The Relationship Between Patient Acceptable Symptom State and Disease Scores in Psoriasis

Patient acceptable symptom state (PASS) is a patient-reported outcome that reects patient’s perspective well. The relationship between the PASS and disease scores in psoriasis has not been described. This study of 198 patients with psoriasis, assessed PASS using a binary question on patient’s feeling on their symptom. The disease scores including Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) affected by lesions and other patient characteristics were collected. Logistic regression was used to investigate the associations. 71.4% patients with mild psoriasis based on PASI and 76.3% based on BSA considered their symptom state acceptable. Female (adjusted OR=0.47; 95% CI: 0.42–0.92) and patients with exposed skin (head, neck, and hands) involved (adjusted OR=0.38; 95% CI: 0.19–0.76) were less likely to report acceptable symptom state. Receiver-Operating Characteristics curve showed that both PASI and BSA have limited capability in differentiating acceptable symptom state in psoriasis, which further indicated the unique value of PASS in the management of psoriasis.


Introduction
Psoriasis is a common chronic, immune-mediated in ammatory skin disease characterized by red and scaly plaques with signi cantly negative impact on quality of life of patients, affecting over 125 million people globally [1][2][3] . Psoriasis Area and Severity Index (PASI) based on severity and area of psoriatic lesions is a common tool to assess the severity of psoriasis 4 . The body surface area (BSA) affected by psoriasis is another common tool that evaluates area of psoriasis lesion only 5,6 . Both tools have corresponding thresholds in differentiating the severity of disease from the clinician's perspective.
Evaluation of the effectiveness of intervention in psoriasis is mostly determined by the change of PASI or BSA score from baseline. However, these changes does not necessarily represent an important improvement from the patient's perspective. Therefore, taking into consideration the patient perspective is needed to evaluate the effect of treatment in addition to the change of score. Some patient-reported measures are commonly used in psoriasis, such as the Dermatology Life Quality Index (DLQI) and EuroQol 5-Dimension (EQ-5D) [7][8][9] . However, these tools focus on speci c aspects of health-related quality of life (HRQoL), and these aspects do not necessarily re ect the overall impact of the disease and patient acceptability. Moreover, health utility-related measures like EQ-5D demonstrates strong ceiling effect and is not sensitive for mild disease condition.
The patient acceptable symptom state (PASS) is a patient-reported measure of well-being [10][11][12] , focusing on the feeling about their symptoms and representing a clinically relevant outcome. The relationship between PASS and disease activity scores or patient-reported outcomes had been evaluated in many diseases, such as ankylosing spondylitis (AS) 10,11 , rheumatoid arthritis (RA) 13 , and psoriatic arthritis (PsA) 14 , lichen planus 15 , scleroderma 16,17 , etc. However, the PASS and its association with objective measures of psoriasis has not been described yet.
The objectives of the current study were to describe the PASS across different severities of psoriasis, investigate factors associated with the PASS, and determine the cut-off points of PASI and BSA for PASS.

Study design and patients
This was a cross-sectional study in patients with psoriasis vulgaris. Patients aged 18 and above who were admitted to the dermatology department of Xiangya Hospital during September and November 2020 were consecutively enrolled. Participants who did not complete questions on the patient-reported outcomes were contacted by phone. Informed consent was obtained from all patients before the investigation. The study followed the Declaration of Helsinki and was approved by the institutional research ethics boards of Xiangya Hospital (approval number: 2018121106).

Data collection
The PASS was assessed by a binary answer to the following question: "Think about all the ways your psoriasis has affected you during the last 48 h. If you were to remain in the next few months as you were during the last 48 h, would this be acceptable to you? A "yes" response to the question was considered as the achievement of the PASS (PASS-Y), and "no" corresponding to PASS-N 14 .
PASI and BSA affected by psoriasis were evaluated by a trained research nurse. The severity (mild, moderate, and severe) of psoriasis was determined by the both score as less than 3, 3 to 10, and more than 10 respectively. Meanwhile, locations of psoriatic lesion were recorded, and if head, neck, or hands was involved, an "exposed lesion" was endorsed.
Other data collected included age, sex, psoriasis duration, education level, comorbidities (hypertension, hyperlipidemia, and diabetes), cigarette smoking, and alcohol drinking. Comorbidities were determined by medical records and self-reported history of disease. Cigarette smoking was de ned as having smoked at least 100 cigarettes in one's lifetime, and alcohol drinking was de ned as consumption of 30g of alcohol per week for at least one year 18 . Height and weight were measured by the research nurse in a standard way. Body mass index (BMI) was calculated as weight /squared height (kg/m 2 ). Overweight and obesity were de ned by the cut-offs of 24 kg/m 2 and 28 kg/m 2 , respectively.

Statistical analysis
Continuous variables with normal distribution were expressed as mean ± standard deviation (SD).
Categorical variables were calculated and summarized as counts (percentages). The t test statistic and Pearson chi-square tests or Fisher exact tests were used to analyze differences in continuous and categorical variables, respectively. The associations of PASS with the disease score and patients' clinical characteristics were analyzed by multivariate logistic regression with adjustments for variables with P value < 0.05 in the univariate analysis. Odds Ratio (OR) and 95% con dence interval were used to present the effect size of the associations. Receiver operating characteristics (ROC) curve was used to determine the PASI/BSA thresholds for PASS based on the maximal Youden' index for sensitivity and speci city 19 . A P value less than 0.05 was deemed statistically signi cant. The data were analyzed with SPSS 23 (IBM, SPSS Statistics 23).

Results
A total of 262 patients met the inclusion criteria, and 64 refused to participate or failed to contact successfully (34 males and 30 females). Table 1 summarizes the demographic characteristics and disease characteristics of the 198 participants who completed this study. The mean age was 41.9 ± 12.6 years, 55 (27.8%) were females, and the mean psoriasis duration was 10.2 ± 8.6 years. PASI, BSA, exposed skin involved, and educational level were signi cantly different between PASS status. No statistical differences were found for comorbidities, smoking, alcohol drinking, and body mass index between PASS status. In total, the proportion of patients who responded "yes" to the PASS was 56.6%, and 71.4% patients with mild psoriasis (de ned by PASI) considered their symptom state acceptable, compared with 48% and 14% in moderate and severe psoriasis, respectively. Similarly, 76.3% patients with mild psoriasis (de ned by BSA) considered their symptom state acceptable, compared with 28% and 23% in moderate and severe psoriasis, respectively.  a Adjusted for sex, PASI, BSA, exposed skin involved, educational level. P value for adjusted OR, estimated from multivariable logistic regression model. a Adjusted for sex, PASI, BSA, exposed skin involved, educational level. P value for adjusted OR, estimated from multivariable logistic regression model.
The threshold for PASI was 3.95 in differentiating psoriasis patients in an acceptable symptom state (PASS-Y) from those not (Fig. 1a). The area under the curve (AUC) was 0.671 (95% CI: 0.596-0.745) with a sensitivity of 0.67 and speci city of 0.60. The threshold for BSA was 2.85%, and the AUC was 0.662 (95% CI: 0.586-0.738) with a sensitivity of 0.79 and speci city of 0.54 (Fig. 1b).

Discussion
The current study brought important information on the relationship between the PASS and disease score in psoriasis. Most patients with mild or moderate psoriasis considered their symptoms acceptable. A dose-response relationship was identi ed in the association between the PASS status and severity of disease. In addition, female sex and exposed skin involved were risk factors for the acceptable status.
Both PASI and BSA showed limited capability in differentiating psoriasis patients in an acceptable symptom state from those not.
The clinician's and patient's perspectives could be different in terms of the severity of disease or therapeutic effect, and the discrepancy might not be conducive to the management of disease 14,20−22 . As a patient-reported measure, acceptable symptom state effectively re ects patient's perception on disease's impact on themselves. In our study, most patients with mild or moderate psoriasis considered their symptoms acceptable; this is consistent with the ndings of studies in RA and PsA 13,14 . Mild severity indicates less time needed for skin care and less visibility of lesions. In addition, we examined the possible factors associated with PASS status, and found that females were less likely to report acceptable symptom state, and similar result was reported in patients who underwent ligament reconstruction 23 . Exposed skin involved also considerably affected patient's acceptable symptom state in our study. In contrast to musculoskeletal diseases such as RA and AS, psoriasis is a skin disease with evidently negative impact on appearance, and is thus more likely to cause psychological distress [24][25][26] .
The degree of emphasis on smooth and beautiful skin in female is stronger than that in male. These characteristics might be the reasons why female and exposed skin involved are risk factors for PASS-N. Subgroup analysis also noted that the effect of exposed skin involved on PASS status was stronger as the severity increased. Patients with severe psoriasis may have larger areas of exposed skin lesion compared with moderate or mild psoriasis, as well as higher levels of systematic in ammation and metabolic disruption, resulting in effect modi cation statistically.
Through the ROC curve analyses, we determined the thresholds of PASI and BSA in differentiating PASS-Y from PASS-N was 3.95 and 2.85%, respectively. The cut-offs were within the moderate severity for PASI and mild for BSA. Previous studies reported the 75th percentile approach was also used to determine the thresholds of disease scores for PASS 11,23 , but the ROC curve analyses may generate a more precise estimate owing to the thresholds de ned by ROC curve analyses are based on the best trade-off for sensitivity and speci city 14 . Our results indicated that the PASI and BSA had limited capability in differentiating acceptable symptom state in psoriasis, and the sensitivity and speci city for the both scores were lower compared with previous studies in other diseases 13,14 . This indicates that cutaneous symptoms and dis gurement may contribute to acceptability which is not captured by the objective measure of psoriasis severity. Therefore, acceptability of patient symptoms should be taken into consideration in treatment decision-making processes in addition to the changes of PASI or BSA, patients who reported PASS-N should receive additional interventions to improve health-related outcome.
Other common patient-reported measures that are used in psoriasis include instruments for health-related quality of life, among which DLQI is the most frequently used 7,8 . However, the tool has weaknesses, such as disordered response thresholds, item bias, and psychometric properties 27 . The bio-psycho-social medical model is proposed as an integrated way to understand diseases 28 , and the acceptability of patients is an outcome of multifaceted factors. Further studies on the association of PASS with other patient-reported measures in psoriasis are warranted.
This study has some limitations. First, selection bias might be introduced in a single-center hospitalbased study that captures patients with severer disease status and stronger willingness to seek help. Second, patients may have different understanding on the single question that was used to assess the outcome. Third, more intermediate and modi able factors for PASS should be investigated, such as psychological resilience, perceived stress, symptoms of depression and anxiety, and social support.
In conclusion, this study accentuated the importance of patient-reported measures, which should be taken into consideration in treatment decision-making processes. To our knowledge, this is the rst study that described PASS and investigated the association of disease severity and patient characteristics with PASS in psoriasis. We found that patients with mild psoriasis had a high proportion of acceptable status, while female sex and exposed skin involved were factors for less acceptability. Poor discrimination capability of PASI and BSA further indicates the unique value of PASS in the management of psoriasis.

Declarations
Data Availability: The datasets generated during and/or analyzed during the current study are available by request.