Received: 28 December 2023
| Revised: 10 March 2024 | Accepted: 16 April 2024
DOI: 10.1111/odi.14975
REVIEW ARTICLE
Efficacy of antimalarials in oral lichen planus: A systematic
review
Rosana Tillero1 | José González-­Serrano2 | Vito Carlo Alberto Caponio2,3
Julia Serrano2 | Gonzalo Hernández2 | Rosa María López-­Pintor2
1
Department of Dental Clinical Specialties,
School of Dentistry, Complutense
University, Madrid, Spain
2
Department of Dental Clinical Specialties,
ORALMED Research Group, School
of Dentistry, Complutense University,
Madrid, Spain
3
Department of Clinical and Experimental
Medicine, University of Foggia, Foggia,
Italy
Correspondence
José González-­Serrano, Departamento
de Especialidades Clínicas Odontológicas,
Facultad de Odontología, Plaza Ramón y
Cajal s/n, 28040, Madrid, Spain.
Email: josego09@ucm.es
|
Abstract
Objective: To evaluate whether hydroxychloroquine (HCQ) or chloroquine (CQ) are
effective for the treatment of oral lichen planus (OLP).
Materials and Methods: A literature search was conducted in four databases. Clinical
studies investigating the effect of HCQ/CQ in patients with OLP were included.
Results: Eleven studies were included. Four were RCTs and seven quasi-­experimental
studies. The studies included 390 patients diagnosed with OLP, of which 326 and 7
received HCQ and CQ, respectively. 46 patients received topical dexamethasone, 5
placebo and 6 griseofulvin as controls. Five studies assessed pain, and all of them
obtained pain reduction with the use of HCQ. Six studies reported objective clinical
improvement of OLP with the use of HCQ. Five studies that used a subjective scale
obtained that 24%–100% of the patients achieved a complete/almost complete improvement of OLP lesions and its symptomatology. The most frequent side effects
were vision problems, gastric discomfort, rash, nauseas, headaches, skin pigmentation, and elevated kidney function. 17 patients had to withdraw from the studies.
Conclusions: Current evidence is scarce to confirm HCQ as a therapeutic option for
OLP. More RCTs are needed to compare its efficacy with topical corticosteroids and
to evaluate whether HCQ reduces relapses of OLP.
KEYWORDS
antimalarials, chloroquine, hydroxychloroquine, oral lichen planus, treatment
1
|
I NTRO D U C TI O N
from atrophic and erosive lesions. These lesions cause discomfort
and pain, decreasing patient's quality of life. In addition, some pa-
Oral lichen planus (OLP) is a chronic mucocutaneous inflammatory
tients with OLP have frequent recurrences and their treatment is a
disease that affects the oral mucosa. This disorder is associated with
challenge for clinicians (Thongprasom, 2018; Wiriyakijja et al., 2020).
the presence of white reticular, papular, erosive, atrophic, or bullous
The pathogenesis of OLP is not fully understood. A chronic T
oral lesions (Carrozzo et al., 2019). Many patients are asymptomatic
cell-­mediated inflammatory tissue reaction has been observed, but
and do not require treatment. However, some OLP patients suffer
there are other specific and non-­specific mechanisms. The main
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2024 The Authors. Oral Diseases published by Wiley Periodicals LLC.
Oral Diseases. 2024;00:1–15.
wileyonlinelibrary.com/journal/odi
| 1
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TILLERO et al.
lymphocytes involved are cytotoxic CD8+ and CD4+ T lymphocytes
2.1 | Focused question
polarized Th1, and other subsets such as Th9, Th17, and Tregs, resulting in a cytotoxic reaction against the epidermal basal cell layer
The objective of the study was to answer the following PICO
(El-­Howati et al., 2023). Several triggers and contributing factors to
(Population, Intervention, Comparison, Outcome) question: In pa-
the occurrence of OLP have been proposed such as local and sys-
tients suffering from symptomatic OLP (Population) are antimalarial
temic inducers of cell-­
mediated hypersensitivity, stress, autoim-
HCQ and/or CQ (Intervention) more effective than placebo or an-
mune response to epithelial antigens, and microorganisms (Cheng
other treatment, if available (Comparison), to improve OLP disease
et al., 2016). OLP has also been observed to be associated with other
activity or severity and/or its symptomatology (Outcome)?
systemic diseases such as thyroid disease, specifically Hashimoto's
thyroiditis, and diabetes mellitus (de Porras-­C arrique et al., 2023).
Nowadays, there are different available therapies to treat OLP in-
2.2 | Eligibility criteria
cluding topical and systemic corticosteroids, immunosuppressants,
and immunomodulators. However, the most effective treatment is
2.2.1 | Inclusion criteria
unknown, and recurrences are common (Lodi et al., 2020; Kerr &
Lodi, 2021). For this reason, it is necessary to search for new treat-
Studies included had to be: (a) research studies that administered sys-
ments to reduce recurrences and improve the quality of life of OLP
temic or topical HCQ or CQ in patients with clinical and/or histologi-
patients.
cal diagnosis of OLP; (b) randomized clinical trials (RCTs), comparative
Hydroxychloroquine (HCQ) is an antimalarial drug derived from
clinical trials, prospective or retrospective studies, quasi-­experimental
chloroquine (CQ) by hydroxylation (Dima et al., 2022). HCQ and CQ
studies (pre-­post), and case series of more than 3 patients; (c) published
have immunomodulatory, anti-­
inflammatory, and photoprotective
in scientific journals; (d) with no date restriction; (e) written in English,
actions. The mechanisms of action of HCQ and CQ remain under
(f) performed only in humans and (g) that collected any outcome meas-
continuous study (Schrezenmeier & Dörner, 2020). HCQ crosses cell
ure that assessed the improvement of disease activity or severity and/
membranes and accumulates in lysosomes. HCQ downregulates the
or symptoms in patients with symptomatic OLP.
immune system by inhibiting certain Tool 7 and 9 receptor signaling
pathways. This results in a decrease in the production of cytokines and
proinflammatory mediators reducing inflammation (Platais et al., 2023;
2.2.2 | Exclusion criteria
Schrezenmeier & Dörner, 2020; Zhu et al., 2014; Wozniacka
et al., 2008). Due to its properties, it has been indicated in rheumatol-
The following studies were excluded: (a) those not reporting the ef-
ogy and dermatology as a first-­line treatment for erythematosus lupus
fects of HCQ/CQ on patients with OLP, either on disease activity or
and it is widely used in multiple autoimmune and chronic inflamma-
severity improvement or symptomatology; (b) systematic reviews,
tory dermatoses (Cai et al., 2022; Lim et al., 2022). There are system-
meta-­analyses, cross-­sectional studies, cases reports, personal opin-
atic reviews that have shown how the use of HCQ is effective in the
ions or comments and book chapters, and (d) non-­human studies.
treatment of systemic lupus erythematosus reducing relapses (Fairley
et al., 2020). HCQ is also useful for the treatment of other autoimmune
diseases such as Sjögren's syndrome (Wang et al., 2021) or rheumatoid
2.3 | Sources of information and search strategy
arthritis (Rempenault et al., 2020). Considering the positive effects of
antimalarials on the immune system, their use in OLP could be useful.
A literature search was performed in the following electronic databases:
In fact, there are different studies that have evaluated their efficacy in
PubMed/MEDLINE, Scopus, Cochrane library, and Web of Science.
the treatment of both, cutaneous lichen planus and/or OLP, showing
The search was performed in February 29, 2024. No filters were used
positive results (Vermeer et al., 2021; Nic Dhonncha et al., 2017; Raj
to perform the search and no publication date limit was established.
et al., 2021; Platais et al., 2023). However, to date, there are no sys-
The search was performed by two investigators (RT and JG-­S).
tematic reviews synthesizing scientific evidence about the efficacy of
The search strategy used a combination of the following key-
antimalarials in the treatment of OLP. Therefore, the aim of this study is
words adapted to each database: (Antimalarials OR chloroquine
to conduct a systematic review to evaluate the efficacy of antimalarials
OR hydroxychloroquine) AND ((oral lichen planus) OR (erosive oral
in the treatment of OLP.
lichen planus) OR (mucocutaneous disorder) OR (oral potentially
malignant disorders)). Detailed search strategy for each database is
2
|
M ATE R I A L S A N D M E TH O DS
This study was conducted according with the Preferred Reporting
reported in Table S1.
2.4 | Data extraction
Items for Systematic Reviews and Meta-­Analyses (PRISMA) checklist (Moher et al., 2009). The protocol for this systematic review was
The studies found in each database were exported to the EndNote
registered in PROSPERO (protocol no. CRD42023398426).
software (Clarivate Analytics). Duplicate references were detected
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2
and eliminated using this program. Two researchers (RT and JG-­S)
two were case reports, one did not apply HCQ or CQ as treatment,
independently examined all existing references, compared search
one was a narrative review, two were in Chinese language and two
results, and removed duplicates. Titles and abstracts were reviewed.
did not specify if the patients presented OLP lesions and its im-
Studies that fulfilled the inclusion criteria were selected and were
provement (Table S3). Finally, 2 articles were added by hand search,
examined in full text. Any disagreement was resolved by consensus
resulting in a total of 11 studies included (Chirravur et al., 2023; Xie
with a third investigator (VCAC). The k-­agreement calculation was
et al., 2023; Platais et al., 2023; Raj et al., 2021; Sondhi et al., 2020;
used to evaluate the reviewer's agreement. K-­agreement between
Yeshurun et al., 2019; Naidu et al., 2018; Rivas-­Tolosa et al., 2016;
the two reviewers obtained an excellent result of 0.81.
Bendas et al., 2013; Bhuiyan et al., 2010; Eisen, 1993). The flowchart
The following data were extracted from the included studies: (a)
is shown in Figure 1.
General characteristics of the selected studies: first author, year of
publication, journal and country where the study was conducted,
article title, study design, sample size of OLP patients, patient's age
3.2 | Characteristics of the studies
and gender (Table 1); (b) Specific characteristics of the studies: inclusion and exclusion criteria, drug regimen, side effects and drop
The included studies were published between 1993 and 2023
outs, and use of alternative drugs during the study (Table 2); (c) Data
(Table 1). Four studies were conducted in India (Raj et al., 2021;
to assess treatment efficacy: outcomes (lesion severity and/or pain
Sondhi et al., 2020; Naidu et al., 2018; Bhuiyan et al., 2010), one in
assessments), recurrences, and follow-­up (Table 3).
UK (Platais et al., 2023), one in China (Xie et al., 2023), one in Israel
(Yeshurun et al., 2019), one in Spain (Rivas-­Tolosa et al., 2016), one
2.5 | Risk of bias assessment
in Egypt (Bendas et al., 2013), and two in USA (Chirravur et al., 2023;
Eisen, 1993). Regarding study design, seven were quasi-­experimental
studies (Chirravur et al., 2023; Platais et al., 2023; Raj et al., 2021;
Because of the different design of included studies, specific tools
Sondhi et al., 2020; Yeshurun et al., 2019; Rivas-­Tolosa et al., 2016;
were employed for assessing bias. The Cochrane Collaboration's tool
Eisen, 1993), and four were RCTs (Xie et al., 2023; Naidu et al., 2018;
for assessing risk of bias (RoB2) was used to evaluate randomized
Bendas et al., 2013; Bhuiyan et al., 2010).
controlled trials (Sterne et al., 2019). This tool consists of 5 domains:
A total of 390 patients with a diagnosis of OLP were included in
risk of bias arising from the randomization process, due to deviations
this systematic review (Table 1). Of these, 326 and 7 received HCQ
from intended interventions, based on missing outcome data, risk
and CQ, respectively. As comparators, 46 patients received topical
of bias in the measurement of the outcome, and in the selection of
dexamethasone, 5 patients received placebo and 6 received griseo-
the reported result. The overall results of each study were classi-
fulvin. 10 of the 11 included studies detailed the age and gender of
fied as low risk of bias, high risk of bias, or some concerns (Higgins
patients with OLP (Chirravur et al., 2023; Xie et al., 2023; Platais
et al., 2020).
et al., 2023; Raj et al., 2021; Sondhi et al., 2020; Yeshurun et al., 2019;
Joanna Briggs Institute (JBI) Critical appraisal tool for quasi-­
Naidu et al., 2018; Rivas-­Tolosa et al., 2016; Bendas et al., 2013;
experimental studies risk of bias checklist was employed for as-
Eisen, 1993). The mean age of the patients in the selected studies
sessing quasi-­experimental studies (Tufanaru et al., 2020). This tool
ranged between 42.09 ± 13.96 and 70 ± 12 years. Regarding gender,
contains nine questions (Table S2) that can be answered with “yes,”
274 were women and 100 men.
“no,” or “unclear.” Quality scores were categorized into three groups:
Four studies had a comparison group: Xie et al. (2023) com-
low (1–4), moderate (5–7), and high (8–9). The evaluation was made
pared oral HCQ with topical dexamethasone; Naidu et al. (2018)
by two independent researchers (JG-­S and VCAC). Any disagree-
compared oral HCQ with topical HCQ gel; Bendas et al. (2013)
ment was resolved by consensus with a third investigator (RMLP).
compared topical HCQ gel with a placebo; and Bhuiyan et al. (2010)
compared oral HCQ with griseofulvin. The remaining seven stud-
3
|
R E S U LT S
3.1 | Selection of studies
ies did not compare oral HCQ with another treatment or placebo (Chirravur et al., 2023; Platais et al., 2023; Raj et al., 2021;
Sondhi et al., 2020; Yeshurun et al., 2019; Rivas-­Tolosa et al., 2016;
Eisen, 1993). Rivas-­Tolosa et al. (2016) used HCQ and CQ in their
study (Table 1).
The search strategy yielded 716 references, of which 585 remained
The type of OLP included in each study, if available, is shown in
after removing duplicates. Subsequently, the researchers (RT and
Table 1. Erosive oral lichen planus was the most frequent OLP form
JG-­S) reviewed all titles and abstracts. A total of 561 references
treated. Patients from 7 of the 11 studies had histological confirma-
were excluded because they were outside the scope of this review,
tion (Xie et al., 2023; Platais et al., 2023; Raj et al., 2021; Yeshurun
resulting in 24 potential references. Seven studies were not re-
et al., 2019; Naidu et al., 2018; Bhuiyan et al., 2010; Eisen, 1993),
trieved because 2 were conference abstracts, 4 were study records
although in one of them the biopsies were taken from the skin
and 1 reported only two cases. Thus, after reading the 17 full-­text
(Bhuiyan et al., 2010). Three studies only had clinical diagnosis
studies, 8 references were excluded due to the following reasons:
(Sondhi et al., 2020; Rivas-­Tolosa et al., 2016; Bendas et al., 2013)
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| 3
TILLERO et al.
Quasi-­
experimental
study
Quasi-­
experimental
study
Hydroxychloroquine is effective in
oral lichen planus: A multicenter,
randomized, controlled trial.
Efficacy of hydroxychloroquine in oral
lichen planus: a retrospective review
Hydroxychloroquine-­A new treatment
option for erosive oral lichen planus
Safety and efficacy of
hydroxychloroquine in patients of
symptomatic oral lichen planus
Hydroxychloroquine sulphate therapy of
erosive oral lichen planus
Topical HCQS vs. Enteral HCQS in Oral
Lichen Planus Comparative Study
Antimalarial Drugs for the Treatment of
Oral Erosive Lichen Planus
Hydroxychloroquine niosomes: A new
trend in topical management of oral
lichen planus
Comparative efficacy of
hydroxychloroquine and griseofulvin
in the treatment of lichen planus
Hydroxychloroquine sulfate (Plaquenil)
improves oral lichen planus: An open
trial
Xie et al., 2023; Oral Diseases;
China
Platais et al., 2023; British
Journal of Dermatology; UK
Raj et al., 2021; Indian Journal of
Dental Research; India
Sondhi et al., Journal of
Pakistan Association of
Dermatologists; 2020; India
Yeshurun et al. 2019;
Australasian Journal of
Dermatology; Israel
Naidu et al., 2018; Oral Health
and Dental Management;
India
Rivas-­Tolosa et al., 2016;
Dermatology; Spain
Bendas et al., 2013; International
Journal of Pharmaceutics;
Egypt
Bhuiyan et al., 2010; Journal
of Pakistan Association of
Dermatologists; India
Eisen et al., 1993; Journal of
the American Academy of
Dermatology; USA
10 with EOLP
HCQ: 10 patients
16 with OLP
HCQ gel: 11
16 with OLP
CQ: 7 patients
8 with EOLP
HCQ gel: 15 (13 AOLP,
2 ROLP)
Griseofulvin: 6
patients
Placebo: 5
HCQ: 1 patient
59 (40–66)
NR
HCQ gel: 44.73
Placebo: 48
66.13 ± 8.43
46 ± 11.39
HCQ gel:
43.87 ± 10.53
Systemic HCQ:
48.13 ± 12.16
55.14 ± 12.2
21 with EOLP
Systemic HCQ: 15 (1
AOLP, 14EOLP)
46.87 ± 12.86
30 with OLP: 19 AOLP, 11 EOLP
30 with OLP
41.3 ± 11.15
59 ± 12.48
30 with EOLP
100 with OLP
HCQ: 42.09 ± 13.96
Topical
dexamethasone:
44.39 ± 11.03
HCQ: 47
Topical
dexamethasone:
46
43.23 ± 2.61
70 ± 12
Mean age (years)
93 with AOLP/EOLP/UOLP
36 with OLP
Sample size of OLP patients
M:1; F:9
NR
M: 4; F:12
HCQ gel: M:2; F:9
Placebo: M:2; F:3
M:2; F:6
M:8; F:22
HCQ gel: M:6; F:9
Systemic HCQ: M:2;
F13
M:6; F:15
M:14; F:16
M:12; F:18
M:15; F:85
HCQ: M:8; F:39
Topical dexamethasone
M:19; F:27
M:27; F:66
M:11; F:25
Gender
|
TILLERO et al.
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Abbreviations: AOLP, atrophic oral lichen planus; CQ, chloroquine; EOLP, erosive oral lichen planus; EOLP, erosive oral lichen planus; F, female; HCQ, hydroxychloroquine; M, male; NR: not reported; OLP,
oral lichen planus; RCT, randomized clinical trial; ROLP, reticular oral lichen planus; UOLP, ulcerative oral lichen planus.
Quasi-­
experimental
study
RCT
RCT
Quasi-­
experimental
study
RCT
Quasi-­
experimental
study
Quasi-­
experimental
study
RCT
Quasi-­
experimental
study
Hydroxychloroquine for the
management of recalcitrant oral
lichen planus
Chirravur et al., 2023; Oral Surg
Oral Med Oral Pathol Oral
Radiol; USA
Study design
Title
Author, year; journal; country
TA B L E 1 General characteristics of the studies.
4
Inclusion criteria
-­Patients with symptomatic OLP
-­Patients with OLP diagnosed
clinically
-­Patients who failed topical
therapy and systemic
corticosteroids
-­Patients with at least 1 follow-­up
visit within 12–24 months of
initiation on HCQ
-­Modified WHO diagnostic
criteria of OLP 2003
-­Age: from 18 to 65 years
-­OLP histologically confirmed
-­Signed informed consent
Chirravur
et al., 2023
Xie et al., 2023
NR
HCQ group: 1 patient dizziness. This
patient dropped out of the study.
HCQ: oral 100 mg twice a day
for 4 weeks
Dexamethasone: topical
0.05% three times a day on
the lesions for 4 weeks
-­Pregnancy, breastfeeding
-­Other oral mucosal disease or
severe
periodontitis
-­Infectious diseases, or
precancerous
lesions and tumor
-­History of immune system diseases
-­Received immunotherapy within
3 months
-­Abnormal liver or kidney function
-­Central/peripheral nervous system
abnormalities
-­Hemolytic anemia or abnormalities
in platelet and leukocytes
-­Ophthalmological abnormalities
-­Glaucoma and cataract
-­Allergy to HCQ sulfate tablets
-­Lesions related to silver amalgam
-­Cardiovascular contraindications
(Continues)
Concomitant drugs:
-­25 (78.1%) patients with
topical corticosteroids:
dexamethasone 0.1 mg/
mL, clobetasol 0.05%
gel, and/or fluocinonide
0.05% gel.
-­3 patients (8.3%)
received intralesional
treatment of ulcers with
triamcinolone acetonide
40 mg/mL
-­11 patients (39.3%) with
severe ulcerations had
completed a course of
prednisone
Rescue medication during
the study
Six patients (16.6%): 5 (13.9%) had a
skin rash and 1 (2.8%) reported
abdominal pain.
The skin rashes developed within
10 to 28 days from starting
the HCQ and resolved after
discontinuation, with only 1
subject (2.8%) treated with a
12 days taper of prednisone.
These 6 patients discontinued
therapy secondary to adverse
events.
Side effects and dropouts
HCQ 200 mg twice a day for
12–24 months
Drug regimen
-­Patients who were already on HCQ
for another condition
-­Patients with less than 12-­month
follow-­up
-­Patients who were not compliant
with HCQ
Exclusion criteria
| 5
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Author, year
TA B L E 2 Specific characteristics of the included studies.
TILLERO et al.
Inclusion criteria
-­OLP histologically confirmed
-­Oral disease severity score
(ODSS) recorded at baseline
-­Active EOLP histologically
confirmed
-­No OLP treatment within
6 months before the study
-­Otherwise Systemically
healthy
-­Supragingival scaling
at baseline and every 4 weeks
-­Patients clinically diagnosed
with OLP
-­OLP histologically confirmed
-­Discontinuation of other
therapies for OLP before
starting the study
-­Clinical evaluation at baseline
Platais et al., 2023
Raj et al., 2021
Sondhi et al., 2020
Yeshurun
et al., 2019
2 severe headache, 3 nausea and
vomiting (withdrawn from study
at 2 months), 1 skin pigmentation
(withdrawn from study at
4 months)
Gastritis, headache, and weakness
in 80%, 33% and 7% of the
patients, respectively
200 mg of oral HCQ twice a
day for 6 months
200 mg of oral HCQ twice
daily for 6 months
400 mg of oral HCQ daily or
1–36 months
-­Pregnancy or lactation
-­Use of tobacco
-­Presence of adjacent amalgam
restoration to the lesion
-­Known hypersensitivity to HCQ
-­LP in any region other than the oral
cavity
-­Age under 18 years
-­Asymptomatic oral lesions
-­Pregnant or lactating women
-­Patients using drugs inducing
lichenoid reaction, or amalgam
filling close to lesions
-­Skin, genital, or other extra oral
lesions
-­Chronic liver disease,
hematological disease and
immune system dysfunction,
other contraindications of use
of HCQ
-­Refusal to participate
NR
5 patients: 1 blurred vision, 1
visual field defects, 1 rash, 1
hyperpigmentation, 1 elevated
kidney function
3 withdrawn due to increased
creatinine levels after 1 month
16 patients reporting 17 mild
and transient side effects: 3
abdominal discomforts, 3 blurred
visions, 2 rash, 2 nauseas, 2
headaches, 2 itches, 1 thinning
hair, 1 seasickness, 1 mood
change.
No interruption from any patient
Side effects and dropouts
Up to 400 mg of oral HCQ
daily
Minimum 6 months to assess
response
Drug regimen
-­Insufficient documentation
Exclusion criteria
NR
NR
NR
Concomitant systemic
drugs: 21 prednisolone,
4 mycophenolate
mofetil, 1 azathioprine.
Rescue medication during
the study
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Author, year
TA B L E 2 (Continued)
6
-­OLP histologically confirmed
-­Recalcitrant EOLP
-­First clinical examination at
1 month of treatment
-­OLP clinically assessed
-­LP with or without oral
involvement with skin
histologically confirmation
-­OLP histologically confirmed
-­Discontinuation of OLP
treatments, 3 weeks before
starting the study
Naidu et al., 2018
Rivas-­Tolosa
et al., 2016
Bendas et al., 2013
Bhuiyan
et al., 2010
Eisen et al., 1993
They did not find any serious
adverse effects
HCQ: 400 mg daily for
6 months
Griseofulvin: 500 mg daily for
6 months
200-­4 00 mg of oral HCQ daily
for 6 months
-­Pregnant or breastfeeding
-­Younger than 20 years or older
than 60
-­Sensitivity to HCQ or griseofulvin
-­Intake of medications that could
interfere with trial drugs
-­Serious systemic diseases
Patients with evidence of CLP or
discoid lupus erythematosus
2 patients: 1 persistent oral pain
and erosions (withdrawn
after 3 months), 1 transient
gastrointestinal pain
3 patients presented burning
and tingling at the end of the
treatment period
Niosomal gel 30 min after
washing their mouth at
night for 4 months
-­Pregnant or breastfeeding
-­Sensitive to HCQ
-­Taking medications that could
interfere with HCQ
-­Severe systemic diseases
5 patients added topical
corticoids to their
regimen after 6 months
NR
NR
NR
3 patients: 1 transient gastric
intolerance, 1 decrease in visual
field (withdrawn after 2 months),
1 patient withdrawn due to
pancytopenia secondary to
chronic liver disease
-­Skin lesions of lichen planus,
lupus erythematosus or other
inflammatory dermatoses
CQ: 125-­250 mg once or twice
daily
HCQ: 200 mg twice/day
1 month, and then once
daily
Rescue medication during
the study
NR
Side effects and dropouts
NR
Drug regimen
HCQ gel group: at 20% 3
times/day
Oral HCQ group: 200-­4 00 mg
once or twice daily
Duration NR in any group
-­Patients with severe systemic
disease.
-­Lichenoid reaction, contact allergy
-­Previous OLP treatment within
1 month
-­Patients with retinopathy or other
hematological disease
-­Patients with CLP
-­Hypersensitivity to HCQ and CQ
Exclusion criteria
| 7
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Abbreviations: CLP, cutaneous lichen planus; HCQ, hydroxychloroquine; LP, lichen planus; NR, not reported.
Inclusion criteria
Author, year
TABLE 2 (Continued)
TILLERO et al.
|
TILLERO et al.
TA B L E 3 Outcome results related to clinical improvement and symptomatology.
Author, year
Assessments
Chirravur
et al., 2023
Pain (NRS 0–10)
REU severity
Xie et al., 2023
Pain (VAS 0–10)
RHU score
Outcomes
Baseline
Final visit (12–24 months)
NRS
1.9 ± 2.2 (n = 30)
0.9 ± 1.7 (n = 27)
REU
16 ± 8 (n = 12)
12 ± 6.3 (n = 12)
Baseline
4 weeks
VAS
HCQ
3.74 ± 2.02
2.47 ± NR
Topical dexamethasone
3.7 ± 2.45
2.11 ± NR
HCQ
10.6 ± 6.9
7.68 ± NR
Topical dexamethasone
12.01 ± 8.22
7.18 ± NR
RHU
Platais
et al., 2023
Oral disease
severity score
(ODSS)
Raj et al., 2021
Pain (VAS 0–10)
REU severity
BURN (0–4)
Global scale
≥25% ODSS: 79% of patients
<25% ODSS: 21% of patients
Baseline
3 months
6 months
VAS
8.73 ± 0.82
5.17 ± 1.11
2.03 ± 1.15
REU
21 ± 4.5
15.08 ± 4.85
11.16 ± 3.96
BURN
2.87 ± 0.77
1.43 ± 0.72
0.63 ± 0.55
23.33% marked improvement, 43,33% almost complete remission, 26.67% absolute remission
Sondhi
et al., 2020
Pain (VAS 0–10)
Thongprasom
scale from 1–5
VAS
Baseline
2 months
4 months
6 months
8 months
5.33 ± 1.21
3.43 ± 1.13
1.57 ± 1.30
0.40 ± 1.10
0.37 ± 0.99
At the time of completion of therapy, 80% of the patients had no lesions
Scale
3.33 ± 0.6
1.4 ± 1.08
0.57 ± 1.2
0.53 ± 1.15
Yeshurun
et al., 2019
Global scale
14% no change; 57% moderate to marked improvement; 24% complete remission after 2–4 months
Naidu et al., 2018
Thongprasom
scale from 1–5
Baseline
2 weeks
4 weeks
6 weeks
HCQ gel
2.2 ± 0.65
2.2 ± 0.65
2.33 ± 0.87
2.07 ± 0.57
Oral HCQ
4.27 ± 0.67
4.27 ± 0.67
3.73 ± 0.93
3.33 ± 0.94
-­
0.005*
0.002*
p value
Rivas-­Tolosa
et al.; 2016
Global scale
Bendas
et al., 2013
Pain (NRS 0–10)
Lesion size
100% almost complete or complete improvement after 2.4 months (1–5 months)
HCQ gel
Placebo
Baseline
4 months
Baseline
4 months
NRS
4
1
3
3
Lesion size
2.00 ± 1.07 cm
0.65 ± 0.82 cm
2.02 ± 0.97 cm
1.92 ± 0.87 cm
72.7% relief of all symptoms when completed the treatment with HCQ gel
Bhuiyan
et al., 2010
Global scale
Eisen et al., 1993
Global scale
HCQ
70% complete response, 30% moderate improvement
Griseofulvin
33.3% complete response, 33.3% moderate improvement, 33.3% no response
Baseline: 70% patients with erosions
6 months: 30% patients with erosions.
Global scale: 2.1 ± 1.22
50% nearly complete or complete improvement, 30% marked improvement, 10%
moderate improvement. Lesions were reduced in size and reepithelialized by ≥50%
compared to baseline
Abbreviations: *, statistically significant differences; *, statistically significant result; BL, baseline; BURN, Severity of burning sensation scale; HCQ,
hydroxychloroquine; NR, not reported; NRS, Numerical rating scales; REU, number of units of reticulation (R), erythema (E) or ulceration (U); RHU,
reticulation (R), hyperemia (H), and ulceration (U); VAS, visual analog scale.
(Table 2). Meanwhile, Chirravur et al. (2023) study included histo-
daily (Chirravur et al., 2023; Xie et al., 2023; Platais et al., 2023;
logically confirmed cases and other cases diagnosed only clinically
Raj et al., 2021; Sondhi et al., 2020; Yeshurun et al., 2019; Naidu
(Table 2).
et al., 2018; Rivas-­
Tolosa et al., 2016; Bhuiyan et al., 2010;
Two studies administered topical HCQ gel (Naidu et al., 2018;
Bendas et al., 2013), ten studies administered oral HCQ 200–400 mg
Eisen, 1993), and one study also administered CQ 125–250 mg once
or twice daily (Rivas-­Tolosa et al., 2016) (Table 2).
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8
p
Recurrences
Follow-­up
NR
Follow-­up between
12–24 months (mean 23.2)
NR
4 weeks
22% of relapses to an ODSS greater than baseline
at least once during follow-­up
Median follow-­up: 20 months
Not significant recurrences
12 months
No recurrence until 6 months after completion of
therapy
12 months
3 patients (14%) with a follow-­up between
8–36 months
Follow-­up between 1–36 months
NR
Follow-­up at 2, 4, 6, 12 weeks
Five patients relapsed with a follow-­up between
2–24 months
Follow-­up between 2–24 months
No recurrence reported in patients treated with
HCQ gel after 4 months
Weekly follow-­up for 4 months
NR
1 year follow-­up after treatment
All patients had exacerbations 3 months after
therapy
6 months
0.028*
0.032*
p
0.0021*
0.00094*
0.022*
0.00058*
BL-­3 months, BL-­6 months, 3–6 months
p < 0.001*
p < 0.001*
p < 0.001*
10 months
12 months
p
0.37 ± 0.99
0.37 ± 0.99
<0.00001*
0.57 ± 1.2
0.57 ± 1.2
NR
12 weeks
2.07 ± 0.57
3.33 ± 0.94
0.002*
p value
NR
0.0019*
p = 0.12
3.3 | Main findings
(RHU) lesions size; while Raj et al. (2021) and Chirravur et al. (2023)
measured reticular, erosive, and ulcerative (REU) lesions size. Bendas
3.3.1 | Disease activity or severity improvement
et al. (2013) measured the lesions size in centimeters. And two studies used Thongprasom scale (Sondhi et al., 2020; Naidu et al., 2018).
Only six studies evaluated the oral clinical improvement (Table 3).
Xie et al. (2023) obtained an RHU score reduction of 27.49%
Xie et al. (2023) assessed reticulation, hyperemia, and ulceration
(from 10.6 ± 6.9 at baseline to 7.68 at 4 weeks) with the use of HCQ,
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| 9
TILLERO et al.
|
TILLERO et al.
Records identified: (n=716)
Databases (n=4)
Pubmed (n=185)
Cochrane (n=17)
Scopus (n=380)
Web of science (n=134)
Records removed before
screening:
Duplicate records removed
(n=131)
Records screened (n=585)
Records excluded:
Title and abstract (n=561)
Reports sought for retrieval
(n=24)
Screening
Identification
Identification of studies via databases and registers
Included
Reports assessed for eligibility
(n=17)
Studies included in review
(n=11)
(9 + 2 from hand search)
Reports not retrieved (n=7):
Conference abstracts (n=2)
Study records (n=4)
Report of 2 cases (n=1)
Reports excluded (n=8)
Reasons:
- Case reports (n=2)
- No HCQ or CQ treatment (n=1)
- Narrative review (n=1)
- Chinese language (n=2)
- Oral lesions not specified (n=2)
Hand search (n=2)
F I G U R E 1 Flow diagram of the
literature search, according to the
Preferred Reporting Items for Systematic
Reviews and Meta-­Analyses (PRISMA).
and a reduction in 40.25% (from 12.01 ± 8.22 at baseline to 7.18 at
In the study of Naidu et al. (2018) to assess OLP disease activity,
4 weeks) using topical dexamethasone. No statistically significant
they used the Thongprasom scale. This study compared the results
differences were obtained in RHU scores (p = 0.21) between groups.
at baseline, 2 weeks, 4 weeks, and 12 weeks in two groups using oral
Both treatments achieved statistically significant differences com-
HCQ and topical HCQ gel. These authors observed that the scores
pared with baseline (HCQ, p = 0.022; topical dexamethasone,
were 2.2 ± 0.65 and 4.27 ± 0.67 at baseline, 2.2 ± 0.65 and 4.27 ± 0.67
p = 0.00058).
at 2 weeks, 2.33 ± 0.87 and 3.73 ± 0.93 at 4 weeks, 2.07 ± 0.57 and
Raj et al. (2021) obtained a mean REU score of 21 ± 4.5 at base-
3.33 ± 0.94 at 6 weeks, and 2.07 ± 0.57 and 3.33 ± 0.94 at 12 weeks
line, 15.08 ± 4.85 at 3 months and 11.16 ± 3.96 at 6 months, achiev-
in topical HCQ gel and oral HCQ groups, respectively. The improve-
ing statistically significant differences between baseline–3 months
ment results were significantly higher in the oral HCQ group than
(p < 0.001), baseline–6 months (p < 0.001), and 3 months–6 months
in the group using topical HCQ at 4, 6, and 12 weeks (p = 0.005,
(p < 0.001). Meanwhile, Chirravur et al. (2023) reported mean REU
p = 0.002, p = 0.002, respectively).
scores of 16.0 ± 8.0 at baseline and 12.0 ± 6.3 at the final visit (mean
follow-­up 23.2 months) in 12 patients. These differences showed
statistically significant differences (p < 0.032).
3.3.2 | Oral clinical symptoms
Bendas et al. (2013) obtained a reduction in the size of lesions
from 2.00 ± 1.07 cm to 0.65 ± 0.82 cm in HCQ gel group (64.28%
Five studies evaluated pain from 0 to 10 using a numeric rating scale
size reduction) and from 2.02 ± 0.97 cm to 1.92 ± 0.87 cm in placebo
(NRS) (Chirravur et al., 2023; Bendas et al., 2013) or a visual analog
group (3.94% size reduction) at 4 months of treatment, obtaining
scale (VAS) (Xie et al., 2023; Raj et al., 2021; Sondhi et al., 2020).
statistically significant reduction between groups after treatment
Moreover, Raj et al. (2021) also used a tool to quantify the severity
(p = 0.019).
of burning sensation (BURN) (Table 3).
Sondhi et al. (2020) using oral HCQ obtained a Thongprasom scale
Bendas et al. (2013) reported a decrease in NRS from 4 to 1 after
results of 3.33 ± 0.6, 1.4 ± 1.08, 0.57 ± 1.2, 0.53 ± 1.15, 0.57 ± 1.2,
topical HCQ gel application, compared with placebo group where the
0.57 ± 1.2 at baseline, 4, 6, 8, 10, and 12 months, respectively.
mean score remained 3 after 4 months of use (p value not reported).
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10
High risk
High risk
High risk
Some concerns
Overall bias
Chirravur et al. (2023) showed a decrease in NRS from a mean
of 1.9 ± 2.2 (n = 30) at the HCQ initiation visit to a mean of 0.9 ± 1.7
(n = 27) at the final visit (mean follow-­up 23.2 months), obtaining statistically significant differences (p < 0.028).
Sondhi et al. (2020) obtained VAS scores of 5.33 ± 1.21,
1.57 ± 1.30,
0.40 ± 1.10,
0.37 ± 0.99,
0.37 ± 0.99,
0.37 ± 0.99 at baseline, 2-­, 4-­, 6-­, 8-­, 10-­and 12-­month visits, achiev(p < 0.00001).
Raj et al. (2021) obtained a VAS score of 8.73 ± 0.82 at baseline, 5.17 ± 1.11 at 3 months and 2.03 ± 1.15 at 6 months, achievLow
Some concerns
Low
ing statistically significant results in every visit compared to baseline
Low
Selection of the reported
result
3.43 ± 1.13,
ing statistically significant differences between baseline–3 months
(p < 0.001), baseline–6 months (p < 0.001), and 3 months–6 months
(p < 0.001). They also reported a BURN score of 2.87 ± 0.77 at baseing statistically significant differences between baseline–3 months
(p < 0.001), baseline–6 months (p < 0.001), and 3 months–6 months
(p < 0.001).
High
Low
High
Low
Xie et al. (2023) obtained a reduction in VAS score from 3.74 ± 2.02
to 2.47 and from 3.7 ± 2.45 to 2.11 at 4 weeks with oral HCQ and
topical dexamethasone, respectively. Both treatments achieved statistically significant results compared to baseline (HCQ, p = 0.0021;
ferences were obtained in VAS (p = 0.35) between groups.
Low
Some concerns
Low
topical dexamethasone, p = 0.00094). No statistically significant dif-
Low
Missing outcome data
Measurement of the
outcome
line, 1.43 ± 0.72 at 3 months and 0.63 ± 0.55 at 6 months, obtain-
3.3.3 | Results of disease activity improvement and
symptoms when shown together
Five studies evaluated the lesions using a subjective global scale
that measured the degree of erythema, erosion, and patients' symp-
Some concerns
Some concerns
Some concerns
Some concerns
achieved a complete or an almost complete improvement. Only one
study found no change in 14% of the patients (Yeshurun et al., 2019).
On the other hand, Platais et al. (2023) used Oral Disease Severity
Score (ODSS) and obtained that 79% of the patients achieved at
least 25% reduction in ODSS in a median time of 6 months.
Side effects are shown in Table 2. Nine studies provided detailed
Low
Some concerns
Some concerns
3.3.4 | Side effects and dropouts
Some concerns
Deviations from intended
interventions
Randomization process
found a moderate to marked improvement, while 24%–100% of them
information on the side effects of HCQ (Chirravur et al., 2023;
Xie et al., 2023; Platais et al., 2023; Raj et al., 2021; Sondhi
Bhuiyan et al., 2010
Bendas et al., 2013
Naidu et al., 2018
Xie et al., 2023
et al., 2020; Yeshurun et al., 2019; Rivas-­Tolosa et al., 2016; Bendas
Author, year
TA B L E 4 Risk of bias assessment using RoB2 tool.
toms (Raj et al., 2021; Yeshurun et al., 2019; Rivas-­Tolosa et al., 2016;
Bhuiyan et al., 2010; Eisen, 1993) (Table 3). A 10%–57% of the patients
et al., 2013; Eisen, 1993), one study did not find adverse effects
(Bhuiyan et al., 2010) and another one did not specify them (Naidu
et al., 2018). The most frequent side effects were vision problems,
gastric discomfort, rash, nausea, headaches, skin pigmentation and
elevated kidney function. In 6 of the 11 included studies, a total of
17 patients had to withdraw from the studies due to side effects
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| 11
TILLERO et al.
|
TILLERO et al.
TA B L E 5 Risk of bias assessment using JBI for quasi-­experimental studies.
Author, year
Q1
Q2
Q3
Q4
Q5
Q6
Q7
Q8
Q9
Total score
Eisen et al., 1993
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
No
7
Rivas-­Tolosa et al., 2016
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
No
7
Yeshurun et al., 2019
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
No
7
Sondhi et al., 2020
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
8
Raj et al., 2021
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
8
Platais et al., 2023
Yes
Yes
Unclear
No
Yes
Yes
Yes
Yes
Yes
7
Chirravur et al., 2023
Yes
Yes
Unclear
No
Yes
Yes
Yes
Yes
No
6
(Chirravur et al., 2023; Xie et al., 2023; Raj et al., 2021; Yeshurun
4
|
DISCUSSION
et al., 2019; Rivas-­Tolosa et al., 2016; Eisen, 1993).
OLP is a chronic mucocutaneous disease that presents with relapses
3.4 | Risk of bias assessment
and recurrences. Although it is usually treated with topical and systemic corticosteroids and immunosuppressants, these treatments
are not always effective. For these reasons, OLP in some cases re-
When analyzing the risk of bias of the RCTs with RoB2 tool
mains a challenge for healthcare professionals (Thongprasom, 2018).
(Table 4), it was determined that one study presented some con-
This systematic review aimed to detect whether antimalarials as
cerns (Xie et al., 2023) and the other three presented high risk of
HCQ or CQ are effective in improving OLP lesions and its symp-
bias (Naidu et al., 2018; Bendas et al., 2013; Bhuiyan et al., 2010).
tomatology. The availability of another treatment for recalcitrant
Two of them presented some concerns in the “randomization pro-
OLP or for those OLP patients who do not respond to conventional
cess,” because they presented statistically significant results be-
therapies would be helpful.
tween groups at baseline (Xie et al., 2023; Naidu et al., 2018), and
In this systematic review, we have included a total of 11 studies
Bendas et al. (2013) did not report p-­value at baseline between
in which 326 patients that received HCQ or CQ were included. The
groups. Three studies presented some concerns in “deviations from
outcome measures differed between the studies. Those that used a
intended interventions” because sample size calculation was not as-
subjective scale found an almost total or total improvement among
sessed (Naidu et al., 2018; Bendas et al., 2013; Bhuiyan et al., 2010),
24%–100% of patients. Furthermore, the five studies evaluating pain
and three of them were not double-­blind (Xie et al., 2023; Naidu
showed that HCQ improved pain in patients with OLP. Moreover,
et al., 2018; Bhuiyan et al., 2010). Two studies (Naidu et al., 2018;
four of the five studies (Bendas et al., 2013; Xie et al., 2023; Raj
Bhuiyan et al., 2010) presented high risk in the “measurement of the
et al., 2021; Sondhi et al., 2020) reported baseline NRS or VAS scores
outcome.” Naidu et al. (2018) did not measure symptomatology and
higher than 2.8, which should be the minimum to assess the efficacy
Bhuiyan et al. (2010) used a subjective scale to measure improve-
of an OLP intervention (Wiriyakijja et al., 2021). And finally, the five
ment. Finally, Bendas et al. (2013) presented some concerns in “se-
studies that evaluated the oral clinical improvement and symptoms
lection of the reported result” because no standard deviation and no
also obtained improvement with the use of HCQ (Raj et al., 2021;
p-­value was reported for pain in any of the groups.
Yeshurun et al., 2019; Rivas-­Tolosa et al., 2016; Bhuiyan et al., 2010;
Based on JBI risk of bias for studies with quasi-­experimental de-
Eisen, 1993).
sign, two studies were evaluated as an overall high quality (Table 5).
In the included studies, there was no agreement in the dosage of
While assessment of measurements was adequate in all the studies,
oral HQC used. The most common was 200–400 mg per day divided
with pre-­and post-­treatment evaluations, all the studies failed in the
into one or two doses for at least 6 months. This duration may be
presence of a control group (however, for one single group pre-­test/
one of the reasons why recurrences are lower compared to other
post-­test studies the patients were the same and “yes” is attributed
treatments such as corticosteroids, where the treatment is usually
as JBI recommendation). Half of the studies lacked adequate statis-
shorter. In studies carried out in diseases such as systemic lupus
tical analysis, and the similarity among participants included in each
erythematosus or Sjögren's syndrome, it is usually applied up to
study were unclear. For these reasons, five studies were evaluated
12 months with doses between 200 and 400 mg per day (Yokogawa
as moderate quality.
et al., 2017; Wang et al., 2021). And in many cases, HQC is used
chronically. The doses of HQC used for the treatment of lupus ery-
3.5 | Data synthesis
thematosus or Sjögren's syndrome are like those used in most of the
included studies in this systematic review.
In the present systematic review, there is one study that com-
A meta-­analysis was not possible to perform in any of the sections
pared oral HCQ to topical dexamethasone (Xie et al., 2023). This
since there is no uniformity in the outcome measures, treatments,
study achieved similar results with both treatments, indicating that
and follow-­ups collected among the studies.
HCQ is as effective and safe as topical dexamethasone in improving
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12
subjective and objective clinical manifestations of OLP. Regarding
assessed in studies evaluating OLP treatment should be appearance
the topical application of HCQ, it seems to be more effective
of lesions, severity of lesions, symptoms, function, social impact,
than placebo in reducing pain and the size of OLP lesions (Bendas
psychological impact, patient compliance and tolerability, overall
et al., 2013). But the only study that compared topical HCQ gel ver-
patient satisfaction, adverse events, timelines, and need for rescue
sus systemic HCQ obtained better results with the systemic admin-
medication (López-­Pintor et al., 2023). As has been observed in this
istration (Naidu et al., 2018). In this last study, adverse effects were
systematic review, the studies included did not include all the out-
not specified in any of the groups. However, Bendas et al. (2013)
comes indicated. Therefore, future studies on this subject should
reported adverse effects as burning and tingling with the use of the
improve in this matter.
HCQ gel. It seems that the adverse effects of the gel are much less
More studies are needed to assess the efficacy of HCQ. It is nec-
serious than those reported by the rest of the studies with the oral
essary to compare HCQ with the standard treatment (use of topical
HCQ intake. However, only 11 patients in this systematic review had
corticosteroids). In fact, of the 11 studies included in this systematic
to drop out of the studies because of these undesirable effects.
review, only one compared HCQ with the use of topical dexameth-
It should be noted that due to the adverse effects of oral HCQ,
asone. This study showed no statistically significant difference be-
it is necessary to periodically monitor patients (Doyno et al., 2021;
tween the two groups (Xie et al., 2023). Clinically, in the presence of
Gisondi et al., 2021). Considering the effects of the drug on the liver,
similar efficacy, the physician/dentist might prefer to use a topical
kidney, lung and, blood cells, protocols should be implemented be-
treatment with a better safety profile. However, the performance of
fore administering the medication to avoid adverse effects on the
these studies is not simple. Since in the studies carried out in other
skin, eyes, and gastric level (Doyno et al., 2021; Gisondi et al., 2021;
autoimmune diseases, such as systemic lupus erythematosus, it has
Maraolo & Grossi, 2021). This drug should be indicated with caution,
been shown that the continued use of HCQ reduces recurrences
with periodic controls by other specialists. Therefore, we believe
(Dima et al., 2021). However, the use of topical corticosteroids
that its use should be reserved for the hospital setting. This is a lim-
should be limited to when symptoms or relapses of OLP appear. In
itation when prescribing this drug in the private clinic. However, the
fact, in this systematic review there are studies that included the
study comparing oral HCQ with topical dexamethasone did not ob-
use of topical corticosteroids and other immunosuppressants as res-
tain statistically differences in the adverse effects between groups
cue medication during the use of HCQ (Chirravur et al., 2023; Platais
(Xie et al., 2023).
et al., 2023; Eisen et al., 1993). In other autoimmune diseases such as
It should be noted that not all cases of OLP were histologically
systemic lupus erythematosus, the patient receives HCQ treatment
confirmed in the studies included in this systematic review. So, it
on a regular basis, and patient is only treated with corticosteroids
cannot be assured that all cases included were OLP. OLP lesions
when he/she has a recurrence of the disease. We believe that this
are clinically like other oral lesions such as oral lupus erythemato-
guideline, which has been used in other types of autoimmune dis-
sus (Chanprapaph et al., 2022). Therefore, if only clinical diagnostic
eases, should be considered in the future in the treatment of OLP.
criteria are followed, it is possible that some patients with oral lupus
For this reason, it would be relevant to perform long-­term studies to
erythematosus were included in the clinical studies that only used
evaluate not only the efficacy of HCQ as a treatment of OLP (com-
clinical criteria.
pared with the use of topical corticosteroids) but also whether HCQ
Regarding limitations, there were only four RCTs, and three
reduces the number of OLP recurrences in these OLP patients with
of them presented a high risk of bias. Furthermore, the sample
many relapses or who do not respond well to conventional treat-
size of these studies was small. The remaining studies were quasi-­
ments over a period of 1–2 years. These types of studies are not sim-
experimental or so-­called pre-­post studies. Therefore, it was not pos-
ple, but they are necessary in order to know how effective HCQ is.
sible to perform a meta-­analysis due to the scarcity of randomized
In conclusion, for HCQ to be considered as a therapeutic option
clinical studies. More well-­designed RCTs with larger samples are
for OLP in the future, more research studies are needed to compare
needed to confirm the efficacy of HCQ in patients with OLP. Another
its efficacy with the usual treatment with topical corticosteroids.
limitation of our systematic review is that we only included studies
Also, there is a need to evaluate whether continued use of HCQ re-
published in English. Although this language is the most widely used
duces the number of OLP recurrences. Further research is needed to
in research studies, it does not ensure that relevant studies on this
consider its indication in the treatment of OLP.
topic published in a different language may have been missed.
We believe it is important to emphasize that the included studies
AU T H O R C O N T R I B U T I O N S
did not use the same outcomes to assess improvement after treat-
Rosana Tillero: Data curation; investigation; resources; writing origi-
ment. And the outcome measures used in the studies for evaluating
nal draft. José González-­Serrano: Conceptualization; methodology;
pain, size, and severity of the lesions were different, making it diffi-
resources; data curation; software; investigation; writing original
cult to compare the results and, hence to perform a meta-­analysis.
draft. Vito Carlo Alberto Caponio: Software; data curation; writing/
Therefore, future studies should follow the World Workshop on Oral
review and editing. Julia Serrano: curation; writing/review and ed-
Medicine consensus study on the core outcome set for OLP (López-­
iting. Gonzalo Hernández: supervision; writing/review and editing.
Pintor et al., 2023) to improve future scientific evidence about this
Rosa María López-­Pintor: Conceptualization; methodology; data cu-
treatment. This consensus study concluded that the outcomes to be
ration; formal analysis; investigation; writing original draft.
16010825, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/odi.14975 by Readcube (Labtiva Inc.), Wiley Online Library on [12/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
| 13
TILLERO et al.
|
TILLERO et al.
C O N FL I C T O F I N T E R E S T S TAT E M E N T
The authors declare no conflict of interest.
DATA AVA I L A B I L I T Y S TAT E M E N T
Data to perform this study are available after a justified request to
the authors.
ORCID
Vito Carlo Alberto Caponio
https://orcid.
org/0000-0001-5080-5921
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S U P P O R T I N G I N FO R M AT I O N
Additional supporting information can be found online in the
Supporting Information section at the end of this article.
How to cite this article: Tillero, R., González-­Serrano, J.,
Caponio, V. C. A., Serrano, J., Hernández, G., & López-­Pintor,
R. M. (2024). Efficacy of antimalarials in oral lichen planus: A
systematic review. Oral Diseases, 00, 1–15. https://doi.
org/10.1111/odi.14975
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TILLERO et al.