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Clinical Oral Investigations

, Volume 22, Issue 7, pp 2487–2493 | Cite as

Treatment of symptomatic benign migratory glossitis: a systematic review

  • Wladimir Gushiken de Campos
  • Camila Vieira Esteves
  • Lígia Gonzaga Fernandes
  • Carina Domaneschi
  • Celso Augusto Lemos Júnior
Review
  • 301 Downloads

Abstract

Objective

The aim of this systematic review is to summarize the results of all published studies on symptomatic benign migratory glossitis and evaluate the best available treatment.

Methods

We searched the Cochrane Library, EMBASE, LILACS, PubMed, Scopus, and Web of Science for articles published up to September 2017, with no time restriction. We considered only articles published in English that evaluated the treatment of symptomatic benign migratory glossitis in children and adults. The protocol for this systematic review was registered at the international prospective register of systematic reviews (PROSPERO) as CRD42017074096.

Results

Of the 840 identified studies, 11 were included in our sample. Multiple treatment modalities were described for the treatment of symptomatic benign migratory glossitis.

Conclusions

There is a very low level of evidence for the treatment of symptomatic benign migratory glossitis, with substantial methodological heterogeneity among the evaluated studies. In summary, we could identify no specific treatment for symptomatic benign migratory glossitis.

Clinical relevance

In clinical practice, at the outpatient clinic of oral medicine, we attend to many patients diagnosed with benign migratory glossitis, with varying intensity of pain ranging from mild to severe. Treating this disease is a formidable challenge for clinicians. Therefore, we performed a systematic review of benign migratory glossitis to identify the best evidence-based treatment available for this condition. We believe that this article may be useful in guiding clinicians on the choice of treatment.

Keywords

Benign migratory glossitis Geographic tongue Treatment Exfoliatio areata linguae 

Introduction

Benign migratory glossitis (BMG) is a pathological condition referred to in literature as geographic tongue, annulus migrans, erythema migrans, benign wandering glossitis, exfoliatio areata linguae, or transitory benign plaque of the tongue [1, 2, 3].

The lesion is an asymptomatic inflammatory disorder of unknown etiology. It is considered by some as a normal variant rather than a pathological finding. It is also considered to be a congenital anomaly, an inflammatory reaction, and an oral symptom of systemic psoriasis by some researchers [1, 3, 4].

BMG occurs commonly on the dorsal surface of the tongue, sometimes involving its lateral borders. The clinical presentation is often described as multifocal, annular, erythematous patches with slightly elevated white margins, resulting in a map-like appearance. (Fig. 1) This occurs due to atrophy of the filiform papillae, which leads to epithelial thinning [1, 2, 4, 5, 6, 7]. Many cases are asymptomatic, requiring no specific treatment other than reassurance regarding the benign and self-resolving nature of the lesion [1, 8].
Fig. 1

BMG is often described as multifocal, annular, erythematous patches with slightly elevated white margins, resulting in a map-like appearance

However, in symptomatic cases, there is no established treatment reported in literature. Multiple treatment modalities are resorted to, including antihistamines, anxiolytics, corticosteroids, topical anesthetics, nutritional supplements, and avoidance of spicy or acidic food [1, 8].

The purpose of this systematic review was to summarize the results of all published studies on symptomatic BMG and evaluate the best available treatment for this condition.

Methods

Protocol and registration

The protocol for this systematic review was registered at the international prospective register of systematic reviews (PROSPERO) as CRD42017074096.

Inclusion criteria

We selected studies that reported on the treatment of symptomatic BMG in children and adults. No time restriction was set for the search. Only articles published in English were considered. The inclusion criteria were based on the PICOS (population, intervention, comparison, outcome, and study design) format. Patients with symptomatic BMG were evaluated. Topical and systemic drugs were evaluated as interventions. The expected outcome of treatment was the resolution of symptoms. We included clinical trials and observational studies.

Exclusion criteria

Studies were excluded for the following reasons [1]: Studies that evaluated patients diagnosed with systemic psoriasis, as we believe these cases, are of a different pathology; (n = 8) [2]; reviews, letters, personal opinions, book chapters, conference abstracts, posters, and patents (n = 2) [3]; studies on patients with asymptomatic BMG (n = 2) [4]; studies that did not involve treatment of patients with symptomatic BMG (n = 8) [5]; studies with no follow-up (n = 1) [6]; misdiagnosis (n = 1) [7]; full text was not available (n = 5); and [8] studies in languages other than English (n = 2).

Study selection

Studies were identified by searching electronic databases including PubMed, Science Direct, LILACS, Scopus, and Web of Science, with additional gray literature search on Google Scholar (Appendix S1). All searches were performed until September 12, 2017. Additionally, we searched reference lists of selected articles for other pertinent studies that may have been missed in the initial search. We removed duplicate studies using reference manager (Mendeley Desktop, Elsevier, New York).

Study selection and data collection

The study was conducted in two phases. In phase 1, two authors (WGC and CVE) independently reviewed titles and abstracts from all electronic databases. The selected studies that fulfilled the inclusion criteria based on information available from the abstracts. In phase 2, the same authors reviewed the full text of the selected articles and excluded studies that did not fulfill the inclusion criteria. Any unresolved discrepancies between both were resolved by a third author (CD). One of the authors (WGC) gathered data of selected articles including authors, year of publication, country, sample size, median ages, study design, methods, results, and main conclusions. A second author (CVE) verified the selected information. Disagreements were resolved by consensus. The third author (CD), when required, made the final decision. The fourth author (LGF) evaluated the risk of bias of the included studies, and the fifth (CALJ) assessed the quality of evidence and carried out the general review.

Summary measures

The primary objective of this systematic review was to evaluate the best treatment for symptomatic BMG. Any type of outcome measurement was considered in this review.

Results

In phase 1, 840 articles were found across the selected databases. After removing duplicate studies, 631 articles remained. After title and abstract screening, 598 of these articles were excluded. Search using the Google Scholar database yielded 479 articles, of which seven were included in this review. After full-text review of the 40 articles selected from phase 1, 29 were excluded, leaving 11 articles for final analyses. A flowchart of the selection methodology is shown in Fig. 2.
Fig. 2

Flow diagram of literature search and selection criteria adapted from PRISMA

Study characteristics

The 11 selected studies included 150 patients with BMG. The number of cases in these studies ranged from 1 [7] to 70 [9]. The Studies were from the USA [1, 2, 10], Hungary [9], Japan [5, 7], India [3, 11, 12], and Iran [4, 6]. All articles were published in English, between 1960 and 2016. A summary of characteristics of the selected studies is listed in Table 1.
Table 1

Description of articles features (n = 11)

Year

Author

Country

Cases of GT

Age (mean of range in years)

Treatment proposed

Results

1960

Zegarelli et al. (Zegarelli et al. 1960)

USA

4

Not informed

Topical triamcinolone acetonide 0.1%

No favorable influence

1964

Redman (Redman 1964)

USA

20

Not informed

Nutritional supplements

No favorable influence

1975

Bánóczy et al. (Bánóczy et al. 1975)

Hungary

70

Not informed

Local/nutritional supplements/antimycotic/sex hormones

No favorable influence

1992

Sigal et al. (Sigal and Mock 1992)

USA

2

3,5

Topical/systemical diphenhydramine (12.5 mg/5 cc, four times per day)

Resolution of symptoms

2007

Abe et al. (Abe et al. 2007)

Japan

1

54

Systemical cyclosporin (3 mg/kg/day)

Resolution of symptoms

2010

Ishibashi et al. (Ishibashi et al 2010)

Japan

2

77

Topical tacrolimus 0.1% (twice daily)

Symptoms significantly improved

2012

Goswami et al. (Goswami et al 2012)

India

1

11

Topical diphenhydramine and lidocaine

Symptoms significantly improved

2014

Purani et al. (Purani and Purani 2014)

India

1

6

Topical tacrolimus 0.1% (twice daily)

Symptoms significantly improved

2014

Tajmirriahi(Tajmirriahi, 2014)

Iran

20

Not informed

Zinc sulfate (110 mg per day)

No favorable influence

2016

Najafi et al. (Najafi et al. 2016)

Iran

28

40

Comparison between topical triamcinolone acetonide 0.1% and a combination of 0.05% retinoic acid + triamcinolone acetonide 0.1% (twice daily)

No favorable influence

2016

Kumar et al. (Kumar et al. 2016)

India

1

2,5

Topical ozone therapy

Symptoms significantly improved

Evaluation of study quality

The GRADE method [13] was used to evaluate study quality, as shown in Table 2. Eight studies were classified as of very low quality, one as low quality, one as moderate quality, and only one as high quality. Common identified weaknesses included small sample size, lack of a control group, unclear methodology, and insufficient statistical analysis and reporting.
Table 2

Recommendations Assessment, Development and Evaluation (GRADE) for impact of treatment of benign migratory glossitis

Article (no. of participants)

Study limitations

Consistency

Directness

Precision

Publication bias

Overall quality

Zegarelli et al. (Zegarelli et al. 1960) (4)

Serious limitations (− 1)

No important inconsistency

Indirect (− 1)

Some imprecision (− 1)

Unlikely

++

Redman (Redman 1964) (20)

Serious limitations (− 1)

Inconsistency (− 1)

Indirect (− 1)

Some imprecision (− 1)

Unlikely

+

Bánóczy et al. (Bánóczy et al. 1975) (70)

No serious limitation

No important inconsistency

Indirect (− 1)

No important imprecision

Unlikely

+++

Sigal et al. (Sigal and Mock 1992) (2)

Very serious limitations (− 2)

No important inconsistency

Direct

Some imprecision (− 1)

Reporting bias (− 1)

+

Abe et al. (Abe et al. 2007) (1)

Very serious limitations (−2)

Inconsistency (− 1)

Indirect (− 1)

Some imprecision (− 1)

Reporting bias (− 1)

+

Ishibashi et al. (Ishibashi et al. 2010) (2)

Very serious limitations (− 2)

No important inconsistency

Direct

Some imprecision (− 1)

Reporting bias (− 1)

+

Goswami et al. (Goswami et al. 2012) (1)

Very serious limitations (− 2)

Inconsistency (− 1)

Direct

Some imprecision (− 1)

Reporting bias (− 1)

+

Purani et al. (Purani and Purani 2014) (1)

Very serious limitations (− 2)

Inconsistency (− 1)

Indirect (− 1)

Some imprecision (− 1)

Reporting bias (− 1)

+

Tajmirriahi (Tajmirriahi 2014) (20)

Serious limitations (− 1)

Inconsistency (− 1)

Direct

Some imprecision (− 1)

Unlikely

+

Najafi et al. (Najafi et al 2016) (28)

No serious limitation

No important inconsistency

Direct

No important imprecision

Unlikely

++++

Kumar et al. (Kumar et al 2016) (1)

Very serious limitations (− 2)

Inconsistency (− 1)

Direct

Some imprecision (− 1)

Reporting bias (− 1)

+

For overall quality of evidence: +, very low; ++, low; +++, moderate; ++++, high

The selected studies did not reveal the best level of evidence available to answer the clinical question in our current systematical review.

Synthesis of results

Widely divergent therapeutic modalities were used in the included studies; topical triamcinolone acetonide 0.1% (n = 2), topical tacrolimus 0.1% (n = 2), topical diphenhydramine (n = 2), and nutritional supplements (n = 2) were the most frequent.

Topical triamcinolone acetonide 0.1% was used alone [10] and in combination with retinoic acid 0.05% [6]. Both studies showed no favorable influence on the treatment of BMG. Redman [2] also reported that the use of nutritional supplements has no favorable influence.

Bánóczy et al. [9] reviewed multiple methods of treatment of BMG over a period of 10 years, with nutritional supplements, antimycotics, and sex hormones and observed no improvement. The authors concluded that no specific therapy is recommended.

Tajmirriahi [14] treated 20 patients with zinc sulfate 110 mg per day, for 30 days, with no reported improvement.

A recent article by Kumar et al. [12] in 2016 reported a 2.5-year-old child who was diagnosed with BMG. The lesion was treated with topically applied ozonized olive oil, leading to improvement of symptoms.

Ishibashi et al. [5] and Purani et al. [3] reported the use of topical tacrolimus 0.1%. In both cases, the medication was applied to the lesion twice daily for 10 to 14 days. Improvement of symptoms was observed in both studies.

Goswami et al. [11] treated an 11-year-old patient with topical diphenhydramine and lidocaine, with improvement of symptoms. Abe et al. [7] described a case of symptomatic BMG treated with systemic administration of cyclosporine (3 mg/kg/day) leading to remarkable improvement of lesions.

There was only one article that reported total resolution of symptoms; Sigal et al. [1], reported two cases of BMG, treated with topical and systemic diphenhydramine (12.5 mg/5 ml, four times per day), with resolution of symptoms within 24 h.

Thus, five studies presented no benefits with treatment while five others reported significant improvement of symptoms; only one study reported total resolution of symptoms.

Risk of bias within studies

Based on the MAStARI [15] assessment of the 11 studies included in this study, nine [1, 3, 5, 7, 9, 10, 11, 12, 14, and] were classified as having a high risk of bias, with methods and results that were unclear or of low quality. One study was classified as having a moderate risk of bias [2] and one with a low risk of bias [6] (Table 3). The articles selected for this study were considered heterogeneous, and therefore, did not provide data compatible for a meta-analysis.
Table 3

Risk of bias assessed by Meta-Analysis of Statistics Assessment and Review Instrument

Question

Zegarelli et al.(Zegarelli et al, 1960)

Redman (Redman, 1964)

Bánóczy et al. (Bánóczy et al, 1975)

Sigal et al.(Sigal and Mock, 1992)

Abe et al.(Abe et al, 2007)

Ishibashi et al.(Ishibashi et al, 2010)

Goswami et al. (Goswami et al, 2012)

Purani et al.(Purani and Purani, 2014)

Tajmirriahi (Tajmirriahi, 2014)

Najafi et al.(Najafi et al, 2016)

Kumar et al.(Kumar et al, 2016)

1. Is the study based on a random or pseudorandom sample?

N

N

NA

NA

NA

NA

NA

NA

N

Y

NA

2. Are the criteria for inclusion in the sample clearly defined?

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

3. Are confounding factors identified and strategies to deal with them stated?

U

U

U

U

U

U

U

U

U

Y

U

4. Are outcomes assessed using objective criteria?

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

5. If comparisons are being made, was there sufficient description of the groups?

U

Y

NA

NA

NA

NA

NA

NA

N

Y

NA

6. Is follow up carried out over a sufficient time period?

U

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

7. Are the outcomes of people who withdrew described and included in the analysis?

N

N

NA

NA

NA

NA

NA

NA

N

N

NA

8. Are outcomes measured in a reliable way?

N

Y

Y

N

N

N

N

N

N

Y

N

9. Is appropriate statistical analysis used?

N

Y

N

N

N

N

N

N

N

Y

N

% yes/risk

22%

66%

44%

33%

33%

33%

33%

33%

33%

88%

33%

Risk of bias

H

M

H

H

H

H

H

H

H

L

H

(MAStARI) (mastari) critical appraisal tools

Risk of bias was categorized as High when the study reaches up to 49% score “yes,” Moderate when the study reached 50 to 69% score “yes,” and Low when the study reached more than 70% score “yes”

Y yes, N no, U unclear, NA not applicable, H high, M moderate, L low

Besides the heterogeneity between studies, there were only a few clinical studies in our search of literature regarding treatment of symptomatic BMG, making it impossible to carry out a meta-analysis.

Discussion

In our research of literature, we found that intermittent worsening and remission are major characteristics of BMG. Recurrent lesions commonly affect new areas, which produce a migratory pattern. Epithelial proliferation at one site, and concomitant exfoliation at another, induce the map-like appearance [1, 4]. Lesions may change in location, intensity, and appearance within minutes to hours [8].

The reported prevalence of BMG in multiple studies varies between 1 and 4.8% [1, 4, 16, 17, 18]. The condition does not have a gender predilection [16, 18]. Further, it seems to occur in children and adults under 30 years of age more frequently [16, 17, 18].

BMG does not have a well-established etiology, with literature suggesting an association with several systemic alterations including psoriasis, nutritional deficiencies, hormonal imbalance, allergies, anemia, Reiter’s syndrome, seborrheic dermatitis, Down syndrome, pregnancy, stress, and diabetes [1, 4, 8, 18]. It may occur in association with a fissured tongue [4, 8, 16]. Hereditary factors are suggested, since there is a positive family history in many cases [1, 8].

Although many authors consider BMG as an oral manifestation of psoriasis, we do not believe in this correlation. In our 25-year clinical experience at a reference center for oral diagnosis, we have never observed such a correlation. Espelid et al. [19] attempted to correlate BMG with psoriasis, but his subjects had a low expression of HLA-DR, an MHC class II cell surface receptor normally associated with psoriasis. Hietanen et al. [20] studied 200 patients with psoriasis and found BMG in 1% of the study sample, an incidence similar to healthy subjects, showing no relation between these diseases. Additionally, Raghoebar et al. [21] concluded that both conditions appeared incidentally, rather than having the same etiological factor. Due to these reasons, we excluded articles involving patients diagnosed with systemic psoriasis, as we believe it is a different pathology.

Diagnosis is usually based on clinical examination and detailed history, with a characteristic description of multiple, migratory lesions that vary in size, affected area, and clinical appearance [1, 4, 8]. Most cases are totally asymptomatic and detected during routine clinical examination, thus requiring no treatment other than reassurance regarding the benign and self-resolving nature of the lesion [1, 8].

However, in symptomatic cases, there is no gold standard or scientifically proven treatment. In this systematic review, we analyzed all published articles on the treatment of symptomatic BMG and found 11 relevant studies [1, 2, 3, 5, 6, 7, 9, 10, 11, 12, 14].

We noted a general lack of good quality, scientific studies on the treatment of symptomatic BMG in literature, with wide heterogeneity between studies. On analysis of the selected studies using the GRADE method, one article was classified as of “moderate” quality and another as “high” quality. All others [9] were classified as of “very low” or “low” quality. The studies classified as of “moderate” quality [9] and “high” quality [6] had no favorable effect on the treatment of symptomatic BMG.

Thus, after analyzing 11 included articles in this study, it is possible to affirm that there are no scientifically proven treatment modalities for symptomatic BMG. We believe the lack of high-quality studies on the treatment of BMG is because of the benign nature of the lesion, as most cases (75.5%) are asymptomatic [4]. It is also difficult to perform a randomized, double-blind study, due to the migratory nature of the lesion.

Limitations

Our review had methodological limitations. Only 11 articles met the inclusion criteria, possibly because of the benign nature of the lesion, with just one randomized clinical trial. The lack of clinical studies published in literature precludes clinical analysis. Hence, we recommend future research to improve our understanding of the treatment of BMG.

Conclusions

There is very low level of evidence for the treatment of symptomatic BMG with substantial methodological heterogeneity among the evaluated studies. In summary, there is no specific treatment for symptomatic BMG. Hence, we cannot propose any recommendation due to the lack of clinical evidence.

Notes

Funding

The work was supported by the Department of Stomatology, College of Dentistry, University of São Paulo in São Paulo, Brazil.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study, formal consent is not required.

Supplementary material

784_2018_2553_MOESM1_ESM.doc (62 kb)
ESM 1 (DOC 62.5 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Stomatology, School of DentistryUniversidade de São PauloSão PauloBrazil

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