Vitiligo in Adults and Children PDF

See discussions, stats, and author profiles for this publication at: https://www.researchgate.
net/publication/50865594
Vitiligo in adults and children
Article in Clinical Evidence · March 2011

Source: PubMed
CITATIONS READS
8 290
1 author:
Rubeta Matin
Oxford University Hospitals NHS Trust
136 PUBLICATIONS 1,147 CITATIONS
SEE PROFILE
Some of the authors of this publication are also working on these related projects:
Accuracy of tests to diagnose skin cancer in adults View project
PROCLIPI View project
All content following this page was uploaded by Rubeta Matin on 23 May 2014.
The user has requested enhancement of the downloaded file.

Skin disorders
..................................................

Search date March 2010
Rubeta Matin
ABSTRACT
INTRODUCTION: Vitiligo is an acquired skin disorder characterised by white (depigmented) patches in the skin, due to the loss of functioning
melanocytes. The extent and distribution of vitiligo often changes during the course of a person's lifetime and its progression is unpredictable.
METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects
of medical treatments, and of ultraviolet light treatments, for vitiligo in adults and in children? We searched: Medline, Embase, The Cochrane
Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically, please check our website for
the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Adminis-
tration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 25 systematic reviews,
RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions:
corticosteroids (oral and topical), oral levamisole, topical immunomodulators, topical vitamin D analogues, ultraviolet A plus psoralen (PUVA
[oral or topical]), and ultraviolet B (narrowband).
QUESTIONS
What are the effects of medical treatments for vitiligo in adults?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
What are the effects of ultraviolet light treatments for vitiligo in adults?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
What are the effects of medical treatments for vitiligo in children?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
What are the effects of ultraviolet light treatments for vitiligo in children?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
INTERVENTIONS
MEDICAL TREATMENTS IN ADULTS MEDICAL TREATMENTS IN CHILDREN
Beneficial Beneficial
Corticosteroids (topical) in adults . . . . . . . . . . . . . . . 4 Corticosteroids (topical) in children . . . . . . . . . . . . 16
Unknown effectiveness Unknown effectiveness

Immunomodulators (topical) in adults . . . . . . . . . . . . 6 Immunomodulators (topical) in children . . . . . . . . . 17
Levamisole (oral) in adults . . . . . . . . . . . . . . . . . . . . 7 Vitamin D analogues (topical) in children . . . . . . . . 17
Unlikely to be beneficial Likely to be ineffective or harmful

Vitamin D analogues (topical) in adults* . . . . . . . . . . 8 Corticosteroids (oral) in children* . . . . . . . . . . . . . . 18
Likely to be ineffective or harmful UV TREATMENTS IN CHILDREN

Corticosteroids (oral) in adults* . . . . . . . . . . . . . . . 10 Likely to be beneficial
Ultraviolet B (narrowband) in children* . . . . . . . . . . 18
UV TREATMENTS IN ADULTS
Likely to be beneficial Likely to be ineffective or harmful
Oral PUVA in adults* . . . . . . . . . . . . . . . . . . . . . . . 11 PUVA (oral or topical) in children* . . . . . . . . . . . . . 19
Ultraviolet B (narrowband) in adults . . . . . . . . . . . . 14
To be covered in future updates
Unlikely to be beneficial Combination treatments of ultraviolet A and ultraviolet
B
Topical PUVA in adults . . . . . . . . . . . . . . . . . . . . . . 15
Footnote
*Categorisation based on consensus.
Key points
• Vitiligo is an acquired skin disorder characterised by white (depigmented) patches in the skin, caused by the loss
of functioning melanocytes.
Vitiligo patches can appear anywhere on the skin, but common sites are usually around the orifices, the genitals,
or sun-exposed areas such as the face and hands.
© BMJ Publishing Group Ltd 2011. All rights reserved. .................... 1 .................... Clinical Evidence 2011;03:1717
Skin disorders
The extent and distribution of vitiligo often changes during the course of a person's lifetime, and its progression
is unpredictable.
• Limited courses of potent topical corticosteroids in adults and children are a safe and effective therapy for localised
vitiligo and are often the first-choice treatment for this disorder.
The consensus is that adverse effects of oral corticosteroids in adults and children outweigh the benefits in vitiligo.
There is currently insufficient RCT evidence available to assess their effectiveness.
• Narrowband ultraviolet B in adults and children is considered a safe and effective therapy for moderate to severe
generalised vitiligo and is often the first-choice treatment for this disorder.
• Tacrolimus requires further evaluation, but is well tolerated in children and adults without the long-term adverse
effects of topical corticosteroids.
There is currently insufficient RCT evidence available to assess other immunomodulators in vitiligo.
• There is insufficient RCT evidence to fully assess levamisole or topical vitamin D analogues in vitiligo in children
or in adults.
• Consensus is that for the treatment of vitiligo in adults, oral psoralen plus ultraviolet A (PUVA) is effective, whereas
topical PUVA is unlikely to be effective. However, topical PUVA has fewer adverse effects than oral PUVA. PUVA
is likely to be harmful in children.
• Vitiligo patches in certain body areas, such as the acral sites, palms and soles, lips, mucosa, and nipples, and
segmental forms in any area are relatively resistant to all conventional treatment modalities.
In these cases, counselling and cosmetic camouflage become a priority, and often no treatments are advocated.
DEFINITION Vitiligo is an acquired skin disorder characterised by white (depigmented) patches in the skin,
caused by the loss of functioning melanocytes. The hair, and rarely the eyes, may also lose colour.
Vitiligo patches can appear anywhere on the skin, but common sites are usually around the orifices,
the genitals, or sun-exposed areas such as the face and hands. The disease is classified according
to its extent and distribution, and can be subdivided into generalised or localised. In practice, there
is considerable overlap between these types, and people often have vitiligo that cannot be cate-
gorised or that will change during the course of their lifetime. Therefore, for the purposes of this
review, we have included all people diagnosed with vitiligo of any type. Children were defined as
people aged 15 years and under.
INCIDENCE/ Vitiligo is estimated to affect 1% of the world's population, regardless of age, sex, and skin colour.
[1] [2]
PREVALENCE Anyone of any age can develop vitiligo, but it is very rarely reported to be present at birth.
In a Dutch study, 50% of people reported that the disease appeared before the age of 20 years.
[3] [4]
It is difficult to assess the true prevalence of vitiligo as the estimate of between 0.5% and
1% prevalence worldwide varies according to cultural and social differences. In countries where
more stigma is attached to the disease for cultural or social reasons or because it is more visible
because of dark skin colour, more people with the disease are likely to consult a doctor than in
other countries where this is not the case, thus reported estimates of prevalence may be high.
Figures as high as 8.8% have been reported in India where stigma associated with the disease is
[5]
high.
AETIOLOGY/ The aetiology of vitiligo is uncertain although genetic, immunological, biochemical (including oxidative
[1] [6] [7] [8]
RISK FACTORS stress), and neurogenic factors may interact to contribute to its development. Although
there are few epidemiological studies of vitiligo, it is believed that one third of people with vitiligo
[9]
report close family members affected by the disorder, suggesting that genetic factors have an
important role in the development of the disease, and this is supported by several genetic suscep-
[10] [11]
tibility studies. In particular, NALP-1 predisposes people to vitiligo as well as to various
[12]
autoimmune diseases. However, certain triggers (e.g., trauma to the skin, hormonal changes,
[13] [14] [4]
and stress) may be necessary for the disease to become apparent. Autoimmune
mechanisms are thought to be responsible in the pathogenesis of vitiligo (especially in generalised
[15]
or focal non-dermatomal vitiligo). This is supported by an increased incidence of antibodies
[16]
found in people with vitiligo. Furthermore, vitiligo is often associated with autoimmune diseases,
[17]
such as thyroid diseases, pernicious anaemia, and diabetes mellitus. Another indication that
vitiligo may be caused by an autoimmune mechanism is that melanocyte antibodies have been
[18] [19]
found in people with vitiligo, and their incidence correlates with disease activity. Involvement
of cellular immunity has been considered because T lymphocytes and macrophages in peri-lesional
[20] [21]
skin have also been frequently reported. Regarding segmental vitiligo, the neural hypothesis
[15]
suggests that it is caused by an accumulation of a neurochemical substance, which decreases
melanin production.
PROGNOSIS Vitiligo is not life threatening and is mostly asymptomatic, although it does increase the risk of
sunburn of the affected areas. The association of vitiligo and skin cancer remains an area of con-
© BMJ Publishing Group Ltd 2011. All rights reserved. ........................................................... 2
Skin disorders
[22]
troversy. The occurrence of skin cancer in long-lasting vitiligo is rare, although studies have
[23]
demonstrated increased PUVA-associated skin cancers. A Swedish study, which followed up
people treated with PUVA over 21 years, demonstrated an increased risk of squamous cell carci-
nomas. Furthermore, the risk of malignant melanoma increases among people treated with PUVA,
[24]
approximately 15 years after the first treatment. The effects of vitiligo can be both cosmetically
[25] [26] [27]
and psychologically devastating, resulting in low self-esteem and poor body image. The
anxieties regarding the disease occur against a background of a lack of understanding of the aeti-
[4]
ology and unpredictability of the course. Progression: The course of generalised vitiligo is un-
predictable: lesions may remain stable for years or (more commonly) may progress alternating
with phases of stabilisation, or (less commonly) may slowly progress for several years to cover the
[28]
entire body surface. In some instances, people may undergo rapid, complete depigmentation
[29]
within 1 or 2 years. In segmental vitiligo, lesions tend to spread rapidly at onset, and show a
[30]
more stable course thereafter. Predicting treatment responsiveness: Certain disease char-
acteristics help predict the outcome of treatment. Besides age, duration of disease, localisation,
[31] [32]
and extent of depigmentation, current disease activity should also be considered during
clinical decision making. This is essential in people with vitiligo vulgaris, when the disease activity
may fluctuate at a given time. Medical therapies and ultraviolet light treatments may be equally
[33]
effective in active and stable disease, but this may not be true for other treatments (e.g., surgery).
[34] [35] [36] [37] [38]
An associated skin manifestation is the phenomenon of "koebnerization",
where pressure or friction on the skin can cause new lesions or worsen existing ones. Koebnerization
[3] [39] [40]
occurs in most people with vitiligo, but elimination of frictional trauma, in the form of
occlusive garments and jewellery, prevents occurrence of new lesions in the cosmetically important
areas in cases of progressive vitiligo. Also, it has been reported that the presence of positive ex-
perimentally induced Koebner phenomenon is associated with active disease, but not necessarily
[41]
more severe disease (that is, in terms of the extent of depigmentation). The presence of
Koebner phenomenon may be a valuable clinical factor for assessing disease activity, and may
[41]
predict responsiveness to certain treatments. A case series reported that people who were
Koebner phenomenon positive (induced experimentally) were significantly more responsive to
topical fluticasone propionate combined with UVA therapy; but, for narrowband UVB treatment,
there was no difference in response, suggesting that people in active and stable stages of the
disease may respond equally well to UVB.
AIMS OF To prevent formation of new skin lesions of the vitiligo; to achieve repigmentation of involved skin,
INTERVENTION thus improving the quality of life, with minimal adverse effects of treatments.
OUTCOMES The degree of repigmentation that defines success has been arbitrarily set in many studies as
[42]
50% to 75% repigmentation, based largely on the global impression of the overall response.
Other outcomes include percentage repigmentation, development of new lesions of vitiligo, and
arrest of vitiligo spread. There is currently no validated quantitative scale that allows vitiligo to be
[43]
characterised parametrically, but a model was developed in one RCT of a novel parametric
tool, which, if used by clinicians, could provide a more quantifiable comparison of the effects of
different interventions. Adverse effects of treatments.
METHODS Clinical Evidence search and appraisal March 2010. The following databases were used to identify
studies for this systematic review: Medline 1966 to March 2010, Embase 1980 to March 2010, and
The Cochrane Database of Systematic Reviews 2010, March issue (1966 to date of issue). When
editing this review we used The Cochrane Database of Systematic Reviews 2010, issue 1. An
additional search within The Cochrane Library was carried out for the Database of Abstracts of
Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for re-
tractions of studies included in the review. Abstracts of the studies retrieved from the initial search
were assessed by an information specialist. Selected studies were then sent to the contributor for
additional assessment, using predetermined criteria to identify relevant studies. Study design criteria
for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language,
at least single blinded, and containing >20 individuals of whom >80% were followed up. There was
no minimum length of follow-up required to include studies. We excluded all studies described as
"open", "open label", or not blinded unless blinding was impossible. We included systematic reviews
of RCTs and RCTs where harms of an included intervention were studied applying the same study
design criteria for inclusion as we did for benefits. In addition we use a regular surveillance protocol
to capture harms alerts from organisations such as the FDA and the MHRA, which are added to
the reviews as required. To aid readability of the numerical data in our reviews, we round many
percentages to the nearest whole number. Readers should be aware of this when relating percent-
ages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed
a GRADE evaluation of the quality of evidence for interventions included in this review (see table,
p 25 ). The categorisation of the quality of the evidence (into high, moderate, low, or very low) reflects
the quality of evidence available for our chosen outcomes in our defined populations of interest.

Skin disorders
These categorisations are not necessarily a reflection of the overall methodological quality of any
individual study, because the Clinical Evidence population and outcome of choice may represent
only a small subset of the total outcomes reported, and population included, in any individual trial.
For further details of how we perform the GRADE evaluation and the scoring system we use, please
see our website (www.clinicalevidence.com).
QUESTION What are the effects of medical treatments for vitiligo in adults?
OPTION CORTICOSTEROIDS (TOPICAL) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Treatment success
Potent topical corticosteroids compared with placebo Potent corticosteroids are more effective at 2 to 21 months at
improving the proportion of people with >75% repigmentation of localised vitiligo (high-quality evidence).
Very potent topical corticosteroids compared with placebo We don't know whether very potent topical corticosteroids
are more effective at improving the number of people with >75% repigmentation of their localised vitiligo (low-quality
evidence).
Potent compared with very potent corticosteroids We don't know how effective potent topical corticosteroids and
very potent corticosteroids are, compared with each other, at improving outcomes in people with vitiligo (very low-
quality evidence).
Potent topical corticosteroids plus UVA compared with topical corticosteroids alone Topical fluticasone propionate
plus UVA may be more effective at increasing the proportion of people achieving >75% repigmentation of affected
lesions at 9 months (low-quality evidence).
Potent topical corticosteroids plus UVA compared with UVA alone We don't know how effective topical fluticasone
propionate plus UVA and UVA alone are, compared with each other, at increasing the proportion of people achieving
>75% repigmentation of affected lesions at 9 months (low-quality evidence).
Potent topical corticosteroids plus topical calcipotriol compared with topical calcipotriol alone Topical betamethasone
diproprionate cream (0.05%) plus topical calcipotriol (0.005%) may be more effective at 3 months at increasing the
proportion of adults and children who achieve >25% repigmentation (low-quality evidence).
Topical betamethasone dipropionate compared with topical calcipotriol Topical betamethasone dipropionate may be
more effective at 3 months at improving the proportion of adults and children who achieve >25% repigmentation
(very low-quality evidence).
Potent topical corticosteroids plus topical calcipotriol compared with potent topical corticosteroids We don't know
how effective potent topical corticosteroids plus topical calcipotriol and potent topical corticosteroids alone are,
compared with each other, at 3 months at improving the proportion of children and adults achieving >50% repigmen-
tation; however potent topical corticosteroids plus topical calcipotriol may be more effective at decreasing the mean
time to initial repigmentation (low-quality evidence).
Disease progression
Levamisole plus potent topical corticosteroids compared with potent topical corticosteroids alone We don't know how
effective levamisole plus topical mometasone furoate and topical mometasone furoate alone are, compared with
each other, at 6 months at preventing the development of new lesions in adults and children with slowly spreading
vitiligo (very low-quality evidence).
Note
We found no clinically important results from RCTs about different strengths of topical corticosteroids compared with
each other or comparing the efficacy of topical corticosteroids on different parts of the body in people with vitiligo.
Corticosteroid use is associated with skin atrophy, drug-induced acne, and hypertrichosis. There is consensus that
a limited course of potent and very potent topical corticosteroids in localised vitiligo is a useful first-line treatment,
particularly in newly formed lesions.
For GRADE evaluation of interventions for vitiligo, see table, p 25 .

[44] [4]
Benefits: We found two systematic reviews (search dates 1998 and 2009 ). The second systematic
[4]
review did not include a meta-analysis of the clinical outcomes of interest.
Potent topical corticosteroids versus placebo:

[44] [45] [46] [47]
The first systematic review identified three RCTs. The systematic review found
that, compared with placebo, potent topical corticosteroids significantly improved the proportion of
people with >75% repigmentation (3 RCTs, 48 people, ages not reported, localised vitiligo, treatment

Skin disorders
over 2–21 months; AR: 16/48 [33%] with potent corticosteroid v 0/48 [0%] with placebo; OR 14.32,
[44]
95% CI 2.45 to 83.72). The authors of the systematic review reported that potent topical corti-
costeroids were the most effective and safe therapies for localised vitiligo.
Very potent topical corticosteroids versus placebo:

[44] [45] [48]
The first systematic review identified two RCTs. It found no significant difference between
very potent topical corticosteroids and placebo in the proportion of people with >75% repigmentation
(2 RCTs, 33 people, age range not reported, localised vitiligo, no time frame for treatment reported;
AR: 2/33 [6%] with very potent corticosteroid v 2/33 [6%] with placebo; OR 1.00, 95% CI 0.16 to
[44]
6.21).
Potent versus very potent corticosteroids:

[44] [45]
The first systematic review identified one RCT. It found that very potent topical corticosteroids
were less effective than potent corticosteroids, although no direct comparison was made (3/10
[30%] with potent corticosteroid v 1/10 [10%] with very potent corticosteroid; significance not report-
ed). No comment was made by the authors as to the unusual result, but in view of the small size
of the study, further RCTs are needed to clarify the results.
Potent topical corticosteroids plus UVA versus topical corticosteroids alone:

[4]
The second systematic review identified one internally controlled trial (135 people, of whom 96
were evaluable; 18–80 years of age; 2 equal, symmetrical, bilateral lesions on the arms, legs, or
[49]
trunk). The trial compared topical fluticasone propionate (a potent corticosteroid, 0.05% flutica-
sone propionate cream applied at night) alone versus topical fluticasone propionate plus UVA (10-
2
J/cm exposure twice weekly for 20 minutes) in 67 people; and compared topical fluticasone propi-
onate plus UVA versus UVA alone in 68 people. It found that, compared with topical fluticasone
propionate alone, topical fluticasone propionate plus UVA significantly increased the proportion of
people achieving >75% repigmentation of affected lesions at 9 months (10/67 [15%] with fluticasone
propionate plus UVA v 2/67 [3%] with fluticasone propionate alone; P = 0.008; intention-to-treat
[ITT] analysis). Repigmentation was evaluated clinically by a single clinician against baseline
photographs (0% = no repigmentation, 75% = significant repigmentation, 100% = complete repig-
mentation). The trial did not explain why only 96 of the 135 enrolled participants were evaluable.
Potent topical corticosteroids plus UVA versus UVA alone:

[4]
The second systematic review identified one internally controlled trial (135 people, see above).
[49]
The trial compared topical fluticasone propionate alone versus topical fluticasone propionate
plus UVA in 67 people and compared topical fluticasone propionate plus UVA versus UVA alone
in 68 people. It found no significant difference between UVA alone and topical fluticasone propionate
plus UVA in the proportion of people achieving >75% repigmentation of affected lesions at 9 months
(AR: 8/68 [12%] with fluticasone propionate plus UVA v 3/68 [4%] with UVA alone; P = 0.06; ITT
analysis).
Potent topical corticosteroids plus topical calcipotriol versus topical calcipotriol alone:
[4]
The second systematic review identified one three-armed RCT (49 people with vitiligo affecting
5% of their skin) comparing topical calcipotriol ointment and betamethasone dipropionate in com-
[50]
bination or alone. The RCT found that topical betamethasone dipropionate cream (0.05% applied
twice daily) plus topical calcipotriol cream (0.005% applied twice daily) significantly increased the
proportion of people who achieved >25% repigmentation (assessed by clinical examination and
comparison with baseline photographs) at 3 months compared with topical calcipotriol cream alone
(31 people, age range 10–60 years, vitiligo affecting <5% body surface area; AR: 11/15 [73%] with
betamethasone dipropionate plus calcipotriol v 6/16 [37%] with calcipotriol alone; P <0.01).
Potent topical corticosteroids plus topical calcipotriol versus potent topical corticosteroids
alone:
See benefits of vitamin D analogues, p 8 .
Topical calcipotriol versus topical betamethasone dipropionate:

See benefits of vitamin D analogues, p 8 .
Potent topical corticosteroids plus levamisole versus potent topical corticosteroids alone:
See benefits of levamisole, p 7 .
Harms: Potent topical corticosteroids versus placebo:

The systematic review reported adverse effects from 6 case series (235 people, treatment duration
2–21 months). It found that potent topical corticosteroid use was associated with atrophy (5/250
[2%]), corticosteroid-induced acne (16/228 [7%]), and hypertrichosis (2/200 [1%]). The RCTs in-
[44]
cluded in the review gave no information on adverse effects.

Skin disorders
Very potent topical corticosteroids versus placebo:
One RCT identified by the systematic review found that all the participants treated with 0.05%
[48]
clobetasol propionate showed evidence of dermal atrophy. The other RCT identified by the
review found striking ecchymoses (1/20 [5%]) and rosacea (1/10 [10%]) with topical betamethasone.
[45]
It reported that the majority of people treated with topical corticosteroids (betamethasone or
clobetasol) had varying degrees of atrophy of the treated skin. The systematic review (search date
[44]
1998) reported adverse effects from 7 case series (277 people, treatment duration 2–12 months).
It found that very potent topical corticosteroid use was associated with atrophy (39/277 [14%]),
telangiectasia (8/267 [3%]), corticosteroid-induced acne (25/277 [9%]), and hypertrichosis (1/100
[1%]).
Potent topical corticosteroids plus UVA versus topical corticosteroids/UVA alone:

The RCT reported no significant skin atrophy or atrophogenic changes on visual examination over
[49]
9 months.
[4]
The RCT identified by the review reported hypertrichosis (1/15 [7%]) and lesional dryness (1/15
[7%]) in people treated with betamethasone dipropionate plus calcipotriol. The calcipotriol-treated
[50]
group reported peri-lesional hyperpigmentation (1/15 [7%]) and an irritant reaction (1/15 [7%]).
Potent topical corticosteroids plus topical calcipotriol versus potent topical corticosteroids
alone:
See harms of vitamin D analogues, p 8 .

See harms of vitamin D analogues, p 8 .
Potent topical corticosteroids plus levamisole versus potent topical corticosteroids alone:
See harms of levamisole, p 7 .
Comment: Clinical guide:

Observational evidence and decades of experience of their use in vitiligo have led to a consensus
that topical corticosteroids are effective. Most clinicians prescribe a course of a moderately potent
or potent corticosteroid for the face, and a potent or very potent topical corticosteroid for the body
as first-line treatment in focal or segmental vitiligo. However, the long-term use of topical corticos-
teroids is not advocated because the adverse effects are irreversible (e.g., skin atrophy, striae,
and telangiectasia). Long-standing lesions have been shown to be relatively resistant to local cor-
ticosteroid treatment — probably because of the depletion of melanocyte reserves in hair follicles.
[51] [52] [42]
Guidelines based on a systematic review suggested a combination of potent topical
corticosteroids plus UVA therapy for people with localised vitiligo. It has been suggested that a
combination of calcipotriol with potent topical corticosteroids may mitigate the local adverse effects
[50]
of topical corticosteroids alone, which may be particularly helpful in children.
OPTION IMMUNOMODULATORS (TOPICAL) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Treatment success
Pimecrolimus compared with placebo cream Topical pimecrolimus cream (1%) may be no more effective at 6 months
at reducing the size of lesions in children and adults with symmetrical vitiligo (very low-quality evidence).
Note
Topical pimecrolimus and tacrolimus may be associated with malignancy.
Benefits: Pimecrolimus versus placebo cream:

[4]
We found one systematic review (search date 2009), which identified one internally controlled
(left–right) RCT (20 people with symmetrical vitiligo, children and adults aged 12–60 years, mean
[53]
age 36.9 years) comparing pimecrolimus cream (1%) versus placebo. The RCT found no sig-
nificant difference in size of target lesion (assessed by planimetry) between topical pimecrolimus
cream (1% applied twice daily) and placebo cream (vehicle applied twice daily to equivalent con-
tralateral lesion) at 6 months (18 people, 2 people lost to follow-up, maximum duration of disease
2 years, with at least one new lesion in the last year; AR for mean difference in size of target lesion:
2 2 2 2 2
+90 mm [range –2046 mm to +509 mm ] with topical pimecrolimus v +114 mm [range –1230 mm
2
to +615 mm ] with placebo; P = 0.5).
Harms: Pimecrolimus versus placebo cream:

[53]
The RCT reported no skin atrophy or adverse effects.
Skin disorders
Comment: Pimecrolimus plus narrowband UVB versus narrowband UVB plus placebo cream:
[4]
The systematic review (search date 2009) identified one RCT (68 people, aged 15–72 years,
with stable symmetrical vitiligo) comparing pimecrolimus cream (1% applied twice daily) plus nar-
rowband UVB versus placebo cream (petroleum applied twice daily to equivalent contralateral lesion)
[54]
plus narrowband UVB. However, the follow-up in this RCT was low (50/68 [73%]). The RCT
found no significant difference in rates of repigmentation between the groups at 3 months' follow-
up. It reported only self-limiting erythema and pruritus as adverse effects with treatments. We will
[54]
address this intervention in full in future updates of this review.
Drug safety alerts:

The FDA issued a public health advisory to inform people about a potential malignancy risk from
the use of topical tacrolimus and pimecrolimus. This concern is based on information from animal
studies, case reports in a small number of people, and a theoretical risk of immunomodulators.
Clinical guide:
Pimecrolimus and tacrolimus are emerging as therapeutic alternatives for many immune-mediated
dermatoses (e.g., atopic eczema). Observational studies in vitiligo report similar efficacy to topical
[55]
corticosteroids, and they may be useful for treating facial skin or eyelids, where the risk of skin
atrophy from topical corticosteroids or phototoxicity from phototherapy is very high. Further RCT
evidence for their use in vitiligo is needed to confirm this, although from this small study it seems
that pimecrolimus is unlikely to be an effective treatment for vitiligo, either as an independent agent
[53] [54]
or as an adjunct to narrowband UVB treatment. RCTs investigating the effects of imiquimod
in vitiligo have not been undertaken.
OPTION LEVAMISOLE (ORAL) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Disease progression
Levamisole plus potent topical corticosteroids compared with potent topical corticosteroids alone We don't know how
effective levamisole plus topical mometasone furoate and topical mometasone furoate alone are, compared with
each other, at 6 months at preventing the development of new lesions in adults and children with slowly spreading
vitiligo (very low-quality evidence).
Note
We found no direct information from RCTs about the benefits of levamisole alone in repigmentation of skin.
Benefits: Levamisole versus placebo:

We found no RCTs determining the benefits of levamisole as a sole agent in the repigmentation
of involved skin.
Levamisole plus potent topical corticosteroids versus potent topical corticosteroids alone:
[4]
We found one systematic review (search date 2009), which found one poor-quality RCT, com-
paring oral levamisole (100–150 mg twice weekly) plus topical mometasone furoate 0.1% (applied
[56]
once daily) versus topical mometasone furoate 0.1% alone. The RCT found no significant dif-
ference between treatments at 6 months in preventing the development of new lesions in people
with "slowly spreading" vitiligo (1 RCT, 60 people [18 children and 42 adults], vitiligo covering <2%
body surface, generalised [acrofacial] and focal; AR for not developing new lesions: 19/23 [83%]
[56]
with levamisole plus mometasone v 12/20 [60%] with mometasone alone; P = 0.19). The study
defined "slowly spreading" as developing one to 5 new lesions in the previous month or 6 to 15
new lesions in the previous 3 months. No indication was given regarding the size of depigmented
areas, and the number of new areas was determined by one clinician. During the study, people
with rapid progression of their vitiligo (>10 new lesions in 1 month) were withdrawn from the study
(3/32 [9%] in the levamisole plus mometasone group v 1/28 [4%] in the mometasone group). In
addition, 10 people were lost to follow-up for unknown reasons, one person discontinued levamisole
owing to adverse effects (specific reason not reported), and two people did not complete 6 months
of treatment. The RCT was probably underpowered to show a significant difference owing to an
unexpected lack of disease progression in the control group.
Harms: Levamisole versus placebo:

We found no RCTs.
Levamisole plus topical potent corticosteroids versus potent topical corticosteroids alone:
The RCT found that, compared with mometasone alone, levamisole plus mometasone increased
nausea and vomiting but not abdominal pain (nausea/vomiting: 3/23 [13%] with levamisole plus
mometasone v 1/23 [4%] with mometasone alone; abdominal pain: 1/23 [4%] with levamisole plus
mometasone v 1/23 [4%] with mometasone alone; significance assessment not performed). The
Skin disorders
RCT also found that levamisole plus mometasone was associated with dizziness (3/23 [13%]),
anxiety (3/23 [13%]), change of taste (3/23 [13%]), insomnia (1/23 [4%]), and dyspepsia (2/23
[9%]), although no direct comparison was made with the group that received mometasone only.
[56]

In clinical practice, levamisole is sometimes used as an immunostimulant to prevent progression
of disease, in conjunction with other treatments (e.g., potent topical corticosteroids).
OPTION VITAMIN D ANALOGUES (TOPICAL) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Treatment success
Topical calcipotriol compared with placebo or no treatment Topical calcipotriol may be no more effective at improving
skin repigmentation in adults and children with localised and generalised vitiligo and symmetrical lesions (very low-
quality evidence).
Topical calcipotriol compared with topical betamethasone dipropionate Topical calcipotriol may be less effective at
3 months at improving the proportion of adults and children who achieve >25% repigmentation (very low-quality ev-
idence).
Topical calcipotriol plus potent topical corticosteroids compared with potent topical corticosteroids We don't know
how effective potent topical corticosteroids plus topical calcipotriol and potent topical corticosteroids alone are,
compared with each other, at 3 months at improving the proportion of children and adults achieving >50% repigmen-
tation; however potent topical corticosteroids plus topical calcipotriol may be more effective at decreasing the mean
time to initial repigmentation (low-quality evidence).
Topical calcipotriol plus potent topical corticosteroids compared with topical calcipotriol alone Topical betamethasone
diproprionate cream (0.05%) plus topical calcipotriol (0.005%) may be more effective at 3 months at increasing the
proportion of adults and children who achieve >25% repigmentation (low-quality evidence).
Topical calcipotriol plus PUVA compared with PUVA alone Topical calcipotriol plus PUVA may be more effective at
achieving complete repigmentation (75–100% repigmentation) of vitiliginous lesions in adults and children, and at
lowering the dose and number of exposures of UVA used (very low-quality evidence).
Topical calcipotriol plus UVB (narrowband) compared with UVB Topical calcipotriol plus UVB (narrowband) may be
no more effective at improving repigmentation (>25%) of lesions in adults and children with vitiligo (very low-quality
evidence).
Topical tacalcitol plus UVB (narrowband) compared with UVB (narrowband) Topical tacalcitol plus UVB (narrowband)
may be more effective at 6 months at improving repigmentation scores in people with generalised vitiligo and sym-
metrical lesions (low-quality evidence).
Note
We found no direct information from RCTs about whether topical tacalcitol is better than no active treatment or no
treatment in people with vitiligo.
Benefits: Topical calcipotriol versus placebo or no treatment:

We found no systematic review or RCTs of sufficient quality. We found one RCT (left–right, non-
blinded, comparative study of a mixed population of adults and children), which found no significant
difference in skin repigmentation at 3 to 6 months between topical calcipotriol and no treatment
(24 people, aged 5–59 years [14 people aged under 15 years], duration of disease 0.5–52 years,
[57]
localised and generalised vitiligo with symmetrical lesions). One child had 5% repigmentation
(% estimated by clinical examination only), one child had 20% repigmentation on the treatment
side and 20% repigmentation on the control side, and another had 30% repigmentation on the
treatment side and 10% repigmentation on the control side. It is likely that the results may be ex-
trapolated to adults and other children, but they would need to be confirmed by larger numbers of
both adults and children.

[4]
We found one systematic review (search date 2009), which identified one three-armed RCT (49
people with vitiligo affecting 5% of their skin) comparing topical calcipotriol ointment and betametha-
[50]
sone dipropionate in combination or alone. The RCT found that proportionally fewer people
achieved >25% repigmentation (assessed by clinical examination and comparison with baseline
photographs) with topical calcipotriol cream (0.005% applied twice daily) compared with topical
betamethasone dipropionate cream (0.05% twice daily) at 3 months (34 people, age range 10–60
Skin disorders
years; AR: 6/16 [38%] with calcipotriol v 9/18 [50%] with betamethasone dipropionate; P value not
reported).
Topical calcipotriol plus potent topical corticosteroids versus potent topical corticosteroids
alone:
[4]
We found one systematic review (search date 2009), which identified one three-armed RCT (49
people with vitiligo affecting 5% of their skin) comparing topical calcipotriol ointment and betametha-
[50]
sone dipropionate in combination or alone. The RCT found no significant difference at 3 months
in people achieving >50% repigmentation (assessed by clinical examination and comparison with
baseline photographs) with topical calcipotriol (0.005% applied twice daily) plus topical betametha-
sone dipropionate cream (0.05% applied twice daily) compared with betamethasone dipropionate
cream alone (30 people, age range 10–60 years; AR: 4/15 [27%] with calcipotriol plus betametha-
sone dipropionate v 2/15 [13%] with betamethasone dipropionate alone; P >0.1). However, the
RCT may have been too small to detect differences between groups. No one in the RCT achieved
>75% repigmentation. The RCT found a significantly decreased mean time to initial repigmentation
at 3 months with topical calcipotriol plus topical betamethasone dipropionate compared with topical
betamethasone dipropionate alone (mean time: 5.17 ± 2.4 weeks with calcipotriol plus betametha-
sone dipropionate v 9.04 ± 2.0 weeks with betamethasone propionate; P <0.01).
Topical calcipotriol plus potent topical corticosteroids versus topical calcipotriol alone:
See benefits of corticosteroids (topical) in adults, p 4 .
Topical calcipotriol plus PUVA versus PUVA alone:

[4]
We found one systematic review (search date 2009), which identified one internally controlled
RCT (35 people, age range 16–64 years, duration of disease 2–20 years, 10–50% body surface
involvement, treatment continued until cosmetically acceptable pigmentation was achieved in re-
sponsive areas, and stopped when repigmentation ceased, clinician assessment of repigmentation
at weekly intervals, UVA dosage determined according to minimal erythema doses of UVA (range
2 [58]
0.75–10.2 J/cm ). It found that calcipotriol cream (0.05 mg/kg) plus PUVA (oral methoxsalen
0.5–0.6 mg/kg plus UVA units) twice weekly was more effective in reaching "complete repigmenta-
tion" (75–100% repigmentation) of vitiliginous lesions compared with PUVA plus placebo (AR:
17/35 [49%] with calcipotriol plus PUVA v 4/35 [11%] with placebo plus PUVA; P value not reported).
For complete repigmentation, the mean cumulative UVA dose and number of UVA exposures were
significantly lower for the calcipotriol-treated side than for the placebo-treated side (mean cumulative
2 2
UVA dose: 232 J/cm for the calcipotriol-treated side v 260 J/cm for the placebo-treated side;
number of UVA exposures: 30 for the calcipotriol-treated side v 27 for the placebo-treated side;
2
P = 0.001), which equated to an approximately 26 J/cm lower cumulative UVA dosage, and ap-
proximately three fewer treatment exposures.
Topical calcipotriol plus UVB (narrowband) versus UVB (narrowband) alone:

[4] [59]
We found one systematic review (search date 2009), which found one RCT, and we found
[60]
one additional RCT.
The RCT (40 people with vitiligo) identified by the review compared topical calcipotriol plus narrow-
[59]
band UVB versus narrowband UVB alone. The RCT found no significant difference in achieving
>25% repigmentation after 30 treatments (clinical response assessed by photographs and visual
2 2
scoring) between narrowband UVB (initial dose 0.1 J/cm followed by increments of 0.05 J/cm as
tolerated, 3 times weekly) plus calcipotriol (0.05% ointment applied twice daily after phototherapy)
and narrowband UVB alone (34 people, aged 17–26 years, stable vitiligo affecting >10% of the
body surface area; AR: 10/13 [77%] with calcipotriol plus narrowband UVB v 19/24 [79%] with
narrowband UVB alone; P value not reported).
[60]
The additional RCT was a left–right comparison RCT, which found no significant difference in
repigmentation of lesions between calcipotriol (0.005% cream applied 2 hours before and after
2
UVB session) plus narrowband UVB (initial dose 0.25 J/cm , increased by 20% for each treatment)
and narrowband UVB alone (evaluated by blinded independent observers comparing photographs
with baseline at 24-session intervals) for a total of 96 treatment sessions (20 people comprising
85 reference lesions, age range 14–49 years, range of disease duration 3–300 months, extensive
vitiligo affecting >30% body surface area, bilateral symmetrical distribution, numbers not reported;
2
P >0.05). The mean total UVB dose delivered was 110 ± 45 J/cm . The authors felt that the 20%
increments in the UVB treatment regimen were too aggressive, thus inhibiting a potential beneficial
response of the addition of calcipotriol. The total number of people in the RCT achieving >50%
repigmentation, irrespective of calcipotriol, was 11/20 [55%].
Topical tacalcitol plus narrowband UVB versus narrowband UVB alone:

We found one systematic review (search date 2009), which found one RCT (32 people with gener-
alised vitiligo and symmetrical lesions) comparing topical tacalcitol plus narrowband UVB versus
Skin disorders
[61]
narrowband UVB alone. The RCT found significantly higher repigmentation scores at 6 months
(clinical response assessed by single-blinded observer at baseline and end of study visually) in
people treated with narrowband UVB (starting with 70% minimal erythema dose followed by 10–30%
2
increments as tolerated) plus topical tacalcitol ointment (dose 10 mg/4 cm applied once daily to
assigned areas as measured by microdosator) compared with narrowband UVB alone (absolute
numbers not reported; P <0.0005).
Harms: Topical calcipotriol versus placebo or no treatment:

We found no RCTs of sufficient quality. The RCT (left–right, non-blinded, comparative study of a
[57]
mixed population of adults and children) gave no information on adverse effects.

[4]
The RCT identified by the review reported significantly fewer adverse effects with calcipotriol
compared with betamethasone dipropionate (peri-lesional hyperpigmentation 1/15 [7%] and an ir-
ritant reaction 1/15 [7%] with calcipotriol v lesional atrophy 5/15 [33%], lesional soreness 4/15
[27%], lesional dryness 1/15 [7%], and hypertrichosis 1/15 [7%] with betamethasone dipropionate;
[50]
P <0.05).
Topical calcipotriol plus potent topical corticosteroids versus potent topical corticosteroids:
[4]
The RCT identified by the review reported a significantly decreased number of adverse effects
with betamethasone dipropionate plus calcipotriol compared with betamethasone dipropionate
alone (hypertrichosis 1/15 [7%] and lesional dryness 1/15 [7%] with calcipotriol plus betamethasone
dipropionate v lesional atrophy 5/15 [33%], lesional soreness 4/15 [27%], lesional dryness 1/15
[50]
[7%], and hypertrichosis 1/15 [7%] with betamethasone dipropionate alone; P <0.05).
Topical calcipotriol plus potent topical corticosteroids versus topical calcipotriol alone:
See harms of corticosteroids (topical) in adults, p 4 .
Topical calcipotriol plus PUVA versus PUVA alone:

[4]
The RCT identified by the review reported mild to moderate erythema, xerosis, and itching for
both active treatment and placebo (2/35 [6%] with calcipotriol v 3/35 [9%] with placebo; significance
[58]
not stated).
Topical calcipotriol plus UVB (narrowband) versus UVB (narrowband) alone:

[4] [59]
The RCT, identified by the review reported transient itching and erythema. The additional
[60]
RCT reported erythema, irritation, and mild vesiculation (1/20 [5%]) in the calcipotriol-treated
sides.
Topical tacalcitol plus narrowband UVB versus narrowband UVB:

[4]
The RCT identified by the review reported minimal adverse effects (mild erythema and itching)
[61]
in the combination therapy group.
Comment: Topical tacalcitol plus sunlight (UVA) versus placebo plus sunlight (UVA):
[4]
The systematic review (search date 2009) identified one RCT (80 people with non-segmental
vitiligo) comparing topical tacalcitol (applied at night) plus sunlight (30 minutes exposure daily)
[62]
versus placebo plus sunlight. The RCT found no significant difference in overall repigmentation
rates between the two groups at 16 weeks. All responses obtained with tacalcitol and sunlight were
<25% repigmentation of treated areas compared with baseline (graded as poor).The RCT reported
higher rates of transient erythema and mild contact dermatitis with tacalcitol plus sunlight compared
[62]
with placebo plus sunlight. It found similar rates of itching between groups. We will assess this
comparison in full in future updates of this review.
Clinical guide:
In the treatment of psoriasis, calcipotriol has a light-saving effect when used in combination with
UVB, and response is achieved at a lower dose of UVB, but calcipotriol does not increase the
overall effectiveness of UVB treatment. However, the role of tacalcitol in the treatment of vitiligo is
yet to be determined. We found no RCTs investigating the effects of other topical vitamin D (cal-
citriol) in vitiligo.
OPTION CORTICOSTEROIDS (ORAL) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
We found no direct information from RCTs about oral corticosteroids in the treatment of people with vitiligo.
There is consensus that the adverse effects associated with oral corticosteroids far outweigh any benefit
that may be achieved in people with vitiligo.
© BMJ Publishing Group Ltd 2011. All rights reserved. .......................................................... 10

Skin disorders
Benefits: We found no systematic review or RCTs.
Harms: We found no RCTs. One case series (29 people with vitiligo [24 with generalised vitiligo and 5 with
[63]
acrofacial vitiligo, and 25 with progressive and 4 with stable disease]; age range 20–54 years)
found that one or more adverse events were reported in 20/29 [69%] participants at a mean treatment
period of 5.2 weeks, including weight gain, arterial hypertension, insomnia, acne, agitation, men-
strual disturbance, and hypertrichosis.

Further RCTs into the effects of oral corticosteroids are unlikely to be undertaken. On the basis of
[63]
observational evidence and experience, oral corticosteroids may arrest the progression of vitiligo,
but fail to induce repigmentation. However, there is consensus that adverse events are common
and can be severe; oral corticosteroids are therefore not commonly used in practice.
QUESTION What are the effects of ultraviolet light treatments for vitiligo in adults?
OPTION PUVA (ORAL) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Treatment success
Methoxsalen plus UVA compared with UVA alone Methoxsalen plus UVA may be no more effective at achieving
>75% repigmentation of all vitiliginous macules at 2 years in adults and children (very low-quality evidence).
Trioxysalen plus UVA compared with UVA alone Trioxysalen plus UVA may be no more effective at achieving >75%
repigmentation of all vitiliginous macules at 2 years in adults and children (very low-quality evidence).
Unsubstituted PUVA compared with UVA alone We don't know whether PUVA is more effective at improving repig-
mentation of affected lesions in adults and children at 18 to 24 months (very low-quality evidence).
Oral PUVA compared with topical PUVA Oral PUVA may be no more effective at 18 months at achieving >50%
repigmentation of all vitiliginous macules (low-quality evidence).
Different oral PUVA derivatives compared with each other Different derivatives and doses of psoralens (methoxsalen,
unsubstituted psoralen, trioxysalen) plus UVA are equally effective at improving repigmentation of >75% of all vitilig-
inous macules at 2 years (moderate-quality evidence).
Oral PUVA compared with UVB (narrowband) We don't know how effective oral PUVA and UVB (narrowband) are,
compared with each other, at improving repigmentation rates in adults with vitiligo (low-quality evidence).
Methoxsalen plus trioxysalen plus UVA compared with different psoralen derivatives plus UVA Methoxsalen plus
trioxysalen plus UVA may be more effective than unsubstituted PUVA at improving repigmentation of >75% of all
vitiliginous macules at 2 years (low-quality evidence).
Oral PUVA compared with oral PUVB (broadband) Oral PUVB (broadband) may be less effective in producing 50%
to 60% repigmentation of extensive vitiligo in adults and children (very low-quality evidence).
Note
There is consensus that PUVA is effective for vitiligo.

[44] [4]
Benefits: We found two systematic reviews (search dates 1998 and 2009 ). They found that the quality
of the methods and reporting of included studies was poor.
Methoxsalen plus UVA versus UVA alone:

Both reviews identified one RCT, which compared sunlight plus oral methoxsalen, sunlight plus
oral unsubstituted psoralen, sunlight plus oral trioxysalen, and placebo over 2 years (596 people,
of whom 366 completed 2 years' treatment with follow-up; age range 12–70 years; most people
with generalised vitiligo with 10–70% skin involvement; duration 1–50 years; people were exposed
in prone and supine positions to the sun [2 hours post-ingestion] for 45–60 minutes in gradually
increasing doses, three times weekly). The degree of repigmentation was rated visually by two in-
dependent investigators against photographs at enrolment and at 6-monthly intervals. People were
randomly assigned to one of the following groups: methoxsalen 0.3 mg/kg (47 people), methoxsalen
0.6 mg/kg (49 people), trioxysalen 0.8 mg/kg (39 people), trioxysalen 1.8 mg/kg (61 people), tri-
oxysalen 3.6 mg/kg (43 people), methoxsalen 0.3 mg/kg plus trioxysalen 1.8 mg/kg (55 people),
unsubstituted psoralen 0.6 mg/kg (35 people), unsubstituted psoralen 1.2 mg/kg (37 people), and
[64]
placebo (24 people). All 8 groups were exposed to UVA (sunlight). The RCT identified by the

Skin disorders
systematic reviews found no significant difference in repigmentation of >75% of all vitiliginous
[64]
macules at 2 years between oral methoxsalen plus UVA and UVA alone (see table 1, p 23 ).
Trioxysalen plus UVA versus UVA alone:

[64]
The RCT identified by the systematic reviews (see above) found no significant difference in
repigmentation of >75% of all vitiliginous macules at 2 years between oral trioxysalen plus UVA
[64]
and UVA alone (see table 1, p 23 ).
Unsubstituted PUVA versus UVA alone:

[4] [44] [64] [65]
The systematic reviews both identified two RCTs. Pooled results from the first
[44]
systematic review found that, compared with sunlight alone, oral unsubstituted PUVA signifi-
cantly improved repigmentation of affected skin (97 people; age range not reported; generalised
vitiligo; exposure to midday sun 2 hours after oral psoralen; exposure time increased according to
tolerance; degree of repigmentation assessed visually by observer and participant at 18 months
[65]
in one RCT and by comparison with initial photographs by two independent investigators at 2
[64]
years in the other; 2 RCTs; AR: 13/46 [28%] with oral unsubstituted PUVA v 0/51 [0%] with
UVA alone; OR 19.87, 95% CI 2.37 to 166.32; P value not reported). The second RCT identified
by the reviews found no significant difference in repigmentation of >75% of all vitiliginous macules
[4]
at 2 years between oral PUVA (at any dose) and UVA alone (see table 1, p 23 ).
Oral PUVA versus topical PUVA:

[4] [65]
The systematic review identified one RCT. It found no significant difference between oral
and topical PUVA (dose and psoralen derivative not specified) in achieving repigmentation in >50%
of all vitiliginous macules at 18 months (AR: 2/20 [10%] with oral unsubstituted PUVA v 2/18 [11%]
with topical psoralen; RR 0.90, 95% CI 0.14 to 5.74; P value not reported).
Different oral PUVA derivatives versus each other:

[4]
The systematic review identified one RCT, which found no significant difference between different
derivatives and doses of psoralen (methoxsalen, unsubstituted psoralen, trioxysalen) plus UVA
[64]
versus each other in repigmentation of >75% of all vitiliginous macules at 2 years (see table
2, p 24 ). The same RCT found that a combination of methoxsalen plus trioxysalen plus UVA sig-
nificantly improved the repigmentation of >75% of vitiliginous macules at 2 years when compared
with UVA alone, but was no more effective compared with methoxsalen plus UVA or trioxysalen
plus UVA, and less effective compared with unsubstituted PUVA (see table 3, p 24 ).
Oral PUVA versus UVB (narrowband):

[4]
The systematic review identified one RCT (56 people, aged 18 years or older, with symmetrical
vitiligo affecting 2–70% of body surface area), which compared oral PUVA (8-methoxypsoralen
2 2
25 mg/m or 5-methoxypsoralen 50 mg/m given 3 hours before phototherapy with UVA given at
2 2
an initial dose of 0.5 J/cm with 0.25 J/cm increments) twice weekly versus narrowband UVB (initial
2 [66]
dose 0.1 J/cm with 20% increments) twice weekly. The RCT found no significant difference
in repigmentation rates with oral PUVA compared with narrowband UVB at the end of treatment
(AR: 16/25 [64%] with oral PUVA v 9/25 [36%] with narrowband UVB; RR 0.50, 95% CI 0.10 to
2.49; P = 0.4). However, the RCT commented that people in the oral PUVA-treated group received
a significantly smaller median number of treatments compared with the narrowband UVB-treated
group, and so results should be interpreted with caution.
Oral PUVA versus oral PUVB (broadband):

[67]
We found one left–right comparison RCT, which found that fewer treatments with oral
2
methoxsalen (0.7 mg/kg) plus UVA (PUVA 320–400 nm; initial dose of UVA 0.5 J/cm increased
2
by 0.5 J/cm at alternate sessions) were required compared with oral methoxsalen plus broadband
2 2
UVB (PUVB 290–320 nm; initial dose of UVB of 0.03 J/cm increased by 0.03 J/cm at each session)
to produce 50% to 60% repigmentation (evaluated clinically by 5 clinicians, 1 of whom was blinded)
at weekly intervals for 30 sessions of treatment (24 people, age range 8–50 years, 3 sessions
weekly, extensive vitiligo affecting >30% body surface area, bilateral symmetrical distribution; AR:
15/22 [68%] with PUVA v 11/22 [50%] with PUVB; P value not reported). The mean number of
sessions needed to achieve 50% to 60% repigmentation was 25 ± 4 with PUVA and 26 ± 3 for
PUVB. To achieve 50% to 60% repigmentation of vitiligo, the mean cumulative dose of UVA was
2 2
45 ± 16 J/cm , and for UVB was 4.6 ± 1.9 J/cm .
Oral PUVA plus topical calcipotriol versus PUVA alone:

See benefits of vitamin D analogues in adults, p 8 .
Harms: Methoxsalen plus UVA versus UVA alone:

One RCT found that methoxsalen plus UVA increased nausea and pruritus compared with UVA
alone (nausea: 20% with methoxsalen plus UVA v 10% with UVA alone; pruritus: 20% with
methoxsalen plus UVA v 10% with UVA alone; significance assessment not performed, absolute
Skin disorders
numbers not reported). It also reported that methoxsalen was associated with gastrointestinal dis-
[64]
comfort (8%).
Trioxysalen plus UVA versus placebo:

[64]
The RCT reported fewer adverse effects with trioxysalen compared with all other psoralen
derivatives. It reported dizziness (7/58 [12%]), pruritus (5/58 [9%]), and nausea (2/58 [3%]) across
both groups, but reported a greater number of adverse effects with the higher dose of trioxysalen
compared with the lower dose.
Unsubstituted PUVA versus UVA alone:

[4] [42] [64] [65] [65]
The systematic reviews identified two RCTs. The first RCT did not search for
or report any adverse effects. The second RCT found that a similar proportion of people taking
unsubstituted psoralen 0.6 mg/kg and placebo had nausea and pruritus (nausea: 9% with unsub-
stituted psoralen v 10% with UVA alone; pruritus: 9% with unsubstituted psoralen v 7% with UVA
alone; significance assessment not performed, absolute figures not reported).The RCT also reported
that people taking unsubstituted psoralen experienced headaches (14%), dizziness (9%), and
miscellaneous complaints (14%). People receiving a higher unsubstituted psoralen dose (1.2 mg/kg)
[64]
were not evaluated.

[65]
The RCT did not search for or report any adverse effects.
Different psoralen derivatives plus UVA versus each other:

[64]
The RCT reported nausea (6/35 [17%]), pruritus (13/35 [37%]), dizziness (2/35 [6%]), and
headaches (1/35 [3%]) in people given the combination of methoxsalen plus trioxysalen. The
placebo group reported nausea (2/24 [8%]) and pruritus (1/24 [4%]). The methoxsalen groups re-
ported dizziness (8/96 [8%]), pruritus (19/96 [20%]), nausea (19/96 [20%]), and vague gastrointestinal
discomfort (8/96 [8%]). The trioxysalen groups reported dizziness (7/58 [12%]), pruritus (5/58 [9%]),
and nausea (2/58 [3%]). The low-dose psoralen group reported dizziness (3/35 [9%]), pruritus (3/35
[9%]), nausea (3/35 [9%]), headaches (5/35 [14%]), and miscellaneous complaints (5/35 [14%]).
Oral PUVA versus UVB (narrowband):

The RCT reported that erythema occurred significantly more often with oral PUVA compared with
UVB (narrowband) (24/25 [96%] with oral PUVA v 17/25 [68%] with narrowband UVB; P = 0.02).
[66]
Oral PUVA versus oral PUVB (broadband):

[67]
We found no systematic review on the harms of broadband UVB. One RCT comparing broadband
oral PUVB versus PUVA reported a phototoxic reaction with both treatments (4/22 [18%] with
broadband oral PUVB v 5/22 [23%] with PUVA) and skin thickening (6/22 [27%] with broadband
oral PUVB v 6/22 [27%] with PUVA).
Oral PUVA plus topical calcipotriol versus PUVA alone:

See harms of vitamin D analogues in adults, p 8 .
Comment: Prognostic factors:

The following prognostic factors are thought to predict improved response rates independently of
the psoralen derivative used: duration of therapy (duration exceeding 9–12 months correlated with
improved repigmentation rate), regular treatment, minimal phototoxicity, and vitiligo site (face and
neck responded best, followed by trunk and back, whereas bony prominences responded worst).
Treatment duration:
Long-term therapy is needed for successful repigmentation of vitiliginous skin. Between 15 and 25
treatments are necessary before perifollicular repigmentation is apparent. Between 100 and 300
treatments are required for complete repigmentation of the neck, trunk, and proximal limbs, with
the face repigmenting faster. At 4 years' follow-up, people neither developed cutaneous malignancies
[64]
nor developed abnormal liver function values.
UVA source:
[64] [68]
It is important to remember that, in studies using sunlight as the source of UVA, variable
factors (compliance, degree of sun exposure, country where the trial was conducted) can limit the
interpretation and applicability of results. Where possible, reliable forms of light therapy such as
UV light devices should be used in trials, but this is not always accessible or feasible in resource-
poor countries. No RCTs have been carried out using different UVA light devices.

Skin disorders
Clinical guide:
The consensus among clinicians is that oral PUVA is effective for vitiligo, and that methoxsalen is
the most effective psoralen derivative. Methoxsalen and 5-methoxypsoralen are the most commonly
used psoralen derivatives in UK; however, no RCTs studying 5-methoxypsoralen or comparing it
with methoxsalen in vitiligo were found. 5-Methoxypsoralen is not available in the US, but is thought
to be associated with a lower incidence of phototoxicity and gastrointestinal adverse effects com-
pared with methoxsalen. Trioxysalen is extremely phototoxic for some individuals, and this limits
its use. Individualisation of treatment is essential. None of the psoralen derivatives overcomes the
limitation of poor response of the fingers, toes, palms, soles, nipples, ankles, and lips. There is
limited evidence for the use of broadband UVB in vitiligo. RCTs would be feasible and should be
undertaken, especially comparison studies with narrowband UVB.
OPTION ULTRAVIOLET B (NARROWBAND) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Treatment success
Narrowband UVB compared with placebo Narrowband UVB may be more effective at 6 months at increasing mean
repigmentation of affected lesions in adults with vitiligo (low-quality evidence).
Compared with topical PUVA We don't know whether narrowband UVB is more effective at 4 months at improving
repigmentation of vitiliginous lesions (very low-quality evidence).
Narrowband UVB compared with oral PUVA We don't know how effective oral PUVA and narrowband UVB are,
compared with each other, at improving repigmentation rates in adults with vitiligo (low-quality evidence).
Narrowband UVB plus topical calcipotriol compared with UVB Topical calcipotriol plus narrowband UVB may be no
more effective at improving repigmentation (>25%) of lesions in adults and children with vitiligo (very low-quality
evidence).
Narrowband UVB plus topical tacalcitol compared with narrowband UVB Topical tacalcitol plus narrowband UVB
may be more effective at 6 months at improving repigmentation scores in people with generalised vitiligo and sym-
metrical lesions (low-quality evidence).
Benefits: Narrowband ultraviolet B (UVB) versus placebo:

We found one internally controlled trial, which found that, compared with placebo, narrowband
UVB significantly increased mean repigmentation of affected lesions after 6 months (70% minimal
erythema doses, increased by 10% increments, 3 times weekly or 60 treatments; 22 people, age
range 23–77 years; duration of disease range 4–51 years; extent of vitiligo determined by Vitiligo
Area Scoring Index [developed in this study as product of area of vitiligo in hand units and extent
of residual depigmentation] and validated by global participant and clinician scoring using baseline
photographs; AR: 43% repigmentation with narrowband UVB v 3% repigmentation with placebo;
[43]
P <0.001; absolute numbers not reported). Lower extremities responded best, but feet responded
worst.
Narrowband UVB versus topical PUVA:

See benefits of topical PUVA in adults, p 15 .
Narrowband UVB versus oral PUVA:

See benefits of oral PUVA in adults, p 11 .
Narrowband UVB plus vitamin D analogues versus narrowband UVB alone:

See benefits of vitamin D analogues in adults, p 8 .
Harms: Narrowband UVB versus placebo:

We found one RCT, which reported hyperpigmentation with narrowband UVB, resulting in one
[43]
person withdrawing from the study, and mild phototoxic effects.

[69]
The RCT did not report any adverse effects with narrowband UVB treatment.
Narrowband UVB versus oral PUVA:

See harms of oral PUVA in adults, p 11 .
Narrowband UVB plus vitamin D analogues versus narrowband UVB alone:

See harms of vitamin D analogues in adults, p 8 .

Skin disorders
Despite only weak RCT evidence to support its use, narrowband UVB is considered safe and ef-
fective by clinicians in the treatment of generalised vitiligo. Because it has relatively few adverse
effects, it is considered to be the first-line treatment of choice for people with moderate or severe
[29] [52]
generalised disease. One report recommended (on the basis of a number of case series
[42]
only) a minimum treatment duration of 6 months with responsive people, with a maximum
treatment duration of 24 months. After the first course of 1 year, a resting period of 3 months was
recommended, to minimise the annual cumulative dose of UVB. Further research is necessary to
determine the relative effectiveness of different treatment regimens.
OPTION PUVA (TOPICAL) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Treatment success
Compared with no treatment Topical PUVA is no more effective at 18 months at achieving >50% repigmentation of
vitiliginous lesions (moderate-quality evidence).
Compared with oral PUVA Topical PUVA may be no more effective at 18 months at achieving >50% repigmentation
of all vitiliginous macules in adults and children (low-quality evidence).
Compared with narrowband UVB We don't know whether topical PUVA is more effective at 4 months at improving
repigmentation of vitiliginous lesions in adults and children (very low-quality evidence).
Benefits: Topical PUVA versus no treatment:

[4]
We found one systematic review (search date 2009), which identified one RCT (88 people; age
range not reported; generalised vitiligo). The RCT had 4 arms: oral PUVA (sunlight), topical unsub-
stituted PUVA (sunlight), oral PUVA (sunlight) plus triamcinolone, and no treatment (cosmetic
[65]
camouflage). It found no significant difference between topical unsubstituted PUVA (dosage
and brand of psoralens not reported; sunlight) and no treatment in the repigmentation of >50% of
vitiliginous lesions at 18 months (exposure to midday sun immediately after topical application of
psoralen, with increasing exposure time according to the person's tolerance of sunlight; degree of
repigmentation assessed visually by observer and participant; AR: 2/18 [11%] with topical PUVA
v 0/27 [0%] with placebo; RR 7.37, 95% CI 0.37 to 145.06).

See benefits of oral PUVA, p 11 .
Topical PUVA versus narrowband UVB:

We found one quasi-RCT (106 people, age range 7–70 years [mean age 36.7 years with PUVA
and 36 years with UVB], active and generalised vitiligo of more than 3 months' duration, 10–50%
[69]
body surface involved), which compared topical unsubstituted PUVA 0.005% versus narrowband
UVB 311 nm treatment twice weekly for 4 months (psoralen administered 15 minutes before UVA;
2
UVA initial dose 0.5 J/cm , increased in 20% increments until erythema and then continued at
2
same dose; narrowband UVB initial dose 0.075 J/cm , increased in 20% increments until erythema).
It found that, compared with narrowband UVB, topical PUVA reduced repigmentation of vitiliginous
lesions at 4 months (treatments assigned alternately; assessment of response by two uninvolved
blinded clinicians using total-body photographs at each visit by means of planimetry: AR: 13/28
[46%] with topical PUVA v 52/78 [67%] with narrowband UVB, significance assessment not per-
[69]
formed). The study reported that, in general, better repigmentation was observed on the face
than on the trunk, with very little on the extremities. There was no subgroup analysis performed.
Harms: Topical PUVA versus placebo:

[65]
The first RCT did not search for or report any adverse effects.

See harms of oral PUVA, p 11 .
Topical PUVA versus UVB (narrowband):

The RCT reported erythema (3/28 [11%]), scaling (3/28 [11%]), and itching (3/28 [11%]) with PUVA.
[69]
Difficulties in uniformly applying the aqueous gel resulted in linear burns of the vitiliginous skin
as well as of the normally pigmented skin. In pigmented skin, hyperpigmented stripes remained.

Studies in psoriasis suggest that topical PUVA is the more acceptable treatment because of nausea
as an adverse effect of oral PUVA, and because of a lower cumulative radiation dose with topical
[70]
PUVA. Despite weak evidence for the use of both oral and topical psoralens in vitiligo, clinicians
Skin disorders
are more likely to recommend oral psoralens over topical psoralens because of the consensus that
oral PUVA is more effective than topical PUVA.
QUESTION What are the effects of medical treatments for vitiligo in children?
OPTION CORTICOSTEROIDS (TOPICAL) IN CHILDREN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Treatment success
Clobetasol propionate compared with PUVA Clobetasol propionate is more effective at increasing the proportion of
children achieving >75% repigmentation at 6 months (moderate-quality evidence).
Clobetasol propionate compared with topical tacrolimus We don't know how effective clobetasol propionate and
topical tacrolimus are, compared with each other, at 2 months at increasing the proportion of children achieving
>75% repigmentation (low-quality evidence).
Benefits: We found one systematic review (search date 2009), which did not include a meta-analysis for the
[4] [38] [42]
clinical outcomes of interest. It identified two RCTs.
Clobetasol propionate versus PUVA:

The first RCT identified by the review compared clobetasol propionate (0.05% cream applied twice
daily) versus topical PUVA (0.1% methoxsalen ointment applied 45 minutes before UVA exposure)
[38]
three times weekly. It found that, compared with topical PUVA, clobetasol propionate signifi-
cantly increased the proportion of children achieving >75% repigmentation at 6 months (50 children
under 12 years old; AR: 9/22 [41%] with clobetasol propionate v 2/23 [9%] with topical PUVA; RR
4.7, 95% CI 1.14 to 19.39; P value not reported). The best response was seen on the face and
neck, followed by the trunk and proximal parts of the extremities.
Clobetasol propionate versus topical tacrolimus:

The second RCT identified by the review (20 children, aged 4–17 years [4 aged 15 years and over],
symmetrical vitiligo lesions, mean duration of disease 2.2 years, variable localisation, segmental
and mucosal vitiligo excluded) was a left–right comparison of topical clobetasol propionate (0.05%)
[42]
versus topical tacrolimus (0.1%) twice daily. It found no significant difference between topical
clobetasol and topical tacrolimus in achieving >75% repigmentation of affected areas at 2 months
(grade of repigmentation evaluated by colour slides at baseline and analysed every 2 weeks by
blinded clinicians not involved in study, and by morphometric digitalised computer program; AR:
5/20 (25%) with clobetasol v 5/20 (25%) with topical tacrolimus 0.1%; P = 1.00).
Potent topical corticosteroids plus topical calcipotriol versus either topical corticosteroid
or calcipotriol alone:
We found no RCTs in children only. See benefits of topical corticosteroids in adults, p 4 and vitamin
D analogues in adults, p 8 .
Topical betamethasone dipropionate versus topical calcipotriol:

We found no RCTs in children only. See benefits of vitamin D analogues in adults, p 8 .
Harms: Clobetasol propionate versus PUVA:

The first RCT identified by the review reported mild atrophy (4/22 [18%]), telangiectasia (2/22 [9%]),
hypertrichosis (1/22 [5%]), and corticosteroid-induced acne (2/22 [9%]) with topical corticosteroids.
[38]
It reported blistering in two people receiving PUVA, requiring cessation of treatment for 1 month.
[38]
Clobetasol propionate versus topical tacrolimus:

The second RCT identified by the review reported atrophy (3/20 [15%]) and telangiectasia (2/20
[42]
[10%]) with clobetasol. It reported a burning sensation (2/20 people [10%]), which did not pre-
[42]
clude the continuation of therapy, with tacrolimus, during the first 2 weeks of therapy.
We found no RCTs in children only. See harms of topical corticosteroids in adults, p 4 and vitamin
D analogues in adults, p 8 .
Topical betamethasone dipropionate versus topical calcipotriol:

We found no RCTs in children only. See harms of vitamin D analogues in adults, p 8 .

Skin disorders
[52]
In developing guidelines for the management of vitiligo, a consensus was agreed among clini-
cians that topical corticosteroid therapy would be chosen as first-line treatment for localised vitiligo
(11/14 respondents [79%]), generalised vitiligo (11/14 respondents [79%]), and stable vitiligo (12/14
respondents [86%]).
OPTION IMMUNOMODULATORS (TOPICAL) IN CHILDREN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Treatment success
Topical tacrolimus compared with clobetasol propionate We don't know how effective topical tacrolimus and clobetasol
propionate are, compared with each other, at 2 months at increasing the proportion of children achieving >75%
repigmentation (low-quality evidence).
Note
We found no direct information from RCTs about whether tacrolimus, pimecrolimus, or imiquimod are better than no
active treatment in the management of children with vitiligo. Topical pimecrolimus and tacrolimus may be associated
with malignancy.
Benefits: Topical tacrolimus versus placebo:

We found no systematic review or RCTs.
Topical tacrolimus versus clobetasol propionate:

See benefits of topical corticosteroids in children, p 16 .
Topical pimecrolimus versus placebo:

We found no RCTs in children only. See benefits of immunomodulators in adults, p 6 .
Topical imiquimod versus placebo:

Harms: Topical tacrolimus versus placebo:

We found no RCTs.
Topical tacrolimus versus clobetasol propionate:

See harms of topical corticosteroids in children, p 16 .
Topical pimecrolimus versus placebo:

We found no RCTs in children only. See harms of immunomodulators in adults, p 6 .
Topical imiquimod versus placebo:

We found not RCTs.
Comment: See comment in immunomodulators in adults, p 6 for comment and drug safety alert on possible
malignancy risk with topical immunomodulators. However, long-term results in children have not
demonstrated an increase in carcinogenicity with topical tacrolimus use, but further studies are
required. The manufacturing company recommends photoprotection while being treated with
[71]
tacrolimus and contraindicates application to malignant or premalignant lesions.
OPTION VITAMIN D ANALOGUES (TOPICAL) IN CHILDREN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
We found no direct information from RCTs about the effects of vitamin D analogues in children with vitiligo
only.
Benefits: Topical calcipotriol versus placebo:

We found no systematic review or good-quality RCTs in children only. See benefits of vitamin D
analogues in adults, p 8 .
Topical calcipotriol plus PUVA versus PUVA:

Topical calcipotriol plus UVB versus UVB:


Skin disorders
Harms: Topical calcipotriol versus placebo:
We found no RCTs.
Topical calcipotriol plus PUVA versus UVA:

Topical calcipotriol plus UVB versus UVB:

Comment: One RCT of poor quality (including adults and children with vitiligo) found no significant difference
[57]
in percentage repigmentation between topical calcipotriol and no treatment at 4 months. We
found no RCTs investigating the effects of other topical vitamin D analogues (tacalcitol) or vitamin
C (calcitriol) in children.
OPTION CORTICOSTEROIDS (ORAL) IN CHILDREN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
We found no direct information from RCTs about the effects of oral corticosteroids in children with vitiligo.
There is consensus that the adverse effects associated with oral corticosteroids far outweigh any benefit
that may be achieved in people with vitiligo.
Benefits: We found no systematic review or RCTs.
Harms: We found no RCTs.

The use of oral pulsed corticosteroids in children has been reported to be successful in uncontrolled
[72]
trials in arresting the progression of vitiligo, but is not advised by dermatologists because of
the risks of suppression of the adrenal cortex, and systemic adverse effects associated with this
therapy (such as facial oedema, weight gain, and growth retardation).
QUESTION What are the effects of ultraviolet light treatments for vitiligo in children?
OPTION ULTRAVIOLET B (NARROWBAND) IN CHILDREN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
We found no direct information from RCTs about the effects of narrowband UVB in children with vitiligo
only. The consensus is that narrowband UVB is safe and effective in children, and may improve quality of
life.
Benefits: Narrowband ultraviolet B (UVB) versus placebo:


We found no systematic review or RCTs in children only. We found one RCT in a mixed population
[69]
of adults and children. See benefits of topical PUVA in adults, p 15 .
Harms: Narrowband UVB versus placebo:

We found no RCTs.

We found no systematic review. We found one RCT, which did not report any adverse effects with
[69]
UVB treatment.
Comment: We found no controlled trials investigating narrowband or broadband UVB in the management of
vitiligo in children. We found one prospective cohort study, which found that narrowband UVB
2
(310–315 nm, initial dose 0.25 J/cm , increased by 20% increments, twice weekly) resulted in >75%
repigmentation at 1 year in about half the participants (51 children, age range 4–16 years, gener-
alised vitiligo affecting >5% body surface area, clinician assessment using baseline photography;
[73]
AR: 27/51 [53%] with narrowband UVB, significance assessment not performed, no control).
The best response was seen on the face and neck, with the poorest response seen in the acral
sites (fingers, feet), areas of bony prominences, and areas of lower hair-growth density (wrists,
ankles, joints). The study reported pruritus (4/51 [8%]) and xerosis with thickening of lesional skin
[73]
(2/20 [10%]) with narrowband UVB. The safe duration of narrowband UVB and maximum cu-
mulative dose compared with other treatment modalities remains undetermined, but the consensus
Skin disorders
is that this form of treatment is safe and effective in children, and may improve their quality of life.
[73]
UVB phototherapy has the advantage of not requiring photoprotective goggles post-treatment.
Furthermore, there is consensus that the risk of developing skin cancers from light treatments is
lowest with narrowband UVB and highest with PUVA.
OPTION PUVA (ORAL OR TOPICAL) IN CHILDREN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Treatment success
Trioxysalen plus UVA compared with UVA alone UVA (sunlight or sun lamp) plus oral trioxysalen may be more ef-
fective at 8 months at achieving cure or clear improvement in skins of children affected by vitiligo (low-quality evidence).
Topical PUVA compared with clobetasol propionate Topical PUVA is less effective at increasing the proportion of
children achieving >75% repigmentation at 6 months (moderate-quality evidence).
Note
There is consensus that PUVA is not recommended in children under the age of 12 owing to the risk of cataract
formation, and an increased risk of skin cancer.
Benefits: Trioxysalen plus UVA versus UVA alone:

We found one systematic review (search date 2009), which did not include a meta-analysis for the
[4]
clinical outcomes of interest. It identified one RCT, which found that, compared with oral placebo
plus UVA (sunlight/sun lamp), trioxysalen (10–30 mg/day) plus UVA (sunlight/sun lamp) significantly
achieved cure/clear improvement in skin affected by vitiligo at 8 months (50 children, average age
9–10 years [minimum of 5% skin affected]; AR: 16/25 [64%] with trioxysalen plus UVA v 7/25 [28%]
[74]
with UVA alone; RR 2.29, 95% CI 1.14 to 4.58; P value not reported). Trioxysalen was given
3 hours before exposure, or in two doses after breakfast and lunch for those using sunlight. Exposure
time to UVA was 3 to 30 minutes daily until erythema appeared in the vitiligo patches.

See benefits of UVB (narrowband) in children, p 18 .
Topical PUVA versus clobetasol propionate:

See benefits of topical corticosteroids in children, p 16 .
Harms: Trioxysalen plus UVA versus UVA alone:

One RCT reported severe pruritus (1/25 [4%]), hyperpigmentation of uninvolved skin (1/25 [4%]),
and blisters (2 people using sun lamp) in those taking trioxysalen plus UVA. There was no evidence
[74]
of liver or blood toxicity in either control or treatment group.

The RCT reported erythema (3/28 [101%]), scaling (3/28 [11%]), and itching (3/28 [11%]) with
PUVA. Difficulties in uniformly applying the aqueous gel resulted in linear burns of the vitiliginous
skin as well as of the normally pigmented skin. In pigmented skin, hyperpigmented stripes remained.
[69]

See harms of UVB (narrowband) in children, p 18 .
Topical PUVA versus clobetasol propionate:

See harms of topical corticosteroids in children, p 16 .

[32]
In general, PUVA is not recommended for children under the age of 12 years. Results from
studies carried out in mixed-age groups should not be extrapolated to children. The phototoxic
potential of psoralens is of great concern in children, where avoidance of excessive sun exposure
may be difficult to regulate. PUVA therapy is not advocated in children under the age of 12 years
because of the risk of cataract formation (because the eye is not fully developed until the age of
12 years), and because of the increased risk of skin cancer. See also comment on oral PUVA in
adults, p 11 .
GLOSSARY
Active vitiligo An extending vitiligo with enlarging lesions or development of new lesions.
Ecchymoses The escape of blood into the tissues from ruptured blood vessels marked by a livid black and blue or
purple spot or area.

Skin disorders
Koebner phenomenon The development of vitiligo at sites of aspecifically traumatised skin.
Localised vitiligo can consist either of focal lesions (macules appear in a non-dermatomal distribution) or a segmental
form (macules are localised in a segmental distribution that is frequently not dermatomal, commonly seen in children).
Segmental vitiligo A form of localised vitiligo where one or more lesions of vitiligo arise in a quasidermatomal pattern.
Vitiligo vulgaris A symmetrical type of generalised vitiligo in which scattered macules are seen over the entire body.
Broadband ultraviolet B 290 nm to 320 nm wavelength ultraviolet radiation.
Generalised vitiligo Characterised by multiple scattered lesions in a symmetrical distribution pattern. It occurs in
acrofacial, periorifacial, and orifacial types, in which the distal extremities and face are involved. In the universal
form, there is more than 80% depigmentation.
High-quality evidence Further research is very unlikely to change our confidence in the estimate of effect.
Hypertrichosis Excessive growth of hair.
Internally controlled trial A trial in which the experimental intervention is compared with either a standard treatment
for the disease, a placebo, or no treatment at all, in the same participant.
Low-quality evidence Further research is very likely to have an important impact on our confidence in the estimate
of effect and is likely to change the estimate.
Moderate-quality evidence Further research is likely to have an important impact on our confidence in the estimate
of effect and may change the estimate.
Narrowband ultraviolet B 310 nm to 315 nm wavelength ultraviolet radiation.
PUVA Combination therapy of ultraviolet A and topical or oral psoralen. The psoralen sensitises the skin to ultraviolet
A and is taken or is applied a set period of time before the ultraviolet A exposure.
Parametrically A set of measurable factors that define a condition and determine its course which are varied in a
trial.
Ultraviolet A 315 nm to 400 nm ultraviolet radiation.
Very low-quality evidence Any estimate of effect is very uncertain.
SUBSTANTIVE CHANGES
[4]
Corticosteroids (topical) in adults New evidence added. Categorisation unchanged (Beneficial).
[4]
Corticosteroids (topical) in children Search updated for already included systematic review. No new evidence
added. Categorisation unchanged (Beneficial).
[4]
Immunomodulators (topical) in adults New evidence added. Categorisation unchanged (Unknown effectiveness)
as there remains insufficient evidence to judge the effects of this intervention.
[4]
Immunomodulators (topical) in children Search updated for already included systematic review. No new evidence
added. Categorisation unchanged (Unknown effectiveness).
[4]
Levamisole (oral) in adults New evidence added. Categorisation unchanged (Beneficial).
[4]
PUVA (oral or topical) in children Search updated for already included systematic review. No new evidence
added. Categorisation unchanged (Likely to be ineffective or harmful).
[4] [66]
PUVA (oral) in adults New evidence added. Categorisation unchanged (Likely to be beneficial).
[4]
PUVA (topical) in adults Search updated for already included systematic review. No new evidence added. Cat-
egorisation unchanged (Unlikely to be beneficial).
[4] [66]
Ultraviolet B (narrowband) in adults New evidence added. Categorisation unchanged (Likely to be beneficial).
[4]
Vitamin D analogues (topical) in adults New evidence added. Categorisation unchanged (Unlikely to be bene-
ficial).
REFERENCES
1. Perrot JL. Thyreopathies et autoimmunisation. Lyon Med 1973;230:325–231. 7. Spritz RA. The genetics of generalized vitiligo and associated autoimmune dis-
2. Srivastava G. Vitiligo update. Asian Clin Dermatol 1994;1:1–4. eases. Pigment Cell Research 2007;20:271–278.[PubMed]
3. Westerhof W, Bolhaar B, Menke HE, et al. Resultaten van een enquete onder 8. Westerhof W, d'Ischia M. Vitiligo puzzle: the pieces fall in place. Pigment Cell
vitiligo patienten. Ned Tjdschr Dermatol Venereol 1996;6:100–105. Res 207;20:345–359.[PubMed]
4. Whitton ME, Pinart M, Batchelor J, et al. Interventions for vitiligo. In: The Cochrane 9. Bhatia PS, Mohan L, Pandey ON, et al. Genetic nature of vitiligo. J Dermatol Sci
Library, Issue 1, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 1992;4:180–184.[PubMed]
2009. 10. Fain PR, Gowan K, LaBerge GS, et al. A genomewide screen for generalised
5. Behl PN, Bhatia RK. 400 cases of vitiligo. A clinico-therapeutic analysis Indian vitiligo: confirmation of AIS1 on chromosome 1p31 and evidence for additional
J Dermatol 1972;17:51–56.[PubMed] susceptibility loci. Am J Hum Genet 2003;72:1560–1564.[PubMed]
6. Schallreuter KU, Bahadoran P, Picardo M, etal.Vitiligo pathogenesis: autoimmune 11. Spritz RA, Gowan K, Bennett DC, et al. Novel vitiligo susceptibility loci on chro-
disease, genetic defect, excessive reactive oxygen species, calcium imbalance, mosomes 7 (AIS2) and 8 (AIS3), confirmation of SLEVI on chromosome 17, and
or what else? Exp Dermatol 2008;17:139–140.[PubMed] their role in autoimmune diathesis. Am J Hum Genet 2004;74:188–191.[PubMed]
12. Jin Y, Mailloux CM, Gowan K, et al. NALP1 in vitiligo-associated multiple autoim-
mune disease. N Engl J Med 2011;356:1216–1225.[PubMed]
Skin disorders
13. Al'Abadie MS, Kent GG, Gawkrodger DJ. The relationship between stress and 46. Koopmans-van Dorp B, Goedhart-van Dijjk B, Neering H, et al. Treatment of vi-
the onset and exacerbation of psoriasis and other skin conditions. Br J Dermatol tiligo by local application of betamethasone 17-valerate in a dimethyl sulfoxide
1994;130:199–203.[PubMed] cream base. Dermatologica 1973;146:310–314.[PubMed]
14. Papadopoulos L, Bor R, Legg C, et al. Impact of life events on the onset of vitiligo 47. Kandil E. Treatment of vitiligo with 0.1% betamethasone 17-valerate in isopropyl
in adults: preliminary evidence for a psychological dimension in aetiology. Clin alcohol – a double blind trial. Br J Dermatol 1974;91:457–460.[PubMed]
Exp Dermatol 1998;23:243–248.[PubMed] 48. Clayton R. A double-blind trial of 0–05% clobetasol proprionate in the treatment
15. Ongenae K, Van Geel N, Naeyaert JM. Evidence for an autoimmune pathogen- of vitiligo. Br J Dermatol 1977;96:71–73.[PubMed]
esis of vitiligo. Pigment Cell Res 2003;16:90–100.[PubMed] 49. Westerhof W, Nieuweboer-Krobotova L, Mulder PG, et al. Left-right comparison
16. Mosher DB, Fitzpatrick TB, Ortonne JP, et al. Disorders in pigmentation. In: study of the combination of fluticasone propionate and UV-A vs. either fluticasone
Fitzpatrick TB, Eisen AZ, Wolff K, et al, eds. Dermatology in general medicine. propionate or UV-A alone for the long-term treatment of vitiligo. Arch Dermatol
New York, NY: McGraw-Hill, 1987:810–821. 1999;135:1061–1066.[PubMed]
17. Rezaei N Gavalas NG, Weetman AP, Kemp EH. Autoimmunity as an aetiological 50. Kumaran MS, Kaur I, Kumar B. Effect of topical calcipotriol, betamethasone
factor in vitiligo. J Eur Acad Dermatol Venereol 2007;21:865–876.[PubMed] dipropionate and their combination in the treatment of localized vitiligo. J Eur
18. Mishima Y, Kawasaki H, Pinkus H. Dendritic cell dynamics in progressive depig- Acad Dermatol Venereol 2006;20:269–273.
mentations. Arch Dermatol Forsch 1972;243:67–87.[PubMed] 51. Geraldez CB, Gutierrez GT. A clinical trial of clobetasol propionate in Filipino vi-
19. Brostoff J. Autoantibodies in patients with vitiligo. Lancet tiligo patients. Clin Ther 1987;9:474–482.[PubMed]
1969;2:177–178.[PubMed] 52. Njoo MD, Westerhof MD, Bos JD, et al. The development of guidelines for the
20. Foley LM, Lowe NJ, Misheloff E, et al. Association of HLA-DR4 with vitiligo. J treatment of vitiligo. Arch Dermatol 1999;135:1514–1521.[PubMed]
Am Acad Dermatol 1983;8:39–40.[PubMed] 53. Dawid M, Veensalu M, Grassberger M, et al. Efficacy and safety of pimecrolimus
21. Naughton GK, Eisinger M, Bystryn JC. Detection of antibodies to melanocytes cream 1% in adult patients with vitiligo: results of a randomized, double-blind,
in vitiligo by specific immunoprecipitation. J Invest Dermatol vehicle-controlled study. J Dtsch Dermatol Ges 2006;4:942–946.[PubMed]
1983;81:540–542.[PubMed] 54. Esfandiarpour I, Ekhlasi A, Farajzadeh S, et al. The efficacy of pimecrolimus 1%
22. Seo SL, Kim IH. Squamous cell carcinoma in a patient with generalised vitiligo. cream plus narrow-band ultraviolet B in the treatment of vitiligo: a double-blind,
J Am Acad Dermatol 2001;45(6 suppl):S227–S229. placebo-controlled clinical trial. J Dermatol Treat 2009;20:14–18.[PubMed]
23. Lindelof B, Sigurgeirsson B, Tegner E, et al. PUVA and cancer risk: the Swedish 55. Travis LB, Weinberg JM, Silverberg NB. Successful treatment of vitiligo with 0.1%
follow-up study. Br J Dermatol 1999;141:108–112.[PubMed] tacrolimus ointment Arch Dermatol 2003;139:571–574.[PubMed]
24. Stern RS, Nichols KT, Vakeva LH. Malignant melanoma in patients treated for 56. Agarwal S, Ramam M, Sharma VK, et al. A randomised placebo-controlled double-
psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The blind study of levamisole in the treatment of limited and slowly spreading vitiligo.
PUVA follow-up study. N Engl J Med 1997;336:1041–1045.[PubMed] Br J Dermatol 2005;153:163–166.[PubMed]
25. Lerner AB, Nordlund JJ. Vitiligo. What is it? Is it important? JAMA 57. Chiaverini C, Passeron T, Ortonne JP. Treatment of vitiligo by topical calcipotriol.
1978;239:1183–1187.[PubMed] J Eur Acad Dermatol Venereol 2002;16:137–138.[PubMed]
26. Papadopoulos L, Bor R, Legg C. Coping with the disfiguring effects of vitiligo: a 58. Ermis O, Alpsoy E, Cetin L, et al. Is the efficacy of psoralen plus ultraviolet A
preliminary investigation into the effects of cognitive behavioural therapy. Br J therapy for vitiligo enhanced by concurrent topical calcipotriol? A placebo-con-
Med Psychol 1999;72:385–396.[PubMed] trolled double-blind study. Br J Dermatol 2001;145:472–475.[PubMed]
27. Porter J, Beuf AH, Nordlund JJ, et al. Psychological reaction to chronic skin dis- 59. Arca E, Tastan HB, Erbil AH, et al. Narrow-band ultraviolet B as monotherapy
orders: a study of patients with vitiligo. Gen Hosp Psychiatry and in combination with topical calcipotriol in the treatment of vitiligo. J Dermatol
1979;1:73–77.[PubMed] 2006;33:338–343.[PubMed]
28. Njoo MD, Westerhof W. Vitiligo: pathogenesis and treatment. Am J Clin Dermatol 60. Ada S, Sahin S, Boztepe G, et al. No additional effect of topical calcipotriol on
2001;2:167–181.[PubMed] narrow-band UVB phototherapy in patients with generalized vitiligo. Photodermatol
Photoimmunol Photomed 2005;21:79–83.[PubMed]
29. Grimes PE. New insights and new therapies in vitiligo. JAMA
2005;293:730–735.[PubMed] 61. Leone G, Pacifico A, Iacovelli P, et al. Tacalcitol and narrow-band phototherapy
in patients with vitiligo. Clin Exp Dermatol 2006;31:200–205.[PubMed]
30. Ortonne JP. Vitiligo. In: Ortonne JP, ed. Vitiligo and other hypomelanoses of hair
and skin. New York, NY: Plenum Medical Books, 1983:163–310. 62. Rodriguez-Martin M, Garcia Bustinduy M, Saez Rodriguez M, et al. Randomized,
double-blind clinical trial to evaluate the efficacy of topical tacalcitol and sunlight
31. Antoniou C, Katsambas A. Guidelines for the treatment of vitiligo. Drugs
exposure in the treatment of adult nonsegmental vitiligo. Br J Dermatol
1992;43:490–498.[PubMed]
2009;160:409–414.[PubMed]
32. Drake LA, Dinehart SM, Farmer ER, et al. Guidelines of care for vitiligo. J Am
63. Radakovic-Fijan S, Furnsinn-Friedl AM, Honigsmann H, et al. Oral dexamethasone
Acad Dermatol 1996;35:620–626.[PubMed]
pulse treatment for vitiligo. J Am Acad Dermatol 2001;44:814–817.[PubMed]
33. Grimes PE. Vitiligo: an overview of therapeutic approaches. Dermatol Clin
64. Pathak MA, Mosher DB, Fitzpatrick TB. Safety and therapeutic effectiveness of
1993;11:325–338.[PubMed]
8-methoxypsoralen, 4,5',8-trimethylpsoralen, and psoralen in vitiligo. Natl Cancer
34. Hatchome N, Kato T, Tagamit H. Therapeutic success of epidermal grafting in Inst Monogr 1984;66:165–173.[PubMed]
generalised vitiligo is limited by the Koebner phenomenon. J Am Acad Dermatol
65. Farah FS, Kurban AK, Chaglassian HT. The treatment of vitiligo with psoralens
1990;22:87–91.[PubMed]
and triamcinolone by mouth. Br J Dermatol 1967;79:89–91.[PubMed]
35. Koebner H. Zur aetologie der Psoriasis. Vierteljahrsschr Dermatol Syphil
66. Yones SS, Palmer RA, Garibaldinos TM, et al. Randomized double-blind trial of
1877;8:559.
treatment of vitiligo: efficacy of psoralen-UV-A therapy vs narrowband-UV-B
36. Kaposi M. Vitiligo. In: Pathologie et traitement des maladies de peau. Paris, therapy. Arch Dermatol 2007;143:578–584.[PubMed]
France: Masson; 1891:105–110.
67. Mofty ME, Zaher H, Esmat S, et al. PUVA and PUVB in vitiligo — are they
37. Beetley F. The provocation of cutaneous disease: Koebner's isomorphic phe- equally effective? Photodermatol Photoimmunol Photomed
nomenon. Arch Middx Hosp 1951;1:279–287.[PubMed] 2001;17:159–163.[PubMed]
38. Khalid M, Mujtaba G, Haroon TS. Comparison of 0.05% clobetasol propionate 68. Tjioe M, Gerritsen MJ, Juhlin L, et al. Treatment of vitiligo vulgaris with narrow
cream and topical Puvasol in childhood vitiligo. Int J Dermatol band UVB (311 nm) for one year and the effect of addition of folic acid and vitamin
1995;34:203–205.[PubMed] B12. Acta Derm Venereol 2002;82:369–372. [Erratum in: Acta Derm Venereol
39. Schallreuter KU, Lemke R, Brandt O, et al.Vitiligo and other diseases: coexistence 2002;82:485][PubMed]
or true association? Dermatology 1994;188:269–275.[PubMed] 69. Westerhof W, Nieuweboer-Krobotova L. Treatment of vitiligo with UV-B radiation
40. Barona MI, Arrunategui A, Falabella R, et al. An epidemiologic case-control study vs topical psoralen plus UV-A. Arch Dermatol 1997;133:1525–1528.[PubMed]
in a population with vitiligo. J Am Acad Dermatol 1995;33:621–625.[PubMed] 70. Lowe NJ, Weingarten D, Bourget T, et al. PUVA therapy for psoriasis: comparison
41. Njoo MD, Das PK, Bos JD, et al. Association of the Koebner phenomenon with of oral and bath-water delivery of 8-methoxypsoralen. J Am Acad Dermatol
disease activity and therapeutic responsiveness in vitiligo vulgaris. Arch Dermatol 1986;14:754–760.[PubMed]
1999;135:407–413.[PubMed] 71. Protopic 0.03%, summary of product characteristics. Astellas; date of last revision
42. Lepe V, Moncada B, Castanedo-Cazares JP, et al. A double-blind randomized 28 February 2002.
trial of 0.1% tacrolimus vs 0.05% clobetasol for the treatment of childhood vitiligo. 72. Pasricha JS, Khaitan BK. Oral mini-pulse therapy with betamethasone in vitiligo
Arch Dermatol 2003;139:581–585.[PubMed] patients having extensive or fast-spreading disease Int J Dermatol
43. Hamzavi I, Jain H, McLean D, et al. Parametric modeling of narrowband UV-B 1993;32:753–757. [PubMed]
phototherapy for vitiligo using a novel quantitative tool: the Vitiligo Area Scoring 73. Njoo MD, Bos JD, Westerhof W. Treatment of generalised vitiligo in children with
Index. Arch Dermatol 2004;140:677–683.[PubMed] narrowband (TL-01) UVB radiation therapy. J Am Acad Dermatol
44. Njoo MD, Spuls PI, Bos JD, et al. Nonsurgical repigmentation therapies in vitiligo. 2000;42:245–253.[PubMed]
Meta-analysis of the literature. Arch Dermatol 1998;134:1532–1540.[PubMed] 74. Maldonado RR, Sanchez LT. 4-5-8 trimethylpsoralen in vitiligo. Actas Dermosifil-
45. Bleehen SS. The treatment of vitiligo with topical corticosteroids. Light and elec- iogr 1975(Sep-Oct):513–526.
tronmicroscopic studies. Br J Dermatol 1976;94(suppl 12):43–50.
Rubeta Matin
MRC Research Fellow
Centre for Cutaneous Research
Queen Mary University Hospital
London
UK
Competing interests: RM declares that she has no competing interests.

Skin disorders
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a
judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and
harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices.
Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research
we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the
categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately
it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest
extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any
person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, inci-
dental or consequential, resulting from the application of the information in this publication.

Skin disorders
[64]
TABLE 1 Methoxsalen, trioxysalen, unsubstituted PUVA versus placebo.
Comparison Outcome Result

Methoxsalen (0.3 mg/kg) plus UVA Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmentation AR: 12/49 [24%] with oral methoxsalen plus UVA v 0/24 [0%] with
v assessed visually by clinician against baseline photographs at 6-monthly intervals) placebo; RR 12.50, 95% CI 0.77 to 202.63
UVA alone
Methoxsalen (0.6 mg/kg) plus UVA Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmentation AR: 12/49 [24%] with oral methoxsalen plus UVA v 0/24 [0%] with
UVA alone
Methoxsalen (any dose) plus UVA Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmentation AR: 24/98 [24%] with oral methoxsalen plus UVA v 0/24 [0%] with
UVA alone
Trioxysalen (0.8 mg/kg) plus UVA Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmentation AR: 7/39 [18%] with trioxysalen plus UVA v 0/24 [0%] with placebo;
v assessed visually by clinician against baseline photographs at 6-monthly intervals) RR 9.38, 95% CI 0.56 to 157.09
UVA alone
UVA alone
UVA alone
Trioxysalen (any dose) plus UVA Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmentation AR: 24/143 [17%] with trioxysalen plus UVA v 0/24 [0%] with placebo;
UVA alone
Unsubstituted PUVA (0.6 mg/kg) Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmentation AR: 3/35 [9%] with 40 mg unsubstituted PUVA v 0/24 [0%] with
UVA alone
Unsubstituted PUVA (1.2 mg/kg) Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmentation AR: 11/37 [30%] with 1.2 mg/kg unsubstituted PUVA v 0/24 [0%] with
UVA alone
Unsubstituted PUVA (any dose) Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmentation AR: 14/72 [19%] with unsubstituted PUVA v 0/24 [0%] with placebo;
UVA alone
© BMJ Publishing Group Ltd 2011. All rights reserved. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Skin disorders
[4] [64]
TABLE 2 Different oral PUVA derivatives versus each other.

Methoxsalen plus UVA Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmentation AR: 24/98 [24%] with oral methoxsalen plus UVA v 24/143 [17%] with
v assessed visually by clinician against baseline photographs at 6-monthly intervals) trioxysalen; RR 1.46, 95% CI 0.88 to 2.42
Trioxysalen (any dose) plus UVA
Methoxsalen plus UVA Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmentation AR: 24/98 [24%] with oral methoxsalen plus UVA v 14/72 [19%] with
v assessed visually by clinician against baseline photographs at 6-monthly intervals) unsubstituted PUVA; RR 1.26, 95% CI 0.70 to 2.26
Unsubstituted PUVA (any dose)
Trioxysalen (any dose) plus UVA Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmentation AR: 24/143 [17%] with trioxysalen plus UVA v 24/98 [24%] with
v assessed visually by clinician against baseline photographs at 6-monthly intervals) methoxsalen; RR 0.69, 95% CI 0.41 to 1.13
Methoxsalen plus UVA
Trioxysalen (any dose) plus UVA Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmentation AR: 24/98 [24%] with trioxysalen plus UVA v 14/72 [19%] with unsub-
v assessed visually by clinician against baseline photographs at 6-monthly intervals) stituted PUVA; RR 1.26, 95% CI 0.70 to 2.26
Unsubstituted psoralen plus UVA
Trioxysalen plus UVA Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmentation AR: 14/72 [19%] with trioxysalen plus UVA v 24/143 [17%] with unsub-
v assessed visually by clinician against baseline photographs at 6-monthly intervals) stituted psoralen (any dose); RR 1.16, 95% CI 0.64 to 2.10
Unsubstituted PUVA (any dose)
[4] [64]
TABLE 3 Methoxsalen plus trioxysalen plus UVA versus placebo/different PUVA derivatives.

Methoxsalen plus trioxysalen plus UVA Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmen- AR: 21/55 [38%] with oral methoxsalen plus trioxysalen plus UVA v 0/24
v tation assessed visually by clinician against baseline photographs at 6-monthly in- [0%] with placebo; RR 19.20, 95% CI 1.21 to 304.50
placebo tervals)
Methoxsalen plus trioxysalen (any dose) plus UVA Repigmentation in >75% of all vitiliginous macules at 2 years (degree of repigmen- AR: 21/55 [38%] with methoxsalen plus trioxysalen plus UVA v 24/98
v tation assessed visually by clinician against baseline photographs at 6-monthly in- [24%] with oral methoxsalen plus UVA; RR 0.64, 95% CI 0.40 to 1.04
Methoxsalen plus UVA tervals)
v tation assessed visually by clinician against baseline photographs at 6-monthly in- [24%] with trioxysalen plus UVA; RR 0.64, 95% CI 0.40 to 1.04
Trioxysalen plus UVA tervals)
v tation assessed visually by clinician against baseline photographs at 6-monthly in- [19%] with unsubstituted PUVA; RR 0.51, 95% CI 0.29 to 0.91
Unsubstituted PUVA tervals)
© BMJ Publishing Group Ltd 2011. All rights reserved. ............................................................................................................ 24

Skin disorders
TABLE GRADE evaluation of interventions for vitiligo
Important out-
comes Treatment success (repigmentation), disease progression (development of new lesions), adverse effects
Type of
Number of studies evi- Consis- Direct- Effect
(participants) Outcome Comparison dence Quality tency ness size GRADE Comment
What are the effects of medical treatments for vitiligo in adults?
[45] [46]
3 (48) Treatment success Potent topical corticosteroids v 4 −1 0 0 +2 High Quality point deducted for sparse data. Effect-size
[47]
placebo points added for OR >5
[45] [48]
2 (33) Treatment success Very potent topical corticosteroids 4 −2 0 0 0 Low Quality points deducted for sparse data and incom-
v placebo plete reporting of results
[45]
1 (20) Treatment success Potent v very potent corticosteroids 4 −2 0 −2 0 Very low Quality points deducted for sparse data and incom-
plete reporting of results. Directness points deducted
for no direct comparison between groups and no clear
measurement of outcome
[49]
1 (67) Treatment success Potent topical corticosteroids plus 4 −2 0 0 0 Low Quality points deducted for sparse data and poor fol-
UVA v topical corticosteroids alone low-up
[49]
1 (68) Treatment success Potent topical corticosteroids plus 4 −2 0 0 0 Low Quality points deducted for sparse data and poor fol-
UVA v UVA low-up
[50]
1 (31) Treatment success Potent topical corticosteroids plus 4 −1 0 −1 0 Low Quality point deducted for sparse data. Directness
topical calcipotriol v topical cal- point deducted for inclusion of children
cipotriol alone
[53]
1 (18) Treatment success Pimecrolimus v placebo cream 4 −2 0 −1 0 Very low Quality points deducted for sparse data and incom-
plete reporting of results. Directness point deducted
for inclusion of children
[56]
1 (60) Disease progression Levamisole plus potent topical 4 −2 0 −2 0 Very low Quality points deducted for sparse data and poor fol-
corticosteroids v potent topical low-up. Directness points deducted for inclusion of
corticosteroids alone children and uncertainty about size of lesions
[57]
1 (24) Treatment success Topical calcipotriol v placebo or no 4 −2 0 −1 0 Very low Quality points deducted for sparse data and incom-
treatment plete reporting of results. Directness point deducted
[50]
1 (34) Treatment success Topical calcipotriol v topical be- 4 −2 0 −1 0 Very low Quality points deducted for sparse data and incom-
tamethasone dipropionate plete reporting of results. Directness point deducted
[50]
1 (30) Treatment success Topical calcipotriol plus potent 4 −1 0 −1 0 Low Quality point deducted for sparse data. Directness
topical corticosteroids v potent point deducted for inclusion of children
topical corticosteroids
[58]
1 (35) Treatment success Topical calcipotriol plus PUVA v 4 −2 0 −1 0 Very low Quality points deducted for sparse data and incom-
PUVA alone plete reporting of results. Directness point deducted
[59] [60]
2 (57) Treatment success Topical calcipotriol plus NB-UVB v 4 −2 0 −1 0 Very low Quality points deducted for sparse data and incom-
UVB plete reporting of results. Directness point deducted

Skin disorders
Important out-
Type of
[61]
1 (32) Treatment success Topical tacalcitol plus NB-UVB v 4 −2 0 0 0 Low Quality points deducted for sparse data and incom-
NB-UVB plete reporting of results
What are the effects of ultraviolet light treatments for vitiligo in adults?
[64]
1 (122) Treatment success Methoxsalen plus UVA v UVA 4 −2 0 −1 0 Very low Quality points deducted for sparse data and poor-
alone quality studies. Directness point deducted for inclusion
of children
[64]
1 (167) Treatment success Trioxysalen plus UVA v UVA alone 4 −2 0 −1 0 Very low Quality points deducted for sparse data and poor-
quality studies. Directness point deducted for inclusion
of children
[64] [65]
3 (195) Treatment success Unsubstituted PUVA v UVA alone 4 −2 −1 −1 0 Very low Quality points deducted for sparse data and incom-
[4]
plete reporting of results. Consistency point deducted
for conflicting results. Directness point deducted for
uncertainty about applicability of results (sunlight
variations)
[65]
1 (38) Treatment success Oral PUVA v topical PUVA 4 −2 0 0 0 Low Quality points deducted for sparse data and incom-
plete reporting of results
1 (at least 241 peo- Treatment success Different oral PUVA derivatives v 4 −1 0 0 0 Moderate Quality point deducted for poor-quality studies
[64]
ple) each other
1 (at least 153 peo- Treatment success Methoxsalen plus trioxysalen plus 4 −2 0 0 0 Low Quality points deducted for sparse data and poor-
[64]
ple) UVA v different psoralen deriva- quality study
tives plus UVA
[66]
1 (56) Treatment success Oral PUVA v NB-UVB 4 −1 0 −1 0 Low Quality point deducted for sparse data. Directness
point deducted for difference in number of treatments
completed between groups
[43]
1 (22) Treatment success NB-UVB v placebo 4 −2 0 0 0 Low Quality points deducted for sparse data and for con-
trolled trial
[67]
1 (22) Treatment success Oral PUVB (broadband) v oral PU- 4 −2 0 −1 0 Very low Quality points deducted for sparse data and incom-
VA plete reporting of results. Directness point deducted
[65]
1 (45) Treatment success Topical PUVA v no treatment 4 −1 0 0 0 Moderate Quality point deducted for sparse data
[69]
1 (106) Treatment success Topical PUVA v NB-UVB 4 −3 0 −1 0 Very low Quality points deducted for sparse data, incomplete
reporting of results, and for quasi-RCT. Directness
point deducted for inclusion of children
What are the effects of medical treatments for vitiligo in children?
[38]
1 (45) Treatment success Clobetasol propionate v PUVA 4 −1 0 0 0 Moderate Quality point deducted for sparse data
[42]
1 (20) Treatment success Clobetasol propionate v topical 4 −1 0 −1 0 Low Quality point deducted for sparse data. Directness
tacrolimus point deducted for inclusion of children aged >15 years
What are the effects of ultraviolet light treatments for vitiligo in children?

Skin disorders
Important out-
Type of
[74]
1 (50) Treatment success Trioxysalen plus UVA v UVA alone 4 −1 0 −1 0 Low Quality point deducted for sparse data. Directness
point deducted for applicability of results
Type of evidence: 4 = RCT.
Consistency: similarity of results across studies.
Directness: generalisability of population or outcomes.
Effect size: based on relative risk or odds ratio.
NB-UVB, narrowband ultraviolet B.
View publication stats

Vitiligo in Adults and Children PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Vitiligo in Adults and Children PDF

Uploaded by

Copyright:

Available Formats

See discussions, stats, and author profiles for this publication at: https://www.researchgate.

Vitiligo in adults and children

Article in Clinical Evidence · March 2011

Accuracy of tests to diagnose skin cancer in adults View project

PROCLIPI View project

The user has requested enhancement of the downloaded file.

Vitiligo in adults and children

Unknown effectiveness Unknown effectiveness

Unlikely to be beneficial Likely to be ineffective or harmful

Likely to be ineffective or harmful UV TREATMENTS IN CHILDREN

© BMJ Publishing Group Ltd 2011. All rights reserved. ........................................................... 3

OPTION CORTICOSTEROIDS (TOPICAL) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

For GRADE evaluation of interventions for vitiligo, see table, p 25 .

Potent topical corticosteroids versus placebo:

© BMJ Publishing Group Ltd 2011. All rights reserved. ........................................................... 4

Very potent topical corticosteroids versus placebo:

Potent versus very potent corticosteroids:

Potent topical corticosteroids plus UVA versus topical corticosteroids alone:

Potent topical corticosteroids plus UVA versus UVA alone:

Topical calcipotriol versus topical betamethasone dipropionate:

Harms: Potent topical corticosteroids versus placebo:

© BMJ Publishing Group Ltd 2011. All rights reserved. ........................................................... 5

Potent topical corticosteroids plus UVA versus topical corticosteroids/UVA alone:

Topical calcipotriol versus topical betamethasone dipropionate:

Comment: Clinical guide:

OPTION IMMUNOMODULATORS (TOPICAL) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

For GRADE evaluation of interventions for vitiligo, see table, p 25 .

Benefits: Pimecrolimus versus placebo cream:

Harms: Pimecrolimus versus placebo cream:

Drug safety alerts:

OPTION LEVAMISOLE (ORAL) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

For GRADE evaluation of interventions for vitiligo, see table, p 25 .

Benefits: Levamisole versus placebo:

Harms: Levamisole versus placebo:

Comment: Clinical guide:

OPTION VITAMIN D ANALOGUES (TOPICAL) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

For GRADE evaluation of interventions for vitiligo, see table, p 25 .

Benefits: Topical calcipotriol versus placebo or no treatment:

Topical calcipotriol versus topical betamethasone dipropionate:

Topical calcipotriol plus PUVA versus PUVA alone:

Topical calcipotriol plus UVB (narrowband) versus UVB (narrowband) alone:

Topical tacalcitol plus narrowband UVB versus narrowband UVB alone:

Harms: Topical calcipotriol versus placebo or no treatment:

Topical calcipotriol versus topical betamethasone dipropionate:

Topical calcipotriol plus PUVA versus PUVA alone:

Topical calcipotriol plus UVB (narrowband) versus UVB (narrowband) alone:

Topical tacalcitol plus narrowband UVB versus narrowband UVB:

OPTION CORTICOSTEROIDS (ORAL) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

For GRADE evaluation of interventions for vitiligo, see table, p 25 .

© BMJ Publishing Group Ltd 2011. All rights reserved. .......................................................... 10

Comment: Clinical guide:

OPTION PUVA (ORAL) IN ADULTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

For GRADE evaluation of interventions for vitiligo, see table, p 25 .

Methoxsalen plus UVA versus UVA alone:

© BMJ Publishing Group Ltd 2011. All rights reserved. .......................................................... 11

Trioxysalen plus UVA versus UVA alone:

Unsubstituted PUVA versus UVA alone:

Oral PUVA versus topical PUVA:

Different oral PUVA derivatives versus each other:

Oral PUVA versus UVB (narrowband):

Oral PUVA versus oral PUVB (broadband):

Oral PUVA plus topical calcipotriol versus PUVA alone:

Harms: Methoxsalen plus UVA versus UVA alone: