Validation of Turkish Psoriatic Arthritis Screening Tool (TurPAS) for Psoriatic Arthritis: A Cross-sectional Comparative Study

doi:10.21203/rs.3.rs-3578012/v1

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Validation of Turkish Psoriatic Arthritis Screening Tool (TurPAS) for Psoriatic Arthritis: A Cross-sectional Comparative Study

https://doi.org/10.21203/rs.3.rs-3578012/v1

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Background: Psoriasis (PsO) is a chronic immune-mediated disease that affects skin, nails, tendons, and joints. Several screening tools such as PEST, PASE, EARP, STRIPP, SIPAS, TOPAS have been developed and validated for identifying patients with suspected PsA in dermatology clinics.

Objective: Herein, we aim to validate and evaluate the performance of TurPAS in patients with PsO compared to the EARP questionnaire.

Methods: This cross-sectional study was carried out in collaboration between dermatology and rheumatology clinics at Aksaray University Hospital, a tertiary referral center. All patients were examined for dermatologic aspects in the dermatology outpatient clinic and TurPAS and EARP questionnaires were performed by the same dermatologist. The patients who met CASPAR criteria were classified as PsA in addition to appropriate clinical findings.

Results: In our study, 119 patients (n=72; 60.5% female) with PsO were included. Mean±Standard deviation (SD) of the patients were 44.9±14.3 (range; 18-83) years and median (IQR) PsO duration were 10 (14) years. Median (IQR) TurPAS and EARP scores were 2 (3) and 3 (5), respectively. Overall, 39 patients (32.8%) met the CASPAR criteria and were classified as PsA. The best diagnostic accuracy was observed in ≥3 positive items with 82% and 70% sensitivity and specificity (PPV: 57.1%, NPV: 89%, Likelihood ratio [LR]: 2.7, diagnostic accuracy: 74%) for TurPAS and ≥4 items with 74.4% and 86.3% (PPV: 72.5%, NPV: 87.3%, LR: 5.4, diagnostic accuracy: 82.4%) for EARP.

Conclusion: In our study approximately one-third of patients with PsO were diagnosed as PsA. TurPAS had acceptable diagnostic performance compared to the EARP questionnaire.

TurPAS

Psoriatic arthritis

Psoriasis

Psoriatic arthritis Screening tool

EARP

Psoriasis (PsO) is a chronic immune-mediated disease that affects skin, nails, tendons, and joints. Approximately 1–2% of the population suffers from PsO (1). Psoriatic arthritis (PsA) is a heterogenous disease associated with PsO. Aproximately 5–40% of patients with PsO develop PsA during the disease course (2). Entesitis, dactylitis, peripheral arthritis as well as axial skelethal involvement are the main features of PsA. Joint involvement of PsA has many subtypes as mono-oligoarthritis, polyarthritis, distal interphalangeal joint (DIP) arthritis, arthritis mutilans and axial disease. Psoriatic patients are also at higher risk for methabolic syndrome and its components such as obesity, diabetes mellitus, hypertension, hyperlipidemia and coronary heart disease (3). Due to the its complex and heteregenous nature, recently ‘Psoriatic disease’ has been using as an umbrella term for all disease related findings reflecting rheumatological, dermatological and metabolic aspects (4). Early treatment in PsA is important to prevent severe joint deformity, work-force loss and other potential complications (5). Therefore, screening and identifying the patients with PsA at early phase of disease are crucial to imrove outcome in patients with PsO in dermatology clinics.

Referring the patients from dermatology to rheumatology clinics is problematic since which PsO patients should be consulted is unclear. Several screening tools such as PEST, PASE, EARP, STRIPP, SIPAS, TOPAS, GEPARD, CONTEST have been developed and validated for identifying patients with suspected PsA in dermatology clinics (6) (7) (8). However, these screening tools are far from being ideal, and there is no widely used screening tool in patients with PsO, so far. TurPAS is a novel screening tool which was recently developed by Turkish rheumatologists and dermatologists (9). TurPAS questionnaire is consisted of six items which reflects many aspects of PsA such as synovitis, enthesitis, dactylitis and axial involvement as well as prior history of drug use and inflammatory disorder diagnosis. Herein, we aim to validate and evaluate the performance of TurPAS in patients with psoriasis compared to EARP questionnaire.

Study group

This cross-sectional study was carried out collaboration between dermatology and rheumatology clinics at Aksaray University Hospital, a tertiary referral center. The patients had diagnosis of PsO who followed-up in dermatology outpatient clinic were included into the study. All patients were examined for dermatological aspects in the dermatology outpatient clinic and TurPAS and EARP questionnaires were performed by the same experienced dermatologist (ŞBK). Afterwards, the patients referred to the rheumatology clinic for rheumatological evaluation regardless of questioannaire results. Therefore, the patients who had no musculoskletal complaint were also included in the study. Prior treatment history of the patients with PsO including conventional synthetic disease modifying antirheumatic drugs (cs-DMARD) and biological disease modifying antirheumatic drugs (b-DMARD) were also noted. The TurPAS questionnaire was shown in Table 1. Rheumatological evaluation was performed by a single experienced rheumatologist (MB) who blinded to relevant the questionnaire results. The patients under 18 years, who had cognitive dysfunction, and/or unable to read were excluded from the study.

Table 1

The new screening tool: TurPAS
Items	Domain	Turkish version	English version
Q1	Joint	El/ayak parmaklarinizda ya da herhangi bir ekleminizde hiç şişlik veya ağri oldu mu?	Have you ever had swelling or pain in your fingers/toes or any of your joints?
Q2	Dactylitis	Resimde gösterildiği gibi el veya ayak parmağinizda sosis şeklinde şişlik oldu mu?	Have you had a sausage-shaped swelling on your fingers or toes as shown in the picture?
Q3	Enthesitis	Topuk ağriniz olur mu?	Do you have heel pain?
Q4	Axial involvement and morning stiffness	Belinizde, sirtinizda veya boynunuzda istirahatle artan, özellikle sabaha karşi kötüleşen veya sabahlari hareketinizi kisitlayan ağriniz olur mu?	Do you have pain in your lower back, back, or neck that increases with rest, worsens especially in the morning, or restricts your movement in the morning?
Q5	Drug use	Eklem şikayetleriniz için zaman zaman ilaç kullanir misiniz?	Do you take medication for your joint complaints from time to time?
Q6	History of rheumatic disease	Size daha önce iltihapli romatizma tanisi konuldu mu?	Have you ever been diagnosed with a rheumatic disease before?

Rheumatological evaluation

Baseline laboratory evaluation such as hemogram, liver enzymes, kidney functions as well as acute phase reactants (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), autoantibodies (rheumatoid factor [RF], anti-cyclic citrullinated peptides ([anti-CCP)] were performed in all participants. Additionally, all patients underwent protocol plain radiography screening for peripheral joints (hand, foot, knee and sacroiliac joints) at baseline and for other symptomatic joints if needed. Magnetic resonansresonance (MR) imaging was also performed if a diagnostic challange was persisted despite the baseline evaluation of peripheral involvement. Axial skeletal MR screening including cervical, thoracic and lumbar spine and sacroiliac joint was performed in patients who had inflammatory neck and/or back pain whose x-ray results were unremarkable. Axial involvement was defined as ASAS axial spondyloarthritis criteria (10). The patients who met CASPAR criteria were classified as PsA in addition to appropriate clinical findings (11).

Statistical analysis:

In our study, 21.0 version (IBM, Armonk, NY, USA) of the SPSS (Statistical Package for the Social Sciences) program was used for statistical analysis of data. Descriptive statistics, discrete and continuous numerical variables were expressed as mean, ± standard deviation or median and interquartile range (IQR). Categorical variables were expressed as number of cases and (%). Cross table statistics were used to compare categorical variables (Chi-Square, Fisher exact test). Normally distributed parametric data were compared with Student's t-test and Paired t-test; non-parametric data that did not meet normal distribution were compared with Mann Whitney U and Kruskal Wallis tests. Multiple intergroup comparisons were made by Post Hoc Tukey analysis. Multivariate analysis was performed by logistic regression. Receiver operating characteristic (ROC) analysis was performed for calculation of sensitivity and spesificity.specificity. P < 0.05 value was considered statistically significant.

In our study, 119 patients (n = 72; 60.5% female) with PsO were included into the study. Mean ± Standard deviation (SD) of the patients were 44.9 ± 14.3 (range; 18–83) years and median (IQR) PsO duration were 10 (14) years. Most of the patients had plaque type PsO (86.6%) and median (IQR) PASI score was 3 (5). Median (IQR) ESR: 12.5 (14) mm/hour and CRP: 11.5 (20) mg/L. Median (IQR) TurPAS and EARP scores were 2 (3) and 3 (5), respectively. While 3 patients (2.6%) had RF positivity, anti-CCP was negative in all patients. Overall, 39 patients (32.8%) met the CASPAR criteria and were diagnosed as PsA. Mono-oligoarthritis was in 19 patients (48.8%), polyarthritis in 10 (25.6%), isolated DIP arthritis in 5 (12.8%), and pure axial involvement in 5 patients (12.8%) in patients with PsA. While overall axial involvement in 9 patients (26.5%), no patients had arthritis mutilans. Enthesitis was observed in 25 patients (64%) and dactylitis in 10 patients (25.6%) in patients with PsA. Mean ± SD (range) tender and swollen joint counts were 1.05 ± 1.5 (0–6) and 1 ± 1.5 (0–6), respectively (Table 2). After the rheumatological evaluation, 39 patients (32.8%) had non-PsA diagnosis as follows; osteoarthritis (OA) in 13 patients (33.3%), lomber disk hernia in 10 (25.6%), non-specific musculokselethal pain in 7 (18%), fibromyalgia (FM) in 3 (7.7%), cervical disk hernia in 2 (5.1%), gout and spina bifida in 1 patient (2.6%), respectively (Supplementary table 1). Phototherapy was used in 7 patients (5.9%), acitretin in 25 (21%), cyclosporin in 6 (5%), methotrexate in 37 (31.1%), b-DMARD treatment in 19 (16%) in patients with PsO (Supplementary table 2).

Table 2

Clinical and laboratory features of study participants
Variables	Results
Age (years), mean ± SD (range)	44.9 ± 14.3 (18–83)
Gender, female, n (%)	72 (60.5)
Duration of PsO (years), median (IQR)	10 (14)
Family history of PsO, n (%)	39 (32.8)
Family history of PsA, n (%)	5 (4.2)
Psoriasis subtypes
Plaque	103 (86.6)
Palmoplantar	6 (5)
Guttat	6 (5)
Invers	2 (1.7)
Nail (only)	2 (1.7)
Special areas of PsO, n (%)
Scalp	76 (64)
Intergluteal	13 (11)
Axillary	12 (10)
Nail (overall)	49 (41.2)
PASI score, median (IQR)	3 (5)
ESR, median (IQR)	12.5 (14)
CRP, median (IQR)	11.5 (20)
RF positivity, n (%)	3/114 (2.6)
Anti-CCP positivity (n = 108)	0
Comorbidities, n (%)
Diabetes mellitus	20 (16.8)
Hypertension	18 (15)
Coronary heart disease	7 (5.9)
Hyperlipidemia	8 (6.7)
Tender joint count, mean ± SD (range)	1.05 ± 1.5 (0–6)
Swollen joint count, mean ± SD (range)	1 ± 1.5 (0–6)
TurPAS score, median (IQR)	2 (3)
EARP score, median (IQR)	3 (5)
Diagnosis of PsA, n (%)	39 (32.8)
PsA subtypes, n (%)
Mono-oligoarthritis	19 (48.8)
Polyarthritis	10 (25.6)
DIP arthritis	5 (12.8)
Pure axial involvement	5 (12.8)
Total axial involvement, n (%)	9 (26.5)
Enthesitis, n (%)	25 (64)
Dactilytis, n (%)	10 (25.6)
SD: Standard deviation, IQR: Interquartile range, PsO: Psoriasis, PsA: Psoriatic arthritis, PASI: Psoriasis area severity index, ESR: Erythrocyte sedimentation rate, CRP: C-reactive protein, RF: Rheumatoid arthritis, anti-CCP: Anti-Cyclic citrullinated peptides, TurPAS: Turkish Psoriatic Arthritis Screening Questionnaire, EARP: Early Psoriatic Arthritis Screening Questionnaire, DIP: Distal interphalangeal phalanx

In univariate analysis, family history of PsA (4 [10.5] vs 1 [1.3]; p = 0.037; Odds ratio [OR]:5.5), CRP levels (16.5 [17] vs 3.5 [8] mg/L; p = 0.003), median (IQR) TurPAS and EARP scores (4 [2] vs 2 [3]; p < 0.001) and (6 [4] vs 2 [4]; p < 0.001) were higher in patients with PsA than those without (Supplementary Table 3). Median (IQR) TurPAS (4 [2] vs 2 [2]) and EARP (6 [4] vs 2 [3]) scores were also higher in patients with PsA compared to patients had non-PsA diagnosis (p < 0.001 and p < 0.001, respectively). In mutivariate analysis, only the TurPAS score (p = 0.003, OR: 3.8; 95% Confidence interval [CI]: 1.56–9.4) was associated with diagnosis of PsA (Supplementary table 4).

ROC analysis revealed Area under curve (AUC): 0.834, p < 0.001, 95% CI: 0.751–0.917) and AUC: 0.862, p < 0.001, 95% CI: 0.784–0.940) for TurPAS and EARP, respectively (figure). Sensitivity and specificity of TurPAS and EARP were 94.9% and 25% (positive predictive value [PPV]:38.1%, negative predictive value [NPV]: 90.9%) and 94.9% and 25% (PPV:38.1%, NPV: 90.9%), respectively for ≥ 1 positive items. ≥3 positive items provide 82% and %70% sensitivity and specificity, respectively (PPV: 57.1%, NPV: 89%, Likelihood ratio [LR]: 2.7, diagnostic accuracy: 74%) for TurPAS. ≥4 positive items also provide 74.4% and 86.3% sensitivity and specificity, respectively (PPV: 72.5%, NPV: 87.3%, LR: 5.4, diagnostic accuracy: 82.4%) for EARP. Diagnostic performances of TurPAS and EARP questionnaires according to item count were described in Table 3. Sensitivity and specificity of item 1 (question; Q1) were 94.9% and 36.3%, 46.2% and 93.8% for item 2, (Q2), 35.9% and 80% for item 3, (Q3), 66.7% and 57.5% for item 4, (Q4), 84.6% and 56.3% for item 5, (Q5), 35.9% and 100% for item 6 (Q6) in TurPAS questionnaire (Table 4).

Table 3

Diagnostic performance of screening tool according to item count in patients with Psoriatic arthritis
Item counts	Sensitivity (%)	Spesificity (%)	PPV (%)	NPV (%)	Accuracy (%)
≥ 1 positive items
Turpas	94.9	25	38.1	90.9	47.9
EARP	94.9	25	38.1	90.9	47.9
≥ 2 positive items
Turpas	88.7	47.5	45.5	90.5	61.3
EARP	92.3	40	42.9	91.4	57.1
≥ 3 positive items
Turpas	82	70	57.1	89	74
EARP	89.7	58.8	51.5	92.2	68.9
≥ 4 positive items
Turpas	61.5	91.3	77.4	83	81.5
EARP	74.4	86.3	72.5	87.3	82.4
≥ 5 positive items
Turpas	30.8	98.8	92.3	74.5	76.5
EARP	74.4	86.3	72.5	87.3	82.4
≥ 6 positive items
Turpas	2.6	100	100	67.8	68%
EARP	64.1	92.5	80.7	84	83.2%
TurPAS: Turkish Psoriatic Arthritis Screening Questionnaire, EARP: Early Psoriatic Arthritis Screening Questionnaire, PPV: Positive predictive value, NPV: Negative predictive value, LR: Likelihood ratio

Table 4

Diagnostic performance of items of TurPAS
Items	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Accuracy (%)	PTP (%)
Item 1	94.9	36.3	42	93.5	55.5	42
Item 2	46.2	93.8	78.3	78.1	78.2	79
Item 3	35.9	80	46.7	71.9	65.6	47
Item 4	66.7	57.5	50	80.6	67.2	44
Item 5	84.6	56.3	48.5	88.2	65.6	48
Item 6	35.9	100	100	76.2	79	NA
PPV: Positive predictive value, NPV: Negative predictive value, LR: Likelihood ratio, PTP: Post-test probability

PsA is a heterogeneous disease that may affect various parts of the body such as skin, nail, enthesis, joints, axial skelethon.skeleton. In our study, about one-third of patients with PsO (32.8%) met the CASPAR classification criteria and were diagnosed as PsA. The frequency of PsA may differ between 5–40% in several studies probably due to differences in study design, diagnosis method and study population (12) (13). In our study, when compared to the patients with and without PsA, only family history of PsA and CRP levels were different which were higher in patients with PsA than those without. These findings were consistent with the literature (14) (15). No significant difference was observed in patients with and without PsA in terms of age, gender, PsO duration, presence of comorbidities, PASI score, PsO subtypes in patients with and without PsA in our study. Zabotti et al. study revealed a weak predictive value of PASI score for development of PsA although others did not confirm this finding (14). Only one study concluded a positive predictive value of special PsO involvement for areas such as scalp and nail for the development of PsA but this finding was not confirmed in other studies similar to our results (16) (12). Higher TurPAS and EARP scores in patients with PsA than those without in our study were also expected findings. In Lopez-Medina study, while polyarticular involvement was the dominant feature of PsA (60%), mono-oligoarthritis was observed in 40%, enthesitis in 45.8%, dactylitis in 37% and axial involvement in 35.5% in patients with PsA (15). In our study, although oligo-monoarticular subtype was the most frequent involvement, other manifestations were similar to the former study. The frequency of subtypes of PsA highly differs across multiple studies may be associated with difference in study population and/or sample size (17).

It is important to identifying the PsA patients from in dermatology clinics for early diagnosis and treatment in patients with PsA. Thus, several screening tools such as Toronto Psoriatic Arthritis Screening Questionnaire (TOPAS), Psoriasis Epidemiology Screening Tool (PEST), Psoriatic Arthritis Screening and Evaluation (PASE), and the Psoriasis and Arthritis Screening Questionnaire (PASQ), Early Arthritis for Psoriatic Patients (EARP) were develeoped and validated, so far (18) (19) (20) (21) (22). Currently, there is no widely accepted and used screening tool with high diagnostic performance, easily applicable and time-saving. Elaine Husni et al. study with 69 participants sensitivity and specificity of PASE (cut-off ≥ 47/75) were 82% and 73%, respectively (18). In Ibrahim et al. study revealed a higher diagnostic performance of PEST quastionnaire (cut-off ≥ 3/5) with 92% sensitivity and 78% specificity (19). Conversly, sensitivity and specificity of PEST questionnaire were 52% and 93.4%, respectively in another study (7). In a multicenter study, sensitivity and specificity of PEST questionnaire were 68% and 71%, PASE questionnaire were 66% and 57%, EARP questionnare were 87% and 34%, respectively (8). Diagnostic performances of relevant questionnares are highly variable according to several studies probably associated with differences in study design, study population and sample size. Furthermore, different cut-off values in item counts also significantly affect sensitivity and specificity analysis for the screening tools. For instance, while cut-off value of ≥ 3 positive items provide 82% sensitivity and 70% specificity; 61.5% sensitivity and 91.3% specificity were observed for ≥ 4 positive items in TurPAS questionnare in our study.

In our study, TurPAS and EARP scores were higher in patients with PsA than those without, as expected. Furthermore, TurPAS and EARP scores were higher in patients who had PsA compared to patients who had non-PsA diagnosis such as OA, other mechanical conditions and FM. These findings are important to make differential diagnosis adequately and allow discrimination from potential mimickers such as OA, FM, gout, and others. In Meling et al. study 18.1% of PsO patients had PsA diagnosis, 73.2% of these patients did not have PsA (7). In Husni et al. study, diagnosis of OA was observed in 24 patients (34.8%) which was higher compared to diagnosis of PsA (24.6%) among 69 PsO patients (18). Due to the common similarities between PsA and OA such as age of incidence, DIP and vertebral involvement as well as new bone formation on plain radiography, osteoarthritis may frequently cause a diagnostic challenge in patients with PsO. Additionally, there is some evidence overlapping with the two diseases (23). FM and mechanical conditions such as lumber and cervical disk hernia were other frequent non-PsA diagnoses in our study, which were consistent with previous results (24). Thus, screening tool results should be assessed cautiously and it should be kept in mind that diagnosis of PsA requires detailed clinical, laboratory and imaging evaluation by an experienced rheumatologist alongside the relevant questionnaire results.

In our study, while sensitivity of TurPAS was higher, its specificity was lower compared to EARP questionnaire. Higher sensitivity of TurPAS compared to EARP is a remarkable finding since TurPAS has lower item counts than EARP questionnaire. Having lower item counts in TurPAS may make it more easily performed compared to EARP. Lower sensitivity of PEST also may be associated with item counts in other studies (7) (8). Q1 has the highest sensitivity in TurPAS, Q6 had the highest specificity in our study. While Q1 does not include axial involvement, highest sensitivity of Q1 is a remarkable finding probably due to the lower frequency of pure axial involvement in our study. The finding of highest specificity of Q6 is expected which is consistent with prior diagnosis.

Our study has some strengths and limitations. This is the first study regarding validation of TurPAS alongside comparison with EARP questionnaire in a relatively large population. Including the patients who had no musculoskeletal complaint to the study may allow to identify real incidence of PsA in patients with PsO and also prevent potential bias. The fact that diagnosis of PsA is made by a single physician via a diagnostic protocol including acute phase reactants, autoantibody as well as imaging results (X-ray and MRI) with clinical examination. Revealing musculoskeletal diseases beyond PsA and their association with relevant questionnaires were also strengths of the current study. On the other hand, relatively higher frequency of patients receiving cs-DMARD and b-DMARD treatments may cause underestimation of the patients’ musculoskletal complaints and may influence the frequency of PsA diagnosis.

In our study approximately one-third of patients with PsO diagnosed as PsA. TurPAS had comparable diagnoostic performance to the EARP questionnaire in our study. More data are needed with further studies to clarify the relevance of TurPAS as a screening tool in patients with PsO.

Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out work described in this article.

Availability of data and material: The Dataset of the study is available from the corresponding author on reasonable request.

Code availability: Not applicable.

Author contributions: MB and ŞBK designed and planned the study, ŞBK, HK, and HS collected the data, MB carried out the data evaluation and basic analyses, all authors contributed to the follow-up of the patients and interpretation of results, ŞBK performed dermatological examination and relevant questionnaires. MB performed rheumatologic evaluation, MB wrote the first draft along with ŞBK, and all authors provided critical feedback for the last version.

Ethics approval: The local Ethics Committee approval was obtained from Aksaray University, Faculty of Medicine (Number: 2022/21-11).

Informed consent: Informed consent was obtained obtained for this study.

Supplementary data: Yes

Acknowledgments: Not applicable.

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No competing interests reported.

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Validation of Turkish Psoriatic Arthritis Screening Tool (TurPAS) for Psoriatic Arthritis: A Cross-sectional Comparative Study

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