Monday, April 29, 2013

VZV Vaccination for the Prevention of Shingles

From: Practical Dermatology March 2013

Increasingly, there is interest in developing a vaccine that would prevent additional outbreaks of HSV among individuals who are already positive for HSV. The vaccine would presumably boost the patient's immunity to prevent subsequent outbreaks.

VZV Vaccine
The shingles vaccine is actually a concentrated form of the vaccine given to children for the prevention of chicken pox. In the original trials for the vaccine, all subjects were age 60 or older. Subjects received either active vaccine or placebo. There was a 51 percent reduction overall in the incidence of shingles among those in their 60's.
These findings would seem to support vaccination in younger elderly patients. For one, the risk of developing shingles increases with age. Furthermore, the vaccine seems to be potentially more effective in younger patients. Overall, there was a 2/3 reduction in the incidence of post-herpetic neuralgia among those subjects who received the vaccination but nonetheless developed shingles.
A subsequent study enrolled patients in their 50s and determined that the efficacy rate of the vaccine was about 70 percent. The vaccine (Zostavax, Merck and Co.) received FDA approval for use in individuals 50 or older.

When To Vaccinate
The average age of patients presenting in Dr. Trying's office with shingles is 51. This suggests that patients who receive the vaccination upon turning 50 may significantly reduce their risk for developing shingles. Increased age is a known risk factor for developing shingles. Although stress has frequently been identified as a risk factor, it appears that only significant, acute stress, such as the loss of a loved one, may be associated with shingles outbreak. Most recently, family history of shingles has emerged as a significant risk factor for developing shingles. Having a first-degree relative with shingles may double an individual's risk for developing shingles.
Vaccination is not recommended for an individual who has recently has shingles. However, individuals who had shingles some time in the past (approximately a decade or so), vaccination may prevent re-emergence of shingles.
Finally, patient recollection of a personal history of chicken pox is rarely reliable. Many individuals simply do not recall having chicken pox as children. Furthermore, many sero-positive patients say that their parents never acknowledged that the patient had chicken pox. Importantly, patients do not require an antibody test prior to receiving the VZV vaccine. Cost of the vaccine, which may not be covered by third-party payors, can remain a limiting factor.

UV Protection from the Patient's Perspective

From: Practical Dermatology March 2013

In a recent survey of American consumers, 86 percent of respondents said they know that sunscreen helps prevent skin cancer when used with other protection measures, yet the majority do not use sunscreen on a regular basis. Reasons consumers gave for not using sunscreen include not thinking about doing it (40 percent), believing that they do not stay out long enough in the sun to burn (44 percent), and having an aversion to sunscreen texture (51 percent).

Memorial Sloan Kettering's Steven Q. Wang, MD, Director of Dermatologic Surgery and Dermatology at Basking Ridge Dermatology, addressed consumer behaviors and strategies to increase UV avoidance. He, along with Stephen Dusza, PhD, conducted the study described above and has written extensively on sunscreen formulations and science. Ahead, he answers questions about UV avoidance and sunscreen formulation and use.

Q. You found that 86 percent of Americans understand the importance of sun protection, yet most don't use sunscreens or use them properly. Why do you think this is and how can this change?
"The public understands the need to use sunscreens and to limit UV exposure, but there is a gap," observes Dr.Wand. "The gap is in how they translate knowledge into motivation and motivation into behavior." He likens adoption of UV avoidance behavior to weight loss or smoking cessation. "People understand this is important, but they just cannot change their behaviors."
There are ways to support patients and facilitate change. "I encourage dermatologists to emphasize comprehensive photoprotective strategies," Dr. Wang says. He argues that the current emphasis on sunscreens, "puts the hierarchy of sun protection strategies in reverse." Over-dependence on sunscreens gives patients a false sense of security.
It is more important, he says, for patients to understand when and how they are exposed to UV radiation and how they can limit exposure through sun avoidance and physical protection strategies: staying out of the sun as much as possible, especially during midday hours, wearing protective hats and clothing, etc. When patients adopt these crucial strategies, then sunscreen becomes a secondary mode of defense to protect minimal exposure rather a first line of defense.
When patients adopt adequate UV avoidance strategies, then use of a daily sunscreen SPF 30 is probably sufficient for day-to-day use. Remind patients that windows block out UVB, Dr. Wang suggests.
Dermatologists should also, "Focus on the need for adequate application of sunscreens," Dr. Wang says. "Most people use about one-third the desired amount of sunscreen, which translates to about one-half or one-third the stated level of protection."

Q. Your research and other surveys have found that patients are concerned about the safety of sunscreen ingredients and the cosmetic elegance of formulations. What should dermatologists know about these topics?
"There have been some overblown concerns regarding sunscreen ingredients," Dr. Wang acknowledges. "Many people voice concern about oxybenzone," he says, noting that the degree of exposure needed to realize theoretical oxybenzone affects on human hormone levels are far above those achieved with normal sunscreen use. In fact, he says, it would take more than 270 years of consistent application to achieve problematic levels.
Additionally, fear of nanotechnology is also "not valid" according to Dr. Wang. Micronized or nanosized TiO and ZnO are important for cosmetic elegance of sunscreen formulations; compared to older, larger particle size formulations that tended to leave white residues on the skin. "Studies to date suggest that micronized and nanosized UV filters do not penetrate beyond the stratum corneum," he explains, meaning little to no risk of systemic exposure. Even if nanosized particles are deposited within the stratum corneum, constant shedding of the SC does not permit accumulation of material.
Furthermore, there are concerns that nanoparticle filters, upon exposure to UV, can generate damaging free radicals in the skin. Free radicals are associated with photoaging, immunosuppression, and photocarcinogenesis. It is shown that excess UVA irradiation and exposure to pollutants are themselves drivers of ROS-generation in human skin.
While in vitro studies using cell culture models did suggest a high level of ROS generation when non-organic nanosized filters were exposed to UV irradiation, subsequent in vitro studies have not borne out these findings. However, Dr. Wang says, most nanosized filters are coated to reduce reactivity and thus limit free-radical formation. Furthermore, the skin's natural antioxidant capacity can readily neutralize any ROS generated through enzymes and nonenzymatic molecules.
As an additional measure of protection, many sunscreen formulations now incorporate topical antioxidants, which may have the potential to diminish the ROS generated from exposure to UVA radiation. This antioxidant capacity may be especially important, given that most sunscreens tend to provide greater protection against UVB than UVA. Dr. Wang and colleagues recently have published on the use and benefits of topical antioxidants within sunscreen formulations, but he cautions that much depends on the quality of the finished product. Failure to provide sufficient concentrations of antioxidants or stable formulations will negate the benefit of the antioxidants.

Q. What are your recommendations for effectively educating patients about UV avoidance? How can this be achieved quickly in the average clinic visit?
"What I find helpful and what I encourage dermatologists to do is to give specific recommendations," Dr. Wang says. "Most people only want to hear what sunscreen and what SPF they should be using."
Dr. Wang also strongly encourages dermatology practices to develop a handout that lays out a specific, appropriate, comprehensive UV avoidance strategy "It is very important to have a sheet of instructions ready."
Specific product recommendations can be made on  this handout. Of course, Dr. Wang says, give a few options across various price points, and encourage patients to seek out a product they like.
"Overall, I think US sunscreen manufactures have done a good job creating products for the American consumer," Dr. Wang says. But patients still have preferences. Common consumer complaints about sunscreen tend to focus on texture, which may be perceived as greasy to some. Formulations intended to be water resistant may have a sticky feel.

Q. What are remaining questions in the area of sunscreens?
The FDA is still trying to determine whether formulations should indicate a level of UVA protection and how to best accomplish this. There also remain questions about certain dosage forms, such as sprays. Under the current FDA proposed ruling, Dr. Wang notes,"wipes, powders, and washes cannot claim SPFs because they were deemed to not provide sufficient protection."
Sprays are popular due to their convenience, ease of application at certain anatomic sites, and the ease of use in children, who may not like creams or lotions. The challenge is in achieving adequate and consistent coverage, Dr. Wang says. Even if a spray is applied imperfectly, "it's better than nothing," he says.
There are methods to optimize use of sprays. One is to spray the product into the hand and then apply to the desired area, though this somewhat defeats the purpose of the spray, Dr. Wang admits. Alternatively, consumers should move the can slowly over the target area to ensure a good amount of coverage. The product should still be rubbed in by hand once on the skin.