Clinical Data
A retrospective review was conducted on 1,500 hospitalized psoriasis patients who were treated with acitretin at the Department of Dermatology, Sichuan Provincial People's Hospital (Chengdu, China) between February 2018 and January 2022 A total of 156 psoriasis patients were included for analysis, and the demographic data and clinical characteristics of the study as shown in Table 1.
Inclusion criteria: Patients diagnosed with psoriasis in the outpatient clinic.
This study has been approved by ethics committee of The First Affiliated Hospital of Chengdu Medical College and the informed consent was obtained from all subjects. All methods were performed in accordance with the relevant guidelines and regulations.
Table 1
Baseline demographic, clinical features of patients
No. | Parameters | Data, rate and details |
1 | Gender, Patients, n (%) | Males 116 (74.36%) | Females 402 (25.64%) | - | - |
2 | Types, patients, n (%) | Vulgaris 87 (55.77) | Pustular 47 (30.13) | Erythrodermic 21 (13.46) | Arthropathic 1 (0.64) |
3 | Stage patients, n (%) | Progress period 78 (50.00) | Stable period 78 (50.00) | Extinction period 0 (0) | - |
4 | Season of onset, patients, n (%) | Spring 45 (28.85) | Summer 28 (17.95) | Autumn 44 (28.21) | Winter 39 (25.00) |
6 | Age of onset, patients, n (%) | Children 2 (1.28) | Youth 34 (21.79) | Middle age 76 (48.72) | Old age 44 (28.21) |
5 | Family history, patients, n (%) | - | 14 (8.79) | - | - |
6 | Age, years, mean ± SD (range) | - | 47.705士16.500 (6–75) | - | - |
7 | Disease duration, years, mean ± SD (range) | - | 13.159士10.8411 (0.08-50) | - | - |
8 | Weight, Kg, mean ± SD (range) | - | 63.994士12.034 (20–105) | - | - |
9 | Lesion area, %, mean ± SD (range) | - | 94.917士5.610 (50–100) | - | - |
10 | PASI Score, mean ± SD (range) | - | 13.949士3.895 (1.6–23.0) | - | - |
11 | Dose, mg/day, mean ± SD (range) | - | 34.955士8.665 (10–60) | - | - |
12 | Unit dose, mg/day, mean ± SD (range) | - | 0.560士0.158 (0.24–1.06) | - | - |
SD, Standard deviation.
Exclusion criteria: (i) Patients who had received methotrexate, cyclosporine, cyclophosphamide, leflunomide, sulfasalazine, mycophenolate mofetil, biologics, tripterygium, or systemic glucocorticoids within the past 6 months, or intravenous immunoglobulin within the past 3 months; (ii) Patients with severe cardiopulmonary disease, severe renal or hepatic dysfunction, or other diseases affecting laboratory test results; (iii) Pregnant or lactating patients; (iv) Patients who had overexertion, alcohol abuse, strenuous exercise, stayed up late, or consumed greasy food in the 3 days prior to admission that could affect aminotransferase results; (v) Patients who were unavailable for retrospective follow-up.
Data Collection
A standardized data collection form was elaborated to collect the date of possible influencing factors from the hospital clinical records. All blood samples were fasting blood collected in the morning after a full-night rest.
The clinical data included: disease subtype, stage, affected skin area, acitretin dosage, treatment duration, PASI scores before and after treatment, adverse reactions after medication (skin dryness, pruritus, cheilitis), etc.
The laboratory data included: WBC, NEU, NEU-R, Hb, PIT, PCT, Hs-CRP, CD4 + T, CD8 + T, IgE, creatinine, glomerular filtration rate, serum calcium, potassium, sodium, magnesium, phosphorus, AST, ALT, uric acid, albumin, globulin, cholesterol, triglycerides, L-LDL, H-LDL, ALP, total bilirubin, etc., before and after acitretin treatment.
Efficacy Evaluation
PASI score is selected as the standard for assessment of extensive psoriasis8. PASI score improvement rate= (pre-treatment PASI score - post-treatment PASI score) / pre-treatment PASI score ×100%. Treatment efficacy were divided into four Grades according to PASI50, PASI75, and PASI90, and responders were defined as Grade 1, Grade 2, or Grade 3, as follows:
Ineffective group (Grade 0): PASI score improvement<50%.
Effective group (Grade 1): 50% =< PASI score improvement < 75%.
Significantly effective group (Grade 2): 75% =< PASI score improvement < 90%.
Clinically cured group (Grade 3): PASI score improvement > = 90%
Analysis Method
All analyses were performed using the software programs SPSS 17.0. Spearman correlation was applied to assess the correlation between acitretin efficacy and relevant clinical and laboratory data. Logistic multiple regression model was established to evaluate the association of AST with acitretin efficacy. Receiver operating characteristic (ROC) analysis was performed to examine the accuracy and specificity of Hs-CRP predicting PASI90. Quantitative data were analyzed by t-test, one-way analysis of variance (ANOVA) test, Kruskal-Wallis H test or Scheffe test. Statistical significance was set at P = 0.05. P values less than 0.05 were considered significant.
Correlation Results
PASI Score
After acitretin treatment, 147 patients (94.2%) achieved PASI50, 81 patients (51.9%) achieved PASI75 and 16 patients (10.3%) achieved PASI90. The overall rate of efficacy was 94.2% (147/156), in which, 42.3% in Grade 1, 41.7% in Grade 2 and 10.3% were in Grade 3.
AST Correlation Analysis
Statistical analysis showed that treatment efficacy was positively correlated with pretreatment PASI score (r = 0.410, p < 0.001). No significant correlations were found between efficacy and other clinical characteristics such as age, gender, obesity, disease duration, treatment season, mean daily acitretin dose, family history, etc. Pre-treatment serum AST (r=-0.160, P = 0.046) was significantly correlated with acitretin efficacy. Table 2 reports the correlations between acitretin efficacy and patient demographics, clinical and laboratory data.
Table 2
The correlation between acitretin efficacy and demographics, clinical and laboratory data of patients
No. | Potential risk | r Value* | P Value |
1 | Age | 0.049 | 0.547 |
2 | Weight | 0.079 | 0.333 |
3 | Duration | 0.077 | 0.339 |
4 | Daily dose | 0.041 | 0.610 |
5 | Unit dose | -0.018 | 0.821 |
6 | Treatment | 0.152 | 0.059 |
Blood routine |
7 | WBC | 0.03 | 0.713 |
8 | NEU | 0.012 | 0.883 |
9 | EOS | -0.061 | 0.453 |
10 | NEU-R | -0.084 | 0.297 |
11 | Hb | 0.029 | 0.724 |
12 | PLT | -0.029 | 0.724 |
13 | Hs-CPR | 0.063 | 0.465 |
A liver function test |
14 | AST | -0.160 | 0.046 |
15 | ALT | 0.032 | 0.687 |
16 | Glb | 0.023 | 0.775 |
17 | Alb | 0.112 | 0.164 |
18 | ALP | -0.070 | 0.387 |
19 | TBIL | 0.053 | 0.514 |
Renal functions |
20 | Cr | 0.153 | 0.057 |
21 | eGFR | -0.046 | 0.702 |
22 | UA | 0.016 | 0.845 |
23 | K | 0.091 | 0.259 |
24 | Na | 0.037 | 0.644 |
25 | Ca | -0.009 | 0.908 |
26 | Mg | 0.028 | 0.731 |
27 | P | 0.040 | 0.627 |
A lipid profile |
28 | TG | -0.028 | 0.732 |
29 | TC | 0.460 | 0.575 |
30 | LDL | 0.004 | 0.960 |
31 | HDL | 0.071 | 0.390 |
32 | CD4 + T | 0.117 | 0.509 |
33 | CD8 + T | 0.102 | 0.568 |
WBC, Leukocyte count; NEU, Neutrophil count; E0S, Eosinophilic granulocyte; NEU-R, Neutrophil rate; Hb, Hemoglobin; PLT, Platelet count; Hs-CRP, High-sensitivity C-reactive protein; AST, Aspartate aminotransferase; ALT, Alanine ami-notransferase; Glb, Globulin; Alb, Albumin; ALP, Alkaline phosphatase; TBIL, Total bilirubin; Cr, Creatinine; eGFR, Glomerular filtration rate; UA, Uric acid; K, Potassium; Na, Sodium; Ca, Calcium; Mg, Magnesium; P, Phosphorus; TG, Triglyceride; TC, Cholesterol; LDL, Low density lipoprotein; HDL, High-density lipoprotein; CD4+T, CD4+ T-lymphocyte count; CD8+T, CD8+ T- lymphocyte count.
*Spearman correlation coefficient.
Normal AST is between 15–40 U/L. In our study, the mean AST differed significantly between Grades, with a mean of 43.89 U/L in Grade 0, 31.65 U/L in Grade 1, 29.95 U/L in Grade 2, and 25.81 U/L in Grade 3. Which indicates that treatment efficacy improved with decreasing AST value. ANOVA showed a P value of 0.045 (P < 0.05), which was statistically significant.
Multivariate logistic regression models were built to evaluate the relationship between AST, gender, age and acitretin efficacy found that this association persisted after adjusting for gender and age. However, the association disappeared when more blood biochemical markers were added, as they could not be included in the model due to significant correlations, as shown in Table 3. After adjusting for gender and age, the regression coefficient for AST was − 0.019 (P = 0.041), which was statistically significant (P < 0.05). The adjusted odds ratio (OR = e-0.019) was 0.98, less than 1. The results indicate that AST is a protective factor.
Table 3
Logistic regression model estimation and test results
Parameters estimation |
- | β | SD | Wald | Variance | P Value | 95% confidence interval |
Lower confidence limite | Upper confidence limite |
Threshold Value | [Grade = 0] | -3.031 | 0.672 | 20.324 | 1 | 0.000 | -4.349 | -1.713 |
[Grade = 1] | -0.249 | 0.581 | 0.184 | 1 | 0.668 | -1.388 | 0.889 |
[Grade = 2] | 2.032 | 0.619 | 10.783 | 1 | 0.001 | 0.819 | 3.245 |
Position | AST | -0.019 | 0.009 | 4.189 | 1 | 0.041 | -0.037 | -0.001 |
Age | 0.009 | 0.009 | 1.027 | 1 | 0.311 | -0.009 | 0.028 |
[Grade = 0] | -0.124 | 0.348 | 0.126 | 1 | 0.723 | -0.806 | 0.559 |
[Grade = 1] | 0 | - | - | 0 | - | - | - |
SD, Standard deviation; AST, aspartate aminotransferase.
†Partial regression coefficient.
*correlation function L: Logarithm.
a means this parameter is redundant and is set to be zero.
Pretreatment serum Hs-CRP, WBC, NEU, NEU-R and Alb seemed to contain some kind of trends among different efficacy improvement Grade and the difference of Hs-CRP, NEU-R and Alb was statistically significant (P < 0.05). The results were summarized in table IV.
WBC、NEU、NEU-R、Hs-CRP、Alb Correlation Analysis
The normal ranges for WBC and NEU are (3.50–9.50)×109/L and (1.80–6.30)×109/L respectively. Comparison of mean values across Grades showed declining trends with increasing Grade from 0 to 2, and values below normal ranges, as shown in Table 4. Lower values were indicative of potentially better efficacy and higher PASI Grade after treatment. In the PASI90 group, the mean of WBC was 10.607×109/L and the mean of NEU was 8.233×109/L, markedly higher than normal ranges, indicating that patients with this range could achieve better efficacy with acitretin treatment for psoriasis. ANOVA showed P values of 0.294 and 0.162 for WBC and NEU respectively, both greater than 0.05. Therefore, the differences in these two indices were not statistically significant.
Table 4
The mean and standard deviation of serum AST, WBC, NEU, NEU-R, Hs-CRP and Alb
Parameters | Grade 0 | Grade 1 | Grade 2 | Grade 3 | Normal value | F value | P value (P < 0.05) |
PASI score improvement rate | PASI score improvement < 50% | 50%=<PASI score improvement < 75% | 75%=<PASI score improvement < 90% | PASI score improvement > = 90% | - | - | - |
Patients, n (%) | 9 (5.8%) | 66 (42.3%) | 65 (41.7%) | 16 (10.3%) | - | - | - |
AST (U/L) | 43.890士33.728 | 31.650士18.393 | 25.950士12.078 | 25.810士14.702 | 15–40 | 2.349 | 0.045 |
WBC (109/L) | 9.312士4.794 | 8.371士3.667 | 8.377士4.869 | 10.607士3.907 | 3.50–9.50 | 1.248 | 0.294 |
NEU (109/L) | 7.410士4.666 | 6.148士3.581 | 5.851士4.705 | 8.233士4.408 | 1.80–6.30 | 1.735 | 0.162 |
NEU-R | 0.763士0.106 | 0.699士0.128 | 0.654士0.117 | 0.748士0.116 | 0.40–0.75 | 4.494 | 0.005 |
Alb (g/L) | 35.433士6.173 | 37.769士5.550 | 39.857士5.308 | 34.800士5.963 | 40–55 | 4.143 | 0.007 |
Hs-CRP (mg/L) | 50.769士58.306 | 29.531士48.176 | 20.839士38.494 | 69.554士62.135 | 0–5 | x2 = 4.425 | 0.005 |
PASI, Psoriasis area and severity index; AST, Aspartate aminotransferase; WBC, Leukocyte count; NEU, Neutrophil count; NEU-R, Neutrophil rate; Hs-CRP, High-sensitivity C-reactive protein; Alb, Albumin.
†one-way analysis of variance test.
‡chi-square test.
The normal range for NEU-R is 0.40 to 0.75. In this study, the mean deviations of NEU-R were 0.763 for Grade 0, 0.699 for Grade 1, 0.654 for Grade 2, and 0.748 for Grade 3, as shown in Fig. 1. ANOVA showed a P value of 0.005 (P < 0.05), indicating a statistically significant. Scheffe Test revealed that the mean NEU-R showed a gradual declining trend from Grade 0 to 2, and lower mean NEU-R was associated with higher post-treatment Grade and better treatment efficacy.
The normal range for Hs-CRP is 0–5 mg/L, the mean Hs-CRP was 50.769 mg/L for Grade 0, 29.531 mg/L for Grade 1, 20.839 mg/L for Grade 2, and 69.554 mg/L for Grade 3, as shown in Table 4. The Kruskal-Wallis H Test showed x2 = 4.425 and P = 0.005 (P < 0.05), indicating a statistically significant. The mean of Hs-CRP for all 4 Grades were markedly higher than the normal range, with a clear declining trend from Grade 0 to 2. Scheffe Test also showed statistically significant differences in Hs-CRP between Grade 3 and Grade 2 (P = 0.009) as well as Grade 1 (P = 0.049), which was analytically meaningful. The receiver operating characteristic (ROC) analysis curve of Hs-CRP predicting PASI90 was plotted to evaluate the accuracy and sensitivity of the efficacy of acitretin treatment. Analysis showed the area under the curve (AUC) was 0.731 (0.7 < AUC < 0.9), indicating good accuracy of Hs-CRP for prediction. By calculating the highest Youden index, the 18.65 mg/L of Hs-CRP was considered to be the cutoff point, as shown in Fig. 2.
The normal range for serum Alb is 40–55 g/L. In this analysis data, the mean of Alb was 35.433 g/L for Grade 0, 37.769 g/L for Grade 1, 39.857 g/L for Grade 2, and 34.800 g/L for Grade 3. ANOVA showed a P value of 0.007 (P < 0.05), indicating significant differences that were statistically meaningful. Scheffe Test showed statistically significant differences in mean Alb only between Grade 3 and 2 (P = 0.021). Higher improvement Grades could be achieved with increasing mean Alb. In PASI90, the mean of Alb was 34.800 g/L, markedly below normal, this value range showed significant therapeutic efficacy of acitretin.
Correlations Between Serum Parameters
Correlation analysis between serum parameters showed good correlations among WBC, NEU, NEU-R, Hs-CRP, and Alb: WBC was positively correlated with NEU (r = 0.959, P < 0.001), NEU-R (r = 0.675, P < 0.001) and Hs-CRP (r = 0.389, P < 0.001); NEU was positively correlated with NEU-R (r = 0.830, P < 0.001) and Hs-CRP (r = 0.431, P < 0.001); Alb was negatively correlated with WBC (r=-0.345, P < 0.001), NEU (r=-0.353, P < 0.001), NEU-R (r=-0.389, P < 0.001) and Hs-CRP (r=-0.348, P < 0.001), as shown in Table 5.
Table 5
Correlation analysis of WBC, NEU, NEU-R, Hs-CRP and Alb
Parameters | NEU | NEU-R | Hs-CRP | Alb |
WBC | r = 0.959 | r = 0.675 | r = 0.389 | r = 0.345 |
P = 0.000 < 0.05 | P = 0.000 < 0.05 | P = 0.000 < 0.05 | P = 0.000 < 0.05 |
n = 155 | n = 155 | n = 137 | n = 155 |
NEU | | r = 0.830 | r = 0.431 | r = 0.353 |
| P = 0.000 < 0.05 | P = 0.000 < 0.05 | P = 0.000 < 0.05 |
| n = 155 | n = 137 | n = 155 |
NEU-R | | | r = 0.477 | r=-0.389 |
| | P = 0.000 < 0.05 | P = 0.000 < 0.05 |
| | n = 137 | n = 156 |
Hs-CRP | | | | r = 0.348 |
| | | P = 0.000 < 0.05 |
| | | n = 138 |
WBC, Leukocyte count; NEU, Neutrophil count; NEU-R, Neutrophil rate; Hs-CRP, High-sensitivity C-reactive protein; Alb, Albumin.
In summary, WBC, NEU, NEU-R and Hs-CRP were positively correlated with each other (P < 0.05), and negatively correlated with Alb (P < 0.05). AST was the only clinical parameter correlated with acitretin efficacy, but not correlated with other serum parameters (P > 0.05).