Although no reports specifically for OLP, low-dose doxycycline has shown a beneficial effect in treating apthous stomatitis and mucositis.14 In vitro, sub-antimicrobial doxycycline (20-40mg/day) reduces pro-inflammatory cytokines and has been proposed as a safe long term therapy for chronic inflammatory diseases like OLP and LP.15 Systemic retinoids, isotretinoin (10-60 mg/day) and acitretin (20-30mg/day), have also shown benefit for recalcitrant OLP and LP; most patients experienced clinical improvement after an eight-week course of isotretinoin and twelve-week course of acitretin that then relapsed about two months after completing each therapy, which the authors argue supports longer term therapy or repeated courses.16,17,18
Azathioprine (AZA) at 50mg twice daily was effective at treating both generalized LP and erosive OLP after only 1 to 2 months; AZA was decreased to 50mg daily and discontinued after 3 months of therapy and patients remained clear at a 6 month follow up exam.19 For severe LP, cyclosporine (CsA) at 6mg/ kg daily resulted in clearance after 8 weeks of therapy without any significant adverse events; patients remained clear 3 and 10 months following therapy.20 A recent study compared mycophenolate mofetil (MMF) and methotrexate (MTX) for vulvar LP; MMF was initiated at 1000mg daily and MTX at 10mg weekly and both were titrated to an average of 1500mg and 13mg respectively. Duration of treatment was an average of 15 months for MMF and 21 months for MTX. Although response rates were similar (64% MMF; 70% MTX), the time until initial response varied (2 months for MMF; 4 months for MTX). Rates of remission also differed (21% MMF; 10% MTX).21
TNF inhibition with adalimumab (40mg q2weeks) caused a 50% reduction in OLP lesions after 4 weeks and almost complete clearance after 6 weeks.22 After standard psoriasis loading doses, secukinumab (300mg q4weeks), ustekinumab (45mg q12weeks), and guselkumab (100mg q8weeks) all showed efficacy in OLP and LP.23 Secukinumab and ustekinumab resulted in 50% reduction of LP and OLP lesions by week 8 and almost clear by week 12. OLP lesions resolved faster than LP lesions, most noticeably with secukinumab. Guselkumab efficacy was similar, but significantly slower as clearance was observed after 30 weeks.23 Many trials are currently underway for OLP and LP; a search for “lichen planus†on clinicaltrial.gov currently yields 120 total results including trials with various oral and topical agents.
Isolated NLP may require focal treatment to prevent dystrophy and permanent disfigurement. Treatment includes topical retinoids, TCS, intralesional or even intramuscular triamcinolone injections. Injecting triamcinolone acetonide (5mg/mL) into the proximal nail matrix is efficacious, although repeated treatments may be necessary as 62% of patients had recurrence of nail disease that was equally responsive.24 Nail matrix injections are tolerable with topical ethyl chloride, “talkasthesiaâ€, and the use of vibrating devices, whereas injections into the nail bed usually require a digital nerve block. Patients with nail bed involvement were more likely to receive intramuscular triamcinolone acetonide (0.5 to 1mg/kg) as well as the prior systemic therapies discussed.24 Combining tazarotene 0.1% gel and clobetasol 0.05% gel twice daily under occlusion for seven months also resulted in resolution of NLP without painful injections in those without a pterygium.25 A retrospective study on NLP found 78.6% of the patients received topical agents including TCS and vitamin D analogs, 64.3% of patients received systemic corticosteroids including prednisone (40-80mg/week) and intramuscular triamcinolone acetonide (40mg/mL monthly). During the median follow-up time of 38.5 months, 66.7% of the patients exhibited minimal to mild improvement (26-50% reduction); the remaining 33.4% showed a moderate to great improvement (51–99% reduction). However, patients with pterygium were excluded from the evaluation of improvement, because it did not respond to any treatment.26
Fewer utilized medications for LP and OLP with reported success include low dose naltrexone (LDN), hydroxychloroquine, thalidomide, and topical rapamycin. Cases of lichen planopilaris (LPP), a variant of lichen planus, have been responsive to 3mg of LDN daily resulting in reduced pruritus, inflammation, and disease progression.27 Hydroxychloroquine (200-400mg/ day) for 6 months resulted in reduced pain and erythema in OLP patients after 1 to 2 months, and erosions healed in 3 to 6 months.28 A retrospective study of thalidomide for OLP initiated thalidomide at 50 to 100mg daily and decreased to the minimal effective dose. Four of six patients were clear after four months. Three of six patients on concomitant prednisone at an average of 37mg daily decreased to 7mg daily after four months. Two patients experienced phlebitis and neuropathy resulting in discontinuation of thalidomide.29 Success with topical rapamycin (1mg/1mL) for erosive OLP and vulvar LP has been reported; 4 of 7 patients experienced complete resolution with twice daily applications for three months, 2 had partial resolution, and 1 patient discontinued due to local discomfort.
In summary, LP is a relatively common inflammatory disorder of the skin, nails, and mucosa, with genital and oral lesions frequently more difficult to treat. Patients should be periodically screened for psychological symptoms with a comprehensive history and cardiovascular symptoms with blood pressure monitoring, lipid profiles, weight monitoring, and blood glucose checks.30,31,32,33 No therapies are currently FDA approved for LP, however the various topical and systemic agents discussed are efficacious in the right circumstances and many clinical studies are ongoing. Ultimately, while numerous options exist for LP, OLP, and NLP, further research and clinical trials are needed to supplement the existing evidence.
Azathioprine (AZA) at 50mg twice daily was effective at treating both generalized LP and erosive OLP after only 1 to 2 months; AZA was decreased to 50mg daily and discontinued after 3 months of therapy and patients remained clear at a 6 month follow up exam.19 For severe LP, cyclosporine (CsA) at 6mg/ kg daily resulted in clearance after 8 weeks of therapy without any significant adverse events; patients remained clear 3 and 10 months following therapy.20 A recent study compared mycophenolate mofetil (MMF) and methotrexate (MTX) for vulvar LP; MMF was initiated at 1000mg daily and MTX at 10mg weekly and both were titrated to an average of 1500mg and 13mg respectively. Duration of treatment was an average of 15 months for MMF and 21 months for MTX. Although response rates were similar (64% MMF; 70% MTX), the time until initial response varied (2 months for MMF; 4 months for MTX). Rates of remission also differed (21% MMF; 10% MTX).21
TNF inhibition with adalimumab (40mg q2weeks) caused a 50% reduction in OLP lesions after 4 weeks and almost complete clearance after 6 weeks.22 After standard psoriasis loading doses, secukinumab (300mg q4weeks), ustekinumab (45mg q12weeks), and guselkumab (100mg q8weeks) all showed efficacy in OLP and LP.23 Secukinumab and ustekinumab resulted in 50% reduction of LP and OLP lesions by week 8 and almost clear by week 12. OLP lesions resolved faster than LP lesions, most noticeably with secukinumab. Guselkumab efficacy was similar, but significantly slower as clearance was observed after 30 weeks.23 Many trials are currently underway for OLP and LP; a search for “lichen planus†on clinicaltrial.gov currently yields 120 total results including trials with various oral and topical agents.
Isolated NLP may require focal treatment to prevent dystrophy and permanent disfigurement. Treatment includes topical retinoids, TCS, intralesional or even intramuscular triamcinolone injections. Injecting triamcinolone acetonide (5mg/mL) into the proximal nail matrix is efficacious, although repeated treatments may be necessary as 62% of patients had recurrence of nail disease that was equally responsive.24 Nail matrix injections are tolerable with topical ethyl chloride, “talkasthesiaâ€, and the use of vibrating devices, whereas injections into the nail bed usually require a digital nerve block. Patients with nail bed involvement were more likely to receive intramuscular triamcinolone acetonide (0.5 to 1mg/kg) as well as the prior systemic therapies discussed.24 Combining tazarotene 0.1% gel and clobetasol 0.05% gel twice daily under occlusion for seven months also resulted in resolution of NLP without painful injections in those without a pterygium.25 A retrospective study on NLP found 78.6% of the patients received topical agents including TCS and vitamin D analogs, 64.3% of patients received systemic corticosteroids including prednisone (40-80mg/week) and intramuscular triamcinolone acetonide (40mg/mL monthly). During the median follow-up time of 38.5 months, 66.7% of the patients exhibited minimal to mild improvement (26-50% reduction); the remaining 33.4% showed a moderate to great improvement (51–99% reduction). However, patients with pterygium were excluded from the evaluation of improvement, because it did not respond to any treatment.26
Fewer utilized medications for LP and OLP with reported success include low dose naltrexone (LDN), hydroxychloroquine, thalidomide, and topical rapamycin. Cases of lichen planopilaris (LPP), a variant of lichen planus, have been responsive to 3mg of LDN daily resulting in reduced pruritus, inflammation, and disease progression.27 Hydroxychloroquine (200-400mg/ day) for 6 months resulted in reduced pain and erythema in OLP patients after 1 to 2 months, and erosions healed in 3 to 6 months.28 A retrospective study of thalidomide for OLP initiated thalidomide at 50 to 100mg daily and decreased to the minimal effective dose. Four of six patients were clear after four months. Three of six patients on concomitant prednisone at an average of 37mg daily decreased to 7mg daily after four months. Two patients experienced phlebitis and neuropathy resulting in discontinuation of thalidomide.29 Success with topical rapamycin (1mg/1mL) for erosive OLP and vulvar LP has been reported; 4 of 7 patients experienced complete resolution with twice daily applications for three months, 2 had partial resolution, and 1 patient discontinued due to local discomfort.
In summary, LP is a relatively common inflammatory disorder of the skin, nails, and mucosa, with genital and oral lesions frequently more difficult to treat. Patients should be periodically screened for psychological symptoms with a comprehensive history and cardiovascular symptoms with blood pressure monitoring, lipid profiles, weight monitoring, and blood glucose checks.30,31,32,33 No therapies are currently FDA approved for LP, however the various topical and systemic agents discussed are efficacious in the right circumstances and many clinical studies are ongoing. Ultimately, while numerous options exist for LP, OLP, and NLP, further research and clinical trials are needed to supplement the existing evidence.
