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


Consistent with previous studies,[15,18,19] the present study exhibited a significantly higher frequency of hematinic deficiencies in OLP patients than in healthy controls. Moreover, a significant association between hematinic deficiencies and OLP was also demonstrated. However, this association should be interpreted with caution. Since OLP is a chronic condition with periods of exacerbation and remission, it may cause discomfort or pain and difficulty in eating and drinking.[20,21,22] A study on dietary changes in 48 patients with oral vesiculoulcerative diseases, of whom most were diagnosed with OLP, showed that even patients with mild forms of the disease would change their eating habits for extended periods, which might negatively affect the patients' nutritional status.[22] From this point of view, it seems reasonable to conclude that the hematinic deficiencies might be the result of OLP. Nevertheless, it should be noted that the occurrence of hematinic deficiencies usually takes several months to years to appear.[8,9] For example, due to the important hepatic stores and enterohepatic circulation, vitamin B12 deficiency would occur only if the daily intake has been insufficient for years.[8] In this study, we found that hematinic deficiencies had already existed in many of the enrolled patients, which were unlikely caused by OLP because of their rather short duration. Hence, we could speculate that, at least for some OLP patients, hematinic deficiencies occur earlier than the onset of OLP.

On the other hand, there is yet no direct evidence suggesting that hematinic deficiencies are involved in the pathogenesis of OLP, but several plausible mechanisms are proposed and need to be investigated in further studies. First, inadequate iron, folate or vitamin B-2 can significantly alter the immune response and affect cell-mediated immunity.[10,11,23,24] For example, significant suppressed natural killer (NK) cell activity was noted in patients with vitamin B12 deficiency compared with control subjects and the decreased activity could be restored after vitamin B12 supplementation.[25] Coincidentally, significantly decreased NK cell activity was also found in LP patients.[26,27] Second, the levels of vascular cell adhesion molecule-1 (VCAM-1), an inducible adhesion protein in endothelial cells, were significantly higher in patients with IDA compared with controls.[28] The expression of VCAM-1 in OLP was equally significantly increased.[29] Third, it has been demonstrated that psychological disorders, such as anxiety and depression, might play an important role as a trigger for OLP and might also be responsible for many relapses.[6] Notably, vitamin B12 deficiency or insufficiency might contribute to the etiopathogenesis of depression. Folic acid and vitamin B12 supplements were recommended for inclusion in treating depression.[30] However, the question remains to be elucidated since more than half of OLP patients did not have hematinic deficiencies in the present study. Prospective studies on the incidence of OLP in patients having hematinic deficiencies with large-sample and long-term follow-up are needed to provide more clinical evidence.

The REU scoring system is a semiquantitative method with less subjectivity and good reproducibility and has been validated to be much more accurate for comparing the severity of oral lichenoid lesions.[31–33] In a previous study, the inter- and intra-observer agreement of this scoring system was assessed with the finding that the Spearman correlation coefficient was 1.0 and 0.98, respectively.[31] To the best of our knowledge, this is the first report of using a disease scoring system (DSS) in investigating the association between the severity of OLP and hematinic deficiencies. In this study, no significant difference in REU scores was found between OLP patients with and without hematinic deficiencies, suggesting that the hematinic deficiencies may not directly correlate with the severity of OLP. This finding might be due to the well-recognized phenomenon that the clinical character of OLP can alleviate or aggravate even in a short time, especially when there are local irritations and trauma in the oral cavity.[2,3] However, the levels of serum ferritin, folate and vitamin B12 in the human body could not fluctuate so rapidly. The biomarkers that can sensitively reflect the severity of OLP still warrant further investigation.

One limitation of the present study is that there are still no "gold standard" laboratory tests for hematinic deficiencies in routine clinical practice.[34,35] The sensitivity and specificity of available assays still need to be improved.[34,35] Some newer assays, such as measuring holotranscobalamin II (holoTC), and additional tests of serum total homocysteine (tHcy), methylmalonic acid (MMA), transferrin receptor and red blood cell folate (RBC folate) are recommended for further studies.[35]

Based on our findings, hematological screening for hematinic deficiencies should be included in routine laboratory examination of OLP patients. Several studies have proposed that vitamin replacement may improve the general health of OLP patients and increase their healing ability.[12,36] Therefore, compensation of hematinic deficiencies with adequate nutritional supplements or in combination with other drugs, is supposed to produce improved therapeutic effects on OLP patients.[12,36] In addition, dietary assessment and guidance to maintain adequate nutrition and optimal quality of life should be considered as a component of OLP management.[20,22]