Photodynamic therapy in oral lichen planus: A prospective case-controlled pilot study

Abstract

Oral lichen planus (OLP) is a common, chronic relapsing inflammatory disorder of the mucous membranes, which causes major discomfort. Current treatment includes topical/systemic glucocorticoids, immune modulators and systemic immunosuppressants, which may lead to considerable side-effects. The aim of this study was to determine the clinical and immunological efficacy of photodynamic therapy (PDT) in OLP as an alternative, easy-to-use, safe and non-invasive treatment. Twenty patients with OLP were treated with PDT in a prospective case-controlled pilot-study. PDT was performed on the most extensive oral lesion in 4 sessions (day 1, 3, 7, 14). Peripheral blood and lesional T cells were analysed before (day 1) and after PDT treatment (day 28). PDT led to a statistically significant reduction of clinical parameters (lesion size, ABSIS, Thongprasom-score) and improvement of all evaluated quality-of-life (QOL) items. The clinical improvement was accompanied by a significant decrease of the relative number of CD4+ and CD8+ T cells in mucosal OLP-lesions. Furthermore, CXCL10 plasma levels were decreased and the number of activated peripheral CD4 + CD137+ and CD8 + CD137+ T cells and IL-17-secreting T cells was diminished. PDT treatment in OLP leads to lesion reduction and improvement of QOL, and induces local and systemic anti-inflammatory effects. The study identifies PDT as a novel therapeutic option in OLP.

Figure 1

Time line of PDT treatment. Clinical and QOL parameters were assessed on day 1 (D1; before therapy), day 28 (D28, 14 days after therapy), day 42 (D42, 28 days after therapy) and day 56 (D56; 42 days after therapy). Samples were collected at D1 and D28. PDT, photodynamic treatment; QOL, quality of life.

Figure 2

PDT leads to clinical amelioration of OLP. (a) PDT induces a reduction of lesion size over time (D1-D56). (b) PDT leads to reduction of ABSIS score I over time (D1-D56). (c) Photographically documentation of lesion size reduction over time (D1-D56). (d) PDT leads to a reduction of ABSIS II score over time (D1-D56). (e) QoL parameters (burning, pain, food, oral hygiene) are improved after PDT treatment (D1-D56). *p < 0.05, **p < 0.01, ***p < 0.001. PDT, photodynamic treatment; QOL, quality of life.

Figure 3

PDT induces systemic anti-inflammatory effects in OLP. (a) Relative number of CD137 expressing peripheral blood CD4+ T- cells is decreased 14 days after PDT treatment. Results based on analysis by flow cytometry. (b) Relative number of CD137 expressing peripheral blood CD8+ T- cells is decreased 14 days after PDT treatment. Results based on analysis by flow cytometry. (c) PDT leads to an increase of the relative number of peripheral blood γδ T cells. Results based on analysis by flow cytometry. (d) Number of peripheral blood IL-17a producing T cells is decreased 14 days after PDT treatment. Results based on ELISpot. analysis. (e) CXCL10 plasma levels are decreased 14 days after PDT treatment. Results based on ELISA analysis.*p < 0.05, **p < 0.01. PDT, photodynamic treatment.

Figure 4

CXCL8 saliva levels are slightly decreased after PDT treatment. Shown are saliva concentrations (pg/ml) of CXCL8 before (day 1, D1) and after (day 28, D28) PDT treatment of oral OLP lesions.

Figure 5

PDT induces local anti-inflammatory effects in OLP. (a) Overview of immunohistochemical staining of mucosal tissue sections with a lesional T- cell infiltrate before and after PDT treatment (D1, D28). (b–d) Relative number of lesional CD3+, CD4+ and CD8+ cells are decreased 14 days after PDT treatment. (e) Relative number of lesional IL-17+ cells is increased 14 days after PDT treatment. **p < 0.01. PDT, photodynamic treatment.

Figure 6

Analysis of T lymphocyte subsets in OLP lesions. The T- cell infiltrate of mucosal sections was quantified by microscopical images (Axiostar, Zeiss, Jena, Germany) in combination with Cell^D (Soft Imaging System, Berlin, Germany) and ImageJ software (freeware). T cells were counted at a 100x magnification. After generating a grid (ImageJ software; area per point: 50.000 pixels^2), all stained T- cells were counted in three squares adjacent to basal membrane zone (ImageJ, cell counter) and their proportion of all infiltrating cells was determined subsequently.