Efficacy of 0.1% topical tacrolimus in the management of symptomatic geographic tongue: A placebo-controlled study

Rahul Srivastava; Devina Pradhan; Lokesh Sharma; Bhuvan Jyoti; Vishal Mehrotra

doi:10.4103/jdrr.jdrr_127_20

ORIGINAL ARTICLE

Year : 2022 | Volume : 9 | Issue : 1 | Page : 73-77

Efficacy of 0.1% topical tacrolimus in the management of symptomatic geographic tongue: A placebo-controlled study

Rahul Srivastava¹, Devina Pradhan², Lokesh Sharma³, Bhuvan Jyoti⁴, Vishal Mehrotra¹
¹ Department of Oral Medicine and Radiology, Rama Dental College Hospital and Research Centre, Kanpur, Uttar Pradesh, India
² Department of Public Health Dentistry, Rama Dental College Hospital and Research Centre, Kanpur, Uttar Pradesh, India
³ Department of Public Health Dentistry, Sardar Patel Post Graduate Institute of Dental and Medical Sciences, Lucknow, Uttar Pradesh, India
⁴ Department of Dental Surgery, Ranchi Institute of Neuro-Psychiatry and Allied Sciences, Ranchi, Jharkhand, India

Date of Submission	16-Oct-2020
Date of Decision	07-Aug-2021
Date of Acceptance	24-Jun-2021
Date of Web Publication	06-Apr-2022

Correspondence Address:
Rahul Srivastava
Department of Oral Medicine and Radiology, Rama Dental College, Hospital and Research Centre, Kanpur, Uttar Pradesh
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jdrr.jdrr_127_20

Abstract

Background: Geographic tongue is characterized by erythematous patches with whitish margins across the surface of the tongue, with periods of exacerbation and remission that confer the typical migratory aspect of this entity. There is no definite treatment for geographic tongue as yet. The present study aims to evaluate the response of treatment with topical tacrolimus ointment 0.1% w/w (Protopic^®) in geographic tongue. Materials and Methods: This was a prospective study involving a total of 14 patients who were randomly divided into two groups, namely Group A and Group B, with 7 patients in each group. Patients were requested to apply 0.1% topical tacrolimus ointment (Protopic^®) in an oral base on their lesions and an identical placebo. At each visit, the burning sensation was tested through the Visual Analog Scale and the treatment responses were tested through Tel Aviv-San Francisco Scale. Data were assessed using IBM Statistical Package for Social Sciences (SPSS) Statistics version 21. Results: Patients in Group A (0.1% topical tacrolimus) depicted lower scores of burning sensation after the treatment as compared to Group B (placebo). The overall treatment response was significantly better in Group A than Group B. Conclusion: The results of the present study suggest that topical application of 0.1% tacrolimus is beneficial in the management of symptomatic geographic tongue.

Keywords: Benign migratory glossitis, geographic tongue, tongue, topical tacrolimus

How to cite this article:
Srivastava R, Pradhan D, Sharma L, Jyoti B, Mehrotra V. Efficacy of 0.1% topical tacrolimus in the management of symptomatic geographic tongue: A placebo-controlled study. J Dent Res Rev 2022;9:73-7

How to cite this URL:
Srivastava R, Pradhan D, Sharma L, Jyoti B, Mehrotra V. Efficacy of 0.1% topical tacrolimus in the management of symptomatic geographic tongue: A placebo-controlled study. J Dent Res Rev [serial online] 2022 [cited 2023 Mar 26];9:73-7. Available from: https://www.jdrr.org/text.asp?2022/9/1/73/342697

Introduction

Geographic tongue is commonly known by the name benign migratory glossitis which was first reported geographic tongue in 1831 by Rayer. He recognized it as a wandering rash of the tongue. Various other terminologies used for this condition are marginal exfoliative glossitis, transitory benign plaque of the tongue, and exfoliatio areata linguae.^[1],[2] Geographic tongue is characterized by erythematous patches with whitish margins across the surface of the tongue, with periods of exacerbation and remission that confer the typical migratory aspect of this entity.^[3]

Geographical tongue etiology remains largely unknown; however, a few hypotheses have been suggested. It was proposed that psychosomatic and genetic influences play a role in the etiology of geographical tongue. Redman et al. have reported higher geographic tongue incidence in mentally ill patients. Ebrahimi et al. reported that decreasing stress can help heal geographical tongue lesions, further showing a connection between stress and geographic tongue.^[4]

In India, the prevalence of geographic tongue is 0.89% and overall prevalence is 1%–2.5% in general population. Redman has reported its prevalence to be 1% in schoolchildren. High prevalence in children was found in Japan (8%) and Israel (14%). Females are more commonly affected.^[5] It is generally seen that there is a transient and recurrent lesion which may sometimes not require any kind of treatment and heals on its own. In addition, treatment of geographic tongue is only required when there are symptomatic cases. The geographic tongue lesion is typically asymptomatic, and sometimes, the patient is unaware of its existence, but seldom can be a cause of pain or burning sensation, with a significant impact on the quality of life. It can occur either solitary/multiple and intermittent/continuous.^[1],[6] The lesions should be treated in case of pain, discomfort, burning sensation, reduced taste, cancer phobia, or esthetic problems.^[7]

However, there is no definitive treatment protocols for this condition but topical anesthetic rinses or gels and nonsteroidal anti-inflammatory drugs have been administered for for symptomatic care. Antihistaminics have been used in case of evident allergic etiology. Topical corticosteroids have been used for management of ulcerative type of lesion. Anti-fungal rinses are used for Candida infection. Antibacterial or sodium bicarbonate rinses are also treatment options for geographic tongue.^[8]

Corticosteroids are considered as being successful among the choices available. Triamcinolone acetonide is compared to other corticosteroids because it contains sodium and similar characteristics to those of other corticosteroids.^[9] Topical tacrolimus is a topical noncorticosteroidal immunomodulator with a low adverse effect that presents a rapid response in the control of symptoms compared to traditional corticosteroids.^[10]

Nevertheless, to our knowledge, very few studies have been conducted which have demonstrated associated clinical features of the lesion. Thus, the present study was conducted to test the efficacy of topical tacrolimus ointment 0.1% w/w (Protopic^®) in geographic tongue.

Materials and Methods

A double-blinded, randomized study was done at the outpatient Department of Oral Medicine and Radiology at Rama Dental College Hospital and Research Centre, Kanpur. The present study was approved by the Institutional Review Board of our college (Ethical approval no/010-A dated June 15, 2019). The aim of the study was briefed to the participants, and thereafter, written informed consent was obtained from them. The participants who agreed to take part in the study and above 18 years old either sex with clinically diagnosed with symptomatic geographic tongue (confirmed by an oral disease specialist) were included. Patients with a known history of systemic diseases, patients with a history of systemic or topical corticosteroid use for at least 1 month before treatment, pregnant ladies, and smokers were excluded from the study. Complete case history was recorded in a predetermined format.

This was a prospective study involving a total of 14 patients who were randomly divided into two groups, namely Group A and Group B, with 7 patients in each group. Patients were requested to apply 0.1% topical tacrolimus ointment (Protopic^®) in an oral base on their lesions and an identical placebo. Patients were also instructed to wash their mouth before the application of drugs and avoid eating and drinking for at least 15 min.

Burning sensation was measured through the Visual Analog Scale with a score of 0–100. The complete treatment observations were measured at baseline, 2 weeks, 30 days, and 60 days. This was measured with Tel Aviv-San Francisco Scale which incorporates scores from 4 to 1.^[11]

Data were analyzed using IBM SPSS Statistics version 21 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, version 21.0. Armonk, NY, USA: IBM Corp.). Descriptive statistics included calculation of percentages, mean, median, and standard deviation. Normality of the data was measured through Shapiro–Wilk test. Wilcoxon signed-rank test was used for comparing intragroups. Mann–Whitney U-test and Fisher's exact test assessed the intergroup observations. All values were considered statistically significant for a value of P ≤ 0.05.

Results

[Table 1] shows that in the study group, there were around nine males and five females. The mean age of the patients was found to be 1.43 ± 0.535 for Group A and 1.45 ± 0.538 for Group B [Table 2]. At baseline, there was no significant difference found between the groups.

Table 1: Gender distribution of the study participants

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Table 2: Age distribution of the study participants

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[Table 3] shows the values regarding burning sensation for Group A which were significantly less after the application of ointment by 75.7% (P = 0.001), with 6.86 ± 0.9 at baseline to 4 ± 0.81 at the end of the 6^th week. There was no significant change in the severity of symptoms after follow-up of the 1^st and 2^nd months. In Group B (placebo), the mean score was less by 24.3% (P = 0.001) after the therapy, i.e. from 7.29 ± 0.48 at baseline to 1.29 ± 0.48 at the end of the 6^th week. The follow-up at the 1^st and 2^nd months did not show any significant change. However, after the therapy, there were decreased scores for burning sensation among both the groups (75.7% and 24.3%, respectively).

Table 3: Burning sensation scores in both the groups according to Visual Analog Scale

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[Table 4] shows that at the end of the therapy in Group A, 6 (85.71%) patients showed 50% or more benefit, with 1 (14.29%) patient showing 30%–50% relief in signs and symptoms. However, in the placebo Group B, 1 (14.29%) patient showed deterioration or regression, 3 (42.86%) patients showed little or no improvement, 2 (28.57%) patients showed 30%–50% improvement and treatment still needed, and 1 (14.29%) patient showed only 50% benefit.

Table 4: Scores of overall treatment at 2, 4, 6, and 8 weeks on the basis of Tel Aviv-San Francisco Scale

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[Table 3] shows that 71.43% of patients were cured in Group A whereas only 28.57% were partially cured/uncured. However, statistically significant differences were observed (P = 0.02).

Discussion

Geographic tongue is of unknown nature. Its clinical features include a well-circumscribed red depapillated area with an annulus that is white-yellow colored and is elevated.^[12] Due to inflammation of lingual mucosa, filiform papillae lose their architecture; irregular erythematous patches or ulcers are noticeable. Although the dorsal surface of the tongue is nonulcerated, because of the lack of keratinization and depapillation of filiform papillae, it gives an ulcerated appearance.^[5]

Geographic tongue may occur as isolated or multiple lesions may be asymptomatic or have symptoms such as pain, burning sensation, discomfort, dysgeusia, sensitivity to ear pain in hot, spicy, and sour food, or ipsilateral submandibular lymphadenopathy.^[1],[13]

The total geographical tongue prevalence is approximately 1%–2.5% of the population. In the pediatric population, the prevalence of geographic tongue ranges from 0.37% to 14.3% with uncertain etiology.^{[14],[15],[16]}

The prevalence of geographic tongue is 0.89% in India. In the age group of 20–29 years, the highest incidence of around 39.4% is present. Geographic tongue is recorded more often in adults than in children, although others suggest it is prevalent in younger people.^{[13],[17],[18],[19]}

Honarmand et al. in 2013 reported the high prevalence of geographic tongue among females than males.^[20] In 2014, Rezaei et al. reported a high prevalence of geographic tongue among males than females.^[6] In the present study, there was male predominance for geographic tongue. The disparity in the outcomes of the various researches may be attributed to the sample population's age and hormone interference.

Several studies documented the frequency of these lesions with the start of the menstrual cycle, pregnancy, and oral contraceptive pill intake. In the present study, this phenomenon may have low occurrence in girls because of their age group, which is more limited in terms of female hormone interference. Hormones, especially female hormones, can interfere with the induction or intensification of lesions in geographical tongue.^{[21],[22],[23]}

Tacrolimus is an immunosuppressive macrolide and its anti-inflammatory action is similar to that of cyclosporine. Currently, topical tacrolimus has proven to be effective in the treatment of dermatoses.^[5] Fortunately, the mucosal surface of the tongue contains highly vascular fungiform papillae that are nonkeratinized. These features reduce barriers to absorption and increase the local permeation of tacrolimus.^[24] The results obtained from the current undertaken study revealed that all participants having geographic tongue were under 30 years of age. The results of the present study are consistent with the findings achieved earlier by Miloglu O et al., Jainkittivony and Langlais, and Avcu and Kanli where the geographic tongue has been reported more in people under 30 years old.^{[13],[25],[26]}

In the present study, seven patients of symptomatic geographic tongue were treated with 0.1% topical tacrolimus twice daily and another seven patients with an identical placebo. Ishibashi et al. reported that when 0.1% tacrolimus ointment is used by the patients, the patients were relieved by the painful geographic tongue. Thus, the application of this ointment two times a day for around 14 days proved to be quite beneficial.^[5] Therefore, it was decided to use topical application of 0.1% tacrolimus ointment twice daily for a period of 8 weeks. In the management of geographic tongue, relief in burning sensation symptoms was a major goal in the current undertaken study. Patients in Group A (0.1% topical tacrolimus) showed a decrease in the burning sensation as compared to Group B (placebo) after the treatment.

At the end of the treatment, 6 (85.71%) patients showed 50% or more benefit, with 1 (14.29%) patient showing 30%–50% relief in signs and symptoms, and did not require further treatment. In addition, in the placebo group, 1 (14.29%) patient showed deterioration or regression, 3 (42.86%) patients showed little or no improvement, 2 (28.57%) patients showed 30%–50% improvement and treatment still needed, and 1 (14.29%) patient showed only 50% benefit. In this way, results obtained from the present study showed that 0.1% tacrolimus ointment was effective in reducing the signs and symptoms in the geographic tongue patients.

Purani and Purani reported a case of geographic tongue in a 6-year-old child and successful management was achieved with topical application of 0.1% tacrolimus. Ishibashi et al. reported that the application of ointment improved the symptoms of the patients.^[5],[27] The results obtained from topical application of 0.1% tacrolimus in the management of persistent and painful geographic tongue were similar to our study. The results of the present study reveal that topical application of 0.1% tacrolimus is beneficial in the management of symptomatic geographic tongue.

As short-term application of tacrolimus can cure geographic tongue without any adverse effect or patient discomfort, this medication can be recommended intraorally. However, the sample size is less in our study, so it is recommended that clinical trials with large sample size must be conducted further to study the efficacy of topical tacrolimus in geographic tongue, but the incidence of the lesion is so low that to perform a clinical trial would be difficult.

Conclusion

Geographic tongue, also known as benign migratory glossitis, is a benign inflammatory condition of unknown etiology characterized by multifocal, irregular, well-defined, ulcer-like erythematous patches with a white rim on the tongue's dorsal surface or lateral borders. The lesions need to be treated in case of the presence of pain, burning sensation, taste diminution, cancer phobia, or esthetic concerns. The results of the present study suggest that topical application of 0.1% tacrolimus is beneficial in the management of symptomatic geographic tongue. Since the sample size in the current study was less, so it is recommended that clinical trials of larger sample size must be conducted to study the efficacy of topical tacrolimus in geographic tongue.

Ethical clearance

The present study was approved by the Institutional Review Board of our college (Ethical approval no/010-A dated June 15, 2019).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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