Volumen 66, Broj 6VOJNOSANITETSKI PREGLEDStrana 435
Correspondence to: Ljiljana Kesić, School of Medicine, Department for Oral Medicine and Periodontology, Bulevar Zorana Đinđića 81,
18 000 Niš, Srbija. Phone: +381 18 514 570. E-mail: firstname.lastname@example.org
O R I G I N A L A R T I C L EUDC: 616.311.4+616.313]:616-006.6-036
Incidence and treatment outcome of oral lichen planus in southeast
Serbia in a 10-year period (1997–2007)
Incidencija i ishod lečenja oralnog lihena planusa u jugoistočnoj Srbiji u
desetogodišnjem periodu (1997–2007)
Ljiljana Kesić*, Radmila Obradović*, Dragan Mihailović†, Goran Radičević‡,
Saša Stanković¶, Kosta Todorović§
School of Medicine, *Department for Oral Medicine and Periodontology, †Department for
Pathology; Dental Clinic, ‡Department for Endodontics, ¶Department for Prothetic Dentistry,
§Department of Oral Surgery, Niš, Serbia
Background/Aim. Lichen planus is a chronic, immuno-
logic, mucocutaneous disease with a wide range of clinical
manifestations. The aim of this retrospective study was to
evaluate the most common forms of oral lichen planus (OLP)
and its symptoms and to describe treatment responses in pa-
tients during 10-year period. Methods. The study was con-
duced on 163 OLP patients who came in the Department of
Oral medicine and Periodontology between 1997 and Sep-
tember 2007. Each case was classified into one of four clinical
subtypes: reticular, atrophic, erosive-ulcerative, bullous. Re-
sults. There was no significant difference in patients age.
Women were found to be significantly more likely to have
OLP (p < 0.001). Corticosteroids were effective in reducing
symptoms, erythema and healing ulcers. Improvement was
shown over a long term in 61.35% patients. Over the long
term 38.65% patients maintained the same type of OLP or it
became a more severe type. Two patients (1.22%) developed
oral carcinoma during the follow-up period. Conclusion.
The response of patients with erosive OLP to a short course
of systemic corticosteroids often was quite remarkable. How-
ever, symptoms and signs tended to recur after this treatment.
Periodic examinations, patient education, medical treatment,
monitoring of side-effects as well as follow-up biopsies are
necessary for management of OLP patients.
lichen planus, oral; mouth neoplasms; drug therapy;
Uvod/Cilj. Lihen planus je hronično, imunološko, mukokuta-
no oboljenje sa brojnim kliničkim manifestacijama. Cilj ovog
retrospektivnog istraživanja bio je da se utvrde najučestaliji ob-
lici oralnog lihen planusa (OLP) i njegovih simptoma, te opišu
reakcije na primenjenu terapiju kod bolesnika u periodu od 10
godina. Metode. Istraživanjem je obuhvaćeno 163 bolesnika sa
OLP koji su se javili u Odeljenje za oralnu medicinu i paro-
dontologiju u vremenskom periodu od 1997. godine do sep-
tembra 2007. godine. Svaki slučaj klasifikovan je u jedan od če-
tiri klinička oblika: retikularni, atrofični, erozivnoulcerozni i
bulozni. Rezultati. Nije postojala statistički značajna razlika u
starosti bolesnika. Uočeno je da žene češće imaju OLP
(p < 0,001). Primena kortkosteroida uspešno je smanjivala sim-
ptome, eritem i ulceracije. Poboljšanje stanja uočeno je kroz
duži vremenski period kod 61,35% bolesnika. Kroz isti vre-
menski period 38,65% bolesnika zadržalo je isti oblik OLP ili je
on prešao u teži oblik. Kod dva (1,22%) bolesnika razvio se
karcinom. Zaključak. Reakcija bolesnika sa erozivnim OLP na
kratkotrajnu sistemsku primenu kortikosteroida veoma je dob-
ra. Ipak, simptomi i znaci oboljenja imaju tendenciju ponovnog
pojavljivanja nakon prestanka terapije. Kako bi se pravilno lečili
bolesnici sa OLP, neophodno je primeniti periodična ispitiva-
nja, edukaciju bolesnika, medicinsku terapiju, praćenje pojave
neželjenih efekata i, kada je potrebno, uzeti biopsiju tkiva.
lihen planus, oralni; usta, neoplazme; lečenje lekovima;
Lichen planus is a chronic, immunologic, mucocutane-
ous disease with a wide range of clinical manifestations 1, 2.
The oral mucosa commonly is involved and may be the only
site of involvement. Oral lichen planus (OLP) is a relatively
common disorder, estimated to affect 0.5% to about 4.0% of
the general population 3–8. Oral lichen planus is found more
frequently in women, and the onset occurs often after the
fourth decade of life 9. The major types of OLP are the fol-
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Kesić Lj, et al. Vojnosanit Pregl 2009; 66(6): 435–439.
lowing: reticular, atrophic, erosive-ulcerative, bullous and
pigmentosus form 10, 11.
Oral lichen planus can develop on any mucosal surface,
including the lips, but most frequently develops on the buc-
cal mucosa. The lesions are often bilateral and develop on
more than one mucosal surface. However, the presentation
can be limited to one site. Although OLP seldom goes into
remission, progression of erosive-ulcerative form to cancer is
Many retrospective and prospective studies, have sug-
gested that OLP has potential for malignant development 12–
22, 23–25. Since OLP is considered a premalignant condition, a
recall system for OLP patients has been recommended to fa-
cilitate the early diagnosis of oral cancer. (The aim of this re-
call system was to reduce morbidity and mortality from oral
cancer arising in OLP patients).
Treatment is administered primarly to control symp-
toms, since there is no established cure. Symptoms can range
from none, with the patient being unaware of the presence of
intraoral lesions, to extremely painful lesions, which may
interfere greatly with eating and thus significantly affect the
quality of life. Close follow-up is suggested, not only to
monitor medications for discomfort, but because of an estab-
lished risk of squamous-cell carcinoma developing in areas
of OLP 24, 26. Systemic and topical corticosteroids have been
the most reproducibly effective medications to control
symptoms and signs of the disease 27. Localized oral lesions
are treated with topical corticosteroides, applied two or four
times daily after meals. Generalized oral lesions are often
treated effectively with a steroid mouth rince twice daily af-
ter meals. Candida albicans superinfection, which may ac-
company any immunosuppressive therapy, should be con-
trolled with topical antimycotics, especially in risk groups
such as xerostomics 28. Treatment of OLP with cyclosporin,
azathioprine, levamisole, griseofulvin, retinoids, hydroxy-
chloroquine sulphate, dapsone and psoralen/UVA, topical
vitamin A, laser/surgical removal has been reported 29–33.
Twice daily topical application of compounded 0.1% tacro-
limus ointment was recently reported to be effective in con-
trolling symptoms, as well as clearing lesions of OLP 10, 34, 35.
Tacrolimus is a macrolide immunosuppressant with a
mechanism of action similar to that of cyclosporine, but is 10
to 100 times more potent and is better able to penetrate the
mucosal surface 10, 35.
The aim of this retrospective study was to evaluate the
most common forms of OLP and its symptoms and describe
treatment responses in patients with OLP who were referred
and examined in our oral medicine department during a 10-
A total of 163 OLP patients were seen by the two doc-
tors in the Department of Oral medicine and Periodontology,
Dental Clinic, School of Medicine Niš, Serbia, between 1997
and 2007. The examined patients originated from southeast
Serbia which includes Vranje, Leskovac, Pirot, Dimi-
trovgrad, Prokuplje and smaller towns and villages in this
area. The group included patients who were being seen for
the first time, as well as the patients attending for a follow-up
At the first clinic visit, the following information from
each patient were collected: age, sex, medical history, family
history and social history, initial clinical presentation, treat-
ments rendered, responses to treatment, side effects and
changes in clinical presentation over time. Each case was
classified into one of four clinical subtypes: reticular, atro-
phic, erosive-ulcerative, bullous.
The OLP diagnosis was based on clinical (Figures 1 and
2) and histopathologic findings (Figure 3). The histopathologic
features of OLP include several epithelial changes: epithelial
hyperkeratosis, atrophy or hyperplasia, acantosis, saw-toothed
rete ridges, liquefaction degeneration of basal cells, and single-
cell keratinization. A homogeneous cell-free zone is frequently
present in the basement membrane zone. The subepithelial
connective tissue shows a band-like inflammatory infiltrate
dominated by lymphocytes and macrophages. Biopsy is an
important tool in the diagnostic process for OLP, but a diagno-
sis of OLP based solely on histopathology in some cases leads
to wrong results. Due to this we combined biopsy (histo-
pathologic results) and clinical criteria.
Fig. 1 – Oral lichen planus reticular form.
Fig. 2 – Oral lichen planus erosive-ulcerative form (ulcera-
tive lesion surrounded with reticular white striations, on the
left buccal mucosa).
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Kesić Lj, et al. Vojnosanit Pregl 2009; 66(6): 435–439.
Fig. 3 – Lichen planus: acantosis, parakeratinization and
degeneration of basal cells; HE, ×100.
All the patients with the diagnosis of OLP who were
seen between 1997 and September 2007 were included in the
There was no significant difference in patients age be-
tween clinical subtypes. Women were found to be signifi-
cantly more affected by OLP than men (p < 0.001). Espe-
cially, the reticular (p < 0.05) and atrophic (p < 0.01) types
of OLP were predominant in women (Table 1). Overall, the
reticular type of OLP was dominant, significantly more than
atrophic, erosive-ulcerative and bullous type of OLP
(p < 0.001). Both men and women, were found to be signifi-
cantly more likely to have the reticular type of OLP than
atrophic (p < 0.01) and bullous types (p < 0.001).
Associated diseases at the initial clinic visit were as
follows: diabetes 4.9%, history of hypertension 22%, im-
munopathic diseases 2%. Family history was known for
28% patients; of these 3% had blood relatives with known
OLP, and the rest did not know of any relatives who had
The patients reported taking the following medica-
tions: 3.8% anti-diabetic drugs, 22% antihypertensive
drugs, 9% antidepressants. Totally 48% of the patients re-
ported in their medical history that they had some type of
allergy, including sensitivities to foods, drugs, pollen, gold,
The treatment was offered to control the symptoms, and
in the case of erosive-ulcerative OLP, to heal ulcers. For
topical corticoid application we used a liquid medicament
form (solution Dexason-Neomycin®) or spray (spray Kena-
log S®, spray Geocorton®). The patients were instructed to
apply this medicament to the lesions three to four times daily
for 7–14 days (depending on severity of lesions). Prednisone
was a systemic corticosteroid used, which we administered
in one or two doses a day, for a total daily dosage ranging
from 20 to 80 milligrams. These were administered primarily
for erosive-ulcerative OLP and severe pain.
We followed short-term and long-term responses to
treatment. Short-term response (one or two weeks after
starting the treatment) was: treatment was effective in re-
ducing symptoms of OLP and in healing ulcers and reducing
enanthema. However, symptoms and signs tended to recur
after this treatment. Improvement was shown over long term
in 61.35% of the patients, especially in reducing symptoms
of OLP. The patients emphasized the improved quality of life
during medicament therapy (topical steroids occasionally).
Complete spontaneous remission (no symptoms and no clini-
cal evidence of disease) without treatment was not noticed.
Over a long term 38.65% patients maintained the same type
of OLP or it became a more severe type. Namely, 24
(15.12%) patients had the same reticular type of OLP, 22
(13.86%) showed the atrophic type, as well as 15 (9.45%)
had a more severe type – erosive-ulcerative. Two patients
(1.22%) developed oral carcinoma during the follow-up pe-
riod. The sites of oral carcinoma were at buccal mucosa in
In the last decade, there have been a number of follow-
up OLP studies. In 1991, Silverman et al. 22 reported a series
of 214 patients with OLP followed up a mean period of 7.5
years, during which time 5 patients had developed squamous
cell carcinoma in the OLP site. In 1993, Barnard et al. 36 re-
ported on a series of 241 patients with OLP followed up for
10 years, with 8 patients developing squamous cell carci-
noma and another developing carcinoma in situ. In 1997,
Silverman and Bahl 13 reported that 3 of 95 patients followed
up for a mean of 6.1 years developed squamous cell carci-
noma. In another study, Silverman 26 reported malignant
transformation in 3.2% of patients with OLP. Gandolfo et
al. 37 reported that 9 of 402 patients followed up for a mean
of 4.9 years developed squamous cell carcinoma. Our find-
ings are in accordance with these reports.
Our findings are in accordance with those of several
authors who reported that malignant transformations are more
Distribution of age and sex for patients with each type of oral lichen planus (OLP)
OLP type at first clinical
visitn (%)ґ ± SD
Reticular56 (70.00)52.44 16.78
Atrophic32 (80.00) 56.24 12.89
Erosive-ulcerative25 (59.52) 55.64 14.80
Bullous1 (100.00)58.00 0.00
Total 114 (69.94)54.26 13.61
ґ ± SD
ґ ± SD
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likely to occur in atrophic and erosive-ulcerose lesions, because
all the malignancies in the present study developed in erosive
and atrophic lesions. Because of all these reasons, periodic
follow-up examinations (2–4 times annually) are important 22.
Early detection of premalignant lesions and small oral cancers
will allow patients to be treated earlier 38. Also, OLP patients
should be instructed to report clinical changes in the condition
and to come to regular follow-up appointments 39.
Because OLP is an incurable disease, treating symp-
toms is extremely important in addressing quality-of-life is-
sues. Use of the required potent medications always involves
a consideration of drug benefits weighed against potential
adverse side effects. Therefore, systemic corticosteroids were
used cautiously and with discretion. However, according to
our objective assessments, the combination of systemic and
topical corticosteroid regimens over time can offer signifi-
cant benefits with minimal risk of unpleasant side effects.
The choice of treatment obviously depends on the sever-
ity of discomfort, the patient’s overall health and compliance
issues. However, initial short course of systemic corticoster-
oids had the advantages of predictability, ease of compliance
and patient optimism necessary for a positive long-term out-
look in regard to living with erosive OLP. In some patients
(17%), occasional short-term daily dosages of systemic pred-
nisone were sufficient for adequate clinical control of symp-
toms 40. In other patients (83%), fairly regular topical applica-
tions were both necessary and effective for the desired control
of discomfort 37. The schedule for using topical steroids in our
study varied between patients since the goal of treatment was
acceptable comfort and compliance with application regi-
ments. Drug tolerance and eventual therapeutic ineffectiveness
with daily use of topical steroids have not been found.
Medical considerations in patients receiving long-term
systemic prednisone include calcium supplements to mini-
mize bone loss, potassium for diuresis, glucose control,
monitoring blood pressure and ophthalmogenic examina-
tions. In this study, fungal overgrowth of normal oral flora
by Candida leading to candidiasis was infrequent (24%), and
was associated primarily with the use of topical corticoster-
oids. This can be explained by the local conversion of
epithelial cell glycogen to glucose, which selectively nur-
tures candidal proliferation. Topical antifungals controlled
this occasional problem.
Following the long-term outcomes for patients with
OLP, it is clear that symptoms persist indefinitely. However,
it is also evident that judicious use of systemic corticoster-
oids, topical steroids or both are more beneficial than detri-
mental in improving patients’ quality of life, which is often
so diminished by pain and uncertainty associated with OLP.
For example, after a long-term follow-up of our patients with
the most severe form of OLP (erosive-ulcerative), the per-
centage with moderate-to-severe pain was reduced from 90
to 35%. It is also apparent that in 61.35% patients, the signs
and form of OLP were reduced to less severe types as a re-
sult of corticosteroid treatment. Erosive-ulcerative and atro-
phic lesions can be converted into reticular lesions using
topical steroids. Hence, treatment of erosive and atrophic le-
sions with topical steroids may reduce the risk of oral cancer.
OLP patients should be advised that a nutritious diet includ-
ing fresh fruit and vegetables (antioxidants) may help reduce
the risk of oral cancer. Due to the potential role of Candida
albicans in the development of oral cancer, fungal superin-
fection should be eliminated with topical antimycot-
ics 5, 9, 14, 18, 23, 27, 28, 33, 40.
The response of patients with erosive OLP to a short
course of systemic corticosteroids often was quite remark-
able. However, symptoms and signs tended to recur after this
treatment. Periodic examinations, patient education, medical
treatment, monitoring of side-effects as well as follow-up bi-
opsies are necessary for management of OLP patients.
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The paper received on October 21, 2008.