Lichen planus

1. Lichen planus Evidence based dermatology Third edition Laurence Le Cleachand Olivier Chosidow

2. Definition • chronic inflammatory disease affecting mainly the oral mucosa and the skin • Cutaneous LP is typically a pruriticeruption of shiny, violaceous, flat, polygonal papules, mainly localized on the front of the wrists, the lumbar region, and around the ankles • The most frequent oral presentation is asymptomatic reticular LP, but painful erosive or ulcerative areas may appear.

3. prevalence • cutaneousLP: • 0.1 %among women • 0.3% among men • Oral LP is: • 2.3% among women • 1.5% among men

4. Etiology • The pathogenesis of LP remains unclear. There is some evidence that CD8+ T lymphocytes infiltrating the epidermis and dermis act as effector agents against keratinocytes, but the target antigens are unknown

5. Prognosis • Spontaneous remission of cutaneous LP treated with various treatment regimens after 1 year occurs in two-thirds of cases • Oral LP is a chronic disease and usually does not resolve spontaneously • A 1% incidence ofSCC has been reported among patients with oral LP

6. Diagnostic tests • Histopathology: • hyperkeratosis • hypergranulosis • acanthosis • basal cell vacuolization • band-like inflammatory infiltrate in the superficial dermis.

7. Treatment • The aim of treatment: • cutaneousLpis to reduce pruritus and time to resolution • Asymptomatic oral LP does not usually require Treatment • Symptomatic oral LP may need aggressive treatment to stop pain and obtain a remission

8. Do corticosteroids improve cutaneous lichen planus?

9. In One RCT : • oral prednisolone, 30 mg/day, and placebo administered for 10 days in 38 patients • Ten out of 38 patients did not complete study • The median time for LP to clear was 18 weeks in the prednisolone group and 29 weeks in the placebo group (P = 0.02)

10. In one randomized, unblinded study: • Calcipotrioloint and betamethasonevalerateoint compared in 31 pts • No differences were observed between the treatments

11. Although topical and systemic corticosteroids are widely used the evidence for efficacy is scant • The poor quality of reporting and the high rate of withdrawn patients in the systemic corticosteroids trial do not allow any conclusions to be drawn regarding the efficacy of these treatments.

12. Do retinoids improve cutaneous lichen planus?

13. In one RCT : • acitretin 30 mg/day versus placebo for 8 weeks in 65 patients • Remissions was 64% versus 13% in the placebo • Tolerability was considered to be good or very good in 73% of the patients • Side effects noted in this study were mainly cheilitisand dry mouth

14. Because of potential side effects, acitretin is recommended as a second-line treatment for cutaneous LP. Acitretin may also be combined with psoralen–ultraviolet A (PUVA) therapy

15. Does photochemotherapy improve cutaneous • lichen planus?

16. In one small RCT: • PUVA therapy on 10 pts • Five out 10 patients cleared completely within a mean of 6 weeks • In the largest retrospective, observational study involving 50 pts that 70% treated within a mean of 11 weeks with UVB

17. No adverse effects were described in the PUVA or UVB trials • Little risk of photoaging or skin cancer exists if the treatment is limited to one or two cycles. • PUVA therapy and UVB TL-01 could be an alternative to oral corticosteroids in moderate to severe cutaneous LP.

18. Does griseofulvin, hydroxychloroquine, or sulfasalazinetreatment improve cutaneous lichen planus?

19. Two RCTs (n = 38, n = 48) compared griseofulvin 500 mg/day versus placebo • and one (n = 80) versus hydroxychloroquine400 mg/day did not report adverse effects • One RCT compared sulfasalazinemaximum 2.5 g/day with placebo No severe adverse effect was observed

20. between trials for cure rate varying between 5 and 80% • Because of phototoxic potential, griseofulvin is not recommended for treatment • Because of the potential life-threatening adverse reaction, sulfasalazine is not recommended for treatment of cutaneous LP.

21. Does methotrexate improve cutaneouslichen planus?

22. There is no RCT • one retrospective (n = 11) and one prospective series (n = 24) • MTX given orally 15–20 mg/week • complete response in 10/11 patients after a median of 9.6 weeks of treatment only one AE was nausea and fatigue • Complete response in 14/24 patients at 24 weeks AE observed in 12 pts( One patient withdrew)

23. MTX used as third-line treatment of generalized LP in case of failure or contraindication to systemic corticosteroids, retinoids, and phototherapy

24. Do topical corticosteroids improve oral lichen planus?

25. Fluocinonide • one RCT, in which fluocinonidein an adhesive base, applied six times per day, was compared with its vehicle in 40 patients with oral LP. At 9 weeks the difference significantly favored treatment

26. Betamethasonevalerate • One RCT : • betamethasonevalerate aerosol, 4sprays per day, with placebo in 23 patients with oral LP • At 2 months, 8of 11 patients had a “good or moderate” response in comparison with two moderate responses in the placebo group.

27. Two study provide a low level of evidence for the efficacy of topical corticosteroids in oral LP. • Despite the absence of evidence, topical corticosteroids are the first-line treatment for oral LP based on clinical practice.

28. Do systemic corticosteroids improve oral lichen planus?

29. One RCT compared : • topical triamcinolonewith oral betamethasone (5 mg/day for 3 months, followed by a slow taper during 3 months) • No difference for number of patients with improvement of signs and symptoms was observed between the two groups.

30. AES were cushingoidfeatures in 7 pts, and one developed diabetes mellitus • 5 pts in topical group developed oral candidiasis • Although systemic corticosteroids are widely used in oral LP, their efficacy has not been documented

31. Based on clinical practice, systemic corticosteroids 0.5–1 mg/kg are recommended as secondline treatment for erosive oral LP in the absence of response to topical corticosteroid treatment and as first-line treatment in severe oral LP.

32. Do retinoids improve oral lichen planus?

33. one RCT (n = 20) comparing: • 0.1% retinoic acid lotion twice daily with placebo in patients with plaque-like LP • After 4 months 97% of pts retinoic group were cured versus 21% of placebo • An RCT compared 0.05% retinoic acid with fluocinoloneacetonide 0.1%, four applications per day

34. At week 4, clinical score improvement was significantly greater for the fluocinoloneacetonide group. • Isotretinoin gel • One RCT compared isotretinoin gel twice daily with excipient alone for 2 months in 20 patients. The improvement in scores was 90% and 10%, respectively.

35. Tazarotene: • One RCT comparedtazarotene gel 0.1% versus placebo in 12 patients withhyperkeratotic oral LP. The clinical score was significantly improved in the treatment group . Only mild local side effects were observed.

36. Despite the low level of evidence and mainly based on clinical experience, topical retinoid can be recommended as first-line treatment alone or in association with topical corticosteroids for papular– plaque-like form without ulceration oral LP.

37. Do topical calcineurin inhibitors improve oral lichen planus?

38. 2 RCTs comparing the efficacy of topical ciclosporin with placebo in 16 and 20 patients • There is a statistically significative difference for reducing pain and clinical signs favoring ciclosporin in these two trials • Tacrolimus • We don’t find a RCT comparing tacrolimus to placebo

39. Pimecrolimus • Three RCTs comparingpimecrolimus cream 1% twice daily during 4week/ 4week/30 days in 12/20/20 pts • No difference for pain reduction or clinical outcomes was observed in these three trials except for the physician global assessment in one trial

40. Topical ciclosporin, tacrolimus or pimecrolimus are not recommended for the treatment of oral LP.

41. Are calcineurin inhibitors more effective than topical corticosteroids for treating oral lichen planus?

42. In some RCTs compared Topical ciclosporinPimecrolimus and Tacrolimuswith topical corticosteroids that There are no reliable results demonstrating that topical calcineurin inhibitors are more effective than topical corticosteroids in oral LP

43. Does topical Aloe vera improve oral lichen planus?

44. two RCTs (n = 54 and n = 64 ) comparing topical Aloe vera with placebo • twice daily for 8 weeks / three times daily for 12 weeks • One RCT found a statistically significant amelioration for pain and clinical outcome, while another RCT found no difference

45. There is weak evidence that Aloe vera may reduce the pain of oral LP and improve the clinical signs of disease compared with placebo Knowledge on safety is lacking. Aloe vera is not recommended for oral LP.

46. Does extracorporeal photochemotherapyimprove oral lichen planus?

47. two prospective series of 7and 12patients with resistant severe erosive LP for a mean of 6 years and 7.5 years • were treated with extracorporeal photochemotherapy, two session per week • Complete remission was obtained in all patients in one series and nine out of 12 patients in the other after a mean of 24and 21sessions

48. A progressive decrease in blood lymphocytes was observed in all patients, but without significant consequences • Because of its cost and availability only in a limited number of centers ,should be restricted to severe erosive LP resistant to other treatments. No comparative studies have yet been conducted.

49. Does other treatment improve oral lichen planus?

50. Each one in a single RCT against placebo (curcuminoids, hyaluronic acid , ignatia , purslane, lycopene orally ) or corticosteroids (intralesional injection of polysaccharide nucleic acid fraction of bacillus Calmette-Guerin or triamcinoloneacetonideintralesionalinjections , and thalidomide paste versus dexamethasone paste ).