⁴ Additionally, individuals living with PsA often report experiencing impaired ability to participate in social activities.⁵ A global study of 1,286 patients under care for PsA found that 45 percent of patients had ceased participating in social activities due to their condition.⁶ 

Though it is understood that diagnostic delay leads to worse patient outcomes, there is limited knowledge on how the delay relates to these emotional burdens.^1,3 Specifically, there is a paucity of research examining real-world data on how PsA diagnostic delay particularly relates to incidence of depression, limitations in social engagement, and overall disease impact on quality of life. Moreover, it remains necessary to explore whether there is a relation between the length of the delay to the severity of these negative outcomes.

The objective of this study was to correlate the time period between PsA symptom onset and diagnosis to depression, social impairment, and impact of disease on quality of life using patient-reported outcome measures in a real-world population of patients with PsA in the United States (US). Real-world research on these effects of PsA diagnostic delay may inform treatment optimization and decrease disease burden for patients.

Methods

The National Psoriasis Foundation (NPF) performed an observational, cross-sectional survey of a random sample of individuals with PsA in the United States from 2019 to 2021. Patients were active members of the NPF within the past two years, age >18 years, carried a self-reported physician-given diagnosis of PsA, were able to read and understand English, and had an active email address in the NPF’s constituent database. A total of 4,019 patients were invited to participate. Incomplete questionnaire responses were included in the analyses for which there were responses provided. 

Time between PsA symptom onset and PsA diagnosis was measured by respondent self-report. Depression was assessed using the two-question Patient Health Questionnaire (PHQ–2) and scores were calculated in a range of 0 to 6 with scores of 3 or greater used to indicate “depression is likely” and scores less than 3 used to indicate “depression is not likely.”⁷ Social participation was assessed using the Patient Reported Outcome Measurement and Information System (PROMIS) Ability to Participate in Social Roles and Activities (sf-4a). Survey participant responses were interpreted in accordance with the scoring instructions established by the PROMIS workgroup, with scores less than 50 indicating increasing limitation in ability to participate in social roles and activities.⁸ Impact of PsA on quality of life and PsA symptom severity were assessed with the Psoriatic Arthritis Impact of Disease (PsAID-9). Acceptable and unacceptable levels of PsA were defined using established cutoff points (acceptable <4; unacceptable >4).^9,10

Chi-square tests of independence were used to assess whether the severity of patient outcomes in the domains of depression, limitations in social participation ability, and symptom state was associated with the length of time between PsA symptom onset and diagnosis. Analysis of covariance (ANCOVA) assessed differences in these outcomes based on the length of diagnostic delay between PsA symptom onset and diagnosis while controlling for age and body mass index. 

Chi-square tests were conducted with SPSS Ver 26 and ANCOVA were conducted in STATA SE Ver 9.

Results

A total of 2,196 patients (mean age 55.2 years; 89.2% White) with PsA completed the survey, yielding a response rate of 54.6 percent. The demographics of our respondents are summarized in Table 1. Overall, fewer participants indicated a likelihood of being depressed (693; 31.8%) than being not depressed (1,485; 68.2%). Patients reported ability to participate in social roles and activities as moderately limited (622; 28.6%), mildly limited (688; 31.6%), and normal (865; 39.8%). Among all participants, 1,701 (77.5%) reported unacceptable level of disease activity (PSAID>4) and 495 (22.5%) reported acceptable level of disease activity (PSAID<4)(Table 2).

Chi-square tests were conducted to assess whether the time between PsA symptom onset and diagnosis was associated with incidence of depression, social participation limitation, and impact on quality of life (Table 3). The likelihood of depression progressively increased when time between PsA symptom onset and diagnosis was beyond six months (28.6% at <6 months; 29.6% at 7–12 months; 38.1% at 13–24 months; 35.4% at >2 years; p<0.01). Individuals with more than six months between PsA symptoms onset and diagnosis reported higher rates of experiencing moderate limitation in their ability to participate in social roles and activities (22.9% at <6 months; 29.2% at 7–12 months; 34.0% at 13–24 months; 35.3% at >2 years; p<0.001). Unacceptable PsA symptom rates (PsAID score >4) increased with time between PsA symptom onset and diagnosis (74.7% at <6 months; 76.4% at 7–12 months; 80.8% at 13–24 months; 81.6% at >2 years; p<0.05).

When controlling for age and body mass index, ANCOVA results suggest that individuals with less than six months between PsA symptom onset and diagnosis report better outcomes when compared to those with more than six months of delay (Table 4). Patients with more than six months of diagnostic delay report higher PhQ-2 scores (1.95 [1.82–2.71] at <6 months; 1.88 [1.70–2.05] at 7–12 months; 2.22 [2.01–2.43] at 13–24 months; 2.19 [2.02–2.35] at >2 years; p<0.05). Patients with greater than six months of diagnostic delay also report lower PROMIS ability to participate in social roles and activities scores (45.94 [45.40–46.48] at <6 months; 45.36 [44.59–46.13] at 7–12 months; 44.16 [43.25–45.07] at 13–24 months; 43.36 [42.65–44.07] at >2 years; p<0.001) as well as higher PSAID-9 scores (4.76 [4.55–4.97] at <6 months; 4.90 [4.61–5.20] at 7–12 months; 5.12 [4.77–5.48] at 13–24 months; 5.47 [5.20–5.74]; p<0.001). A score of 3 or more on the PhQ-2 is indicative of depression. Individuals with a score of 2 have a 48.3 percent probability of experiencing depression.⁶ For the PROMIS ability to participate in social roles and activities, a score of 50 indicates normal ability, with lower scores indicating increased limitations.⁷ Prior studies have established PsAID-9 cutoff points such that a PsAID score >4 indicates an unacceptable symptom state.^8,9 Thus, these age and Body Mass Index (BMI) adjusted results indicate that PsA diagnostic delay of more than six months is associated with increased likelihood of depression, limitations in social engagement, and uncontrolled symptom state. Our results trend also suggest that increased delay time correlates to increased severity of these negative outcomes.

Discussion

Our study results demonstrate that PsA diagnostic delay is associated with higher rates of depression, increased limitations in social participation, and greater disease impact on quality of life in a real-world population of patients. Chi-square tests reveal that the likelihood of depression significantly increases beyond six months of diagnostic delay, and individuals with greater than six months of delay report significantly higher rates of moderate limitation in social roles and activities. Moreover, unacceptable levels of disease activity are significantly more prevalent in patients with greater than six months delay. These findings persist in ANCOVA models adjusted for age and BMI, both of which are independently linked to both PsA development as well as many of its comorbidities.^11,12

These findings are consistent with and build upon previous studies demonstrating that six-month delay from symptom onset to first-time rheumatology assessment can lead to worsened peripheral joint erosions and poorer long-term physical function.³ When considered together, it is evident that even a six-month delay can have detrimental effects on a patient’s physical and mental well-being.

Additionally, our findings indicate a discernible trend wherein prolonged diagnostic delay corresponds to increased severity of adverse consequences. Survey respondents with longer delays reported higher likelihoods of depression, limitations in social participation, and profound disease impact. Hence, our findings reveal that the unfavorable outcomes in these domains associated with diagnostic delay persist even beyond the initial six-month period, indicating that longer delays are linked to increasingly negative consequences.

Nevertheless, patients continue to experience these diagnostic delays. A retrospective, population-based study of 164 incident PsA cases from 2000 to 2017 in the US found an average diagnostic delay of 2.5 years.² Younger age of PsA symptom onset, higher BMI, and enthesitis were associated with a diagnostic delay of more than two years, whereas sebopsoriasis made diagnostic delay less likely.² Another cross-sectional, US-based study of 203 patients with self-reported PsA found that approximately one third of the cohort was diagnosed within a timeframe of six months to four years, while another third experienced even greater delays of greater than five years.¹³ Other international studies report variable time frames of diagnostic lag, from 3.4 to 11 years.^14,15

Recently, there has appropriately been increased attention paid toward understanding PsA risk factors and the psoriasis-to-PsA transition. An understanding of this process may elucidate the subset of patients at risk for the development of PsA, enabling appropriate screening strategies that may effectively decrease diagnostic delay.^13,16 Given the variability in disease progression among patients with PsA, identifying high-risk subgroups can help stratify those who would derive maximum benefit from early and aggressive therapy.¹⁷

As psoriatic skin disease precedes PsA development in more than 80 percent of patients, dermatologists may be best positioned to aid in the screening and timely detection of PsA in patients.¹⁸ Dermatologists may consider using validated screening tools, such as the Psoriasis Epidemiology Screening Tool (PEST), to screen patients with psoriasis for PsA at each visit.¹⁹ Maintaining a low threshold to evaluate and investigate musculoskeletal symptoms in psoriatic patients can help to decrease diagnostic delay.¹⁸

Within the limitations to the study, it is important to acknowledge the possible
bi-directional relationship and potential inverse temporal correlation between depression and diagnostic delay of PsA, whereby depression may have contributed to the delay in PsA diagnosis, possibly through factors such as patients’ delayed self-referral, self-care, and follow-up.

Conclusion

Our results reflect the negative ramifications that PsA diagnostic delay has on patient outcomes. Specifically, delays of even as little as six months can lead to increased likelihoods of depression, social disengagement, and impaired quality of life. Moreover, our study results indicate that longer delays lead to increasingly worse outcomes in these domains. Increased awareness of PsA and the emotional burden of diagnostic delay among healthcare providers remains necessary to optimize treatment and improve patient outcomes. Providers should remain alert and screen their patients routinely to prevent undetected disease.

References:

1. Scher JU, Ogdie A, Merola JF, et al. Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition. Nat Rev Rheumatol. 2019;15(3):153–166. 
2. Karmacharya P, Wright K, Achenbach SJ, et al. Diagnostic delay in psoriatic arthritis: a population-based study. J Rheumatol. 2021;48(9):1410–1416. 
3. Haroon M, Gallagher P, FitzGerald O. Diagnostic delay of more than 6 months contributes to poor radiographic and functional outcome in psoriatic arthritis. Ann Rheum Dis. 2015;74(6):1045–1050.
4. Zhao SS, Miller N, Harrison N, et al. Systematic review of mental health comorbidities in psoriatic arthritis. Clin Rheumatol. 2020;39:217–225.
5. Gudu T, Kiltz U, de Wit M, et al. Mapping the effect of psoriatic arthritis using the international classification of functioning, disability and health. J Rheumatol. 2017;44:193–200.
6. Coates LC, Orbai AM, Azevedo VF, et al. Results of a global, patient-based survey assessing the impact of psoriatic arthritis discussed in the context of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire. Health Qual Life Outcomes. 2020;18(1):173.
7. Kroenke K, Spitzer RL, Williams JB. The Patient Health Questionnaire-2: validity of a two-item depression screener. Med Care. 2003;41(11):1284–1292.
8. Cella D, Riley W, Stone A, et al. The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008. J Clin Epidemiol. 2010;63(11):1179–1194.
9. Lubrano E, Scriffignano S, Azuaga AB, et al. Assessment of the Patient Acceptable Symptom State (PASS) in psoriatic arthritis: association with disease activity and quality of life indices. RMD Open. 2020;6(1):e001170.
10. Gossec L, de Wit M, Kiltz U, et al. A patient-derived and patient-reported outcome measure for assessing psoriatic arthritis: elaboration and preliminary validation of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, a 13-country EULAR initiative. Ann Rheum Dis. 2014;73(6):1012–1019.
11. Kumthekar A, Ogdie A. Obesity and psoriatic arthritis: a narrative review. Rheumatol Ther. 2020;7(3):447–456. 
12. Fragoulis GE, Nikiphorou E, McInnes IB, et al. Does age matter in psoriatic arthritis? a narrative review. J Rheumatol. 2022;49(10):1085–1091. 
13. 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.
14. Sørensen J, Hetland ML; all departments of rheumatology in Denmark. Diagnostic delay in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: results from the Danish nationwide DANBIO registry. Ann Rheum Dis. 2015;74(3):e12.
15. Gladman DD, Thavaneswaran A, Chandran V, et al. Do patients with psoriatic arthritis who present early fare better than those presenting later in the disease? [published correction appears in Ann Rheum Dis. 2012 Sep;71(9):1592]. Ann Rheum Dis. 2011;70(12):2152–2154.
16. Ogdie A, Rozycki M, Arndt T, et al. Longitudinal analysis of the patient pathways to diagnosis of psoriatic arthritis. Arthritis Res Ther. 2021;23(1):252.
17. Karmacharya P, Wright K, Achenbach SJ, et al. Time to transition from psoriasis to psoriatic arthritis: a population-based study. Semin Arthritis Rheum. 2022;52:151949.
18. Gottlieb AB, Mease PJ, Mark Jackson J, et al. Clinical characteristics of psoriatic arthritis and psoriasis in dermatologists’ offices. J Dermatolog Treat. 2006;17(5):279–287. 
19. Perez-Chada LM, Kohn A, Gottlieb AB, et al. Report of the Skin Research Working Groups From the GRAPPA 2020 Annual Meeting. J Rheumatol Suppl. 2021;97:10–16.