Dentistry Review 2 (2022) 100007

Contents lists available at ScienceDirect

Dentistry Review
journal homepage: www.elsevier.com/locate/dentre

Oral Lichen Planus: A review of clinical features, etiologies, and treatments

Andrea Elenbaas 1,∗, Reyes Enciso 2, Kamal Al-Eryani 3
1
Master’s Program in Orofacial Pain and Oral Medicine, Herman Ostrow School of Dentistry of University of Southern California, 925 W 34th St. Los Angeles, CA
90089, USA
2
Associate Professor, Division of Geriatrics, Special Patients and Behavioral Dentistry, Herman Ostrow School of Dentistry of University of Southern California, 925 W
34th St. Los Angeles, CA 90089, USA
3
Assistant Professor of Clinical Dentistry, Division of Periodontology, Diagnostic Sciences and Dental Hygiene, Herman Ostrow School of Dentistry of University of
Southern California, 925 W 34th St. Los Angeles, CA 90089, USA

a r t i c l e i n f o a b s t r a c t

KEYWORDS: Lichen Planus (LP) is an immune-mediated inflammatory condition that can affect the oral cavity, skin, nails,
Literature review hair, eyes, esophagus, and other mucous membranes. The clinicians should be familiar with the clinical features
lichen planus of all clinical subtypes for LP, including oral LP’s (OLP) etiologies, risk factors, and possible treatments. This
oral lichen planus
comprehensive review discusses LP/OLP etiologies, including dental materials’ allergies, pharmaceuticals’ side
etiology
VZV
effects, genetics’ predisposition, and systemic diseases, including autoimmune and nutritional deficiencies. In ad-
EBV dition, possible associations with OLP and viruses, such as Varicella-Zoster Virus (VZV), Epstein Barr Virus (EBV),
HHV-6 Human Herpes Virus-6 (HHV-6), Hepatitis C Virus (HCV), and Human Papilloma Virus (HPV) are discussed. Au-
treatment thors also summarized OLP’s treatment with glucocorticosteroid therapy or other modalities that could reduce
the patient’s symptoms while investigating the possibility of having an underlying cause.

1. INTRODUCTION lence of 1.01%.[14] In another systematic review and meta-analysis of

First described in 1869 by British physician Wilson Erasmus, lichen
planus (LP) is an autoimmune condition present on the skin, hair, eyes,
mucous membranes, and nails. [1–3] LP lesions on the skin have a pur-
plish raised flat appearance with no particular pattern.[4] When the
lesions present in the oral cavity, it is referred to as oral lichen planus
(OLP), with OLP being found in 53.6% of cutaneous LP patients.[5] OLP
lesions appear as inflamed ulcerations that may have a white linear or
lacy pattern.[6] Usually, there is a constant presence of the lesions; how-
ever, the lesions will not remain in one area of the mouth or skin and
tend to migrate over time.[7] The lesions characterize by remissions and
flares, "flare," meaning that the lesions will become much more prolif-
erative and painful.[8] When OLP is present, it is challenging for the
patient to eat, drink, and function because of constant pain.[9] OLP is
more common in females over the age of 40 and in non-Asian coun-
tries.[10] It is a chronic T-cell mediated disease of the oral mucosa.
Increased numbers of mast cells with significant degranulation are a
consistent finding in OLP.[11] The mechanism of action appears to be
mediated by an antigen-specific mechanism that activates T-cells. There
is also a non-specific mechanism of mast cell degranulation.[12]-[13]
In a systematic review and meta-analysis, OLP had a worldwide preva-
46 studies, the overall global prevalence of OLP was 0.89%.[10]
There are numerous possible causative agents for LP/OLP, the most
common being pharmaceuticals and dental materials that produce a
lichenoid reaction. If the lesions resolve when the causative agent is re-
moved, it confirms a lichenoid reaction. If the lesions continue, then it is
given the diagnosis of LP/OLP.[3, 15] Viruses have also been implicated
in OLP/LP, specifically varicella-zoster virus (VZV), Epstein Barr virus
(EBV), human herpesvirus 6 (HHV-6), human herpesvirus 7 (HHV-7),
Hepatitis C virus (HCV), and human papillomavirus (HPV).[16]-[17]
Systemic diseases associated with OLP include hypertension, dyslipi-
demia, thyroid dysfunction, liver dysfunction, and cholecystitis.[18–22]
Autoimmune disorders have also been associated with LP/OLP, includ-
ing diabetes mellitus type I, Sjogren’s syndrome, systemic lupus ery-
thematosus (SLE), multiple sclerosis, celiac disease, ulcerative colitis,
and Hashimoto’s thyroiditis (hypothyroidism).[23]-[24] Nutritional de-
ficiencies have also been widely observed in patients with OLP.[25] Nu-
merous genetic polymorphisms that are involved with the regulation of
the immune system have been associated with OLP.[26]
This comprehensive review article focuses on the clinical features of
LP/OLP, etiologies, and treatments.

∗
Corresponding author. Andrea Elenbaas, Master’s Program in Orofacial Pain and Oral Medicine, University of Southern California Herman Ostrow School of
Dentistry, 925 W 34th St. room 4268, Los Angeles, CA 90089, USA, Phone: +39 349 885 5021
E-mail addresses: DrElenbaas@gmail.com (A. Elenbaas), renciso@usc.edu (R. Enciso), aleryani@usc.edu (K. Al-Eryani).

https://doi.org/10.1016/j.dentre.2021.100007
Received 25 October 2021; Accepted 23 November 2021
2772-5596/© 2021 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
A. Elenbaas, R. Enciso and K. Al-Eryani
2. SUBTYPES OF LP
Classic LP (CLP) is a flat papule, which is reddish, purple, and shiny.
Wickham’s striae, described as white lacy lines, may be seen on the
papule’s surface.[5] A common way to remember the appearance of LP
is by the "Six Ps," which are pruritic, purple, polygonal, planar, papules,
and plaques.[23] LP has 17 different subtypes throughout the body: hy-
pertrophic, vesiculobullous, actinic, annular, linear, zosterform, nail, at-
rophic, inverse, eruptive, erosive, pigmentosus, planopilaris, vulvovagi-
nal, erythematous overlap syndrome, pemphigoides, and oral LP. The
subtypes of LP are as follows:[6, 23]
• Hypertrophic LP commonly involves the interphalangeal joints or
front portion of the legs and is described as red/brown or purple-
gray plaques with a hyperkeratotic appearance.[27]
• Vesiculobullous has blisters present within the plaques. These lesions
may also develop on the legs. This type needs to be biopsied to rule
out pemphigoid.[28]
• Actinic CLP is more present in Indian, African, and Middle-Eastern
populations and presents with plaques with a hypo-pigmented halo
around a pigmented center.[29, 30]
• Annular CLP affects the male genitalia, axilla extremities, and groin.
It is rare and usually asymptomatic.[31]
• Linear LP is a distinct rare form of LP. A linear distribution has pru-
ritic eruptions and violaceous papules and is seen more prominently
in darker-skinned individuals. In some cases, the lesions follow a
linear pattern along the lines of Blaschko.[23] This form has been
reported extraorally with continuation intraorally.[32]
• Zosteriform LP has a dermatomal or zonal pattern and may arise
spontaneously, at the site of trauma or as Wolf’s isotopic response
in the area of healed zoster.[33] The zoster rash may have healed
months to years previous to the current LP lesions.[34]
• Nail LP shows fissuring and thinning of the nails with multiple nails
affected. Nail LP occurs in 25% of patients with oral lesions.[35]
• Atrophic LP has a tendency to occur in the same area which had LP
lesions previously, usually annular or ulcerative lesions. Cutaneous
lesions appear as brown or white-bluish papules and plaques.[6] This
variant has also been reported with a linear configuration along the
lines of Blaschko.[36]
• Inverse LP may not have a classic appearance and present with
poorly defined borders of erythematous lesions, sometimes having
keratotic papules. Inverse LP is confined to the intertriginous zones.
These may include limb flexures, submammary region, axillae, in-
guinal creases, and gluteal cleft.[37] Psoriasis and inverse intertrigo
are often should be part of the differential diagnosis with inverse
LP.[6]
• Eruptive LP is also known as exanthematous or generalized LP. It
is rapidly spreading, erythematous, flat-topped, polygonal papules
and may have a violaceous color. After the lesions resolve, hyper-
pigmented macules may be present.[6]
• Erosive LP has painful and ulcerated lesions which may involve the
mucosal tissues. The erosive form tends to scar and mutilate the
area.[38] This is the most advanced subtype of oral LP.[23]
• LP pigmentosus is a pigmented variant of LP. It consists of black,
grey, or brown small macules, which later merge to create large hy-
perpigmented areas. This takes place in sun-exposed areas of the
skin. It is reported predominantly in people with darker skin.[39]
• LP planopilaris involves hair follicles in which alopecia may develop.
Irregularly shaped areas on the scalp develop, which may be painful,
pruritic, hyperkeratotic, or fibrotic.[38]
• Vulvovaginal LP may be present in peri or post-menopausal women.
Erosive, hypertrophic, and papulosquamous are the three subtypes
associated with it. Vulvovaginal LP has a similar pattern to OLP.
Studies have shown that 43%-100% of vulvovaginal LP patients may
have oral involvement. Twenty-five percent of OLP patients have
2
Dentistry Review 2 (2022) 100007
vulvar involvement. A vulvovaginal-gingival syndrome is the coex-
istence of genital and oral lesions.[23]
• Erythematosus overlap syndrome is a condition where lupus ery-
thematosus and LP can be detected both clinically and histopatho-
logically within the same patient. Both conditions are common, but
overlapping is not.[40]
• LP pemphigoid is characterized by lichenoid plaques, tense blisters,
and bullae. In perilesional skin biopsies, the gold standard for diag-
noses is autoantibody deposition along the dermal-epidermal junc-
tional zone.[41]
• OLP is described in section 3.
3. SUBTYPES OF OLP
There are six different subtypes of OLP: reticular, papular, plaque-
like, erosive, atrophic, and bullous.
• Reticular OLP is the most common form of OLP. It contains "Whick-
ham striae," an asymptomatic white lace type pattern on the cheek
or buccal mucosa.[28] It can be erythematous or non-erythematous.
[6]
• Papular OLP is a rare form that contains small white raised (popular)
areas and can generate fine striae. It usually contains another variant
described.[3]
• Plaque-like OLP appears similar to leukoplakia. It has a whitish color
usually found on the cheek and dorsum of the tongue.[3] Papular,
plaque-like, and reticular are usually asymptomatic and hyperkera-
totic (white in color).[42]
• Erosive OLP is described as an ulcerative red, inflamed area that
may contain a white lacy pattern. It is usually sore or painful to the
patient. It is also described as burning or uncomfortable.[23]
• Atrophic is a rare form of OLP which has diffuse red lesions. It
may have two different variants of OLP within the lesion, such as
white striae (reticular) in the center and redness (erythematous) sur-
rounding it. [3] It usually appears where previous lesions of LP were
present.[6]
• Bullous OLP has a painful ulcerative surface. It contains blisters that
usually rupture, causing ulcerations. It may be positive for Nikolsky’s
sign.[28] Erosive, atrophic, and bullous are the "red form" of OLP and
are painful.[42]
Some patients with OLP will develop extraoral lesions; therefore, a
thorough exam should be performed, and a multidiscipline group put in
place. In a study with 584 OLP patients, other manifestations occurred
with cutaneous involvement in 93 patients, nail involvement in 11 pa-
tients, lichen planopilaris in 6 patients, esophageal LP in 6 patients, and
conjunctival LP in 1 patient.[43] Of the 584 patients, 399 were women
with OLP, 19% had genital involvement, and of the 174 men, 4.6% had
genital lesions present. LP in three or more sites was present in 33 pa-
tients.[43] In a descriptive study of 274 patients with cutaneous, genital,
and OLP, 37 patients with OLP had simultaneous involvement at more
than one site. This demonstrates the importance of a multidisciplinary
approach.[5]
4. RISK FACTORS FOR LP/OLP
OLP is considered a multifactorial disease with many triggers and
exacerbating agents, including psychological stress, medications, den-
tal materials, EBV, VZV, HHV-6, HHV-7, HPV, hepatitis C, and liver
dysfunction. OLP is also associated with systemic conditions of dyslipi-
demia, diabetes, hypertension, and hypothyroidism.
4.1. Psychological Stress
The role of psychological stress on the immune system and inflam-
matory processes influences the neuroendocrine, cardiovascular, gas-
trointestinal, and central nervous systems, along with infection, de-
A. Elenbaas, R. Enciso and K. Al-Eryani Dentistry Review 2 (2022) 100007

Table 1
Pharmaceuticals shown to induce or exacerbate OLP/OLR.[23,50–53]

Angiotensin-converting enzyme (ACE) inhibitors Antimicrobials Indomethacin

Hydrochlorothiazide Para-aminosalicylic acid Rofecoxib

Captopril Antipsychotic Selective serotonin reuptake inhibitor
Enalapril Methopromazine Escitalopram
Antibiotics Antiretrovirals Statins
tetracycline Zidovudine Pravastatin
sulfamethoxazole Antituberculosis drugs Thyroid disease
Anticonvulsants Ethambutol Levothyroxine
Carbamazepine Pyrazinamide Thyrokinase-selective immunosuppressors
Oxcarbazepine Isoniazid Imatinib
Valproate sodium Rifampin Tumor necrosis factor-alpha (TNF-a) inhibitors
Antifungals Benzodiazepine Infliximab
Ketoconazole Lorazepam Adalimumab
Antihypertensives Disease Modifying Anti-rheumatic Drug (DMARD) Certolizumab
Atenolol Penicillamine Etanercept
Methyldopa Glycemic drugs Miscellaneous
Nifedipine Tolbutamide Adalimum (hepatitis B vaccine)
Propranolol Glipizide Allopurinol
Antimalarials Insulin Amiphenazole
Chloroquine Immunomodulatory drugs Clopidogrel
Pyrimethamine Gold salts Interferon-alpha
Quinine NSAIDs Levamisole
Quinidine Ibuprofen Lithium

pression, psychosocial events, autoimmune disease, and ultimately can- Table 2

cers by viral mediation.[44, 45] Stress can be physically or psycho- Triggers and exacerbation agents of OLP/OLR.
logically driven. The immune-suppressing properties of catecholamines [8,17,20,22,24,26,51,56–78]
have been shown following stress.[45] Viruses Nutritional Deficiencies
Stress-related release of cortisol, which produces inflammatory me-
Varicella Zoster Virus Vitamin B12
diators such as cytokines with a T helper cell 1 [Th1], could contribute Epstein Barr Virus Hemoglobin
to OLP.[46] In a case-control study of 65 patients, 40 with OLP and 25 Human Herpes Virus - 6 Iron
controls, prolonged emotional stress was shown to initiate the physical Human Herpes Virus - 7 Vitamin A, C, and E
presentation of OLP lesions.[47] In this study, serum cortisol levels were Human Papilloma Virus Folic Acid
Hepatitis B Virus Vitamin D
significantly elevated and correlated with elevated clinical scales for de-
Hepatitis C Virus Dental Restorative Materials
pression and hysteria. This may reflect a compensatory up-regulation Liver Dysfunction Metals
of the hypothalamus, pituitary, and adrenal gland (HPA) axis.[47] In Cholecystitis Dental amalgam
a prospective study of 13 OLP patients compared with age- and sex- Chronic liver disease Cobalt
Primary sclerosing cholangitis Palladium
matched controls, authors found that nuclear factor-kappa B (NF-kB)
Abnormal Liver function tests (LFT) Chromium
inflammatory cytokines (TNF-alpha, IL-1-alpha, IL-6, and IL-8) were de- Systemic Diseases Copper
tected at significantly increased levels in OLP tissue transudates com- Diabetes mellitus Gold
pared to controls (p < 0.0001).[48] In a prospective cohort study, it Hypertension Nickel
was found that anxiety and depressive symptoms were correlated with Dyslipidemia Mercury
Thyroid Dysfunction Nonmetals
symptomatic reticular forms of OLP.[49]
Autoimmune Diseases Epoxy resins
Celiac Disease Composite restorations
4.2. Medications Sjogren’s Syndrome BPA
Systemic Lupus Erythematosus Oral health
Ulcerative Colitis Dental tartar
A number of medications have been shown to induce or exacerbate
Multiple Sclerosis Mouth breathing
OLP or an Oral Lichenoid Reaction (OLR) (Table 1). [23,50–53] OLP Pulmonary Fibrosis Hypo-salivary function
and OLRs are indistinguishable clinically and histologically challeng- Primary Biliary Cholangitis Plaque
ing to diagnose. One definitive diagnosis between the two is to remove Myasthenia Gravis/thymoma Lifestyle factors
the offending agent. If the lesions resolve, they are termed OLR.[54] Genetics Stress
Graft versus host disease (GVHD) Tobacco chewing
In many instances, the lesions do not develop quickly but may appear
years after a patient taking the medication. Usually, upon cessation
of the medication, the lesions resolve.[8, 51] A position paper by the
American Academy of Oral and Maxillofacial Pathology stated that both lichenoid reaction. If the lesions continue after the material is removed,
histopathologic and clinical features are needed to diagnose OLP.[55] then the diagnosis of OLP is confirmed.[79, 80] The number of mast
cells is also increased in OLP when compared to a lichenoid reaction,
4.3. Dental restorative materials which may help distinguish OLP from lichenoid reaction histopatholog-
ically.[11]
The most common dental materials associated with OLP that cause
a lichenoid reaction are amalgam, composite resins, nickel, and gold, 4.4. Genetics
which cause a contact sensitivity reaction (Table 2). [8, 17, 20, 22, 24,
26, 51, 56–78] A patch test can assess these allergens. Dental amalgam Familial OLP has an early age onset, and it may become severe
and nickel have the highest reaction rate. OLRs subside with the removal and chronic. It tends to have an atypical and widespread clinical pre-
of the material. Corrosion of amalgams or a galvanic corrosion from sentation.[81] Genetic polymorphisms have also been linked with LP.
dissimilar materials in alloys in continuous contact may also cause a The most prevalent genes associated are HLA-DR1, DR2, DR3, DR4,

3
A. Elenbaas, R. Enciso and K. Al-Eryani
DR7DR9, HLA- DRB1, HLA-DQA1, and HLA-DQB1 and HLA-DR6. [26,
82, 83] A meta-analysis showed that the A allele and AA genotype in
IL 10-592 C/A increased OLP susceptibility.[84] Other polymorphisms
associated with the susceptibility of OLP include TNF-alpha (-308A),
TNF-B (+252A/G), and IL (-10G/A, -819C/T, and -592C/A).[85]
4.5. Systemic diseases
4.5.1. Diabetes mellitus (DM)
In a recent meta-analysis study of 11 case-control studies, researchers
concluded that the risk of OLP in DM was higher than control subjects
with an odds ratio of 1.584 (p=0.044).[24] OLP prevalence was signifi-
cantly higher in patients with type 1 DM (5.76%) (p=0.412) and slightly
high in type 2 DM (2.83%) (p=0.03) as compared to controls (1.82%). In
patients with type 1 DM, there was a significant difference in prevalence
but not in type 2 DM.[86] In a retrospective study of 633 OLP patients in
Romania, 10% presented with type 2 diabetes compared to the general
population (8-9%).[22] In a case-control study of 40 OLP patients and
40 sex- and age-matched controls, 15% of OLP patients were already
diagnosed with DM. After glucose analysis, 28% of OLP patients were
diagnosed with DM compared to 3% of the control group.[87]
4.5.2. Hypertension
In a retrospective study of 808 patients with OLP that were followed
from 6 months to 17 years, 20.5% had primary hypertension. The most
prescribed pharmaceuticals in the entire group were anti-hypertensives
at 17.1%.[88] In another retrospective analysis with 87 participants, it
was found that hypertension (39-44.8%) was the most frequent associ-
ated comorbidity with OLP.[42]
4.5.3. Thyroid dysfunction
The association of thyroid gland disease and OLP has conflicting re-
sults in the literature. In a recent retrospective case-control study of
102 OLP patients with equal age and gender-matched controls without
OLP, thyroid gland disease and related medications were similar in both
groups.[89] While in another prospective case-control study with 215
OLP patients and 215 subjects matched for age and gender, OLP was
associated with thyroid disease, specifically hypothyroidism. Thyroid
disease was found in 15.3% of OLP patients compared to 5.2% of con-
trols with an odds ratio of 3.06 of having thyroid disease in OLP patients
compared to controls.[90]
In a case-control study of 192 OLP patients, 123 patients with oral
lichenoid lesions (OLL), and 162 controls, the prevalence of thyroid dis-
ease was 72.4% (OLP), 68.3% (OLL) and 49.4% (controls) with sta-
tistical significance (p < 0.0001).[57] In OLP patients, the most com-
monly identified types of thyroid disease were Hashimoto’s thyroiditis
and hypothyroidism. The odds ratio for Hashimoto’s thyroiditis was 3.16
for OLP patients and 2.09 for OLL patients compared to controls. The
odds ratio for thyroid nodules was 2.31 for OLP and none with OLL
compared to controls. This study suggests a close relationship between
OLP/OLL and thyroid disease, specifically Hashimoto’s thyroiditis and
thyroid nodules.[57] In a prospective case-control analysis of 549 pa-
tients (307 with OLP and 242 healthy controls), those suffering from
thyroid diseases had an almost 3-fold increase in OLP odds compared
to controls (OR 2.85). Over half of the thyroid pathologies in this study
were of autoimmune etiology for the OLP patients.[20]
4.5.4. Abnormal liver function and primary biliary cirrhosis
Aside from a dental materials allergy, the majority of the risk factors
associated with OLP correlate with the liver. Cytochrome P450 enzymes
metabolize the pharmaceuticals group to induce or exacerbate OLP/OLR
(Table 1) in the liver. Three retrospective studies showed an association
between elevated serum aminotransferases and OLP lesions. One study
with 71 OLP patients showed an elevation in serum hepatic aspartate
(AST) and alanine (ALT) with the OLP’s severity and frequency.[21]
4
Dentistry Review 2 (2022) 100007
In a study of 187 OLP patients, 21.4% had elevated serum transami-
nase levels, and all of these patients were ultimately proven to have
chronic liver disease through complementary diagnostic methods. This
study also stated that the severity of OLP is related to an increase in
liver alteration.[62] In a retrospective case-control study of 136 patients
with LP and 193 controls, 52% of the LP patients had liver function test
abnormalities. This prevalence rate was significantly higher than the
control rate at 36% (p < 0.025).[63] A diagnostic protocol for OLP to
include a complete blood count, complete liver profile including serum
transaminase levels, total bilirubin, antibodies to hepatitis virus B, C,
and hepatitis B surface antigens has been published.[65] In a retrospec-
tive study with 770 OLP patients using those serum markers, more than
21% of the total cases had liver abnormalities, 83.5% had hepatitis C
virus, 3 cases had hepatitis B, and 24 had non-viral hepatopathies.[88]
4.5.5. Primary sclerosing cholangitis and cholecystitis
Acute acalculous cholecystitis is an inflammatory condition of the
gallbladder when no gallstones are present.[91] A retrospective study
of 633 patients with OLP showed that 19% had cholecystitis compared
to 8.4% of Romania’s general population.[22] A case series of 4 patients
with OLP, primary sclerosing cholangitis, and abnormal liver tests raised
a possible link between OLP and primary sclerosing cholangitis.[67] In
two case reports, the patients had total resolution of OLP/LP after liver
transplants because of primary biliary cirrhosis.[92] In this case report,
Oleaga et al., [93] concluded there was pronounced clinical improve-
ment almost immediately after the liver transplant and complete reso-
lution of LP in 4 weeks.
4.5.6. Chronic hepatitis C virus (HCV)
A systematic review and meta-analysis with 19 studies (1,807 OLP
cases and 2,519 controls) studied the prevalence of HCV infection in
OLP disease. It concluded that patients with OLP have a six-fold higher
risk of HCV infection than controls with large variability among studies
due to different geographical areas.[94] In a cross-sectional case-control
study of 25 patients with OLP and an equal number of controls, sera for
HCV was tested along with liver function tests. Of the 25 patients with
OLP, 12% had HCV infection, and none of the controls was positive for
the virus. It was reported that 44% of OLP patients showed abnormal-
ities in liver tests (elevated bilirubin and transaminases), where earlier
studies cited 7-60%.[69] One study considered that the pathogenesis of
OLP in HCV infection was not directly related to the virus itself but to
the response by host factors, insulin resistance, genetics, and immuno-
logic factors.[65] In a cohort study of 9396 liver disease patients, 522
were HCV antibody positive. After exclusion criteria, 87 patients with
HCV-related diseases had oral and medical exams. Of these 87 patients,
the presence of LP, including oral lesions, was 19.5% (17 patients. Risk
factors associated with LP and HCV status are smoking, hypertension,
insulin resistance, extrahepatic malignant tumor, and hypertension. Pa-
tients who have HCV and any form of LP should be closely monitored
for extrahepatic malignancy.[95] Another case report showed full res-
olution of OLP after liver transplant and direct-acting antiviral medi-
cation.[96] In a prospective study of 7 patients with HCV related OLP,
four patients had a total solution, and three had lesion improvement
after continual use of direct-acting antivirals.[97]
4.6. Autoimmune diseases
OLP is an immune-mediated mucocutaneous disorder with autoim-
mune tendencies. People diagnosed with an autoimmune disease have a
25% chance of developing an additional autoimmune disease.[98] In a
case-control study of 320 Chinese OLP patients and 53 healthy controls,
autoantibodies were found in 60.9% of OLP patients. The frequencies in
OLP patients of the presence of serum anti-nuclear (ANA) was 28.1%,
gastric parietal cell (GPCA) was 26.3%, thyroglobulin (TGA) was 21.3%,
and anti-thyroid microsomal antibodies was 24.4%. The controls’ fre-
quencies were 5.7% for ANA, 1.9% for GPCA, 1.9% for TGA and 1.9%
A. Elenbaas, R. Enciso and K. Al-Eryani
for TMA. There were significantly higher frequencies in the OLP pa-
tients than healthy controls (all P-values were <0.005).[99] In a cross-
sectional study of 260 patients, in which 130 had OLP, there was no
statistical difference in autoimmune disease occurrence compared with
the controls.[100]
In a cross-sectional epidemiological study of 100 LP patients, it was
found that 65% of the patients tested positive for at least one of the six
autoantibodies under study. Positivity included anti-keratinocyte anti-
body 26% (autoimmune bullous disease), anti-nuclear antibody 22%,
anti-desmoglein 1 antibody 19% (Celiac disease), anti-desmoglein 3 an-
tibody 16% (Celiac disease), anti-mitochondrial antibody 9% (primary
biliary cholangitis), and anti-thyroglobulin antibody 6% (autoimmune
thyroid disease). In this study, 71.4% of the patients had cutaneous LP,
46.1% had mucosal LP, and 40% had cutaneous and mucosal LP. Thirty-
five percent of the group tested negative for all six of the antibodies. The
frequency of serum antibodies was higher in cutaneous LP than in mu-
cosal or mucosal and cutaneous LP (p= 0.046).[101]
4.6.1. Sjogren’s syndrome
A multi-center retrospective cohort study, including 155 primary Sjo-
gren’s syndrome patients, found oral lesions of autoimmune etiology
with a prevalence range between 7.3-21.2% for different clinics.[59] In
a prospective clinical study that examined the prevalence of OLP/OLL in
30 primary and secondary Sjogren’s syndrome patients, 9 patients had
oral lesions. Of the 7 secondary Sjogren’s syndrome patients, 2 patients
had OLP (28%); Of the 23 patients with primary Sjogren’s syndrome, 6
patients had OLP (26%) and 1 had OLL (4%).[102]
4.6.2. Systemic Lupus Erythematosus
Approximately 50 cases of erythematosus overlap syndrome have
been discussed in the literature.[103] It is described as a mixture of the
clinical and histopathological features of lupus and LP.[40] In a clini-
cal, histopathological and immunopathological study, 51 patients with
systemic lupus erythematosus (SLE) were found to have positive oral
direct immunofluorescence (DIF) biopsies in 45% of the patients.[104]
There may be histological overlap between SLE and OLP; therefore, a
DIF assay must be obtained.[105]
4.6.3. Thymoma
The presentation of thymoma accompanied by LP has been described
in 20 published case reports.[106] In a review of 50 patients with
LP, three patients (6.0%) had an accompanying thymoma. In English-
language published works, 29 LP patients were reported to have thy-
moma. Of these patients, 27 had undergone thymectomy, and 25.9%
(7/27) had improvement, inferring thymectomy may not be an effec-
tive treatment for LP. In these 29 patients with LP and thymoma, 58.6%
presented with hypogammaglobulinemia, alopecia 13.8%, myasthenia
gravis 17.2%.[107]
4.6.4. Ulcerative colitis
A pilot study of 15 ulcerative colitis patients with age- and sex-
matched controls revealed a 20% occurrence of OLL and OLP in ulcera-
tive colitis patients. OLP, minor aphthous ulcers, and pyostomatitis veg-
etans were reported to have exacerbations during their ulcerative coli-
tis relapses.[61] In a retrospective post-mortem study of 50 LP patients
compared to 50 patients with psoriasis, it was found that ulcerative col-
itis, multiple sclerosis, and pulmonary fibrosis were three autoimmune
diseases found in death certificates of all 100 patients. The average LP
patient died at 71.3 years of age compared to an average age of death in
Genoa, Italy of 74.3 years of age. In LP, the prevalence of bladder can-
cer was seven times, and intestinal cancer was twice that of the general
population. Malignant hemopathies also exceeded the expected preva-
lence.[108]
5
Dentistry Review 2 (2022) 100007
4.7. Nutritional deficiencies
4.7.1. Vitamin B12
B12 deficiency has been demonstrated in patients with OLP. In a
study of 352 patients with OLP with age- and sex-matched controls,
7.1% of OLP patients had B12 deficiency than controls (p < 0.001).[109]
A case-control study of 32 OLP patients and 16 healthy controls found
Vitamin B12 deficiency in 25% of OLP patients and 12.5% in con-
trols. B12 deficiency in OLP was not statistically significant compared
to healthy subjects, although it was about twice as much as the con-
trol group.[110] Gastric parietal cells (GPC) secrete hydrochloric acid
and intrinsic factors. When GPCs are damaged, it can result in a lack of
intrinsic factors and hydrochloric acid. In order to be absorbed by the
ilium, B12 must bind to the intrinsic factor. A lack of intrinsic factors
can cause B12 deficiencies. High antibody titers to GPCA may result in
hemoglobin deficiency anemia, B12 deficiency, and elevated homocys-
teine.[58] In a case-control study with 307 erosive OLP patients and
218 healthy controls, erosive OLP patients with positive autoantibodies
to gastric parietal cells, thyroglobulin and thyroid microsomal showed
deficiencies in hemoglobin (31%), iron (10.3%), B12 (31%) and an ele-
vated homocysteine level (37.9%). These frequencies were statistically
significantly higher than in healthy subjects (all p < 0.001).[111] One
case-control of 352 OLP patients with matched age and sex healthy con-
trols found high homocysteine levels to be prevalent in 14.8% of OLP
patients compared to 3.1% in controls (p< 0.001). This study also sug-
gested that high blood homocysteine levels may be related to the sever-
ity of OLP.[109]
4.7.2. Hemoglobin deficiency
A study of 352 OLP patients with 352 age- and sex-matched con-
trols found a significantly higher prevalence of hemoglobin deficiency
in 21.9% of OLP patients compared to 0% in the control group (p <
0.001).[109] In a study of 103 patients with OLP and 100 controls,
17.5% had hematological abnormalities as compared to 0.7% of con-
trols (p = 0.05).[72]
4.7.3. Iron deficiency
Lack of hydrochloric acid can result in iron deficiency, malabsorp-
tion of iron, and iron-deficient anemia. Iron deficiency was present
in 13.6% of OLP patients compared to 0% in the control group out
of 325 OLP patients and matched controls (p < 0.001).[109] In 75
iron-deficient anemia patients compared with 150 healthy age- and
sex-matched controls, OLP was present in 33.3% of the iron-deficient
patients, and serum testing in all matched controls was normal (p <
0.001).[111]
4.7.4. Vitamin A, C, and E deficiency
In a case-control investigation of 36 patients with erosive OLP with
36 age- and sex-matched controls, it was observed that vitamins A, C,
and E were significantly lower in patients with OLP (p < 0.001). The
total antioxidant capacity levels were also low in the erosive OLP pa-
tients.[73]
In an observational study of 90 subjects, 30 with potentially ma-
lignant disorders, 30 with oral cancer, and 30 healthy controls, it was
found that salivary Vitamin C levels were lower in patients with poten-
tially malignant disorders and oral cancer. This observation was made
when compared to healthy controls. Healthy controls had serum Vitamin
C levels of 1.379mg/dl, potentially malignant lesions patients’ levels
dropped to 1.1 mg/dl, and oral cancer patients’ levels dropped further
to 0.7833mg/dl.[74]
4.7.5. Folic acid deficiency
There have been mixed results in studies of folic acid deficiency and
OLP. In two different studies, folic acid was not found to be a risk factor
in OLP.[72, 110] In a comparison study of 41 patients, folate levels were
checked in patients with oral lesions. The results demonstrated low red
A. Elenbaas, R. Enciso and K. Al-Eryani
cell folate levels in 44% of OLP patients and 56% in stomatitis or glossitis
patients (p<0.001).[112]
4.7.6. Vitamin D deficiency
In 2018, vitamin D serum levels were not found to be statistically sig-
nificantly different between 18 OLP patients and healthy controls, but
the sample size was small in this study, and it was suggested to repeat
the study with larger sample sizes for future studies.[75] In a 2019 case-
control study with 40 OLP patients and 40 healthy controls evaluating
serum Vitamin D deficiency in OLP, 60% of OLP patients had a Vitamin
D deficiency compared to 22.5% in the control group (p<0.001). Vita-
min D deficiency was related to the development, symptoms, and type
of OLP.[113]
4.8. Other risk factors of OLP
4.8.1. Smoking
Smokeless tobacco (but not cigarette smoking) had a strong correla-
tion with OLP in a case-control study. Out of 450 subjects with smoking
and/or chewing habits aged 15 years and older, 150 patients were diag-
nosed with oral mucosal lesions, and 300 lesion-free patients were used
as controls. "OLP-like" lesions were present in 83.3% of tobacco chewers.
OLP occurred in 16.7% of patients with mixed habits. This study sug-
gested tobacco chewing as a risk factor for OLP. No cigarette smokers
had OLP.[70] In a case-control study of 34 patients with OLP (16 non-
smokers and 18 smokers) and 12 healthy controls without OLP (6 non-
smokers, 6 smokers), OLP patients had significantly higher blood vessel
density and overexpression of c-Met receptor in microvessels compared
to normal controls (p < 0.05). The microvessel density in OLP patients
who smoked was higher than in the non-smokers (p < 0.05). The cor-
relation between smoking and c-Met expression in OLP was statistically
significant (p < 0.05).[114]
4.8.2. Graft versus host disease
Graft versus host disease (GVHD) is a serious complication and lead-
ing cause of mortality in hematopoietic stem cell transplantation pa-
tients. It is estimated that between 35% and 60% of transplant patients
will have oral manifestations of acute GVHD.[115] The lesions usually
appear 100 days or more after the bone marrow transplant.[71] Com-
mon oral GVHD features include lichenoid changes and ulcerations. This
condition can mirror OLP. [71, 115]
4.9. Herpetic family of viruses and OLP
4.9.1. Varicella Zoster Virus (VZV)
Linear LP and zosteriform LP may both develop from VZV.[116] Zos-
teriform LP can occur in a zonal area, dermatomal region, or a site of
trauma. It can also be located in the area of healed zoster known as
Wolf’s isotopic response.[117–118] In a literature review by Wolf in
2011, the author reviewed 176 cases with Wolf’s isotopic response. The
initial occurring disease was herpes zoster in 89% of the cases, with
herpes simplex virus (HSV) in 11% of the cases. Of the 176 cases, 9
presented with LP.[76, 119] In a literature review, 17 cases of Wolf’s
isotopic phenomenon in which zoster LP developed after a herpetic
zoster infection were described. These lesions appeared 15 days to 5
years later. The authors concluded that persisting viral proteins, even in
very small amounts, rather than the viral genome, were responsible for
the reaction.[120] In 8 patients with LP lesions (5 with zosteriform and
3 with linear LP), immunohistochemically presence of in vivo localiza-
tion of VZV antigen was assessed. The VZV antigens were found in the
eccrine epithelium in zosteriform LP but not in linear LP. The presence
of VZV antigens indicates a possible triggering role in zosteriform LP.
LP occurring at a site previously involved by herpes zoster, including
zoster sin herpete, may not be a rare phenomenon. It could be the link
between the herpes zoster and LP, and unless diligent attention is used,
it may be unrecognized; however, only case reports have been published
6
Dentistry Review 2 (2022) 100007
so far.[34, 121] Wolf’s response should not be confused with Koebner’s
(or isomorphic) phenomenon. This is where the same disease is present
at a different location at a site that has had trauma.[122]
4.9.2. Epstein Barr Virus
Epstein Barr virus (EBV) is in the herpes family of viruses known as
HHV-4 and is present in over 90% of the population.[123–124] Most
people are never aware that they have been infected with the virus
as it will present as a transient cold or fever. Others will present with
the symptoms of swollen tonsillar lymph nodes, fever, and malaise and
will seek medical treatment.[124] In a study to assess the prevalence
of viruses using histopathological antibody testing tissue, samples of 65
patients with OLP and 15 normal mucosal controls demonstrated that
35% of OLP cases were positive for EBV (p = 0.006) compared to none
of the controls and 21% OLP patients were positive for HPV compared
to zero for the controls (p = 0.048). HSV was not statistically significant
compared to controls (p = 0.588).[17] In a case-control study, DNA PCR
analysis was used to detect EBV in 23 patients with OLP, 29 patients with
oral squamous cell carcinoma (OSCC), and 67 healthy controls. 26.1%
of OLP cases were EBV positive, 37.9% of OSCC patients were positive,
and 7.3% of the controls were positive. EBV prevalence was statistically
significantly higher in OLP and OSCC than controls. EBV prevalence was
not statistically significantly different between the smoking group and
nonsmoking control. Alcohol and increased age were not risk factors for
EBV presence.[125]
4.9.3. HHV-6
Oral tissue samples containing 51 SCC lesions, 18 non-malignant le-
sions (OLP and oral leukoplakia) and 7 normal mucosa samples were
tested for HHV-6. HHV-6 was found in cases of OLP with a rate of 85.7%
and oral leukoplakia with a rate of 100% with in situ hybridization and
immunohistochemical techniques. All normal samples were HHV-6 neg-
ative. SCC lesions had positivity for HHV-6 of 79-80% with various de-
tection methods. The high frequency of HHV-6 with OLP and leuko-
plakia suggests a possible etiopathogenesis role in the oral cavity.[126]
4.9.4. HHV-7
In a study by de Vries et al. (2007), HHV-7 was measured histologi-
cally and by PCR testing during the outbreak and after remission of LP. It
was found that before treatment, 61% of the biopsies (18 patients) con-
tained HHV-7 deoxyribonucleic acid (DNA), and after remission, only
8% contained HHV-7 DNA (13 patients). This confirmed their theory
that nucleic acid sequences were present at a cellular level.[78]
4.9.5. Human papillomavirus (HPV) and OLP
A recent meta-analysis, including 835 OLP cases and 734 controls,
showed that the association of HPV and OLP vary according to geo-
graphic populations, HPV genotypes, and clinical types of OLP. The au-
thors also found that OLP patients had an odds ratio of about 7-fold
higher risk of HPV infection than controls. HPV-16 and 18 both showed
strong associations with OLP, with an odds ratio of 11.27 and 6.54, re-
spectively.[127]
In a study containing tissue samples of 65 OLP patients using
histopathological antibody testing and 15 normal mucosal controls,
HPV-16 was positive in 21% of OLP patients compared to none in con-
trols (p = 0.048). EBV was shown to be positive in 35% of the OLP cases
compared to zero in controls (p = 0.006).[17] In a cohort study using
salivary and tissue samples from 40 OLP patients and 40 healthy con-
trols, based on DNA PCR testing, HPV tested positive at a rate of 27.5%
compared with 7.5% saliva specimens (p = 0.0367). Biopsies were more
reliable than saliva in detecting HPV. Healthy controls had 12.5% posi-
tivity for HPV-16, and no controls were positive for HPV-18.[128] One
study compared DNA PCR in the mucosa of 68 oral leukoplakia patients,
71 OLP patients, and 90 controls. HPV prevalence was 19.7% in OLP,
17.6% in oral leukoplakia compared with 5.6% in controls. A higher risk
of HPV infection was statistically significant in both groups compared
to controls (OR = 3.64 OL; OR = 4.17 OLP).[129]
A. Elenbaas, R. Enciso and K. Al-Eryani
5. RISK FACTORS FOR MALIGNANT TRANSFORMATION OF OLP
Oral squamous cell carcinoma (OSCC) is the sixth leading malig-
nancy worldwide.[130] OSCC comprises 90% of malignant tumors of
the head and neck.[131] The average age of onset of OSSC is 60-70
years old. Genetic and environmental factors are the basis for tumor
development. The main risk factors for malignant transformation of a
lesion to OSCC are tobacco and/or alcohol consumption, immunosup-
pressive agents, particular viruses, chronic inflammation, genetic single
nucleotide polymorphism (SNP), and a diet low in fresh fruits and veg-
etables.[130, 132] OSCC usually arises from a pre-existing potentially
malignant lesion or a field of precancerous epithelium.[130]
5.1. Malignant transformation rate of OLP lesions onto OSCC
The World Health Organization categorized OLP as a potentially ma-
lignant disorder in 2005.[133] In a systematic review, 92 of 6,559 OLP
patients developed OSCC, with an overall malignant transformation rate
of 1.40%.[134] A recent meta-analysis from 57 studies (19,676 patients)
found that 1.1% of OLP progresses into OSCC.[77] A systematic re-
view of 16 studies with 7,806 patients with OLP revealed 85 developed
SSC, and among 125 OLL patients, 4 developed SSC. Clinical features of
OLP/OLL with OSSC development revealed 52% red lesions, 24% white
lesions, and 24% mixed red and white lesions.[135] In a systematic re-
view with 6,353 patients with OLP and 206 with OLL, 92 developed
OSSC (1.37% of OLP and 2.43% of OLL). In pooled data of OLP/OLL,
the meantime for transformation was 61.9 months, and the mean age for
diagnosis was 62.9 years old. The male to female ratio was 1:2.3.[134]
However, in a 2019 retrospective study with 281 patients, it was found
that 0.49% (1/206) of OLP, 0% of OLL cases (0/31), and 6.81% (3/44)
of oral lichenoid dysplasia developed into OSSC.[136]
The relative risk of malignant transformation of patients with OLP
and HCV was reported to be 3.16 times of patients with OLP without
HCV.[137] In a meta-analysis of data based on 561 OLP cases included
in two studies, authors found that OLP patients infected with HCV had
an odds ratio for malignant transformation of 5 times compared to pa-
tients who were not infected. OLP patients who smoked had twice the
rate of non-smokers, and alcoholics were 3.52 times more likely to suffer
malignant transformation compared to non-alcoholics. [77]
5.2. Molecular genetics of premalignant oral lesions
In a review article on premalignant oral lesions, genetic alterations
in OLP lesions with malignant transformation were reviewed. These ge-
netic alterations included the monosomy of chromosome 9, expression
of p53 tumor suppressor gene concurrently with an increase in PCNA
expression, loss of c-erbB2 function, and an increase of telomerase ac-
tivity.[138]
6. TREATMENT OF OLP
6.1. Glucocorticosteroids
The "gold standard" treatment for OLP is glucocorticosteroids. They
can be prescribed topically or systemically. The severity of the lesions
usually determines the delivery method. Topical glucocorticosteroids
are the first line of treatment and do not have as many side effects as
systemic steroids. Systemic glucocorticosteroids are used for the more
aggressive forms or the cases that do not respond to topical therapy,
multisite disease, or diffused disease.[139] Treatment with both topical
and systemic glucocorticosteroids are used for the most severe cases.
While uncommon, localized steroid injections can be used in cases that
do not respond to topical or systemic treatment.[140] It is very impor-
tant to take a thorough medical history on the patient before prescrib-
ing the glucocorticosteroid. Glucocorticosteroid therapy is contraindi-
cated in patients with stomach ulcers, diabetes mellitus, tuberculosis,
7
Dentistry Review 2 (2022) 100007
hypertension, hypersensitivity, and viral infections.[141] Glucocorticos-
teroids can also induce osteoporosis.[142] Table 3 presents the different
treatment modalities used for OLP.[139-140, 143-153] Steroid sparing
agents, Mycophenolate mofetil (MMF) and Sirolimus, can be used in
severe or refractory cases of OLP or when glucocorticosteroids are con-
traindicated or need to be reduced.[145] MMF is an immunosuppres-
sant and has shown to be beneficial in oral or patch form. [145, 154]
Sirolimus has both antitumor and immunosuppressive properties and
may be used for recalcitrant OLP. Calcineurin inhibitors may be used if
glucocorticosteroids are contraindicated, but caution should be advised
because they have a "Black Box" warning as a possible carcinogen. A few
studies have been completed on retinoids for treatment of OLP but these
are contraindicated in child-bearing women because of their teratogenic
effects.[143]
6.2. Oral care
Maintaining proper oral health is necessary to reduce the occurrence
and severity of OLP.[51] OLP lesions close to the gingival crest can make
it very painful for the patient to practice proper oral hygiene, in which
case techniques to reduce the chance of further irritating the tissue
(e.g., avoiding abrasive toothpaste and hard bristle toothbrushes) should
be discussed with the patient. Any restorations, fractured teeth, or ap-
pliances causing impingement on the mucosa should be adjusted, and
agents are known to cause OLP (e.g., dental restorative material, cer-
tain medications) should be investigated. Asymptomatic patients (most
often the case with reticular OLP) do not require treatment. Erosive and
atrophic OLP usually require intervention.[143]
6.3. Plant-based interventions
6.3.1. Aloe Vera
In a double-blind, randomized placebo-controlled study using aloe
vera as a topical agent for OLP in 54 patients, it was found that aloe vera
gel was significantly more effective than a placebo in improving OLPs (p
< 0.001). Its improvement was both clinical and symptomatologic.[147]
6.3.2. Lycopene
Lycopene is a red, fat-soluble carotenoid that gives tomatoes and
other vegetables its color. It has antioxidant activity by reducing free
radicals. In a randomized placebo-controlled study of 30 patients, 15
patients were given 8mg/day of lycopene for 8 weeks; the other 15 pa-
tients were given a placebo. In the study, 100% of the lycopene group
patients showed a 50% benefit, and 73.3% showed a 70-100% benefit.
In the placebo group, 26.7% were cured as compared to the lycopene
group, 73.3% were cured. The response to overall treatment was better
in the lycopene group than the placebo group (p < 0.05).[148]
6.3.3. Antioxidants
Many patients have contraindications for conventional steroid treat-
ment because of systemic diseases. Antioxidants, anthocyanins, and
flavonoids found in the diet could be advantageous.[155] Anthocyanins
are natural antioxidants that can be found in grape skins. In a prospec-
tive, non-randomized study with a control group, 52 patients with OLP
were given local treatment with anthocyanins from grapes. The con-
trols were provided clobetasol propionate -neomycin-nystatin cream
(CP-NN). They were broken into two groups erosive OLP (17 cases and
21 controls) and non-erosive OLP (9 cases and 5 controls). They were
followed for 6 months. Erosive OLP patients had a favorable response to
the anthocyanins from grapes in the measured areas and it was equal or
better than the CP-NN control group (p = 0.02). There was no significant
difference in the non-erosive OLP group (p = 0.38).[149]
A. Elenbaas, R. Enciso and K. Al-Eryani Dentistry Review 2 (2022) 100007

Table 3
Treatments for OLP. [139,140][143–153]

Medication Dosage Side Effects

Topical • 0.025% or 0.05% clobetasol propionate gel • Candidiasis,

Glucorticosteroids • 0.1% or 0.05% betamethasone valerate gel, • bad taste,
[139, 143, 144] • 0.05% fluocinonide gel, • dry mouth,
• 0.05% clobetasol butyrate ointment or cream, • sore throat,
• 0.1% triamcinolone acetonide ointment • swollen mouth
• thinning of the oral mucosa
• cushingoid features

• Oral rinses-suspension of triamcinolone acetonide 0.1% or • Candidiasis,

0.3% or 0.5% as oral rinse • thinning of the oral mucosa
• dexamethasone elixir (5mL of a 5mg/5mL suspension) • discomfort at the application site
mouth rinse
• hydrocortisone hemisuccinate in aqueous solution,
• betamethasone valerate pellets or aerosol
• clobetasol propionate mouthwash or aerosol

Glucocorticosteroid • Route: Intralesional and perilesional injection of steroids. Significantly fewer side effects than topicals:
localized injection • Generic: Dexamethasone, hydrocortisone, triamcinolone
• Tingling or burning at the injection site
[140] acetonide, methylprednisolone.
• Reversible cushingoid features

Systemic • Systemic prednisone 30-60mg is given once daily for 2-4 Contraindications:
Glucocorticosteroids weeks. Active disease Tb, HIV, HBV, HCV, stomach ulcers,
[[139,143,144] hypertension, viral infections, hypersensitivity, causes
immunosuppression and may induce osteoporosis
• Levamisole (150mg/d) with prednisone 25mg/d for 3 Fatigue, insomnia, psychosis, diabetes mellitus, weight gain,
consecutive days each week for 4-6 wks., this will reduce cataracts fluid retention, hypertension, epigastric pain
the amount of prednisone given.

Steroid sparing agents • Mycophenolate mofetil (MMF): Max dose 2g/day (divided Pregnancy category D, malignancy risk, e.g. skin cancer,
[143,145,146] dose) lymphoma; infection; progressive multifocal
leukoencephalopathy, bone marrow depression
• Sirolimus topical (1mg/ml) Monitor systemic blood levels, hyperlipidemia,
myelosuppression, impaired wound healing, proteinuria,
pneumonitis and thrombotic micro-angiopathy
Calcineurin inhibitors • Cyclosporin A topical (100mg/ml solution, 5mL), Burning sensation, bad taste, itching, swelling lips, and
[143] • Cyclosporin A systemic (5 - 6 mg/kg per day), petechial hemorrhages, cost of drug,

• Tacrolimus topical (0.1%) Affects local irritation due to burning sensation. Potential
cancer risk long term. "Black box warning" theoretical
increased risk of malignancy
• Pimecrolimus topical (1%) Burning sensation, decreased expression of a molecule in
apoptosis (Fas) pruritis and erythema on the application;
"Black Box warning" a theoretical increased risk of malignancy
skin cancer and lymphoma have been reported in patients
treated with topical calcineurin inhibitors, including
pimecrolimus 1% cream
Retinoids [143,144] Topical retinoids Irritation, burning sensation

• 0.1% Vitamin A,
• 0.05% tretinoin ointment,
• isotretinoin 0.1% gel

Systemic retinoids Elevated/deranged transaminase levels, hyperlipidemia,

cheilitis, dryness and desquamation of the skin, alopecia,
• isotretinoin,
dystrophic nail formation, teratogenic
• temarotene,
• tretinoin

Plant-based
Aloe Vera [147] • Aloe vera gel to be placed on lesions 2 times a day. Food allergy to aloe vera, stinging and mild itching at localized
site but only lasted 1 week then spontaneously disappeared
with continued use
Lycopene [148] • Lycopene 8mg/d softgel • none reported

Anthocyanins- grape • 100 mg./doses diluted in 5 ml of water, mouth rinses, • food allergy
skins, fruits, vegetables during 5 minutes and spit, three times a day
[149]

Alternative Therapies

Hyaluronic Acid 0.2% • Apply gel to ulcerated area 3 times a day after meals • none reported
gel [150]
(continued on next page)

8
A. Elenbaas, R. Enciso and K. Al-Eryani
Table 3 (continued)
Medication Dosage
Ultraviolet • TheraLight UV 120-2 system emits UVB radiation 290-320
phototherapy [144, nm. 3 times a week with gradual increase in UVB dose
151] every other session.
Photodynamic therapy • 5% methylene blue mediated photodynamic therapy
[152] (wavelengths 630nm and 7.2J/cm2 dose for 4 sessions)
Low-level laser therapy
[153]
• 630nm,10 mill watts, 1.5J/cm2 for 150 seconds, 3 times
week, 1 month
Surgical
excision/Cryosurgery
[144]
6.4. Alternative treatments
6.4.1. Hyaluronic acid
In a randomized controlled trial of 50 patients with OLP, twenty-
five test patients were given 2% hyaluronic acid, and 25 patients given
a placebo. The test patients showed a highly significant positive clinical
response VAS pain score test 1.48 with controls 7.76 (p < 0.001) and
the degree of erythema test 0.48 and control 1.35 (p = 0.0001).[150]
6.4.2. Laser therapy and ultraviolet phototherapy
In a randomized clinical trial of 30 OLP patients, 15 were treated
with photodynamic therapy, and 15 were treated with 0.5mg dexam-
ethasone solution in 5cc water. Methylene blue was used as the pho-
tosensitizer, and photodynamic therapy was used for the 30s (630 nm
wavelength and 7.2-14.4 J/cm2 dose) for 4 sessions, and 0.5mg dexam-
ethasone solution was used 2 minutes four times a day for two weeks.
Photodynamic therapy was found to be as effective as the dexametha-
sone mouth rinse in the treatment of OLP.[152]
In an observational study of 12 patients with OLP, low-level laser
therapy (LLLT) showed a significant reduction in pain. 66% of the pa-
tients felt only mild discomfort, and 37.3 had complete resolution at the
end of the treatment (p = 0.0005). LLLT has been shown to be an effec-
tive treatment with no side effects and may be considered an alternative
therapy for OLP.[156] In a study of 6 patients, direct irradiation from
a 308-nm excimer laser was found to be safe and effective, with half of
the patients’ lesions shrinking by more than 50%.[157] A study of 14
patients with OLP who were recalcitrant to previous medical therapy re-
ceived ultraviolet B phototherapy with the TheraLight U 120-2-system
(UVB radiation range 290-320 nm). Local phototherapy was delivered 3
times a week, with a gradual increase in UVB every other session. Five
patients received a partial response, and nine achieved full remission af-
ter 8 weeks. 10 of the patients continued with Theralight maintenance
treatment and had benefits for another 29 weeks.[151]
6.4.3. Surgical excision
Surgical excision is recommended for non-healing lesions as it might
cure the disease but is not recommended for atrophic or erosive forms.
Cryosurgery has also been used in erosive OLP, but recurrences are com-
mon.[144]
In a systematic review of 35 randomized controlled trials of the med-
ical management of OLP, no strong evidence suggested the superiority
of any specific intervention reducing signs or pain from OLP.[158] The
findings were similar to a Cochrane Systematic Review on the medical
management of OLP, which included 35 studies and 1,474 participants.
Corticosteroids have been the first line of treatment for OLP either topi-
cally or systemically and may be more effective than placebo for reduc-
ing pain. However, the clinical response was inconclusive, and there is
uncertainty about adverse effects.[159]
9
Dentistry Review 2 (2022) 100007
Side Effects
• UVA known oncogenic potential, pain at laser site
• pain on mucosa from probe tip
• none reported
• pain at the surgical site
In cases that do not resolve quickly with traditional therapy or where
traditional therapy is contraindicated, it would be prudent to check
for the underlying trigger or exacerbating agent. This would include
cross-referencing all pharmaceuticals for OLP reactions, offering allergy
testing to dental materials, and creating a patient’s timeline to check
for exposures to chemicals, metals, carcinogens, electromagnetic fields,
viruses, and stressful events. Further tests may include:
• A complete blood count (CBC) with differential, thyroid panel, com-
plete liver profile including serum transaminase levels, total biliru-
bin, antibodies to hepatitis virus B, C, and hepatitis B surface anti-
gens, viral titers for EBV,[17] VZV,[34],[121] HHV- 6, [126] HHV-
7,[78] thyroid, [57] CBC with differential liver panel, hepatitis B
and C.[65]
• Check vitamin status of vitamins A, C, E [73] D,[113] folic
acid,[112] B12,[109] iron[109] and homocysteine.[109]
By investigating and treating the underlying cause of OLP, the pa-
tient may have the best long-term remission. Currently, less than 20%
of OLP lesions regress spontaneously.[58] A diet high in fruits, vegeta-
bles, and low-saturated fat is recommended because plant-based nutri-
tion has been shown to protect against the 15 leading causes of death
worldwide.[160]
7. CONCLUSIONS
OLP is a multifactorial disease of the oral mucosa and is categorized
as a potentially malignant disorder that may transform into OSCC in
1.10 - 1.40% of the cases. While a definitive causative agent for OLP
is still unknown, there are a number of possible etiologies, including
psychological and physical stress, side effects from medications, irrita-
tion and allergic reactions from dental materials, genetic predisposition,
systemic diseases, viral exposures, and nutritional deficiencies. Certain
medications and dental restorative materials have been shown to both
induce or exacerbate OLP or cause a lichenoid reaction. Specific genetic
polymorphisms and systemic diseases (including diabetes, hypertension,
dyslipidemia, thyroid and liver disease, and a host of autoimmune con-
ditions) have been shown to be associated with OLP. Nutritional and
vitamin deficiencies (in particular iron, Vitamins B12, A, C, and E) are
often present in OLP cases. Corticosteroids are the ’gold standard’ for
the treatment of OLP but have shown limited efficacy. Alternative med-
ications and/or treatments have been shown to improve OLP. Some
evidence points to viruses as risk factors for OLP. Similar VZV and OLP
patient demographics and VZV presentation, including a wide variety
of painful skin ulcerations, point to VZV as a possible risk factor for
OLP. The presence of VZV in the liver is suggested as an area of further
research on the causes of OLP.
A. Elenbaas, R. Enciso and K. Al-Eryani
8. Credit authors
Drs Elenbaas, Enciso and Al-Eryani contributed to the conceptual-
ization and methodology of the study. Dr. Elenbaas wrote the original
draft and participated in the writing (review and editing) of the final
manuscript. Dr. Enciso and Dr. Al-Eryani participated in the writing (re-
view and editing) of the final manuscript.
Declarations of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Data Sharing
This review did not access, analyze or create any relevant data.
REFERENCES
[1] Pandhi D, Singal A, Bhattacharya SN. Lichen planus in childhood: A series of 316
patients. Pediatr. Dermatol. 2014;31(1):59–67. doi:10.1111/pde.12155.
[2] Pakravan M, Klesert T, Akpek E. Isolated lichen planus of the conjunctiva. Br. J.
Ophthalmol. 2006;90(10):1325–6. doi:10.1136/bjo.2005.088625.
[3] Canto H, Müller Alan, Sérgio P. Oral lichen planus (OLP): clinical
and complementary diagnosis ∗ . An Bras Dermatol 2010;85(5):669–75.
doi:10.1590/S0365-05962010000500010.
[4] Sumit Bhateja AB, Satoskar S. Lichen Planus-A Mucocutaneous Pig-
mentary Disorder-Review. J. Pigment. Disord. 2015;02(09):9–11.
doi:10.4172/2376-0427.1000209.
[5] Cassol-Spanemberg J, Blanco-Carrión A, Rodríguez-de Rivera-Campillo ME,
Estrugo-Devesa A, Jané-Salas E, López-López J. Cutaneous, genital and oral lichen
planus: A descriptive study of 274 patients. Med. Oral Patol. Oral Cir. Bucal
2019;24(1):0–6. doi:10.4317/medoral.22656.
[6] Weston G, Payette M. Update on lichen planus and its clinical variants. Int. J.
Women’s Dermatology 2015;1(3):140–9. doi:10.1016/j.ijwd.2015.04.001.
[7] I.-K. Choi et al., “ Signaling by the Epstein–Barr virus LMP1 protein induces potent
cytotoxic CD4 + and CD8 + T cell responses,” Proc. Natl. Acad. Sci., vol. 115, no.
4, pp. E686–E695, 2018, doi: 10.1073/pnas.1713607115.
[8] Ismail SB, Kumar SKS, Zain RB. Oral lichen planus and lichenoid reactions:
etiopathogenesis, diagnosis, management and malignant transformation. J Oral Sci
2007;49(2):89–106.
[9] Boorghani M, Gholizadeh N, Taghavi Zenouz A, Vatankhah M, Mehdipour M.
Oral lichen planus: clinical features, etiology, treatment and management; a
review of literature. J. Dent. Res. Dent. Clin. Dent. Prospects 2010;4(1):3–9.
doi:10.5681/joddd.2010.002.
[10] Li C. Global Prevalence and Incidence Estimates of Oral Lichen Planus: A Systematic
Review and Meta-analysis. JAMA Dermatol 2020;156(2):172–81. doi:10.1001/ja-
madermatol.2019.3797.
[11] Ramalingam S, Malathi N, Thamizhchelvan H, Sangeetha N, Rajan ST. Role of
Mast Cells in Oral Lichen Planus and Oral Lichenoid Reactions. Autoimmune Dis
2018;2018. doi:10.1155/2018/7936564.
[12] Zhao Z, Sugerman P, Zhou X, Walsh L, Savage N. Mast cell degranulation and the
role of T cell RANTES in oral lichen planus. Oral Dis 2001;7(4):246–51.
[13] Zhou XJ, Sugerman PB, Savage NW, Walsh LJ. Matrix metalloproteinases and their
inhibitors in oral lichen planus. J. Cutan. Pathol. 2001;28:72–82.
[14] González-Moles MÁ, et al. Worldwide prevalence of oral lichen planus: A systematic
review and meta-analysis. Oral Dis 2020;00:1–16 March. doi:10.1111/odi.13323.
[15] Eisenberg E. Oral lichen planus: A benign lesion. J. Oral Maxillofac. Surg.
2000;58(11):1278–85. doi:10.1053/joms.2000.16629.
[16] Pedersen A. Abnormal EBV immune status in oral lichen planus. Oral Dis
2010;2(2):125–8. doi:10.1111/j.1601-0825.1996.tb00212.x.
[17] Yildirim B, Sengüven B, Demir C. Prevalence of herpes simplex, Epstein Barr and
human Papilloma viruses in oral lichen planus. Med. Oral Patol. Oral Cir. Bucal
2011;16(2):170–4. doi:10.4317/medoral.16.e170.
[18] Kumar P, Mastan KMK, Chowdhary R, Shanmugam K. Oral manifestations in hyper-
tensive patients: A clinical study. J. Oral Maxillofac. Pathol. 2012;16(2):215–21.
doi:10.4103/0973-029X.99069.
[19] López-Jornet P, Camacho-Alonso F, Rodríguez-Martnes MA. Alterations in serum
lipid profile patterns in oral lichen planus: A cross-sectional study. Am. J. Clin.
Dermatol. 2012;13(6):399–404. doi:10.2165/11633600-000000000-00000.
[20] Arduino PG, et al. Evidence of earlier thyroid dysfunction in newly diag-
nosed oral lichen planus patients: A hint for endocrinologists. Endocr. Connect.
2017;6(8):726–30. doi:10.1530/EC-17-0262.
[21] Bombeccari GP, Tettamanti M, Pallotti F, Spadari F, Giannì AB. Exacerbations
of oral lichen planus and elevated levels of aminotransferases. Int. J. Dermatol.
2017;56(8):842–9. doi:10.1111/ijd.13626.
[22] Tovaru S, Parlatescu I, Gheorghe C, Tovaru M, Costache M, Sardella A. Oral lichen
planus: A retrospective study of 633 patients from Bucharest, Romania. Med. Oral
Patol. Oral Cir. Bucal 2013;18(2). doi:10.4317/medoral.18035.
10
Dentistry Review 2 (2022) 100007
[23] Gorouhi F, Davari P, Fazel N. Cutaneous and mucosal lichen planus: a comprehen-
sive review of clinical subtypes, risk factors, diagnosis, and prognosis. Sci. World
J. 2014;2014:742826. doi:10.1155/2014/742826.
[24] Mozaffari HR, Sharifi R, Sadeghi M. Prevalence of oral lichen planus in dia-
betes mellitus: A meta-analysis study. Acta Inform. Medica 2016;24(6):390–3.
doi:10.5455/aim.2016.24.390-393.
[25] Nosratzehi T. Oral lichen planus: An overview of potential risk factors,
biomarkers and treatments. Asian Pacific J. Cancer Prev. 2018;19(5):1161–7.
doi:10.22034/APJCP.2018.19.5.1161.
[26] Luis-Montoya P, et al. HLA-DRB1∗ 0101 is associated with the genetic susceptibility
to develop lichen planus in the Mexican Mestizo population. Arch. Dermatol. Res.
2007;299(8):405–7. doi:10.1007/s00403-007-0769-2.
[27] Welsh JP, Skvarka CB, Allen HB. A Novel Visual Clue for the Diagnosis of Hy-
pertrophic Lichen Planus. Arch. Dermatol. 2006;142(7):954. doi:10.1001/arch-
derm.142.7.954.
[28] Gupta S, Jawanda MK. Oral Lichen Planus: An Update on Etiology, Patho-
genesis, Clinical Presentation, Diagnosis and Management. Indian J. Dermatol.
2015;60(3):222–9. doi:10.4103/0019-5154.156315.
[29] Dekio I, Matsuki S, Furumura M, Morita E, Morita A. Actinic lichen planus in a
Japanese man: First case in the East Asian population. Photodermatol. Photoim-
munol. Photomed. 2010;26(6):333–5. doi:10.1111/j.1600-0781.2010.00548.x.
[30] Verhagen A, Koten J. Lichenoid melanodermatitis. A clinicopathological study
of fifty-one Kenyan patients with so-called tropical lichen planus. Br J Dermatol
1979;101:651–8.
[31] Badri T, Kenani N, Benmously R, Debbiche A, Mokhtar I, Fenniche S. Isolated gen-
ital annular, lichen planus. Acta Dermatovenerologica Alpina, Pannonica Adriat
2011;20(1):31–3.
[32] Thomas MG, Betsy A. Linear Lichen Planus: Continuum From Skin to Mucosa. J.
Cutan. Med. Surg. 2018;22(2):232–3. doi:10.1177/1203475417733463.
[33] Kota R, Jivani N, Nair P. Lichen planus: Zosteriform or along the lines of Blaschko?
Pigment Int 2016;3(1):43. doi:10.4103/2349-5847.184262.
[34] Mizukawa Y, Horie C, Yamazaki Y, Shiohara T. Detection of varicella-zoster virus
antigens in lesional skin of zosteriform lichen planus but not in that of linear lichen
planus. Dermatology 2012;225(1):22–6. doi:10.1159/000339771.
[35] A. Tosti and B. M. Piraccini, “Dermatological Diseases,” Nails, pp. 105–121, 2005,
doi: 10.1016/B978-141602356-2.50017-7.
[36] Lakshmi C, Divakaran J, Sivaraman A, Srinivas C. Painful linear atrophic
lichen planus along lines of Blaschko. Indian J. Dermatol. 2006;51(1):42–3.
doi:10.4103/0019-5154.25190.
[37] Wagner G, Rose C, Sachse MM. Der Lichen ruber planus und seine klinisch-
morphologischen Varianten. JDDG - J. Ger. Soc. Dermatology 2013;11(4):309–19.
doi:10.1111/ddg.12031.
[38] Lehman J, Tollefson M, Gibson L. Lichen planus. Arch. Derm. Syphilol.
1947;55(1):153.
[39] Ghosh A, Coondoo A. Lichen planus pigmentosus: The controversial consensus.
Indian J. Dermatol. 2016;61(5):482–6. doi:10.4103/0019-5154.190108.
[40] Demirci GT, Altunay IK, Sarikaya S, Sakiz D. Lupus erythematosus and lichen
planus overlap syndrome: A case report with a rapid response to topical corticos-
teroid therapy. Dermatology Reports 2011;3(3):107–8. doi:10.4081/dr.2011.e48.
[41] Hübner F, Langan EA, Recke A. Lichen planus pemphigoides: From lichenoid in-
flammation to autoantibody-mediated blistering. Front. Immunol. 2019;10(JUL).
doi:10.3389/fimmu.2019.01389.
[42] Lauritano D, et al. Oral lichen planus clinical characteristics in Ital-
ian patients: A retrospective analysis. Head Face Med 2016;12(1):1–6.
doi:10.1186/s13005-016-0115-z.
[43] Eisen D. Ocular Involvement in Patients With Oral Lichen Planus,” Oral Surg. Oral
Med. Oral Pathol. 1999:431–6.
[44] Kruk J, Aboul-Enein BH, Bernstein J, Gronostaj M. Psychological Stress and Cel-
lular Aging in Cancer: A Meta-Analysis. Oxid. Med. Cell. Longev. 2019;2019.
doi:10.1155/2019/1270397.
[45] Yaribeygi H, Panahi Y, Sahraei H, Johnston TP, Sahebkar A. The impact of stress on
body function: A review. EXCLI J 2017;16:1057–72. doi:10.17179/excli2017-480.
[46] Wang Y, Zhou J, Fu S, Wang C, Zhou B. A Study of Association Between Oral Lichen
Planus and Immune Balance of Th1/Th2 Cells. Inflammation 2015;38(5):1874–9.
doi:10.1007/s10753-015-0167-4.
[47] Nares S, et al. Psychological profile in oral lichen planus. J. Clin. Periodontol.
2005;32(10):1034–40. doi:10.1111/j.1600-051x.2005.00829.x.
[48] Rhodus NL, Cheng B, Ondrey F. Th1/Th2 cytokine ratio in tissue transudates
from patients with oral lichen planus. Mediators Inflamm 2007(2007):15–18.
doi:10.1155/2007/19854.
[49] Adamo D, et al. Psychological profiles in patients with symptomatic reticular
forms of oral lichen planus: A prospective cohort study. J. Oral Pathol. Med.
2017;46(9):810–16. doi:10.1111/jop.12577.
[50] Yuan A, Bin Woo S. Adverse drug events in the oral cavity,” Oral Surg. Oral Med.
Oral Pathol. Oral Radiol. 2015;119(1):35–47. doi:10.1016/j.oooo.2014.09.009.
[51] Kamath V, Setlur K, Yerlagudda K. Oral lichenoid lesions - A review and update.
Indian J. Dermatol. 2014;60(1):102. doi:10.4103/0019-5154.147830.
[52] Lu SY, Lin LH, Lu SN, Wang JH, Hung CH. Increased oral lichen planus
in a chronic hepatitis patient associated with elevated transaminase levels
before and after interferon/ribavirin therapy. J. Dent. Sci. 2009;4(4):191–7.
doi:10.1016/S1991-7902(09)60026-X.
[53] Arirachakaran P, Hanvanich M, Kuysakorn P, Thongprasom K. Antiretroviral Drug-
Associated Oral Lichenoid Reaction in HIV Patient : A Case Report. Int. J. Dent.
2010(2010) Article ID 291072. doi:10.1155/2010/291072.
[54] Alsarraf A, Mehta K, Khzam N. The gingival oral lichen planus: A periodontal-oral
medicine approach. Case Rep. Dent. 2019;2019:1–4. doi:10.1155/2019/4659134.
A. Elenbaas, R. Enciso and K. Al-Eryani
[55] Cheng YSL, Gould A, Kurago Z, Fantasia J, Muller S. Diagnosis of oral lichen
planus: a position paper of the American Academy of Oral and Maxillofa-
cial Pathology. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2016;122(3).
doi:10.1016/j.oooo.2016.05.004.
[56] Arias-Santiago S, et al. Cardiovascular risk factors in patients with lichen planus.
Am. J. Med. 2011;124(6):543–8. doi:10.1016/j.amjmed.2010.12.025.
[57] Zhou T, Li D, Chen Q, Hua H, Li C. Correlation between oral lichen planus and
thyroid disease in China: A case-control study. Front. Endocrinol. (Lausanne).
2018;9(JUN):1–6. doi:10.3389/fendo.2018.00330.
[58] Chiang CP, Yu-Fong Chang J, Wang YP, Wu YH, Lu SY, Sun A. Oral
lichen planus – Differential diagnoses, serum autoantibodies, hematinic de-
ficiencies, and management. J. Formos. Med. Assoc. 2018;117(9):756–65.
doi:10.1016/j.jfma.2018.01.021.
[59] Likar-Manookin K, et al. Prevalence of oral lesions of autoimmune etiology
in patients with primary Sjogren’s syndrome. Oral Dis 2013;19(6):598–603.
doi:10.1111/odi.12044.
[60] Qiao J, Zhou G, Ding Y, Zhu D, Fang H. Multiple paraneoplastic syndromes: Myas-
thenia gravis, vitiligo, alopecia areata, and oral lichen planus associated with thy-
moma. J. Neurol. Sci. 2011;308(1–2):177–9. doi:10.1016/j.jns.2011.05.038.
[61] Kumar K, Nachiammai N, Madhushankari G. Association of oral manifestations
in ulcerative colitis: A pilot study. J. Oral Maxillofac Pathol 2018;22(2):199–203.
doi:10.4103/jomfp.JOMFP.
[62] Bagán JV, et al. Oral lichen planus and chronic liver disease: A clinical and morpho-
metric study of the oral lesions in relation to transaminase elevation. Oral Surgery,
Oral Med. Oral Pathol. 1994;78(3):337–42. doi:10.1016/0030-4220(94)90065-5.
[63] Korkij W, Chuang TY, Soltani K. Liver abnormalities in patients with lichen planus:
A retrospective case-control study. J. Am. Acad. Dermatol. 1984;11(4):609–15.
doi:10.1016/S0190-9622(84)70215-5.
[64] Boda D, et al. Human papilloma virus: Apprehending the link with carcinogenesis
and unveiling new research avenues (Review. Int. J. Oncol. 2018;52(3):637–55.
doi:10.3892/ijo.2018.4256.
[65] Carrozzo M, et al. Hepatitis C virus infection in italian patients with oral lichen
planus: A prospective case-control study. J. Oral Pathol. Med. 1996;25(10):527–
33. doi:10.1111/j.1600-0714.1996.tb01726.x.
[66] Branco L, Vieira M, Couto C, Coelho MD, Laranjeira C. Acute acalculous chole-
cystitis by epstein-barr virus infection: A rare association. Infect. Dis. Rep.
2015;7(4):77–80. doi:10.4081/idr.2015.6184.
[67] Tong DC, Ferguson MM. Concurrent oral lichen planus and pri-
mary sclerosing cholangitis. Br. J. Dermatol. 2002;147(2):356–8.
doi:10.1046/j.1365-2133.2002.04773.x.
[68] Gheorghe C, Mihai L, Parlatescu I, Tovaru S. Association of oral lichen planus
with chronic C hepatitis. Review of the data in literature. Maedica (Buchar)
2014;9(1):98–103.
[69] Konidena A, Pavani B. Hepatitis C virus infection in patients with oral lichen planus.
Niger. J. Clin. Pract. 2011;14(2):228–31. doi:10.4103/1119-3077.84025.
[70] Behura SS, Masthan MK, Narayanasamy AB. Oral mucosal lesions associated with
smokers and chewers – A case-control study in chennai population. J. Clin. Diag-
nostic Res. 2015;9(7):17–22. doi:10.7860/JCDR/2015/14008.6169.
[71] Imanguli M, Alevizos I, Brown R, Pavletic S, Atkinson J. Oral graft-versus-host
disease. Oral Dis 2008;14(5):396–412. doi:10.1038/jid.2014.371.
[72] Challacombe SJ. Haematological abnormalities in oral lichen planus, candidi-
asis, leukoplakia and nonspecific stomatitis. Int. J. Oral Maxillofac. Surg.
1986;15(1):72–80. doi:10.1016/S0300-9785(86)80013-8.
[73] Abdolsamadi H, et al. Levels of Salivary Antioxidant Vitamins and Lipid Peroxida-
tion in Patients with Oral Lichen Planus and Healthy Individuals. Chonnam Med.
J. 2014;50(2):58. doi:10.4068/cmj.2014.50.2.58.
[74] Bhat S. Status of serum andsalivary ascorbic acid in oral potentially ma-
lignant disorders and cancer. Indian J. Med. Paediatr. Oncol. 2018:16–20.
doi:10.4103/ijmpo.ijmpo.
[75] Bahramian A, et al. Comparing Vitamin D Serum Levels in Patients with Oral Lichen
Planus and Healthy Subjects. J. Dent. (Shiraz, Iran) 2018;19(3):212–16.
[76] Wolf R, Wolf D, Ruocco E, Brunetti G, Ruocco V. Wolf’s isotopic response. Clin.
Dermatol. 2011;29(2):237–40. doi:10.1016/j.clindermatol.2010.09.015.
[77] Menshawy A, et al. Malignant transformation of oral lichen planus and oral
lichenoid lesions: A meta-analysis of 20095 patient data. Oral Oncol 2017;68:92–
102. doi:10.1016/j.oraloncology.2017.03.012.
[78] De Vries HJC, Teunissen MBM, Zorgdrager F, Picavet D, Cornelissen M. Lichen
planus remission is associated with a decrease of human herpes virus type 7 protein
expression in plasmacytoid dendritic cells. Arch. Dermatol. Res. 2007;299(4):213–
19. doi:10.1007/s00403-007-0750-0.
[79] Thornhill MH, Pemberton MN, Simmons RK, Theaker ED. Amalgam-contact hyper-
sensitivity lesions and oral lichen planus,” Oral Surg. Oral Med. Oral Pathol. Oral
Radiol. Endod. 2003;95(3):291–9. doi:10.1067/moe.2003.115.
[80] Ahlgren C, et al. Contact allergy to gold in patients with oral lichen lesions. Acta
Derm. Venereol. 2012;92(2):138–43. doi:10.2340/00015555-1247.
[81] Lu SL, et al. Clinical characteristics and analysis of familial oral lichen
planus in eight Chinese families. Exp. Ther. Med. 2016;12(4):2281–4.
doi:10.3892/etm.2016.3597.
[82] Hassan HF, Abbas AA, Kadhim Al-Malkey M, Abbas Hassan S. Determination of
HLA-DR Genotyping in a Sample of Iraqi Patients with Oral Lichen Planus. Curr.
Res. Microbiol. Biotechnol. 2017;5(6):1289–94.
[83] Carrozzo M, et al. Increased frequency of HLA-DR6 allele in Italian patients with
hepatitis C virus-associated oral lichen planus. Br. J. Dermatol. 2001;144(4):803–8.
doi:10.1046/j.1365-2133.2001.04136.x.
[84] Q. Shi, T. Zhang, N. Huo, Y. Huang, J. Xu, and H. Liu, “Association between poly-
11
Dentistry Review 2 (2022) 100007
morphisms in interleukins and oral lichen planus,” Med. (United States), vol. 96,
no. 11, p. e6314, 2017, doi: 10.1097/MD.0000000000006314.
[85] Al-Mohaya MA, Al-Harthi F, Arfin M, Al-Asmari A. TNF-𝛼, TNF-𝛽 and IL-10 gene
polymorphism and association with oral lichen planus risk in Saudi patients. J.
Appl. Oral Sci. 2015;23(3):295–301. doi:10.1590/1678-775720150075.
[86] Petrou-Amerikanou A, Markopoulos C, Belazi M, Karamitsos D, Papanayotou P.
Prevalence of oral lichen planus in diabetes mellitus according to the type of dia-
betes. Oral Dis 1998;4(1):37–40.
[87] Lundström IMC. Incidence of diabetes mellitus in patients with oral lichen planus.
Int. J. Oral Surg. 1983;12(3):147–52. doi:10.1016/S0300-9785(83)80060-X.
[88] Carbone M, et al. Course of oral lichen planus: A retrospective
study of 808 northern Italian patients. Oral Dis 2009;15(3):235–43.
doi:10.1111/j.1601-0825.2009.01516.x.
[89] Kats L, Goldman Y, Kahn A, Goldman V, Gorsky M. Oral lichen planus and
thyroid gland diseases: possible associations. BMC Oral Health 2019;19(1):1–5.
doi:10.1186/s12903-019-0859-5.
[90] Garcia-Pola MJ, Llorente-Pendás S, Seoane-Romero JM, Berasaluce MJ, García-
Martín JM. Thyroid Disease and Oral Lichen Planus as Comorbidity: A Prospective
Case-Control Study. Dermatology 2016;232(2):214–19. doi:10.1159/000442438.
[91] Owen CC, Jain R. Acute Cholecystitis. Curr. Treat. Options Gastroenterol.
2005;8:99–104.
[92] Nagao Y, Sata M. Disappearance of oral lichen Planus after liver transplantation for
primary Biliary cirrhosis and immunosuppressive therapy in a 63-year-old Japanese
woman. Hepat. Mon. 2014;14(3):1–5. doi:10.5812/hepatmon.16310.
[93] Oleaga J, Gardeazabal J, Sanz de Galdeano C, Diaz P. Generalized lichen planus
associated with primary biliar cirrhosis which resolved after liver transplantation.
Acta Derm Venereol 1995;75(1):87.
[94] Alaizari N, Al-Maweri S, Al-Shamiri H, Tarakji B, Shugaa-Addin B. Hepatitis C virus
infections in oral lichen planus: a systematic review and meta-analysis. Aust. Dent.
J. 2016;61(3):282–7.
[95] Nagao Y, Kawasaki K, Sata M. Insulin resistance and lichen planus in patients
with HCV-infectious liver diseases. J. Gastroenterol. Hepatol. 2008;23(4):580–5.
doi:10.1111/j.1440-1746.2007.04835.x.
[96] Nagao Y, et al. Genome-Wide Association Study Identifies Risk Variants for Lichen
Planus in Patients With Hepatitis C Virus Infection. Clin. Gastroenterol. Hepatol.
2017;15(6):937–44 e5. doi:10.1016/j.cgh.2016.12.029.
[97] Nagao Y, Kimura K, Kawahigashi Y, Sata M. Successful Treatment of Hepatitis C
Virus-associated Oral Lichen Planus by Interferon-free Therapy with Direct-acting
Antivirals. Clin. Transl. Gastroenterol. 2016;7(7):e179. doi:10.1038/ctg.2016.37.
[98] CojocaruMultiple autoimmune syndrome. Indian J. Dermatol. Venereol. Leprol.
2003;69(4):298–9.
[99] Chang JY, Chiang C, Hsiao CK, Sun A. Significantly higher frequencies of presence
of serum autoantibodies in Chinese patients with oral lichen planus. J Oral Pathol
Med 2009;38(1):48–54. doi:10.1111/j.1600-0714.2008.00686.x.
[100] López-Jornet P, Parra-Perez F, Pons-Fuster A. Association of autoimmune diseases
with oral lichen planus: A cross-sectional, clinical study. J. Eur. Acad. Dermatology
Venereol. 2014;28(7):895–9. doi:10.1111/jdv.12202.
[101] RambhiaThe study of prevalence of autoantibodies in patiens with LP. Indian J.
Dermatol. Venereol. Leprol. 2018;84(1):6–15. doi:10.4103/ijdvl.IJDVL.
[102] Belkacem Chebil R, et al. Oral Lichen Planus and Lichenoid Lesions in
Sjogren’s Syndrome Patients: A Prospective Study. Int. J. Dent. 2019;2019.
doi:10.1155/2019/1603657.
[103] Inalöz HS, Chowdhury MMU, Motley RJ. Lupus erythematosus/lichen planus
overlap syndrome with scarring alopecia. J. Eur. Acad. Dermatology Venereol.
2001;15(2):171–4. doi:10.1046/j.1468-3083.2001.00223.x.
[104] Jonsson R, Heyden G, Westberg N, Nyberg G. Oral mucosal lesions in systemic
lupus erythematosus–a clinical, histopathological and immunopathological study.
J Rheumatol 1984;11(1):38–42.
[105] Nico MMS, Vilela MAC, Rivitti EA, Lourenço SV. Oral lesions in lupus erythemato-
sus: Correlation with cutaneous lesions. Eur. J. Dermatology 2008;18(4):376–81.
doi:10.1684/ejd.2008.0388.
[106] Hayashi A, Shiono H, Okumura M. Thymoma accompanied by lichen planus. Inter-
act. Cardiovasc. Thorac. Surg. 2007;7(2):347–8. doi:10.1510/icvts.2007.164178.
[107] Motegi SI, Uchiyama A, Yamada K, Toki S, Amano H, Ishikawa O. Lichen planus
complicated with thymoma: Report of three Japanese cases and review of the pub-
lished work. J. Dermatol. 2015;42(11):1072–7. doi:10.1111/1346-8138.12987.
[108] Anonide A, Rebora A. What Lichen Planus Patients Die Of: A Retrospective Study.
Int. J. Dermatol. 1989;28(8):524–6. doi:10.1111/j.1365-4362.1989.tb04605.x.
[109] Chen HM, Wang YP, Chang JYF, Wu YC, Cheng SJ, Sun A. Significant association
of deficiencies of hemoglobin, iron, folic acid, and vitamin B12 and high homo-
cysteine level with oral lichen planus. J. Formos. Med. Assoc. 2015;114(2):124–9.
doi:10.1016/j.jfma.2014.10.004.
[110] Sahebjamee M. Assessment of Serum vit B12 and folic acid in pts with oral lichen
planus: A case control study,” Shiraz univ. Dent J 2010;10:1.
[111] Wu YC, Wang YP, Chang JYF, Cheng SJ, Chen HM, Sun A. Oral manifestations
and blood profile in patients with iron deficiency anemia. J. Formos. Med. Assoc.
2014;113(2):83–7. doi:10.1016/j.jfma.2013.11.010.
[112] Thongprasom K, Youngnak P, Aneksuk V. Folate and vitamin B12 levels in patients
with oral lichen planus, stomatitis or glossitis. Southeast Asian J. Trop. Med. Public
Health 2001;32(3):643–7.
[113] Ahmed S. The Role of Serum Vitamin D Deficency in oral Lichen Planus Case Con-
trol Study. Diyala J. Med. 2019;17(2):189–98. doi:10.26505/djm.17024991005.
[114] Kłosek SK, Sporny S, Stasikowska-Kanicka O, Kurnatowska AJ. Cigarette smoking
induces overexpression of c-Met receptor in microvessels of oral lichen planus.
Arch. Med. Sci. 2011;7(4):706–12. doi:10.5114/aoms.2011.24143.
A. Elenbaas, R. Enciso and K. Al-Eryani
[115] Schubert MM, Pizzigatti Correa M. Oral Graft-Versus-Host Disease. Dent Clin N Am
2008;52:79–109. doi:10.1016/j.cden.2007.10.004.
[116] el Hayderi L, Libon F, Tassoudji NN-, Ruebben A, Dezfoulian B, Nikkels A.
Zosteriform dermatoses-A review. Glob. Dermatology 2015;2(4):163–73.
doi:10.15761/god.1000146.
[117] Wolf R, Brenner S, Ruocco V, Filioli F. Isotopic Response. Int. J. Dermatol.
1995;34(5):341–8. doi:10.1111/j.1365-4362.1995.tb03616.x.
[118] da S Queiroz MT, de Almeida JRP, Sementilli Â, Mattos e Dinato SL, Romiti N.
Wolf’s isotopic response, presenting as lichen planus. An. Bras. Dermatol.
2015;90(3):S91–3. doi:10.1590/abd1806-4841.20153763.
[119] Ruocco V, Brunetti G, Puca RV, Ruocco E. The immunocompromised dis-
trict: A unifying concept for lymphoedematous, herpes-infected and other-
wise damaged sites. J. Eur. Acad. Dermatology Venereol. 2009;23(12):1364–73.
doi:10.1111/j.1468-3083.2009.03345.x.
[120] Lora V, Cota C, Kanitakis J. Zosteriform lichen planus after herpes zoster: report of
a new case of Wolf’s isotopic phenomenon and literature review. Dermatol. Online
J. 2014;20(11).
[121] Möhrenschlager M, Engst R, Hein R, Ring J. Primary manifestation of a zosteri-
form lichen planus: Isotopic response following herpes zoster sine herpete? Br. J.
Dermatol. 2008;158(5):1145–6. doi:10.1111/j.1365-2133.2008.08472.x.
[122] Sagi L, Trau H. The Koebner phenomenon. Clin. Dermatol. 2011;29(2):231–6.
doi:10.1016/j.clindermatol.2010.09.014.
[123] Ali NH, Abou-Saleh H, Smatti MK, Al-Sadeq DW, Pintus G, Nasrallah GK.
Epstein–Barr Virus Epidemiology, Serology, and Genetic Variability of LMP-1
Oncogene Among Healthy Population: An Update. Front. Oncol. 2018;8(June).
doi:10.3389/fonc.2018.00211.
[124] Abbott RJ, et al. Asymptomatic Primary Infection with Epstein-Barr Virus: Observa-
tions on Young Adult Cases. J. Virol. 2017;91(21):1–23. doi:10.1128/jvi.00382-17.
[125] Sand LP, Jalouli J, Larsson PA, Hirsch JM. Prevalence of Epstein-Barr virus
in oral squamous cell carcinoma, oral lichen planus, and normal oral mu-
cosa. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2002;93(5):586–92.
doi:10.1067/moe.2002.124462.
[126] Arivananthan M, Hashim BY, Tan BS, Yadav M, Chandrashekran A. Human
herpesvirus-6 (HHV-6) DNA and virus-encoded antigen in oral lesions. J. Oral
Pathol. Med. 2006;26(9):393–401. doi:10.1111/j.1600-0714.1997.tb00238.x.
[127] Ma J, Zhang J, Zhang Y, Lv T, Liu J. The magnitude of the association be-
tween human papillomavirus and oral lichen planus: A meta-analysis. PLoS One
2016;11(8):1–12. doi:10.1371/journal.pone.0161339.
[128] Jalouli J, Sahebjamiee M, Sand L, Karimi S, Biettolahi J, Jabalameli F. Prevalence of
human papillomavirus in oral lichen planus in an Iranian cohort. J. Oral Maxillofac.
Pathol. 2015;19(2):170. doi:10.4103/0973-029x.164528.
[129] Campisi G, et al. HPV DNA in clinically different variants of oral leukoplakia and
lichen planus. Oral Surgery, Oral Med. Oral Pathol. Oral Radiol. Endodontology
2004;98(6):705–11. doi:10.1016/j.tripleo.2004.04.012.
[130] Feller L, Lemmer J. Oral Squamous Cell Carcinoma: Epidemiology, Clin-
ical Presentation and Treatment. J. Cancer Ther. 2012;03(04):263–8.
doi:10.4236/jct.2012.34037.
[131] Pires FR, Ramos AB, de Oliveira JBC, Tavares AS, de Luz PSR, dos Santos TCRB. Oral
squamous cell carcinoma: Clinicopathological features from 346 cases from a single
oral pathology service during an 8-year period. J. Appl. Oral Sci. 2013;21(5):460–
7. doi:10.1590/1679-775720130317.
[132] Tampa M, et al. Markers of Oral Lichen Planus Malignant Transformation. Dis.
Markers 2018;2018:1–13. doi:10.1155/2018/1959506.
[133] Van der Waal I. Oral potentially malignant disorders: Is malignant transforma-
tion predictable and preventable? Med. Oral Patol. Oral Cir. Bucal 2014;19(4):1–5.
doi:10.4317/medoral.20205.
[134] Giuliani M, et al. Rate of malignant transformation of oral lichen planus: A system-
atic review. Oral Dis 2019;25(3):693–709. doi:10.1111/odi.12885.
[135] Fitzpatrick SG, Hirsch SA, Gordon SC. The malignant transformation of oral
lichen planus and oral lichenoid lesions A systematic review. J. Am. Dent. Assoc.
2014;145(1):45–56. doi:10.14219/jada.2013.10.
[136] Shearston K, Fateh B, Tai S, Hove D, Farah CS. Oral lichenoid dysplasia and not
oral lichen planus undergoes malignant transformation at high rates. J. Oral Pathol.
Med. 2019;48(7):538–45. doi:10.1111/jop.12904.
[137] Gandolfo S, Richiardi L, Carrozzo M, Broccoletti R, Carbone M. Risk of
oral squamous cell carcinoma in 402 patients with oral lichen planus :
a follow-up study in an Italian population. Oral Oncol 2004;40:77–83.
doi:10.1016/S1368-8375(03)00139-8.
12
Dentistry Review 2 (2022) 100007
[138] Mithani SK, Mydlarz WK, Grumbine FL, Smith IM, Califano JA. Molec-
ular genetics of premalignant oral lesions. Oral Dis 2007;13(2):126–33.
doi:10.1111/j.1601-0825.2006.01349.x.
[139] Carbone M, et al. Systemic and topical corticosteroid treatment of oral lichen
planus: A comparative study with long-term follow-up. J. Oral Pathol. Med.
2003;32(6):323–9. doi:10.1034/j.1600-0714.2003.00173.x.
[140] Lee YC, Shin SY, Kim SW, Eun YG. Intralesional injection versus mouth
rinse of triamcinolone acetonide in oral lichen planus: A randomized con-
trolled study. Otolaryngol. - Head Neck Surg. (United States) 2013;148(3):443–9.
doi:10.1177/0194599812473237.
[141] Sugerman PB, Savage NW. Oral lichen planus: Causes, diagnosis and management.
Aust. Dent. J. 2002;47(4):290–7. doi:10.1111/j.1834-7819.2002.tb00540.x.
[142] Briot K, Roux C. Glucocorticoid-induced osteoporosis. RMD Open 2015;1(1).
doi:10.1136/rmdopen-2014-000014.
[143] Schifter M, Yeoh SC, Coleman H, Georgiou A. Oral mucosal diseases:
the inflammatory dermatoses. Aust. Dent. J. 2010;55(Suppl 1):23–38.
doi:10.1111/j.1834-7819.2010.01196.x.
[144] GangshetttyOLP, etiology pathogenesis, diagnosis and management. WoldJ Stom-
alology 2015(August).
[145] Wee JS, Shirlaw PJ, Challacombe SJ, Setterfield JF. Efficacy of my-
cophenolate mofetil in severe mucocutaneous lichen planus: A retro-
spective review of 10 patients. Br. J. Dermatol. 2012;167(1):36–43.
doi:10.1111/j.1365-2133.2012.10882.x.
[146] Soria A, Agbo-Godeau S, Taïeb A, Francès C. Treatment of refractory oral erosive
lichen planus with topical rapamycin: 7 Cases. Dermatology 2008;218(1):22–5.
doi:10.1159/000172830.
[147] Choonhakarn C, Busaracome P, Sripanidkulchai B, Sarakarn P. The efficacy of aloe
vera gel in the treatment of oral lichen planus: A randomized controlled trial. Br.
J. Dermatol. 2008;158(3):573–7. doi:10.1111/j.1365-2133.2007.08370.x.
[148] Saawarn N, Shashikanth M, Saawarn S, Jirge V, Chaitanya N, Pinakapani R. Ly-
copene in the management of oral lichen planus: A placebo-controlled study. Indian
J. Dent. Res. 2011;22(5):639–43. doi:10.4103/0970-9290.93448.
[149] Rivarola de Gutierrez E, Di Fabio A, Salomón S, Lanfranchi H. Topical treat-
ment of oral lichen planus with anthocyanins. Med. Oral Patol. Oral Cir. Bucal
2014;19(5):e459–66. doi:10.4317/medoral.19472.
[150] Shetty RR, Burde KN, Guttal KS. The efficacy of topical hyaluronic acid 0.2%
in the management of symptomatic oral lichen planus. J. Clin. Diagnostic Res.
2016;10(1):ZC46–50. doi:10.7860/JCDR/2016/15934.7101.
[151] Kassem R, Yarom N, Scope A, Babaev M, Trau H, Pavlotzky F. Treatment of erosive
oral lichen planus with local ultraviolet B phototherapy. J. Am. Acad. Dermatol.
2012;66(5):761–6. doi:10.1016/j.jaad.2011.04.017.
[152] Bakhtiari S, Azari-Marhabi S, Mojahedi SM, Namdari M, Rankohi ZE, Jafari S. Com-
paring clinical effects of photodynamic therapy as a novel method with topical
corticosteroid for treatment of Oral Lichen Planus. Photodiagnosis Photodyn. Ther.
2017;20(June):159–64. doi:10.1016/j.pdpdt.2017.06.002.
[153] Mahdavi O, Boostani N, Jajarm H, Falaki F, Tabesh A. Use of low level laser therapy
for oral lichen planus: report of two cases. J. Dent. (Shiraz, Iran) 2013;14(4):201–4.
[154] Samiee N, Taghavi Zenuz A, Mehdipour M, Shokri J. Treatment of oral lichen
planus with mucoadhesive mycophenolate mofetil patch: A randomized clinical
trial. Clin. Exp. Dent. Res. 2020;6(5):506–11. doi:10.1002/cre2.302.
[155] Kristo AS, Klimis-Zacas D, Sikalidis AK. Protective role of dietary berries in cancer.
Antioxidants 2016;5(4):1–23. doi:10.3390/antiox5040037.
[156] Mutafchieva MZ, Draganova-Filipova MN, Zagorchev PI, Tomov GT. Effects of Low
Level Laser Therapy on Erosive-atrophic Oral Lichen Planus. Folia Med. (Plovdiv).
2018;60(3):417–24. doi:10.2478/folmed-2018-0008.
[157] Liu WB, Sun LW, Yang H, Wang YF. Treatment of oral lichen planus using 308-nm
excimer laser. Dermatol. Ther. 2017;30(5):3–5. doi:10.1111/dth.12510.
[158] Ali AA, Suresh CS. Oral lichen planus in relation to transaminase lev-
els and hepatitis C virus. J. Oral Pathol. Med. 2007;36(10):604–8.
doi:10.1111/j.1600-0714.2007.00581.x.
[159] Lodi G, Manfredi M, Mercadante V, Murphy R, Carrozzo M. Interventions for
treating oral lichen planus: corticosteroid therapies. Cochrane Database Syst. Rev.
2020;2020(2). doi:10.1002/14651858.CD001168.pub3.
[160] Madigan M, Karhu E. The role of plant-based nutrition in cancer prevention. J
Unexplored Med Data 2018;3(9):1–16. doi:10.20517/2572-8180.2018.05.