To compare the effectiveness and safety of hydroxychloroquine and methotrexate added to standard treatment (systemic steroids) versus standard treatment alone in the treatment of moderate to severe oral lichen planus (OLP) with or without skin involvement

Study setting: The study will be conducted at the Oral Medicine Clinic, Faculty of Dental Sciences, University of Peradeniya.

Intervention: This is a three armed clinical trial, intended to compare effectiveness of two new treatments + standard treatment regimen (the study arm with standard treatment regime alone used as the control arm.) Therefore, to calculate the number required for each arm with 5% error (level of significance at 95%) and 10% error (power of the test at 90%), it is essential to have exact effectiveness of the standard treatment method as a percentage. However, there is no consensus on the effectiveness of the standard treatment among experts in the field. Therefore it was decided to recruit 25 subjects to each arm using the block randomization method until the completion of 75 subjects. Once this number is reached, an interim data analysis will be carried out to assess the effectiveness of different treatment regimes in three arms. These values will be used to calculate the exact number required in each arm to achieve a valid and reliable outcome at 5% error and 10% error. This is an internationally accepted method and widely used when required information is not available. After completion of collecting 75 subjects and interim analysis, the newly calculated sample size will be submitted to the ethical clearance committee with the progress report for approval. Once the study subjects are randomized to three treatment arms, the baseline clinical condition of the subjects will be assessed using the Guy’s score assessment method. This has three components, namely site, activity and pain score. In addition, Lichen Planus severity index and VAS scale to assess the thickness of the lesion will be used. The full blood count, SGOT/SGPT, serum creatinine, and FBS levels of patients will be collected to assess the possible adverse effects.

Arm 1 : Standard Treatment - Oral Prednisolone will be started with 0.5 mg / kg and If there is a 50% recovery of Guy’s Oral Disease Severity Score, prednisolone dose will be reduced by 50%. - Vitamin D and Calcium Supplements will be provided. - Omeprazole will be given for required patients.

Arm 2 : Standard Treatment + hydroxychloroquine (HCQ) - Oral Prednisolone will be started with 0.5 mg / kg and If there is a 50% recovery of Guy’s Oral Disease Severity Score, prednisolone dose will be reduced by 50%. - Vitamin D and Calcium Supplements will be provided. - Omeprazole will be given for required patients. - HCQ will be given at a dose of 200 mg daily at night for a period of 16 weeks

Arm 3 : Standard Treatment + methotrexate (MTX) - Oral Prednisolone will be started with 0.5 mg / kg and If there is a 50% recovery of Guy’s Oral Disease Severity Score, prednisolone dose will be reduced by 50%. - Vitamin D and Calcium Supplements will be provided. - Omeprazole will be given for required patients. - MTX will be commenced at a dose of 5 mg once a week (Sunday). The dose will be increased by 2.5mg every two weeks (if needed depending on the clinical response and adverse events) up to a maximum weekly dose of 10 mg, which will be continued for the rest of the study period. - Folic acid supplementation will be continued for the duration of MTX therapy at a dose of 1 mg once a week (Wednesday).

This trial uses standard treatment as the control. This is an open labeled study

Assessment: Every fortnight for a total duration of 16 weeks, Documentation of all skin and oral lesions. The oral lesions will be documented and numbered on a diagram. A minimum of six photographs will be taken from the oral cavity to cover the six areas; left buccal mucosa, right buccal mucosa, palate, dorsal surface of the tongue, ventral surface of the tongue and the floor of the mouth.

1. Age 18-60 years, both male and female.
2. Patients with histologically confirmed moderate to severe OLP with or without skin involvement (a pain score of 6 or greater on a VAS of 0 to 10)
3. Histological confirmation of diagnosis from an incisional biopsy from oral mucosa
4. Sinhala / English speaking patients

1. Patients with psychiatric disorders
2. Pregnant or lactating women (to exclude pregnancy in premenopausal women, treatment will be commenced after the next menstrual period or if still unsure, after a negative urine hCG test.)
3. Patients with contraindications for HCQ or MTX
4. Patients with poorly controlled diabetes
5. Patients with known retinal diseases
6. Patients with other dermatological conditions in addition to LP
7. Patients who have received treatment for LP previously
8. Patients with contraindications to long-term steroids