Photodynamic Therapy For Actinic Keratosis

  • Priyanka ThakurBachelor in Medicine, Bachelor in Surgery (MBBS), DRPGMC, India
  • Richard StephensDoctor of Philosophy(PhD), St George's, University of London

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Introduction

Definition and overview of actinic keratosis (AK)

Actinic Keratosis is a condition that causes dry, scaly skin patches and if not treated it can lead to a type of skin cancer. To prevent AK is to protect yourself from any kind of sun damage or UV lights. If you notice new red dry bumps on the skin, it is best to talk with your local GP who can advise on better help.1 

Introduction to photodynamic therapy 

Photodynamic therapy (PDT) is a form of therapy that uses light energy and photosensitising education combined for the treatment of different types of cancer and other health conditions, such as psoriasis, acne and infections.2

Understanding actinic keratosis 

Characteristics

Actinic Keratosis (AK), is a skin disorder that causes scaly, dry patches on the skin. It can be a type of precancer, meaning if this is not treated then it could turn into a skin cancer, called squamous cell carcinoma.1,3

Causes and risk factors 

AK is caused by too much exposure to ultraviolet (UV) lights. This damages the outermost layer of skin cells, called the keratinocytes. The damage to the skin from UV rays can build up over time, so this means short-term exposure to the sun on a regular basis can build up over time increasing the risk of AK. Some individuals are more at risk than others:3

  • Those with pale skin
  • Blond or red hair
  • Blue, Green, grey eyes
  • Those with darker skin and eyes and don't use skin protection
  • Elderly
  • Has severe sunburns
  • Weak immune system from illness or immunotherapy treatment for cancer

Clinical presentation and diagnosis

The first signs of AK include dry, raised bumps in the skin that can vary in colour from yellow to brown. But they can also be grey, pink, red and/or the same colour as your skin. You may also experience bleeding, burning, itching, pain and tenderness in the area affected.1,3

So how is AK diagnosed?

A dermatologist or your local GP would carefully analyse your skin with the use of magnification. For further examination, they may take a skin biopsy to be examined under the microscope for a more specific diagnosis.3

The importance of treatment

AK is a serious skin disorder that can turn into skin cancer so it is important to take immediate treatment. In most cases, it can completely go away with topical treatment or surgery, but it is important to take early action.

Overview of photodynamic Therapy (PDT)

Development and history

The first attempts at using PDT as treatment were in 1903, but it wasn't until 1972, that scientists found that tumour cells were killed by visible light after sensitisation using a drug derivative called hematoporphyrin.4

How does PDT work?

PDT works by using photosensitising agents, light and oxygen, to create a chemical reaction that can selectively destroy the more “dangerous” cells. The photosensitising agents, in the body, are concentrated around the cells and only become active when light of a certain wavelength is directed to the area, resulting in the reaction between the agents, light and oxygen to produce oxygen species that interact with the cells, causing cell death.4

Types of photosensitisers used 

There are different types of photosensitising agents, including:5

  • BF-200 ALA gel – used with blue light8
  • Methyl aminolevulinic acid cream - used with daylight or red light. Effects start after 24 hours
  • Porfimer sodium – given intravenously and the effects on the skin can last for a few months
  • Aminolevulinic acid hydrochloride topical solution - used with a blue light
  • Benzoporphyrin derivative monoacid ring A - undergoing evaluation9

Light sources and activation wavelengths 

Different light sources can be used, depending on the agents used, including:5

Advantages and limitations of PDT 

The advantages and limitations of PDT include:6

Advantages

  • No long-term side effects
  • It can be targeted to the region very precisely
  • Less invasive than surgery
  • Costs less than other other cancer treatments
  • Requires a short amount of time
  • There is little to no scarring after it heals
  • PDT can be repeated many times in the same area if it is needed 

But PDT also has some limitations

  • PDT can only be treated where light can reach, like skin and lining of organs that can reach the light source 
  • Medication used in PDT can leave people sensitive to light 
  • PDT cannot be used in people with certain blood diseases
  • PDT cannot be used to treat AK that spread in many areas of the body

The procedure of photodynamic therapy

There are 2 ways in which PDT is given:7

  • Conventional PDT - using light from a lamp or laser
  • Natural daylight

Application of photosensitiser

Conventional PDT

  1. You will be given the photosensitising agent medication and depending on the area that is being treated you may be given medication, cream, injection or a special drink
  2. After you are given the agent, you will be asked to go home and return in a few hours or days, to give a chance for the medication to build up in the abnormal cells

Light exposure and activation

  1. You will return to the hospital for the light treatment, which will involve either a lamp or laser, that will be shone on the treatment area for 10 to 45 minutes 
  2. Sometimes, a local or a general anaesthetic can be used to numb the treatment area and to help you relax during the procedure

Natural daylight PDT

A cream is applied to the affected area at the hospital or sometimes at home. Then you will have to spend 2 hours outdoors in the daylight to activate the medication. It is important to make you put on sunscreen when doing natural light PDT. 

Post-treatment care and follow-up

Conventional PDT 

  1. If your skin was treated, then the area treated will be covered in a dressing. It is best to avoid scratching and keep it as dry as possible
  2. A follow-up appointment with your doctor will then be arranged, to make the treatment was successful
  3. It should take around 2-6 wells for the area treated to completely heal

Natural daylight 

  1. The medicine cream in the area will be wiped off and it will be covered for the rest of the day to prevent any kind of inflammation
  2. It is also a good idea to use sunscreen that is at least SPF 50
  3. A follow-up appointment will then be arranged to check if the treatment worked 

Efficacy and safety of photodynamic therapy 

Clinical outcomes and efficacy rates

PDT is a very safe and effective treatment and it has been shown to be successful in treating conditions, but there are some side effects to it:6

Potential side effects and complications

  • Burning and stinging sensation 
  • Skin or eyes can become sensitive to sunlight for up to 6 weeks
  • Sometimes the immune system changes, by becoming weaker for a certain period of time 

Summary

AK is a serious skin disorder that can turn into skin cancer if not recognised appropriately and given treatment at the right time. Photodynamic therapy can minimise the damage to the healthy cells as it only targets the damaged cells. It also has no long-term side effects and can be performed as an outpatient procedure. The sooner you seek treatment, the less the chances of developing skin cancer. 

References

  1. Overchuk M, Weersink RA, Wilson BC, Zheng G. Photodynamic and Photothermal Therapies: Synergy Opportunities for Nanomedicine. ACS Nano [Internet]. 2023 [cited 2024 Jun 3]; 17(9):7979–8003. Available from: https://pubs.acs.org/doi/10.1021/acsnano.3c00891.
  2. Marques E, Chen TM. Actinic Keratosis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Jun 3]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK557401/.
  3. Gunaydin G, Gedik ME, Ayan S. Photodynamic Therapy for the Treatment and Diagnosis of Cancer–A Review of the Current Clinical Status. Front Chem [Internet]. 2021 [cited 2024 Jun 3]; 9. Available from: https://www.frontiersin.org/articles/10.3389/fchem.2021.686303.
  4. Correia JH, Rodrigues JA, Pimenta S, Dong T, Yang Z. Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions. Pharmaceutics [Internet]. 2021 [cited 2024 Jun 3]; 13(9):1332. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470722/.
  5. Kwiatkowski S, Knap B, Przystupski D, Saczko J, Kędzierska E, Knap-Czop K, et al. Photodynamic therapy – mechanisms, photosensitizers and combinations. Biomedicine & Pharmacotherapy [Internet]. 2018 [cited 2024 Jun 3]; 106:1098–107. Available from: https://www.sciencedirect.com/science/article/pii/S0753332218341611.
  6. Casari A, Chester J, Pellacani G. Actinic Keratosis and Non-Invasive Diagnostic Techniques: An Update. Biomedicines [Internet]. 2018 [cited 2024 Jun 3]; 6(1):8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874665/.
  7. Reinehr CPH, Bakos RM. Actinic keratoses: review of clinical, dermoscopic, and therapeutic aspects. An Bras Dermatol [Internet]. 2019 [cited 2024 Jun 3]; 94(6):637–57. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939186/.
  8. González-Guerra E, Taboada AC, Muñoz LC, Fructuoso AIS. Photodynamic therapy with BF-200 ALA gel for the treatment of actinic keratosis, Bowen´s disease and basal cell carcinoma in long term immunosuppressed patients after organ transplantation. Photodiagnosis Photodyn Ther. 2024; 45:103882.
  9. Benzoporphyrin Derivative - an overview | ScienceDirect Topics [Internet]. [cited 2024 Jun 3]. Available from: https://www.sciencedirect.com/topics/medicine-and-dentistry/benzoporphyrin-derivative.

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Anjali Tulcidas

Master of Science- MSc Advanced Biomedical Sciences, De Montfort University

My name is Anjali, and I am an aspiring medical communications professional from Portugal. I have a life-science background with a Bachelor’s degree in Biomedical science, along with experience as a Research Intern in the Fiji Islands. I pursued my Master’s in Advanced Biomedical Sciences because I was looking into enriching my understanding of different diseases and their therapeutic areas. I hope you enjoy reading this article!

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