ARTICLE
Auteur(s) : Barbara Boone, Katia Ongenae,
Nanny Van Geel, Sander Vernijns, Stefanie De Keyser, Jean-Marie
Naeyaert
Department of Dermatology, University Hospital of Ghent, De
Pintelaan 185, 9000 Ghent, Belgium
accepté le 4 Octobre 2006
Vitiligo is an acquired depigmenting disorder characterized by loss
of functional melanocytes. It is estimated that about 0.5 to 1% of
the world’s population suffers from vitiligo with an uneven
distribution over different continents, probably to be explained by
different rates of inbreeding [1, 2]. The onset of vitiligo is
usually in childhood or young adulthood. Men and women are equally
affected. The course of the disease is usually unpredictable, but
is often slowly progressive. Depending on the extent of the
lesions, vitiligo can be classified into two main categories:
generalized and localized. Generalized vitiligo is the most common
presentation with milky white patches in a symmetrical
distribution. Patients with vitiligo have an increased risk of
developing autoimmune diseases. Thyroid disorders are most commonly
associated with vitiligo [3]. Although vitiligo is asymptomatic and
does not adversely affect mortality and physical morbidity, it may
cause a considerable psychosocial stress and potential psychiatric
comorbidity, with effects on the person’s self-esteem [4]. The
etiology of vitiligo is still largely unknown. Several theories
have been proposed. The autoimmune hypothesis is the most important
and popular. This theory is supported by the clinical association
of vitiligo with autoimmune disorders, the frequent detection of
circulating auto-antibodies to surface and cytoplasmatic antigens
of melanocytes and the finding of activated T-cells in the
periphery of actively progressing lesions in some vitiligo patients
[1, 5, 6].Although different treatment options of vitiligo are
available, no curative therapy exists. Treatment of vitiligo aims
at stabilization and/or repigmentation of the lesions. Standard
nonsurgical therapeutic options include topical corticosteroids,
topical calcipotriol, photochemotherapy (PUVA) or narrow band UV-B
phototherapy. Surgical modalities are based on autologous grafting
of non-lesional epidermis or cultured melanocytes to depigmented
areas [7]. Furthermore, cosmetic camouflage and supplementation of
antioxidants are adjuvant therapeutic options. Patients with
extensive vitiligo can be further depigmented with monobenzyl ether
of hydroquinone [3, 8, 9].As all treatment modalities are limited
by adverse effects or poor efficacy, new therapies are needed.
Recently, tacrolimus ointment (FK 506, Protopic®,
Astellas) and pimecrolimus cream (SDZ ASM 981, Elidel®,
Novartis) have been introduced in the treatment of the disorder.
They were originally developed for the treatment of inflammatory
skin disorders and both are FDA/EMEA approved for use in atopic
dermatitis. Tacrolimus and pimecrolimus are topical ascomycin
immunomodulating macrolactams and act as calcineurin inhibitors
affecting the activation/maturation of T-cells and subsequently
inhibit the production of various Th1 and Th2 type of cytokines as
IL-2, IL-3, IL-4, IL-5, IL-10, GMCS-factor, TNFα and IFNγ [5, 6,
10, 11]. This mechanism may interfere with the autoimmune mediated
destruction of melanocytes by activated T-cells in vitiligo
lesions. However, as the lymphocytic infiltrate in perilesional
skin is not present in all vitiligo patients, other mechanisms may
play a role in TIM (topical immunomodulator) induced
repigmentation. Recently in vitro evidence of a direct interaction
between tacrolimus and keratinocytes creating a favourable milieu
for melanocytic growth and migration has been obtained [12]. Most
clinical trials investigating the use of TIMs in the treatment of
vitiligo have been performed with tacrolimus and show beneficial
effects (table 4). The aim of our open proof of concept study was
to evaluate the efficacy and safety profile of pimecrolimus as a
treatment modality in vitiligo patients. In addition a review of
the literature concerning the treatment of vitiligo with TIMs is
presented.
Materials and methods
( Table 1 )( Table
2 )( Table 3 )( Table 4 )A prospective, open proof of concept study
was conducted at the department of dermatology at the university
hospital of Ghent. Approvement by the Ethical Committee was
obtained (October 23th 2003, project 2003/275) and all
participants provided signed informed consent. In May 2004 a total
of 26 patients were recruited for a 6 month trial. All patients
were at least 6 years old with active or stable (not expanding
during the last year) vitiligo and at least lesions in the head or
neck region. Other body parts could be affected. Patients with
segmental/focal vitiligo or with generalized vitiligo explosively
expanding or spontaneously regressing during 3 months before study
onset were excluded. Previous topical treatment was interrupted at
least 2 weeks before inclusion, whereas photo(chemo)therapy was
stopped at least 1 month before study onset. Detailed history and
clinical examination were performed at the baseline visit.
The total vitiligo affected area was estimated by using the
patient’s palm as a template representing 1% of the body surface
area. A reference lesion in the head and neck region was chosen and
investigated with Wood light. Digital pictures of the lesion were
taken. To obtain an accurate measurement of the size of the
reference lesion the contours were traced on transparent sheets at
baseline and follow up visits in 20 of 26 patients. These sheets
were scanned at a predefined resolution and analyzed using a
digital image analysis software (Matlab; Mathworks, Inc, Natik,
Mass) as previously described [13].
Patients were asked to apply topical pimecrolimus twice daily,
primarily over the reference lesion and optionally at other
affected body sites. During the spring and summer patients were
advised to avoid sun exposure and to apply sunscreen of at least
SPF 20 with frequent reapplication.
Follow up visits were scheduled 3 and 6 months after the
baseline visit. At that moment a clinical and Wood light assisted
assessment of repigmentation of the reference lesion was made by
the clinician. Doubt about possible repigmentation was interpreted
as absence of repigmentation. Following clinical and Woodlight
assessment, the reference lesion was traced on a transparent sheet
and by means of digital analysis software the surface area of the
lesion was measured. Subsequently the percentage of area reduction
or repigmentation in the reference lesion during the trial could be
calculated. This percentage of repigmentation was the main
parameter to measure treatment efficacy. Finally, patients were
questioned about adverse effects.
Descriptive and explorative statistical analyses were performed.
Changes in pigmentation were evaluated with a Wilcoxon Ranked Sign
test with a p-value less than 0.05 indicating statistical
significance. In order to identify prognostic factors of disease
improvement multiple linear and logistic regression was
performed.
Table 1 Demographic data
|
Number (Percentage)
|
Mean (SD)
|
Median (IQR)
|
|
Sex (n = 26)
|
|
|
|
|
Male
|
8 (30.8%)
|
|
|
|
Female
|
18 (69.2%)
|
|
|
|
Vitiligo activity (n = 26)
|
|
|
|
|
Active
|
16 (61.5%)
|
|
|
|
Stable
|
10 (38.5%)
|
|
|
|
Depigmentation of scars (n = 26)
|
|
|
|
|
Present
|
11 (42.3%)
|
|
|
|
Absent
|
15 (57.7%)
|
|
|
|
Halo nevi (n = 26)
|
|
|
|
|
Present
|
3 (11.5%)
|
|
|
|
Absent
|
23 (88.5%)
|
|
|
|
Thyroid disease (n = 26)
|
|
|
|
|
Present
|
4 (15.4%)
|
|
|
|
Absent
|
22 (84.6%)
|
|
|
|
Other autoimmune diseases (n = 26)
|
|
|
|
|
Present
|
0 (0%)
|
|
|
|
Absent
|
26 (100%)
|
|
|
|
Family history of vitiligo (n = 26)
|
|
|
|
|
Present
|
8 (30.8%)
|
|
|
|
Absent
|
18 (69.2%)
|
|
|
|
Family history of autoimmune diseases (n = 26)
|
|
|
|
|
Present
|
5 (19.2%)
|
|
|
|
Absent
|
21 (80.8%)
|
|
|
|
Previous vitiligo treatment (n = 26)
|
|
|
|
|
Yes
|
23 (88.5%)
|
|
|
|
No
|
3 (11.5%)
|
|
|
|
Phototype (n = 26)
|
|
|
|
|
I
|
1 (3.8%)
|
|
|
|
II
|
4 (15.4%)
|
|
|
|
III
|
21 (80.8%)
|
|
|
|
Age (years) (n = 26)
|
|
36.4 (18.1)
|
35.5 (19.0-53.0)
|
|
ARRAY(0x2ed19c)
|
|
Duration of vitiligo (years) (n = 26)
|
|
12.8 (10.0)
|
8 (5.0-18.0)
|
Table 2 Clinical assessement of total vitiligo affected
area at baseline (palm = 1%)
|
Mean (SD) %
|
Median (IQR) %
|
|
Head and neck (n = 26)
|
1.5 (1.8)
|
1.0 (0.5-2.0)
|
|
Trunk (n = 26)
|
4.7 (6.1)
|
3.0 (0.5-5.5)
|
|
Upper limbs (n = 26)
|
2.9 (2.5)
|
2.0 (1.0-5.0)
|
|
Lower limbs (n = 26)
|
1.6 (1.8)
|
0.8 (0.3-2.5)
|
|
Total affected area (n = 26)
|
10.7 (9.0)
|
8.4 (3.3-15.5)
|
Table 3 Clinical assessment of repigmentation of the
target lesion
|
Number (percentage)
|
Number (percentage)
|
|
Month 3
|
Month 6
|
|
Repigmentation (clinical) (n = 26)
|
10 (38.5%)
|
13 (50.0%)
|
|
Repigmentation (Woodlight) (n = 26)
|
13 (50.0%)
|
15 (57.7%)
|
|
Mean period to initial repigmentation (± SD) (n = 26)
|
6.9 (± 2.4) weeks
|
7.4 (± 2.8) weeks
|
Table 4 Case reports and clinical studies on tacrolimus
in the treatment of vitiligo
|
Tacrolimus
|
|
Reference
|
Study design
|
Number of patients
|
Study duration
|
Treatment regimen
|
Materials and methods
|
Results
|
Adverse effects
|
|
Randomized, placebo-controlled, double-blind trial
|
9
|
12 weeks
|
0.1% tacrolimus + UVB versus placebo + UVB
|
2 paired vitiligo patches, digital photography, computerized area
measurement
|
No statistically significant difference
|
Redness, pruritus, burning (most likely related to light
therapy)
|
|
- Comparative
- prospective, non blind, pilot study
|
9
|
12 weeks
|
0.1% tacrolimus + UVB versus 0.1% tacrolimus
|
2 paired vitiligo patches, digital photography, 6-point scale for
grading repigmentation by 2 investigators
|
No repigmentation with tacrolimus monotherapy
|
Erythema (most likely related to light therapy)
|
|
Open pilot study
|
12
|
8 months
|
0.1% tacrolimus twice daily
|
- Digital photography,
- 3-point scale for grading repigmentation
|
Good to excellent repigmentation in 50% of patients
|
Pruritus at initial application
|
|
Open pilot study
|
25 children
|
12 weeks
|
0.03% tacrolimus twice daily
|
Digital photography, serial mapping of body lesions, 3-point scale
for grading repigmentation
|
Complete repigmentation in 57.9% of patients, best results in face
and hear bearing sites
|
Pruritus and burning
|
|
Retrospective review
|
57 children
|
3 months
|
0.03% or 0.1% tacrolimus once or twice daily
|
Digital photography, 3-points scale for grading repigmentation
|
At least partial repigmentation in 84% of patients, best results in
head and neck region
|
Burning at initial application
|
|
Comparative, prospective, randomized, intra-individual study
|
14
|
12 weeks
|
0.1% tacrolimus + excimer laser versus excimer laser
|
2 to 5 paired lesions, digital photography, 6- points scale for
grading repigmentation
|
Combination therapy is superior to excimer laser monotherapy
|
Erythema, bullae (most likely related to light therapy)
|
|
Prospective, double-blind, placebo-controlled study
|
8
|
10 weeks
|
0.1% tacrolimus + excimer laser versus placebo + excimer laser
|
24 symmetric patches, photography, 4-point scale for grading
repigmentation
|
Significantly greater degree of repigmentation when treatment with
combination therapy
|
- Excimer: erythema, blistering
- Tacrolimus: tingling, burning, erythema
|
|
Open prospective study
|
23
|
24 weeks
|
0.1% tacrolimus twice daily
|
6-points disease severity scale
|
Varying levels in 89% of patients, best result head and neck
region
|
Burning, stinging, pruritus, verruca vulgaris
|
|
Randomized, double-blind, comparative trial
|
20 children
|
2 months
|
0.1% tacrolimus versus 0.05% clobetasol propionate
|
2 symmetrical lesions, color slides, morphometric digitalized
computer program
|
Tacrolimus almost as effective as clobetasol propionate
|
- Clobetasol propionate: atrophy, telangiectasia
- Tacrolimus: burning
|
|
Case report
|
3
|
2 to 4 months
|
0.1% tacrolimus twice daily
|
Lesions on face and eyelids
|
Complete repigmentation in 100% of patients
|
None
|
- Castanedo-Cazares [48]
- 2003
|
Case report
|
1
|
4 months
|
0.1% tacrolimus + UV-B
|
Lesions on face
|
Percentage of repigmentation area: 95%
|
Not mentioned
|
|
Open pilot study
|
15
|
1.5 to 9.5 months
|
0.1% tacrolimus twice daily (+ sunlight exposition in some
patients)
|
4-points scale for grading overall repigmentation
|
At least partial repigmentation in 87% of patients
|
None
|
|
Open pilot study
|
6
|
1 to 5 months
|
0.03% or 0.1% tacrolimus twice daily
|
Application on all vitiliginous lesions, 4-points scale for grading
overall repigmentation
|
Moderate to excellent repigmentation in 83% of patients
|
Burning and stinging at initial application, tinea corporis
|
|
Case report
|
1
|
18 months
|
0.1% tacrolimus twice daily
|
Lesions on face
|
90% repigmentation in face and scalp region
|
Not mentioned
|
Results
A total of 26 Causasian patients (8 males and 18 females) with a
median age of 35.5 years was recruited for participation in a study
with a mean (± SD) study duration of 186 (± 17) days. No
patients were lost during follow up. The duration of vitiligo
varied from 2 to 38 years with a median of 8 years. In 16 (61.5%)
patients vitiligo was actively spreading during the past year.
Depigmentation of scars was noticed in 11 (42.3%) patients whereas
halo naevi were present in 3 (11.5%) patients. Twenty one (80.8%)
patients could be categorized as phototype III whereas 4 (15.4%)
patients were classified as phototype II and only one (3.8%)
patient as phototype I. Based on history, thyroid disease was
present in 4 (15.4%) patients. No other autoimmune diseases were
associated. A family history of vitiligo was noticed in 8 (30.8%)
patients. A family history of autoimmune disease was present in 5
(19.2%) patients (4 thyroid disease, 1 Crohn’s disease). In total,
23 (88.5%) patients had used topical and/or photo(chemo)therapy
before the introduction of pimecrolimus cream with limited or no
improvement. Three patients had no prior therapy (table 1).
The median total affected body surface area at baseline was 8.4%
ranging from 1.1% to 38.0% which indicates a broad vitiligo
severity spectrum of the participants. The median affected area in
head and neck region amounted to 1% with an interquartile range
from 0.5 to 2.0% (table 2).
Repigmentation of the target lesion was clinically marked in 10
of 26 (38.5%) patients after 3 months and in 13 of 26 (50.0%)
patients after 6 months. Assessment of repigmentation with
Woodlight revealed even better results with repigmentation in 13 of
26 (50.0%) patients after 3 months and in 15 of 26 (57.7%) patients
after 6 months. The mean (± SD) period to initial
repigmentation ran up to 7.4 (± 2.8) weeks (table 3).
At baseline the median surface area of the reference lesion in
head and neck region was 5.8 cm2 (interquartile
range (IQR) 3.3-16.8 cm2). At month 3 the median
target lesion area was statistically significantly reduced to
3.6 cm2 (IQR 0.7-12.0 cm2)
(Wilcoxon Ranked Sign test, p = 0.0023) with a median relative area
reduction of 26.2% (IQR 16.8-47.4%). At month 6 the median target
lesion area was further reduced to 1.4 cm2 (IQR
0.0-9.4 cm2), a statistically significant reduction
versus baseline (Wilcoxon Ranked Sign test, p = 0.0007) with a
median relative area reduction of 72.9% (IQR 30.5-98.3%) versus
baseline ( (figure
1) ). Only 1 of 20 (5%) patients presented with enlargement
of the initial reference lesion, whereas stabilization
(repigmentation < 10%), reduction and even complete
disappearance of the lesion were noticed in 3 of 20 (15%), 11 of 20
(55%) and 5 of 20 (25%) patients respectively.
Due to the small sample size of the pilot study no statistically
significant predictors of response rate could be identified.
However, some tendencies were noted. Duration of vitiligo and total
affected body surface area influenced treatment outcome. The
shorter the duration of vitiligo and the smaller the total affected
body surface area, the better the probability on
repigmentation.
Side effects of therapy were mainly limited to application site
symptoms. Twelve of 26 (46.2%) patients mentioned a burning
sensation at initial application, for which therapy was not
discontinued. At the end of the study 2 of 26 (8%) patients
developed an acneiform eruption at the application site.
Discussion
Since 2002 several case reports and small studies on the use of
TIMs in vitiligo have been published (tables 4 and 5)( Table 5 ). Most studies have been performed with
tacrolimus and show beneficial results, mainly in the head and neck
region. This may be explained by the greater density of hair
follicles in these areas and thus the greater melanocyte reservoir.
Moreover, the head and neck are sun-exposed areas and UV therapy is
a well-known treatment option of vitiligo. One randomized, double
blind, left-right comparative trial has been conducted and showed
tacrolimus to be almost as effective as clobetasol propionate in
the treatment of vitiligo [14]. The first report on pimecrolimus in
the treatment of vitiligo was published in 2003. A patient with
lesions on the face treated with 1% pimecrolimus during 5 months
showed repigmentation of more than 90% [15]. Equal efficacy of 1%
pimecrolimus versus 0.05% clobetasol propionate was found in one
trial [16].
In our study 26 vitiligo patients were asked to apply 1%
pimecrolimus twice daily over a 6 month period, which is longer
than the follow up time in most similar studies so far. Moreover,
digital image analysis software was used in order to obtain
objective repigmentation area measurements instead of the commonly
used subjective repigmentation scaling scores. Clinical assessment
revealed repigmentation of the target lesion on the face or neck in
10 of 26 (38.5%) patients after 3 months and in 13 of 26 (50.0%)
patients after 6 months. Objective measurement of the target lesion
showed a median relative area reduction of 26.2% and 72.9% after 3
and 6 months respectively. Based on these results, patients with a
good initial response to pimecrolimus treatment should be
encouraged to continue therapy as further improvement can be
expected.
Two prospective studies showed the synergistic effect of
tacrolimus ointment and 308-nm excimer laser treatment [17, 18].
However, it is still uncertain whether combination of topical
immunomodulators with UV treatment is safe in the long-term with
respect to photocarcinogenesis. Systemic treatment with tacrolimus
in organ transplant patients increases the risk for the development
of cutaneous cancer. This finding has led to the restriction of UV
exposure during topical treatment with TIMs. In animal studies a
combination of topical immunomodulators with ultraviolet exposure
revealed an enhanced risk of the development of skin cancer.
However animal models are a poor predictor of human carcinogenesis.
Moreover, studies in humans with inflammatory skin disease treated
with topical immunomodulators show there is no evidence that the
combination of UV and TIMs is more carcinogenic than UV alone [19,
20]. Studies in mouse skin have shown that pimecrolimus and
tacrolimus applications even can protect against UV induced damage
on DNA [21-23]. In addition, in patients with vitiligo the
occurrence of non-melanoma skin cancer is uncommon and the
important tumor suppressor p53 is upregulated, suggesting an
inherent resistence to the development of cutaneous malignancies in
vitiliginous skin [24, 25]. Postmarketing epidemiological studies
to assess the long-term risk of skin cancer in patients treated
with topical pimecrolimus are underway. Until further evidence is
available an adequate UV protection should be advised and a
combination therapy of TIM and UV should only be performed in
controlled settings.
As not all vitiligo patients show repigmentation upon
pimecrolimus treatment, it would be interesting to know if certain
predictors of considerable disease improvement exist. We were not
able to identify statistically significant predictors, but some
tendencies were noted. An inverse correlation between duration of
the disease and total affected body surface area versus response
rate was noted. The correlation between short vitiligo duration and
promising response rate upon pimecrolimus therapy has already been
noticed by another open pilot study conducted by Sendur N et al.
[26]. Studies with larger series are required to support these
findings and to identify other possible predictors in order to
enable the physician to select those vitiligo patients with a high
probability of successful treatment with pimecrolimus.
As vitiligo tends to be chronic and requires quite a long
therapeutic course to achieve satisfactory results, tolerability
and safety are important issues. Few side effects were mentioned by
patients participating in our study. Twelve patients mentioned a
burning sensation upon initial application which resolved after a
few days. This application site reaction is the most frequently
reported side effect upon treatment with topical immunomodulators.
However, the incidence is lower in the vitiligo population compared
to the atopic dermatitis population. This is probably due to the
presence of an intact epidermis in vitiligo patients versus the
excoriated skin of an atopic dermatitis patient [6]. At the end of
the study two patients developed an acneiform eruption at the
application site. While not previously observed in vitiligo trials
with TIM treatment, this adverse event has occasionally been
observed in atopic dermatitis patients treated with both tacrolimus
[27-29] and pimecrolimus [30, 31]. Although skin infections did not
occur within our study population, molluscum contagiosum infection
during the treatment of vitiligo with tacrolimus has been reported
[32]. However, treatment with TIMs has not been associated with a
statistically significant increase of skin infections in patients
with atopical dermatitis [33-35]. Analogously there is no increased
incidence of systemic infections in patients treated with topical
calcineurin inhibitors [36].
Controversy exists concerning the possible association between
the use of topical immunomodulators and the occurrence of
malignancies in humans. Since January 2006 a black box warning for
tacrolimus and pimecrolimus has been enacted by the FDA because of
concerns of potential safety risks including skin cancer and
lymphoma. However there is no evidence of a causal relation between
the sporadically reported lymphomas and the use of a topical
calcineurin inhibitor. As a small percentage of patients treated
with TIMs have a significant absorption of these agents [27, 37]
and phase 4 studies have only just begun to enroll patients,
conclusive safety data will only be available after many years [19,
34, 36, 38]. It should be noted that most studies with TIMs are
conducted in patients with atopic dermatitis in which the barrier
function of the skin is disturbed. In vitiligo the barrier function
of the skin is normal which results in a lesser degree of
penetration of TIMs. Moreover, due to a higher lipophilicity,
pimecrolimus has a more skin-selective profile than tacrolimus,
which theoretically results in a lower potential for systemic
immunosuppression and the development of cancer [39].
Despite above mentioned safety issues, we demonstrated
pimecrolimus to be a useful alternative in the treatment of
vitiligo in the head and neck region. Treatment of vitiligo with
pimecrolimus (and tacrolimus) enables the physician to circumvent
side effects of currently available therapeutic options [8]. Most
importantly, topical immunomodulators have an advantage over
topical corticosteroids as they do not induce atrophy, striae and
telangiectasia. Moreover, application of topical steroids to the
eyelids can cause glaucoma and cataracts whereas this has not been
reported to treatment with TIMs [40, 41]. Unfortunately topical
calcineurin inhibitors are up to 10 times more expensive than
corticosteroids.
Table 5 Case reports and clinical studies on
pimecrolimus in the treatment of vitiligo
|
Pimecrolimus
|
|
Reference
|
Study design
|
Number of patients
|
Study duration
|
Treatment regimen
|
Materials and methods
|
Results
|
Adverse effects
|
|
Comparartive prospective, non blind trial
|
10
|
2 months
|
1% pimecrolimus versus 0.05% clobetasol propionate
|
2 paired vitiligo patches digital photography, 4-points scale for
grading repigmentation
|
Comparable rate of repigmentation
|
- Clobetasol propionate: telangiectasia, atrophy
- Pimecrolimus: burning
|
|
Case report
|
1
|
5 months
|
1% pimecrolimus
|
Lesions on the face, scalp, trunk (+ atopic dermatitis)
|
Percentage of repigmentation: >90%
|
None
|
Conclusion
Data from case reports and smaller pilot studies investigating the
use of topical calcineurin inhibitors in the treatment of vitiligo
are promising. However, placebo-controlled prospective studies with
larger patient series should be conducted in order to further
investigate the efficacy of pimecrolimus in the treatment of
vitiligo. Trials comparing the efficacy of pimecrolimus versus
corticosteroids could help to resolve the present disagreement on
the topic. Identification of predictors of considerable disease
improvement would enable the physician to select those vitiligo
patients with a high probability of successful treatment with
pimecrolimus. As vitiligo has an important effect on the
psychological well-being of a patient, quality of life scales
should be included in future trials. It is also unknown whether a
relapse will occur when pimecrolimus treatment is stopped and
whether continuous or intermittent therapy will be needed.
Moreover, safety issues concerning the treatment with topical
immunomodulators are still pending and vitiligo tends to be chronic
and requires quite a long therapeutic course to achieve
satisfactory results. Therefore long-term follow up studies are
required. Awaiting larger studies, the use of topical pimecrolimus
in the treatment of vitiligo could be an alternative in the
treatment of head and neck lesions where chronic use of potent
corticosteroids is contra-indicated.
Acknowledgements
Financial support: Medication was kindly provided by Novartis
Belgium. Statistical analysis was performed in collaboration with
Novartis Belgium and General Biometric Services and Consulting
(Ghent). The authors thank M. Dierick, and M. De Backer, for their
support and assistance in completing this trial.
Conflict of interest: None
References
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