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. 2008 Apr 18;2008:1717.

Vitiligo in adults and children

Rubeta Matin 1
PMCID: PMC2907927  PMID: 19450313

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 children and in adults? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2007 (BMJ 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 Administration (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 levamisole, topical immunomodulators, topical Vitamin D analogues, ultraviolet A plus psoralen (PUVA), and ultraviolet B (narrowband, and broadband).

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.

  • 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 are a safe and effective therapy for localised vitiligo and are often the first-choice treatment for this.

  • The consensus is that adverse effects of oral corticosteroids outweigh the benefits in vitiligo. There is currently insufficient evidence available to assess their effectiveness.

Narrowband UVB is considered a safe and effective therapy for moderate to severe generalised vitiligo and is often the first-choice treatment for this.

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 evidence available to assess other immunomodulators in vitiligo.

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.

There is insufficient evidence to assess topical vitamin D analogues, levamisole, and broadband UVB in vitiligo.

Consensus is that for the treatment of vitiligo in adults, oral 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.

About this condition

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 categorised 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/ Prevalence

Vitiligo is estimated to affect 1% of the world's population, regardless of age, sex, and skin colour. 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.

Aetiology/ Risk factors

The aetiology of vitiligo is uncertain although genetic, immunological, and neurogenic factors seem to play a role. In about a third of people affected with vitiligo there is a family history, but there are few epidemiological studies to confirm this. Current research focuses on finding the genes responsible. However, certain triggers (e.g. trauma to the skin, hormonal changes, 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 or focal non-dermatomal vitiligo). This is supported by an increased incidence of antibodies found in people with vitiligo. Furthermore, vitiligo is often associated with autoimmune diseases, such as thyroid diseases, pernicious anaemia, and diabetes mellitus. Another indication that vitiligo may be due to an autoimmune mechanism is that melanocyte antibodies have been 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 perilesional skin have also been frequently reported. Regarding segmental vitiligo, the neural hypothesis suggests that it is due to 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 controversy. The occurrence of skin cancer in long-lasting vitiligo is rare, although studies have 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 carcinomas. Furthermore, the risk of malignant melanoma increases among people treated with PUVA, approximately 15 years after the first treatment. The effects of vitiligo can be both cosmetically 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 aetiology and unpredictability of the course. Progression: The course of generalised vitiligo is unpredictable: 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 entire body surface. In some instances, people may undergo rapid, complete depigmentation within 1 or 2 years. In segmental vitiligo, lesions tend to spread rapidly at onset, and show a more stable course thereafter. Predicting treatment responsiveness: Certain disease characteristics help predict the outcome of treatment. Besides age, duration of disease, localisation, 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 effective in active and stable disease, but this may not be true for other treatments (e.g. surgery). 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 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 experimentally induced Koebner phenomenon is associated with active disease, but not necessarily 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 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 ultraviolet A therapy; but, for narrowband ultraviolet B treatment, there was no difference in response, suggesting that people in active and stable stages of the disease may respond equally well to ultraviolet B.

Aims of intervention

To prevent formation of new skin lesions of the vitiligo; to achieve repigmentation of involved skin, 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 50-75% 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 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.

Methods

BMJ Clinical Evidence search and appraisal March 2007. The following databases were used to identify studies for this review: Medline 1966 to March 2007, Embase 1980 to March 2007, and The Cochrane Database of Systematic Reviews 2006, Issue 1. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and NICE clinical guidelines. Abstracts of the studies retrieved were assessed independently by two information specialists, using predetermined criteria to identify relevant studies. Study-design criteria for inclusion in this review were: published systematic reviews and RCTs in any language; at least single blinded; and containing more than 20 individuals, of whom more than 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 also searched for cohort studies on specific harms of named interventions. In addition, we used a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which have been added to the review as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).

Table.

GRADE evaluation of interventions for vitiligo

Important outcomes Treatment success, development of new lesions, disease progression, adverse effects
Number of studies (participants) Outcome Comparison Type of evidence Quality Consistency Directness Effect size GRADE Comment
What are the effects of medical treatments for vitiligo in adults?
3 (48) Treatment success Potent topical corticosteroids v placebo 4 −1 0 0 +2 High Quality point deducted for sparse data. Effect size points added for odds ratio greater than 5
1 (96) Treatment success Potent topical corticosteroids plus ultraviolet A v topical corticosteroids alone 4 −1 0 0 0 Moderate Quality point deducted for sparse data
1 (96) Treatment success Potent topical corticosteroids plus ultraviolet A v ultraviolet A 4 −1 0 0 0 Moderate Quality point deducted for sparse data
2 (33) Treatment success Very potent topical corticosteroids v placebo 4 −1 0 0 0 Moderate Quality point deducted for sparse data
1 (20) Treatment success Potent v very potent corticosteroids 4 −2 0 −2 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Directness points deducted for no direct comparison between groups and for no clear measurement of outcome
1 (31) Treatment success Potent topical corticosteroids plus topical calcipotriol v topical calcipotriol alone 4 −1 0 −1 0 Low Quality point deducted for sparse data. Directness point deducted for inclusion of children
1 (18) Treatment success Pimecrolimus v placebo cream 4 −2 0 −1 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for inclusion of children
1 (60) Disease progression Levamisole plus potent topical corticosteroids v potent topical corticosteroids alone 4 −2 0 −2 0 Very low Quality points deducted for sparse data and poor-quality RCT. Directness points deducted for inclusion of children and uncertainty about size of lesions
1 (24) Treatment success Topical calcipotriol v placebo or no treatment 4 −2 0 −1 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for inclusion of children
1 (34) Treatment success Topical calcipotriol v topical betamethasone dipropionate 4 −2 0 −1 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for inclusion of children
1 (30) Treatment success Topical calcipotriol plus potent topical corticosteroids v potent topical corticosteroids 4 −1 0 −1 0 Low Quality point deducted for sparse data. Directness point deducted for inclusion of children
1 (35) Treatment success Topical calcipotriol plus PUVA v PUVA alone 4 −2 0 −1 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for inclusion of children
2 (57) Treatment success Topical calcipotriol plus NB-UVB v ultraviolet B 4 −2 0 −1 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for inclusion of children
1 (32) Treatment success Topical tacalcitol plus NB-UVB v NB-UVB 4 −2 0 0 0 Low Quality points deducted for sparse data and incomplete reporting of results
What are the effects of ultraviolet light treatments for vitiligo in adults?
1 (122) Treatment success Methoxsalen plus ultraviolet A v ultraviolet A 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
1 (167) Treatment success Trioxysalen plus ultraviolet A v ultraviolet A 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
3 (195) Treatment success Unsubstituted PUVA v ultraviolet A alone 4 −2 −1 −1 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted for conflicting results. Directness point deducted for uncertainty about applicability of results (sunlight variations)
1 (38) Treatment success Oral PUVA v topical PUVA 4 −2 0 0 0 Low Quality points deducted for sparse data and incomplete reporting of results
1 (at least 241 people) Treatment success Different oral PUVA derivatives v each other 4 −1 0 0 0 Moderate Quality point deducted for poor-quality studies
1 (at least 153 people) Treatment success Methoxsalen plus trioxysalen plus ultraviolet A v different psoralen derivatives plus ultraviolet A 4 −2 0 0 0 Low Quality point deducted for sparse data and poor-quality study
1 (22) Treatment success NB-UVB v placebo 4 −2 0 0 0 Low Quality points deducted for sparse data and for controlled trial
1 (22) Treatment success Oral PUVB (broadband) v oral PUVA 4 −2 0 −1 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for inclusion of children
1 (45) Treatment success Topical PUVA v no treatment 4 −1 0 0 0 Moderate Quality point deducted for sparse data
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?
1 (45) Treatment success Clobetasol propionate v PUVA 4 −1 0 0 0 Moderate Quality point deducted for sparse data
1 (20) Treatment success Clobetasol propionate v topical tacrolimus 4 −1 0 0 0 Moderate Quality point deducted for sparse data
What are the effects of ultraviolet light treatments for vitiligo in children?
1 (50) Treatment success Trioxysalen plus ultraviolet A v ultraviolet A alone 4 −1 0 −1 0 Low Quality point deducted for sparse data. Directness point deducted for applicability of results
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Type of evidence: 4 = RCT; 2 = Observational; 1 = Non-analytical/expert opinion. Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratioNB-UVB, narrowband ultraviolet B

Glossary

Active vitiligo

An extending vitiligo with enlarging lesions or development of new lesions.

Broadband ultraviolet B

290–320 nm wavelength ultraviolet radiation.

Ecchymoses

The escape of blood into the tissues from ruptured blood vessels marked by a livid black and blue or purple spot or area.

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.

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).

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

310–315 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.

Segmental vitiligo

A form of localised vitiligo where one or more lesions of vitiligo arise in a quasidermatomal pattern.

Ultraviolet A

315–400 nm ultraviolet radiation.

Very low-quality evidence

Any estimate of effect is very uncertain.

Vitiligo vulgaris

A symmetrical type of generalised vitiligo in which scattered macules are seen over the entire body.

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, incidental or consequential, resulting from the application of the information in this publication.

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BMJ Clin Evid. 2008 Apr 18;2008:1717.

Corticosteroids (topical) in adults

Summary

TREATMENT SUCCESS Compared with placebo: Potent corticosteroids are more effective at 2–21 months at improving the proportion of people with more than 75% repigmentation of localised vitiligo ( high-quality evidence ). Potent topical corticosteroids plus ultraviolet A compared with topical corticosteroids: Topical fluticasone propionate plus ultraviolet A is more effective at increasing the proportion of people achieving more than 75% repigmentation of affected lesions at 9 months ( moderate-quality evidence ). Potent topical corticosteroids plus ultraviolet A compared with ultraviolet A: Topical fluticasone propionate plus ultraviolet A is no more effective at increasing the proportion of people achieving more than 75% repigmentation of affected lesions at 9 months (moderate-quality evidence). Very potent topical corticosteroids compared with placebo: Very potent topical corticosteroids are no more effective at improving the number of people with more than 75% repigmentation of their localised vitiligo (moderate-quality evidence). Potent compared with very potent corticosteroids: We don't know whether potent topical corticosteroids are more effective than very potent corticosteroids ( very 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 more than 25% repigmentation ( low-quality evidence ). NOTE We found no clinically important results 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.

Benefits

We found two systematic reviews (search date 1998 and 2006). The second systematic review did not include a meta-analysis of the clinical outcomes of interest.

Potent topical corticosteroids versus placebo:

We found one systematic review (search date 1998), which identified three RCTs. The systematic review found that, compared with placebo, potent topical corticosteroids significantly improved the proportion of people with more than 75% repigmentation (3 RCTs, 48 people, ages not reported, localised vitiligo, treatment over 2–21 months; AR 16/48 [33%] with potent corticosteroid v 0/48 [0%] with placebo; OR 14.32, 95% CI 2.45 to 83.72). The authors of the systematic review reported that potent topical corticosteroids were the most effective and safe therapies for localised vitiligo.

Potent topical corticosteroids plus ultraviolet A versus topical corticosteroids alone:

We found one systematic review, which identified one internally controlled trial. This trial found that, compared with topical fluticasone propionate (a potent corticosteroid) alone, topical fluticasone propionate plus ultraviolet A significantly increased the proportion of people achieving more than 75% repigmentation of affected lesions at 9 months. There was also no significant difference between ultraviolet A alone and topical fluticasone propionate plus ultraviolet A (135 people, of whom 96 were evaluable; 18–80 years of age; 2 equal, symmetrical, bilateral lesions on the arms, legs, or trunk, 0.05% fluticasone propionate cream applied at night, ultraviolet A (10 J/cm2 ) exposure twice weekly for 20 minutes; outcome assessed as percentage repigmentation, evaluated clinically by a single clinician against baseline photographs: 0% = no repigmentation, 75% = significant repigmentation, 100% = complete repigmentation; AR 10/67 [15%] with fluticasone propionate plus ultraviolet A v 2/67 [3%] with fluticasone propionate alone, P = 0.008; AR 8/68 [12%] with fluticasone propionate plus ultraviolet A v 3/68 [4%] with ultraviolet A alone, P = 0.06). The trial did not explain why only 96 of the 135 enrolled participants were evaluable.

Potent topical corticosteroids plus ultraviolet A versus ultraviolet A alone:

See potent topical corticosteroids plus ultraviolet A versus topical corticosteroids alone, above.

Very potent topical corticosteroids versus placebo:

We found one systematic review (search date 1998), which identified two RCTs. It found no significant difference between very potent topical corticosteroids and placebo in the proportion of people with over 75% repigmentation (2 RCTs, 33 people, age range not reported, localised vitiligo, no time frame for treatment reported; AR 2/33 [6.1%] with very potent corticosteroid v 2/33 [6.1%] with placebo; OR 1.00, 95% CI 0.16 to 6.21).

Potent versus very potent corticosteroids:

We found one systematic review (search date 1998), which 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 reported). 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 topical calcipotriol versus topical calcipotriol alone:

We found one RCT (45 people with vitiligo affecting 5% of their skin) comparing topical calcipotriol ointment and bethamethasone dipropionate in combination 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 more than 25% repigmentation (assessed by clinical examination and comparison to baseline photographs) at 3 months compared with topical calcipotriol cream alone (31 people, age range 10–60 years, vitiligo affecting less than 5% body surface area; AR 11/15 [73%] with betamethasone dipropionate plus calcipotriol v AR 6/16 [37%] with calcipotriol alone; P less than 0.01)

Harms

Potent topical corticosteroids versus placebo:

The systematic review (search date 1998) reported adverse effects from six 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 contained in the review gave no information on adverse effects.

Very potent topical corticosteroids versus placebo:

One RCT identified by the systematic review found that all the participants treated with 0.05% 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. 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 1998) reported adverse effects from seven 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 topical calcipotriol versus topical calcipotriol alone:

The RCT reported hypertrichosis (1/15 [6.7%]) and lesional dryness (1/15 [6.7%]) in people treated with betamethasone dipropionate plus calcipotriol. The calcipotriol-treated group reported peri-lesional hyperpigmentation (1/15 [6.7%]) and an irritant reaction (1/15 [6.7%]).

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 corticosteroids 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 corticosteroid treatment — probably because of the depletion of melanocyte reserves in hair follicles. Guidelines based on a systematic review suggested a combination of potent topical corticosteroids and ultraviolet A 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 of topical corticosteroids alone, which may be particularly helpful in children.

Substantive changes

Corticosteroids (topical) in adults: One RCT added comparing potent topical corticosteroids plus topical calcipotriol versus topical calcipotriol alone.The RCT found that topical betamethasone dipropionate cream plus topical calcipotriol cream significantly increased the proportion of people who achieved more than 25% repigmentation at 3 months compared with topical calcipotriol cream alone. This supports the categorisation of Beneficial.

BMJ Clin Evid. 2008 Apr 18;2008:1717.

Immunomodulators (topical) in adults

Summary

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 or at improving the number of children and adults with low-grade repigmentation (1–25%) of lesions at 9 months ( very low-quality evidence ). NOTE Topical pimecrolimus and tacrolimus may be associated with malignancy.

Benefits

Pimecrolimus versus placebo cream:

We found one intra-patient (left/right) RCT (20 people with symmetrical vitiligo, children and adults aged 12–60 years) comparing pimecrolimus cream (1%) versus placebo. The RCT found no significant 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 contralateral lesion) at six 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: mean difference in size of target lesion 90 mm2 (range –2046, 509) with topical pimecrolimus v 114 mm2 (range –1230, 615) with placebo; P = 0.5). The RCT also found no difference in the number of people experiencing a low-grade repigmentation (1–25%; percentage assessed by degree of peppering) of target lesions at nine months; a further four people were lost to follow-up (AR 3/14 [21%] with pimecrolimus v 2/14 [14%] with vehicle alone; P value not given).

Harms

Pimecrolimus versus placebo cream

: We found one RCT, which reported no skin atrophy or adverse effects.

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.

Comment

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 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. RCTs investigating the effects of imiquimod in vitiligo have not been undertaken.

Substantive changes

Immunodulators (topical) in adults One RCT added comparing pimecrolimus cream with placebo. The RCT found no significant difference in size of target lesion between topical pimecrolimus cream and placebo cream at six months. The RCT also found no difference in the number of people experiencing a low-grade repigmentation. The RCT was small with only some of the people included in the target population, therefore we don't know if pimecromlimus cream is an effective treatment for adults with acne. Categorisation unchanged (Unknown effectiveness)

BMJ Clin Evid. 2008 Apr 18;2008:1717.

Levamisole (oral) in adults

Summary

DISEASE PROGRESSION Levamisole plus potent topical corticosteroids compared with potent topical corticosteroids alone: Levamisole plus topical mometasone furoate 0.1% may be no more effective 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 about the benefits of levimasole 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:

We found one poor-quality RCT, which compared oral levamisole (100–150 mg twice weekly) plus topical mometasone furoate 0.1% (applied once daily) versus topical mometasone furoate 0.1% alone. It found no significant difference 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 less than 2% body surface, generalised [acrofacial] and focal; AR for not developing new lesions 19/23 [83%] with levamisole plus mometasone v 12/20 [60%] with mometasone alone; P = 0.19). The study defined “slowly spreading” as developing 1–5 new lesions in the previous month or 6–15 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 (more than 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 reasons unknown, 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 topical corticosteroids alone:

We found one poor-quality RCT. It 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; abdominal pain: 1/23 [4%] with levamisole plus mometasone v 1/23 [4%] with mometasone; significance assessment not performed). The 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 which received mometasone only.

Comment

Clinical guide:

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).

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Apr 18;2008:1717.

Vitamin D analogues (topical) in adults

Summary

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 more than 25% repigmentation (very low-quality evidence). Topical calcipotriol plus potent topical corticosteroids compared with potent topical corticosteroids: Topical calcipotriol plus potent topical corticosteroids may be no more effective at 3 months at improving the proportion of children and adults achieving more than 50% repigmentation, but may be more effective at decreasing the mean time to initial 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 ultraviolet A used (very low-quality evidence). Topical calcipotriol plus ultraviolet B (narrowband) compared with ultraviolet B: Topical calcipotriol plus ultraviolet B (narrowband) may be no more effective at improving repigmentation (more than 25%) of lesions in adults and children with vitiligo (very low-quality evidence). Topical tacalcitol plus narrowband ultraviolet B compared with narrowband ultraviolet B: Topical tacalcitol plus narrowband ultraviolet B may be more effective at 6 months at improving repigmentation scores in people with generalised vitiligo and symmetrical lesions (low-quality evidence). NOTE We found no direct information about whether topical calcipotriol 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 reviews 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 3–6 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, 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 extrapolated to adults and other children, but they would need to be confirmed by larger numbers of both adults and children.

Topical calcipotriol versus topical betamethasone dipropionate:

We found one RCT (49 people with vitiligo affecting 5% of their skin) comparing topical calcipotriol versus betamethasone. The RCT found that proportionally fewer people achieved more than 25% repigmentation (assessed by clinical examination and comparison to 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 years; AR 6/16 [38%] with calcipotriol v AR 9/18 [50%] with betamethasone dipropionate; P value not given).

Topical calcipotriol plus potent topical corticosteroids versus potent topical corticosteroids alone:

We found one RCT (49 people with vitiligo affecting 5% of their skin) comparing topical calcipotriol plus potent corticosteroid versus potent corticosteroid. The RCT found no significant difference at 3 months in people achieving more than 50% repigmentation (assessed by clinical examination and comparison with baseline photographs) with topical calcipotriol (0.005% applied twice daily) plus topical betamethasone 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 betamethasone dipropionate v AR 2/15 [13%] with betamethasone dipropionate; P greater than 0.1). However the RCT may have been too small to detect differences between groups. No one in the RCT achieved more than 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 betamethasone dipropionate v 9.04 ± 2.0 weeks with betamethasone propionate; P less than 0.01).

Topical calcipotriol plus PUVA versus PUVA alone:

We found one systematic review (search date 2006), 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 responsive areas, and stopped when repigmentation ceased, clinician assessment of repigmentation at weekly intervals, ultraviolet A dosage determined according to minimal erythema doses of ultraviolet A (range 0.75–10.2 J/cm2). It found that calcipotriol cream (0.05 mg/kg) plus PUVA (oral methoxsalen 0.5–0.6 mg/kg plus ultraviolet A units) twice weekly was more effective in reaching “complete repigmentation” (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 ultraviolet A dose and number of ultraviolet A exposures were significantly lower for the calcipotriol-treated side than for the placebo-treated side (mean cumulative ultraviolet A dose: 232 J/cm2 for the calcipotriol-treated side v 260 J/cm2 for the placebo-treated side; number of ultraviolet A exposures: 27 for the placebo-treated side v 30 for the calcipotriol-treated side; P = 0.001), which equated to an approximately 26 J/cm2 lower cumulative ultraviolet A dosage, and approximately three fewer treatment exposures.

Topical calcipotriol plus ultraviolet B (narrowband) versus ultraviolet B (narrowband) alone:

We found one left–right comparison RCT, which found no significant difference in repigmentation of lesions between calcipotriol (0.005% cream applied 2 hours before and after ultraviolet B session) plus narrowband ultraviolet B (NB-UVB) (initial dose 0.25 J/cm2, increased by 20% for each treatment) and narrowband ultraviolet B 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 more than 30% body surface area, bilateral symmetrical distribution, numbers not reported; P greater than 0.05). The mean total ultraviolet B dose delivered was 110 ± 45 J/cm2. The authors felt that the 20% increments in the ultraviolet B 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 more than 50% repigmentation, irrespective of calcipotriol, was 11/20 [55%]. We found a second RCT (40 people with vitiligo) comparing topical calcipotriol plus NB-UVB versus NB-UVB alone. The RCT found no significant difference in achieving more than 25% repigmentation after 30 treatments (clinical response assessed by photographs and visual scoring) between NB-UVB (initial dose 0.1 J/cm2 followed by increments of 0.05 J/cm2 as tolerated, three times weekly) plus calcipotriol (0.05% ointment applied twice daily after phototherapy) and NB-UVB alone (34 people, aged 17–26 years, stable vitiligo affecting more than 10% of the body surface area, AR 10/13 [77%] with calcipotriol plus NB-UVB v AR 19/24 [79%] with NB-UVB alone; P value not reported).

Topical tacalcitol plus narrowband ultraviolet B versus narrowband ultraviolet B alone:

We found one RCT (32 people with generalised vitiligo and symmetrical lesions) comparing topical tacalcitol plus NB-UVB versus NB-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 NB-UVB (starting with 70% minimal erythema dose followed by 10–30% increments as tolerated) plus topical tacalcitol ointment (dose 10 mg/4 cm2 applied once daily to assigned areas as measured by microdosator) compared with NB-UVB alone (absolute numbers not reported; P less than 0.0005).

Harms

Topical calcipotriol versus placebo or no treatment:

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

Topical calcipotriol versus topical betamethasone dipropionate:

The RCT reported significantly fewer adverse effects with calcipotriol compared with betamethasone dipropionate (peri-lesional hyperpigmentation (1/15 [7%]), and an irritant reaction with calcipotriol (1/15 [7%]) v lesional atrophy (5/15 [33%]), lesional soreness (4/15 [27%]), lesional dryness (1/15 [7%]), and hypertrichosis (1/15 [7%]) with betamethasone dipropionate; P less than 0.05).

Topical calcipotriol plus potent topical corticosteroids versus potent topical corticosteroids:

The RCT 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 [7%])and hypertrichosis (1/15 [7%]) with betamethasone dipropionate alone; P less than 0.05.

Topical calcipotriol plus psoralen plus PUVA versus PUVA plus placebo:

We found one systematic review, which identified one internally controlled RCT. This 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 not stated).

Calcipotriol plus ultraviolet B versus ultraviolet B:

We found one left–right comparison RCT, which reported erythema, irritation, and mild vesiculation (1/20 [5%]) in the calcipotriol-treated sides.

The second RCT reported transient itching and erythema.

Topical tacalcitol plus narrowband ultraviolet B versus narrowband ultraviolet B:

We found one RCT, which reported minimal adverse effects (mild erythema and itching) in the combination therapy group.

Comment

In the treatment of psoriasis, calcipotriol has a light-saving effect when used in combination with ultraviolet B, and response is achieved at a lower dose of ultraviolet B, but calcipotriol does not increase the overall effectiveness of ultraviolet B treatment. However, the role of calcipotriol in the treatment of vitiligo is yet to be determined. We found no RCTs investigating the effects of other topical vitamin D analogues (tacalcitol) or vitamin D (calcitriol) in vitiligo.

Substantive changes

Vitamin D analogues (topical) Three RCTs added. The first RCT compared calcipotriol with topical betamethasone dipropionate and with potent topical corticosteroids. The RCT found that proportionally fewer people achieved more than 25% repigmentation with topical calcipotriol cream compared with topical betamethasone dipropionate cream and found no significant difference at 3 months in people achieving more than 50% repigmentation with topical calcipotriol plus topical betamethasone dipropionate cream compared with betamethasone dipropionate cream alone. The second RCT compared topical calcipotriol plus ultraviolet B (narrowband) with ultraviolet B (narrowband) alone. The RCT found no significant difference in achieving more than 25% repigmentation after 30 treatments between NB-UVB plus calcipotriol and NB-UVB alone. The third RCT compared topical tacalcitol plus narrowband ultraviolet B with narrowband ultraviolet B. The RCT found significantly higher repigmentation scores at 6 months in people treated with NB-UVB plus topical tacalcitol ointment compared with NB-UVB alone. Recategorised from Unknown effectiveness to Unlikely to be beneficial.

BMJ Clin Evid. 2008 Apr 18;2008:1717.

Corticosteroids (oral) in adults

Summary

We found no direct information 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.

Benefits

We found no systematic reviews or RCTs.

Harms

We found no RCTs. One case series (29 people with vitiligo [24 with generalised vitiligo and 5 with 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, menstrual disturbance, and hypertrichosis.

Comment

Clinical guide:

Further RCTs into the effects of oral corticosteroids are unlikely to be undertaken. On the basis of 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.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Apr 18;2008:1717.

Oral PUVA in adults

Summary

TREATMENT SUCCESS Methoxsalen plus ultraviolet A compared with ultraviolet A alone: Methoxsalen plus ultraviolet A may be no more effective at achieving more than 75% repigmentation of all vitiliginous macules at 2 years in adults and children ( very low-quality evidence ). Trioxysalen plus ultraviolet A compared with ultraviolet A alone: Trioxysalen plus ultraviolet A may be no more effective at achieving more than 75% repigmentation of all vitiliginous macules at 2 years in adults and children (very low-quality evidence). Unsubstituted PUVA compared with ultraviolet A alone: We don't know whether PUVA is more effective at improving repigmentation of affected lesions in adults and children at 18–24 months (very low-quality evidence). Oral PUVA compared with topical PUVA: Oral PUVA may be no more effective at 18 months at achieving more than 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 ultraviolet A are equally effective at improving repigmentation of more than 75% of all vitiliginous macules at 2 years ( moderate-quality evidence ). Methoxsalen plus trioxysalen plus ultraviolet A compared with different psoralen derivatives plus ultraviolet A: Methoxsalen plus trioxysalen plus ultraviolet A may be more effective than unsubstituted PUVA at improving repigmentation of more than 75% of all vitiliginous macules at 2 years (low-quality evidence). NOTE There is consensus that PUVA is effective for vitiligo.

Benefits

We found two systematic reviews (search dates 1998 and 2006). They found that the quality of the methods and reporting of included studies was poor. Both 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 people 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 independent investigators against photographs at enrolment and at 6-monthly intervals. People were randomly assigned to one of the following groups: 0.3 mg/kg methoxsalen (47 people), 0.6 mg/kg methoxsalen (49 people), 0.8 mg/kg trioxysalen (39 people), 1.8 mg/kg trioxysalen (61 people), 3.6 mg/kg trioxysalen (43 people), 0.3 mg/kg methoxsalen plus 1.8 mg/kg trioxysalen (55 people), 0.6 mg/kg unsubstituted psoralen (35 people), 1.2 mg/kg unsubstituted psoralen (37 people), and placebo (24 people). All eight groups were exposed to ultraviolet A (sunlight).

Methoxsalen plus ultraviolet A versus ultraviolet A alone:

One RCT identified by two systematic reviews found no significant difference in repigmentation of more than 75% of all vitiliginous macules at 2 years between oral methoxsalen plus ultraviolet A and ultraviolet A alone (see table 1 ).

Table 1.

Methoxsalen, trioxysalen, unsubstituted PUVA versus placebo.

Comparison Outcome Result
Methoxsalen (0.3 mg/kg) plus UVA vUVA alone Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6 monthly intervals) AR 12/49 [24%] with oral methoxsalen plus UVA v 0/24 [0%] with placebo; RR 12.50, 95% CI 0.77 to 202.63
 
Methoxsalen (0.6 mg/kg) plus UVA vUVA alone Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 12/49 [24%] with oral methoxsalen plus UVA v 0/24 [0%] with placebo; RR 12.50, 95% CI 0.77 to 202.63
 
Methoxsalen (any dose) plus UVA vUVA alone Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 24/98 [24%] with oral methoxsalen plus UVA v 0/24 [0%] with placebo; RR 12.37, 95% CI 0.78 to 196.56
 
Trioxysalen (0.8 mg/kg) plus UVA vUVA alone Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 7/39 [18%] with trioxysalen plus UVA v 0/24 [0%] with placebo; RR 9.38, 95% CI 0.56 to 157.09
 
Trioxysalen (1.8 mg/kg) plus UVA vUVA alone Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 9/61 [15%] with trioxysalen plus UVA v 0/24 [0%] with placebo; RR 7.66, 95% CI 0.46 to 126.70
 
Trioxysalen (3.6 mg/kg) plus UVA vUVA alone Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 8/43 [19%] with trioxysalen plus UVA v 0/24 [0%] with placebo; RR 9.66, 95% CI 0.58 to 160.37
 
Trioxysalen (any dose) plus UVA vUVA alone Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 24/143 [17%] with trioxysalen plus UVA v 0/24 [0%] with placebo; RR 8.51, 95% CI 0.53 to 135.43
 
Unsubstituted PUVA (0.6 mg/kg) vUVA alone Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 3/35 [9%] with 40 mg unsubstituted PUVA v 0/24 [0%] with placebo; RR 4.86, 95% CI 0.26 to 90.03
 
Unsubstituted PUVA (1.2 mg/kg) vUVA alone Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 11/37 [30%] with 1.2 mg/kg unsubstituted PUVA v 0/24 [0%] with placebo; RR 15.13, 95% CI 0.93 to 245.39
 
Unsubstituted PUVA (any dose) vUVA alone Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 14/72 [19%] with unsubstituted PUVA v 0/24 [0%] with placebo; RR 9.93, 95% CI 0.61 to 160.47
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UV, ultraviolet.

Trioxysalen plus ultraviolet A versus ultraviolet A alone:

One RCT identified by two systematic reviews found no significant difference in repigmentation of more than 75% of all vitiliginous macules at 2 years between oral trioxysalen plus ultraviolet A and ultraviolet A alone (see table 1 ).

Unsubstituted PUVA versus ultraviolet A alone:

We found two systematic reviews (search dates 1998, 2006), which both identified two RCTs. Pooled results from the first systematic review found that, compared with sunlight alone, oral unsubstituted PUVA significantly improved repigmentation of affected skin (97 people; age range not reported; generalised vitiligo; exposure to mid-day sun 2 hours after oral psoralen; exposure time increased according to tolerance; degree of repigmentation assessed visually by observer and participant at 18 months in one RCT and by comparison with initial photographs by two independent investigators at 2 years in the other; 2 RCTs; AR 13/46 [28%] with oral unsubstituted PUVA v 0/51 [0%] with ultraviolet A alone; OR 19.87, 95% CI 2.37 to 166.32; P value not reported). The second RCT identified by the review found no significant difference in repigmentation of more than 75% of all vitiliginous macules at 2 years between oral PUVA (at any dose) and ultraviolet A alone (see table 1 ).

Oral PUVA versus topical PUVA:

We found one systematic review, which identified one RCT. It found no significant difference between oral and topical PUVA (dose and psoralen derivative not specified) in achieving repigmentation in more than 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:

The systematic review identified one RCT, which found no significant difference between different derivatives and doses of psoralen (methoxsalen, unsubstituted psoralen, trioxysalen) plus ultraviolet A versus each other in repigmentation of more than 75% of all vitiliginous macules at 2 years (see table 2 ). The same RCT found that a combination of methoxsalen plus trioxysalen plus ultraviolet A significantly improved the repigmentation of more than 75% of vitiliginous macules at 2 years when compared with ultraviolet A alone, but was no more effective compared with methoxsalen plus ultraviolet A or trioxysalen plus ultraviolet A, and less effective compared with unsubstituted PUVA (see table 3 ).

Table 2.

Different oral PUVA derivatives versus each other.

Comparison Outcome Result
Methoxsalen plus UVA vTrioxysalen (any dose) plus UVA Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 24/98 [24%] with oral methoxsalen plus UVA v 24/143 [17%] with trioxysalen; RR 1.46, 95% CI 0.88 to 2.42
 
Methoxsalen plus UVA vUnsubstituted PUVA (any dose) Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 24/98 [24%] with oral methoxsalen plus UVA v 14/72 [19%] with unsubstituted PUVA; RR 1.26, 95% CI 0.70 to 2.26
 
Trioxysalen (any dose) plus UVA vMethoxsalen plus UVA Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 24/143 [17%] with trioxysalen plus UVA v 24/98 [24%] with methoxsalen; RR 0.69, 95% CI 0.41 to 1.13
 
Trioxysalen (any dose) plus UVA vUnsubstituted psoralen plus UVA Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 24/98 [24%] with trioxysalen plus UVA v 14/72 [19%] with unsubstituted PUVA; RR 1.26, 95% CI 0.70 to 2.26
 
Trioxysalen plus UVA vUnsubstituted PUVA (any dose) Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 14/72 [19%] with trioxysalen plus UVA v 24/143 [17%] with unsubstituted psoralen (any dose); RR 1.16, 95% CI 0.64 to 2.10
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UV, ultraviolet.

Table 3.

Methoxsalen plus trioxysalen plus ultraviolet A versus different PUVA derivatives .

Comparison Outcome Result
Methoxsalen plus trioxysalen plus UVA vPlacebo Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 21/55 [38%] with oral methoxsalen plus trioxysalen plus UVA v 0/24 [0%] with placebo; RR 19.20, 95% CI 1.21 to 304.50
 
Methoxsalen plus trioxysalen (any dose) plus UVA vMethoxsalen plus UVA Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 21/55 [38%] with methoxsalen plus trioxysalen plus UVA v 24/98 [24%] with oral methoxsalen plus UVA; RR 0.64, 95% CI 0.40 to 1.04
 
Methoxsalen plus trioxysalen (any dose) plus UVA vTrioxysalen plus UVA Repigmentation in moer than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 21/55 [38%] with methoxsalen plus trioxysalen plus UVA v 24/98 [24%] with trioxysalen plus UVA; RR 0.64, 95% CI 0.40 to 1.04
 
Methoxsalen plus trioxysalen (any dose) plus UVA vUnsubstituted PUVA Repigmentation in more than 75% of all vitiliginous macules at 2 years (degree of repigmentation assessed visually by clinician against baseline photographs at 6-monthly intervals) AR 21/55 [38%] with methoxsalen plus trioxysalen plus UVA v 14/72 [19%] with unsubstituted PUVA; RR 0.51, 95% CI 0.29 to 0.91
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UV, ultraviolet.

Harms

Methoxsalen plus ultraviolet A versus ultraviolet A alone:

One RCT found that methoxsalen plus ultraviolet A increased nausea and pruritus compared with ultraviolet A alone (nausea: 20% with methoxsalen v 10% with ultraviolet A alone; pruritus: 20% with methoxsalen v 10% with ultraviolet A alone; significance assessment not performed, absolute figures not reported). It also reported that methoxsalen was associated with gastrointestinal discomfort (8%).

Trioxysalen plus ultraviolet A versus placebo:

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 ultraviolet A alone:

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 0.6 mg/kg unsubstituted psoralen and placebo had nausea and pruritus (nausea: 9% with unsubstituted psoralen v 10% with ultraviolet A alone; pruritus: 9% with unsubstituted psoralen v 7% with ultraviolet A 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) were not evaluated.

Oral PUVA versus topical PUVA:

The RCT did not search for or report any adverse effects.

Different psoralen derivatives plus ultraviolet A versus each other:

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 and trioxysalen. The placebo group reported nausea (2/24 [8%]) and pruritus (1/24 [4%]). The methoxsalen groups reported 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%]).

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 nor developed abnormal liver function values.

Ultraviolet A source:

It is important to remember that, in studies using sunlight as the source of ultraviolet A, 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 ultraviolet 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 ultraviolet A light devices.

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 USA, but is thought to be associated with a lower incidence of phototoxicity and gastrointestinal adverse effects compared 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.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Apr 18;2008:1717.

Ultraviolet B (narrowband) in adults

Summary

TREATMENT SUCCESS Narrowband ultraviolet B compared with placebo: Narrowband ultraviolet B may be more effective at 6 months at increasing the mean repigmentation of affected lesions ( low-quality evidence ). Compared with topical PUVA: We don't know whether narrowband ultraviolet B is more effective at 4 months at improving repigmentation of vitiliginous lesions ( very low-quality evidence ).

Benefits

Narrowband ultraviolet B versus placebo:

We found one internally controlled trial, which found that, compared with placebo, narrowband ultraviolet B (NV-UVB) significantly increased mean repigmentation of affected lesions after 6 months (70% minimal erythema doses, increased by 10% increments, three 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 scoring [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 NB-UVB v 3% repigmentation with placebo; P less than 0.001, absolute figures not reported). Lower extremities responded best, but feet responded worst.

Narrowband ultraviolet B versus topical PUVA:

We found one RCT. See benefits of topical PUVA in adults section.

Harms

Narrowband ultraviolet B versus placebo:

We found one RCT, which reported hyperpigmentation, resulting in one person withdrawing from the study, and mild phototoxic effects.

Narrowband ultraviolet B versus topical PUVA:

The RCT did not report any adverse effects with NB-UVB treatment.

Comment

Despite only weak RCT evidence to support its use, NB-UVB is considered safe and effective 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 generalised disease. One report recommended (on the basis of a number of case series 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 ultraviolet B. Further research is necessary to determine the relative effectiveness of different treatment regimens.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Apr 18;2008:1717.

ultraviolet B (broadband) in adults

Summary

TREATMENT SUCCESS Oral PUVB (broadband) compared with oral PUVA: Oral PUVB (broadband) may be less effective in producing 50–60% repigmentation of extensive vitiligo in adults and children ( very low-quality evidence ).

Benefits

Oral PUVB (broadband) versus oral PUVA:

We found no systematic reviews or RCTs. We found one left–right comparison RCT, which found that fewer treatments with oral methoxsalen (0.7 mg/kg) plus ultraviolet A (PUVA 320–400 nm; initial dose of ultraviolet A 0.5 J/cm2 increased by 0.5 J/cm2 at alternate sessions) were required compared with oral methoxsalen plus broadband ultraviolet B (PUVB 290–320 nm; initial dose of ultraviolet B of 0.03 J/cm2 increased by 0.03 J/cm2 at each session) to produce 50–60% 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 more than 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 50–60% repigmentation was 25 ± 4 with PUVA, and 26 ± 3 for PUVB. To achieve 50–60% repigmentation of vitiligo, the mean cumulative dose of ultraviolet A was 45 ± 16 J/cm2, and for ultraviolet B was 4.6 ± 1.9 J/cm2.

Harms

We found no systematic reviews on the harms of broadband ultraviolet B. One RCT comparing broadband oral PUVB versus PUVA reported a phototoxic reaction with both treatments (4/22 [18%] with broadband oral PUVBv 5/22 [23%] with PUVA) and skin thickening (6/22 [27%] with broadband oral PUVB v 6/22 [27%] with PUVA).

Comment

There is limited evidence for the use of broadband ultraviolet B in vitiligo. RCTs would be feasible and should be undertaken, especially comparison studies with narrowband ultraviolet B.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Apr 18;2008:1717.

Topical PUVA in adults

Summary

TREATMENT SUCCESS Topical PUVA compared with no treatment: Topical PUVA is no more effective at 18 months at achieving more than 50% repigmentation of vitiliginous lesions ( moderate-quality evidence ). Compared with oral PUVA: Topical PUVA may be no more effective at 18 months at achieving more than 50% repigmentation of all vitiliginous macules in adults and children ( low-quality evidence ). Compared with narrowband ultraviolet B: 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:

We found one systematic review (search date 2006), which identified one RCT (88 people; age range not reported; generalised vitiligo), which had four arms: oral PUVA (sunlight), topical unsubstituted PUVA (sunlight), oral PUVA (sunlight) plus triamcinolone, and no treatment (cosmetic camouflage). It found no significant difference between topical unsubstituted PUVA (dosage and brand of psoralens not given) (sunlight) and no treatment in the repigmentation of more than 50% of vitiliginous lesions at 18 months (exposure to mid-day 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).

Oral PUVA versus topical PUVA:

The RCT found no significant difference at 18 months between topical and oral psoralens (see benefits of oral PUVA).

Topical PUVA versus narrowband ultraviolet B:

One additional quasi-RCT (106 people, age range 7–70 years [mean age 36.7 years with PUVA and 36 years with ultraviolet B], active and generalised vitiligo of more than 3 months' duration, 10–50% body surface involved) compared topical 0.005% unsubstituted PUVA versus narrowband ultraviolet B 311 nm treatment twice weekly for 4 months (psoralen administered 15 minutes prior to ultraviolet A; ultraviolet A initial dose 0.5 J/cm2, increased in 20% increments until erythema and then continued at same dose; narrowband ultraviolet B [NB-UVB] initial dose 0.075 J/cm2, increased in 20% increments until erythema). It found that, compared with NB-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 NB-UVB, significance assessment not performed). 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:

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

Topical PUVA versus narrowband ultraviolet B:

The additional RCT reported erythema (3/28 [11%]), 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.

Comment

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 PUVA. Despite weak evidence for the use of both oral and topical psoralens in vitiligo, clinicians are more likely to recommend oral psoralens over topical psoralens because of the consensus that oral PUVA is more effective than topical PUVA.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Apr 18;2008:1717.

Corticosteroids (topical) in children

Summary

TREATMENT SUCCESS Clobetasol propionate compared with PUVA: Clobetasol propionate is more effective at increasing the proportion of children achieving more than 75% repigmentation at 6 months ( moderate-quality evidence ). Clobetasol propionate compared with topical tacrolimus: Clobetasol propionate and topical tacrolimus are equally effective at 2 months at increasing the proportion of children achieving more than 75% repigmentation (moderate-quality evidence).

Benefits

Clobetasol propionate versus PUVA:

We found one systematic review (search date 2006), which did not include a meta-analysis for the clinical outcomes of interest. It identified two RCTs. 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 prior to ultraviolet A exposure) three times weekly. It found that, compared with topical PUVA, clobetasol propionate significantly increased the proportion of children achieving more than 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%) versus topical tacrolimus (0.1%) twice daily. It found no significant difference between topical clobetasol and topical tacrolimus in achieving more than 75% repigmentation of affected areas at 2 months (grade of repigmentation evaluated by colour slides at baseline and analysed fortnightly 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 0.1% tacrolimus; P = 1.00).

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%]).

Clobetasol propionate versus topical tacrolimus:

The second RCT identified by the review reported atrophy (3/20 [15%]) and telangiectasia (2/20 [10%]).

Comment

Clinical guide:

In developing guidelines for the management of vitiligo, a consensus was agreed among clinicians 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%]).

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Apr 18;2008:1717.

Immunomodulators (topical) in children

Summary

TREATMENT SUCCESS Topical tacrolimus compared with clobetasol propionate: Topical tacrolimus and clobetasol propionate are equally effective at 2 months at increasing the proportion of children achieving more than 75% repigmentation ( moderate-quality evidence ). Pimecrolimus compared with placebo cream: Topical pimecrolimus cream (1%) may be no more effective at 6 months at reducing the size of lesions, or at improving the number of children and adults with low-grade repigmentation (1–25%) of lesions at 9 months ( low-quality evidence ). NOTE We found no direct information 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 reviews or RCTs.

Topical tacrolimus versus clobetasol propionate:

We found one systematic review (search date 2006), which did not include a meta-analysis for the clinical outcomes of interest. It identified one RCT, which was a left–right comparison of 0.05% clobetasol propionate versus 0.1% tacrolimus. See benefits of topical corticosteroids in children.

Topical pimecrolimus versus placebo:

We found one RCT of a mixed population of adults and children comparing topical pimecrolimus versus placebo. See benefits of immunomodulators in adults.

Topical imiquimod versus placebo:

We found no systematic reviews or RCTs.

Harms

The RCT reported a burning sensation (2/20 people [10%]), which did not preclude the continuation of therapy, during the first 2 weeks of therapy. See also harms of topical immunomodulators in adults.

Pimecrolimus vs placebo cream:

We found one RCT of a mixed population of adults and children. See harms of immunomodulators in adults.

Comment

See above for comment and drug safety alert on possible malignancy risk with topical immunomodulators compared with topical corticosteroids in adults. 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 tacrolimus and contraindicates application to malignant or premalignant lesions.

Substantive changes

Immunomodulators (topical) in children One RCT added comparing pimecrolimus cream with placebo. The RCT found no significant difference in size of target lesion between topical pimecrolimus cream and placebo cream at six months. The RCT also found no difference in the number of people experiencing a low-grade repigmentation. The RCT was small with only some of the people included in the target population, therefore we dont know if pimecromlimus cream is an effective treatment for children with acne. Categorisation unchanged (Unknown effectiveness).

BMJ Clin Evid. 2008 Apr 18;2008:1717.

Vitamin D analogues (topical) in children

Summary

TREATMENT SUCCESS 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 children and adults and at lowering the dose and number of exposures of Ultraviolet A used ( very low-quality evidence ). Topical calcipotriol plus ultraviolet B (narrowband) compared with ultraviolet B: Topical calcipotriol plus ultraviolet B (narrowband) may be no more effective at improving repigmentation (more than 25%) of lesions in children and adults with vitiligo (very low-quality evidence).

Benefits

Topical calcipotriol versus placebo:

We found no systematic reviews or good quality RCTs (see comment on vitamin D analogues in adults).

Topical calcipotriol plus PUVA versus PUVA:

We found one RCT in a mixed population of adults and children (see benefits of vitamin D analogues in adults).

Topical calcipotriol plus ultraviolet B versus ultraviolet B:

We found one RCT in a mixed population of adults and children (see benefits of vitamin D analogues in adults).

Harms

Topical calcipotriol versus placebo:

We found no systematic reviews or RCTs.

Topical calcipotriol plus PUVA versus ultraviolet A:

We found one RCT in a mixed population of adults and children (see harms of vitamin D analogues in adults)

Topical calcipotriol plus ultraviolet B versus ultraviolet B:

We found one RCT in a mixed population of adults and children (see harms of vitamin D analogues in adults).

Comment

One RCT of poor quality (including adults and children with vitiligo) found no significant difference 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.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Apr 18;2008:1717.

Corticosteroids (oral) in children

Summary

We found no direct information 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 reviews or RCTs.

Harms

We found no RCTs.

Comment

Clinical guide:

The use of oral pulsed corticosteroids in children has been reported to be successful in uncontrolled 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 moon face, weight gain, and growth retardation).

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Apr 18;2008:1717.

Ultraviolet B (narrowband) in children

Summary

TREATMENT SUCCESS Compared with topical PUVA: We don't know whether narrowband ultraviolet B is more effective at 4 months at improving repigmentation of vitiliginous lesions in adults and children ( very low-quality evidence ). NOTE We found no direct information about whether narrowband ultraviolet B is better than no active treatment in children with vitiligo. The consensus is that narrowband ultraviolet B is safe and effective in children, and may improve quality of life.

Benefits

Narrowband ultraviolet B versus placebo:

We found no systematic reviews or RCTs.

Narrowband ultraviolet B versus topical PUVA:

We found no systematic reviews. We found one RCT in a mixed population of adults and children. See benefits of topical PUVA in adults.

Harms

Narrowband ultraviolet B versus placebo:

We found no systematic reviews or RCTs.

Narrowband ultraviolet B versus topical PUVA:

We found no systematic reviews. We found one RCT, which did not report any adverse effects with ultraviolet B treatment.

Comment

We found no controlled trials investigating narrowband or broadband ultraviolet B in the management of vitiligo in children. We found one prospective cohort study, which found that narrowband ultraviolet B (NB-UVB)(310–315 nm, initial dose 0.25 J/cm2, increased by 20% increments, twice weekly) resulted in more than 75% repigmentation at 1 year in about half the participants (51 children, age range 4–16 years, generalised vitiligo affecting more than 5% body surface area, clinician assessment using baseline photography; AR 27/51 [53%] with NB-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 (2/20 [10%]) with NB-UVB. The safe duration of NB-UVB and maximum cumulative dose compared with other treatment modalities remains undetermined, but the consensus is that this form of treatment is safe and effective in children, and may improve their quality of life. Ultraviolet B 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 NB-UVB and highest with PUVA.

Substantive changes

No new evidence

BMJ Clin Evid. 2008 Apr 18;2008:1717.

PUVA (oral or topical) in children

Summary

TREATMENT SUCCESS Trioxysalen plus ultraviolet A compared with ultraviolet A alone: Ultraviolet A (sunlight or sun lamp) plus oral trioxysalen may be more effective at 8 months at achieving cure or clear improvement in skins of children affected by vitiligo ( low-quality evidence ). Topical PUVA compared with narrowband ultraviolet B: 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 ). Topical PUVA compared with clobetasol propionate: Topical PUVA is less effective at increasing the proportion of children achieving more than 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 ultraviolet A versus ultraviolet A alone:

We found one systematic review (search date 2006), which did not include a meta-analysis for the clinical outcomes of interest. It identified one RCT, which found that, compared with oral placebo plus ultraviolet A (sunlight/sun lamp), trioxysalen (10–30 mg daily) plus ultraviolet A (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 ultraviolet A v 7/25 [28%] with ultraviolet A alone; RR 2.29, 95% CI 1.14 to 4.58; P value not given). Trioxysalen was given 3 hours before exposure, or in two doses after breakfast and lunch for those using sunlight. Exposure time to ultraviolet A was 3–30 minutes daily until erythema appeared in the vitiligo patches.

Topical PUVA versus narrowband ultraviolet B:

We found one RCT (see benefits of topical PUVA in adults).

Topical PUVA versus clobetasol propionate:

We found one RCT (see benefits of topical corticosteroids in children).

Harms

Trioxysalen plus ultraviolet A versus ultraviolet A 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 ultraviolet A. There was no evidence of liver or blood toxicity in either control or treatment group.

Topical PUVA versus narrowband ultraviolet B:

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.

Topical PUVA versus clobetasol propionate:

The RCT reported blistering in two people receiving PUVA, requiring cessation of treatment for 1 month.

Comment

Clinical guide:

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.

Substantive changes

No new evidence

Articles from BMJ Clinical Evidence are provided here courtesy of BMJ Publishing Group

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