Bangladesh Journal of Medical Science Vol. 13 No.

03 July14

Original article
Safety of 0.1% topical tacrolimus in the treatment of vitiligo
Hazra SC1, Ahmed N2, Ghosh JC3
Abstract:
Cure rates for vitiligo are significantly lower because of problems to different studies have
reported different response rate and different adverse effect for the treatment of vitiligo. This
study was conducted to evaluate the response rate and adverse effect of topical tacrolimus
0.1% ointment in the treatment of vitiligo patients in the department of Dermatology and
venereology, Bangladesh Medical college (BMC), Dhaka from January 2010 to July 2010. In
this clinical trial, 30 newly diagnosed vitiligo (focal and segmental) patients, aged between 10
to 50 years were assigned for therapy and to observe the response and adverse effect. Each
individual lesion was treated with topical tacrolimus 0.1% ointment twice daily for three
months. All the patients completed three months treatment and available for statistical
analysis. The highest percentage 13(43.3%) was in the age of 11-20 years. Sex ratio revealed
higher in case of female 18(60%), with a male-female ratio 1:1.5 and 5(16.67%) patients had
vitiligo among their families. Repigmentation was observed in 8 (26.7%) subjects at the end
of 4th week, 15 (50.1%) subjects at 8th week and 25 (83.3%) subjects after 12 weeks of
therapy. 25 (83.33%) subjects did not complain any adverse effect (like pruritus, burning etc.)
and 5 (16.67%) subjects were suffered from different adverse effect of drug, like pruritus
observed in 2 (6.7%) subjects and burning in 6 (20%) subjects. This study found that
tacrolimus 0.1% ointment to be safe in the treatment of vitiligo, with reduction in the number
of vitiliginous spots by increased repigmentation significantly.
Key Words: safety of tacrolimus; treatment of vitiligo
DOI: http://dx.doi.org/10.3329/bjms.v13i3.1914
Bangladesh Journal of Medical Science Vol. 13 No. 03 July '14. Page: 255-259

Introduction:
Vitiligo is a common, acquired, discoloration of the
skin, characterized by well circumscribed, ivory or
chalky white macules which are flush to the skin surface. The hair over the lesion may be either normal
or white (poliosis) 1. Vitiligo usually begins in childhood or young adulthood; approximately one half of
those with vitiligo acquire the disease before the age
of 20 years and the incidence decreases with increasing age2. Vitiligo is a multifactorial polygenic disorder with a complex pathogenesis. Although several
theories have been proposed to explain the loss of
epidermal melanocyte in vitiligo, the exactcause
remains unknown3. Phototherapy and applications

of topical steroids are most commonly prescribed.

However, these are not always effective and corticosteroids on the face may lead to cutaneous atrophy, telangiectasias and ocular (applied to periorbital
region) complications. Successful treatment of vitiligo with topical calcineurin inhibitors has been
reported. Tacrolimus, a macrolide immune suppressant that comes from the fungus Streptomyces tsukuba is used as novel treatment option for vitiligo4,5.
This drug act on T cells and mast cells inhibiting T
cell activation the release of pro-inflammatory mediators in mast cells by degranulation. Tacrolimus
therapy does not cause atrophy, telengiactesia and
ocular side effects like topical steroids, when applied

1. Dr. Samaresh Chandra Hazra, Medical officer, Infectious Diseases Hospital, Mohakhali, Dhaka.
2. Dr. Nafiza Ahmed, Associate Professor, Dept. of Dermatology and Venereology, Dhaka Medical
College Hospital, Dhaka.
3. Dr. Jagodish Chandra Ghosh, Senior Consultant, Infectious Diseases Hospital, Mohakhali, Dhaka.
Corresponds to:
Dr.Samaresh Chandra Hazra. Medical officer, Infectious Diseases Hospital Mohakhali, Dhaka.
E-mail: samohazra@yahoo.com
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Safety of 0.1% topical tacrolimus

to face and intertriginous areas6. Inclinical trials, the

common adverse effects were burning, pruritus, and
erythema of skin. Burning sensation at the site of
application is by far the most frequently reported
adverse effect and is found in roughly 37 to 46% of
adults and children treated with 0.03%
tacrolimus,and 26 to 58% of those treated with 0.1%
tacrolimus ointment7. Particular attention has been
paid to skin infections as a potential complication of
topical treatment with an immunosuppressive agent.
Viral, fungal, and bacterial infections have all been
reported8. Apart from mild to moderate burning,
erythema, and pruritus, the use of tacrolimus ointment can cause folliculities,acne, Kaposi's varicelliform eruptions, eczema herpeticum and herpes simplex infections. Increased skin sensitivity to hot and
cold and alcohol intolerance have also been reported9. Occurrence of recurrent skin tags, rosacea like
granulomatous eruptions, rosaceiform dermatitis,
mucosal hyperpigmentation, tinea incognito, molluscumcontagiosumand verruca vulgarishave recently been reported. The cutaneous viral infection in
particular is alarming and may be caused by local
immunosuppressions10. Although there is a theoretic concern that topical immunomodulatory therapy
with tacrolimus and pimecrolimus may increase the
risk of cancer, there is no evidence to date to suggest
an increased risk of cutaneous or visceral cancer.
The European Agency for the Evaluation of
Medicinal Products has not recommended any
change in labeling or approval of these topical
agents. There may still be clinical situations where
such off-label treatment is seen as a lesser risk than
available alternatives such as oral administration of
an immunosuppressant, and limited data on safety
are emerging11. There are numerous treatment
options available for vitiligo but none is universally
safe. Very recently topical tacrolimus 0.1% is being
produced and marketed in our country but its safety
has not been studied in our population yet. This
study is designed to observe the safety of using topical tacrolimus 0.1% in patients of vitiligo.
Materials and Methods
A clinical trial was conducted in the department of
Dermatology and Venereology, BMC, Dhaka. Study
period of the trial was January 2010 to July 2010 and
patients with vitiligo (focal and segmental) were the
study population. Finally thirty patients, who
matched the inclusion criteria, were selected for the

study. Sampling technique was purposive type.

History and physical findings were recorded in a
structured questionnaire. Ethical approval was taken
from ethical Committee of BMC, Dhaka.
Inclusion criteria:

Vitiligo patients of both sex and above 2 years of

age.

Patient who had not received any treatment for

vitiligo (both systemic and topical) in the previous 2 months prior to inclusion.

Vitiligoof focal and segmental.

Exclusion criteria:

Pregnant women and lactating mother.

Known case of tacrolimus hypersensitivity.
Vitiligouniversalis with widespread involvement.
Procedure of data collection:
A total number of thirty subjects of vitiligo were primarily selected from thedepartment of Dermatology
and Venereology, BMC, Dhaka and complete history, general physical and dermatological examinations was done for all enrolled subjects. For women
of reproductive age reproductive history, menstrual
history, lactation and pregnancy plan was carefully
judged. Before inclusion in the study, all the participants and parents of children wereelaborately
informed about the natural history and the prognosis
of the disease, proper application procedures for the
therapy, possible therapeutic outcomes and adverse
effects associated with therapy, so that they can
make independent decision about their participation.
They were assured of strict privacy and secrecy of
information on all occasions as such necessary
measures were taken before hand. Photographs of all
lesions and clinical assessment at baseline and follow-up visit after three months were taken for subsequent assessment and further comparison. Each individual lesion was treated with tacrolimus 0.1% ointment twice daily for three months. Generally, the
repigmentation was recorded every 4 weekly for
three months and outcome measures graded as none
(no repigmentation), mild (less than 50% repigmentation), moderate (5075% regimentation), and complete (more than 75% repigmentation). Observation
and results of the clinical study and statistical analysis were presented by suitable chart, tables, graphics
and diagram.
Result
This study was carried out on thirty vitiligo (focal
256

Hazra SC, Ahmed N, Ghosh JC

and segmental) patients for a period of 12 weeks at

the department of Dermatology and Venereology,
BMC, Dhaka. Majority of patients suffering from
vitiligo 20(66.6%) were under the age of 40 years.
The highest percentage 13(43.3%) was in the age of
11-20 years. Sex ratio revealed higher in case of
female 18(60%), with a male-female ratio
Table I: Distribution of the study subjectsby age and sex

Table IV: Distribution of the study subject's adverse

effects (n=6) at base line and 4th and 8th week follow up.
Adverse effects

Base line 4th week 8th week

Pruritus
2 (6.7)
Irritation/burning 3 (10.0)

2 (6.7)
2 (6.7)

0 (.0)
1 (3.3)

90%
80%

Age group

Frequency

Percent

70%

<10
11-20
21-30
31-40
41-50
Sex
Male
Female

1
13
6
4
6

3.3
43.3
20.0
13.3
20.0

60%
40%
30%
20%
10%
0%

12
18

40.0
60.0

Table II: Distribution of the study subject by family

history of vitiligo

Yes
No

50%

Frequency

Percent

5
25

16.67
83.33

1:1.5(table-I). Table II showed 5(16.67%) patients

No side effect

Having side effect

Figure I: Distribution of the subjects by adverse effects.

had vitiligo among their families. Repigmentation
was observed in 8(26.7%) subjects at the end of 4th
week, 15 (50.1%) subjects at 8th week and
25(83.3%) subjects after 12 weeks of therapy. It was
seen from figure I that 25(83%) subjects had no
adverse effect and 5(17%) subjects were suffered
from different adverse effects of the drug. Pruritus
observed 2(6.7%)subjects and burning in3(10%)
subjects.

Table III: Distribution of the study subjects on the basis of repigmentation score in three follow up visits
Repigmentation score

4th week

8th week

12th week

None
Mild (<50%)
Moderate (50-70%)
Complete (>75%)

22 (73.3)
5 (16.7)
2 (6.7)
1 (3.3)

15 (50.0)
8 (26.7)
5 (16.7)
2 (6.7)

5 (16.7)
12 (40.0)
7 (23.3)
6 (20.0)

Values were expressed as number (cent).

Discussion
In this study, 43.3% subjects were within the age
group of 11-20 years and 20% were in the age group
of 21-30 years which mostly correlates with the findings of many other study, like the percentage of subjects in the age group of 11-20 years was 46% in one
study12 and 29.7% in another study 13. Sex ratio
revealed higher in case of female (60%), with a
male-female ratio 1:1.5. According to different previous studies adults and children of both sexes are
equally affected although the greater number of
reports among females is probably due to the greater

social consequences to women and girls affected by

this condition14, 15, 16. Family history has variously been reported with a range between 6.25% to
38%17. However, in our study family history was
5(16.67 %)which corroborates with another study
(12%)18. Though it is very difficult to judge the efficacy of treatment without studying the compliance
rate and follow-up for a long time; in this study overall response to topical tacrolimus in the treatment of
vitiligo has been observed, which shows 25 (83.3%)
subjects had at least some repigmentation at the end
of study, which concurs with other similar studies; as
257

Safety of 0.1% topical tacrolimus

for example 83.3%11,100%19, 86.4%20and

84%21.Xu AE et al. treated focal, segmental and
generalized vitiligo with 0.1% topical tacrolimus for
four months11,but we treated focal and segmental
vitiligo for three months with same repigmentation
score, so it was faster in our study. Skin typing of
Bangladeshi subjects and UVB exposure may stimulate the efficacy of topical tacrolimus, because
most of the population of our country is worked in
sun light.In this study only two subjects reported
pruritus (6.7%), and three mild irritation and burning
(10%). These are the clinical adverse effects of topical tacrolimus described in the literature which
includes pruritus, irritation, burning and erythema of
skin. No serious adverse events occurred during the
12 week study. The symptoms are mild intensity that
concurs with the references; as we find burning sen-

sation found in 13.3%11, 3.5%21 of cases and pruritus and burning in 12% 20 of cases.
Nobody discontinued the therapy for serious adverse
effects. In this study dermatological adverse effects
were infrequent and mild, so all the patients completed the therapy. This study found that topicaltacrolimus 0.1% ointment to be safe in the treatment
of vitiligo, with reduction in the number of vitiligenous spots by increased repigmentation significantly.
Conclusion:
This study reflects that topicaltacrolimus ointment
0.1% is a safe topical therapeutic option for the treatmentvitiligo. Proper selection of patient as well as
appropriate topical use of drug for adequate duration
responds well to reduce the number and size of
vitiligenous spots with minimum adverse effects.

258

Hazra SC, Ahmed N, Ghosh JC

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