From Volume 46, Issue 6, June 2019 | Pages 573-579
Oral lichen planus is frequently encountered in primary and secondary dental care. The soft tissues of the mouth should always be examined carefully at check-ups and any abnormality be palpated to detect change in consistency (induration) along with any changes in colour or general appearance. Such changes should prompt a referral for specialist review.
Oral lichen planus (OLP) is one of the most frequently encountered mucous membrane conditions within the oral cavity. The overall age-standardized prevalence of the condition has been reported at 1.27% (0.96% in males and 1.57% in females).1 The condition usually manifests itself between the 3rd and 6th decade of life and affects women more than men.2 Nevertheless, OLP has been known to become apparent in the earlier age groups and has been reported in adolescents,3 and childhood OLP can present in patients as young as 5 years of age.4 Lichen planus is not restricted to the oral cavity, with dermatological manifestations being reported as high as 44%.5 Extra-oral distribution follows (in order of decreasing frequency) skin (shin and flexor surface of wrist), genital, nail and scalp.6 OLP is described as a chronic inflammatory condition of unknown origin.7
The pathogenesis is a T cell-mediated autoimmune reaction. Once activated, these cells migrate to the oral epithelium aided by specific signalling pathways (CXR3 and CCR5). This is compounded by secretion of pro-inflammatory cytokines (TNF-α and certain interleukins). The T-cells then bind to keratinocytes at the basement membrane triggering apoptosis (cellular death).8 The combination of liquefaction of the basal cell layer, sub-epithelial lymphocytic inflammatory infiltrate, along with the absence of epithelial dysplasia, are the three typical histological criteria for OLP.9 The white appearance on the surface of some forms of OLP is due to keratinocyte hyperproliferation as a result of chronic inflammation.10
The classification of OLP has undergone some change over the years. Andreasen had previously described OLP as fitting six different discrete clinical entities.5 These are:
Different classifications of OLP have been proposed, including that of white and red forms: reticular (Figure 1), plaque-like and papular being classified as white and erosive and atrophic and bullous corresponding to the red sub-type, which are generally considered to be the more painful variants of the disease.11,12 The most frequently reported site associated with a variant of OLP exists as gingival lichen planus (Figures 2 and 3), which has been documented to exist in 10% of all patients with the condition.13 The gingival lesions can take on two forms, either that of a desquamative type with erythematous features, or multiple white raised or ‘lacy’ lesions resembling that of frictional keratosis.8 The desquamative form (Figures 4 and 5) of the disease can also be particularly difficult to diagnose due to the resemblance that the condition has to vesiculo-bullous diseases.3 In addition to this, some more severe forms of atrophic OLP may have painful ulcers associated with the condition (Figure 6). The most commonly affected sites are the buccal mucosae, dorsum of the tongue, labial mucosa and gingivae, with the condition usually presenting bilaterally up to 95% of the time.2,14 The palate, floor of the mouth and upper lip are rarely involved.
A further condition that has a similar clinical presentation to OLP is a lichenoid reaction (LR) (Figure 7). This is a condition that resembles lichen planus both clinically and histologically, but usually has known a recognized aetiological factor.8 The histological similarities of the two conditions cause great difficulty to discriminate between them. A study asking pathologists to differentiate histological sections of OLP and (LR) found a sensitivity to specificity ratio of 40% to 32%, respectively. The study concluded the need for a holistic approach to diagnosis, including the importance of a thorough history, examination and even the use of skin patch testing.15 A lichenoid reaction has classically been associated with direct contact with dental amalgam restorations and also following the use of specific systemic drug therapies. A prospective study explored the effects of amalgam removal and replacement by gold, composite, porcelain, glass-ionomer cement or metal-ceramic crowns, in patients with confirmed LR lesions. The results showed a cure rate of 29.5%, partial resolution of 7.6% and a patient-reported improvement of 60% over a 34 month period.16 This demonstrates the justification of the replacement of an amalgam restoration in patients with a clinically and histologically suspected LR lesion in close proximity or contact with the restoration. Interestingly, within the same study, only 27.1% of patients demonstrated a positive result with skin patch testing to amalgam, whilst improvement was either observed or reported in 97.1% following amalgam removal. These findings highlight the need to view the role of cutaneous patch testing for determination for hypersensitivity to amalgam with caution since the occurrence of false negatives would appear to be high.
The drugs most frequently implicated in the development of LR are non-steroidal anti-inflammatories (NSAIDs) since the withdrawal of these drugs have been shown to provide improvement for patients.17 Other drugs have been documented to be implicated in the initiation of LR, including angiotensin-converting enzyme inhibitors (ACE inhibitors),17,18 β-blockers, methyldopa, quinine, penicillamine and oral hypoglycaemic agents. Although less evidence exists for their implication, other agents associated with LR include gold, sulfonylurea, lithium and carbamazepine.19
Given the inflammatory and erosive nature of OLP, there can sometimes be difficulty discriminating the condition from other more vesiculo-bullous diseases such as mucous membrane pemphigoid, pemphigus vulgaris or linear IgA disease. Nevertheless, the key feature of OLP distinguishing it from these related conditions is the reticular pattern that usually manifests in relation with the erythematous/erosive background. This is unique to OLP and is a useful adjunct to aid clinical diagnosis.3
The potentially malignant nature of OLP is well documented in retrospective and prospective follow-up studies.5,14,20 Despite some uncertainty concerning the exact rate of malignant transformation, a recent systematic review of the literature involving 7,806 patients across 16 studies reported transformation being of up to 3.5%.21 The same study found the average time of transformation from initial diagnosis to be 51.4 months (approximately 4.5 years following diagnosis) with the tongue being the most commonly involved site.21 Dysplasia is not categorized as one of the histopathological criteria of OLP. Further, it is important to note that the degree of epithelial dysplasia does not always reflect the likelihood of malignant transformation. A study of 368 patients with oral dysplasia reported a transformation in 26 (7.1%) patients, of which dysplasia was recorded at mild, moderate or severe.22 In a study of 723 patients followed up to an 8-year period (4.5 year mean), none of the patients with the reticular form OLP developed malignancy whilst, of the 0.8% patients who developed malignancy, all had the erosive or erythematous form of OLP.3 Within the same study, none of those patients who developed malignant lesions had any significant history of tobacco or heavy alcohol use, which is also reported in a number of other studies.23,24 Nevertheless, the development of malignancy within erosive lesions alone is not an absolute rule. In a follow-up study of 502 patients over a 5-year period, 21 patients (3.7%) went on to develop oral squamous cell carcinoma (OSCC). Of these 21 patients, 2 OSCC arose from erosive/atrophic lesions, with the remainder arising from a plaque/reticular form of the disease,23 demonstrating that malignant conversion of OLP is not exclusive to the erosive or atrophic forms. Nevertheless, as documented, patients with erosive or ulcerative forms of OLP are generally considered to have the documented higher incidence of malignant transformation.25
The majority of OLP is asymptomatic and is often detected in routine dental check-ups, and up to 82% of all patients with a diagnosis of OLP will initially present to their GDP rather than general medical practitioner (GMP).2 In the first instance, patients with a suspected diagnosis of OLP must be referred to secondary care for a specialist opinion. OLP will often display pathognomonic features which may be sufficient to make the diagnosis. A biopsy is usually performed in cases where there is doubt in the diagnosis, or if there is a need to rule out underlying dysplasia or malignancy.7
If a diagnosis of LR is supported then a causal link can be explored. As referenced earlier in the text, there is a strong documented association between amalgam restorations and the propagation of LR. Therefore, if the patient is experiencing symptoms, consideration for removal and replacement for a non-amalgam alternative would be the most appropriate initial approach. Clearly, if the patient is asymptomatic, then the lesion can be carefully monitored. If there is any doubt as to whether replacement of an amalgam restoration should be performed, then referral to secondary care for specialist opinion is advised.
Furthermore, the Koebner phenomenon has been observed in patients with OLP or LR. This is described as the isomorphic manifestation of the cutaneous condition (in this case OLP) in response to trauma.26 In a prospective review of 723 patients, causal factors of OLP/LR included mechanical trauma of dental procedures, friction from sharp cusps, rough dental restorations, or even poorly-fitting dentures.3 In addition to this, poor oral hygiene has been shown to exacerbate the underlying condition.3 This clearly demonstrates that the GDP has a pivotal role in managing those patients with diagnosed OLP to prevent exacerbation of the disease. Simply by identifying potential sources of trauma and correcting these could prove very useful.
The majority of patients with OLP do not require management in secondary care with continuing supervision of a specialist. In circumstances that are deemed suitable by the secondary care supervising clinician, patients can usually be discharged back to primary care for ongoing review and management. Given the documented range of malignancy transformation rate, which can be up to 3.5% (0.4−5.6%),21 both GDPs and patients must remain vigilant of these lesions. Of all the sub-types of OLP, the erosive and erythematous forms are documented as having the highest rate of malignant conversion compared to the other types.25 These patients will therefore usually be followed up in secondary care by a specialist since further biopsy to exclude malignant conversion may be required.
It is likely that the GDP will be reviewing the patient for his/her regular dental check-ups in parallel with a specialist. These check-ups may be more regular and earlier than the patient's hospital review appointments. Therefore, it is possible that the GDP may encounter a known OLP patient with a lesion that is undergoing malignant conversion prior to the patient's next appointment with the specialist. Therefore, it is essential to know what to look for that should arouse suspicion. A study referred to earlier of 502 patients found that, of the 21 patients with OSCC arising from known OLP sites, 11 (45.8%) had indurated or non-healing ulcers with elevated margins, 8 (33.3%) had keratotic masses (white, hard raised patches) and 5 (20.8%) had red patches with speckling. Clearly, should a GDP see a patient with OLP at check-up displaying any of the features above, he/she should contact the patient's specialist to consider an early follow-up that will already be scheduled for the patient. In addition to this, a simple clinical tool that is under-utilized in primary care is palpation. This technique is key and gives a lot of information with regards to the nature of a lesion. Digital examination (manual palpation) is a vital clinical tool for the detection of a clinically sinister lesion. Not all SCCs have visible mucosal changes such as ulceration, red or white patches, but rather present with induration (firmness) in keeping with a mass only detectable on palpation.27 Therefore, all patients who have regular follow-up with their GDP should have palpation of the known OLP lesions to feel for any textural changes, such as newly detected induration.
Where possible, GDPs should use clinical photography. This is commonly used in secondary care and provides an invaluable tool for the ongoing monitoring of existing lesions. Photography is not a replacement for, but rather an additional means of monitoring, in combination with thorough clinical examination. Features such as induration, pain on palpation or contact bleeding cannot be formally assessed on a clinical photograph and therefore this tool should be used in conjunction.
Furthermore, as stated earlier, despite the condition being considered to manifest itself in those between the 3rd and 6th decade of life, there have been cases of OLP presenting in children.28 This has led to a delay in diagnosis as these individuals had been treated for herpes simplex, oral candidiasis or recurrent aphthous stomatitis.3 This ultimately has delayed diagnosis and, subsequently, treatment. Therefore, the GDP must always have an index of suspicion for OLP, even in the younger age groups, and should not hesitate to refer to secondary care for a specialist opinion and diagnosis.
It is important to recognize that OLP is not a curable disease and emphasis is placed on symptomatic relief. Due to the nature of OLP, patients do go through stages of ‘flare-ups’ that can be considered painful exacerbations of the existing disease. The cause of these exacerbations is not well known, however they have been linked with episodes of stress.29 Nevertheless, the reticular and plaque forms of the disease are usually asymptomatic and, as such, do not usually require treatment.30 Usually patients who suffer this will have a management strategy given to them by their specialist. Management primarily is by removal of causal factors, which is usually identified and advised from secondary care. Upon removal of factors, the next stage is symptomatic relief. A simple measure is the use of benzydamine hydrochloride 0.15% mouth spray to apply topically. This is a non-steroidal anti-inflammatory (NSAID) and has a local affect which a proportion of patients report gives relief. Where simple topical relief is ineffective, corticosteroid (eg topical hydrocortisone muco-adhesive buccal lozenges) can be used and have been reported as highly effective at reducing pain.31 Due to the potency of corticosteroids, these should be administered by an oral physician from secondary care. GDPs should be aware of these patients, as candidiasis has been reported secondary to topical corticosteroid treatment.31 Beyond topical therapy, systemic treatment can be given for refractory cases using drugs such as prednisolone or azathioprine. However, the use of these drugs is entirely restricted to secondary care as they require ongoing liver function and bone marrow monitoring.
The GDP can play a central role in identification, management and reassurance for patients with OLP. Simple interventions, such as removing physical stimuli, or improving oral hygiene, have been reported to reduce the frequency of exacerbations. The majority (82%) of patients diagnosed with OLP initially presented at their GDP.2 This fact highlights the vital role that GDPs play in early identification and referral. Furthermore, of those patients with a diagnosis of OLP, regular dental check-ups are likely and the GDPs should be aware of the development of sinister clinical features due to the malignant conversion. All patients discharged from secondary care for exclusive management by their GDP should be carefully monitored and mucosa inspected and palpated. The use of clinical photography is invaluable to increase the ability to detect any clinical change between appointments. Ultimately, where there is evidence of changes in clinical appearance, the patient should be re-referred or the patient's specialist notified since the follow-up should be arranged and the need for biopsy considered.31
