Abstract
Background
Psoriatic arthritis (PsA) develops in up to one-third of patients with psoriasis over the disease course, and the genetic factors are thought to modulate susceptibility. Although HLA-B27 has long been implicated in PsA, its clinical utility for identifying PsA in East Asian populations remains uncertain.
Objective
We aimed to estimate the clinic-based prevalence of PsA among Korean psoriatic patients, and to evaluate the diagnostic value of HLA-B27, along with other clinical markers, for PsA.
Methods
We conducted a retrospective, cross-sectional study of 209 patients with psoriasis who presented for their initial dermatology clinic visit at a tertiary referral center.
Results
The clinic-based prevalence of PsA was 13.9%. HLA-B27 positivity did not show significant difference between patients with PsA and psoriasis not fulfilling Classification Criteria for Psoriatic Arthritis criteria (13.8% vs. 7.8%) and was not associated with PsA or cutaneous disease severity in multivariable analyses. In contrast, nail dystrophy and elevated C-reactive protein (CRP) levels were independently associated with PsA. In this cohort, HLA-B27 demonstrated limited predictive value, whereas nail involvement and elevated CRP levels emerged as more reliable indicators of joint involvement.
Conclusion
In this dermatology-based cohort of unselected Korean patients with psoriasis at the initial clinic visit, routine HLA-B27 testing showed limited utility as a screening tool for PsA, whereas nail involvement and elevated CRP levels served as more practical clinical cues for closer joint involvement.
Keywords: C-reactive protein, HLA-B27 antigen, Nail disease, Psoriasis, Psoriatic arthritis
INTRODUCTION
Psoriasis vulgaris is a common, chronic immune-mediated dermatosis, affecting 2%–3% of the global population1. Among comorbidities, psoriatic arthritis (PsA) occurs in up to one-third of patients over the disease course and is a major driver of disability and healthcare costs2.
Accumulating evidence suggests that genetic background modulates the heterogeneity of PsA. While HLA-C06 is the strongest susceptibility allele for cutaneous psoriasis, HLA-B27 has been implicated in PsA, particularly in patients with axial involvement2,3,4,5. However, the reported frequency of HLA-B27 among Asian PsA patients (≈15%) is much lower than in Caucasian cohorts, raising questions about its diagnostic utility in Korea6.
Beyond HLA typing, several cutaneous and laboratory markers have emerged as practical clinical clues for identifying patients with psoriasis at risk of PsA. Nail disease is an established cutaneous risk factor, while inflammatory indices such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) have been associated with musculoskeletal involvement in prior studies2,7,8,9.
However, data from Korean dermatology practice that comprehensively evaluate HLA-B27 status and these emerging clinical predictors of PsA remain limited. The present retrospective study therefore aims to estimate the clinic-based prevalence of PsA in Korean patients with psoriasis and to examine the diagnostic relevance of HLA-B27, along with the cutaneous and inflammatory markers associated with joint involvement.
MATERIALS AND METHODS
Study subjects
We conducted a retrospective, cross-sectional study of adult patients (≥18 years) with dermatologist-confirmed psoriasis (International Classification of Diseases 10, L40.08) who presented as new patients to the Severance Dermatology Clinic between 1 January 2021 and 31 July 2023. Thirteen patients with palmoplantar psoriasis confined to the palms and soles were excluded. Clinical variables were extracted from the electronic medical records at the first clinic visit. At our institution, HLA-B27 testing is routinely performed as part of the baseline evaluation of psoriasis patients at the first clinic visit, and therefore the study cohort was not restricted to patients with clinical suspicion of PsA.
PsA was classified according to the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria10. Axial type PsA was considered present when there was radiological evidence of sacroiliitis and/or syndesmophytes, vertebral squaring, ligamentous ossification and shining corners of the spine. Peripheral type PsA was defined by clinical and radiographic evidence of peripheral joint involvement without axial disease.
Statistical analysis
Continuous variables were compared using Mann–Whitney U test, and categorical variables using χ2 test or Fisher’s exact test. Associations with PsA were examined using logistic regression, and determinants of psoriasis severity (PASI) were evaluated using linear regression. Statistical significance was set at two-sided p<0.05. All analyses were performed with R version 4.3.3 (R Foundation for Statistical Computing, Vienna, Austria). The study was approved by the Institutional Review Board (IRB) of Severance Hospital (IRB No. 4-2023-1268), and informed consent was waived.
RESULTS
Baseline characteristics
Table 1 summarizes the demographic profile of the 209 enrolled patients. Psoriasis began at a median age of 26 years with a median disease duration of 9 years. Demographic characteristics were comparable between patients with PsA and psoriasis not fulfilling CASPAR criteria.
Table 1. Baseline demographic and clinical characteristics of the total population according to the presence of PsA.
| Variables | Total (n=209) | PsA* (n=29) | CASPAR-negative psoriasis(n=180) | p | |
|---|---|---|---|---|---|
| Age (yr) | 38 (29–50) | 39 (33–45) | 37 (29–52) | 0.802 | |
| Onset age (yr) | 26 (20–38) | 26 (20–37) | 26 (20–39) | 0.314 | |
| Disease duration (yr) | 9 (3–17) | 11 (5–20) | 9 (3–15) | 0.228 | |
| Sex (male) | 143 (68.4) | 21 (72.4) | 122 (67.8) | 0.777 | |
| Family history | 29 (13.9) | 5 (17.2) | 24 (13.3) | 0.565 | |
| Clinical characteristics | |||||
| Scalp involvement | 149 (71.3) | 23 (79.3) | 126 (70) | 0.419 | |
| Nail change | 123 (58.9) | 25 (86.2) | 98 (54.4) | 0.002 | |
| Peripheral arthritis | 31 (14.7) | 17 (58.6) | 14 (7.8) | <0.001 | |
| Axial arthritis | 30 (14.4) | 16 (55.2) | 14 (7.8) | <0.001 | |
| Enthesopathy | 11 (5.3) | 8 (27.6) | 3 (1.7) | <0.001 | |
| PsA | 29 (13.9) | ||||
| Peripheral type | 14 (6.7) | ||||
| Axial type | 10 (4.8) | ||||
| Both | 5 (2.4) | ||||
| HLA-B27 positivity | 18 (8.6) | 4 (13.8) | 14 (7.8) | 0.286 | |
| PASI score | 7.2 (3.6–11.3) | 10.2 (6.3–14.4) | 6.8 (3.3–11.0) | 0.011 | |
| Laboratory parameters | |||||
| ESR | 7 (2–15) | 11.5 (2.0–16.8) | 7 (2–15) | 0.216 | |
| RDW | 12.8 (12.2–13.3) | 13.1 (12.6–13.8) | 12.7 (12.1–13.3) | 0.017 | |
| CRP | 1.5 (0.8–3.7) | 3.9 (0.9–9.7) | 1.4 (0.8–3.5) | 0.025 | |
| Negative rheumatoid factor† | 200 (95.7) | 28 (96.6) | 172 (95.6) | 0.768 | |
Values are presented as median (interquartile range) or number (%).
PsA: psoriatic arthritis, CASPAR: Classification Criteria for Psoriatic Arthritis, PASI: psoriasis area and severity index, ESR: erythrocyte sedimentation rate, RDW: red cell distribution width, CRP: C-reactive protein.
*PsA was diagnosed according to the CASPAR criteria.
†Negative rheumatoid factor was defined as <15 IU/ml.
Clinical characteristics of PsA patients
The clinic-based proportion of PsA was 13.9% (Table 1), exceeding the 9% previously reported in a Korean multicenter cohort11. Among PsA patients, scalp involvement and nail dystrophy were common, with peripheral and axial arthritis observed in over half of cases. Nail changes were markedly more frequent in PsA than in CASPAR-negative psoriasis patients (86.2% vs. 54.4%, p=0.002) and remained independently associated with PsA on multivariable regression (adjusted odds ratio [OR], 7.88; p=0.015; Tables 1 and 2).
Table 2. Logistic regression analysis identifying predictors of psoriatic arthritis.
| Variables | Univariable analysis | Multivariable analysis | |||
|---|---|---|---|---|---|
| OR | p | Adjusted OR | p | ||
| Disease duration | 1.02 | 0.231 | |||
| Family history | 1.35 | 0.573 | |||
| Clinical characteristics | |||||
| Scalp involvement | 1.64 | 0.307 | |||
| Nail change | 5.23 | 0.003 | 7.88 | 0.015 | |
| PASI score | 1.08 | 0.015 | 1.07 | 0.066 | |
| Laboratory parameters | |||||
| ESR | 1.02 | 0.055 | |||
| RDW | 1.55 | 0.021 | 1.19 | 0.467 | |
| CRP | 1.15 | 0.001 | 1.13 | 0.004 | |
| Negative RF* | 0.77 | 0.807 | |||
| HLA-B27 positivity | 1.90 | 0.291 | 1.93 | 0.345 | |
OR: odds ratio, PASI: psoriasis area and severity index, ESR: erythrocyte sedimentation rate, RDW: red cell distribution width, CRP: C-reactive protein, RF: rheumatoid factor.
*Negative RF was defined as <15 IU/ml.
HLA-B27 status
HLA-B27 was detected in 4 of 29 PsA patients (13.8%) and in 14 of 180 CASPAR-negative psoriasis patients (7.8%), a difference that did not reach statistical significance (Table 1). No demographic, clinical, or laboratory variables differed between HLA-B27–positive and –negative subgroups (Supplementary Table 1), and HLA-B27 status was not significantly associated with PsA or cutaneous severity in regression models (Tables 2 and 3). We additionally performed phenotype-stratified analyses to evaluate the association between HLA-B27 positivity and PsA subtype (Supplementary Table 2). HLA-B27 positivity was similar between patients with axial and non-axial PsA (13.3% [2/15] vs. 14.3% [2/14]). Likewise, no significant difference was observed according to peripheral involvement (15.8% [3/19] vs. 10.0% [1/10]). No statistically significant associations were identified (Fisher’s exact test, p=1.00 for both comparisons). An additional analysis was performed using a separate cohort of PsA patients identified from the Rheumatology department during the same study period, distinct from those included in the Dermatology department-based cohort. A total of 71 patients were included, among whom 15 (21.1%) were HLA-B27 positive. HLA-B27 positivity was more frequent in patients with axial involvement than in those without, although this did not reach statistical significance (Fisher’s exact test, p=0.22). No significant association was observed between HLA-B27 status and peripheral involvement (p=0.45). Detailed results are presented in Supplementary Table 3.
Table 3. Linear regression analysis identifying predictors of cutaneous psoriasis severity.
| Variables | Univariable analysis | Multivariable analysis | |||
|---|---|---|---|---|---|
| β | p | Adjusted β | p | ||
| Disease duration | 0.04 | 0.364 | |||
| Family history | −1.38 | 0.225 | |||
| Clinical characteristics | |||||
| Scalp involvement | 2.19 | 0.012 | 1.55 | 0.067 | |
| Nail change | 3.35 | <0.001 | 2.92 | <0.001 | |
| Peripheral arthritis | 0.31 | 0.777 | |||
| Axial arthritis | 0.67 | 0.551 | |||
| Enthesopathy | 3.07 | 0.081 | |||
| Psoriatic arthritis | 2.89 | 0.011 | 1.89 | 0.089 | |
| Laboratory parameters | |||||
| ESR | 0.01 | 0.680 | |||
| RDW | −0.08 | 0.848 | |||
| CRP | 0.03 | 0.728 | |||
| Negative RF* | 2.52 | 0.193 | |||
| HLA-B27 positivity | −0.94 | 0.504 | −1.18 | 0.384 | |
ESR: erythrocyte sedimentation rate, RDW: red cell distribution width, CRP: C-reactive protein, RF: rheumatoid factor.
*Negative RF was defined as <15 IU/ml.
Laboratory indices
Initial red cell distribution width (RDW) and CRP levels were higher in PsA than in CASPAR-negative psoriasis (RDW, 13.1% vs. 12.7%, p=0.017; CRP, 3.9 mg/L vs. 1.4 mg/L, p=0.025). Although ESR level trended higher in PsA, the difference was not statistically significant (Table 1). In univariable logistic regression, both RDW (OR, 1.55; p=0.021) and CRP (OR, 1.15; p=0.001) levels were significantly associated with PsA; however, in the multivariable model, the association for RDW level was attenuated and no longer significant (adjusted OR, 1.19; p=0.467), whereas CRP level remained an independent predictor of PsA (adjusted OR, 1.13, p=0.004; Table 2).
Disease severity
The PASI was higher in patients with PsA than in those with CASPAR-negative psoriasis (10.2 vs. 6.8, p=0.011; Table 1). In univariable logistic regression, PASI (OR, 1.08; p=0.015) was associated with PsA; however, this association was attenuated after adjustment for nail dystrophy and inflammatory indices and was no longer statistically significant in the multivariable model (Table 2). In univariable linear regression, both scalp involvement and nail dystrophy were associated with higher PASI (scalp involvement β=2.19, p=0.012; nail dystrophy, β=3.35, p<0.001). After adjustment, only nail dystrophy remained independently associated with higher PASI (adjusted β=2.92, p<0.001), whereas scalp involvement showed only a borderline association (adjusted β=1.55, p=0.067; Tables 2 and 3).
DISCUSSION
In this cohort of 209 Korean patients with psoriasis, HLA-B27 was not associated with either the presence of PsA or the severity of cutaneous disease. In contrast, nail dystrophy and elevated CRP levels emerged as independently associated with the presence of PsA, whereas overall skin severity measured by PASI score did not independently distinguish joint involvement. The clinic-based prevalence of PsA was 13.9%, which was broadly consistent with prior estimates and the meta-analytic studies12. Based on previous reports, approximately 30% of patients with psoriasis are estimated to develop PsA within 10 years; however, PsA patients in the present study were not older than those with psoriasis not fulfilling the CASPAR criteria, suggesting that clinical phenotype rather than chronological progression may better characterize PsA in this setting13.
Traditionally, PsA has been recognized as a part of the HLA-B27-associated spondyloarthritis spectrum, and numerous studies have demonstrated that HLA-B27 is more frequently observed in patients with PsA than in those with psoriasis alone3,4. HLA-B27 has also been linked to characteristic PsA phenotypes, particularly axial disease3,4,5. However, in our cohort, HLA-B27 positivity was not significantly associated with either the presence of PsA or axial involvement. In a phenotype-stratified analysis among PsA patients, the frequency of HLA-B27 positivity was comparable between those with axial and non-axial disease (13.3% vs. 14.3%, Supplementary Table 2). Although the number of HLA-B27 positive cases was small, this finding should be interpreted with caution, as the study may have been underpowered to detect phenotype-specific associations. To further explore potential selection bias related to the dermatology-based cohort, we performed an additional analysis of PsA patients identified from the Rheumatology department during the same study period. In this cohort, HLA-B27 positivity showed a non-significant trend toward higher frequency in patients with axial involvement, while no association was observed with peripheral disease (Supplementary Table 3). Although these findings did not reach statistical significance, they may be compatible with the established biological association between HLA-B27 and axial disease. Taken together, these analyses suggest that the relationship between HLA-B27 and axial PsA in Korean patients remains inconclusive in our dataset and should be interpreted cautiously given the limited sample size.
Similar patterns have been observed in a prior Korean study, which reported no clear association between HLA-B27 and axial involvement among patients with PsA, suggesting that the contribution of this allele to psoriatic musculoskeletal disease may be limited in East Asian populations11. The prevalence of PsA itself shows substantial geographic variation, with pooled estimates of approximately 20%–25% in Western populations, compared with 10%–15% in East Asian populations12. Importantly, these epidemiologic differences coexist with marked ethnic variation in background HLA-B27 frequency in the general population, with carriage rates in Western populations (approximately 7%–24%) compared with 4%–6% in Koreans and 0.1%–0.5% in Japanese populations14. In this context, the absence of a significant association between HLA-B27 and PsA in our Korean cohort is consistent with prior regional studies, suggesting that the contribution of HLA-B27 to psoriatic musculoskeletal disease may be attenuated in East Asian populations.
Several methodological considerations should be acknowledged. The cross-sectional design, based on data obtained at the initial clinic visit, precluded assessment of the temporal progression from psoriasis to PsA. As a result, early or prodromal cases—defined as patients with inflammatory musculoskeletal symptoms that do not yet meet CASPAR criteria—may have been misclassified as having skin-limited disease. The limited sample size, together with the low background frequency of HLA-B27 in East Asian populations, may have reduced statistical power to detect modest genetic associations. Therefore, the possibility of a Type II error cannot be excluded. In addition, inflammatory markers such as CRP and RDW may also be influenced by systemic treatments for psoriasis, including methotrexate, cyclosporine, or biologic agents. Because detailed treatment status at the time of laboratory testing was not consistently available in this retrospective dataset, potential treatment-related confounding cannot be excluded. Notably, no patients in our cohort were documented to have dactylitis, a key clinical domain of PsA, precluding domain-specific analyses incorporating this feature and potentially limiting the comprehensiveness of phenotype-based evaluation in this study.
Although HLA-B27 showed no relationship to PsA or PASI in our cohort, nail dystrophy and elevated CRP levels were independently associated with the presence of PsA. Nail dystrophy is a component of the CASPAR classification criteria, and therefore its association with PsA in this study may partly reflect a degree of circularity inherent to the diagnostic framework. Accordingly, this finding should be interpreted with caution and considered primarily as a practical clinical indicator rather than an independent predictive factor. Nevertheless, our results are consistent with prior studies identifying nail dystrophy as one of the strongest cutaneous predictors of PsA and acute-phase reactants, particularly CRP, as indicators of systemic inflammation related to musculoskeletal involvement and structural progression2,7,8,9. RDW also exhibited a significant association with PsA only in univariate analysis, consistent with prior reports indicating that RDW reflects overall systemic inflammatory burden in psoriasis, rather than an independent predictor of PsA15. Notably, neither CRP nor RDW correlated with PASI, supporting their role as markers of systemic or musculoskeletal inflammation rather than skin-limited disease. In this context, CRP likely reflects overall systemic inflammatory burden rather than acting as a disease-specific predictor of PsA. Clinically, these findings suggest that HLA-B27 testing has limited predictive utility in unselected Korean psoriasis patients, whereas readily identifiable clinical features and inflammatory markers, particularly nail involvement and elevated CRP levels, may provide more practical guidance for identifying high-risk individuals who could benefit from closer musculoskeletal evaluation.
In summary, this study highlights population-specific differences in the immunogenetic context of PsA, demonstrating that genetic associations established in Western cohorts may not directly translate to Korean patients. Despite the relatively small number of PsA cases, our findings provide insight into an East Asian population, in which both the prevalence of PsA and the background frequency of HLA-B27 differ substantially from those reported in Western cohorts. Although HLA-B27 was not significantly associated with PsA or axial involvement in this cohort, the limited number of HLA-B27–positive cases may have reduced the statistical power to detect modest associations. From a dermatology-based clinical perspective, where the early identification of psoriasis patients at risk of PsA is essential, our findings suggest that routine HLA-B27 testing in unselected psoriasis patients has limited utility as a screening tool. However, this should not be interpreted as excluding the potential value of phenotype-directed testing, particularly in patients with suspected axial involvement or features suggestive of spondyloarthritis. Instead, clinical features such as nail dystrophy and elevated CRP levels may provide more practical guidance for identifying patients who warrant closer musculoskeletal evaluation. These findings underscore the importance of integrating genetic context with clinical and inflammatory features when assessing PsA risk.
ACKNOWLEDGMENT
We thank the patients for their cooperation.
Footnotes
FUNDING SOURCE: This study was supported by a faculty research grant of Yonsei University College of Medicine (6-2024-0095).
CONFLICTS OF INTEREST: The authors have nothing to disclose.
DATA SHARING STATEMENT: The data that support the findings of this study are available from the corresponding author upon reasonable request.
SUPPLEMENTARY MATERIALS
Comparison of clinical characteristics according to HLA-B27 status
Association between HLA-B27 positivity and involvement types in PsA patients from the dermatology-based cohort
Association between HLA-B27 positivity and involvement types in PsA patients from the Rheumatology-based cohort
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Comparison of clinical characteristics according to HLA-B27 status
Association between HLA-B27 positivity and involvement types in PsA patients from the dermatology-based cohort
Association between HLA-B27 positivity and involvement types in PsA patients from the Rheumatology-based cohort