ARTICLE
Auteur(s) :, Basak
Coskun*, Yunus Saral, Dilara Turgut
Firat University Faculty of Medicine, Department of Dermatology,
Elazig-Turkey
accepté le 27 Novembre 2004
Vitiligo is a common skin disease characterized by loss of normal
melanin pigments and producing white patches on the skin. Current
treatment options are far from ideal and there is still a search
for a treatment that would give consistent, safe and long-term cure
by repigmentation. Topical corticosteroids are indicated for the
treatment of limited areas of vitiligo [1]. Considering the
autoimmune hypothesis of vitiligo pathogenesis due to humoral and
cellular dysfunction, the use of calcineurin inhibitors tacrolimus
and pimecrolimus for the treatment of vitiligo seems
reasonable.Pimecrolimus (SDZ ASM 981), an ascomycin derivative, is
one of the new classes of immunomodulating macrolactams and was
specifically developed for the treatment of inflammatory skin
diseases [2]. Recently, reports of successful monotherapy with
pimecrolimus in the treatment of vitiligo have appeared [3-5]. We
performed a prospective study to compare the efficacy of two
treatment modalities in vitiligo patients using 0.05% clobetasol
propionate on one side versus 1% pimecrolimus on the other side in
the same patient.
Methods
Patients admitted to our clinic between January-May 2004 with
generalized vitiligo were considered for this prospective study. It
was assured that none of the patients had any of the following
conditions: thyroid or parathyroid disease, cardiovascular or
malignant diseases, impaired renal and/or liver function,
pregnancy, lactation. Ten patients (3 males and 7 females) with
virtually bilaterally symmetrical lesions of generalized vitiligo
were included. 0.05% clobetasol propionate cream
(Dermovate®, GlaxoSmithKline, Istanbul, Turkey) was
applied twice daily over the right side and topical 1% pimecrolimus
cream (Elidel®, Novartis, Istanbul, Turkey) was applied
twice daily over the left side of the body in the same patient.
The efficacy of 2 treatment modalities were analyzed by 2
clinicians unrelated to the study. These analyses involved
evaluation of the level of repigmentation, time of response,
assessment of side symptoms related to treatment including
telangiectasia, burning sensation and atrophy. Results of the
treatment were visually assessed. Photographs of the lesions of all
the patients were taken prior to commencement of the treatment and
on every 2-weekly examination during the 2-months treatment and the
patients were also clinically examined at every visit. The grade of
repigmentation was evaluated from these color slides.
Evaluation of repigmentation involved comparison between 2
bilaterally symmetrical lesions of about the same size.
Repigmentation was evaluated as follows: 0-25% repigmentation,
minimal (poor); 26-50% repigmentation, moderate; 51-75%
repigmentation, good; and 76-100% repigmentation, excellent.
Statistical analysis was performed using SPSS for windows.
Results
Ten patients, mean age 31.8 years (range 12-66 years)
with virtually bilaterally symmetrical lesions of generalized
vitiligo were included. The duration of vitiligo was varied from 2
to 40 years (average 14.7 years). The acral region was
affected in 2 (20%), trunk in 4 (40%), and extremities in 4 (40%)
patients. New lesions had developed in 4 patients during the
previous 6 months and in 2 patients during the previous 12 months
while there was no recent development of new lesions in the other 4
patients.
No statistically significant difference was observed between the
evaluations of the two dermatologists (p = 0.850). The
results of the treatment are presented in table 1( Table 1 ). All patients had different degrees
of pigmentation. There was no significant difference between the
two treatment modalities (p = 0.980). But, the response
rate of lesions varied according to their anatomical location for
both treatment modalities (table 1). Response to treatment was
better on the trunk and extremity lesions in all treatment
modalities (figures 1 and 2).
With regard to the time of response, repigmentation had started
after about 3 weeks on the lesions of the trunk and extremities.
Regarding the side effects of the drugs used; atrophy was found in
one lesion and telangiectasia in another lesion due to clobetasol
propionate. In response to topical pimecrolimus, two patients
reported an experience of burning sensation but it was not to a
degree to stop the treatment.
Table 1 Response rates for the treatment with 1%
pimecrolimus and 0.05% clobetasol propionate in accordance to the
localization of lesions
|
Lesion site
|
No. of patients
|
1% pimecrolimus
|
0.05% clobetasol propionate
|
|
E
|
G
|
M
|
P
|
E
|
G
|
M
|
P
|
|
Trunk
|
4
|
3
|
—
|
1
|
—
|
3
|
1
|
—
|
—
|
|
Acral region
|
2
|
—
|
—
|
—
|
2
|
—
|
—
|
—
|
2
|
|
Extremities
|
4
|
3
|
1
|
—
|
—
|
3
|
1
|
—
|
—
|
Discussion
Vitiligo is a common skin disorder characterized by loss of skin
color. It mainly affects a younger population and can cause serious
cosmetic and social problems. At least three theories about the
underlying mechanism of vitiligo have been proposed. Release of a
chemical that is toxic to melanocytes is one theory, while another
theory says that the melanocytes simply self-destruct. According to
the third theory, vitiligo is a type of autoimmune disease [1, 8].
A satisfactory treatment that would give a consistent, long-term
cure by repigmentation is still not available [1, 9]. Given the
autoimmune hypothesis of vitiligo pathogenesis, the use of
immunomodulating calcineurin inhibitors (i.e. pimecrolimus), in
addition to glucocorticoids which are also immunosuppressive, for
the treatment of vitiligo is reasonable [5, 6, 9]. We performed a
prospective study to evaluate efficacy of the 0.05% clobetasol
propionate and pimecrolimus in the treatment of vitiligo.
Topical corticosteroids are indicated and have been used during
the last three decades for the treatment of limited areas of
vitiligo [1, 6]. The ease of application, high rate of compliance,
and low cost are the advantages of topical corticosteroid therapy
for vitiligo treatment. Recurrence after cessation of treatment and
the side effects of the corticosteroids (i.e. skin atrophy,
telangiectasia, striae, and contact dermatitis) are the limiting
factors. These potential side effects should be monitored closely,
particularly in children [1, 9, 10]. Several studies have reported
use of topical steroids with varying degrees success in vitiligo
treatment [11]. Kumari et al. [12] conducted a study with
seventy-five patients with vitiligo who were treated with
intermittent topical applications of clobetasol propionate for
varying times within a three-year period. The best results occurred
in the facial lesions of Asian or black patients. Repigmentation of
90% to 100% was achieved in more than 80% of patients with vitiligo
of the face and more than 40% of patients with vitiligo on other
parts of the body. In another study by Geraldez et al. [13], 22 of
the 25 patients showed at least 90% repigmentation with clobetasol
propionate after six months of treatment. Clayton [14] obtained
partial repigmentation during 4 months’ treatment with clobetasol
propionate in twelve of twenty-three patients. In another clinical
study by Khalid et al. [5] by using 0.05% clobetasol propionate
cream, more than 50% repigmentation was obtained in most of the
patients involved.
Pimecrolimus (SDZ ASM 981), an ascomycin derivative, is one of
the new classes of immunomodulating macrolactams and was
specifically developed for the treatment of inflammatory skin
diseases. There has been a substantial interest in pimecrolimus
because of its significant anti-inflammatory and immunomodulatory
activities. It also has a low systemic immunosuppressive potential.
The mechanism of action of pimecrolimus is the blockage of T cell
activation [2, 3, 5]. Lepe et al. [15] conducted a double-blind
randomized trial of 0.1% tacrolimus vs. 0.05% clobetasol for the
treatment of childhood vitiligo. They reported 0.1% tacrolimus as
effective as clobetasol propionate for treatment of vitiligo. In
another study, Mayoral et al. [7] conducted a repigmentation of
vitiligo study with pimecrolimus cream. Travis et al. [16] found
successful treatment of vitiligo with 0.1% tacrolimus ointment.
Grimes et al. [17], Smith et al. [18] and Tanghetti [19] conducted
studies on patients with vitiligo who responded to treatment with
tacrolimus ointment. They concluded that tacrolimus ointment may be
an efficacious and safe treatment option for vitiligo.
We think that topical 1% pimecrolimus is as effective as
clobetasol propionate to restore skin discoloring in vitiligo.
Because it does not produce atrophy or other adverse effects,
topical 1% pimecrolimus may be very useful for patients and for
sensitive areas of the skin such as eyelids, and it should be
considered in other skin disorders currently treated with topical
steroids for prolonged periods. Further studies investigating the
safety and efficacy of topical 1% pimecrolimus ointment either as
monotherapy or in combination with other therapeutic measures are
warranted.
References
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