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GENTIAN VIOLET: RE-EXPLORING IT'S POTENTIALS IN ORAL ULCERS: A CASE

SERIES

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 International Journal of Dental and Health Sciences
Case Report Volume 03, Issue 06

GENTIAN VIOLET: RE-EXPLORING IT’S POTENTIALS IN

ORAL ULCERS: A CASE SERIES
1 2 3 4 5
Nisheeth Saawarn , Christopher Vinay Shinde , Harshkant P Gharote , Swati Saawarn , Pearl Helena Chand ,
6 7
Shantala Naik , Raju Raghavendra T.
1. MDS, Department of Oral Medicine &Radiology, People’s College of Dental Sciences & Research Centre, Bhopal
2. MDS, Department of Oral Medicine &Radiology, People’s College of Dental Sciences & Research Centre, Bhopal
3. MDS, Department of Oral Medicine &Radiology, People’s College of Dental Sciences & Research Centre, Bhopal
4. MDS, Department of Oral Pathology &Microbiology, People’s Dental Academy, Bhopal
5.Post Graduate Student, Department of Oral Medicine &Radiology, People’s College of Dental Sciences & Research Centre,
Bhopal
6. MDS, Department of Oral Medicine &Radiology, People’s College of Dental Sciences & Research Centre, Bhopal
7.MDS,Department of Oral Pathology Division Oral Basic and Clinical Sciences, College of Dentistry, Qassim Private Colleges,
Buraidah, Kingdom of Saudi Arabia.

ABSTRACT:
Gentian or Crystal violet, an atriarylmethane dye used as a histological stain and in Gram’s
staining of bacteria, has antibacterial, antifungal and antihelmintic properties and was a
popular topical antiseptic. It’s medical usage has been largely superseded by modern
antimicrobials and other antiseptics, although it is still listed by the World Health
Organization as a topical antiseptic agent. It has been frequently used in the management of
various dermatological lesions like fungal skin infections, vulvovaginal candidiasis (vaginal
thrush), bacterial skin infections such as infected eczema, boils, and chronic (long-
standing) leg ulcers. Gentian violet may also be active against Methicillin-
resistant Staphylococcus aureus (MRSA) and oral lesions like oral thrush and a variety of oral
ulcers. However, there is hardly any scientific clinical evidence available to support its
effectiveness in the management of oral ulcers except for few reviews and case reports.
Here, we are sharing our clinical experience with it in the management of 40 cases of oral
ulcers, where the results were encouraging.
Key words: Oral ulcers, Gentian violet, Management of oral ulcers.

INTRODUCTION allergy, nutritional deficiency, blood

dyscrasias, malignancy etc.[1]
An ulcer is a breach in the continuity of
the epithelium, which typically exposes Although the exact microbial cause of oral
nerve endings in the underlying lamina ulcers is unknown but the microorganisms
propria, resulting in pain or soreness. Oral suggested to cause infection in oral ulcers
ulcer is a common disease we come are gram positive oral (viridans)
across, with an estimated 4% world-wide streptococci like S. mitis, S. sanguis, S.
point prevalence. The most common oral oralis and gram negative bacteria H.
ulcer is traumatic ulcer followed by pylori.[2]
recurrent aphthous ulcers. The etiology
for oral ulcers is multifactorial like trauma, An oral ulcer on an average takes five to
infections caused by bacteria, virus and seven days to heal. Common symptoms
fungi, immunologically mediated diseases, include pain, burning sensation, difficulty
in eating and chewing. The management

*Corresponding Author Address: Dr.Pearl Chand Email:[email protected]

 Saawarn N. et al., Int J Dent Health Sci 2016; 3(6): 1184-1192
of oral ulcer is usually complicated due to ulcerated infantile hemangiomas,
presence of saliva; persistent moist cutaneous melanoma metastasis,
environment, food, food debris, water, transgredientpachyonychia congenital,
oral microorganisms etc.[3]The treatment tinea infestation like athlete's foot and
begins with identification of the ringworm and impetigo.[4,5] The medical
underlying cause; and usually when the use of the dye has been largely
cause is removed it takes three to four superseded by more modern drugs,
days to heal. although it is still listed by the World
Health Organisation.[6,7]
The goal of treatment is to alleviate
symptoms, accelerate healing time and Apart from being an antiseptic agent
prevent recurrence. Current treatments Gentian violet also acts as a surface
mainly used are topical agents such as astringent and coagulates the proteins on
anesthetics, analgesics, antimicrobials, the ulcer surface.[8] Thus, it coats the
steroids depending on etiology and type surface of the ulcer and protects it from
of ulcers. Some systemic agents like hostile oral environment and accelerates
steroids, steroid sparing agents and healing of ulcer. Therefore, by virtue of
immunomodulators like azathioprin, these properties usage of gentian violet is
cyclosporine, thalidomide, levamisole, advocated in the management of oral
cyclophosphamide, dapsone, colchicines ulcers and few studies have reported
and pentoxiphylline may be reserved for quoting its effectiveness in management
severe and refractory cases as these ulcers on other parts of the body. [ 9,10 ] We
medications are associated with many used this antiseptic dye in the
adverse effects when compared to topical management of few cases oral ulcers and
medications.[1] share our clinical experience.

Crystal violet or Gentian violet belongs to METHODS AND MATERIALS:

di- and triaminophenylmethanes class of
A total of 40 patients, 22 males and 18
dyes .This dye is used as
females, in the age range of 10 to 70 years
a histological stain and in Gram’s method
were treated in the outpatient
of classifying bacteria. Gentian violet has
department of our institute between
shown to have antibacterial, antifungal
January 15th, 2014 andJune 1st, 2014 after
and antihelminthic properties [3] and has
obtaining informed consent from the
been used as an antiseptic agent since
patient. Patients of any age and either sex
early 19th century. It was widely used in
presenting with oral ulcers regardless of
World War II as a topical antiseptic agent
the etiology except malignant ulcers and
on war wounds.[4] Further it has been
ulcers secondary to systemic causes were
being used in atopic eczema, pressure
treated. Patient having known
sores, decubitus ulcers, pyodermas,
hypersensitivity to the dye, ulcers due to
oropharyngeal and vaginal candidiasis,
systemic diseases or malignancies were
HIV associated oral hairy leukoplakia,
not considered for the dye application.
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 Saawarn N. et al., Int J Dent Health Sci 2016; 3(6): 1184-1192
Patient’s demographic data, history of follow up was used for statistical analysis
illness and clinical findings were entered (Table 1).
in a structured proforma. Elective
In these 27 patients, a total of 38 ulcers
coronoplasty of the offending tooth,
were evaluated, out of which 24 had
wherever required was done prior to
healed by 3rd day and remaining 14 had
application of medication. After
healed on 2nd follow up by the 6th day
evaluation of the oral ulcers patients were
after second application of the drug (Table
made to rinse mouth thoroughly with
2).
water to get rid of any debris present over
the ulcer and a drop of gentian violet was There was 89.41% mean reduction in size
applied topically directly above the ulcer of ulcer, 37% reduction in mean morbidity
with the help of a cotton pellet and and 41.22% mean improvement in the
tweezer. Patients were refrained from quality of life on the third day. Pain on
eating, drinking or rinsing mouth for at VAS showed significant improvement with
least 30 minutes post application. Patients mean value reducing from 21.48 to 4.54
were recalled on the 3rd day for evaluation post treatment at first follow up and being
and medication was re-applied if needed zero at second follow up. (Table 3)
and reviewed again on the 6th day. The
parameters evaluated were pain DISCUSSION
associated with ulcers on VAS, size of Oral ulcer is a common disease we come
ulcers in mm, morbidity in percentage and across, presenting with a 4% world-wide
effect on the quality of life in percentage. point prevalence and a multifactorial
etiology.
The data collected from each patient was
entered in a master chart, tabulated and Oral ulcers lead to significant morbidity
subjected to statistical analysis using ‘t- due to pain, burning sensation, difficulty
test’ and ‘Wilcoxon signed ranks’ tests. in eating, chewing and speech. The
management is difficult due to presence
RESULTS: of saliva; a moist environment, presence
of food, bacteria and debris. Usually they
A total of 40 patients, 22 males and 18
are self healing due to high vascularity of
females, in the age range of 10 to 70 years
the mucosa and heal in 5-7 days if the
presenting with a total of 51 ulcers were
etiology is taken care of.
initially treated. Out of these, 27 patients
(16 males and 11 females) came for However, apart from removing etiology
regular follow up and three could be wherever possible, the goal of
followed up only telephonically, while management is to accelerate healing time,
remaining 10 were lost to follow up. decrease pain, reduce ulcer size and
Those contacted telephonically on the erythema. Many therapies both topical
fourth day reported relief from ulcer and and systemic have been suggested to
pain. The data of 27 patients with regular treat the disease with varying success
rates. Current treatments mainly used are
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 Saawarn N. et al., Int J Dent Health Sci 2016; 3(6): 1184-1192
topical agents such as anesthetics, follow up, which may be due to the fact
analgesics, antimicrobials, steroids that our institute is little far from the city
depending on etiology and type of ulcers. and possibly patients were relieved of the
These agents provide localized action pain. Three patients who we could contact
without systemic adverse effects. Some telephonically on 3rd day informed that
systemic agents like steroids, steroid their ulcer had got healed and they were
sparing agents and immunomodulators free from pain. These 13 patients were
like azathioprin, cyclosporine, not considered for the statistical analysis.
thalidomide, levamisole, Also, there was a significant reduction in
cyclophosphamide, dapsone, colchicines the size of the ulcer, pain and morbidity
and pentoxiphylline may be reserved for associated with the ulcer after application
severe and refractory cases as these of the dye. Thus it can be concluded that
medications are associated with many topical application of gentian violet on
adverse effects when compared to topical intraoral ulcers not only results in faster
medications.[1] healing time but also in significant
reduction of pain and improvement in
Gentian violet, a forgotten topical
quality of life.
antiseptic, is being sporadically and
successfully used in the management of There is little scientific literature available
these ulcers by many clinicians and dentist quoting gentian violet in the management
but there is lack of sufficient accredited of oral ulcers, hence we are not able to
scientific literature supporting its efficacy. compare our results directly with that of
The aim of the present study was to re- other studies, however, the findings of
explore the efficacy of this antiseptic dye our study are quite encouraging.
in the management of oral ulcers and to
By means of it’s astringent, antiseptic,
evaluate whether the sporadic claims
protective and healing properties gentian
made about the so called healing
violet can be suggested in the
properties can be proved.
management of oral ulcers. The mean
Interestingly on a positive note the healing time with topical gentian violet in
findings of our study were quite our study was 4.10 days which was near
encouraging as we found good response or better than the commonly prescribed
to topical gentian violet in the medications for oral ulcers (Table-
management of oral ulcers. Out of 41 4).Gentian violet has no reported
ulcers in 30 patients, 27 had healed by the potential adverse-effects when used
end of third day of application or probably topically in such small quantities and
even prior to this. The remaining 14 hence is a cheaper and safer alternative to
ulcers were healed when patients were other topically applied medications like
re-evaluated at 6th day; these ulcers too corticosteroids and can be recommended
probably may have had healed prior to for almost all population groups.
the 6th day. Ten patients were lost to

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 Saawarn N. et al., Int J Dent Health Sci 2016; 3(6): 1184-1192
Most commonly prescribed medications altered taste sensation, and discoloration
for the management of oral ulcers include of the teeth and mucosa on prolonged
local anesthetic ointments, topical anti- use.[15]
inflammatory drugs and antiseptics.
Another commonly prescribed or rather
Chlorhexidinegiuconate both as a
misused and abused medication for oral
mouthwash and gel preparations has
ulcers is topical anesthetic agents. These
been reported to produce significant
agents include different formulations and
reduction in the duration and discomfort
different active compounds that provide a
of aphthous ulcers. The broad spectrum
symptomatic relief by virtue of their
antibacterial effect of
anesthetic properties and also cover the
chlorhexidinegluconate is the major factor
lesion and provide a barrier when
which accounts for the reduction in
formulated with orabase or sucralfate as
duration and severity of ulceration in
base. Some of these are also
recurrent oral ulceration.[11] Bacterial
mouthwashes containing benzydamine or
colonization of the wound surface in the
diphenhydramine. Most are available in
mouth always tends to occur and there
gel form containing local anesthesics like
will be a tendency for delayed healing as a
benzocaine in varying percentages (6.4%
result of increased inflammation and
to 20%), lidocaine (2% to
granulation tissue formation, presumably
5%),benzalkonium chloride 0.01% or
with increased pain.[12] It is probable that
choline salicylate 8.7%.[16]Further it needs
chlorhexidine negates this bacterial
to be applied repeatedly for better
colonization at least to some degree and
results, however gentian violet application
this is consistent with the findings that
even once in office provides better or
anti-bacterial agents, including
equivalent results. Probably if applied
chlorhexidine used on healing surgical
daily or may be twice a day may fetch
wounds, reduce the incidence of pain and
even faster healing.
facilitate healing.[11] Chlorhexidine is
generally used as a 0.2% w/w mouth Descroix V in a randomized, double-blind,
rinse, but the 0.10% w/w mouthwash or placebo-controlled, parallel-group trial
1% gel can also be beneficial.[13] The concluded that topical application of a 1%
average duration of healing with lidocaine cream for 1 minute to an
chlorhexidine assessed in different studies aphthous ulcer produces a significant
was in near concordance with study done reduction in pain intensity 3 minutes after
by Addy M, Carpenter R, Roberts WR, application. The lidocaine cream does not
1976 with 1% Chlorhexidine gel was 4.8 elicit any side effects. Thus, a benefit/risk
days(mean)[11] while it was superior to ratio positive for the application of a 1%
study done by Hunter L, Addy M, 1987 lidocaine cream in the symptomatic
with 0.2% Chlorhexidine mouthwash a treatment of acute pain resulting from
healing time of 5.02 days (mean) [14]. The traumatic or aphthous lesions of the oral
adverse drug reactions included nausea, mucosa. The pain decreased by

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 Saawarn N. et al., Int J Dent Health Sci 2016; 3(6): 1184-1192
approximately 50% on average.[16] Since the concentration of sensitized
However this painrelief is transient and lymphocytes occurs before and during the
there is no acceleration of the healing early stages of oral ulceration, it follows
time. So patient has to apply multiple that the drugs exert their maximum effect
times in a day for consistent pain relief. at this time.[13]

Another antimicrobial agent commonly Commonly prescribed topical steroids are

prescribed is Tetracycline. Tetracyclines hydrocortisone hemisuccinate (as pellets
are broad spectrum antimicrobials with of 2.5 mg) and triamcinolone acetonide
bacteriostatic activity and are effective 0.1% in orabase. Other agents include:
against large number of gram positive and dexamethasone rinse 0.05mg/ml,
gram negative bacteria. Tetracyclines clobetasol ointment 0.05% in orabase,
when used topically are reported to flucinonide ointment 0.05% in orabase.
reduce pain and duration of ulcers as a orabase or other adherent base is used in
result of the less heavily colonized formulation provides a protective local
environment.[13] Graykowski EA, Kingman coating for the ulcer. Early initiation
A, 1978 conducted a double-blind trial (within 72 hours) of this treatment may
with topical 5% Tetracycline rinse in result in a more rapid response. There is
recurrent aphthous ulceration and little risk of adrenal suppression provided
recorded a mean healing time of 5.46 that the recommended dose (four times
days.[17] Here too the limitations are same daily) is adhered to.[18]
as seen in case of chlorhexidine along with
Merchant HW, Gangarosa LP, Glassman
the risk of hypersensitivity reactions,
AB et al, 1978 investigated healing time of
growth of resistant organisms and loss of
< 6 days with topical 0.025%
symbiotic microflora.[13]
betamethasone benzoate gel.[19]
Topical immunmodulators including Prolonged use of potent topical
corticosteroids too are found to be corticosteroids carries a risk of systemic
effective in the management of oral ulcers absorption and associated adverse effects
and are one of the most prescribed like bad taste, nausea, dry mouth,
agents. They are intended to limit the mucosal atrophy; delayed healing, allergy
inflammatory process associated with the and may also predispose to secondary
formation of ulcers and suppress the oral candidosis.[13]
process of autoimmunity. The anti-
Amlexanox is a topical anti-inflammatory,
inflammatory action of corticosteroids
anti-allergic drug. It has been developed
modifies, in a minor way, the progress of
as a 5% topical oral paste for the
the inflammation at all stages and to
treatment of patients with oral ulcers. It
some extent reduces the discomfort
inhibit the formation and release of
experienced. The second effect of steroids
histamine and leukotrienes from mast
is the specific blocking effect of the T
cells, neutrophils, and mononuclear cells,
lymphocyte-epithelial cell interaction.
possibly through increasing intracellular c-
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 Saawarn N. et al., Int J Dent Health Sci 2016; 3(6): 1184-1192
AMP content in inflammatory cells, and a with limited success in the management
membrane-stabilizing effect or inhibition of major aphthae. Dapsone is given
of calcium influx. The paste is applied to 100mg orally in divided doses and may be
ulcers two to four times a day. Meng W et increased at the rate of 50mg/day per
al, 2009 in a randomized, blinded, placebo week to a maximum of 300mg/day.
controlled, parallel, multicentre, clinical Dapsone is a potentially toxic drug, can
design concluded that amlexanox group precipitate hemolyticanemia, hence, the
had a statistically significant higher patients should be monitored for
"improvement" rate 66.67% vs 43.81% in hemolysis, methemoglobinemia, anemia
placebo control group.[20] and agranulocytosis.[13] Sharquie et al,
2002 found that dapsone was effective at
Levamisole is an immunomodulatory drug
decreasing the number, duration of oral
which makes it useful in controlling oral
ulcers in 20 patients. [22]
ulcers.Levamisole has demonstrated the
ability to normalize the CD4+ cell/CD8+ However, larger controlled or blinded
cell ratio and improve symptoms in RAU studies using a placebo or a comparative
patients. Correction of T-suppressor cell arm medication is advocated preferably in
deficiency may reduce the inflammatory a long term clinical trial to substantiate
response resulting from cellular immunity the results reported from the present case
and promote resolution of aphthae.[15]The series.
major adverse effects associated with
CONCLUSION
levamisole were nausea, hyperosmia,
dysgeusia, and agranulocytosis.[2] Olson The primary goals of therapy for oral
JA, Silverman S, 1978 conducted a double- ulcers are relief of pain, reduction of ulcer
blind study in 48 patients of recurrent duration, and restoration of normal oral
aphthous stomatitis with levamisole function. Localized topical regimens can
dosage of 150 mg/day × 3 days every achieve the primary goals and are
week at first sign of ulcers. 65% of considered to be the standard treatment
patients reporting moderately or of oral ulcers. In the present prospective
markedly reduced pain against 28% in study gentian violet was found as an
placebo control group.[21] effective potential drug in management of
oral ulcers. Hence its potentials should be
Diaminodiphenylsulphone (Dapsone) a
re-explored since it is easily available, cost
widely used drug in the long-term
effective, safe and shows good efficacy.
treatment of leprosy and some
dermatologic conditions have been tried
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9. Farid KJ, Kelly K, Roshin S. Gentian violet amlexanox oral adhesive pellicles in the
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Management of recurrent aphthous aphthous stomatitis. J Oral Pathol1978;
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Chlorhexidinegluconate mouthwash in

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 Saawarn N. et al., Int J Dent Health Sci 2016; 3(6): 1184-1192
TABLES:
Table-1: Age And Sex Distribution
Sex Age range(years) Mean age(years)
MALE (16) 10-70 33.87
FEMALE (11) 20-40 28.72
TOTAL (27) 10-70 31.77

Table-2 :Treatment Summary

Criteria Number of ulcer/total
numbers of ulcers
rd
Number of patients with 50% relief in ulcer on 3 day 14/38
rd
Number of patients with 100% relief in ulcer on 3 day 24/38
rd
Number of patients with 50% healing in ulcer on 3 day 14/38
rd
Number of patients with 100% healing in ulcer on 3 day 24/38
rd
Number of patients with 100% relief in ulcer on 3 day 38/38
rd
Number of patients with 100% healing in ulcer on 3 day 38/38

Table-3: Criteria Evaluated Pre- Treatment And Post- Treatment

rd th
3 day 6 day
Criteria evaluated Pre-treatment p-value
Post-treatment Post- treatment
Size of the ulcer (in 0.2504 0.0265
0 0.0348 (S)
mm; mean±SD) ±0.6593 ±0.0516
Percentage
41.67 4.67
morbidity 0 <0.0001 (S)
±19.79 ±7.43
(mean±SD)
Effect on the
50.750 9.525
quality of life 0 <0.0001 (S)
±13.79 ±13.79
(mean±SD)
Pain on VAS 21.48 4.54 0 <0.0001 (S)

Table-4: Healing Time Of Some Commonly Prescribed Medications.

Healing time
11
Addy M, Carpenter R, Roberts WR, 1976.
1% Chlorhexidine gel Mean = 4.8 days
14
Hunter L, Addy M, 1987.
0.2% Chlorhexidine mouthwash Mean = 5.02 days
17
Graykowski EA, Kingman A,1978.
5% Tetracycline rinse Mean = 5.46 days
19
Merchant HW, Gangarosa LP, Glassman AB et al, 1978. < 6 days
0.025% Betamethasone benzoate gel
23
Mostafa A A E and Ibrahem A EM, 2009. 4 to 7 days
Topical application of Quercetin

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