Comparison between topical tacrolimus and potent topical steroids in treatment of childhood vitiligo

Qiuyu Wang,Mahdi K.Fattah,Liang Wang,Jiangui Liao,Wenping Wang,Chuan Cao△

(1.Department of Plastic Surgery,Southwest Hospital,Third Military Medical University,Chongqing 400038, China;2.Department of Dermatology,Halabja General Hospital,Halabja City,Kurdistan Region of Iraq)

·循证医学·

Comparison between topical tacrolimus and potent topical steroids in treatment of childhood vitiligo

Qiuyu Wang1,Mahdi K.Fattah2,Liang Wang1,Jiangui Liao1,Wenping Wang1,Chuan Cao1△

(1.Department of Plastic Surgery,Southwest Hospital,Third Military Medical University,Chongqing 400038, China;2.Department of Dermatology,Halabja General Hospital,Halabja City,Kurdistan Region of Iraq)

[Abstract] Objective To assess which of topical tacrolimus and topical highly potent steroids,is more effective and safer in the treatment of pediatric vitiligo.Methods The PubMed,Cochrane library,Scopus and CINAHL plus databases were retrieved.The search was confined to English language articles.The randomized controlled trial(RCT) articles were included in our study.The quality of the identified articles was examined by using the CASP Randomised Controlled Trials Checklist.Results As a result,there were only a few studies related to the comparison.However,there were only two RCTs regarding a comparison of topical tacrolimus 0.1% and clobetasol propionate 0.05% in childhood vitiligo.Conclusion When the body surface area (BSA) involved in the child is <20%,and the disease is not rapidly spreading,topical therapy is the first choice.Topical tacrolimus may be considered as an alternative therapy for childhood vitiligo,especially for acrofacial and segmental types,before considering other modalities,but still need to observe long-term side effects.

topical tacrolimus;potent topical steroids;children;vitiligo

Vitiligo is a relatively common,acquired and depigmented skin disease[1].Around half or the patients have onset prior to the age of 20 years[2].Childhood vitiligo most often presents first on the head or neck and it seems to be a distinct subtype of vitiligo[3].At the moment there is no cure for vitiligo,but many treatments can often slow down its progress or,in some cases,bring about repigmentation[4].Therefore,timely treatments and choosing medications with fewer side-effects are very important for children.This is intended to minimize psychosocial and long lasting effects on the self-esteem of the affected children and their parents[5].However,topical steroids have been observed to have many side effects which can affect children′s appearance[6].Since 2002,some studies have confirmed the calcineurin inhibitor tacrolimus is effective in the treatment of vitiligo and is catching up fast[7].Additionally,there have been a few studies to observe the safety of tacrolimus[8-10].Unfortunately,there is a lack of literature reviews to compare the efficacy and safety of these topical treatment modalities in childhood vitiligo.Furthermore,most authors have to extrapolate the results form adults′ data[11].Therefore,it is essential to survey the findings and results from different studies and research in order to make the decision regarding the choice of suitable treatments for childhood vitiligo.

1 Materials and Methods

Searches were made of the PubMed,Cochrane library,Scopus and CINAHL plus databases.The search was confined to English language articles.After reading these papers,a retrospective review was performed of two randomised controlled trials(RCTs) regarding a comparison of topical tacrolimus 0.1% and clobetasol propionate 0.05% in childhood vitiligo.The quality of the identified articles was examined by using the CASP Randomised Controlled Trials Checklist (table 1).

Table 1 CASP Randomised Controlled Trials Checklist

Continued Table 1 CASP Randomised Controlled Trials Checklist

Table 2 Details of two RCTs.

2 Conclusion

The two RCTs demonstrated both topical tacrolimus and topical CS had similar efficacy in repigmenting paediatric vitiligo.The authors stated no significant clinical adverse events were noted in any group[12].Another RCT showed lesions in 3 patients using clobetasol presenting atrophy and 2 lesions incurred telangiectasias;tacrolimus caused a burning sensation in 2 lesions[13].When the body surface area (BSA) involved in the child is<20%,and the disease is not rapidly spreading,topical therapy is the first choice.Topical tacrolimus may be considered as an alternative therapy for childhood vitiligo,especially for acrofacial and segmental types,before considering other modalities,but still need to observe long-term side effects.

3 Discussion

Topical tacrolimus has similar efficacy as highly potent topical steroids (CP 0.05% ointment) in the treatment of childhood vitiligo.Although topical tacrolimus has some side effects,such as burning or pruritus,compared with topical CS,the studies showed fewer and lighter side effects had been observed.Tacrolimus does not interfere with collagen synthesis or have an effect on keratinocyte proliferation in vitro[14].Due to segmental vitiligo more commonly occurs in children with characteristics of fewer lesions and less body skin involvement[15-18],there is some merit of tacrolimus in the treatment of childhood vitiligo,such as using on sensitive areas and no atrophy,telangiectasia,and ocular complications.It is also useful for use on the acrofacialis.

There is a need to consider that topical steroids use could cause steroid acne on the face,upper chest,neck and back and systemic absorption of topical steroids could occur especially in younger children and can lead to iatrogenic Cushing syndrome[19].Hence,the current European Dermatology Forum consensus group guidelines recommend topical calcineurin inhibitors as a first line treatment for the face and neck because of lesser side effects[20].Nevertheless,mid to high potent topical steroids are still the first line treatment for body vitiligo in children except genital and intertriginous areas[19].There must some tips to improve efficiency and avoid side effects of topical steroids usage on childhood vitiligo.Firstly,the high potency topical steroids better not to be used for longer than 2-4 months[21].Secondly,depends on the condition,usage of topical potent steroids as a sequential or discontinuous or (sequential and discontinuous) combination should be schemed.For instance,one week on one week off or weekend only usage helps to minimize its non-desired effects[19].Thirdly,topical steroid sparing agents should be considered in long term use on the vitiliginous areas on the body.For example,pimecrolimus cream which has been shown effective to repigment vitiligo leasions in a comparable level with clobetasol in a split body studies[22].Fourthly,addition of oral zinc supplementation with topical steroids leads to higher response rate than topical steroids alone[23].Lastly,topical Vitamin D derivatives should be used together with topical steroids[24].

Tacrolimus was first reported in 2002 to be effective in the treatment of vitiligo[25].Until now there have been only two RCTs compared with these two medications in the treatment of childhood vitiligo.There is still a lack of large sample size research and long duration observation of the safety of tacrolimus.In addition,Abu et al.[26]reported molluscum contagiosum infection was suspected during the treatment of vitiligo with tacrolimus ointment and Kanwar et al.[27]stated that,in 2005,the Pediatric Advisory Committee of US FDA implemented a black box warning for tacrolimus and pimecrolimus due to the lack of long-term safety data and the potential risk of the development of malignancies[26-28].However,McCallum et al.showed extensive safety data of the 8-year availability when there was no increased incidence for cutaneous infections,and no evidence suggesting an increased risk of lymphoma or non-melanoma skin cancer in adults and children[29].So a conclusion about a firm long-term safety outcome cannot be drawn.

According to the results of the chosen papers,the repigmentation is associated with proper patient selection.The best response seen was in lesions over face and neck in many of the studies.Since the initial report of repigmentation in vitiliginous lesions by tacrolimus in adults,it has been observed that tacrolimus had similar efficacy as potent topical steroids,but fewer adverse effects[30].However,both of the studies which I chose were using 0.1% tacrolimus ointment.Side effects such as pruritus and burning were still reported.It is worth researching whether a lower concentration of tacrolimus has similar efficacy with much fewer side effects.Moreover,there is a possibility of spontaneous repigmentation.It seems that large enough samples are quite essential.In addition,the results can be impacted by no standard measurement.Tacrolimus has proposed that there is different efficacy in different Fitzpatrick Skin Types and it is superior to Fitzpatrck Skin Typers 3 to 4[31].Tacrolimus had been observed more response in the summer than in the winter[32].Last but not least,Byun et al.treated one child with vitiligo successfully combination helium-neon laser and 0.03% topical tacrolimus.There should be more consideration for childhood vitiligo treatment in the future[33].

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Qiuyu Wang(1981-)，Resident，Ph.D.candidate in plastic surgery of Third Military Medical University，The author mainly engage in clinical and research work of skin and skin related diseases,also participate in the National High Technology Research and Development Program of China (863 Program).The main direction is biological tissue engineering material。△

，E-mail:dr.caochuan@hotmail.com。

R758.4 +1

A

1671-8348(2017)09-1226-04

2016-07-22

2016-11-20)

2016年度重庆市出版专项资金资助项目

10.3969/j.issn.1671-8348.2017.09.025