Photodynamic therapy and pain: A systematic review
Introduction
Photodynamic therapy (PDT) is a safe and effective method of treating a variety of skin conditions including diffuse actinic keratoses and skin cancers (superficial and nodular basal cell carcinoma, squamous cell carcinoma in situ). Importantly, it is the only FDA-approved treatment modality that can be used by dermatologists in the clinic to treat field cancerization. The three components of PDT are photosensitizer, oxygen, and light source. The two primary photosensitizers used in dermatology are 5-aminolevulinic acid (ALA) and methyl-5-aminolevulinate (MAL) [48]. Use of 5-aminolevulinic acid nanoemulsion gel (BF-200 ALA) has also been investigated in the literature [23]. These photosensitizers are precursors to the active metabolite protoporphyrin IX (PpIX), which, after activation by visible light (usually in the blue or red spectra) in the presence of oxygen, causes formation of reactive oxygen species (ROS) and ROS-mediated selective tissue injury and cell death [1]. Unfortunately, pain during illumination can be significant and can interfere with desire for and completion of PDT treatments. A number of interventions have been investigated to mitigate treatment-related pain. Some can be considered to be canonical measures of reducing pain by the use of various pain medications with different application protocols. Other interventions, which aim to mitigate pain, modify procedure parameters including light sources, irradiance (fluence rate or intensity) or dose (fluence). The goal of this systematic review is to investigate the impact of reported interventions and parameter adjustments on PDT-associated pain to provide guidance for future studies and for clinicians aiming to better understand PDT-associated pain.
Section snippets
Methods
We systematically searched and assessed all scientific reports on treatment of patients with actinic keratoses and/or non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma in situ) treated with photodynamic therapy (PDT) (see Fig. 1). Inclusion criteria were mention of quantitative pain scores during PDT (primary outcome measurement) and use of topical photosensitizers during PDT for conditions mentioned above (see search terms below). Observational studies or studies that
Results
Forty-eight studies were included in the systematic review. The included studies were divided into two main groups based on type of modifying factor used in the study: control of pain with pharmacologic or physical measures without modifying PDT parameters (category 1, n = 13), or studies that modified PDT by altering the type of photosensitizer or photo-irradiation used (category 2, n = 35). The resultant quantitative effect on pain was reported. The pain scales included the visual analog scale
Discussion
No standard protocol exists for photodynamic therapy. Within studies included in this analysis alone, there are variations in the type of photosensitizer used (ALA, BF-200 ALA, MAL), skin preparation prior to treatment (light curettage, keratolytics, prep tape), the occlusion of the photosensitizer, duration of photosensitizer application (up to six hours), type of light source, irradiance, routine pain interventions, potential for interruption of illumination, and number of total treatments,
Conflict of interest
All 5 authors report no disclosures.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sections.
Category 1 RCT.
Category 2 RCT.
Acknowledgement
Authors report no disclosures.
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- 1
Present address: Kaiser Permanente Panorama City Medical Center, Department of Dermatology 13651 Willard Street Panorama City, CA 91402, United States.
- 2
Present address: Bronx Lebanon Hospital Center, Mount Sinai School of Medicine, 1650 Grand Concourse, Bronx, NY, 10457, United States.