The Profile of Hematinic Deficiencies in Patients With Oral Lichen Planus

A Case-control Study

Zhe-xuan Bao; Xiao-wen Yang; Jing Shi; Yu-feng Wang


BMC Oral Health. 2020;20(252) 

In This Article


A total of 236 OLP patients (41 males and 195 females, mean age, 51.70 ± 13.99 years) and 226 gender- and age-matched healthy controls (52 males and 174 females, mean age, 49.46 ± 17.26 years) were enrolled in this retrospective study (Table 1). All patients were diagnosed consecutively from July 2015 to March 2019 at the Department of Oral Medicine, Shanxi Provincial People's Hospital, China. Healthy controls were recruited from December 2014 to August 2017 at the same hospital. Sample size estimation was performed using two independent groups for binary data; the sample size formula was provided by Machin et al..[17] Sample size calculation was based on the 2% prevalence of OLP, and the odds ratio (OR) was 5.0. Alpha was set as 0.05; the value of beta was considered as 0.1 in the formula. The required sample size for the OLP group and control group was at least 221, respectively. Hence, this study fulfilled the sample size requirements for further data analysis.

The diagnosis of OLP was established according to the recommended diagnostic criteria.[3] The characteristic clinical manifestations alone, such as bilateral grayish-white Wickham striae or papules, may allow diagnosis, especially if classic skin or other extraoral lesions exist concomitantly. Besides the clinical examination, a biopsy for histopathological examination was routinely performed. When necessary, direct immunofluorescence (DIF) was employed to differentiate from autoimmune blistering diseases, such as pemphigus and pemphigoid. Specifically, any patient suspected of having oral lichenoid lesions, including contact hypersensitivity reactions, drug-induced reactions, paraneoplastic pemphigus and chronic graft-vs-host disease, was not enrolled in the present study. A thorough medical history was obtained from each participant, and a standard clinical examination of the oral cavity was also performed. The duration of OLP, which was estimated from the first notice of oral discomfort, was recorded for each patient. All patients who were histologically confirmed to have epithelial dysplasia or diagnosed as having other oral mucosal lesions, such as leukoplakia, mucosal hyperkeratosis, erythema multiforme or discoid lupus erythematosus, were also excluded. In addition, patients having concomitant systemic disease, including benign or malignant tumors, HIV, rheumatic or autoimmune disease, uncontrolled thyroid disease, liver or kidney disease, gastrointestinal disease or a history of alcoholism were equally excluded from the study. None of the healthy controls exhibited any oral mucosal lesions or had relevant systemic disease. None of the participants had taken any nutritional supplements, including (but not limited to) folate, vitamin B12 or iron supplements, at least 3 months before the study.

This study was conducted in accordance with the Helsinki Declaration and approved by the ethics committee of Shanxi Provincial People's Hospital (No. 20190302), and informed consent was obtained from each of the participants.

Laboratory Methods

After 12 h of overnight fasting, blood samples were obtained from all participants. The serum was separated and tested immediately. After internal quality control, the serum levels of folate, vitamin B12 and ferritin were measured by the chemiluminescence method (Beckman Coulter, DXI-800-Immunoassay System) in the Clinical Laboratory of Shanxi Provincial People's Hospital. The accepted normal serum folate level and serum vitamin B12 level was 4.0–18.7 ng/mL and 180–914 ng/L, respectively. Serum ferritin level was used to assess iron status with a normal level of 11.0–306.8 ng/mL for females and 15–336.2 ng/mL for males. Serum vitamin B12, folate and ferritin deficiencies were defined as a serum level below their lower cutoff values, respectively. The hemoglobin (Hb) level was also determined and anemia was diagnosed when the Hb level was lower than the lower cut-off value (male, < 13 g/dL; female, < 12 g/dL).

Clinical Examination and Scoring

The REU (reticular/hyperkeratotic, erosive/erythematous, ulcerative) scoring system was adopted to evaluate the severity of OLP as previously reported.[13,14] Briefly, the oral cavity of each OLP patient was divided into 10 sites and the severity of the mucosal lesions in each site was scored according to the presence of reticular/hyperkeratotic, erosive/erythematous, and ulcerative lesions. Here, the REU score of each OLP patient was determined by the same well-trained specialist (ZX Bao).

Data Analysis

Statistical analyses were performed with SPSS software, version 22.0 (SPSS Inc., Chicago, Ill). The independent-samples t test was used to compare age between OLP patients and healthy controls. The mean serum levels of vitamin B12, folate, ferritin, and hemoglobin were compared using Wilcoxon's rank-sum test. The male-to-female ratio, the frequencies of hematinic deficiencies and anemia between OLP patients and healthy controls were compared using the chi-square test. When the observed frequency was less than 1, Fisher's exact test was applied. The Wilcoxon-Mann-Whitney rank sum test (U test) was used to statistically compare REU scores between the OLP patients with and without hematinic deficiencies. Logistic regression analysis was conducted to assess whether the age and gender were significant factors related to the presence of hematinic deficiencies (ferritin, folate and vitamin B12 deficiency) in the OLP patients and healthy controls, respectively. Spearman's correlation coefficient was applied to evaluate the association between OLP and hematinic deficiencies. A P-value < 0.05 was accepted as statistically significant.