By Abby S. Van Voorhees, MD, December 03, 2012
In this month’s Acta Eruditorum column, Physician Editor Abby S. Van Voorhees, MD, talks with Jennifer K. Chen, MD, about her recent Journal of the American Academy of Dermatology article, “An overview of clinical and experimental treatment modalities for port wine stains.”
Dr. Van Voorhees: What is the frequency of port wine stains?
Dr. Chen: Port wine stains are the most common vascular malformation of the skin. They occur in about 0.3 to 0.5 percent of infants.
Dr. Van Voorhees: What currently is the most commonly used treatment modality? How is it thought to work? How successful is it at clearing treated lesions? What are the most common limitations/risks of this modality?
Dr. Chen: The pulsed dye laser (PDL) is the most commonly used treatment modality. Lasers work by photocoagulating the blood vessels in a port wine stain. Full regional clearance is seen in about 40 percent of cases, with suboptimal clearance seen in about 20 to 46 percent of cases and no clearance in 14 to 40 percent of cases. The efficacy of the pulsed dye laser may be limited by darker skin types and by the presence of a tan. The most common risks include bruising, pigmentary changes of the skin, pain, incomplete resolution of the condition, and recurrence of the condition. Blistering and scabbing can occur and in some cases can result in scarring so it’s important not to be overly aggressive. We also tell our patients to prepare for multiple treatments. [pagebreak]
Dr. Van Voorhees: Is there an optimum age for the treatment of lesions?
Dr. Chen: At our institution we always try to treat earlier; we believe this results in a better treatment outcome. Also, you want to start before the child starts to feel different or socially stigmatized. The goal is to improve quality of life so we like to start early.
Dr. Van Voorhees: Do we know what factors cause patients to have a poor outcome from treatment with the pulsed dye lasers? Have modifications been made to either the lasers or to protocols to try to enhance their response rates?
Dr. Chen: Several factors have been recognized in patients with a poor treatment outcome. We know that the extent of epidermal pigmentation plays a role, as well as shielding by blood and superimposed vessels. Large port wine stains and those with deep or dense vasculature are also harder to treat. Following treatment, blood vessels may also grow back within the treatment site.
Several modifications have been made to the pulsed dye laser to try to improve response rates. Initially the 577 nm wavelength was used; it was found that increasing the wavelength to 585 or 595 nm increased the depth of penetration. Increasing the spot size was also found to increase the depth of penetration and allow for more uniform energy transmission and shorter treatment times, as long as the spot size was not larger than the target lesion. Changing these settings may enhance the response rate. Epidermal cooling has also been used to decrease non-selective epidermal thermal injury to epidermal melanocytes, allowing the treatment of darker skin types and the use of higher fluences, and also decreasing the patient’s level of pain and discomfort. [pagebreak]
Dr. Van Voorhees: Can you predict which patients require these steps to ensure a response to treatment?
Dr. Chen: It’s difficult. Purple, hypertrophic port wine stains tend to not respond as well to the pulsed dye laser, but otherwise it can be difficult to predict which lesions will respond and which ones won’t.
Dr. Van Voorhees: Do the modifications that have been made to the lasers to enhance their response rate, such as changing the wavelength and spot size or providing cooling, have disadvantages? Or have they only improved our techniques and strategies?
Dr. Chen: There is a clear benefit in going from 577 nm to 585 nm. Going from 585 nm to 595 nm the data was not as strong. Every patient is going to be different; there are variations in the anatomy from one area to another in the same patient. So it’s very difficult to predict the optimum wavelength. It’s not that you want to just increase the settings to get a better result. You want to tailor them to your patient. There’s no magic formula that tells you that a certain appearance equals a certain setting. [pagebreak]
Dr. Van Voorhees: Are there negative consequences to providing cooling to the skin?
Dr. Chen: We use cryogen spray cooling and we haven’t had any complications. There are some small potential risks: if cooling is excessive then it can decrease the temperature of the blood vessels, which may affect treatment. Also, some have argued that there is a slight risk of discoloration with cooling if it is excessive, but this has not been our experience.
Dr. Van Voorhees: What are the other modalities used to treat port wine stains? Can you talk us through their advantages and disadvantages?
Dr. Chen: The alexandrite laser has been used in patients who have failed the pulsed dye laser. The greater wavelength allows for increased penetration, making it especially useful for hypertrophic or nodular port wine stains that may contain deeper blood vessels. The Nd:YAG has also been used in some patients. The main disadvantage of the alexandrite and Nd:YAG is that they’re associated with an increased risk of pigmentary changes and scarring, both due to the increased penetration and the decreased absorption by hemoglobin, which necessitates the use of higher fluences. The Nd:YAG especially can cause significant scarring and we recommend its use only to those who are experienced with it. Intense pulsed light has also been shown to be useful, although a head-to-head comparison showed that PDL resulted in significantly better lesional clearance. [pagebreak]
Dr. Van Voorhees: Let’s talk about the new treatments on the horizon. Maybe you can tell us from your perspective how these compare and what their advantages and disadvantages might be.
Dr. Chen: The strongest body of evidence is for photodynamic therapy (PDT). When treating vascular lesions PDT entails activation of an intravenously administered photosensitizer by a wavelength of light that in the presence of oxygen leads to the formation of reactive oxygen species. These cause direct damage to endothelial cells, leading to thrombosis and occlusion of the blood vessel. Damage is limited to areas containing sufficient photosensitizer concentration, imparting some degree of site-specificity. Some studies have shown that PDT is equivalent or even superior to PDL treatment, especially in the treatment of purple, flat lesions, but more studies are needed. There may be a role for combination therapy with PDT followed by PDL, which appears to act synergistically, and this is an area of active research. One particular advantage of PDT is the ability to treat all skin types. Disadvantages include the generalized photosensitivity that occurs after therapy, which can last from five days to four weeks depending on the photosensitizer used, and the expense of photosensitizers.
Dr. Van Voorhees: If taken intravenously, how does the photosensitizer know to target the lesion?
Dr. Chen: You only get a treatment effect when you have both the photosensitizer and the selected wavelength of light in the same place. The photosensitizer is first given intravenously and then you illuminate only the area of skin that you are treating. Photosensitizers that have been used include benzoporphyrin monoacid A, photocarcinorin, and hematoporphyrin monomethyl ether. Topical and oral photosensitizers have not shown efficacy. [pagebreak]
Dr. Van Voorhees: What other new treatments are on the horizon?
Dr. Chen: Angiogenesis inhibitors are another exciting new area of investigation. Angiogenesis is now thought to be a critical factor limiting treatment efficacy due to post-treatment vascular repair of PWS blood vessels. There have been some data showing that immune response modifiers such as imiquimod and rapamycin possess anti-angiogenic properties. Preliminary data suggest that these agents actually have potential to increase treatment efficacy when applied topically following pulsed dye laser treatment of port wine stains. The advantage of this treatment is that these topical treatments are well-tolerated with good safety profiles, although further study is required.
Another therapeutic option under investigation is the use of hypobaric pressure devices, or pressure cuffs, to alter the hemodynamics of PWS vasculature in order to increase susceptability to photo-induced damage. With hypobaric pressure devices such as pressure cuffs or suction devices, blood vessel dilation can be induced in the PWS vasculature, making these vessels easier to target. It is still too early to know what the advantages and disadvantages of this would be, but preliminary data are promising.
Lastly, site-specific pharmaco-laser therapy is a treatment modality that targets vessels that are only partially occluded by PDL treatment, which may play a role in treatment failure. Following PDL treatment, liposomes are injected that contain pro-thrombotic and anti-fibrinolytic drugs. These liposomes accumulate in the thrombi of partially occluded vessels and drug release is triggered by heat via heating pad or near infrared light. This leads to complete occlusion of blood vessels, potentially improving lesional clearance rates. It’s still too early to know what the advantages and disadvantages of this system would be but this is another modality we may be hearing about more over the next few years. [pagebreak]
Dr. Van Voorhees: What advice would you give to dermatologists who are managing these patients about improving their clinical outcomes?
Dr. Chen: A good place to start would be the pulsed dye laser. Changing the wavelength, increasing the spot size, or varying the pulse duration might be helpful. The alexandrite laser might be useful for patients with purple, nodular port wine stains. It’s very important to be careful to avoid being overly aggressive as this can lead to scarring. It will also be important to keep up with the literature because it’s likely that there will be new data coming out in the future that may give us new protocols.