Table 1 Key characteristics of the included randomized clinical trials in this systematic review
From: Oral lichen planus: comparative efficacy and treatment costs—a systematic review
Topical steroids | Reference Study | Intervention | Comparative agent | No. of pts | Indication | Duration | Frequency | Outcome measure | Results | ADRs | Efficacy Comparison | Level of evidence |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Dexamethasone | Bakhtiari [27] | Dex solution 0.5 mg/5 mL | PDT | 30; Dex: 15, PDT:15 | Bx-proven clinical OLP | 2 wks | QID | VAS, Thongprasom clinical score, clinical severity index | No significant difference between the two gps in efficacy index, sign score, symptom score or clinical severity on post-treatment days 15, 30, 60 and 90; Decreases in symptoms statistically significant in both (p-value NS) | PDT: 3 pts-pain from manipulation of the probe tip | Dex = PDT | High risk of bias |
Hambly [28] | Dex solution 0.5 mg/5 mL | Dex solution 0.5 mg/5 mL self-compounded | 9; Dex:4, Dex self-compounded: 5; then cross-over | Symptomatic OLP | 7 wks | TID | VAS, TSQM-9, photos, self-assessment | TSQM-9 revealed the compounded mouth rinse more favorable than the self-formulation rinse, with a mean improv. in convenience of therapy (22.25%), onset of action (8.48%), and attained symptom relief (4.18%) (p-value NS) | None | Commercial dex > self-formulated dex | High risk of bias | |
Mirza [29] | Dex solution 0.5 mg/5 mL | LLLT vs. PDT | 45; 15 in each group (dex, LLLT, PDT) | Erosive OLP | 4 wks | QID | VAS and clinical score | Significant difference in sign score changes before and after the treatment in the PDT group (p = 0.03), LLLT group (p = 0.04) and in dex group (p = 0.02); statistically significant difference between PDT (p = 0.001) and LLLT (p = 0.001) against dex group before and after treatment. Mean improv. in pain significantly greater in dex group in comparison with the PDT and LLLT gps (p < 0.001). Efficacy index of PDT group improved significantly more than the LLLT (p = 0.001) and corticosteroid gps (p = 0.001) | None | VAS: Dex > LLLT = PDT;Efficacy: PDT > LLLT = Dex | High risk of bias | |
Clobetasol | Rödström [33] | Clo oint. 0.05% | TA paste 0.1% | 40; 20 in each | Erosive OLP | 9 wks | BIDx3wks, QDx 3wks, once every other dayx3 wks | VAS and 4-point clinical score | Clo more effective than TA at 3 wks (p < 0.05). No significant difference following 6 and 9 wks of treatment | NS | Clo > TA (at 3 wks); Clo = TA (6 & 9 wks) | Low risk of bias |
Muzio [30] | Clo oint. 0.05% | Clo in analgesic base vs. Clo in denture paste | 24; 8 in each | Bx-proven OLP | 2 wks | TID | VAS | Clo effective in each group (p < 0.05) | candidiasis (number NS) | Clo oint = Clo + analgesic base = Clo + denture paste | Low risk of bias | |
Carbone [31] | Clo oint. 0.025% | Clo oint. 0.05% | 35; 15 in | Bx- proven symptomatic OLP | 8 wks | BID | VAS and clinical score | VAS improved in both (p = 0.001); clinical score improved (p < 0.05 in both gps). No statistically significant differences b/w gps | None | Clo oint 0.025% = clo oint 0.05% | Low risk of bias | |
Kaur [32] | Clo oint. 0.025% | TC oint. 0.1% | 40; 20 in each | Bx- proven symptomatic OLP | 4 wks | BID | Symptom and clinical grading score | Improv. in both groups. No statistically significant differences b/w gps | None | Clo oint. 0.025% = TC oint. 0.1% | Low risk of bias | |
Arduino [8] | Clo gel 0.05% | Placebo | 32; 16 in each group | OLP | 8 wks | BID | VAS and 4-point clinical score | Clo: reduction in VAS and clinical score in tx (p = 0.005) | Clo: 1 pt-GERD; 1pt- mild elevated FBS; placebo: 1pt- skin rxn | Clo > placebo | Low risk of bias | |
Fluocinonide | Voute [10] | Fluocinonide oint. 0.025% | Placebo | 40; 20 in each group | Bx- proven OLP | 9 wks | 6 × daily | VAS; 4-point clinical score | Statistically significant improv. in fluocinonide group objectively (p = 0.0013) and symptoms (p = 0.008) | None | Flu > placebo | Low risk of bias |
Carbone [34] | Fluocinonide oint 0.025% | Clo oint. 0.05% vs. placebo | 60 (Flu:25, Clo:24, placebo:11) | Atrophic-erosive symptomatic OLP | 24 wks | TIDx 8wks; BIDx 8wks; QDx 4 wks | Objective and subjective clinical progress score | Clo more effective in atrophic areas (75% vs 25% of total response, respectively) (p = 0.004) | None | Clo > Flu | Low risk of bias | |
Triamcinolone | Sieg et al. [43] | TA paste 0.1% | Cyclosporin oily liquid preparation | 13; CsA:6, TA:7 | Bx-proven OLP | 6 wks | TID | 7-point mucosal lesion scoring | Clinical improv. in both gps, no statistically significant difference between gps (no p-value) | CsA: precipitation of waxy particles during 'swishing' the oily solution; TA: 3 pts- burning | TA = CsA | Some concerns |
Ungrouphaiboon et al. [35] | TA paste 0.1% | TA solution 0.1% | 20; TA paste:11, TA rinse:9 | Bx-proven symptomatic OLP | 4 wks | QID | Clinical response: none, partial (1–33% reduction in lesion), good (34–99% lesion reduction, complete response | No statistically significant difference b/w 2 gps | TA paste group: 2 pts- oral candidiasis | TA paste = TA rinse | Some concerns | |
Laeijendecker et al. [38] | TA oint 0.1% | TC oint. 0.1% | 40; 20 in each | OLP | 6 wks | QID | Reduction in pain | TA: 6 pts healed, 12 showed improv.; TC: 2 pts healed, 7 improved. Initial results better in TC group (p = 0.007) | Temporary pain and burning sensation in both gps | TC > TA | Some concerns | |
Malhotra et al. [67] | TA paste 0.1% | Oral betamethasone mini pulse (5 mg twice/wk) | 49 (TA: 24, BM: 25) | Bx-proven symptomatic OLP | 24 wks | TA: TID × 12 wks, BID × 4 wks, QD × 4 wks, alternate days × 4 wks; BM: 5 mg × 12 wks, 4 mg × 4 wks; 3 mg x 4wks; 2 mg × 4 wks | Clinical score (based on number of sites and area affected) and change in symptoms | Clinical score: reduction in severity score more in TA group (p = .026); No statistical difference in symptomatic improv. b/w 2 gps | TA group: 5 pts-candidiasis, 1 pt epigastric discomfort; BM group: 7 pts- facial edema, 7 pts epigastric discomfort, 5 pts-fatigue, 4 pts hand/foot edema, 1pt diabetes mellitus | Clinical score: TA > ; Symptoms: TA = BM | High risk of bias | |
Mansourian et al. [47] | TA paste 0.1% | AV solution | 46; 23 in each | Bx-proven OLP | 4 wks | QID | VAS, Thongprasom score, lesion size (grid) | Both AV and TA significantly reduced VAS, Thongprasom score and lesion size (p < 0.001). No significant difference b/w 2 gps | None | TA = AV | Low risk of bias | |
Handa [37] | TA paste 0.1% | Fluticasone propionate spray 0.05% | 40; 20 in each group | Symptomatic OLP | 8 wks, 2 wks washout, 8 wks crossover | TA: QID; Fluticasone: 50 μg, 2 dose unit BID | Clinical scoring, VAS, OHIP-14 | No statistically significant difference b/w 2 gps (p value NS) | NS | TA = fluticasone spray | Some concerns | |
Amanat et al. [54] | TA paste 0.1% in orabase | Cryotherapy (NO) | 30 (one side intervention, the other side control) | Bx-proven, bilateral OLP | 4 wks | TID | Lesion size, RPAE score | Both treatments reduced the sign scores and severity significantly (p < 0.05), no significant differences between gps (p > 0.05) | Cryotherapy: 17 pts- minor swelling. 12 pts- pain in first 7–10 days | TA = cryotherapy | High risk of bias | |
Kia et al. [48] | TA paste 0.1% | Curcumin paste 5% | 50; 25 in each group | Clinical and bx-proven OLP | 4 wks | TID | VAS and Thongprasom score | No significant difference between the two gps in VAS (VAS at baseline: p = 0.17; VAS two weeks later: p = 0.3; VAS four weeks later: p = 0.46) or Thongprasom score (baseline: p = 0.77, two weeks later: p = 0.92, four weeks later: p = 0.31) | Curcumin: burning sensation, itching, mild swelling and xerostomia, yellow gingiva; TA: 1 burning and 1 mucosal desquamation | TA = Curcumin | Some concerns | |
Sivaraman et al. [36] | TA paste 0.1% | Clo oint. 0.05%, vs. TC oint. 0.03% | 30; 10 in each of the 3 gps | Atrophic, ulcerative OLP | 6 wks | QID | Reduction in lesion size | TA and Clo: significant reduction in lesion size than Tac gp; overall better results with Clo (p = 0.005) | None | Clo > TA > TC | Some concerns | |
Thomas et al. [49] | TA paste 0.1% | Curcumin gel 1% TID vs. curcumin gel 6x/d | 75; 25 in each of the 3 gps | Bx-proven symptomatic OLP | 12 wks | TA: TID; curcumin: TID; 6x/d | Numerical Rating Score (burning) and Modified Oral Mucositis Index | Reduction in burning and erythema/ulceration (p < 0.001) in all 3 gps. TA showed max. reduction in burning sensation (77% change) and erythema/ulceration (67% change) (p < 0.001) | None | TA > curcumin gel 1% 6x > curcumin gel 1% TID | High risk of bias | |
Singh et al. [40] | TA paste 0.1% | Dapsone 100 mg vs. TC oint. 0.1% vs. topical retinoid (type NS) | 40; 10 in each of the 4 gps | Reticular, erosive, atrophic, plaque-like OLP | 12 wks | BID | Symptoms and signs scored according to Raj et al. and Kaliakatsou et al. scales | All clinical improv. (p < 0.05), steroidal and non-steroidal agents had equal efficacy. Of the non-steroidal drugs, oral dapsone had greater efficacy than topical retinoid (p < 0.05); no significant differences between oral dapsone and topical tacrolimus (p > 0.05) or between topical retinoid and TC (p > 0.05) | Mild tingling in the oral cavity in patients treated with topical agents | Dapsone > TA = TC = retinoid | Some concerns | |
Siponen et al. [39] | TA paste 0.1% | TC oint. 0.1% vs. placebo | 18; TA: 7, TC: 11, placebo: 9 | Bx-proven symptomatic OLP | 9 wks | TID | VAS and clinical score | Reduction in both TC and TA gps as compared to placebo (p = 0.012 and 0.031). No statistically significant difference b/w 2 gps | TA: 3 pts-burning, tingling, gingival tenderness, 2 pts-candidiasis | TA = TC | Low risk of bias | |
Li et al. [1] | TA paste 0.1% | S. Salivarius K12 lozenge | 40; 20 in each | Symptomatic OLP | 4 wks | TA: TID; Lozenges: BID | Sign scores and VAS | No statistical difference was observed between two gps after 4-week treatment in sign scores (p = 0.063) or VAS (p = 0.698) | None | TA = S. Salivarius K12 | High risk of bias | |
Bakshi et al. [27] | TA solution 0.1% | Nanocurcumin gel 1% | 31; 17 in TA + placebo, 14 in TA + NC | Symptomatic OLP | 4 wks | TID | REU score and efficacy index | Both had significant improv. in REU score and efficacy score, TA + NC group significantly better in both measures than TA + placebo (p < 0.001) | NS | Nanocurcumin gel > TA | Low risk of bias | |
Betamethasone | Tyldesley and Harding[11] | BM valerate aerosol (2 puffs/dose); daily dose: 800/ug | Placebo | 23; BM: 12, placebo: 11 | Symptomatic OLP | 8 wks | QID | Lesion size, discomfort/pain | BM: improv. of lesion size and pain in 8 vs. 2 in placebo (p < 0.05) | BM: 1 pt-oral candidiasis | BM > placebo | Low risk of bias |
Fluocinolone | Thongprasom et al. [7] | Fluocinolone acetonide 0.025% in orabase | TA 0.1% in orabase | 40; 20 in each | Bx-proven OLP | 4 wks | QID | 5-point Thongprasom clinical score | Fl: lesions in 13/19 pts effectively cured, TA: 8/19 pts cured (p < 0.05) | Oral candidiasis: Fl- 9 pts; TA-4pts | Fluocinolone > TA | High risk of bias |
Calcineurin inhibitors | ||||||||||||
Tacrolimus | Radfar et al. [55] | TC oint. 0.1% | Clobetasol gel 0.05% | 29; TC:15, clo:14 | Erosive OLP | 6 wks | QID x 2wk; TID X 2wk; BID X1 wk; QHS × 1 wk | Complete resolution of the clinical signs and symptoms | 82.6% in tacrolimus and 81.6% in the clobetasol group – improv., (p < .0001) | Discomfort, burning and tingling | TC > Clo | Low risk of bias |
Corrocher et al. [56] | TC oint. 0.1% | Clobetasol oint. 0.05% | 32; 16 in each | OLP | 4 wks | QID | Pain severity, burning sensation, 4-point clinical score | TC group- low median pain score p < 0.001; Clo group- low pain score p < 0.05 but mild increase in the median severity scores | None | TC > Clo | Low risk of bias | |
Sonthalia and Singal [57] | TC oint. 0.1% | Clobetasol oint. 0.05% | 40; 20 in each | OLP | 8 wks | TID | VAS, Clinical score | VAS and clinical score decreased (p < 0.05) in both gps, but no significant diff b/w 2 gps | Burning and increased sensitivity | TC = Clo | Low risk of bias | |
Vohra et al. [59] | TC oint. 0.1% | PI cream 1% | 40; 20 in each | Erosive, OLP | 8 wks | BID | Clinical score | Significant reduction in the clinical severity score in both pimecrolimus and tacrolimus (p < 0.05) | None | TC = PI | Low risk of bias | |
Hettiarachchi et al. [58] | TC cream 0.1% | Clobetasol cream 0.05% | 68; 34 in each | OLP | 3 wks | BID | VAS, Thongprasom clinical response | TC: mean pain score dropped by 1.59 (R) and 1.53 (L), clinical score reduced by 1.18 (R) and 1.0 (L); Clo: VAS drop by 0.94(R) and 0.85 (L) & clinical score reduced by 0.5 (R) and 0.26 (L) (p < 0.05) | None | TC > Clo | Low risk of bas | |
Pimecrolimus | Swift et al. [12] | PI cream 1% | Placebo | 20; 10 in each | Erosive OLP | 4 wks | BID | Lesion size, VAS | PI more effective; VAS decreased (p = 0.02) | None | PI > Placebo | Low risk of bias |
Passeron et al. [13] | PI cream 1% | Placebo | 12; 6 in each | Erosive OLP | 4 wks | BID | 12-point clinical score & VAS | PI effective; Mean score 6.83 on day 0 vs. 3.33 on day 28 in PI arm (p = 0.04) | PI: 2 pts transient burning sensation | PI > Placebo | Low risk of bias | |
Gorouhi et al. [41] | PI cream 1% | TA cream 0.1% | 40; 20 in each | OLp > 8 yrs | 8 wks | QID | VAS, OHIP score & objective clinical score | No significant difference b/w 2 arms in VAS (p = 0.70), OHIP (p = 0.38), clinical score (p = 0.86) | PI: 2pts- transient burning; TA: none | PI = TA | Low risk of bias | |
Volz et al. [14] | PI cream 1% | Placebo | 20; 10 in each | Erosive OLP | 4 wks | BID | Composite score (mucosal erosions and pain sensation) | Composite score reduced in PI arm (p = 0.025) | PI: 4 pts-burning sensation, 1 pt- mucosal paresthesia; Placebo:1 pt- mucosal paresthesia | PI > Placebo | Low risk of bias | |
McCaughey et al. [15] | PI cream 1% | Placebo | 21; PI: 10, placebo: 11 | Erosive OLP | 6 wks | BID | Investigator’s Global Assessment of severity, pain, erosion size | PI superior in reducing mean pain and erosion size (mean size 11.10 at baseline vs. 3.70 at week 6) (p = 0.02) | None | PI > Placebo | Low risk of bias | |
Arduino et al. [9] | PI cream 1% | TC oint. 0.1% | 30; 15 in each | Topical steroid refractory OLP | 8 wks | BID | Symptomatic improv., therapeutic effectiveness | Both effective; no statistically significant difference b/w 2 arms | PI: 2pts- xerostomia, 2pts-GERD, 1pt-herpes labialis; TC: 2pts burning, | PI = TC | Low risk of bias | |
Arunkumar et al. [46] | PI cream 1% | TA paste 0.1% | 30; 15 in each | Bx-proven symptomatic OLP | 8 wks | QID | VAS, mean clinical score and erythematous area | Reduced clinical score in PI arm (p < 0.01); no statistically significant diff in reduction of VAS (p = 0.18) & erythema (p = 0.07) | None | Clinical score: PI > TA; VAS: PI = TA | Low risk of bias | |
Pakfetrat et al. [42] | PI cream 1% | TA cream 0.1% | 28; 14 in each | Atrophic-erosive OLP | 8 wks | TID | Thongprasom lesion scoring, VAS | Both effective; No statistically significant difference | None | PI = TA | Low risk of bias | |
Ezzatt and Helmy [60] | PI cream 1% | Betamethasone valerate cream 0.1% | 30; 15 in each | Atrophic-erosive OLP | 4 wks | QID | Clinical score, VAS | Both showed reduction in clinical score and VAS (p < 0.001) but no statistically significant diff b/w 2 arms in 4 wks; PI: 33% clinical score reduction, 57.5% VAS reduction; BM:13.9% clinical score reduction and 30.6% VAS reduction after 1 wk | PI: 4 pts-burning,2 pts-dysguesia; BM: 2pts-burning, 1pt-dysguesia | PI = BM | Low risk of bias | |
Cyclosporine | Eisen et al. [16] | CsA solution 100 mg/ml | Placebo | 16; 8 in each | Bx-proven symptomatic OLP | 8 wks | TID | Pain (4-grade scale), erosion (4-grade scale) | CsA: improv. in erythema (p = 0.003), erosion (p = 0.02), reticulation (p = 0.007), pain (p = 0.002) | CsA: transient burning on swishing in all pts | CsA > placebo | Low risk of bias |
Harpenau et al. [17] | CsA solution 100 mg/ml | Placebo | 14; 7 in each | Bx-proven erosive OLP | 4 wks | QD | VAS; lesion character (ulcer, erythema & reticulation) & size | CsA: significant reduction in erythema, ulceration, and VAS; p-value NS | None | CsA > placebo | Low risk of bias | |
Lopez [61] | CsA solution 1% | TA solution 0.1% | 20; 10 in each | Bx proven OLP | 8 wks | TID | Symptom, erosion and erythema score | CsA: greater decrease of symptoms (90% vs. 60% in TA), erythema and erosion; p-value NS | NS | CsA > TA | Low risk of bias | |
Femiano et al. [63] | CsA solution 100 mg/ml | IM sul 600 IU, then oral doses 250 IU | 20; 10 in each | Topical steroid recalcitrant bx-proven OLP | 4 wks | CsA: TID, Sul:BID | Pain relief, clinical resolution of erosion/ulceration | Sulodexide more effective- clinical resolution faster than CsA at a mean of 36 days and pain resolution in 90% by mean 6.4 days (p < 0.004) | CsA: None; Sul: vertigo, vomiting and hot flushes | Sul > CsA | High risk of bias | |
Yoke et al. [44] | CsA solution 100 mg/ml | TA paste 0.1% | 139; CY: 68; TA:71 | Bx proven OLP | 8 wks | TID | VAS; Thongprasom clinical grading | No statistically significant difference b/w two arms | TA: 3 pts- transient burning; CsA: 14 pts- burning; 4 pts- GI upset; 1pt- lip swelling & itching | CsA = TA | Low risk of bias | |
Thongprasom et al. [45] | CsA solution 100 mg/ml | TA paste 0.1% | 13; CsA:6, TA:7 | Bx proven symptomatic OLP | 8 wks | TID | VAS, Thongprasom clinical grading (5-point) | No statistically significant differences b/w 2 gps | CsA: 5 pts- burning sensation, itching, swelling lips, petechial hemorrhage; TA: None | CsA = TA | Low risk of bias | |
Georgaki et al. [62] | CsA solution 100 mg/ml | Dex rinse 0.5 mg/5 ml | 32; 16 in each | Bx proven symptomatic OLP | 4 wks | TID | VAS; Thongprasom clinical grading, dysphagia and speech difficulties | Dex: better in clinical scoring (p = 0.001). No significant diff b/w 2 gps in improv. of pain, dysphagia and speech difficulties | NS | ClinicaL score: Dex > CsA; VAS: Dex = CsA | Low risk of bias | |
Other topical agents | ||||||||||||
Amlexanox | Verma [52] | AX paste 5% | TA paste 0.1% | 60; 30 in each | Symptomatic reticular/erosive OLP | 12 wks | QID | VAS; clinical sign stage: erythematous areas, white striae + lesion size | TA more effective > AX. AX: 60% reduction in the clinical sign stage & TA: 98% reduction (p < 0.05); VAS = no significant difference | None | Clinical score: TA > AX; VAS: TA = AX | Low risk of bias |
Retinoid | Giustina et al. [18] | isotretinoin gel 0.1% | Placebo | 22;11 in each | Ulcerated lichen planus | 8 wks | BID | Reduction in pain and erythema-severity scale (0–5) | Significant improv. in topical retinoid group with statistically significant (p < .002); Reduction in severity scale 3.0 to 1.7 after 8 weeks | Burning and superficial desquamation | Isoretinoin > Placebo | Low risk of bias |
Petruzzi et al. [20] | Tazarotene cream 0.1% | Placebo | 12; 6 in each | Hyperkeratotic OLP | 8 wks | BID | 6-degree score scale, reduction in lesion | 4 patients healed, 2 patients improved in tazarotene and 5 patients with no improv. and 1 worsening (p = 0.0049) | Burning, taste abnormalities | Tazarotene > Placebo | Low risk of bias | |
Piattelli et al. [19] | Isotretinoin gel 0.1% | Placebo | 20; 10 in each | Bx proven OLP | 16 wks | TID | Complete healing of the lesions | Isoretinoin: 60% complete healing (p = 0.029) | NA | Isoretinoin > Placebo | Low risk of bias | |
Tocopherol | Bacci et al. [21] | Tocopherol acetate (gelly formulation) | Placebo | 33; Tocopherol = 17, Placebo = 16; then cross-over | Bx-proven reticular OLP | 4 wks, 2 wk washout, 4 wks crossover | TID | VAS, length of striae, surface area of lesion, Thongprasom score | Significant difference in surface area of lesion (p = 0.0045) and Thongprasom score (p = 0.0052) in tocopherol group | None | Tocopherol > Placebo | Low risk of bias |
Intralesional | ||||||||||||
Triamcinolone | Ahuja et al. [65] | Intralesional triamcinolone (10 mg/ml) | PRP 0.5 ml | 20; 10 in each | Erosive OLP | 8 wks | Weekly injection—for 2 to 4 months | VAS, reduction in erythema and size of the lesions | Statistically significant reduction in both gps (p < 0.005); no significant difference b/w 2 gps | Intralesional TA: Erythema in 1 pt; PRP: increased VAS score in 1 pt | TA = PRP | Low risk of bias |
BCG-PSN | Xiong et al. [64] | Bacillus Calmette–Guerin polysaccharide nucleic acid (BCG‐PSN) | Intralesional triamcinolone (10 mg/ml) | 56; BCG-PSN = 31 & TA = 25 | Bx-proven erosive OLP | 2 wks | BCG-PSN: every other day. TA: every week | VAS & measured erosive areas | No statistical differences b/w 2 gps in erosive areas (p = 0.801) and VAS scores (p = 0.946) | Burning/swelling at injection site in 9.7% of BCG-PSN group and 8% in TA group | BCG = TA | Low risk of bias |
Systemic Therapies | ||||||||||||
Systemic retinoids | Hersle et al. [22] | Etretinate 25 mg | Placebo | 28; 14 in each | Bx-proven OLP for atleast 6 mths | 8 wks | TID | 4-point clinical scoring | Etretinate: 93% improv. vs. 5% in placebo (p < 0.001) | Etretinate: all pts- skin and mucosa dryness; 6 pts-keratoconjunctivitis, rash, headache, itchiness & hair loss | Etretinate > Placebo | Some concerns |
Levamisole | Lin et al. [66] | Levamisole 50 mg | (Levamisole + vit B12) and (Vit B12 only) | 147; 100 in L + B12 gp, 37 in L gp, & 10 in B12 gp | OLP | 2–50 months (mean = 14) | BID if 30–50 kg or TID if 50–70 kg, for 3 days at 2 wk interval | Size & distribution of lesions, pain & burning symptoms | L only group & L + B12 group: 100% objective & subjective improv.; Vit B12 alone: 13% improv. in symptoms and 20% improv. in signs (p-value NS) | None | Levamisole = Levamisole + B12 > B12 only | High risk of bias |
Natural alternative | ||||||||||||
Lycopene (systemic) | Saawaran et al. [23] | Lycopene 4 mg | Placebo | 30; 15 in each | Bx proven symptomatic OLP | 8 wks | BID | VAS; Tel Aviv-San Francisco scale | Lycopene: 84% VAS reduction, 100% showed > 50% benefit; Placebo: 67% VAS reduction, 66.6% showed > 50% benefit (p < 0.05) | None | Lycopene > Placebo | Low risk of bias |
Ignatia (topical) | Mousavi et al. [24] | Ignatia 30C liquid | Placebo | 30; 15 in each | Bx proven atrophic/erosive OLP | 12 wks | QD | VAS and mean lesion size (cm) | Ignatia more effective; Ignatia: mean lesion size- 2.2 cm, VAS-13 mm; Placebo: mean lesion size-4 cm, VAS-40 mm (p < 0.05) | None | Ignatia > Placebo | Low risk of bias |
Aloe Vera (topical) | Choonhakarn et al. [25] | AV gel 70% | Placebo | 54; 27 in each | Bx proven OLP | 8 wks | BID | VAS and Thongprasom clinical scale | AV: improved clinical response in 88% and improved burning in 33% vs. 4% in placebo group (p < 0.001) | None | AV > Placebo | Low risk of bias |
Salazar-Sánchez et al. [26] | AV gel 70%- 0.4 ml/dose | Placebo | 64; 32 in each | Bx proven OLP | 12 wks | TID | VAS, Thongprasom clinical scale, OHIP-49 | No statistically significant diff in VAS and clinical score at 12 wk; AV showed improv. in total OHIP score (p = 0.046) | None | AV = Placebo | Low risk of bias | |
Reddy et al. [51] | AV gel 70% | TA 0.1% paste | 40; 20 in each | Erosive & atrophic OLP | 8 wks | TID | VAS & clinical score | AV: clinical score and VAS significantly better than TA (p < 0.05) | None | AV > TA | Low risk of bias | |
Other procedural modalities | ||||||||||||
LLLT | Jajarm et al. [68] | Low intensity laser therapy (LILT) 630 nm diode laser | Dexamethasone solution 0.5 mg/5 ml | 30 (one side intervention, the other side control) | Erosive-atrophic OLP | 4 wks | LILT: BID; Dex: QID | Thongprasom clinical scale, VAS, RAE | Appearance score, pain score, and lesion severity was reduced in both gps (p value NS). No significant differences b/w the treatment gps regarding the response rate and relapse | None | LLLT = Dex | Some concerns |
Laser | Agha-Hosseini et al. [72] | CO2 laser irradiation | low-level laser therapy (LLLT) | 28 (one side intervention, the other side control) | Oral lichen planus | 2 wks | CO2 laser: 1 session; LLLT: 5 sessions | Thongprasom clinical scale, VAS, size of lesions | Lesion size reduction significantly higher in LLLT compared to CO2 (p < 0.05). Improv. in clinical signs significantly higher in LLLT (p < 0.05). Symptom reduction was significantly higher in LLLT group (p < 0.05) | NS | LLLT > CO2 laser | High risk of bias |
LLLT | Dillenburg et al. [70] | Laser phototherapy (LPT) 660 nm diode laser | Clobetasol gel 0.05% | 42 (one side intervention, the other side control) | Atrophic/erosive OLP | 4 wks | LPT- 3x/wk; Clo: TID | Clinical, symptoms, and functional scores | The LPT group had significantly lower clinical scores compared to clobetasol group (p = 0.001). Symptom score was maintained at a stable level for the LPT group in the follow up period, whereas a significant increase was found in the clobetasol group (p = 0.05) | Clo: 3 pts- Transient burning sensation; LPT: None | LPT > Clo | Low risk of bias |
PDT | Jajarm et al. [68] | Toluidine blue for 10 min followed by photodynamic therapy | Dexamethasone rinse 0.5 mg/5 ml | 25 (one side intervention, the other side control) | Erosive/atrophic OLP | 4 wks | PDT:2x/wk; Dex:QID | Thongprasom clinical scale, efficacy indices, and experienced pain | Statistically significant reduction in sign score for the experimental (p = 0.021) and control (p = 0.002) gps. Efficacy index of the control group improved significantly more than the experimental group (p = 0.001) | None | Dex > PDT | High risk of bias |
Laser | Kazancioglu (2015) | A diode laser 808 | Ozone vs. dex rinse vs. placebo | 120; 30 in each gp | atrophic-erosive OLP | 4 wks | Laser:2x/wk; Ozone:2x/wk; Dex: QID | Thongprasom clinical scale, VAS, RAE score | Improv. in all gps but significantly better in Ozone and steroid gps (p < 0.05) as compared to laser and placebo | None | Ozone = Dex > Laser > placebo | Some concerns |
Laser | Othman et al. [74] | A diode laser 970 | TA 0.1% orabase | 24 (one side intervention, the other side control) | Erosive-atrophic Reticular | 4–5 wks | Laser: 2x/wk; TA: QID | Thongprasom clinical scale, RAE score, TNF α level | TA group showed statistically significantly lower mean RAE score than Laser group (p = 0.02) as well as lower TNF-α level | None | TA > laser | Some concerns |
Laser | El Shenawy et al. [75] | A diode laser 970 | TA 0.1% orabase | 24; 12 in each | Erosive-atrophic | Laser: 8 wks; TA: 4 wks | Laser: 2x/wk; TA: QID | VAS, RAE score | Significant improv. in TA group than laser group (p < 0.05) | NS | TA > laser | Some concerns |
PDT | Lavaee and Shadmanpour [69] | 660-nm diode laser for 10 min | Topical TA 0.1% | 8 (one side intervention, the other side control) | Atrophic/erosive OLP | PDT: 3 wks; TA: 4 wks | PDT: 1x/wk; TA: TID | Thongprasom clinical scale, VAS, size of lesions | Significant difference in all scores between session 0 and 4 in both gps (p < 0.05). Changes in scores between the intervention and comparative gps were not statistically significant (p = 0.340) | None | PDT = TA | Low risk of bias |
LLLT | Ferri et al. [71] | Clo gel 0.05% | Photobiomodulation (PBM) | 34; 17 in each group | Reticular,atrophic, and erosive OLP | 4 wks | Clo: TID; PBM: 2x/wk | VAS; Thongprasom clinical score | Decreased pain in both; clinical resolution: clo- 79.4%, PBM- 64.7% (p < 0.05) | None | Clo > PBM | Low risk of bias |