Get access

Interventions for erosive lichen planus affecting mucosal sites

  • Review
  • Intervention

Authors


Abstract

Background

Erosive lichen planus (ELP) affecting mucosal surfaces is a chronic autoimmune disease of unknown aetiology. It is often more painful and debilitating than the non-erosive types of lichen planus. Treatment of erosive lichen planus is difficult and aimed at palliation rather than cure. Several topical and systemic agents have been used with varying results. Another Cochrane review has already assessed interventions for lichen planus affecting the mouth.

Objectives

To assess the effects of interventions in the treatment of erosive lichen planus affecting the oral, anogenital, and oesophageal regions.

Search methods

We searched the following databases up to September 2009: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), and LILACS (from 1982). We also searched reference lists of articles and online trials registries for ongoing trials.

Selection criteria

We considered all randomised controlled trials (RCTs) that evaluated the effectiveness of any topical or systemic interventions for ELP affecting either the mouth, genital region, or both areas, in participants of any age, gender, or race.

Data collection and analysis

The primary outcome measures were as follows:

(a) Pain reduction using a visual analogue scale rated by participants;
(b) Physician Global Assessment; and
(c) Participant global self-assessment.

Changes in scores at the end of therapy compared with baseline were analysed.

Main results

Fifteen RCTs were included, giving a total of 473 participants with ELP (study sizes ranged between 8-94). All studies involved oral sites only. Six studies included participants with non-erosive lichen planus but only the erosive subgroup was included for intended subgroup analysis. We were unable to pool data from any of the nine studies with only ELP participants or any of the six studies with the ELP subgroup, due to small numbers and the heterogeneity of the interventions, design methods, and outcome variables between studies.

One study involving 50 participants found that 0.025% clobetasol propionate administered as liquid microspheres significantly reduced pain compared to ointment (Mean difference (MD) -18.30, 95% confidence interval (CI) -28.57 to -8.03), but outcome data was only available in 45 participants (high risk of performance bias for blinding of participants, low/unclear risk of bias overall). However, in another study, a significant difference in pain was seen in the small subgroup of 11 ELP participants, favouring ciclosporin solution over 0.1% triamcinolone acetonide in orabase (MD -1.40, 95% CI -1.86 to -0.94) (high risk of performance and detection bias due to likely lack of blinding, low/unclear risk of bias overall). Aloe vera gel was 6 times more likely to result in at least a 50% improvement in pain symptoms compared to placebo in a study involving 45 ELP participants (Risk ratio (RR) 6.16, 95% CI 2.35 to 16.13) (low risk of bias overall). No significant difference was seen in Physician Global Assessment in these three studies.

In a small single study involving 20 ELP participants, 1% pimecrolimus cream was 7 times more likely to result in a strong improvement as rated by the Physician Global Assessment when compared to vehicle cream (RR 7.00, 95% CI 1.04 to 46.95) (low risk of bias overall). In a study involving a small subgroup of 8 ELP participants, a significant difference was seen for an improvement in the severity of the disease as rated by the Physician Global Assessment, in favour of the ciclosporin group when compared to the vehicle (MD -1.40, 95% CI -1.86 to -0.94) (unclear risk of selection bias for allocation concealment, overall risk of bias low).

No statistically significant benefits were shown for topical tacrolimus or fluticasone spray in two separate studies of 29 and 44 participants respectively.

There is no overwhelming evidence for the efficacy of a single treatment, including topical steroids, which are the widely accepted first-line therapy for ELP. Several side-effects were reported, but none were serious. With topical corticosteroids, the main side-effects were oral candidiasis and dyspepsia.

Authors' conclusions

This review suggests that there is only weak evidence for the effectiveness of any of the treatments for oral ELP, whilst no evidence was found for genital ELP. More RCTs on a larger scale are needed in the oral and genital ELP populations. We suggest that future studies should have standardised outcome variables that are clinically important to affected individuals. We recommend the measurement of a clinical severity score and a participant-rated symptom score using agreed and validated severity scoring tools. We also recommend the development of a validated combined severity scoring tool for both oral and genital populations.

Plain language summary

Treatments for erosive lichen planus affecting mucosal sites

Erosive lichen planus (ELP) is a condition that affects the mouth, oesophagus (food pipe or gullet), and anogenital region. It is caused by an over-active immune system. It is often more painful and debilitating than the non-erosive types of lichen planus. Depending on the site involved, affected individuals may experience pain, and difficulty eating; passing urine; or having sexual intercourse. Treatment is difficult and aimed at controlling symptoms, rather than cure. Several creams and tablets have been used with varying results.

This review looked at the effectiveness of treatments for ELP and included 15 studies, with 473 participants with ELP. All involved oral, but not genital, disease. Many studies were excluded either because they were not randomised controlled trials (where participants are divided into two groups at random) or because they recruited participants with all types of lichen planus, rather than just the erosive subtypes. All of these studies recruited small numbers of participants (12 to 94) and used a variety of different assessment methods and timings; hence, it was not possible to combine or compare results between studies directly.

We found only weak evidence for the effectiveness of any of the treatments for oral ELP. None of the studies involved genital or oesophageal disease; hence, no evidence was found for the treatment of these conditions. One small study found that 0.025% clobetasol propionate (a very potent topical steroid) administered as a spray significantly reduced pain when compared to ointment. In another study, a significant difference in pain was seen in the small subgroup of 11 ELP participants, favouring ciclosporin solution over 0.1% triamcinolone acetonide in orabase (a potent topical steroid). In a study involving 45 ELP participants, aloe vera gel was 6 times more likely to result in at least a 50% improvement in pain symptoms compared to placebo. In a study involving a small subgroup of 8 ELP participants, a significant difference was seen for an improvement in the severity of the disease in favour of the ciclosporin group when compared to the vehicle.

Several side-effects were reported, but none were serious. With topical corticosteroids, the main side-effects were oral candida (yeast) infection and pain or discomfort in the upper abdomen. Temporary burning was a common side-effect reported with tacrolimus 0.1% ointment and pimecrolimus 0.1% cream.

Overall, there was no overwhelming evidence for the effectiveness of any single treatment, including topical steroids, which are the widely accepted first-line therapy for ELP. This was mainly due to the lack of good-quality, well-conducted trials and small participant numbers. Another Cochrane review has already assessed interventions for lichen planus affecting the mouth.

Laički sažetak

Liječenje erozivnog lihen planusa koji zahvaća sluznice

Erozivni lihen planus (ELP) je bolest koja pogađa usta, jednjak i regiju spolovila i anusa (anogenitalnu regiju). Nastaje zbog pretjerane aktivnosti imunološkog sustava. To je često bolnije i teže stanje od neerozivne vrste lihen planusa. Ovisno o zahvćenom dijelu tijela, pogođene osobe mogu doživjeti bol i poteškoće tijekom prehrane, mokrenja ili seksualnog odnosa. Liječenje je teško i usmjereno je na kontroliranje simptoma, a ne na liječenje. Za liječenje tog stanja koristi se nekoliko krema i tableta koje daju varijabilne rezultate.

Ovaj Cochrane sustavni pregled je istraživao učinkovitosti terapija za ELP. Nakon pretraživanja literature uključeno je 15 studija s ukupno 473 sudionika koji su bolovali od ELP. Svi uključeni ispitanici su imali oralnu bolest (koja zahvaća usta), ali ne i genitalnu bolest. Mnoge studije su isključene ili zato što ta istraživanja nisu bili randomizirani kontrolirani pokusi (gdje su sudionici nasumično podijeljeni u dvije skupine) ili zato što su uključili sudionike sa svim vrstama lihen planusa, a ne samo s erozijskim podtipovima. Sve uključene studije imale su mali broj sudionika (12 - 94) i koristile su različite metode procjenjivanja i vremena procjene. Stoga nije bilo moguće statistički kombinirati ili usporediti rezultate između studija izravno.

Pronašli smo samo slabe dokaze za učinkovitost bilo kojeg oblika liječenja za oralni ELP. Niti jedna studija nije uključivala genitalnu ili bolest jednjaka; stoga, nema dokaza za liječenje tih stanja. Jedno malo istraživanje pokazalo je da 0,025% klobetazol propionata (vrlo snažan lokalni steroid) u obliku spreja značajno smanjuje bol u odnosu na mast. U drugoj studiji, značajna razlika u boli je uočena u maloj podskupini od 11 sudionika s ELP, pri čemu je otopina ciklosporina s preko 0,1% bilja bola nego triamcinolon acetonida (snažan lokalni steroid). U istraživanju koje je uključilo 45 sudionika, aloa vera gel je imao 6 puta veću vjerojatnost da će dovesti do poboljšanja simptoma boli u usporedbi s placebom. U studiji koja je uključila malu podgrupu od 8 ​​sudionika s ELP, značajna razlika je uočena u poboljšanju u ozbiljnosti bolesti u korist skupine koja je koristila ciklosporin za razliku od skupine koja je primila placebo.

Prijavljeno je nekoliko nuspojava, ali nisu bile ozbiljne. S lokalnim kortikosteroidima, glavne nuspojave su infekcija oralnom kandidijazom(kvasac) i bol ili nelagoda u gornjem dijelu trbuha. Kratki osjećaj žarenja je česta nuspojava opisana za takrolimus 0,1% mast i pimekrolimus 0,1% kremu.

Zaključno, nije bilo uvjerljivih dokaza za učinkovitost nekog od analiziranih oblika terapije, uključujući i lokalne steroide, koji su općenito prihvaćena prva linija terapije za oralni ELP. To je uglavnom zbog nedostatka kvalitetnih, dobro provedenih ispitivanja i malog broja sudionika. Drugi Cochrane sustavni pregled već je procijenio intervencijeza lichen planus koji pogađa usta.

Bilješke prijevoda

Hrvatski Cochrane
 Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr