|Year : 2020 | Volume
| Issue : 4 | Page : 199-204
C-reactive protein to albumin ratio: Is a new parameter for the disease severity in patients with psoriasis vulgaris?
Funda Kemeriz1, Burcu Tuğrul2, Sibel Çiğdem Tuncer3
1 Department of Dermatology, Faculty of Medicine, Aksaray University, Aksaray, Turkey
2 Department of Dermatology, Health Science University Ankara Oncology Training and Research Hospital, Ankara, Turkey
3 Department of Biochemistry, Faculty of Medicine, Aksaray University, Aksaray, Turkey
|Date of Submission||06-May-2020|
|Date of Decision||07-Jul-2020|
|Date of Acceptance||24-Jul-2020|
|Date of Web Publication||16-Dec-2020|
Dr. Funda Kemeriz
Department of Dermatology, Aksaray University Faculty of Medicine 68200 Aksaray
Source of Support: None, Conflict of Interest: None
Background: C-reactive protein to albumin ratio (CAR) is an inflammatory marker that is considered to have prognostic value in many inflammatory diseases. Objectives: In this study, we aimed to investigate whether there is a correlation between CAR value and disease severity in patients with psoriasis. Methods: The study included 70 plaque-type psoriasis patients and 67 healthy controls. CAR value was calculated after C-reactive protein (CRP) and albumin analysis was performed, Psoriasis Area and Severity Index (PASI) scores were documented. CAR value was compared with PASI scores in patient group. White blood cell count, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, erythrocyte sedimentation rate (ESR), and mean platelet volume and CAR values were compared among these groups. We investigated the most significant parameter for disease severity. In addition, to detect relationship between CAR, disease duration and patients' age and healthy controls, correlation analysis was performed. Results: The median CAR value was found statistically significant higher in the patient group than in the control group (P < 0.001). A significant difference of median CRP, albumin, CAR (all P values are <0.001) and ESR (P = 0.024) were found among the three groups which were arranged according to the severity of the disease. Among these parameters, CAR was found as the most associated parameter with the severity of psoriasis using receiving operator characteristic analysis. Conclusion: CAR value could be a useful parameter for evaluating disease severity, management of disease activity, and follow-up strategies.
Keywords: Albumin, C-reactive protein, C-reactive protein to albumin ratio, disease severity, psoriasis
|How to cite this article:|
Kemeriz F, Tuğrul B, Tuncer S&. C-reactive protein to albumin ratio: Is a new parameter for the disease severity in patients with psoriasis vulgaris?. Dermatol Sin 2020;38:199-204
|How to cite this URL:|
Kemeriz F, Tuğrul B, Tuncer S&. C-reactive protein to albumin ratio: Is a new parameter for the disease severity in patients with psoriasis vulgaris?. Dermatol Sin [serial online] 2020 [cited 2021 Jun 18];38:199-204. Available from: https://www.dermsinica.org/text.asp?2020/38/4/199/303704
| Introduction|| |
Psoriasis is a chronic immune-mediated inflammatory disease with unknown etiology. The prevalence of the disease is approximately 2%–11% in Caucasians; and significantly lower in Asian population. Psoriasis and its related systemic comorbidities have a major impact on the patients' health-related quality of life. The pathogenesis of the disease is associated with excessive secretion of dermal, systemic, and pro-inflammatory cytokines such as interleukins and tumor necrosis factor alpha.,, Over-secretion of these agents results in inflammatory cell infiltration, keratinocyte differentiation, and proliferation and vascular changes and the formation of clinically erythematous and scaly plaques located on the scalp, knee, or elbow.,
C-reactive protein (CRP) is an easily detectable acute-phase protein with a short half-life that is synthesized by the liver following stimulation by cytokines in response to infection, trauma, and other inflammatory conditions; so it is used by clinicians as a marker for these events., Some studies have suggested that CRP could also be used to evaluate disease severity, and treatment effectiveness in patients with psoriasis vulgaris.,,
Albumin, which is synthesized by the liver, is a negative acute-phase protein and that shows decreased levels in acute inflammation. Some studies have also suggested that it can be used as a prognostic marker in patients with inflammation and infection.,
On the basis of the findings for these two markers, the CRP/albumin ratio (CAR) has been recently studied as an independent prognostic marker in patients with systemic inflammation, such as a those with infection, malignancy, and other inflammatory diseases, and higher CAR values have been suggested to be effective indicators of poor prognosis in these patients.,,,,
Nevertheless, to the best of our knowledge, the prognostic significance of CAR in patients with chronic plaque-type psoriasis has not been studied to date. In this study, we aimed to evaluate the association of CAR values with disease severity in patients with psoriasis vulgaris, determine whether it can be used as a prognostic marker, and investigate other inflammatory parameters such as erythrocyte sedimentation rate (ESR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), white blood cell count (WBC), and mean platelet volume (MPV) in patients with plaque-type psoriasis.
| Materials and Methods|| |
This single-center, prospective-controlled study was performed with Institutional Review Board protocol approval (dated June 24, 2019; number 06/18 from the Local Committee of Clinical and Laboratory Research Ethics in Aksaray University). Seventy patients aged 18–65 years, with clinically and histologically diagnosed psoriasis vulgaris admitted to our dermatology outpatient clinics between July and December 2019, were enrolled in this study. Sixty-seven healthy controls without a family history of psoriasis vulgaris were also included in the study. The study group consisted of patients with plaque-type psoriasis. We excluded patients with psoriatic arthritis, pustular psoriasis, palmoplantar psoriasis, obvious malignancies, active and chronic infections, metabolic syndrome, or systemic inflammatory and immunosuppressive diseases; participants who were receiving any topical therapy within the past 2 weeks or systemic therapy within the past 3 months; and smokers, and patients drinking alcohol. Written informed consent was obtained from all participants before the study.
Psoriasis Area and Severity Index (PASI) scores were used for assessing disease severity. Patients were divided into three groups according to disease severity: mild psoriasis, PASI scores below 7; moderate psoriasis, PASI scores of 7–15; severe psoriasis PASI scores above 15. Demographic features of the patients and the mean PASI scores were recorded and documented for the patient group.
An automated blood cell counter was used for complete blood count measurements (Mindray BC-6000, Shenzhen, China). Serum CRP and albumin levels were measured using the nephelometric method (Beckman Coulter Inc, Brea, CA, USA). Ves-Matic Cube 80 automatic analyser was used for the determination of ESR. We examined blood test parameters including, CRP, and albumin levels; WBC, neutrophil, lymphocyte, and platelet counts; and MPV and ESR. Then, we calculated the CAR, NLR, and PLR values of the study and control groups. The reference CRP levels were 0–5 mg/L, while the reference albumin levels were 3.5–5.2 g/L in our biochemistry laboratory.
We first compared the CAR values of the patients with different PASI scores to determine whether they showed a correlation with disease severity, and CAR values in three groups based of PASI scores were also compared.
The data were statistically analyzed using SPSS 20.0 software (IBM Corp, Armonk, NY, USA). A P < 0.05 was considered statistically significant.
The distribution pattern of the data was determined using the Kolmogorov–Smirnov normality test. Results are presented as mean ± standard deviation for normally distributed data and median (min-max) for abnormally distributed data. The data of age; gender; albumin level; WBC, neutrophil, lymphocyte, and platelet counts; and MPV showed a normal distribution (P > 0.05), so we used the t-test. On the other hand, CAR, CRP level, NLR, PLR, and ESR values did not show a normal distribution (P < 0.05), so we used the Mann–Whitney U test to compare the medians values for patients and healthy controls.
We used one-way analysis of variance (ANOVA) to compare the albumin level; WBC, neutrophil, lymphocyte, and platelet counts; and MPV values in the three groups categorized on the basis of PASI scores. We used Kruskal–Wallis test to compare the median CAR, CRP, NLR, PLR, and ESR values of three PASI-based groups. To detect the parameter most significantly associated with the severity of psoriasis; and to determine a cut off value, we used the receiving operator characteristic (ROC) curve analysis test.
To detect the relationship among CAR, disease duration, and age of patients and healthy controls, bivariate correlation was performed. To control the effect of the age of the patients on the relationship between disease duration and CAR, partial correlation was performed.
| Results|| |
A total of 70 patients were diagnosed with psoriasis in this study, including 37 (52.9%) males and 33 (47.1%) females. The mean patient age was 38.38 ± 13.89 years. In the control group, 40.3% (n = 27) of the participants were male, while 59.7% (n = 40) were female. The mean age in the control group was 34.58 ± 15.06 years. There were no significant differences between patient and control groups in terms of age and sex (P > 0.05). Demographic characteristics and median values for CRP; and albumin levels, ESR, and mean values for WBC, neutrophil, lymphocyte, and platelet counts; and MPV are presented in [Table 1].
|Table 1: Comparison of demographic features, biochemical parameters and C-reactive protein to albumin ratio, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio values between patient and control groups|
Click here to view
The median CAR values were significantly higher in the patient group compared to the control group (P < 0.001). However, the median NLR value and the mean PLR values did not show any significant difference between groups (P values respectively: 0.56; 0.796) [Table 1].
The median PASI was 11.75 (range = 3.6–37.8) in the patient group. The number of patients with PASI scores below 7 (mild psoriasis), 7–15 (moderate), and above 15 (severe psoriasis) was 19 (27.1%), 26 (37.1%), and 25 (35.7%), respectively. One-way ANOVA did not show significant difference in the mean WBC, neutrophil, lymphocyte, and platelet counts; MPV and PLR values among the three groups (P > 0.05). The mean and P values are presented in [Table 2]. The median values of CAR, WBC count, NLR, PLR, and MPV are presented in [Table 2]. In the Kruskal–Wallis test, the median NLR value did not significantly differ among the three patient groups (P = 0.491). However, significant differences of median CRP; and albumin levels, CAR (all P values were <0.001), and ESR (P = 0.024) were evident among the three groups.
|Table 2: Comparison of biochemical parameters and C-reactive protein to albumin ratio, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio values according to the Psoriasis Area and Severity Index scores in the patient group|
Click here to view
[Figure 1] presents the graph of the ROC analysis of the parameters, including CAR, CRP; and albumin levels, and ESR. ROC analysis revealed that; CAR had a greater area under curve (0.928) than both CRP level (0.909) and ESR (0.510), while albumin had an area above the curve (0.814) showing a negative correlation with severity. Thus, CAR was the parameter showing the greatest association with the severity of psoriasis. The cut off CAR value for severe psoriasis was 2.58, with a sensitivity of 81% and specificity of 77%.
|Figure 1: The graph of the receiving operator characteristic analysis ROC-receiver operating characteristic; CAR: C-reactive protein to albumin ratio, CRP: C-reactive protein, ESR: Erythrocyte sedimentation rate|
Click here to view
A very strong positive statistically significant correlation was detected between CAR values and PASI scores in psoriasis patients (r = 0.873 P < 0.001).
The median disease duration was 8 years (range = 1–50 years) (min: 1-max: 50). We found a positive statistically significant correlation between CAR values and disease duration in the patient group (r = 0.386 P = 0.001). Although CAR values and age showed no positive correlation in the control group (r = 0.049 P = 0.694), the two parameters showed a positive correlation in the patient group (r = 0.347 P = 0.003). The CAR value also showed a statistically significant positive correlation with disease duration after controlling the findings for age in the patient group (r = 0.36 P = 0.002).
| Discussion|| |
Psoriasis is a chronic inflammatory skin disease. Immunological and inflammatory mechanisms along with the genetic background are known to play roles in the disease course, the etiopathogenesis of the disease has not been completely understood. In addition to presenting with typical skin lesions such as erythematous, scaly plaques, the disease also shows severe systemic involvement and comorbidities, including psoriatic arthritis, cardiometabolic disease, gastrointestinal disease, chronic kidney disease, malignancy, psychiatric disorders, and infections., These comorbidities and systemic involvement have been associated with disease severity and duration. The PASI score has been used for evaluating psoriasis severity and is a gold standard assessment tool to determine the need for systemic therapy.
In patients with psoriasis vulgaris, increased serum CRP levels have been identified as a biomarker of acute inflammation in previous studies and some of which suggested that it was correlated with disease severity.,,,,,,
Similarly, reduced albumin levels in psoriasis patients have been attributed to lowered rates of albumin synthesis or increased rates of turnover. Hypoalbuminemia in psoriasis patients may also be the result of increased endogenous catabolism of albumin without significant loss through urine, stools, or skin. Increased uptake of albumin by liver and splenic macrophages has also been discussed as one of the potential mechanisms.,,
CAR has been recently used to predict patient prognosis in various types of malignancies, including pancreatic cancer, gastric cancer, colorectal cancer, and small cell lung carcinoma. These studies suggested that tumor-elicited inflammation plays a crucial role in various types of malignant transformation and tumor progression; thus, high CAR value may be a potential prognostic indicator in these malignancies.,,,,
Previous studies have also demonstrated that the CAR value could be used as a prognostic parameter in many inflammatory diseases such as recurrent aphthous stomatitis, Crohn's disease, sepsis, and acute pancreatitis.,, Since overexpression of interleukin-6 is associated with increased CRP and decreased albumin levels, the CAR value may have prognostic significance in the inflammatory response in these diseases.
In a study assessing 72 patients with recurrent aphthous stomatitis and 60 controls, Kayabasi et al. found that the median CAR value was significantly higher in the active lesion group, than in the inactive lesion group and the control group, and they suggested that CAR could be used as a predictive parameter for assessing inflammation and oral ulcer activity in patients with recurrent aphthous stomatitis. Qin et al. evaluated CAR values in 100 Crohn's disease patients, and they suggested that the CAR value was a useful biomarker for identifying Crohn's disease activity. Ranzani et al. evaluated 334 patients with septicemia and suggested that the CAR value was an independent risk factor for mortality at 90 days in patients with septicemia.
To the best of our knowledge, our study is the first to evaluate the CAR value in relation to disease severity in patients with plaque-type psoriasis. The CAR value was found to be higher in the patient group than in the control group and showed strong correlation with PASI scores. Moreover, in comparison with CRP and albumin levels and ESR, CAR showed more significant predictive ability to determine the severity of psoriasis. The cut off CAR value for severe psoriasis was determined to be 2.58, with a sensitivity of 81% and specificity of 77%. In addition, increased CAR value was shown to be associated with disease duration.
Despite these findings, our study had some limitations. First, we did not compare the CAR values before and after systemic therapy in patients, which could be the topic of future research. Second, we did not evaluate the CAR values in patients with other types of psoriasis.
The CAR value, which has been used for the prediction of prognosis and mortality in many inflammatory diseases, might yield some clues about disease severity, progression, and the long-term destructive effects of psoriasis. Previous studies on albumin and CRP levels in psoriasis reported; decreased albumin and increased CRP levels, but these studies did not evaluate the CAR value to determine whether it could be a prognostic marker for psoriasis, especially in patients with severe disease. In addition, some studies, suggested that NLR, PLR, MPV, and ESR could be used in psoriasis patients due to the presence of inflammation. However, our study showed no significant intergroup difference in the NLR, PLR, and MPV values and indicated the CAR value showed greater correlation with the severity of psoriasis than CRP, and albumin levels and ESR.
| Conclusion|| |
Psoriasis is a chronic, inflammatory skin disease that has even been considered as a systemic inflammatory disease because it shows some severe systemic effects and comorbidities. CAR has been suggested as a novel prediction parameter in many inflammatory diseases. Thus, we think the CAR value may be used as a prognostic marker for assessing disease severity, managing disease activity, and evaluating treatment procedures and follow-up strategies.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Chiu HY, Wang TS, Chen PH, Hsu SH, Tsai YC, Tsai TF. Psoriasis in Taiwan: From epidemiology to new treatments. Dermatol Sin 2018;36:115-23.
Ghatnekar O, Ljungberg A, Wirestrand LE, Svensson A. Costs and quality of life for psoriatic patients at different degrees of severity in southern Sweden-A cross-sectional study. Eur J Dermatol 2012;22:238-45.
Yu S, Wu X, Zhou Y, Sheng L, Jena P.K, Han D, et al
. A western diet, but not a high-fat and low-sugar diet, predisposes mice to enhanced susceptibility to imiquimod-induced psoriasiform dermatitis. J Investig Dermatol 2019; 139: 1404-7.
Yu S, Wu X, Shi Z, Huynh M, Jena PK, Sheng L, et al
. Diet-induced obesity exacerbates imiquimod-mediated psoriasiform dermatitis in anti-PD-1 antibody-treated mice: Implications for patients being treated with checkpoint inhibitors for cancer. J Dermatol Sci 2020;97:194-200.
Shi Z, Wu X, Yu S, Huynh M, Jena P.K, Nguyen M, et al
. Short-term exposure to a western diet induces psoriasiform dermatitis by promoting accumulation of IL-17A-producing γδ T cells. J Investig Dermatol 2020; S0022-202X(20)30140-8.
Wahl AK, Robinson HS, Langeland E, Larsen MH, Krogstad AL, Moum T. Clinical characteristics associated with illness perception in psoriasis. Acta Derm Venereol 2014;94:271-5.
Kemeriz F, Gönül M, Cengiz FP, Emiroğlu N, Cemil BÇ. Evaluation of neopterin level and disease severity in patients with psoriasis vulgaris treated with narrowband UVB. Indian J Dermatol 2019;64:447-50.
] [Full text]
Kinoshita A, Onoda H, Imai N, Nishino H, Tajiri H. C-reactive protein as a prognostic marker in patients with hepatocellular carcinoma. Hepatogastroenterology 2015;62:966-70.
Póvoa P, Coelho L, Almeida E, Fernandes A, Mealha R, Moreira P, et al
. Early identification of intensive care unit-acquired infections with daily monitoring of C-reactive protein: A prospective observational study. Crit Care 2006;10:R63.
Gerkowicz A, Pietrzak A, Szepietowski JC, Radej S, Chodorowska G. Biochemical markers of psoriasis as a metabolic disease. Folia Histochem Cytobiol 2012;50:155-70.
Coimbra S, Oliveira H, Reis F, Belo L, Rocha S, Quintanilha A, et al
. C-reactive protein and leucocyte activation in psoriasis vulgaris according to severity and therapy. J Eur Acad Dermatol Venereol 2010;24:789-96.
Coimbra S, Oliveira H, Reis F, Belo L, Rocha S, Quintanilha A, et al
. Circulating adipokine levels in portugese patients with psoriasis vulgaris according to body mass index, severity and therapy. J Eur Acad Dermatol Venereol 2010;24:1386-94.
Don BR, Kaysen G. Semin. Serum albumin: Relationship to inflammation and nutrition. Dial 2004;17:432-7.
Kayabasi S, Hizli O, Cayir S. A novel predictor parameter for active recurrent aphthous stomatitis: C-reactive protein to albumin ratio. Cureus 2019;11:e5965.
Ranzani OT, Zampieri FG, Forte DN, Azevedo LC, Park M. C-reactive protein/albumin ratio predicts 90-day mortality of septic patients. PLoS One 2013;8:e59321.
Saito H, Kono Y, Murakami Y, Shishido Y, Kuroda H, Matsunaga T, et al
. Prognostic significance of the preoperative ratio of C-reactive protein to albumin and neutrophil-lymphocyte ratio in gastric cancer patients. World J Surg 2018;42:1819-25.
Povoa P, Almeida E, Moreira P, Fernandes A, Mealha R, Aragao A, et al
. C-reactive protein as an indicator of sepsis. Intensiv. Care Med. 1998;24:1052-1056.
Wu M, Guo J, Guo L, Zuo Q. The C-reactive protein/albumin ratio predicts overall survival of patients with advanced pancreatic cancer. Tumour Biol 2016;37:12525-33.
Llamas-Velasco M, de la Cueva P, Notario J, Martínez-Pilar L, Martorell A, Moreno-Ramírez D. Moderate psoriasis: A proposed definition. Actas Dermosifiliogr 2017;108:911-7.
Bae YS, Van Voorhees AS, Hsu S, Korman NJ, Lebwohl MG, Young M, et al
. Review of treatment options for psoriasis in pregnant or lactating women: From the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol 2012;67:459-77.
Takeshita J, Grewal S, Langan SM, Mehta NN, Ogdie A, Van Voorhees AS, et al
. Psoriasis and comorbid diseases: Implications for management. J Am Acad Dermatol 2017;76:393-403.
Acar EM, İlter N, Elbeg S. Association of leptin, resistin, and high-molecular-weight adiponectin levels with psoriasis area and severity index scores, obesity, and insulin resistance in psoriasis patients. Dermatol Sin 2019;37:33-9. [Full text]
Christophers E, van de Kerkhof PCM. Severity, heterogeneity and systemic inflammation in psoriasis. J Eur Acad Dermatol Venereol 2019;33:643-7.
Yazici C, Köse K, Utaş S, Tanrikulu E, Taşlidere N. A novel approach in psoriasis: First usage of known protein oxidation markers to prove oxidative stress. Arch Dermatol Res 2016;308:207-12.
Asahina A, Umezawa Y, Yanaba K, Nakagawa H. Serum C-reactive protein levels in Japanese patients with psoriasis and psoriatic arthritis: Long-term differential effects of biologics. J Dermatol 2016;43:779-84.
Ferretti G, Bacchetti T, Campanati A, Simonetti O, Liberati G, Offidani A. Correlation between lipoprotein(a) and lipid peroxidation in psoriasis: Role of the enzyme paraoxonase-1. Br J Dermatol 2012;166:204-7.
Gokalp H. Effect of psoriasis severity on inflammation parameters: Controlled study. Turkderm-Turk Arch Dermatol Venereol 2018;52:91-4.
Worm AM, Rossing N. Transcapillary escape rate of albumin and plasma volume in patients with varying degrees of psoriasis. Br J Dermatol 1977;97:423-7.
Worm AM, Taaning E, Rossing N, Parving HH, Clemmensen OJ. Distribution and degradation of albumin in extensive skin disease. Br J Dermatol 1981;104:389-96.
Altmeyer P, Munz D, Holzmann H, Hör G. Functional studies of sessile macrophages in liver and spleen of psoriatics. Dermatologica 1983;166:15-22.
Wu J, Tan W, Chen L, Huang Z, Mai S. Clinicopathologic and prognostic significance of C-reactive protein/albumin ratio in patients with solid tumors: An updated systemic review and meta-analysis. Oncotarget 2018;9:13934-47.
Fu YJ, Li KZ, Bai JH, Liang ZQ. C-reactive protein/albumin ratio is a prognostic indicator in Asians with pancreatic cancers: A meta-analysis. Medicine (Baltimore) 2019;98:e18219.
Shibutani M, Maeda K, Nagahara H, Iseki Y, Ikeya T, Hirakawa K. Prognostic significance of the preoperative ratio of C-reactive protein to albumin in patients with colorectal cancer. Anticancer Res 2016;36:995-1001.
Zhou T, Zhan J, Hong S, Hu Z, Fang W, Qin T, et al
. Ratio of C-reactive protein/albumin is an inflammatory prognostic score for predicting overall survival of patients with small-cell lung cancer. Sci Rep 2015;5:10481.
Qin G, Tu J, Liu L, Luo L, Wu J, Tao L, et al
. Serum albumin and C-reactive protein/albumin ratio are useful biomarkers of crohn's disease activity. Med Sci Monit 2016;22:4393-400.
Wang X, Cui Z, Li H, Saleen AF, Zhang D, Miao B, et al
. Nosocomial mortality and early prediction of patients with severe acute pancreatitis. J Gastroenterol Hepatol 2010;25:1386-93.
Fairclough E, Cairns E, Hamilton J, Kelly C. Evaluation of a modified early warning system for acute medical admissions and comparison with C-reactive protein/albumin ratio as a predictor of patient outcome. Clin Med (Lond) 2009;9:30-3.
Sen BB, Rifaioglu EN, Ekiz O, Inan MU, Sen T, Sen N. Neutrophil to lymphocyte ratio as a measure of systemic inflammation in psoriasis. Cutan Ocul Toxicol 2014;33:223-7.
Ünal M, Küçük A, Ünal GÜ, Balevi Ş, Tol H, Aykol C, et al
. Psoriasiste ortalama trombosit hacmi, nötrofil/lenfosit oranı ve trombosit/lenfosit oranı. Turkderm 2015; 49: 112-6.
[Table 1], [Table 2]