nach oben

Erschienen in:

20.09.2021 | Review

Efficacy of hyaluronic acid for recurrent aphthous stomatitis: a systematic review of clinical trials

verfasst von: Sadeq Ali Al-Maweri, Nader Alaizari, Rawan Hejji Alanazi, Sajna Ashraf, Rania Hejji Alanazi, Hesham Mohammed Al-Sharani, Esam Halboub

Erschienen in: Clinical Oral Investigations | Ausgabe 12/2021

Einloggen, um Zugang zu erhalten

Abstract

Objectives

Recurrent aphthous stomatitis (RAS) is a very common oral mucosal disease, and its management is quite challenging with no definitive cure being available so far. Many studies have tried hyaluronic acid (HA) for alleviating signs and symptoms of RAS. The present systematic review sought to assess the available evidence regarding the efficacy of HA in management of RAS.

Methods

Two reviewers independently conducted extensive search in four online databases (PubMed, Scopus, Web of Science, and Google Scholar) and the gray literature, with no restriction to date or language of the publication. All clinical trials that assessed the efficacy of HA in reducing signs and symptoms of RAS were included. Risk of bias was assessed by two reviewers independently, using the Cochrane assessment tool. Due to substantial heterogeneity, no meta-analysis was feasible.

Results

Out of the 75 identified articles, nine clinical trials involving 538 RAS patients (259 in HA group) were included. The risk of bias was high in five studies, low in one study, and unclear in three studies. The comparative groups varied greatly across the included studies: triamcinolone (in three studies), chlorhexidine mouthwash, lidocaine, placebo, iodine glycerin, diclofenac, and laser therapy. Overall, the results revealed a good efficacy of HA in alleviating pain and shortening the healing time of RAS, without any reported side effects. Compared to triamcinolone, HA showed superior results in one study, and comparable results in two studies.

Conclusions

The available evidence suggests that HA is a promising treatment option for RAS. However, given the huge heterogeneity of the included studies and high risk of bias in some of these studies, the evidence is inconclusive. Further well-designed clinical trials with standardized methodologies and adequate sample sizes are warranted to discern the efficacy of HA for RAS.

Clinical relevance

Hyaluronic acid might be a viable alternative therapeutic option for patients with RAS.

Nur mit Berechtigung zugänglich

Saikaly SK, Saikaly TS, Saikaly LE (2018) Recurrent aphthous ulceration: a review of potential causes and novel treatments. J Dermatolog Treat 29:542–552. https://doi.org/10.1080/09546634.2017.1422079CrossRefPubMed

Tarakji B, Gazal G, Al-Maweri SA, Azzeghaiby SN, Alaizari N (2015) Guideline for the diagnosis and treatment of recurrent aphthous stomatitis for dental practitioners. J Int Oral Health 7:74–80PubMedPubMedCentral

Yang C, Liu L, Shi H, Zhang Y (2018) Psychological problems and quality of life of patients with oral mucosal diseases: a preliminary study in Chinese population. BMC Oral Health 18:226. https://doi.org/10.1186/s12903-018-0696-yCrossRefPubMedPubMedCentral

Al-Johani K (2019) Prevalence of recurrent aphthous stomatitis among dental students: a cross sectional study. J Contemp Dent Pract 20:893–895CrossRef

Al-Maweri SA, Halboub E, Al-Sharani H, Shamala A, Al-Kamel A, Al-Wesabi M, Albashari A, Al-Sharani A, Abdulrab S (2020) Association between serum zinc levels and recurrentaphthous stomatitis: a meta-analysis with trial sequentialanalysis. Clin Oral Investig 25(2):407–415 CrossRef

Al-Maweri SA, Halboub E, Al-Sufyani G, Alqutaibi AY, Shamala A, Alsalhani A (2019) Is vitamin D deficiency a risk factor for recurrent aphthous stomatitis? A systematic review and meta-analysis. Oral Dis. https://doi.org/10.1111/odi.13189CrossRefPubMed

Mohammad R, Halboub E, Mashlah A, Abou-Hamed H (2013) Levels of salivary IgA in patients with minor recurrent aphthous stomatitis: a matched case-control study. Clin Oral Investig 17:975–980. https://doi.org/10.1007/s00784-012-0785-2CrossRefPubMed

Ruan HH, Li GY, Duan N, Jiang HL, Fu YF, Song YF, Zhou Q, Wang X, Wang WM (2018) Frequencies of abnormal humoral and cellular immune component levels in peripheral blood of patients with recurrent aphthous ulceration. J Dent Sci 13:124–130. https://doi.org/10.1016/j.jds.2017.09.003CrossRefPubMed

Shen C, Ye W, Gong L, Lv K, Gao B, Yao H (2021) Serum interleukin-6, interleukin-17A, and tumor necrosis factor-alpha in patients with recurrent aphthous stomatitis. J Oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol 50:418–423. https://doi.org/10.1111/jop.13158CrossRef

10.

Xu K, Zhou C, Huang F, Duan N, Wang Y, Zheng L, Wang X, Wang W (2021) Relationship between dietary factors and recurrent aphthous stomatitis in China: a cross-sectional study. J Int Med Res 49:3000605211017724. https://doi.org/10.1177/03000605211017724CrossRefPubMed

11.

Ozyurt K, Celik A, Sayarlıoglu M, Colgecen E, Incı R, Karakas T, Kelles M, Cetin GY (2014) Serum Th1, Th2 and Th17 cytokine profiles and alpha-enolase levels in recurrent aphthous stomatitis. J Oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol 43:691–695. https://doi.org/10.1111/jop.12182CrossRef

12.

Al-Maweri SA, Alaizari N, Alharbi AA, Alotaibi SA, AlQuhal A, Almutairi BF, Alhuthaly S and Almutairi AM (2020) Efficacy of curcumin for recurrent aphthous stomatitis: a systematic review. J Dermatolog Treat:1–6. https://doi.org/10.1080/09546634.2020.1819529

13.

Halboub E, Al-Maweri SA, Parveen S, Al-Wesabi M, Al-Sharani HM, Al-Sharani A, Al-Kamel A, Albashari A, Shamala A (2021) Zinc supplementation for prevention and management of recurrent aphthous stomatitis: a systematic review. J Trace Elem Med Biol Organ Soc Miner Trace Elem (GMS) 68:126811. https://doi.org/10.1016/j.jtemb.2021.126811CrossRef

14.

Al-Maweri SA, Halboub E, Ashraf S, Alqutaibi AY, Qaid NM, Yahya K, Alhajj MN (2020) Single application of topical doxycycline in management of recurrent aphthous stomatitis: a systematic review and meta-analysis of the available evidence. BMC Oral Health 20:231. https://doi.org/10.1186/s12903-020-01220-5CrossRefPubMedPubMedCentral

15.

El-Haddad SA, Asiri FY, Al-Qahtani HH, Al-Ghmlas AS (2014) Efficacy of honey in comparison to topical corticosteroid for treatment of recurrent minor aphthous ulceration: a randomized, blind, controlled, parallel, double-center clinical trial. Quintessence Int (Berlin, Germany: 1985) 45:691–701. https://doi.org/10.3290/j.qi.a32241CrossRef

16.

Yarom N, Zelig K, Epstein JB, Gorsky M (2017) The efficacy of minocycline mouth rinses on the symptoms associated with recurrent aphthous stomatitis: a randomized, double-blind, crossover study assessing different doses of oral rinse. Oral Surg Oral Med Oral Pathol Oral Radiol 123:675–679. https://doi.org/10.1016/j.oooo.2017.02.013CrossRefPubMed

17.

Lu J, Zhang N, Qian W (2020) The clinical efficacy and safety of traditional Chinese medicine in the treatment of recurrent aphthous stomatitis: a protocol of systematic review and meta-analysis. Medicine 99:e22588. https://doi.org/10.1097/md.0000000000022588CrossRefPubMedPubMedCentral

18.

Hamishehkar H, Nokhodchi A, Ghanbarzadeh S, Kouhsoltani M (2015) Triamcinolone acetonide oromucoadhesive paste for treatment of aphthous stomatitis. Adv Pharm Bull 5:277–282. https://doi.org/10.15171/apb.2015.038CrossRefPubMedPubMedCentral

19.

Halboub E, Alkadasi B, Alakhali M, AlKhairat A, Mdabesh H, Alkahsah S and Abdulrab S (2019) N-acetylcysteine versus chlorhexidine in treatment of aphthous ulcers: a preliminary clinical trial. J Dermatolog Treat:1–5. https://doi.org/10.1080/09546634.2019.1688231

20.

Brocklehurst P, Tickle M, Glenny AM, Lewis MA, Pemberton MN, Taylor J, Walsh T, Riley P and Yates JM (2012) Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database Syst Rev:Cd005411. https://doi.org/10.1002/14651858.CD005411.pub2

21.

Zeng Q, Shi X, Yang J, Yang M, Zhao W, Zhao X, Shi J, Zhou H (2020) The efficacy and safety of thalidomide on the recurrence interval of continuous recurrent aphthous ulceration: a randomized controlled clinical trial. J Oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol 49:357–364. https://doi.org/10.1111/jop.12960CrossRef

22.

Chen LH, Xue JF, Zheng ZY, Shuhaidi M, Thu HE, Hussain Z (2018) Hyaluronic acid, an efficient biomacromolecule for treatment of inflammatory skin and joint diseases: a review of recent developments and critical appraisal of preclinical and clinical investigations. Int J Biol Macromol 116:572–584. https://doi.org/10.1016/j.ijbiomac.2018.05.068CrossRefPubMed

23.

Salwowska NM, Bebenek KA, Żądło DA, Wcisło-Dziadecka DL (2016) Physiochemical properties and application of hyaluronic acid: a systematic review. J Cosmet Dermatol 15:520–526. https://doi.org/10.1111/jocd.12237CrossRefPubMed

24.

Casale M, Moffa A, Sabatino L, Pace A, Oliveto G, Vitali M, Baptista P, Salvinelli F (2015) Hyaluronic acid: perspectives in upper aero-digestive tract. A systematic review. PloS one 10:e0130637. https://doi.org/10.1371/journal.pone.0130637CrossRefPubMedPubMedCentral

25.

Graça MFP, Miguel SP, Cabral CSD, Correia IJ (2020) Hyaluronic acid-based wound dressings: a review. Carbohyd Polym 241:116364. https://doi.org/10.1016/j.carbpol.2020.116364CrossRef

26.

Wu S, Deng L, Hsia H, Xu K, He Y, Huang Q, Peng Y, Zhou Z, Peng C (2017) Evaluation of gelatin-hyaluronic acid composite hydrogels for accelerating wound healing. J Biomater Appl 31:1380–1390. https://doi.org/10.1177/0885328217702526CrossRefPubMed

27.

Iturriaga V, Bornhardt T, Manterola C, Brebi P (2017) Effect of hyaluronic acid on the regulation of inflammatory mediators in osteoarthritis of the temporomandibular joint: a systematic review. Int J Oral Maxillofac Surg 46:590–595. https://doi.org/10.1016/j.ijom.2017.01.014CrossRefPubMed

28.

Yasuda T (2010) Hyaluronan inhibits prostaglandin E2 production via CD44 in U937 human macrophages. Tohoku J Exp Med 220:229–235. https://doi.org/10.1620/tjem.220.229CrossRefPubMed

29.

Casale M, Moffa A, Vella P, Rinaldi V, Lopez MA, Grimaldi V, Salvinelli F (2017) Systematic review: the efficacy of topical hyaluronic acid on oral ulcers. J Biol Regul Homeost Agents 31:63–69PubMed

30.

Dubovina D, Mihailović B, Bukumirić Z, Vlahović Z, Miladinović M, Miković N, Lazić Z (2016) The use of hyaluronic and aminocaproic acid in the treatment of alveolar osteitis. Vojnosanit Pregl 73:1010–1015. https://doi.org/10.2298/vsp150304125dCrossRefPubMed

31.

Hashem AS, Issrani R, Elsayed TEE, Prabhu N (2019) Topical hyaluronic acid in the management of oral lichen planus: A comparative study. J Investig Clin Dent 10:e12385. https://doi.org/10.1111/jicd.12385CrossRefPubMed

32.

Jacobus Berlitz S, De Villa D, MaschmannInacio LA, Davies S, Zatta KC, Guterres SS, Külkamp-Guerreiro IC (2019) Azelaic acid-loaded nanoemulsion with hyaluronic acid–a new strategy to treat hyperpigmentary skin disorders. Drug Dev Ind Pharm 45:642–650CrossRef

33.

Fariba I, Taghi G, Mazdak E, Maryam T, Hossein S, Shahla E, Zabiholah S (2005) The efficacy of 3% diclofenac in 2.5% hyaluronan gel base for treatment of recurrent aphthous stomatitis (RAS): A double blind study. Egypt Dermatol Online J 1:4

34.

Hamed GY (2015) The efficacy of hyaluronic acid spray in treatment of recurrent aphthus ulcer. Int J Enhanc Res Sci Technol Eng 4:82–86CrossRef

35.

Koray M, Ofluoglu D, Senemtasi A, İşsever H, Yaltirik M (2016) The efficacy of hyaluronic acid gel in pain control of recurrent Aphthous stomatitis. Int J Dent Oral Sci 3:273–275

36.

Mustafa BN, Alzubaidee AF (2020) Comparative evaluation of the efficacy of topical hyaluronic acid (0.2%) and topical triamcinolone acetonide (0.1%) in the treatment of recurrent aphthous stomatitis. Diyala J Med 19:107–117CrossRef

37.

Shalaby HKM (2019) Effect of diode laser combined with hyaluronic acid gel in treatment of recurrent aphthous stomatitis in children: randomized clinical trial. Egypt Dent J 65:3555–3566CrossRef

38.

Zakaria M, Abdelwhab A, Hassan S (2020) Effectiveness of topical hyaluronic acid versus chlorhexidine mouthwashes in the treatment of recurrent aphthous stomatitis: a randomized clinical trial. Egypt Dent J 66:1537–1543CrossRef

39.

Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–9, w64. https://doi.org/10.7326/0003-4819-151-4-200908180-00135CrossRef

40.

Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA (2011) The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ (Clinical research ed) 343:d5928. https://doi.org/10.1136/bmj.d5928CrossRef

41.

Saxen MA, Ambrosius WT, al KF R, Russell AL, Eckert GJ (1997) Sustained relief of oral aphthous ulcer pain from topical diclofenac in hyaluronan: a randomized, double-blind clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 84:356–361. https://doi.org/10.1016/s1079-2104(97)90031-7CrossRefPubMed

42.

Nolan A, Baillie C, Badminton J, Rudralingham M, Seymour RA (2006) The efficacy of topical hyaluronic acid in the management of recurrent aphthous ulceration. J Oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol 35:461–465. https://doi.org/10.1111/j.1600-0714.2006.00433.xCrossRef

43.

Tan R, D-m HU, K-e HU (2012) Study on the effect of hyaluronic acid on the treatment of recurrent oral ulceration. Chin J Aesthet Med 2012:14

44.

Lopez MA, Manzulli N, D’Angelo A, Candotto V, Casale M, Lauritano D (2017) The use of hyaluronic acid as an adjuvant in the management of mucositis. J Biol Regul Homeost Agents 31:115–118PubMed

45.

Lee JH, Jung JY, Bang D (2008) The efficacy of topical 0.2% hyaluronic acid gel on recurrent oral ulcers: comparison between recurrent aphthous ulcers and the oral ulcers of Behcet’s disease. J Eur Acad Dermatol Venereol: JEADV 22:590–595. https://doi.org/10.1111/j.1468-3083.2007.02564.xCrossRefPubMed

46.

Yang Z, Li M, Xiao L, Yi Z, Zhao M, Ma S (2020) Hyaluronic acid versus dexamethasone for the treatment of recurrent aphthous stomatitis in children: efficacy and safety analysis. Braz J Med Biol Res 53:e9886. https://doi.org/10.1590/1414-431X20209886CrossRefPubMedPubMedCentral

47.

Dalessandri D, Zotti F, Laffranchi L, Migliorati M, Isola G, Bonetti S, Visconti L (2019) Treatment of recurrent aphthous stomatitis (RAS; aphthae; canker sores) with a barrier forming mouth rinse or topical gel formulation containing hyaluronic acid: a retrospective clinical study. BMC Oral Health 19:153. https://doi.org/10.1186/s12903-019-0850-1CrossRefPubMedPubMedCentral

48.

Romanò CL, De Vecchi E, Bortolin M, Morelli I, Drago L (2017) Hyaluronic acid and its composites as a local antimicrobial/antiadhesive barrier. J Bone Joint Infect 2:63–72. https://doi.org/10.7150/jbji.17705CrossRef

49.

Hatoum HT, Fierlinger AL, Lin SJ, Altman RD (2014) Cost-effectiveness analysis of intra-articular injections of a high molecular weight bioengineered hyaluronic acid for the treatment of osteoarthritis knee pain. J Med Econ 17:326–337. https://doi.org/10.3111/13696998.2014.902843CrossRefPubMed

Titel: Efficacy of hyaluronic acid for recurrent aphthous stomatitis: a systematic review of clinical trials
verfasst von: Sadeq Ali Al-Maweri
Nader Alaizari
Rawan Hejji Alanazi
Sajna Ashraf
Rania Hejji Alanazi
Hesham Mohammed Al-Sharani
Esam Halboub
Publikationsdatum: 20.09.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Clinical Oral Investigations / Ausgabe 12/2021
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-021-04180-4

Update Zahnmedizin

Bestellen Sie unseren kostenlosen Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Efficacy of hyaluronic acid for recurrent aphthous stomatitis: a systematic review of clinical trials