Discussion
Oral lichen planus (OLP) is a chronic inflammatory disease of unknown
etiology that can occur as either a single condition of the oral mucosa
or in association with lesions in genital mucosae, skin, or nails (7).
This disease is believed to affect around 0.2 to 2.3 percent of the
overall population and accounts for nearly 0.6 percent of all conditions
discovered by dentists regularly (7). OLP is widely distributed and
affects all racial and ethnic groups, but it is most frequent in
middle-aged female adults (8).
The clinical manifestations of OLP are largely polymorphic. Keratotic
lesions, such as papules, reticular, or plaque-like lesions, are
frequently associated with atrophic, erosive, ulcerative, or bullous
forms (9). The erosive form is characterized by a variety of symptoms
ranging from moderate discomfort to severe functional disturbances that
affect the quality of life. Lesions are usually found bilaterally on the
posterior buccal mucosa. The dorsal tongue, labial mucosa, and gingiva
might also be impacted. Gingival mucosa involvement is referred as
desquamative gingivitis (7).
The numerous factors that can trigger a cell-mediated reaction that
results in OLP are discussed elsewhere. (7) Among the exogenous factors,
several infectious agents, including viruses, have been associated with
OLP.
Among the eight recognized human herpesviruses four (Herpes
simplex 1, Cytomegalovirus, Epstein-Barr virus, Herpesvirus 6 ) have
been implicated in OLP as well as the human papillomavirus , thehuman immunodeficiency virus, and hepatitis viruses B and
mainly C (10).
HCV infection is a common illness, with an estimated 71 million people
worldwide chronically afflicted (11). Extrahepatic manifestations (EHMs)
afflict about 74 percent of persons with HCV. (12).
Xerostomia, sialadenitis, Sjögren’s disease, OLP, oral verrucous and
squamous cell carcinomas (13), bleeding disorders, cheilitis,
gingivitis, smooth and atrophic tongue, autoimmune bullous diseases such
as Pemphigus Vulgaris and bullous pemphigoid (14, 15) are among the
recorded EHMs in the oral cavity (15). As hepatitis C is most often
asymptomatic, EHMs may be the first symptom of infection.
A recent systematic review and meta‐analysis concluded that the overall
prevalence of HCV in OLP patients was 22.3% (16). This prevalence
varies according to geographical variations. A possible explanation is
that the high co-occurrence of HCV and OLP in some geographic regions
may be linked to an endemic distribution of HCV in those world
regions(17).
Globally, the prevalence of HCV shows regional variations with an
average of 3%, which is very likely to be underestimated. According to
the latest World Health Organization global hepatitis Report in 2017
(18), the prevalence is the highest in the Eastern Mediterranean region
(2.3%), followed by the European region (1.5%), whereas the South-East
Asia region has the lowest prevalence (0.5%). Inside these regions, the
difference in prevalence can be important (19).
In North Africa, the prevalence of HCV in the general population is
estimated between 1.2 and 1.9 percent (20). Although, a recent
systematic review showed that the prevalence in Tunisia between 1991 and
2019 did not exceed 1% in the general population, making it a
low-endemic country (21).
Even though the association between OLP and chronic HCV infection seems
to be well developed, the pathogenesis raises questions. Several
hypotheses are currently being useful in explaining this association:
- The Hepatitis C virus initiates an auto-immune process, and the
association of LP with other auto-immune diseases such as
diabetes, vitiligo, or myasthenia gravis lends support to this theory
(22).
- HCV directly affects cellular replication and causes immunological
changes that lead to the occurrence of LP (23).
- In chronic HCV immunological alterations and circulating
autoantibodies can emerge: anti-cardiolipin antibodies, anti-nuclear
autoantibodies, anti-mitochondrial antibodies, anti-smooth muscle
antibodies, rheumatoid factor, and anti-thyroperoxidase
antibodies. The lymphotropism of HCV explains the serological
auto-immune expressions (24).
Several differences were observed when comparing OLP patients who
have liver diseases and those who have a normal liver function. Thus,
patients with chronic liver diseases exhibit extensive forms of OLP,
with frequent periods of exacerbation of symptoms refractory to
treatment, which is commensurate with the severity of the liver disease
(25).
The acute erosive form of OLP is mostly related to chronic HCV
infection in a phase that is biologically revealed by elevated serum
levels of transaminases and increased viral replication.
Although in a recent study published by Arduino et al. (26) the
automatic screening for HCV in OLP patients must be discussed since the
general prevalence of HBV in the younger population is remarkably
decreased.
However, in our case, it was important to investigate the viral
implication of HCV since the patient was an old female living in a rural
community, where there is a shortage of investigational, preventive, and
educational campaigns on infectious diseases, also to manage the OLP
with the collaboration of infectious disease specialists to balance the
underlying and appropriate therapy.
Another issue is the necessity to test all patients diagnosed with OLP
for the presence of HCV infection, as this liver disease often
progresses asymptomatically for a long period and goes undetected (1).
In determining the therapeutic approach of OLP, several factors must be
considered; cost-effectiveness, patient’s medical and dental history,
drug interactions, treatment adherence, and psychological conditions.
Early therapy based on a clear diagnosis is crucial (27).
Topical corticosteroids are recommended as first-line therapy for OLP
(28). These drugs control inflammation and immunological response (29).
If topical treatments are ineffective, systemic corticosteroids may be
more useful.
Other Immunomodulatory drugs such as calcineurin inhibitors or retinoids
or systemic immunosuppressives may be beneficial when topical and
systemic corticosteroids are ineffective (28).
Biologic agents ( such as alefacept, efalizumab, basilixima,
polysaccharide nucleic acid fraction of bacillus Calmette–Guerin
(BCG-PSN)…) have recently been used (28). However, due to the
high cost, their application in OLP is limited to severe and
refractory cases (28).
In OLP patients with localized plaques or non-healing erosions, surgical
excision can be indicated (30). Cryosurgery has been used to treat
erosive and drug-resistant OLP, however lesions may turn into
scars (31).
Several research explored desquamative gingivitis in OLP patients, where
gingival lesions are chronic and severe. This is caused by plaque
accumulation which is higher in OLP patients, due to a decreased
frequency of tooth brushing, leading to an increased risk of long-term
periodontal disorders(32). Periodontal therapy including biofilm
reduction, scaling, and root planning in association with a decay
treatment and strict oral hygiene must be carried out with topical
corticosteroids prescription for a better result (33).
In severe and refractory cases of erosive OLP, ultraviolet A (PUVA)
therapy and photodynamic therapy have been employed (34).
The effect of laser therapy on erosive forms of OLP was reported in
different studies (Diode laser (35), biostimulation with a pulsed diode
laser (36), carbon dioxide laser evaporation (37), and low dose excimer
laser with ultraviolet B rays (38)). Although promising results were
reported, the effectiveness of this treatment approach is yet to be
proven (34).
For HCV management, interferon-alpha (IFN-α) monotherapy or combined
therapy of IFN-α and ribavirin are typical treatments for chronic HCV.
Several studies investigated the effect of IFN-α therapy on HCV patients
with OLP, finding that IFN-α either improved, triggered, or exacerbated
OLP lesions (6, 34, 39).
This suggests that HCV was not the primary cause of OLP and that other
host-related factors, according to the authors, may have a role in the
pathogenesis of HCV-related OLP (40).
Direct-acting antiviral (DAA) therapy is currently recommended as a
treatment for chronic HCV, based on the degree of liver fibrosis, HCV
genotype, resistance variants, previous treatment failure, and
comorbidities. The advantages of DAA over IFN-α and ribavirin therapy
are an increased response rate and reduced length of therapy (34, 39).
The effectiveness of DAA on OLP lesions was studied, and there are
reports of improvement (41), In contrast, cases of OLP worsening and
development of new cutaneous and genital LP were observed (42).
The studies of Nagao Y. and Tsuji M. (43) highlighted the importance of
dentists in detecting HCV infection in patients with oral mucosal
disorders who have not yet been treated. In the present case, we should
emphasize that HCV infection could be discovered with OLP as a result of
a dentist’s demand for a complete investigation of hepatic disease.
Dentists can also play an important role in the improvement of patients’
life quality by providing adequate dental care. Periodic follow-ups are
mandatory to prevent malignant transformation. It has been shown that
oral cancer can be developed on OLP, particularly if associated with
Hepatitis C infection (44).
Sources of financial support. None
Acknowledgments. The authors are grateful to the patient and
her family for their cooperation.
Conflict of Interest. The authors declare that there is no
conflict of interest.
Informed consent was obtained from the patient. The treatment
was conducted following the Helsinki Declaration.
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