Daylight-mediated PDT

Dr Hans Christian Wulf has been a pioneer for the growing trend in Denmark of using daylight-mediated PDT. Two worldwide experts, Dr Haedersdal and Dr Peter Bjerring, heads of the Department of Dermatology at Molhom Private Hospital in Denmark, use it in their practice with great success. Dr Haedersdal uses the standard protocol of daylight PDT by putting sunscreen on her patients and sending them outside: patients need to be outside within 30 minutes after the application of Metvix and for a total amount of 2 hours. According to Dr Haedersdal, it works best if the zones to be cured are easy to expose.

Dr Bjerring has developed a unique daylight PDT protocol, by using a special greenhouse for his PDT patients to treat AK. The glass in the greenhouse absorbs all the UVB, so the patient does not need any sunscreen, making the application of Metvix easier as it removes the need to mix it with sunscreen. After the application, the patient is sent to the greenhouse, seated facing south for 3 hours where he/she will be irradiated by UVB-filtered sunlight. When leaving the greenhouse, patients wash the treated skin area with soap and water to remove any remaining drugs. Dr Bjerring then measures the remaining activity of the Metvix using the hand-held FluoDerm fluorescence meter (Dia Medico, Gentofte, Denmark), to ensure that enough light has been delivered. The main advantage of the greenhouse, other than staying in the doctor’s office for 3 hours during the drug incubation period, is that it removes the pain associated with PDT. Standard PDT is typically a very painful treatment, so why does daylight PDT cause no pain at all?

According to Dr Bjerring, pain is caused by the strong phototoxicity. Although the mechanism behind the pain during standard PDT is not well understood, the process releases inflammatory mediators, which sensitise heat‑sensitive sensory nerves so that even normal body temperatures are perceived as a burn. In the daylight treatment, Dr Bjerring says that the phototoxic reaction happens much slower than in the standard PDT protocol.

PDT for skin rejuvenation

The use of PDT for cosmetic purposes is more controversial, and has not yet been embraced by many physicians. Most argue that as a newer application, there is not enough scientific data to back this use at the moment. The protocols are not clearly defined. Dr Marini explains the function of PDT for skin rejuvenation by saying that in a standard PDT, altered pre‑cancerous cells are destroyed by inducing either apoptotic or necrotic death. By using PDT for skin rejuvenation, inadequately functioning cutaneous cells are eliminated and normal cells are exposed to thermal and chemical stresses that eventually make them work better (hormetic stress rejuvenation). Heat shock proteins are triggered by thermal pulses which work as ‘chaperones’, recognising altered endo-cellular proteins, and directing them to ‘endocellular waste bins’. When these waste deposits are full, cells are induced to commit suicide through apoptosis.

Dr Bjerring uses a cosmetic dose of 5-ALA to treat brown spots as a treatment of choice, especially when there is a mixture of brown solar lentigines and brown pigmented AKpresent at the same time. He uses a spray form of 0.5% 5-ALA encapsulated in liposomes. His patients are put in a dim room for 3 hours and they are asked to spray themselves with 0.5% ALA every 12 minutes. Back in his office, they are irradiated with intense pulsed light (IPL). According to Dr Bjerring, IPL alone compared with his protocol of 0.5% ALA with IPL, will not effectively treat the faintly pigmented AK. Also, there is no more pain involved than with the IPL treatment alone (no more discomfort and heat sensation).

Dr Marini uses a 5% liposome encapsulated 5-ALA gel, a short incubation period (only 1 hour occlusion) followed by IPL irradiation. He claims the technique works well for superficial wrinkling and superficial benign photo‑induced dyspigmentation. According to Dr Marini, it’s very important to keep measuring the fluorescence before 5-ALA application (baseline natural fluorescence), after occlusion (primary induced PpIX fluorescence), and after irradiation (residual PpIX fluorescence) to be aware and monitor PpIX levels.

At-home PDT for skin rejuvenation may be the future

PDT for home use is an emerging trend, with some worldwide cosmetic giants already beginning to look into its applications. However, more research will be necessary to find the right concentration of the 5-ALA, as well as the right vehicle for its application.

Dr Bjerring prescribes at‑home PDT to his patients. He starts with a 0.05% tretinoin cream once daily for 2 weeks before the at-home PDT to increase the penetration of the 5-ALA. Patients then apply the 0.5% 5-ALA in liposomes in the morning (once per day) for 1 week. Then the treatment is repeated for 1 week every 3 months.

Dr Marini also prescribes his patients with a ‘preventive’ soft PDT with a topical cream containing 0.2% 5-ALA to be applied 1–2 minutes after the 0.05% tretinoin cream at bedtime. It’s a very light concentration to be used daily every other week during spring, summer, and autumn. Preventive PDT enhances the short- and long-term topical anti-ageing cosmeceutical strategies.