The Open Dentistry Journal


ISSN: 1874-2106 ― Volume 11, 2017

Xerostomia and Salivary Gland Hypofunction in Patients with Oral Lichen Planus Before and After Treatment with Topical Corticosteroids



Hala Al-Janaby1, Haytham El-Sakka1, Manal Masood1, Walimuni Ashani W. Mendis1, Linda M. Slack-Smith1, Richard Parsons2, Agnieszka M. Frydrych1, *
1 School of Dentistry, The University of Western Australia, Perth, Western Australia
2 School of Occupational Therapy and Social Work, Curtin University, Perth, Western Australia

Abstract

Background:

Oral lichen planus and mouth dryness are common pathoses, yet not entirely understood. These two conditions may be associated, with a few studies investigating the relationship between mouth dryness and oral lichen planus providing conflicting results. None of the studies have explored the specific impact of disease treatment on mouth dryness.

Objective:

The purpose of this observational before and after comparison study was to examine the effect of treatment of oral lichen planus with topical corticosteroids on mouth dryness.

Methods:

Nineteen subjects with oral lichen planus were evaluated for the severity of xerostomia using a xerostomia inventory and a visual analogue scale. Stimulated and unstimulated whole salivary flow rates, unstimulated salivary pH and buffering capacity were also measured. All subjects were evaluated before and after treatment with topical corticosteroids.

Results:

All subjects reported xerostomia before treatment with topical corticosteroids, with 79% reporting a significant improvement (P = 0.03) after treatment. Topical corticosteroid treatment was not associated with statistically significant differences in stimulated or unstimulated salivary flow rates, unstimulated salivary pH or buffering capacity.

Conclusion:

The results of this study suggest that treatment of oral lichen planus with topical corticosteroids may decrease the severity of dry mouth symptoms.

Keywords: Dry mouth, Oral lichen planus, Salivary gland hypofunction, Topical corticosteroids, Xerostomia.


Article Information


Identifiers and Pagination:

Year: 2017
Volume: 11
First Page: 155
Last Page: 163
Publisher Id: TODENTJ-11-155
DOI: 10.2174/1874210601711010155

Article History:

Received Date: 05/10/2016
Revision Received Date: 16/02/2017
Acceptance Date: 28/02/2017
Electronic publication date: 31/03/2017
Collection year: 2017

© 2017 Al-Janaby et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the School of Dentistry, The University of Western Australia, (M512) 35 Stirling Highway, Crawley, Perth, Western Australia; Tel: +618 9346 7670; Fax: +618 9346 7666; E-mail: agnieszka.frydrych@uwa.edu.au




INTRODUCTION

Oral lichen planus (OLP) is a chronic, systemic, immunologically mediated disease, affecting about 0.1 - 2.0% of the general adult population [1Parashar P. Oral lichen planus. Otolaryngol Clin North Am 2011; 44(1): 89-107, vi. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.otc.2010.09.004] [PMID: 21093625]
-3Jensen JL, Barkvoll P. Clinical implications of the dry mouth. Oral mucosal diseases. Ann N Y Acad Sci 1998; 842: 156-62. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/j.1749-6632.1998.tb09643.x] [PMID: 9599305]
]. It affects men and women of all ethnic groups, however, women are more commonly affected and there is a higher prevalence in the Indian population [1Parashar P. Oral lichen planus. Otolaryngol Clin North Am 2011; 44(1): 89-107, vi. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.otc.2010.09.004] [PMID: 21093625]
]. The disease can occur at any age with the typical age at presentation ranging from 30-60 years [1Parashar P. Oral lichen planus. Otolaryngol Clin North Am 2011; 44(1): 89-107, vi. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.otc.2010.09.004] [PMID: 21093625]
]. The pathogenesis of this disease is not completely understood, although a cell-mediated immune response appears to play a major role [4Ergun S, Troşala SC, Warnakulasuriya S, et al. Evaluation of oxidative stress and antioxidant profile in patients with oral lichen planus. J Oral Pathol Med 2011; 40(4): 286-93. [Available from: Science Direct].
[http://dx.doi.org/10.1111/j.1600-0714.2010.00955.x] [PMID: 21039889]
]. At present, treatment of OLP is palliative only and topical corticosteroids (TC) are accepted as the first line of treatment [5Thongprasom K, Carrozzo M, Furness S, Lodi G. Interventions for treating oral lichen planus. Cochrane Database Syst Rev 2011; (7): CD001168. [Available from: Cochrane Database of Systematic Reviews].
[PMID: 21735381]
].

Oral lichen planus can affect any oral site and is present in various forms including: reticular, papular, plaque-like, atrophic, erosive and the rare bullous form [1Parashar P. Oral lichen planus. Otolaryngol Clin North Am 2011; 44(1): 89-107, vi. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.otc.2010.09.004] [PMID: 21093625]
]. The clinical features alone may be sufficient to make a diagnosis [5Thongprasom K, Carrozzo M, Furness S, Lodi G. Interventions for treating oral lichen planus. Cochrane Database Syst Rev 2011; (7): CD001168. [Available from: Cochrane Database of Systematic Reviews].
[PMID: 21735381]
, 6Al-Hashimi I, Schifter M, Lockhart PB, et al. Oral lichen planus and oral lichenoid lesions: Diagnostic and therapeutic considerations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 103(Suppl: S25): e1-e12. Available from: Science Direct.].

Oral lichen planus has been associated with other disorders including infection with the hepatitis C virus [1Parashar P. Oral lichen planus. Otolaryngol Clin North Am 2011; 44(1): 89-107, vi. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.otc.2010.09.004] [PMID: 21093625]
], disturbances in glucose metabolism [7Seyhan M, Özcan H, Sahin I, Bayram N, Karincaoğlu Y. High prevalence of glucose metabolism disturbance in patients with lichen planus. Diabetes Res Clin Pract 2007; 77(2): 198-202. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.diabres.2006.12.016] [PMID: 17275122]
], Sjögren’s syndrome [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
], and has been linked to psychological factors [1Parashar P. Oral lichen planus. Otolaryngol Clin North Am 2011; 44(1): 89-107, vi. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.otc.2010.09.004] [PMID: 21093625]
]. While controversy surrounds the potential for malignant transformation of OLP, currently the World Health Organization (WHO) classifies this disease as a potentially malignant disorder [9Schlosser BJ. Lichen planus and lichenoid reactions of the oral mucosa. Dermatol Ther (Heidelb) 2010; 23(3): 251-67. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/j.1529-8019.2010.01322.x] [PMID: 20597944]
-11van der Meij EH, Mast H, van der Waal I. The possible premalignant character of oral lichen planus and oral lichenoid lesions: A prospective five-year follow-up study of 192 patients. Oral Oncol 2007; 43(8): 742-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.oraloncology.2006.09.006] [PMID: 17112770]
].

Mouth dryness is one of the most common oral health conditions and has been associated with OLP [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
, 10Artico G, Freitas RS, Santos Filho AM, Benard G, Romiti R, Migliari DA. Prevalence of Candida spp., xerostomia, and hyposalivation in oral lichen planusa controlled study. Oral Dis 2014; 20(3): e36-41. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/odi.12120] [PMID: 23656547]
, 12Bokor-Bratic M, Cankovic M, Dragnic N. Unstimulated whole salivary flow rate and anxiolytics intake are independently associated with oral Candida infection in patients with oral lichen planus. Eur J Oral Sci 2013; 121(5): 427-33. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/eos.12073] [PMID: 24028590]
-16Ramon C, Bagan JV, Milian MA, Jimenez Y, Lloria E. Quantitative analysis of saliva in patients with oral lichen planus: A study of 100 cases. Med Oral 2000; 5(3): 187-92. [Available from: Medline].
[PMID: 11507555]
]. It may be attributed to xerostomia, salivary gland hypofunction (SGH) or both [17Thomson WM. Dry mouth and older people. Aust Dent J 2015; 60(Suppl. 1): 54-63. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/adj.12284] [PMID: 25762042]
]. Salivary gland hypofunction refers to a diminished salivary flow rate and is based on objective measures of saliva production [18Nederfors T. Xerostomia and hyposalivation. Adv Dent Res 2000; 14: 48-56. [Available from: EBSCOhost].
[http://dx.doi.org/10.1177/08959374000140010701] [PMID: 11842923]
]. Xerostomia is the subjective experience of mouth dryness [18Nederfors T. Xerostomia and hyposalivation. Adv Dent Res 2000; 14: 48-56. [Available from: EBSCOhost].
[http://dx.doi.org/10.1177/08959374000140010701] [PMID: 11842923]
]. The relationship between SGH and xerostomia is a complex one and although the two conditions are related, the mechanisms by which decreases in salivary output are interpreted as the sensation of mouth dryness are not well understood [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
]. Unlike the causes of SGH, the causes of xerostomia are poorly established, and have been linked to: medication use [19Shetty SR, Bhowmick S, Castelino R, Babu S. Drug induced xerostomia in elderly individuals: An institutional study. Contemp Clin Dent 2012; 3(2): 173-5. l [Available from: EBSCOhost].
[http://dx.doi.org/10.4103/0976-237X.96821] [PMID: 22919217]
], impaired oral fluid balance [20Thelin WR, Brennan MT, Lockhart PB, et al. The oral mucosa as a therapeutic target for xerostomia. Oral Dis 2008; 14(8): 683-9. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/j.1601-0825.2008.01486.x] [PMID: 19193197]
], changes in salivary composition [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
], inflammatory oral mucosal alterations [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
], deficiency states [21Ghom AG, Ghom SA. Textbook of Oral Medicine. 3rd ed. New Delhi: Jaypee Brothers Medical Publishers 2014; pp. 608-9.
[http://dx.doi.org/10.5005/jp/books/12631]
], and changes in patient’s perception mechanisms [22van der Putten G-J, Brand HS, Schols JM, de Baat C. The diagnostic suitability of a xerostomia questionnaire and the association between xerostomia, hyposalivation and medication use in a group of nursing home residents. Clin Oral Investig 2011; 15(2): 185-92. [Available from: SpringerLink].
[http://dx.doi.org/10.1007/s00784-010-0382-1] [PMID: 20165967]
].

The literature pertaining to the associations between OLP and xerostomia and/or SGH is limited [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
, 10Artico G, Freitas RS, Santos Filho AM, Benard G, Romiti R, Migliari DA. Prevalence of Candida spp., xerostomia, and hyposalivation in oral lichen planusa controlled study. Oral Dis 2014; 20(3): e36-41. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/odi.12120] [PMID: 23656547]
, 12Bokor-Bratic M, Cankovic M, Dragnic N. Unstimulated whole salivary flow rate and anxiolytics intake are independently associated with oral Candida infection in patients with oral lichen planus. Eur J Oral Sci 2013; 121(5): 427-33. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/eos.12073] [PMID: 24028590]
-16Ramon C, Bagan JV, Milian MA, Jimenez Y, Lloria E. Quantitative analysis of saliva in patients with oral lichen planus: A study of 100 cases. Med Oral 2000; 5(3): 187-92. [Available from: Medline].
[PMID: 11507555]
]. Some studies have demonstrated a relationship between OLP and SGH [10Artico G, Freitas RS, Santos Filho AM, Benard G, Romiti R, Migliari DA. Prevalence of Candida spp., xerostomia, and hyposalivation in oral lichen planusa controlled study. Oral Dis 2014; 20(3): e36-41. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/odi.12120] [PMID: 23656547]
, 12Bokor-Bratic M, Cankovic M, Dragnic N. Unstimulated whole salivary flow rate and anxiolytics intake are independently associated with oral Candida infection in patients with oral lichen planus. Eur J Oral Sci 2013; 121(5): 427-33. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/eos.12073] [PMID: 24028590]
-16Ramon C, Bagan JV, Milian MA, Jimenez Y, Lloria E. Quantitative analysis of saliva in patients with oral lichen planus: A study of 100 cases. Med Oral 2000; 5(3): 187-92. [Available from: Medline].
[PMID: 11507555]
]. In a cross-sectional study, Lundström, et al. evaluated salivary flow rate, pH and buffering capacity in 39 OLP subjects [15Lundström IM, Anneroth KG, Bergstedt HF, Bergstedt HF. Salivary gland function and changes in patients with oral lichen planus. Scand J Dent Res 1982; 90(6): 443-58. [Available from: EBSCOhost].
[PMID: 6961510]
]. Authors demonstrated that unstimulated salivary flow rate (USFR) was significantly lower in OLP subjects compared to normal reference tables of healthy controls [15Lundström IM, Anneroth KG, Bergstedt HF, Bergstedt HF. Salivary gland function and changes in patients with oral lichen planus. Scand J Dent Res 1982; 90(6): 443-58. [Available from: EBSCOhost].
[PMID: 6961510]
]. The reduction in USFR was greater in the OLP subjects, with increasing disease duration [15Lundström IM, Anneroth KG, Bergstedt HF, Bergstedt HF. Salivary gland function and changes in patients with oral lichen planus. Scand J Dent Res 1982; 90(6): 443-58. [Available from: EBSCOhost].
[PMID: 6961510]
]. Gandara, et al. in two separate studies, examined age-related changes in salivary flow rates, electrolyte and protein concentrations of whole, parotid and labial minor salivary gland saliva in 25 OLP subjects and 25 age and sex matched controls [13Gandara BK, Izutsu KT, Truelove EL, Ensign WY, Sommers EE. Age-related salivary flow rate changes in controls and patients with oral lichen planus. J Dent Res 1985; 64(9): 1149-51. [Available from: EBSCOhost].
[http://dx.doi.org/10.1177/00220345850640091101]
, 14Gandara BK, Izutsu KT, Truelove EL, Mandel ID, Sommers EE, Ensign WY. Sialochemistry of whole, parotid, and labial minor gland saliva in patients with oral lichen planus. J Dent Res 1987; 66(11): 1619-22. [Available from: EBSCOhost].
[http://dx.doi.org/10.1177/00220345870660110201] [PMID: 10872393]
]. No significant differences in USFR and stimulated salivary flow rates (SSFR) were noted between the cases and controls [13Gandara BK, Izutsu KT, Truelove EL, Ensign WY, Sommers EE. Age-related salivary flow rate changes in controls and patients with oral lichen planus. J Dent Res 1985; 64(9): 1149-51. [Available from: EBSCOhost].
[http://dx.doi.org/10.1177/00220345850640091101]
, 14Gandara BK, Izutsu KT, Truelove EL, Mandel ID, Sommers EE, Ensign WY. Sialochemistry of whole, parotid, and labial minor gland saliva in patients with oral lichen planus. J Dent Res 1987; 66(11): 1619-22. [Available from: EBSCOhost].
[http://dx.doi.org/10.1177/00220345870660110201] [PMID: 10872393]
]. A study by Ramon, et al. investigated how different clinical forms of OLP and the extent of oral mucosal involvement affect whole USFR and SSFR in 100 OLP subjects compared to 42 healthy controls [16Ramon C, Bagan JV, Milian MA, Jimenez Y, Lloria E. Quantitative analysis of saliva in patients with oral lichen planus: A study of 100 cases. Med Oral 2000; 5(3): 187-92. [Available from: Medline].
[PMID: 11507555]
]. The study found no statistically significant relationships between these variables [16Ramon C, Bagan JV, Milian MA, Jimenez Y, Lloria E. Quantitative analysis of saliva in patients with oral lichen planus: A study of 100 cases. Med Oral 2000; 5(3): 187-92. [Available from: Medline].
[PMID: 11507555]
]. Lastly, Bokor-Bratic, et al. studied USFRs in 90 OLP subjects and 90 age and sex matched controls and concluded that the mean USFR was within normal range compared to controls [12Bokor-Bratic M, Cankovic M, Dragnic N. Unstimulated whole salivary flow rate and anxiolytics intake are independently associated with oral Candida infection in patients with oral lichen planus. Eur J Oral Sci 2013; 121(5): 427-33. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/eos.12073] [PMID: 24028590]
].

Only two studies investigated the relationship between xerostomia and OLP [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
, 10Artico G, Freitas RS, Santos Filho AM, Benard G, Romiti R, Migliari DA. Prevalence of Candida spp., xerostomia, and hyposalivation in oral lichen planusa controlled study. Oral Dis 2014; 20(3): e36-41. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/odi.12120] [PMID: 23656547]
]. Colquhoun and Ferguson examined the relationship between these variables in 77 OLP subjects and 169 age and sex matched controls [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
]. A statistically significant association was found between OLP and dry mouth symptoms [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
]. Artico, et al. examined both xerostomia and salivary gland hypofunction in 38 OLP subjects, 28 subjects with non-OLP mucosal lesions, and 32 healthy controls [10Artico G, Freitas RS, Santos Filho AM, Benard G, Romiti R, Migliari DA. Prevalence of Candida spp., xerostomia, and hyposalivation in oral lichen planusa controlled study. Oral Dis 2014; 20(3): e36-41. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/odi.12120] [PMID: 23656547]
]. Authors concluded that xerostomia and SGH occurred at similar levels within these three groups [10Artico G, Freitas RS, Santos Filho AM, Benard G, Romiti R, Migliari DA. Prevalence of Candida spp., xerostomia, and hyposalivation in oral lichen planusa controlled study. Oral Dis 2014; 20(3): e36-41. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/odi.12120] [PMID: 23656547]
].

To date, to the best of our knowledge, no study exploring the relationship between OLP and mouth dryness has investigated the effect of treatment of OLP, and therefore disease activity, on xerostomia or SGH in those individuals. The aim of this study was therefore to examine the effect of treatment of OLP with TC on xerostomia and SGH in subjects diagnosed with OLP requiring treatment. It is anticipated that results of this study may further improve our understanding of the symptomatology of OLP and some of the mucosal factors contributing to xerostomia.

MATERIALS AND METHODS

This was an observational before and after comparison study. Participants were selected from a pool of patients attending the oral medicine clinic of the Oral Health Centre of Western Australia (OHCWA), School of Dentistry, University of Western Australia between August 2015 and April 2016.

Subjects included in this study were diagnosed with OLP and presented with symptomatic disease and/or ulcerative/erosive mucosal lesions requiring treatment with TCs. Oral lichen planus subjects who did not speak English; did not consent to participate; did not require treatment with TC, or reported changes in their medical history during the course of the study were excluded.

All subjects were identified following manual screening of OHCWA patient records for the diagnosis of OLP, and all were assessed at the Oral Medicine Clinic between August 2015 and April 2016. At initial presentation and prior to initiating treatment with TC, the age, gender, presence or absence of systemic disease and related medication use were recorded for all participants. All subjects underwent clinical oral examination by an Oral Medicine Specialist, and the presence of OLP lesions was recorded for all intraoral sites. Most cases of OLP [16] were diagnosed on clinical presentation alone (WHO clinical diagnostic criteria) with the remaining cases [3] fulfilling both the WHO clinical and histopathologic criteria [5Thongprasom K, Carrozzo M, Furness S, Lodi G. Interventions for treating oral lichen planus. Cochrane Database Syst Rev 2011; (7): CD001168. [Available from: Cochrane Database of Systematic Reviews].
[PMID: 21735381]
]. For the purposes of this study, OLP lesions were categorised into two basic types: reticular and ulcerative/erosive. All subjects were asked to complete the 11-question XI [22van der Putten G-J, Brand HS, Schols JM, de Baat C. The diagnostic suitability of a xerostomia questionnaire and the association between xerostomia, hyposalivation and medication use in a group of nursing home residents. Clin Oral Investig 2011; 15(2): 185-92. [Available from: SpringerLink].
[http://dx.doi.org/10.1007/s00784-010-0382-1] [PMID: 20165967]
]. A 10 cm VAS was also used to assess the severity of their xerostomia [23Pai S, Ghezzi EM, Ship JA. Development of a visual analogue scale questionnaire for subjective assessment of salivary dysfunction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001; 91(3): 311-6. [Available from: Science Direct].
[http://dx.doi.org/10.1067/moe.2001.111551] [PMID: 11250628]
]. Both USFR and SSFR were measured. Salivary gland hypofunction for whole USFR was considered to be ≤ 0.1ml/min [24Sreebny LM. Saliva in health and disease: an appraisal and update. Int Dent J 2000; 50(3): 140-61. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/j.1875-595X.2000.tb00554.x] [PMID: 10967766]
]. Subjects were requested to refrain from eating or drinking for one hour prior to undertaking the saliva testing. Saliva testing was conducted in three-hour blocks either from 9 am to 12 pm or 1pm to 4pm. Unstimulated saliva was collected by the spitting method [25Navazesh M. Methods for collecting saliva. Ann NY Acad Sci 1993; 694(1): 72-7. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/j.1749-6632.1993.tb18343.x] [PMID: 8215087]
] over a 10-minutes period. Stimulated saliva was also collected by the spitting method [25Navazesh M. Methods for collecting saliva. Ann NY Acad Sci 1993; 694(1): 72-7. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/j.1749-6632.1993.tb18343.x] [PMID: 8215087]
]. Subjects were requested to chew on a piece of paraffin wax for five minutes and then spit the saliva into a cup. The collected saliva was weighed in grams and converted to millilitres. The density of saliva is considered to be about 1g/cm3 [26Johansson A-K, Jorkjend L, Marthinussen MC, Johansson A. A comparison of two clinical methods for measuring saliva in patients with Sjögrens syndrome. Acta Odontol Scand 2012; 70(3): 251-4. [Available from: EBSCOhost].
[http://dx.doi.org/10.3109/00016357.2011.640285] [PMID: 22364259]
]. The pH and buffering capacity of unstimulated saliva was measured using the GC America: Saliva-Check BUFFER® kit (GC America Inc., IL, USA).

Following initiation of treatment with a topical corticosteroid, subjects were reviewed in the Oral Medicine Clinic at time intervals deemed appropriate by the treating consultant. All subjects were followed-up until they became asymptomatic and all ulcerated lesions healed and subjects were no longer using the TC for at least 24 hours to allow for the washout period. At each visit, participants were monitored for changes in their medical conditions and associated medication use.

Statistical analysis was undertaken using the Stata® (version 13.0, Stata Corp LP, College Station, TX, USA) and SAS® (version 9.4, SAS Institute Inc., Cary, NC, USA) software programs. Paired Student’s t-test was used to examine associations between OLP and salivary flow rates, pH, buffering capacity, XI and VAS before and after treatment with TC. Multivariate analysis (Generalised linear model in SAS) was used to assess the correlation of results between the xerostomia tools, as well as between the VAS and systemic medications taken by the subjects and between the VAS and the age of subjects. A probability value of less than 0.05 was considered statistically significant in both univariate and multivariate analyses.

Ethics approval was sought and obtained from the Human Research Ethics Committee of the University of Western Australia.

RESULTS

Fifty-three subjects diagnosed with OLP were recruited for the study with 19 individuals meeting all inclusion criteria during the eight-months data collection period. Reasons for exclusions and characteristics of the 34 excluded individuals are summarised in (Table 1) . The characteristics of participants are presented in (Table 2).

Table 1
Characteristics of excluded individuals and reasons for exclusions.


All nineteen subjects reported xerostomia before and after treatment with TC. When measuring xerostomia using the VAS tool, there was a statistically significant improvement after treatment with TC (t18=-2.4, P = 0.03) (Fig. 1). A positive change in xerostomia was experienced by 79% of participants. No statistically significant difference in xerostomia was found using the 11-question XI, although a random effects regression model identified a strong correlation between the XI and the VAS (P < 0.001) (Fig. 2).

Table 2
Characteristics of participants included in study.


Fig. (1)
Random effects regression analysis model of correlation of VAS and XI (P < 0.001).


When the analysis was restricted to OLP type, a statistically significant reduction in xerostomia was observed on VAS in the subjects with ulcerative OLP (t11=-2.5, P = 0.03) but not for the subjects with the reticular type (t6=-0.8, P = 0.47). No statistically significant relationship was found between medication use and the change in xerostomia based on VAS. Similarly, no significant association was found between age and the change in xerostomia based on VAS.

Fig. (2)
Random effects regression analysis model of correlation of VAS and XI (P < 0.001).


Salivary gland hypofunction was observed in 47% of OLP subjects before treatment and in 37% of subjects after treatment, and there was no significant change in the USFR (t18=-0.1, P = 0.88). Treatment with TC was not associated with statistically significant differences in stimulated or unstimulated whole salivary flow rates, unstimulated salivary pH or buffering capacity.

DISCUSSION

The literature pertaining to the associations between mouth dryness and OLP is limited. While these conditions constitute common oral pathoses, both are complex and not entirely understood [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
]. Results of studies investigating the relationship between OLP and xerostomia and / or SGH have been conflicting and none of the studies have explicitly taken the effect of treatment of OLP into account [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
, 10Artico G, Freitas RS, Santos Filho AM, Benard G, Romiti R, Migliari DA. Prevalence of Candida spp., xerostomia, and hyposalivation in oral lichen planusa controlled study. Oral Dis 2014; 20(3): e36-41. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/odi.12120] [PMID: 23656547]
, 12Bokor-Bratic M, Cankovic M, Dragnic N. Unstimulated whole salivary flow rate and anxiolytics intake are independently associated with oral Candida infection in patients with oral lichen planus. Eur J Oral Sci 2013; 121(5): 427-33. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/eos.12073] [PMID: 24028590]
-16Ramon C, Bagan JV, Milian MA, Jimenez Y, Lloria E. Quantitative analysis of saliva in patients with oral lichen planus: A study of 100 cases. Med Oral 2000; 5(3): 187-92. [Available from: Medline].
[PMID: 11507555]
]. Given that inflammatory mucosal changes have been linked to xerostomia [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
], the impact of treatment influencing the inflammatory process warrants investigation. To the best of the authors’ knowledge, this is the first study specifically examining the effect of treatment of OLP with TC on xerostomia and SGH.

Nineteen subjects satisfied all inclusion criteria, ranging in age from 53-80 years consistent with previous studies [10Artico G, Freitas RS, Santos Filho AM, Benard G, Romiti R, Migliari DA. Prevalence of Candida spp., xerostomia, and hyposalivation in oral lichen planusa controlled study. Oral Dis 2014; 20(3): e36-41. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/odi.12120] [PMID: 23656547]
, 12Bokor-Bratic M, Cankovic M, Dragnic N. Unstimulated whole salivary flow rate and anxiolytics intake are independently associated with oral Candida infection in patients with oral lichen planus. Eur J Oral Sci 2013; 121(5): 427-33. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/eos.12073] [PMID: 24028590]
, 15Lundström IM, Anneroth KG, Bergstedt HF, Bergstedt HF. Salivary gland function and changes in patients with oral lichen planus. Scand J Dent Res 1982; 90(6): 443-58. [Available from: EBSCOhost].
[PMID: 6961510]
, 16Ramon C, Bagan JV, Milian MA, Jimenez Y, Lloria E. Quantitative analysis of saliva in patients with oral lichen planus: A study of 100 cases. Med Oral 2000; 5(3): 187-92. [Available from: Medline].
[PMID: 11507555]
]. Women were overrepresented in our study, accounting for 89% of all participants, also in keeping with previous publications [10Artico G, Freitas RS, Santos Filho AM, Benard G, Romiti R, Migliari DA. Prevalence of Candida spp., xerostomia, and hyposalivation in oral lichen planusa controlled study. Oral Dis 2014; 20(3): e36-41. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/odi.12120] [PMID: 23656547]
, 12Bokor-Bratic M, Cankovic M, Dragnic N. Unstimulated whole salivary flow rate and anxiolytics intake are independently associated with oral Candida infection in patients with oral lichen planus. Eur J Oral Sci 2013; 121(5): 427-33. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/eos.12073] [PMID: 24028590]
]. Women have a higher prevalence of OLP [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
]; are more likely to seek medical treatment and are therefore more likely to be overrepresented [27Kandrack MA, Grant KR, Segall A. Gender differences in health related behaviour: Some unanswered questions. Soc Sci Med 1991; 32(5): 579-90. [Available from: Science Direct].
[http://dx.doi.org/10.1016/0277-9536(91)90293-L] [PMID: 2017726]
]. The female dominance in our study population may also partly explain why all subjects reported xerostomia at presentation. It is well known that the prevalence of SGH and xerostomia is more common in women than men [28Liu B, Dion MR, Jurasic MM, Gibson G, Jones JA. Xerostomia and salivary hypofunction in vulnerable elders: prevalence and etiology. Oral Surg Oral Med Oral Pathol Oral Radiol 2012; 114(1): 52-60. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.oooo.2011.11.014] [PMID: 22727092]
]. Some of the reasons for this include: women having smaller salivary glands; producing less saliva; and having lower salivary gland functional capacity than men [28Liu B, Dion MR, Jurasic MM, Gibson G, Jones JA. Xerostomia and salivary hypofunction in vulnerable elders: prevalence and etiology. Oral Surg Oral Med Oral Pathol Oral Radiol 2012; 114(1): 52-60. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.oooo.2011.11.014] [PMID: 22727092]
]. In addition to this, women are generally likely to take more medications than their male counterparts [28Liu B, Dion MR, Jurasic MM, Gibson G, Jones JA. Xerostomia and salivary hypofunction in vulnerable elders: prevalence and etiology. Oral Surg Oral Med Oral Pathol Oral Radiol 2012; 114(1): 52-60. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.oooo.2011.11.014] [PMID: 22727092]
].

The majority of our participants presented with other co-morbidities (Table 2) and two of the participants had a concurrent diagnosis of Sjögren’s Syndrome. Furthermore, 63% of the participants took medications which have been associated with mouth dryness. These co-morbidities have also contributed to the high prevalence of xerostomia and SGH in our study population. Nonetheless, none of the participants reported any changes to their medical conditions or any changes to their prescribed medications, including dose changes, over the course of this study.

All subjects reported xerostomia before commencing treatment with TC. When measuring xerostomia using the VAS tool, 79% reported a statistically significant improvement after treatment with TC. No statistically significant difference in xerostomia was found using the XI, although a correlation was observed between the two xerostomia tools. A correlation between VAS and Likert scale based assessments of xerostomia has been previously demonstrated [29Gerdin EW, Einarson S, Jonsson M, Aronsson K, Johansson I. Impact of dry mouth conditions on oral health-related quality of life in older people. Gerodontology 2005; 22(4): 219-26. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/j.1741-2358.2005.00087.x] [PMID: 16329230]
]. Lack of a statistically significant difference in xerostomia using the XI in this study may be due to a number of factors, including our small sample size. Additionally, the XI has a tendency to assess xerostomia over time while VAS assesses the condition at a specific point in time [30Kersten P, White PJ, Tennant A. Is the pain visual analogue scale linear and responsive to change? An exploration using Rasch analysis. PLoS One 2014; 9(6): e99485. [Available from: Proquest Public Health].
[http://dx.doi.org/10.1371/journal.pone.0099485] [PMID: 24921952]
], which arguably may be more applicable in a study of a dynamic disease such as OLP, where the specific aim is to establish the effect of treatment at a particular point in time [31Crichton N. Visual Analogue Scale (VAS). J Clin Nurs 2001; 10(5): 706. [Available from: EBSCOhost].]. Furthermore, the XI includes questions relating to extra-oral symptoms, which were not the focus of our study [32Thomson WM, van der Putten GJ, de Baat C, et al. Shortening the xerostomia inventory. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011; 112(3): 322-7. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2011.03.024] [PMID: 21684773]
] and the answer options may have been confusing to some participants [22van der Putten G-J, Brand HS, Schols JM, de Baat C. The diagnostic suitability of a xerostomia questionnaire and the association between xerostomia, hyposalivation and medication use in a group of nursing home residents. Clin Oral Investig 2011; 15(2): 185-92. [Available from: SpringerLink].
[http://dx.doi.org/10.1007/s00784-010-0382-1] [PMID: 20165967]
]. Finally, Likert scales, of which the XI is an example, have a tendency for scores towards the midline instead of scores at the extremes, whereas VAS is a continuous scale and is more sensitive at detecting small differences [33Bots CP, Beest AV, Brand HS. The assessment of oral dryness by photographic appearance of the tongue. Br Dent J 2014; 217(2): E3. [Available from: British Dental Journal].
[http://dx.doi.org/10.1038/sj.bdj.2014.597] [PMID: 25060478]
].

Xerostomia is a complex, multifactorial and, overall, a poorly understood phenomenon [20Thelin WR, Brennan MT, Lockhart PB, et al. The oral mucosa as a therapeutic target for xerostomia. Oral Dis 2008; 14(8): 683-9. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/j.1601-0825.2008.01486.x] [PMID: 19193197]
]. While xerostomia has been linked to mucosal diseases such as OLP, the exact mechanisms have not been explained. It has been proposed that the inflamed mucosa in OLP subjects may be associated with altered surface texture, contributing to the sensation of mouth dryness [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
]. How altered surface texture may contribute to xerostomia has not been clarified [8Colquhoun AN, Ferguson MM. An association between oral lichen planus and a persistently dry mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1): 60-8. [Available from: Science Direct].
[http://dx.doi.org/10.1016/j.tripleo.2003.11.003] [PMID: 15243472]
]. Results of our study seem to support a role for inflammatory mucosal injury (as occurs in OLP) in xerostomia, as suppression of inflammation with TC has been associated with improvement in dry mouth symptoms, in the absence of any significant changes in salivary flow rates. This is further supported by the fact that the most significant improvement in xerostomia occurred in individuals with the more severe disease, namely with erosive/ulcerative lesions, as compared to individuals with reticular disease only.

Impaired oral fluid balance has been linked to xerostomia and may be impacted by mucosal disease [20Thelin WR, Brennan MT, Lockhart PB, et al. The oral mucosa as a therapeutic target for xerostomia. Oral Dis 2008; 14(8): 683-9. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/j.1601-0825.2008.01486.x] [PMID: 19193197]
]. Saliva forms a thin film that covers the oral cavity, varying in thickness from about 72-100 microns, depending on the site [20Thelin WR, Brennan MT, Lockhart PB, et al. The oral mucosa as a therapeutic target for xerostomia. Oral Dis 2008; 14(8): 683-9. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/j.1601-0825.2008.01486.x] [PMID: 19193197]
]. This steady state volume of residual fluid reflects a balance between fluid secretion by the salivary glands and fluid loss, as can occur through swallowing, absorption across the mucosal epithelium and evaporation [34Zhang GH, Castro R. Role of oral mucosal fluid and electrolyte absorption and secretion in dry mouth. Chin J Dent Res 2015; 18(3): 135-54. [Available from: Medline].
[PMID: 26485506]
]. It has been shown that individuals with xerostomia, who do not necessarily present with SGH, exhibit abnormally low salivary film thicknesses [20Thelin WR, Brennan MT, Lockhart PB, et al. The oral mucosa as a therapeutic target for xerostomia. Oral Dis 2008; 14(8): 683-9. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/j.1601-0825.2008.01486.x] [PMID: 19193197]
]. Chronic mucosal inflammation, as occurs in OLP, may disturb this oral fluid balance by compromising the integrity and function of the oral epithelium, specifically, by adversely affecting the normal fluid and electrolyte absorption, and secretion by the epithelium, a dysfunction which has been attributed to xerostomia [34Zhang GH, Castro R. Role of oral mucosal fluid and electrolyte absorption and secretion in dry mouth. Chin J Dent Res 2015; 18(3): 135-54. [Available from: Medline].
[PMID: 26485506]
-36Riber E, Kaaber S. Barrier properties of inflamed denture-loaded palatal mucosa to water. Scand J Dent Res 1978; 86(5): 386-91. [Available from: EBSCOhost].
[PMID: 281759]
]. Loss of epithelium, as occurs in ulceration, also likely affects the formation of oral mucosal pellicle, which lubricates the oral soft tissues [34Zhang GH, Castro R. Role of oral mucosal fluid and electrolyte absorption and secretion in dry mouth. Chin J Dent Res 2015; 18(3): 135-54. [Available from: Medline].
[PMID: 26485506]
]. Heat associated with an inflammatory reaction may enhance surface fluid evaporation.

While the exact mechanisms require investigation, results of this study support a link between OLP and xerostomia and suggest that the suppression of the inflammatory reaction, the healing of mucosal lesions and restoration of mucosal integrity following the use of TC contributed to the improvement in the severity of xerostomia in the OLP subjects studied. Control of OLP with TC was not associated with complete resolution of xerostomia and this was not expected due to the comorbidities of the study population and the associated high prevalence of SGH. Results of this study also support earlier observations that xerostomia may form part of the symptomatology of OLP in some individuals.

Treatment with TC was not associated with statistically significant differences in stimulated or unstimulated whole salivary flow rates, unstimulated salivary pH or buffering capacity. This again was not unexpected. OLP is not primarily a disease of the salivary glands [37Sugerman PB, Savage NW. Oral lichen planus: causes, diagnosis and management. Aust Dent J 2002; 47(4): 290-7. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/j.1834-7819.2002.tb00540.x] [PMID: 12587763]
] and therefore treatment with TC was not expected to significantly influence salivary gland function nor the salivary pH or the buffering capacity, both of which are flow rate dependent [38Fenoll-Palomares C, Muñoz Montagud JV, Sanchiz V, et al. Unstimulated salivary flow rate, pH and buffer capacity of saliva in healthy volunteers. Rev Esp Enferm Dig 2004; 96(11): 773-83. [Available from: Medline].
[http://dx.doi.org/10.4321/S1130-01082004001100005] [PMID: 15584851]
]. While it was not possible to collect all salivary samples at the same time of day to compensate for the potential influence of the circadian rhythm, Osalin, et al. have questioned the significance of the circadian rhythm on USFR, suggesting that USFR can be measured during normal clinic hours [39Osailan S, Pramanik R, Shirodaria S, Challacombe SJ, Proctor GB. Investigating the relationship between hyposalivation and mucosal wetness. Oral Dis 2011; 17(1): 109-14. [Available from: Wiley Online Library].
[http://dx.doi.org/10.1111/j.1601-0825.2010.01715.x] [PMID: 21029258]
].

This study has limitations including a small sample size due to limited availability of patients and absence of histological confirmation of diagnosis in some cases. Nonetheless, all participants presented with clinically obvious diagnosis [6Al-Hashimi I, Schifter M, Lockhart PB, et al. Oral lichen planus and oral lichenoid lesions: Diagnostic and therapeutic considerations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 103(Suppl: S25): e1-e12. Available from: Science Direct.], as was determined by an Oral Medicine Specialist, and all subjects responded to treatment with TC, as was expected of the condition. The value of histological confirmation of the classic reticular form of OLP has also been previously questioned [6Al-Hashimi I, Schifter M, Lockhart PB, et al. Oral lichen planus and oral lichenoid lesions: Diagnostic and therapeutic considerations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 103(Suppl: S25): e1-e12. Available from: Science Direct.]. Future studies examining the relationship between OLP and mouth dryness should consider the potential impact of OLP treatment and disease activity and further explore the mechanism underpinning xerostomia in OLP subjects.

CONCLUSION

To the best of the authors’ knowledge, this is the first study examining the effect of treatment of OLP with TC on xerostomia and SGH. Within the limitations of this study, results obtained suggest that treatment of OLP with TC may decrease the severity of dry mouth symptoms and that xerostomia may form part of the symptomatology of OLP in some individuals.

CONFLICT OF INTEREST

The authors confirm that this article content has no conflict of interest.

ACKNOWLEDGEMENTS

The authors acknowledge the School of Dentistry, University of Western Australia for providing consumables for this study.

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