Treatment of Facial Vitiligo by 0.1% Topical Tacrolimus in the Iraqi Patients

Abstract

Background: Although the treatment options of vitiligo have been increased during the last decades, therapy is still not satisfactory for many patients. Considering the autoimmune hypothesis of vitiligo pathogenesis, the use of topical calcineurin inhibitors seems reasonable. Objective: To evaluate the effectiveness and safety of 0.1% Tacrolimus ointment in the treatment of vitiliginous lesions on the face Patients and Methods: This is an open therapeutic trial. A total of 50 patients with facial vitiligo were seen and studied in the Department of Dermatology and Venereology, Ramadi Teaching Hospital, Al-Anbar, Iraq from March 2010 February 2011. Patients asked to apply topical Tacrolimus) twice daily for three months then follow up 3 months with weekly application with regular visit each month to estimate the area of reduction and record the side effect. Results: All patients' ages were at least 15 years old with stable vitiligo, (38 females and 12 males). In 85 (70.8%) of 120 treated patches marked repigmentation (Grade III) was noted after 6 months treatment. Side effects were mild burning like sensation at the application site. Conclusion: Facial vitiligo can be successfully treated with topical tacrolimus ointment 0.1% with fewer side effects.

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Iraqi J. Comm. Med., July. 2012 (3)
265
Treatment of Facial Vitiligo by 0.1% Topical
Tacrolimus in the Iraqi Patients
Zeya T. Al-Ani MD, FIBMS* Thamir A Kubiasi*, MD, FIBMS.
Abstract
Background: Although the treatment options of vitiligo have been increased during the last decades, therapy is still not
satisfactory for many patients. Considering the autoimmune hypothesis of vitiligo pathogenesis, the use of topical
calcineurin inhibitors seems reasonable.
Objective: To evaluate the effectiveness and safety of 0.1% Tacrolimus ointment in the treatment of vitiliginous lesions on
the face
Patients and Methods: This is an open therapeutic trial. A total of 50 patients with facial vitiligo were seen and studied in
the Department of Dermatology and Venereology, Ramadi Teaching Hospital, Al-Anbar, Iraq from March 2010
February 2011. Patients asked to apply topical Tacrolimus) twice daily for three months then follow up 3 months
with weekly application with regular visit each month to estimate the area of reduction and record the side effect.
Results: All patients' ages were at least 15 years old with stable vitiligo, (38 females and 12 males). In 85 (70.8%) of 120
treated patches marked repigmentation (Grade III) was noted after 6 months treatment. Side effects were mild
burning like sensation at the application site.
Conclusion: Facial vitiligo can be successfully treated with topical tacrolimus ointment 0.1% with fewer side effects.
Keywords: Tacrolimus, facial vitiligo, Iraqi patients.
Introduction:
itiligo is an acquired depigmenting disorder
characterized by loss of functional
melanocytes. It is estimated that about 1-2% of
population (1) suffers from vitiligo.
The onset of vitiligo is usually in childhood or
young adulthood. Men and woman are equally
affected; all races are affected, in 50% of cases the
age of onset fall within the first two decade of life.
in Iraq the mean age of onset 17.9 years and in 60%
of patients it develops before the age of 20years,
25% of patients had family history of vitiligo(2).
Current treatment of vitiligo e.g. topical
corticosteroid, topical tincture iodine 5% (3), narrow
band UVB (4) and PUVA are the most prescribed,
corticosteroid applied to the face may lead to
cutaneous atrophy, telangiectasia and ocular
complication, narrow bad UVB requires expensive
equipments and trained personnel and PUVA has
been associated with risk of carcinogenesis,
phototherapy and corticosteroid have limited
effectiveness particularly on the face (5).
Immunomodulator such as Tacrolimus 0.1% and
0.03 %, and pimecrolimus cream 1 % are approved
for treating atopic dermatitis in adult patients and
pediatric patients over 2 years of age.(5)
Tacrolimus (FK-506) is an immunosuppressive
drug membred macrolide lactone discovered in
1984(6) from the fermentation broth of Japanese soil
sample that contained the bacteria streptomyces
tsukubaensis can be used as an alternative to topical
steroids in many other forms of dermatitis. This
ointment does not cause atrophy, telangectasiae or
adverse ocular effects of topical corticosteroids
which has limited application to the face and
intertregnous areas (7).
Tacrolimus acts on T cells and mast cells
inhibiting T cell activation and the production of
proinflammatory cytokines such as tumor necrosis
factor (TNF) whose level are higher in vitiligo
lesional skin. Moreover it prevents the release of
proinflammatory mediators in mast cells by
degranulation (6).
The aim of the study is to evaluate the
effectiveness and safety profile of tacrolimus
ointment 0.1% as a treatment modality in facial
vitiligo patients.
Patients and Methods:
This is an open therapeutic trial. Total of 50
patients with facial vitiligo were seen and studied in
the Department of Dermatology and Venereology,
Ramadi Teaching Hospital, Al-Anbar, Iraq from
March 2010 till February 2011, A detailed history
was taken regarding the age, sex, residence, history
of previous treatment, onset, duration of illness,
aggravating factors like stress and sun.
The lesions on the face was examined with
wood’s light when needed and digital pictures of the
lesions were taken to obtain an accurate
measurement of the size of the lesions the contours
were traced on transparent sheets at baseline and
followed each visit (7).
Patients asked to apply topical Tacrolimus twice
daily for three months then up to 3 months with
weekly application with regular visit each month to
estimate the area of reduction and record the side
effect. During spring and summer time the patients
were advised to avoid sun exposure and put sun
block, Thyroid function test done for patients
suspected to have thyroid problem. Clinical
examination was done for other autoimmune
diseases. Patients on other treatment and pregnant
females were excluded.
Each monthly visit clinical and wood light
assessment of repigmentation of the lesions was
made; the outline of the lesion was drawn on
transparent paper and measures the surface area of
the lesions each month. Side effects were also
checked up. Subsequently the percentage of the area
V

Treatment of Facial Vitiligo by 0.1% Topical Tacrolimus in the Iraqi Patients Zeyad T. Al-Ani & Thamir A Al-Kubiasi
Iraqi J. Comm. Med., July. 2012 (3)
266
reduction or repigmentation in the lesions was
calculated. This percentage of repigmentation was
the main parameter to measure treatment
effectiveness.
The responses to therapy were evaluated according
to the following scale (8).
Grade 0: no response.
Grade I: slight response, when there is quarter of
size of patch or less showed marginal or
follicular repigmentation.
Grade II: moderate response, when there is half of
size of path showed marginal or follicular
repigmentation.
Grade III: marked response, when there is more than
half of size of patch showed marginal or
follicular repigmentation.
Results:
A total of 50 patients 38 females and 12 males
were recruited for 6 months therapeutic trial , ,their
ages ranged from15-22 years with mean±SD years
19.1±3.4,all patients had multiple patches on the
face with duration ranged from 9-24 months with
mean ±SD 17.22±12 months, the size of patches
ranged from 1-5 cm2 in diameter.
The number of patches in 45 patients was 120
with a mean of 3-6 patches in each patient.
All patients were at least 15 years old with stable
vitiligo (not expanding during the last 1 year) on the
face, 5 patients were defaulted for unknown reason
Before treatment the mean± SD of sizes of
patches were 3.4cm2 ± 1.94, after 1 month the mean
±SD of the sizes of patches were 2.9cm2 ±1.69, after
2 months the mean ±SD of the sizes of patches were
2.1cm2 ±1.145, after 3 months of treatment the
mean SD of the sizes of patches were 0.7cm2 ±0.43,
after 3 months of follow up the mean±SD of sizes of
patches were 0.4cm2 ±0.32 (Table 1).
Table 1: Shows the treatment response regarding the
size of patches
No. of
patches
Mean size
cm2
SD
Before
treatment
120
3.4cm2
1.94116
After 1 month
120
2.9cm2
1.69312
After 2
months
120
2.1cm2
1.14641
After 3
months
120
0.7cm2
0.89521
Follow up 3
months
120
0.4cm2
0.49651
Regarding the grades of response, after 1 month
of treatment Grade: 65 patches (54.1%), Grade II: 40
patches (33.33%), Grade III: 15 patch (12.5%).
After 2 months of treatment:
Grade I: 50 patches (41.6%).
Grade II: 45 patches (37.5%).
Grade III: 25 patch (20.8%).
After 3 months of treatment:
Grade I: 33 patches (27.5%).
Grade II: 62 patches (51.6%).
Grade III: 25 patches (20.8%).
After 6 months:
Grade I: 8 patches (6.66%),
Grade II: 27 patches (22.5%),
Grade III: 85 patches (70.8month %) (Table 2).
Side effects of the drug were limited to mild
erythema with slight tingling sensation.
Table 2: Shows Grades of response to treatment after six months
Grades
no. and% of patches
response after 1 month
no. and% of
patches response
after 2 months
no. and% of
patches response
after 3 months
no. and% of
patches response
after 3months
Grade I
65(54.1%)
50(41.6%)
33(27.5%)
8(6.66%)
Grade II
40(33.33%)
45(37.5%)
62(51.66%)
27(22.5%)
Grade III
15(12.5%)
25(20.8%)
25(20.8%)
85(70.8%)
Discussion:
Vitiligo is a common skin disease seen every
day. High number of patients has limited areas of
vitiligo especially on the face that not need systemic
treatment, in this area topical treatment like
corticosteroid, tincture iodine and other modalities
of treatments are considered. the use of topical
steroids on the face for a long time lead to many side
effects like atrophy, telangiectasia while this study
showed that tacrolimus is safe even if used for a
long period with mild reversible side effects(5).
The present work was arranged to evaluate the
effectiveness of topical tacrolimus ointment.1% in
treatment of facial vitiligo.
Topical FK 506 (Protopic, Astella) is
approved for the treatment of atopic dermatitis (9)
growing number of case reports and small series
demonstrate that it can also induce repigmentation in

Treatment of Facial Vitiligo by 0.1% Topical Tacrolimus in the Iraqi Patients Zeyad T. Al-Ani & Thamir A Al-Kubiasi
Iraqi J. Comm. Med., July. 2012 (3)
267
vitiligo especially on the face and neck (10).
The full role of autoimmune T-cells in vitiligo
remains unclear. Thus, it is uncertain if the anti T-
cell activity of FK 506 underlies its mechanism in
treating vitiligo recent studies have investigated how
topical FK 506 alters the inflammatory environment
on the skin (11).
Topical tacrolimus may also act on keratinocytes
to create signals that cause proliferation of
melanocytes (12), in addition tacrolimus may act on
suppression of autoantibody recognition of cell
surface melanocyte antigen and inhibition of
subsequent cytotoxic T lymphocytes reactions.(13)
The result of topical tacrolimus ointment in
treatment of facial vitiligo is promising since 85
patches (70.8%) showed marked response after 6
months when there is more than half of the size of
patch showed marginal repigmentation. (14)
Also we found that more than half of patients
showed clinical repigmentation at the end of first
month of treatment this will encourage the patient to
continue the treatment course and this explain the
small number of patient defaulted.
Conclusion:
In conclusion patients with facial vitiligo can be
successfully treated with topical tacrolimus
ointment0.1% with fewer side effects.
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*Department of Medicine (Dermatology & Venereology),
Collage of Medicine, Al-Anbar University. Tel.
(+964)7901431836.
E-mail: thameralkubaisi@yahoo.com.
Conflicts of interest: This study and the authors were not
supported by any company with a vested interest in the
product being studied.