Oral Lichen Planus – A Relapsing and Remitting Mucocutaneous Disease

ABSTRACT

Objectives: Lichen planus is a mucocutaneous disease that can manifest in the oral cavity. Although commonly described as bilateral reticular lesions on the buccal mucosa, there are 6 oral subtypes of oral lichen planus. The purpose of this paper is to give an overview of oral lichen planus including differentiation from oral lichenoid lesions, proposed etiology, diagnosis, treatment, malignant transformation, prevention and future directions.

Materials and methods: The PubMed/MEDLINE search engine was used to gather information on lichen planus restricted to a five-year period (11 August 2019 – 10 July 2023). Only English-language studies and reviews with the best sensitivity and specificity were considered. A Boolean search of the PubMed data set was implemented with the following combination of key words: (“oral lichen planus” OR “oral lichenoid lesions” OR “oral lichenoid reactions”) which yielded 164 publications. Additional articles were selected through Google Scholar.

Results: By this process, many articles and studies were obtained, and the 45 most relevant published studies were chosen and used in the current review. The selected articles are in the reference list.

Conclusions: Oral lichen planus is one of the most observed pathologies in dentistry. Although some subtypes are relatively asymptomatic and harmless, others cause patients pain and discomfort and may result in an increased risk of oral squamous cell carcinoma. It is important for general dentists to be able to identify all types of oral lichen planus to monitor and prevent malignancies as well as treat the discomforting lesions. Future considerations in improving diagnostics and standardizing promising therapies like photobiomodulation therapy are needed.

Keywords: lichen planus, oral lichen planus, oral lichenoid lesions, oral lichenoid reactions, oral potentially malignant disorder(s), topical corticosteroids, systemic corticosteroids, calcineurin inhibitors.

Oral lichen planus (OLP) is a chronic autoimmune disease of unknown etiology.¹ It is termed a mucocutaneous disease since it can affect the skin, scalp, nails and mucous membranes.² Extra-oral lesions tend to be self-limiting, whereas oral lesions are chronic. These chronic lesions are seen on the tongue and buccal mucosa more often than on the gingiva.¹ Lichen planus (LP) is Greek for flat tree moss which is fitting since it often presents as a symmetrical bilateral pattern of reticular lesions.^1,3 However in more severe cases, there can also be erosions due to mucosal thinning as well as redness and increased sensitivity.³ OLP varies from asymptomatic lesions to severe ulcerations. Exacerbations of more severe disease coincide with factors like stress, anxiety, trauma, exposure to a low chronic irritant like plaque or tobacco or a new dental filling.³ Overall, there are 17 subtypes of lichen planus on the body including: vesiculobullous, hypertrophic, actinic, linear, annular, nail, zosteriform, inverse, atrophic, erosive, eruptive, planopilaris, pigmentosus, erythematous overlap syndrome, vulvovaginal, pemphigoid, and the focus of this paper oral lichen planus.¹

OLP usually presents as lesions limited to the oral cavity, but in 20% of cases lesions may also be noted in the genital region and in 15% of cases there may be lesions on the skin.³ In contrast, 70% of individuals with cutaneous LP (CLP) have OLP, making it important for clinicians to perform extraoral and intraoral examinations. The worldwide prevalence of LP is 0.22-5% and the prevalence of OLP is 1-2%.¹ Interestingly, the prevalence of OLP is the lowest in India (0.49%) due to masking of the disease by hyperkeratosis from tobacco products.⁴ OLP has a female predilection of 1.5:1 and is more frequently seen in women between the ages of 30-60.¹ In a systematic review by González-Moles et al., it was found that the risk of developing OLP increases significantly at 40 years and progressively continues to increase with age.⁴ Ciesielska and colleagues also noted that OLP is more common in perimenopausal women than premenopausal women and is frequently seen in those with depression and other psychological disorders.⁵ In this subpopulation, alterations in sex hormones may provoke OLP by causing these disorders.

An association between psychological disorders (e.g., anxiety, depression) and OLP has been well documented in literature.⁶ This association exists in both symptomatic and asymptomatic states. Stress and poor sleep quality are also considered risk factors for OLP. Interestingly, worrying about potential malignancy due to OLP may also cause psychological disorders and thus practitioners should be sensitive to the mental health of their patients. There are many other associations with OLP and here a few will be described in further detail. For example, in a review on intraoral manifestations of celiac disease by Lucchese et al., many extra-intestinal manifestations were described including OLP.⁷

Moreover, in a systematic review by Sanadi and colleagues, it was determined that probing depths and bleeding on probing were significantly associated with OLP.⁸ Erosive and atrophic subtypes of OLP also cause painful lesions on the oral mucosa which results in poor oral hygiene thus increasing the risk of plaque-induced periodontal destruction. Thus, there is potential for OLP to aggravate or cause periodontal destruction. A systematic review and meta-analysis by Nunes and colleagues further supports this, since a significant relationship between the severity of periodontal disease and the presence of oral lichen planus was noted.⁹ In this review, increased probing depths and clinical attachment loss were found in all studies of patients with OLP as well as greater tooth loss. Increased inflammatory markers like interleukins and MMPs were observed in patients with OLP and periodontitis which also may indicate that OLP worsens periodontal damage.

OLP is also frequently associated with other autoimmune disorders like type 1 diabetes, thyroid diseases and rheumatoid arthritis.¹⁰ Other associations also exist for example: HPV, candida albicans, nutrient deficiency, food allergy, Good’s syndrome, hepatitis C, and hypertension.^2,3,11 Lastly, in light of the recent pandemic, LP is also a rare complication after COVID-19 vaccination probably due to overstimulated T cell responses and proinflammatory cytokine production.¹²

In this article, an overview of oral lichen planus including differentiation from oral lichenoid lesions, proposed etiology, diagnosis, treatment, malignant transformation, prevention and future directions will be discussed.

ETIOLOGY

The pathogenesis of OLP is not completely understood.³ It is proposed that cytotoxic T lymphocytes (CTLs) against basal keratinocytes may be the cause of this mucocutaneous disease.¹³ El‐Howati and colleagues described this T cell mediated response as a dysregulated immune response that results in keratinocyte death, basement membrane destruction and disease chronicity.³ Antigens presented by basal cells as well as foreign antigens may induce this immune response, but there is no single antigen that can trigger OLP. So, there may be multiple viral or microbial antigens that drive the T cell-mediated destruction.

There are many proposed mechanisms for OLP pathogenesis. Here, four mechanisms described by Afzali and colleagues are summarized.¹ The first proposed mechanism is cell-mediated antigen-specific immunity. This is where CTLs are activated by factors like drugs and dental materials resulting in basal keratinocyte death. It is possible that these factors may unmask or alter self-antigens resulting in this auto-immune response.³ The second proposed mechanism is non-specific in which matrix metalloproteinases (MMPs) cause degradation of connective tissue and disrupt the basement membrane.¹ These non-specific mechanisms are associated with MMPs, macrophages, degranulated mast cells and association of the chemokine RANTES-CCR5. Third is autoimmunity. OLP has some features of autoimmune diseases like female predilection, adult-onset, chronicity, CTLs. An example of an autoimmune mechanism in OLP is the production of autoreactive T cells. The last proposed mechanism of OLP pathogenesis is via humoral immunity (circulating autoantibodies).

There are also factors that make some individuals more susceptible to OLP. These predisposing factors include genetic background, psychological factors such as anxiety and depression, as well as trauma.² In the case of trauma, some people are more prone to trauma than others and this can present as trauma to the buccal mucosa and lateral surface of the tongue. Lastly, there are thought to be specific mechanisms of pathogenesis (CD4 and CD8 T cells) and non-specific mechanisms (epithelial basement membrane, MMPs, chemokines, mast cells). All in all, although there are many associations and theories for the pathogenesis of OLP, the etiology has not been fully elucidated.

CLINICAL AND HISTOLOGICAL PRESENTATION

As mentioned, OLP is classically found symmetrically and bilaterally on the buccal mucosa.² It can also be found on the tongue, gingiva as well as the labial mucosa and is uncommonly found on the palate, floor of the mouth, and upper lip. Ideally, the diagnosis of OLP is via clinical and histological examination. There are six oral subtypes of OLP, namely: reticular, plaque-like, atrophic, erosive/ulcerative, papular and bullous. The most common subtypes are: reticular, plaque-like and erosive/ulcerative, of which the reticular subtype may be diagnosed solely through clinical examination. Since the majority of individuals with CLP also have OLP it is also important to discuss key features of this and stress the importance of both intraoral and extraoral patient examinations.³ The common clinical features of OLP and CLP are described in Table 1.

Table 1: Common clinical features of the OLP and CLP

Subtype	Common Clinical Features
Reticular (oral)	– Most common subtype ^1,2 – Hallmark feature: symmetrical bilateral lacy lesions on the mucosa and cheek coined Wickham striae ^1,2,14 – Tends to be asymptomatic but occasionally results in taste alterations and burning tongue sensation ^2,14 – Palatal Lesion of Reverse Smoking
Plaque-like (oral)	– Resembles leukoplakia (white, homogenous, elevated, multifocal, smooth keratotic lesions) ^1,2,14 – Commonly on the dorsum of the tongue and buccal mucosa ^1,2,14 – May have striations ¹⁴
Atrophic (oral)	– Usually does not spontaneously remit ² – Diffuse red lesions ¹ – Can be seen as reticular lesions with central erythema ¹ – Often mistaken for vesiculo-bullous diseases ² – May have previous reticular lesions ¹⁴ – Symptoms vary from burning sensation to intense pain ¹⁵ – Difficulty eating, swallowing, burning sensation with hot and spicy food ¹⁵
Erosive/ulcerative (oral)	– Usually does not spontaneously remit ² – Redness, inflammation, epithelium thinning, ulceration with pseudomembrane and lesions surrounded by peripheral reticular keratotic striae ^1,2,14 – Can see lesions, ulcers, bullae ¹⁴ – Often mistaken for vesiculo-bullous diseases ² – Symptoms vary from burning sensation to intense pain ¹⁵ – Difficulty eating, swallowing, burning sensation with hot and spicy food ¹⁵
Papular (oral)	– Rare ¹ – Tiny white papules (1 mm in diameter) with peripheral striae, usually on buccal mucosa ^1,14
Bullous (oral)	– Most rare ¹ – Severe erosions that result in epithelial rupture and bullae formation ^1,14
CLP (extraoral)	– Self-limiting² – Cutaneous lesions are described by 6Ps: planar, purple polygonal, pruritic, papule and plaque ¹⁶ – Presents as pink, flat, pruritic lesions that may have Wickham striae surrounding the lesions ^17,18 – Found on skin, nails, scalp and other mucosal sites ¹³ – Most common extraoral site in females: genital mucosa (usually erosive lesions) ¹³ – Males can have penogingival involvement ¹³ – Rare extraoral mucosal sites: ears, eyes, nose, larynx, esophagus, gastric ¹³

The signs and symptoms of OLP vary depending on the subtype and individual. Some patients may have no symptoms as described earlier, however others may experience multiple such as roughness on the mouth lining, sensitivity of oral mucosa to hot or spicy foods and pain.² About two thirds of patients experience some level of discomfort and patients undergo relapses and remissions. Triggers of relapses include: sharp cusps, ill-fitting dentures and the accumulation of plaque and calculus. Some patients may also present with recession because of OLP or even brown-black oral post-inflammatory pigmentation.

It is also important to discuss the histology of OLP since the gold standard to diagnose all OLP lesions is via biopsy (16). Briefly, the histological features of OLP are as outlined: ^2,3

Liquefactive degeneration of basal cells to form colloid (civatte) bodies
Homogenous sub-epithelial band-like lymphocytic infiltrate
Normal epithelium maturation
May see ulceration/erosion, irregular acanthosis, saw-tooth rete ridges, fibrous sub-epithelial precipitate and hyperkeratosis

DIAGNOSIS

As mentioned, the diagnosis of OLP is via clinical and histological presentation. The original diagnostic criteria for OLP was developed by the World Health Organization in 1978.¹⁹ This was later revised in 2003 by van der Meij and van der Waal. The most current diagnostic criteria was updated by the American Academy of Oral and Maxillofacial Pathology (AAOMP) in 2016 and consists of the clinical and histologic criteria in Table 2.

Table 2: American Academy of Oral and Maxillofacial Pathology OLP Diagnostic Criteria ¹⁹

Clinical Criteria

– Multifocal symmetric distribution of white and red lesions exhibiting one or more of the following forms: reticular/papular, atrophic (erythematous), erosive (ulcerative), plaque, bullous
– Lesions are not localized to the sites of smokeless tobacco placement or adjacent to and in contact with dental restorations
– Lesion onset does not correlate with the start of a medication or with the use of cinnamon-containing products

Histopathologic criteria

– Band-like or patchy, predominately lymphocytic infiltrate in the lamina propria confined to the epithelium-lamina propria interface
– Basal cell liquefactive (hydropic) degeneration
– Lymphocytic exocytosis
– Absence of epithelial dysplasia
– Absence of verrucous epithelial architectural change

There is currently no standardized scoring system for reporting the severity of OLP. However, the most reported system by Thongprasom et al. may be useful for clinical monitoring.²⁰ This system evaluates white striae, atrophic mucosa and erosive mucosa as outlined in Table 3.

Table 3: Thongprasom and colleagues’ OLP scoring system ²⁰

Score	Criteria
0	No lesion, normal mucosa
1	Mild white striae, no erythematous area
2	White striae with atrophic area <1 cm2
3	White striae with an atrophic area >1 cm2
4	White striae with erosive area <1 cm2
5	White striae with erosive area >1 cm2

OLP AND ORAL LICHENOID LESIONS

Oral lichenoid reactions (OLR) are often confused for OLP and vice versa, and in some of the literature OLR are considered a variant of OLP.² However, as can be deciphered by the name, OLR are caused by a reaction to something – whether it be a medication or material. OLP on the other hand has an unknown etiology. To better differentiate OLR and OLP, the three types of lichenoid lesions (OLLs) will be further described here.

The first type of OLL is a contact lichenoid lesion (CLL), or type IV hypersensitivity reaction. These are due to prolonged contact of the oral mucosa with dental materials like amalgam, composite, nickel or cobalt.^2,21 As González-Moles and colleagues highlighted in their paper, one becomes suspicious of a CLL in cases like: the presence of unilateral lesions, lesions in intimate contact with amalgam restorations, lesions that do not respond to typical OLP treatment and lesions without an extraoral component or desquamative gingivitis.²¹ To manage CLLs a dentist may remove the material in question such as amalgam, however doing this to someone with OLP will not ameliorate any symptoms. In fact, through patch testing it was found that 70% of CLLs were positive for amalgam or mercury compared to only 3.9% positivity for OLP lesions. Therefore, there is no benefit to replacing amalgam restorations in an individual with OLP.²

The second type of OLL is a lichenoid drug reaction (LDR). These are caused by drugs such as antihypertensives, dapsone, oral hypoglycemics, non-steroidal anti-inflammatory drugs, penicillamine, phenothiazines, anti-malarials, sulfonylureas, gold salts, antiretroviral medications for HIV, diuretics, antifungals (ketoconazole) as well as anti-convulsant drugs (carbamazepine).^2,21 The clinical presentation of LDRs can resemble reticular, plaque-like, erosive and erythematous variations of OLP. However, unlike OLP these lesions tend to be unilateral and appear after taking medications.²¹ It can take months to clear up a LDR.

The third type of oral lichenoid reaction is in the context of graft versus host disease (GVHD). The clinical and histological presentation of GVHD and OLP are similar. GVHD is often seen in haematopoietic stem cell transplant recipients and is treated via topical corticosteroids.²¹

Overall, the treatment and presentation of OLP and OLR may be different which is why it is important to be able to distinguish the two. For example, studies have shown that malignant transformation is seen only in OLP.²¹ However, other authors like González-Moles and colleagues believe there is not enough evidence for this and OLP and OLL should not be separated due to fears of undertreating OLP or potential malignant transformation. Moreover, although OLRs closely resemble OLP clinically and histologically, there are some differences to account for. As mentioned, OLR tend to be unilateral.^3,21 Moreover, OLP is often accompanied by extraoral lesions, however OLRs are not. Lastly, histologically OLRs may have a more diffuse lymphocytic infiltrate with more eosinophils, plasma cells and colloid bodies.^2,3

TREATMENT AND MANAGEMENT

Since the etiology of OLP isn’t fully known, the treatment is symptomatic (Table 4). Thus, if there are no symptoms (such as the case in most reticular lesions and occasionally plaque-like lesions) treatment is not necessary.^2,14 For symptomatic lesions the treatment algorithm is generally topical corticosteroids as a first-line approach and systemic corticosteroids as a second-line approach for severe cases.^2,6,14 Although not recommended by all, calcineurin inhibitors may be considered if the OLP does not respond to the corticosteroids.²² If lesions are widespread, mouth rinse treatments are preferred over gels and ointments to cover a larger surface.^2,14 It is important to alleviate symptoms to reduce the risk of malignant transformation.² This is why, if mechanical trauma or irritants such as sharp or rough surfaces are noted they should be adjusted. Likewise, taking a drug history is important to resolve any OLRs. Moreover, regular follow-up every 2-12 months is essential to screen for malignant transformation. At minimum, the clinician should follow-up with the patient every year and biopsy new lesions. If new lesions are noted, it is also recommended that the follow-up interval be shortened.

Table 4: Simplified treatment algorithm for OLP adapted from Alrashdan and colleagues’ Oral lichen planus: a literature review and update ²

Treatment options	Indications	Effectiveness	Adverse Effects
First Line of Treatment ² Topical Corticosteroids: – Midpotency corticosteroids: triamcinolone – Potent fluoridated corticosteroids: fluocinolone acetonide, fluocinonide – Superpotent halogenated corticosteroids (clobetasol)	Symptomatic OLP ⁶	Response in 30-100% of treated patients ²	– Secondary candidiasis ^2,6,15 – Nausea/ GI upset ^2,15 – Oral use not tolerated ² – Refractory response ² – Mucosal atrophy ² – Oral Dryness ² – Sore throat ² – Bad taste ² – Delayed healing ²
Second Line of Treatment ² Systemic Corticosteroids: – Prednisone	Cases where topical treatment did not work, often in diffuse and erosive OLP ⁶	No difference in effectiveness of systemic vs. topical corticosteroids.² Reserved for use when topical treatments are refractory, in cases of recalcitrant, erosive or erythematous OLP or widespread OLP involving skin/ genitals/ esophagus/ scalp.²	– Adrenal suppression ^2,6,23 – Latrogenic Cushing’s syndrome ⁶
Third Line of Treatment ² Calcineurin inhibitors – Tacrolimus	Severe disease or disease resistant to topical/systemic corticosteroid treatment ^22,24	Topical tacrolimus (0.01%) is shown to be as effective as clobetasol.²	– Potential carcinogenicity ² – Burning or stinging during application²² – Taste alteration ²²

After OLP lesions are diagnosed, one may ask who is responsible for dictating treatment. In a paper by Shavit and colleagues a simplified classification of OLP is defined in which each disease stage has a recommended discipline for treatment.²⁴ The simplified stages of OLP are as followed: mild (no symptoms, no pharmacotherapy required), moderate (mild to moderate symptoms, treatment with low potency corticosteroids) and severe (severe/recalcitrant symptoms or systemic/diffuse involvement, treatment with high potency corticosteroids or systemic treatment). For the mild stage of OLP, general dentists are the recommended discipline and treatment involves regular dental cleaning to reduce any OLP exacerbations from poor oral hygiene. For the moderate stage, oral maxillofacial surgeons or dermatologists are the recommended discipline. Lastly, in the severe stage, a dermatology or immunotherapy specialist is the recommended discipline, and this may involve consultations with an ENT physician. This highlights the need for interdisciplinary management of OLP patients.

Alongside the simplified treatment and staging algorithms described, a variety of alternative treatments for OLP exist. The following is a non-comprehensive list of additional treatment options in development and developed for OLP: purslane, aloe vera, photodynamic therapy, amlexanox paste, curcumin gel, immunosuppressants (e.g., cyclosporine, tacrolimus), retinoids (vitamin A metabolites), dapsone, photochemotherapy, antibiotics, antimalarial drugs (hydroxychloroquine sulfate, not a recommended form of treatment), glycyrrhinzin, interferon, levamisole, mesalazine, phenytoin, monoclonal antibodies (efalizumab), sulodexide, surgery (cryosurgery and surgical excision of erosive lesions), vitamin D, NAVS naphthalan, photobiomodulation therapy, hyaluronic acid, platelet rich plasma protein, zinc and palmitoylethanolamide.^{6,15,17,23,25–31}

Of this list, photobiomodulation therapy (PBMT) and photodynamic therapy will be discussed in further detail. PBMT, previously known as low-level laser therapy, is a proposed treatment option for OLP.^6,17 This therapy involves the use of a laser beam with a wavelength of 630-1100 nm and power of 2-200 mW.¹⁷ PBMT accelerates healing and reduces pain through the stimulation of blood circulation, revascularization, improvement of hemoglobin dissociation and growth of various cell types (e.g., nerve, fibroblast, collagen). On the other hand, photodynamic therapy uses a photochemical reaction between a photosensitizer, visible light and oxygen to produce cytotoxic free radicals which destroy abnormal cells.²³ This therapy has shown to reduce pain and lesion size in OLP and can be as effective as topical corticosteroids.^6,23 Although these are both promising treatment options for resistant cases of OLP, more investigation is required to standardize a clinical protocol and investigate different outcome measures.

IMPACT OF OLP ON PATIENTS

OLP can negatively impact patient health, whether it be oral health or their general health. Although some forms of OLP discussed are relatively asymptomatic, other forms can be debilitating and cause painful erosions as well as healing with scarring and adhesions.¹³ This can result in pain and discomfort when patients perform daily activities such as eating and speaking.³² Patients may also experience soreness when brushing their teeth, smiling, breathing through their mouth, drinking liquids and when the lesions are touched.³³ Since OLP can be triggered or worsened by some foods and drinks, patients may avoid these which impacts their quality of life. In a study conducted by Yuwanati et al., the impact of OLP on the oral health-related quality of life (OH-QoL) via the short-form Oral Health Impact Profile-14 was assessed.³⁴ In general, the OH-QoL of OLP patients is poor but it improves with treatment. This poor OH-QoL is caused by the pain, burning sensation, discomfort, psychological disorders resulting from OLP (anxiety and depression) and subpar treatment options due to OLP’s unclear etiology. Understandably, Yuwanati and colleagues also found that patients with symptomatic OLP have a greater negative impact on their OH-QoL.

There is also a subset of studies that look at OLP and dental implants. Overall, OLP does not impact implant treatment and implant treatment does not impact OLP.^35-36 It is possible that OLP can affect the attachment of titanium implants, however this can be minimized by avoiding the placement of dental implants during disease exacerbation such as during active or erosive phases of OLP. The overall survival of implants in patients with OLP is about 94% and this requires frequent follow-ups and oral hygiene instructions.

Lastly, a very concerning impact of OLP on patients is malignant transformation. OLP is classified as an oral potentially malignant disorder (OPMD) by the World Health Organization (WHO).³⁷ As defined by the WHO, OPMDs are “characterized by a variably increased risk of developing cancers of the lip and the oral cavity”, or in other words they can precede the diagnosis of oral squamous cell carcinoma (OSCC). This will be further discussed in the next section.

PREVENTION/EARLY MANAGEMENT

As mentioned, OLP is an OPMD.³⁷ Malignant transformation of OLP was first reported in 1910 and most tumours detected in OLP are well-differentiated SCCs that have higher rates of survival but also higher rates of relapse.^2,38 Risk factors for malignant transformation in OLP include: erosive or ulcerative or atrophic forms, tongue lesions, chronic inflammation, candida albicans, smoking, alcohol consumption, HCV infection and being a female between 60-70 years of age.^2,13,39,40 Although malignant transformation can be diagnosed anywhere from 1.5-10 years after OLP diagnosis, the highest risk for malignant transformation is between three to six years.² Overall, the risk of malignant transformation of OLP is low (2.28%).²

Based on all this information, it is important to detect, monitor and treat OLP lesions early to aid against transformation. In a literature review by Moosavi and Tavakol, it was determined that cancer stem cell (CSC) marker expression seen in OSCC is increased in OLP.⁴⁰ This is important because measuring these CSC markers in OLP may help determine the prognosis of OLP in the future – and thus monitor for malignant transformation. In a separate review article, Birur and colleagues recommended surveillance guidelines for OLP.⁴¹ They recommended regular follow-up of symptomatic erosive and ulcerative OLP up to three times a year, as well as 2–3-month follow-up for dysplastic OLP lesions. On the other hand, reticular lesions can be assessed annually. Lastly, any change of clinical appearance or pain symptoms associated with OLP lesions warrant a shortened follow-up interval as well as a biopsy.

FUTURE CONSIDERATIONS AND CONCLUSIONS

Aside from obvious future considerations mentioned in the Treatment and Management section of this paper, other thoughts to leave readers with include autoimmunity, the oral microbiome, improving diagnostics and psychoneuroimmunology. First, it is evident that OLP is frequently associated with other autoimmune disorders. In a paper by Porras-Carrique et al., it is questioned whether individuals with OLP are developing an autoimmune status resulting in other autoimmune disorders.¹⁰ For example, individuals with OLP have twice the risk of developing thyroid disease and a 1.64 times higher risk of developing diabetes than the general population. This begs the question, should we screen individuals with OLP for potentially undiagnosed diseases like diabetes?

Second, the microbiome is intertwined with our health. So, what is the relationship between OLP and our microbiome? In OLP the oral microbiota undergoes dysbiosis, however there is no specific organism associated with OLP yet.³²This is why researchers such as Villa et al., indicate that micro-organisms don’t cause OLP and instead one should focus on OLP as an immunological disease until further research becomes available.⁴² However, there is potential for oral microbiota to play a role in the malignant transformation of OLP and it may play a large role in its pathogenesis, prognosis and treatment.³² With additional research and the elucidation of a role for the microbiome in OLP, personalized therapies may be developed.

Third, the diagnosis of OLP often involves both clinical and histological examination. Thus, screening may be lengthy, costly and invasive. What if saliva could be used as a screening tool for OLP? Salivary biomarkers unique to OLP as well as those seen in malignant transformation may prove to be an effective tool.⁴³ One such biomarker may be cortisol due to the association of OLP exacerbations with anxiety and stress. Moreover, microRNAs may be useful to evaluate OLP prognosis in the future.⁴⁴

Lastly, psychoneuroimmunology (PNI) is the interaction between psychological, neuronal, endocrine and immunological processes.⁴⁵ As mentioned, cortisol is elevated in OLP and results in exacerbations. Individuals with OLP tend to have depression, anxiety, less effective coping and more stressful life events. It is also known that stress is associated with OLP relapses. Therefore, there is an interaction between psychological, neuronal, endocrine and immunological processes in OLP. Further understanding of stress mechanisms in OLP may elucidate if stress management can prevent worsened OLP and reduce treatment costs.

It is evident that OLP is a complex mucocutaneous disease with a multitude of presentations and treatments. It is important for all clinicians to complete intraoral and extraoral examinations of their patients to help screen for things like OLP and work with other health care professionals for accurate and timely diagnosis. Although the etiology of OLP is not completely clear, with continued research the development of unique and personalized treatment options for OLP are possible.

Oral Health welcomes this original article.

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About the Authors:

Gurleen Kaur Dhaliwal is a 4th year dental student at the University of Toronto Faculty of Dentistry. She is excited to join a private practice in Northern Ontario upon graduation.

Dr. Aviv Ouanounou is an associate professor of Pharmacology & Preventive Dentistry at the Faculty of Dentistry, University of Toronto, and a clinical instructor and Treatment Plan Coordinator in the clinics. He is a Fellow of the International College of Dentists, American College of Dentists and Pierre Fouchard Academy. Dr. Ouanounou maintains a private practice in Toronto. He can be reached at aviv.ouanounou@dentistry.utoronto.ca