Red cell distribution width as a biomarker of disease activity in ulcerative colitis and Crohn’s disease

Abstract

BACKGROUND

Red cell distribution width (RDW) has emerged as a potential inflammatory marker in various chronic inflammatory conditions, yet its role in inflammatory bowel disease (IBD) remains insufficiently understood.

AIM

To investigate the association between RDW parameters [RDW-coefficient of variation (RDW-CV) and RDW-standard deviation (RDW-SD)] and disease activity in patients with ulcerative colitis (UC) and Crohn’s disease (CD).

METHODS

This retrospective study included 455 patients diagnosed with IBD (365 UC, 90 CD) who were followed at a tertiary referral center between 2018 and 2025. Disease activity was classified using the UC endoscopic index of severity for UC and the CD activity index for CD. RDW-CV and RDW-SD values were compared across disease activity categories (remission, mild, moderate, severe) and between remission vs active disease groups. Statistical analyses included Mann-Whitney U, Kruskal-Wallis, χ² tests, and receiver operating characteristic analysis. Ethical approval was obtained (E-25/735).

RESULTS

In CD, RDW-CV values were significantly higher in patients with moderate disease activity compared with those in remission and mild activity groups (P = 0.02). However, this significance was observed only across activity categories; when disease activity was dichotomized as remission vs active disease, RDW-CV did not show a significant difference (P = 0.25). In UC, RDW-CV was progressively higher in moderate and severe disease compared with remission and mild disease (P < 0.001). When evaluated as remission vs active disease, RDW-CV was also significantly higher in active UC (P = 0.002). RDW-SD did not show significant differences across activity groups in either disease.

CONCLUSION

RDW-CV is associated with increased disease activity in UC and may partially reflect disease severity in CD. As an inexpensive and easily accessible biomarker, RDW may provide supportive information when evaluating inflammatory burden in IBD; however, prospective multicenter studies are needed to validate its clinical utility. These findings suggest that RDW-CV may serve as a practical adjunct biomarker for disease activity assessment, particularly in settings where endoscopic evaluation is not readily available.

Key Words: Inflammatory bowel disease; Ulcerative colitis; Crohn’s disease; Red cell distribution width; Disease activity

Core Tip: Red cell distribution width (RDW) is an inexpensive and widely available parameter reflecting systemic inflammation. In this study, RDW-coefficient of variation was significantly associated with disease activity in ulcerative colitis, suggesting its potential as a supportive biomarker in clinical practice. However, its utility in Crohn’s disease appears limited.

INTRODUCTION

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), comprises chronic, relapsing inflammatory disorders of the gastrointestinal tract driven by a complex interplay of genetic susceptibility, immune dysregulation, environmental influences, and alterations in the gut microbiome[1,2]. The global prevalence of IBD continues to rise, placing a substantial burden on healthcare systems and highlighting the need for accurate assessment of disease activity.

Endoscopic evaluation remains the gold standard for determining disease severity in IBD, as endoscopic activity strongly correlates with clinical outcomes and guides therapeutic decision-making[3,4]. However, endoscopy is invasive, costly, time-consuming, and often impractical for frequent monitoring. For this reason, non-invasive biomarkers capable of reliably reflecting intestinal inflammation are of significant clinical interest.

Among non-invasive tests, C-reactive protein (CRP), fecal calprotectin, and stool lactoferrin are widely used, yet their diagnostic performance varies across disease phenotypes and activity states[3]. CRP is often nonspecific and may be normal in isolated colonic CD or mild UC, while fecal calprotectin despite its high accuracy faces limitations related to patient compliance, sample handling, and cost[3-6]. Serological biomarkers have been explored as alternatives, though their predictive value for endoscopic activity remains inconsistent[4,5].

Red cell distribution width (RDW), routinely reported in complete blood count, reflects the degree of anisocytosis and is influenced by systemic inflammation, oxidative stress, impaired erythropoiesis, and iron metabolism abnormalities. RDW has emerged as a potential inflammatory marker across various chronic diseases due to its pathophysiological association with cytokine-mediated erythropoietic dysfunction[7]. Growing evidence indicates that RDW may serve as a useful marker of IBD activity, with studies suggesting an association between RDW levels and inflammatory burden in both UC and CD[8].

Given its simplicity, low cost, wide availability, and potential mechanistic linkage to systemic and mucosal inflammation, RDW may represent a practical biomarker for assessing disease severity in IBD. The present study aims to investigate the association between RDW parameters and disease activity in UC and CD using a large, single-center cohort.

MATERIALS AND METHODS

This retrospective, single-center cohort study was conducted at the Gastroenterology Department of Ankara Training and Research Hospital after obtaining approval from the Institutional Ethics Committee (Decision No: E-25/735). Medical records of patients diagnosed with IBD who presented between January 1, 2018, and January 1, 2025, were reviewed. Initially, 1739 patients with UC or CD were screened, and after applying inclusion and exclusion criteria, 455 patients constituted the final study cohort, including 365 UC and 90 CD patients.

Inclusion criteria were age ≥ 18 years, a confirmed diagnosis of UC or CD based on clinical, endoscopic, radiologic, and histopathologic findings, and availability of complete blood count parameters including RDW-coefficient of variation (RDW-CV), RDW-standard deviation (RDW-SD), and CRP. Exclusion criteria consisted of pregnancy, active malignancy, hematologic disorders affecting erythrocyte morphology, blood transfusion within the previous three months, coexisting autoimmune or systemic inflammatory diseases, non-IBD acute infections, severe hepatic or renal dysfunction, and incomplete clinical or laboratory data.

Demographic characteristics, clinical features, laboratory parameters, endoscopic findings, and pathology reports were retrieved from the hospital electronic medical record system. Disease activity in UC was assessed using the UC endoscopic index of severity (UCEIS) and categorized as remission (0-1), mild (2-4), moderate (5-6), and severe disease (7-8)[9]. Disease extent in UC was defined according to the Montreal classification as E1, E2, and E3[10]. Disease activity in CD was determined using the CD activity index (CDAI) and categorized as remission (0-149), mild (150-219), moderate (220-450), and severe disease (> 450)[11].

Laboratory analyses included complete blood count parameters such as hemoglobin, mean corpuscular volume (MCV), platelet count, CRP, and RDW. RDW was evaluated in two forms. RDW-CV, an index expressing anisocytosis relative to MCV, is calculated as the coefficient of variation of erythrocyte volume and is influenced by changes in MCV[4]. RDW-SD, expressed in femtoliters, reflects the absolute width of erythrocyte volume distribution and is independent of MCV, thus representing true anisocytosis[12]. All measurements were performed using automated hematology analyzers, and both RDW parameters were analyzed in relation to disease activity.

Statistical analysis

Statistical analyses were performed using SPSS software. Distribution of continuous variables was assessed with the Kolmogorov-Smirnov test. Parametric or nonparametric tests were applied as appropriate. Categorical variables were compared using the χ² test. Logistic regression analyses were conducted to evaluate the independent association between RDW parameters and disease activity. Diagnostic performance of RDW-CV and RDW-SD for predicting active disease was assessed using receiver operating characteristic (ROC) curve analysis, with area under the curve (AUC) values, confidence intervals, and optimal cut-off points calculated. A P value < 0.05 was considered statistically significant. Potential confounding factors affecting RDW, including anemia-related parameters and inflammatory markers, were considered during the analysis.

RESULTS

A total of 455 patients were included in the study, comprising 365 with UC and 90 with CD. The baseline demographic and laboratory characteristics of the study population are presented in Table 1. UC and CD patients demonstrated comparable age and sex distributions; however, both RDW-CV and RDW-SD values were significantly higher in CD compared with UC (P = 0.008 and P < 0.001, respectively). Overall, 30.1% of UC and 26.7% of CD patients were in remission based on disease activity indices.

Table 1 Baseline demographic, laboratory, and activity characteristics of the study population, median (interquartile range).

Variable	Ulcerative colitis (n = 365)	Crohn’s disease (n = 90)	P value
Age (years)	43.0 (32-58)	43.0 (34-55)	0.59
Sex, male (%)	58.4	53.3	0.39
Platelet (× 103/μL)	293 (241-351)	299 (244-376)	0.36
CRP (mg/L)	3.7 (1.3-10.3)	4.8 (1.5-15.6)	0.08
RDW-CV (%)	13.3 (12.9-14.5)	13.9 (13.1-15.5)	0.008
RDW-SD (fL)	41.8 (39.8-44.2)	43.4 (40.8-46.9)	< 0.001
Remission (%)	30.1	26.7	0.52
Active disease (%)	69.9	73.3

RDW-CV: Red cell distribution width-coefficient of variation; RDW-SD: Red cell distribution width-standard deviation; CRP: C-reactive protein.

RDW across disease activity categories

UC: A stepwise increase in RDW-CV was observed across UCEIS groups (as shown in Table 2). RDW-CV values increased from remission to mild, moderate, and severe disease (P < 0.001), mirroring progressive elevations in CRP and platelet counts. RDW-SD did not differ significantly across activity categories (P = 0.32).

Table 2 Red cell distribution width and laboratory parameters across ulcerative colitis disease activity groups, median (interquartile range).

Variable	Remission (n = 110)	Mild (n = 75)	Moderate (n = 116)	Severe (n = 64)	P value
RDW-CV (%)	13.1 (12.7-13.7)	13.2 (12.8-13.9)	13.6 (13.0-14.8)	14.2 (13.4-16.0)	< 0.001
RDW-SD (fL)	41.5 (39.5-43.5)	41.2 (39.4-43.4)	42.1 (40.1-44.3)	42.8 (40.5-45.3)	0.32
CRP (mg/L)	1.2 (0.5-3.2)	2.4 (0.8-6.4)	6.7 (2.6-15.1)	11.8 (4.9-27.8)	< 0.001
Platelets	275 (230-324)	286 (239-342)	302 (254-357)	338 (276-396)	< 0.001

Disease activity was classified according to the ulcerative colitis endoscopic index of severity. RDW-CV: Red cell distribution width-coefficient of variation; RDW-SD: Red cell distribution width-standard deviation; CRP: C-reactive protein.

CD: RDW-CV varied significantly across CDAI-defined activity groups (Table 3) (P = 0.02), with the highest values in severe disease. RDW-SD showed no significant differences (P = 0.56). CRP and platelet levels rose progressively with disease severity.

Table 3 Red cell distribution width and laboratory parameters across Crohn’s disease activity groups, median (interquartile range).

Variable	Remission (n = 24)	Mild (n = 35)	Moderate (n = 24)	Severe (n = 7)	P value
RDW-CV (%)	13.8 (12.9-14.8)	13.6 (13.0-14.8)	14.3 (13.5-16.7)	15.2 (14.1-16.2)	0.02
RDW-SD (fL)	43.0 (40.2-45.4)	42.6 (40.4-46.0)	43.9 (41.1-48.6)	45.3 (41.0-48.9)	0.56
CRP (mg/L)	2.0 (0.9-7.7)	4.7 (1.7-13.0)	11.8 (4.6-32.7)	18.4 (7.2-41.5)	< 0.001
Platelets	265 (224-322)	298 (251-348)	321 (263-389)	369 (298-414)	< 0.001

Disease activity was categorized according to the Crohn’s disease activity index. RDW-CV: Red cell distribution width-coefficient of variation; RDW-SD: Red cell distribution width-standard deviation; CRP: C-reactive protein.

Remission vs active disease

Detailed remission vs active comparisons are presented in Table 4. In UC, RDW-CV was significantly higher in active disease (P = 0.002), while RDW-SD showed no significant difference. In CD, neither RDW-CV nor RDW-SD distinguished disease activity, though CRP and platelet levels were markedly higher in active disease (P < 0.001).

Table 4 Red cell distribution width comparison between remission and active disease in ulcerative colitis and Crohn’s disease, median (interquartile range).

Variable	Remission	Active disease	P value
UC: RDW-CV (%)	13.1 (12.7-13.7)	13.6 (13.0-15.0)	0.002
UC: RDW-SD (fL)	41.5 (39.5-43.5)	42.0 (40.0-44.7)	0.30
CD: RDW-CV (%)	13.8 (12.9-14.8)	14.2 (13.3-15.8)	0.25
CD: RDW-SD (fL)	43.0 (40.2-45.4)	43.4 (40.6-47.1)	0.75

RDW-CV: Red cell distribution width-coefficient of variation; RDW-SD: Red cell distribution width-standard deviation; UC: Ulcerative colitis; CD: Crohn’s disease.

ROC analysis for active UC

ROC analysis was performed to assess the diagnostic utility of RDW-CV for identifying active UC. RDW-CV demonstrated a modest discriminatory ability, yielding an AUC of 0.604 (95% confidence interval: 0.543-0.665; P = 0.002). Using an optimal cut-off value of 14.85%, RDW-CV achieved high specificity (92.7%) but low sensitivity (27.8%), indicating that elevated RDW-CV is highly specific for active disease but insufficiently sensitive to exclude it. The positive predictive value was 89.9%, whereas the negative predictive value was limited at 35.7%. RDW-SD did not exhibit meaningful discriminatory performance and therefore was not subjected to ROC analysis. Because no significant differences in RDW values were observed between remission and active disease in CD, ROC analysis was not performed for this subgroup. The ROC curve for RDW-CV in UC is presented in Figure 1. In addition, multivariate logistic regression analysis confirmed that RDW-CV was independently associated with disease activity in UC after adjustment for potential confounders, whereas no independent association was identified in CD.

Figure 1 Receiver operating characteristic curve of red cell distribution width-coefficient of variation for detecting active ulcerative colitis (area under the curve = 0.604, P = 0.002).

DISCUSSION

IBD encompasses a heterogeneous group of chronic immune-mediated conditions characterized by recurrent mucosal or transmural inflammation. Despite advances in endoscopic scoring systems and cross-sectional imaging, clinicians still rely heavily on laboratory biomarkers to assess inflammatory burden, monitor treatment response, and predict clinical outcomes. Traditional markers such as CRP and fecal calprotectin remain useful but are not universally reliable; both exhibit interpatient variability, can be influenced by extra-intestinal factors, and are not always accessible in all clinical settings[13-15]. Therefore, there is a growing interest in alternative, inexpensive, and universally available biomarkers, such as RDW, which may reflect systemic inflammation through hematologic pathways[3]. In this context, the present study provides a detailed evaluation of RDW-CV and RDW-SD in a large cohort of UC and CD patients, analyzing their association with disease activity across multiple validated clinical and endoscopic indices. While previous studies have reported associations between RDW and disease activity in IBD, this study adds to the existing literature by including a relatively large cohort, evaluating both RDW-CV and RDW-SD simultaneously, and applying validated endoscopic and clinical activity indices.

A major finding of this study is the strong association between RDW-CV and disease activity in UC. RDW-CV levels demonstrated a progressive increase from remission to mild, moderate, and severe activity groups, supporting the hypothesis that mucosal inflammation exerts a measurable effect on erythropoiesis. The biological plausibility of this relationship is supported by inflammatory pathways, including cytokine-mediated impairment of iron metabolism and erythropoiesis, leading to increased anisocytosis[16-18].

Our ROC analysis further supports the clinical relevance of RDW-CV in UC by demonstrating high specificity despite modest overall discriminatory performance. Although the AUC of 0.604 indicates only modest discriminative ability, the biomarker exhibited high specificity. This means that when RDW-CV exceeds the calculated cut-off, the probability of active disease is relatively high, even though normal values do not reliably exclude active inflammation. From a practical perspective, RDW-CV may help reinforce clinical suspicion in symptomatic patients or provide supportive evidence when endoscopy is delayed or unavailable. RDW-CV should therefore be considered a complementary biomarker rather than a standalone diagnostic tool[19,20]. Although RDW-CV demonstrated statistical significance, its modest discriminative performance (AUC = 0.604) indicates limited standalone clinical utility. Therefore, RDW-CV should be interpreted in conjunction with established biomarkers and clinical findings rather than as an independent diagnostic tool. The lack of association between RDW and disease activity in CD may reflect its biological heterogeneity and the influence of confounding factors such as anemia and malabsorption[17,21].

RDW-SD, on the other hand, did not demonstrate clinically meaningful variation with disease activity in either UC or CD. This may reflect fundamental differences in how RDW-SD and RDW-CV behave physiologically. RDW-SD represents the absolute standard deviation of erythrocyte size distribution, whereas RDW-CV is a relative measure that normalizes variability to MCV. Because RDW-CV amplifies proportional changes, it may be better suited to detecting subtle erythrocyte size fluctuations attributable to low-grade inflammation. RDW-SD may require more pronounced or prolonged hematopoietic disruption to exhibit measurable variation. Consequently, the differential performance of RDW-CV and RDW-SD in our dataset is consistent with their underlying biological definitions[19,22,23]. This likely explains why RDW-SD remained unchanged across disease activity levels, even in the presence of measurable inflammation.

CRP and platelet levels were elevated in active disease, consistent with known inflammatory pathways, supporting the overall validity of the findings[13,14,24]. The strengths of this study include its large sample size, comprehensive inclusion of both major IBD subtypes, and systematic evaluation of RDW using validated disease activity scores (UCEIS and CDAI). The single-center nature ensures methodological consistency, reducing interlaboratory variability. Moreover, assessing two RDW components CV and SD allowed a nuanced evaluation of erythrocyte size heterogeneity and its relation to inflammatory burden[22,23,25].

Nevertheless, several limitations should be acknowledged. The retrospective design limits causal inference and prevents assessment of longitudinal RDW dynamics in response to therapeutic interventions. Prospective studies incorporating serial RDW measurements would help clarify whether RDW changes parallel clinical improvement or worsening. The absence of comprehensive iron studies including ferritin, transferrin saturation, vitamin B12, and folate levels in a subset of patients restricts our ability to fully account for nutritional and hematologic confounders, which may have particular relevance in CD where malabsorption and chronic anemia are common[17]. In addition, subclinical variations in iron metabolism and other unmeasured nutritional factors may further influence RDW values and could not be fully accounted for in this retrospective design. Therefore, the observed associations between RDW and disease activity should be interpreted with caution, particularly in CD. Additionally, because fecal biomarkers and cross-sectional imaging were not available for all patients, the study could not directly compare RDW with other objective measures of intestinal inflammation[15]. This limitation precluded a direct comparison between RDW and established fecal biomarkers such as fecal calprotectin. Finally, although RDW-CV demonstrated statistically significant associations in UC, the modest AUC suggests that it should be interpreted as an adjunctive rather than standalone biomarker[19,20].

In summary, this study shows that RDW-CV is significantly associated with endoscopic and clinical disease activity in UC and may provide practical, easily accessible supportive information in routine evaluation. Its high specificity suggests potential value in strengthening diagnostic confidence when active inflammation is suspected, although its limited sensitivity underscores that RDW cannot function as a primary stand-alone biomarker. In contrast, RDW parameters did not demonstrate meaningful associations with disease activity in CD, reflecting the biologic heterogeneity of CD and the greater influence of confounding hematologic factors. Overall, RDW-CV may serve as an adjunctive biomarker that complements established inflammatory markers, particularly in UC. Future prospective, multicenter studies with detailed hematologic and nutritional assessment are needed to validate these findings and clarify how RDW might be integrated into multimodal prediction models for IBD activity.

CONCLUSION

RDW-CV was significantly associated with disease activity in UC but showed no meaningful relationship with activity in CD. As a simple, inexpensive, and widely available hematologic parameter, RDW-CV may serve as a supportive biomarker in the clinical assessment of UC, although its limited sensitivity restricts its use as a standalone diagnostic tool. Further prospective and multicenter studies are needed to clarify its predictive value and its integration into multi-parameter models for monitoring IBD activity.