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Evaluation of red blood cell distribution width in patients with psoriatic arthritis
The Egyptian Rheumatologist xxx (xxxx) xxx
Contents lists available at ScienceDirect
The Egyptian Rheumatologist journal homepage: www.elsevier.com/locate/ejr
Evaluation of red blood cell distribution width in patients with psoriatic arthritis Cem Ozisler ⇑, Sevinc Can Sandikci Department of Rheumatology, University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey
a r t i c l e
i n f o
Article history: Received 7 June 2019 Accepted 8 June 2019 Available online xxxx Keywords: C-reactive protein Erythrocyte sedimentation rate Inflammation Psoriatic arthritis Red blood cell distribution width
a b s t r a c t Aim of the work: To evaluate the red blood cell distribution width (RDW) values in psoriatic arthritis (PsA) patients and to study the relationship between these values and disease activation. Patients and methods: Forty seven patients with PsA and 56 age- and sex matched healthy controls were included in this study. Laboratory test results of both groups were retrospectively collected from medical records; these included levels for white blood cell count, hemoglobin, platelet, RDW, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Disease activity score (DAS28) was used to evaluate disease activity. Results: The study comprised 47 PsA patients (32 females and 15 males) (F:M 2.1:1) with a mean age of 39.2 ± 9.9 (20–54) years and mean disease duration was 3.3 ± 1.94 (1–8) years. 39 (83%) patients were receiving monotherapy, 8 (17%) were receiving combined therapy. The RDW values were significantly higher when comparing active disease period (16 ± 3.9) of PsA patients versus inactive disease period (14.2 ± 1.04) and controls (14.03 ± 1.2) (p < 0.001). Otherwise, no significant differences were found when comparing inactive disease period of PsA patients versus controls (p = 0.18). RDW values of active disease period of PsA patients significantly correlated with ESR (r = 0.57, p < 0.001), CRP (r = 0.4, p = 0.006) and DAS28 (r = 0.42, p = 0.003). Conclusions: Increased RDW is associated with active disease period of PsA patients. RDW seems to be a surrogate marker of the inflammation, like CRP and ESR. It is included in the complete blood count thus its measurement does not need any additional costs. RDW may be a potential marker to evaluate disease activity of PsA. Ó 2019 Egyptian Society of Rheumatic Diseases. Publishing services provided by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction Psoriatic arthritis (PsA) is a complex type of progressive inflammatory arthritis associated with psoriasis. The pooled prevalence and incidence rates of PsA are 133 patients/100,000 subjects and 83/100,000 person-years, respectively [1,2]. Prevalence of PsA has been reported 5.8–40.9% among patients suffering from psoriasis [1]. A recent meta-analysis indicated that there is no gender predilection in patients with PsA [2]. PsA shares genetic and clinical features with other forms of spondyloarthritis and affects different structures of the musculoskeletal system in addition to the skin and the nail [1,3]. In 1973, Moll and Wright described 5 major phenotypes of PsA: symmetrical polyarthritis, asymmetrical
Peer review under responsibility of Egyptian Society of Rheumatic Diseases. ⇑ Corresponding author at: Department of Rheumatology, University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Sehit Omer Halisdemir Street, Altindag, Ankara TR-06100, Turkey. E-mail address: [email protected] (C. Ozisler).
oligoarthritis, distal interphalangeal joint involvement, axial disease, and arthritis mutilans [4]. The red blood cell distribution width (RDW) is a simple and inexpensive parameter included in the hemogram with automatic analyzers. RDW is a morphological index of circulating red blood cells (RBC) and reflects the degree of heterogeneity of erythrocyte volume (traditionally known as anisocytosis) [5,6]. The standard deviation of RBC volumes is divided by the mean corpuscular volume (MCV) to determine the RDW [5]. Previously, the clinical use of RDW was limited to the differential diagnosis of anemias. During the past decade, RDW has been used as an inflammatory marker, similar to the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Increased RDW has been reported to reflect systemic inflammation [7]. Recent studies have demonstrated that RDW values were increased in many cardiovascular diseases (CVD), such as acute coronary syndrome, atrial fibrillation, heart failure, and hypertension. It has been also reported that an increased RDW is associated with an increased mortality and morbidity in patients with CVD
https://doi.org/10.1016/j.ejr.2019.06.001 1110-1164/Ó 2019 Egyptian Society of Rheumatic Diseases. Publishing services provided by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article as: C. Ozisler and S. C. Sandikci, Evaluation of red blood cell distribution width in patients with psoriatic arthritis, The Egyptian Rheumatologist, https://doi.org/10.1016/j.ejr.2019.06.001
2
C. Ozisler, S.C. Sandikci / The Egyptian Rheumatologist xxx (xxxx) xxx
[5,8–11]. However, RDW is increased in a variety of other diseases, including diabetes mellitus, kidney disease, colorectal cancer and inflammatory bowel disease [5,12–14]. To date, many studies have investigated the value of RDW to assess the disease activity of rheumatologic disorders, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), polymyositis and dermatomyositis [15–18]. To the best of our knowledge, there have been no reports regarding RDW in patients with PsA, to date. Therefore the current study aimed to investigate the RDW values in PsA patients and to study the relationship between these values and disease activity.
2. Patients and methods Forty seven patients with PsA and 56 age- and sex-matched healthy controls were included in this study. Medical records of patients and controls were reviewed retrospectively from the electronic database of University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital. All PsA patients fulfilled the Classification criteria for the diagnosis of Psoriatic Arthritis (CASPAR) [19]. Patients and controls were excluded if they had one of the following comorbidites/conditions: other autoimmune diseases, such as RA, SLE, Sjögren’s syndrome, malignancy, acute or chronic infection, renal disease, liver disease, hypertension, diabetes mellitus, coronary artery disease, cerebrovascular disease, pregnancy or postpartum 6 months, hematologic disease or received blood transfusion during the past 4 months. The study protocol was approved by the Clinical Trials Ethics Committee of Diskapi Yildirim Beyazit Training and Research Hospital, University of Health Sciences, Ankara, Turkey. Laboratory test results were collected from medical records including the white blood cell (WBC) count, hemoglobin (Hb), platelet (PLT), RDW, ESR and CRP. Disease activity score 28 (DAS28) was evaluated [20]. All PsA subjects had at least one clinically active and inactive disease per-
Table 1 Medications used by the psoriatic arthritis patients. Medications n (%)
PsA patients (n = 47)
Methotrexate (MTX) Sulfasalazine (SAZ) Leflunomide (LFN) MTX + SAZ Etanercept Etanercept + MTX Adalimumab Adalimumab + MTX Golimumab
33 (70.2) 1 (2.1) 1 (2.1) 4 (8.5) 2 (4.3) 2 (4.3) 1 (2.1) 2 (4.3) 1 (2.1)
PsA: psoriatic arthritis
iod. Thus, RDW levels in both the active and inactive disease periods of all patients were compared. The active disease period was considered with at least one swollen and tender joint and DAS28 2.6, while in inactive disease period the patient had no symptoms, swollen or tender joint and DAS28 was <2.6. Statistical analysis: The statistical package for social sciences program version 10 (SPSS Inc., Chicago, IL) was used. Descriptive statistics were expressed as mean ± standard deviation, frequency and percentages. Shapiro-Wilk test was used to check the normality of distribution. Student’s t-test and Mann-Whitney U test were used to compare between two independent groups parametrically and non-parametrically distributed. The Pearson Chi-square test was used to evaluate categorical variables. Wilkonson test and paired-t test was used to measure the significance between two dependent groups parametrically and non-parametrically distributed. The relationships between variables were analyzed using Spearman’s correlation coefficients. A p value of <0.05 was considered significant. 3. Results The study comprised 47 PsA patients (32 females and 15 males) (F:M 2.1:1) with a mean age of 39.2 ± 9.9 (20–54) years and 56 age (39.6 ± 9.8; 21–55 years) and sex (37 females and 19 males; F:M 1.9:1) matched controls (p = 0.78, p = 0.83, respectively). Mean disease duration was 3.3 ± 1.94 (1–8) years. 39 (83%) patients were receiving monotherapy, 8 (17%) were receiving combined therapy. Current treatment characteristics are summarized in Table 1. The DAS28 levels in the active disease period of PsA patients were significantly higher than the inactive disease period (p < 0.001). The RDW was significantly higher when comparing active disease period of PsA patients versus inactive disease period and controls (p < 0.001). No significant differences were found when comparing inactive disease period of PsA patients versus controls (p = 0.18). WBC, PLT, ESR and CRP levels were significantly higher in active disease period of PsA patients compared to the controls and inactive disease period (p < 0.05). There were no significant differences between inactive disease period of PsA patients and controls in terms of these parameters (p > 0.05). The clinical characteristics of patients and controls were summarized in Table 2. RDW values of the active disease period of PsA patients significantly correlated with ESR (r = 0.57, p < 0.001), CRP (r = 0.4, p = 0.006) and DAS28 (r = 0.42, p = 0.003) values (Table 3). 4. Discussion The RDW is a reflection of the heterogeneity of erythrocyte volume and is traditionally used for the differential diagnosis of ane-
Table 2 Clinical characteristics of psoriatic arthritis patients during their active and inactive disease periods and the control. Variables
PsA patients (n = 47)
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WBC (x10 /mL) Hb (g/dL) PLT (x103/mL) RDW (%) ESR (mm/h) CRP (mg/L) DAS28
Controls (n = 56)
Active disease period
_ Inactive disease period
8.6 ± 2.2 13.4 ± 1.6 305.6 ± 80.6 16 ± 3.9 24 (2–79) 13.6 (1.3–115) 4.1 ± 0.7
7.4 ± 1.02 13.5 ± 1.5 279.9 ± 63.4 14.2 ± 1.04 13 (2–28) 4.4 (1.4–7.9) 1.89 ± 0.53
7.1 ± 1.6 13.9 ± 1.2 265.4 ± 59.6 14.03 ± 1.2 11 (2–20) 3.6 (1.4–7.9) –
Significance p1
p2
p3
<0.001 0.009 0.02 <0.001 <0.001 <0.001 –
0.08 0.09 0.28 0.18 0.11 0.06 –
0.001 0.24 0.02 <0.001 <0.001 <0.001 <0.001
PsA: psoriatic arthritis; WBC: white blood cell count; Hb: hemoglobin; PLT: platelet; RDW: red cell distribution width; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; DAS28: disease activity score 28. Data are presented as mean ± SD or median (range). P1: The difference between active disease period of PsA patients and controls; p2: The difference between inactive disease period of PsA patients and controls; p3: The difference between active and inactive disease periods of PsA patients. Bold values are significant at p < 0.05
Please cite this article as: C. Ozisler and S. C. Sandikci, Evaluation of red blood cell distribution width in patients with psoriatic arthritis, The Egyptian Rheumatologist, https://doi.org/10.1016/j.ejr.2019.06.001
C. Ozisler, S.C. Sandikci / The Egyptian Rheumatologist xxx (xxxx) xxx Table 3 Correlation between red cell distribution width in active disease period of PsA patients. Variables
ESR CRP DAS28
RDW in PsA patients (n = 47) r
p
0.57 0.4 0.42
<0.001 0.006 0.003
RDW: red cell distribution width; PsA: psoriatic arthritis; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; DAS28: disease activity score 28. Bold values are significant at p < 0.05
mias (eg, b-thalassemia minor and iron deficiency anemia) [5,7]. In the last years, a number of studies have demonstrated that this quick, simple and inexpensive parameter have multiple clinical applications; such as an inflammatory marker, a predictor of allcause mortality and a prognostic tool for morbidity and mortality in patients with acute or chronic conditions [5,7,21]. In rheumatologic disorders, such as RA, SLE and AS, many studies have investigated the value of RDW to assess the disease activity [15–17]. To the best of our knowledge, this retrospective study is the first to evaluate RDW levels in PsA patients. It was found that RDW values were increased significantly in active disease period of PsA patients than inactive disease period of PsA patients and controls. RDW values significantly correlated with ESR, CRP and DAS28 levels in active disease period of PsA patients. RDW can be considered a potential predictor of disease activity in PsA patients. To date, many studies have investigated the association between RDW and rheumatologic disorders. Tecer et al. showed that RA patients had higher RDW values than the controls and RDW values significantly correlated with DAS28 [15]. Results in another study indicated that RDW level was significantly increased in RA patients compared to osteoarthritis patients and healthy donors, and high levels of RDW were associated with elevated levels of inflammatory marker as CRP and ESR [22]. It has been recently reported that RDW was significantly higher in patients with AS compared with controls and was directly correlated with ESR, CRP and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [16,23]. In another study, Hu et al. showed that RDW was increased in SLE patients compared with controls and correlated with CRP, ESR and SLE disease activity [17]. Similarly, it was observed that RDW in familial Mediterranean fever (FMF), Henoch-Schonlein purpura (HSP), dermatomyositis and polymyositis patients was higher compared with that in the control [18,24,25]. Kim et al. reported that RDW was significantly correlated with Birmingham vasculitis activity score (BVAS) and predicts vasculitis activity and poor prognosis in patients with granulomatosis with polyangiitis [26]. RDW was significantly higher in Behçet’s disease patients, suggesting their value as promising inflammatory biomarkers [27]. The exact pathophysiologic mechanism of elevated RDW in inflammatory conditions remains unclear. Inflammatory diseases have various effects on hematopoiesis, so complete blood count is also affected. Proinflammatory cytokine levels become chronically increased in diseases which have prolonged inflammation [15]. These cytokines such as interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-a) can modulate erythropoiesis through inhibition of synthesis or activity of erythropoietin (EPO) and via desensitization of erythroid progenitors to EPO in bone marrow (disruption of response to EPO). Then, immature erythrocytes are _ released into the peripheral blood stream [5–7,15]. Inflammation can also lower erythrocyte survival via increasing RBC destruction [5,14]. These mechanisms leads to a more mixed population of erythrocyte volumes in the circulation. Thus, inflammation could contribute to anisocytosis, resulting in the increase of RDW level [5,15,22].
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The present study had some limitations that should be considered. First, this was a retrospective and single center study. Second, the number of patients was relatively low. But, this was due to the strict exclusion criterias. Third, the relationship between RDW and other more sensitive inflammatory markers such as IL-1, IL-6 and TNF-a were not evaluated. Comparing the RDW and other variables between active and inactive periods proved that RDW is a marker of inflammation in PsA which was the most powerful aspect of this study. In conclusion, increased RDW is associated with active disease period of PsA patients. So, RDW seems to be a surrogate marker of the inflammation, like CRP and ESR. Furthermore, RDW is included in the CBC test, which is routinely performed for followup of rheumatic diseases. For this reason, the measure of RDW doesn’t need any additional costs. RDW may provide extra information about inflammatory process and might be a potential marker to evaluate the disease activity of PsA. However, further prospective, multicenter and controlled studies with larger sample size are needed to validate the clinical value of RDW in patients with PsA and to determine a cut-off level of RDW for assessing disease activity with a high sensitivity and specifity. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Competing Interest None. References [1] Solmaz D, Eder L, Aydin SZ. Update on the epidemiology, risk factors, and disease outcomes of psoriatic arthritis. Best Pract Res Clin Rheumatol 2018;32:295–311. [2] Scotti L, Franchi M, Marchesoni A, Corrao G. Prevalence and incidence of psoriatic arthritis: a systematic review and meta-analysis. Semin Arthritis Rheum 2018;48:28–34. [3] Ritchlin CT, Colbert RA, Gladman DD. Psoriatic Arthritis. N Engl J Med 2017;376:2095–6. [4] Moll JM, Wright V. Psoriatic arthritis. Semin Arthritis Rheum 1973;3:55–78. [5] Salvagno GL, Sanchis-Gomar F, Picanza A, Lippi G. Red blood cell distribution width: a simple parameter with multiple clinical applications. Crit Rev Clin Lab Sci 2015;52:86–105. [6] Horta-Baas G, Romero-Figueroa MDS. Clinical utility of red blood cell distribution width in inflammatory and non-inflammatory joint diseases. Int J Rheum Dis 2019;22(1):47–54. [7] Silva Litao MK, Kamat D. Back to Basics: Red Blood Cell Distribution Width: Clinical Use beyond Hematology. Pediatr Rev 2018;39:204–9. [8] Avci E, Kiris T, Demirtas AO, Kadi H. Relationship between high-density lipoprotein cholesterol and the red cell distribution width in patients with coronary artery disease. Lipids Health Dis 2018;17:53. [9] Danese E, Lippi G, Montagnana M. Red blood cell distribution width and cardiovascular diseases. J Thorac Dis 2015;7:E402–11. [10] Lippi G, Turcato G. Cervellin G, Sanchis-Gomar F. Red blood cell distribution width in heart failure: a narrative review. World J Cardiol 2018;10:6–14. [11] Arbel Y, Weitzman D, Raz R, Steinvil A, Zeltser D, Berliner S, et al. blood cell distribution width and the risk of cardiovascular morbidity and all-cause mortality. A population-based study. Thromb Haemost 2014;111:300–7. [12] Al-Kindi SG, Refaat M, Jayyousi A, Asaad N, Al Suwaidi J, Abi Khalil C. Red Cell Distribution Width Is Associated with All-Cause and Cardiovascular Mortality in Patients with Diabetes. Biomed Res Int 2017;2017:5843702. [13] Yang D, Quan W, Wu J, Ji X, Dai Y, Xiao W, et al. The value of red blood cell distribution width in diagnosis of patients with colorectal cancer. Clin Chim Acta 2018;479:98–102. [14] Song CS, Park DI, Yoon MY, Seok HS, Park JH, Kim HJ, et al. Association between red cell distribution width and disease activity in patients with inflammatory bowel disease. Dig Dis Sci 2012;57:1033–8. _ NA, Çimen ÖB, Biçer A, et al. Can mean [15] Tecer D, Sezgin M, Kanık A, Incel platelet volume and red blood cell distribution width show disease activity in rheumatoid arthritis? Biomark Med 2016;10:967–74. [16] Peng YF, Zhang Q, Cao L, Liu Y, Chen D, Sun YK, et al. blood cell distribution width: a potential maker estimating disease activity of ankylosing spondylitis. Int J Clin Exp Med 2014;7:5289–95.
Please cite this article as: C. Ozisler and S. C. Sandikci, Evaluation of red blood cell distribution width in patients with psoriatic arthritis, The Egyptian Rheumatologist, https://doi.org/10.1016/j.ejr.2019.06.001
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[17] Hu ZD, Chen Y, Zhang L, Sun Y, Huang YL, Wang QQ, et al. Red blood cell distribution width is a potential index to assess the disease activity of systemic lupus erythematosus. Clin Chim Acta 2013;425:202–5. [18] Gao MZ, Huang YL, Wu XD, Xu QW, Ji R, Gu B, et al. blood cell distribution width and neutrophil to lymphocyte ratio are correlated with disease activity of dermatomyositis and polymyositis. J Clin Lab Anal 2018;32(1).. [19] Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H, CASPAR Study Group. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006;54:2665–73. [20] Prevoo MLL, Van’t Hof MA, Kuper HH, Van Leeuwen MA, Van De Putte LBA, Van Riel P. Modified disease activity scores that include twenty-eight-joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis. Rheumatol 1995;38:44–8. [21] Montagnana M, Danese E. Red cell distribution width and cancer. Ann Transl Med 2016;4:399.
[22] He Y, Liu C, Zeng Z, Ye W, Lin J, Ou Q. Red blood cell distribution width: a potential laboratory parameter for monitoring inflammation in rheumatoid arthritis. Clin Rheumatol 2018;37:161–7. [23] Gorial FI, Hassan AM. Diagnostic performance of red cell distribution width in adult Iraqi patients with ankylosing spondylitis. Arthritis 2018;2018:2904694. [24] Uslu AU, Yonem O, Aydin B, Uncu T, Seven D, Balta S, et al. cell distribution width is associated with albuminuria in adults with familial Mediterranean fever. Kaohsiung J Med Sci 2016;32:216–20. [25] Xu H, Li W, Mao JH, Pan YX. Association between red blood cell distribution width and Henoch-Schonlein purpura nephritis. Medicine (Baltimore) 2017;96:e7091. [26] Kim HJ, Yoo J, Jung SM, Song JJ, Park YB, Lee SW. Red blood cell distribution width can predict vasculitis activity and poor prognosis in granulomatosis with polyangiitis. Yonsei Med J 2018;59:294–302. [27] Gheita TA, Sakr BR, Rabea RE, Abd ElHamid SM. Value of hematological indices versus VEGF as biomarkers of activity in Behçet’s disease. Clin Rheumatol. 2019 epub ahead of print.
Please cite this article as: C. Ozisler and S. C. Sandikci, Evaluation of red blood cell distribution width in patients with psoriatic arthritis, The Egyptian Rheumatologist, https://doi.org/10.1016/j.ejr.2019.06.001
Contents lists available at ScienceDirect
The Egyptian Rheumatologist journal homepage: www.elsevier.com/locate/ejr
Evaluation of red blood cell distribution width in patients with psoriatic arthritis Cem Ozisler ⇑, Sevinc Can Sandikci Department of Rheumatology, University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey
a r t i c l e
i n f o
Article history: Received 7 June 2019 Accepted 8 June 2019 Available online xxxx Keywords: C-reactive protein Erythrocyte sedimentation rate Inflammation Psoriatic arthritis Red blood cell distribution width
a b s t r a c t Aim of the work: To evaluate the red blood cell distribution width (RDW) values in psoriatic arthritis (PsA) patients and to study the relationship between these values and disease activation. Patients and methods: Forty seven patients with PsA and 56 age- and sex matched healthy controls were included in this study. Laboratory test results of both groups were retrospectively collected from medical records; these included levels for white blood cell count, hemoglobin, platelet, RDW, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Disease activity score (DAS28) was used to evaluate disease activity. Results: The study comprised 47 PsA patients (32 females and 15 males) (F:M 2.1:1) with a mean age of 39.2 ± 9.9 (20–54) years and mean disease duration was 3.3 ± 1.94 (1–8) years. 39 (83%) patients were receiving monotherapy, 8 (17%) were receiving combined therapy. The RDW values were significantly higher when comparing active disease period (16 ± 3.9) of PsA patients versus inactive disease period (14.2 ± 1.04) and controls (14.03 ± 1.2) (p < 0.001). Otherwise, no significant differences were found when comparing inactive disease period of PsA patients versus controls (p = 0.18). RDW values of active disease period of PsA patients significantly correlated with ESR (r = 0.57, p < 0.001), CRP (r = 0.4, p = 0.006) and DAS28 (r = 0.42, p = 0.003). Conclusions: Increased RDW is associated with active disease period of PsA patients. RDW seems to be a surrogate marker of the inflammation, like CRP and ESR. It is included in the complete blood count thus its measurement does not need any additional costs. RDW may be a potential marker to evaluate disease activity of PsA. Ó 2019 Egyptian Society of Rheumatic Diseases. Publishing services provided by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction Psoriatic arthritis (PsA) is a complex type of progressive inflammatory arthritis associated with psoriasis. The pooled prevalence and incidence rates of PsA are 133 patients/100,000 subjects and 83/100,000 person-years, respectively [1,2]. Prevalence of PsA has been reported 5.8–40.9% among patients suffering from psoriasis [1]. A recent meta-analysis indicated that there is no gender predilection in patients with PsA [2]. PsA shares genetic and clinical features with other forms of spondyloarthritis and affects different structures of the musculoskeletal system in addition to the skin and the nail [1,3]. In 1973, Moll and Wright described 5 major phenotypes of PsA: symmetrical polyarthritis, asymmetrical
Peer review under responsibility of Egyptian Society of Rheumatic Diseases. ⇑ Corresponding author at: Department of Rheumatology, University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Sehit Omer Halisdemir Street, Altindag, Ankara TR-06100, Turkey. E-mail address: [email protected] (C. Ozisler).
oligoarthritis, distal interphalangeal joint involvement, axial disease, and arthritis mutilans [4]. The red blood cell distribution width (RDW) is a simple and inexpensive parameter included in the hemogram with automatic analyzers. RDW is a morphological index of circulating red blood cells (RBC) and reflects the degree of heterogeneity of erythrocyte volume (traditionally known as anisocytosis) [5,6]. The standard deviation of RBC volumes is divided by the mean corpuscular volume (MCV) to determine the RDW [5]. Previously, the clinical use of RDW was limited to the differential diagnosis of anemias. During the past decade, RDW has been used as an inflammatory marker, similar to the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Increased RDW has been reported to reflect systemic inflammation [7]. Recent studies have demonstrated that RDW values were increased in many cardiovascular diseases (CVD), such as acute coronary syndrome, atrial fibrillation, heart failure, and hypertension. It has been also reported that an increased RDW is associated with an increased mortality and morbidity in patients with CVD
https://doi.org/10.1016/j.ejr.2019.06.001 1110-1164/Ó 2019 Egyptian Society of Rheumatic Diseases. Publishing services provided by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article as: C. Ozisler and S. C. Sandikci, Evaluation of red blood cell distribution width in patients with psoriatic arthritis, The Egyptian Rheumatologist, https://doi.org/10.1016/j.ejr.2019.06.001
2
C. Ozisler, S.C. Sandikci / The Egyptian Rheumatologist xxx (xxxx) xxx
[5,8–11]. However, RDW is increased in a variety of other diseases, including diabetes mellitus, kidney disease, colorectal cancer and inflammatory bowel disease [5,12–14]. To date, many studies have investigated the value of RDW to assess the disease activity of rheumatologic disorders, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), polymyositis and dermatomyositis [15–18]. To the best of our knowledge, there have been no reports regarding RDW in patients with PsA, to date. Therefore the current study aimed to investigate the RDW values in PsA patients and to study the relationship between these values and disease activity.
2. Patients and methods Forty seven patients with PsA and 56 age- and sex-matched healthy controls were included in this study. Medical records of patients and controls were reviewed retrospectively from the electronic database of University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital. All PsA patients fulfilled the Classification criteria for the diagnosis of Psoriatic Arthritis (CASPAR) [19]. Patients and controls were excluded if they had one of the following comorbidites/conditions: other autoimmune diseases, such as RA, SLE, Sjögren’s syndrome, malignancy, acute or chronic infection, renal disease, liver disease, hypertension, diabetes mellitus, coronary artery disease, cerebrovascular disease, pregnancy or postpartum 6 months, hematologic disease or received blood transfusion during the past 4 months. The study protocol was approved by the Clinical Trials Ethics Committee of Diskapi Yildirim Beyazit Training and Research Hospital, University of Health Sciences, Ankara, Turkey. Laboratory test results were collected from medical records including the white blood cell (WBC) count, hemoglobin (Hb), platelet (PLT), RDW, ESR and CRP. Disease activity score 28 (DAS28) was evaluated [20]. All PsA subjects had at least one clinically active and inactive disease per-
Table 1 Medications used by the psoriatic arthritis patients. Medications n (%)
PsA patients (n = 47)
Methotrexate (MTX) Sulfasalazine (SAZ) Leflunomide (LFN) MTX + SAZ Etanercept Etanercept + MTX Adalimumab Adalimumab + MTX Golimumab
33 (70.2) 1 (2.1) 1 (2.1) 4 (8.5) 2 (4.3) 2 (4.3) 1 (2.1) 2 (4.3) 1 (2.1)
PsA: psoriatic arthritis
iod. Thus, RDW levels in both the active and inactive disease periods of all patients were compared. The active disease period was considered with at least one swollen and tender joint and DAS28 2.6, while in inactive disease period the patient had no symptoms, swollen or tender joint and DAS28 was <2.6. Statistical analysis: The statistical package for social sciences program version 10 (SPSS Inc., Chicago, IL) was used. Descriptive statistics were expressed as mean ± standard deviation, frequency and percentages. Shapiro-Wilk test was used to check the normality of distribution. Student’s t-test and Mann-Whitney U test were used to compare between two independent groups parametrically and non-parametrically distributed. The Pearson Chi-square test was used to evaluate categorical variables. Wilkonson test and paired-t test was used to measure the significance between two dependent groups parametrically and non-parametrically distributed. The relationships between variables were analyzed using Spearman’s correlation coefficients. A p value of <0.05 was considered significant. 3. Results The study comprised 47 PsA patients (32 females and 15 males) (F:M 2.1:1) with a mean age of 39.2 ± 9.9 (20–54) years and 56 age (39.6 ± 9.8; 21–55 years) and sex (37 females and 19 males; F:M 1.9:1) matched controls (p = 0.78, p = 0.83, respectively). Mean disease duration was 3.3 ± 1.94 (1–8) years. 39 (83%) patients were receiving monotherapy, 8 (17%) were receiving combined therapy. Current treatment characteristics are summarized in Table 1. The DAS28 levels in the active disease period of PsA patients were significantly higher than the inactive disease period (p < 0.001). The RDW was significantly higher when comparing active disease period of PsA patients versus inactive disease period and controls (p < 0.001). No significant differences were found when comparing inactive disease period of PsA patients versus controls (p = 0.18). WBC, PLT, ESR and CRP levels were significantly higher in active disease period of PsA patients compared to the controls and inactive disease period (p < 0.05). There were no significant differences between inactive disease period of PsA patients and controls in terms of these parameters (p > 0.05). The clinical characteristics of patients and controls were summarized in Table 2. RDW values of the active disease period of PsA patients significantly correlated with ESR (r = 0.57, p < 0.001), CRP (r = 0.4, p = 0.006) and DAS28 (r = 0.42, p = 0.003) values (Table 3). 4. Discussion The RDW is a reflection of the heterogeneity of erythrocyte volume and is traditionally used for the differential diagnosis of ane-
Table 2 Clinical characteristics of psoriatic arthritis patients during their active and inactive disease periods and the control. Variables
PsA patients (n = 47)
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WBC (x10 /mL) Hb (g/dL) PLT (x103/mL) RDW (%) ESR (mm/h) CRP (mg/L) DAS28
Controls (n = 56)
Active disease period
_ Inactive disease period
8.6 ± 2.2 13.4 ± 1.6 305.6 ± 80.6 16 ± 3.9 24 (2–79) 13.6 (1.3–115) 4.1 ± 0.7
7.4 ± 1.02 13.5 ± 1.5 279.9 ± 63.4 14.2 ± 1.04 13 (2–28) 4.4 (1.4–7.9) 1.89 ± 0.53
7.1 ± 1.6 13.9 ± 1.2 265.4 ± 59.6 14.03 ± 1.2 11 (2–20) 3.6 (1.4–7.9) –
Significance p1
p2
p3
<0.001 0.009 0.02 <0.001 <0.001 <0.001 –
0.08 0.09 0.28 0.18 0.11 0.06 –
0.001 0.24 0.02 <0.001 <0.001 <0.001 <0.001
PsA: psoriatic arthritis; WBC: white blood cell count; Hb: hemoglobin; PLT: platelet; RDW: red cell distribution width; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; DAS28: disease activity score 28. Data are presented as mean ± SD or median (range). P1: The difference between active disease period of PsA patients and controls; p2: The difference between inactive disease period of PsA patients and controls; p3: The difference between active and inactive disease periods of PsA patients. Bold values are significant at p < 0.05
Please cite this article as: C. Ozisler and S. C. Sandikci, Evaluation of red blood cell distribution width in patients with psoriatic arthritis, The Egyptian Rheumatologist, https://doi.org/10.1016/j.ejr.2019.06.001
C. Ozisler, S.C. Sandikci / The Egyptian Rheumatologist xxx (xxxx) xxx Table 3 Correlation between red cell distribution width in active disease period of PsA patients. Variables
ESR CRP DAS28
RDW in PsA patients (n = 47) r
p
0.57 0.4 0.42
<0.001 0.006 0.003
RDW: red cell distribution width; PsA: psoriatic arthritis; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; DAS28: disease activity score 28. Bold values are significant at p < 0.05
mias (eg, b-thalassemia minor and iron deficiency anemia) [5,7]. In the last years, a number of studies have demonstrated that this quick, simple and inexpensive parameter have multiple clinical applications; such as an inflammatory marker, a predictor of allcause mortality and a prognostic tool for morbidity and mortality in patients with acute or chronic conditions [5,7,21]. In rheumatologic disorders, such as RA, SLE and AS, many studies have investigated the value of RDW to assess the disease activity [15–17]. To the best of our knowledge, this retrospective study is the first to evaluate RDW levels in PsA patients. It was found that RDW values were increased significantly in active disease period of PsA patients than inactive disease period of PsA patients and controls. RDW values significantly correlated with ESR, CRP and DAS28 levels in active disease period of PsA patients. RDW can be considered a potential predictor of disease activity in PsA patients. To date, many studies have investigated the association between RDW and rheumatologic disorders. Tecer et al. showed that RA patients had higher RDW values than the controls and RDW values significantly correlated with DAS28 [15]. Results in another study indicated that RDW level was significantly increased in RA patients compared to osteoarthritis patients and healthy donors, and high levels of RDW were associated with elevated levels of inflammatory marker as CRP and ESR [22]. It has been recently reported that RDW was significantly higher in patients with AS compared with controls and was directly correlated with ESR, CRP and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [16,23]. In another study, Hu et al. showed that RDW was increased in SLE patients compared with controls and correlated with CRP, ESR and SLE disease activity [17]. Similarly, it was observed that RDW in familial Mediterranean fever (FMF), Henoch-Schonlein purpura (HSP), dermatomyositis and polymyositis patients was higher compared with that in the control [18,24,25]. Kim et al. reported that RDW was significantly correlated with Birmingham vasculitis activity score (BVAS) and predicts vasculitis activity and poor prognosis in patients with granulomatosis with polyangiitis [26]. RDW was significantly higher in Behçet’s disease patients, suggesting their value as promising inflammatory biomarkers [27]. The exact pathophysiologic mechanism of elevated RDW in inflammatory conditions remains unclear. Inflammatory diseases have various effects on hematopoiesis, so complete blood count is also affected. Proinflammatory cytokine levels become chronically increased in diseases which have prolonged inflammation [15]. These cytokines such as interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-a) can modulate erythropoiesis through inhibition of synthesis or activity of erythropoietin (EPO) and via desensitization of erythroid progenitors to EPO in bone marrow (disruption of response to EPO). Then, immature erythrocytes are _ released into the peripheral blood stream [5–7,15]. Inflammation can also lower erythrocyte survival via increasing RBC destruction [5,14]. These mechanisms leads to a more mixed population of erythrocyte volumes in the circulation. Thus, inflammation could contribute to anisocytosis, resulting in the increase of RDW level [5,15,22].
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The present study had some limitations that should be considered. First, this was a retrospective and single center study. Second, the number of patients was relatively low. But, this was due to the strict exclusion criterias. Third, the relationship between RDW and other more sensitive inflammatory markers such as IL-1, IL-6 and TNF-a were not evaluated. Comparing the RDW and other variables between active and inactive periods proved that RDW is a marker of inflammation in PsA which was the most powerful aspect of this study. In conclusion, increased RDW is associated with active disease period of PsA patients. So, RDW seems to be a surrogate marker of the inflammation, like CRP and ESR. Furthermore, RDW is included in the CBC test, which is routinely performed for followup of rheumatic diseases. For this reason, the measure of RDW doesn’t need any additional costs. RDW may provide extra information about inflammatory process and might be a potential marker to evaluate the disease activity of PsA. However, further prospective, multicenter and controlled studies with larger sample size are needed to validate the clinical value of RDW in patients with PsA and to determine a cut-off level of RDW for assessing disease activity with a high sensitivity and specifity. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Competing Interest None. References [1] Solmaz D, Eder L, Aydin SZ. Update on the epidemiology, risk factors, and disease outcomes of psoriatic arthritis. Best Pract Res Clin Rheumatol 2018;32:295–311. [2] Scotti L, Franchi M, Marchesoni A, Corrao G. Prevalence and incidence of psoriatic arthritis: a systematic review and meta-analysis. Semin Arthritis Rheum 2018;48:28–34. [3] Ritchlin CT, Colbert RA, Gladman DD. Psoriatic Arthritis. N Engl J Med 2017;376:2095–6. [4] Moll JM, Wright V. Psoriatic arthritis. Semin Arthritis Rheum 1973;3:55–78. [5] Salvagno GL, Sanchis-Gomar F, Picanza A, Lippi G. Red blood cell distribution width: a simple parameter with multiple clinical applications. Crit Rev Clin Lab Sci 2015;52:86–105. [6] Horta-Baas G, Romero-Figueroa MDS. Clinical utility of red blood cell distribution width in inflammatory and non-inflammatory joint diseases. Int J Rheum Dis 2019;22(1):47–54. [7] Silva Litao MK, Kamat D. Back to Basics: Red Blood Cell Distribution Width: Clinical Use beyond Hematology. Pediatr Rev 2018;39:204–9. [8] Avci E, Kiris T, Demirtas AO, Kadi H. Relationship between high-density lipoprotein cholesterol and the red cell distribution width in patients with coronary artery disease. Lipids Health Dis 2018;17:53. [9] Danese E, Lippi G, Montagnana M. Red blood cell distribution width and cardiovascular diseases. J Thorac Dis 2015;7:E402–11. [10] Lippi G, Turcato G. Cervellin G, Sanchis-Gomar F. Red blood cell distribution width in heart failure: a narrative review. World J Cardiol 2018;10:6–14. [11] Arbel Y, Weitzman D, Raz R, Steinvil A, Zeltser D, Berliner S, et al. blood cell distribution width and the risk of cardiovascular morbidity and all-cause mortality. A population-based study. Thromb Haemost 2014;111:300–7. [12] Al-Kindi SG, Refaat M, Jayyousi A, Asaad N, Al Suwaidi J, Abi Khalil C. Red Cell Distribution Width Is Associated with All-Cause and Cardiovascular Mortality in Patients with Diabetes. Biomed Res Int 2017;2017:5843702. [13] Yang D, Quan W, Wu J, Ji X, Dai Y, Xiao W, et al. The value of red blood cell distribution width in diagnosis of patients with colorectal cancer. Clin Chim Acta 2018;479:98–102. [14] Song CS, Park DI, Yoon MY, Seok HS, Park JH, Kim HJ, et al. Association between red cell distribution width and disease activity in patients with inflammatory bowel disease. Dig Dis Sci 2012;57:1033–8. _ NA, Çimen ÖB, Biçer A, et al. Can mean [15] Tecer D, Sezgin M, Kanık A, Incel platelet volume and red blood cell distribution width show disease activity in rheumatoid arthritis? Biomark Med 2016;10:967–74. [16] Peng YF, Zhang Q, Cao L, Liu Y, Chen D, Sun YK, et al. blood cell distribution width: a potential maker estimating disease activity of ankylosing spondylitis. Int J Clin Exp Med 2014;7:5289–95.
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C. Ozisler, S.C. Sandikci / The Egyptian Rheumatologist xxx (xxxx) xxx
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Please cite this article as: C. Ozisler and S. C. Sandikci, Evaluation of red blood cell distribution width in patients with psoriatic arthritis, The Egyptian Rheumatologist, https://doi.org/10.1016/j.ejr.2019.06.001