Path to cure port-wine stains

There are several different approaches currently used for the treatment of port-wine stain (PWS) including various laser and light modalities; however, none can truly effectively address this common vascular malformation.

While approximately 80% of port-wine stains improve with laser treatment, less than 20% clear completely, begging the need for more optimal treatment solutions. According to one expert, much more can be done to achieve better outcomes.

Dr. Rubin“Port-wine stains are not a solved problem and to date, while there are good laser treatment options, multiple treatments are required. Most PWS do not clear completely and a cure for PWS remains elusive. Continued research, however, has born new and exciting strategies for PWS, some of which could prove to be much more effective than the currently used treatment approaches,” says Iris Kedar Rubin M.D., assistant clinical professor of dermatology, George Washington University.

Port-wine stains is a commonly seen vascular malformation involving post-capillary venules. Most frequently occurring on the head and neck, these lesions will typically darken over time and may become hypertrophic and nodular with age, and hence more difficult to treat, underscoring the need for an early therapeutic intervention.

Current treatment modalities such as the pulsed dye lasers have been shown to be effective in the treatment of PWS, however, according to Dr. Rubin, these treatments are far from optimal because complete clearance is only achieved in less than 20% of patients. Moreover, multiple treatment procedures are required, which can be painful for young patients or it may require repeated anesthetics. Those patients who do not achieve clearance require many maintenance treatments throughout their lifetime.

“When we take a pulsed dye laser to an adult or a child’s skin, we are taking our best guess concerning the treatment parameters. We are guessing as to what the sizes of the vessels are in the target region, as well as the depth and configuration of the vessels. Is that good enough? In my opinion, we can do better and need to re-think our current strategies for PWS,” Dr. Rubin says.

Next: Treatment strategies

Treatment strategies

There are a number of treatment strategies, Dr. Rubin says, many of which are still under conception that could significantly impact treatment outcomes of PWS. According to Dr. Rubin, one solution would be the use of smarter lasers, which could generate pre-treatment road map imaging of the lesion, and allow clinicians to tailor treatment parameters optimizing wavelength, pulse duration and fluence to the specific vascular lesion to be treated.

“Ideally, it would be much smarter if we had a way to get a road map before we went and treated with a laser. Here, an imaging modality can be used to visualize the vessels in real-time, allowing the clinician to appropriately tailor the laser parameters specific to the targeted vessels,” Dr. Rubin says.

Vein selective photothermolysis would be another new approach that could more effectively address PWS. Port-wine stains are composed of post-capillary venules and targeting venous blood could perhaps improve treatment efficacy and safety. According to Dr. Rubin, in vitro studies suggest the 680 nm wavelength to be optimal for venous selectivity by maximizing Hb/HbO2 and Hb/metHb.

“When we think about targeting blood, the traditional target has been oxyhemoglobin, but veins have both deoxyhemoglobin and oxyhemoglobin. So, if you want to selectively target the veins and avoid the arteries, you can do that by going after deoxyhemoglobin,” she says.

Next: Heart attack for the skin

Heart attack for the skin

Clipping off an artery with a laser can be likened to a heart attack for the skin where necrosis and scarring can ensue. One of the benefits of vein selective photothermolysis would be that potentially, one could have a more safe and effective treatment by avoiding the arteries and arterioles and only selectively targeting the venules. Targeting the venules could potentially also help reduce the hypoxic stimulus and angiogenesis often seen following traditional laser therapy, and result in a higher efficacy and efficiency of PWS treatment.

Using multiple pulses, multiple passes, and tailoring the pulse duration, are other smart strategies that can help improve outcomes in PWS treatment. Employing multiple pulses can increase the depth of penetration, and a lower radiant exposure is required for each pass. According to Dr. Rubin, one of the main limitations with pulsed dye is that the depth of penetration is less than some port-wine stains require.

“Physicians typically treat port-wine stains with a single pulse duration, however port-wine stains can be heterogeneous, composed of vessels of various sizes. What if we had a smarter laser that could vary the pulse duration as it moved along to match the size of the vessels? A tailored pulse duration throughout the treatment would be a significant procedural benefit, treating vessels of all sizes,” she says.

Next: Drug/device combination treatment

Drug/device combination treatment

Other treatment approaches include the targeting of the feeder vessels that, in part, serve as a pipeline for these vascular malformations, as well as drug and device combination therapies. Port-wine stain vessels lack normal sympathetic tone. One potential example of a drug/device combination would be to treat with a laser and a medication to address the neural deficit. Other examples of medications that may be useful in conjunction with laser and light sources are angiogenesis inhibitors, photosensitizers implemented with photodynamic therapy, or drugs with molecular targets based on genetic mutations. These approaches could increase the long-term therapeutic outcomes of PWS.

“The ultimate vision and goal is a single laser treatment at an early age. This is not just a cosmetic issue. We know that the majority of port-wine stains hypertrophy, and that can lead to functional issues in addition to the disfigurement and social distress that port-wine stains can cause. In full disclosure, I don’t know if we can cure port-wine stains. We owe it to our patients to try to do better and apply these new strategies that could be a part of that path to a cure for PWS,” Dr. Rubin says.