A new spin

By Victoria Houghton, assistant managing editor

Professional football players, world-renowned golfers, hall-of-fame baseball players…and your 10:00 alopecia patient? For more than a decade, some athletes have been treated with platelet rich plasma (PRP) in hopes of a swift recovery from injury. “The first reports of its use in orthopedic surgery were in 2005,” said Shilpi Khetarpal, MD, from the department of dermatology at the Cleveland Clinic. “They were finding after surgeries that people were healing faster with PRP injections. I think it got a lot of press when athletes started getting PRP injections after sports injuries.” Recently, however, the use of PRP treatments has been bleeding from the orthopedic realm into the dermatologic space. “Everyone kept saying, ‘if we’re delivering all of these growth factors, surely we can use those benefits not only for hair growth but for the skin.’”

Where does PRP stand in dermatology? Dermatology World examines what’s known, and unknown, about using PRP to treat various dermatologic conditions.

PRP and dermatology

The theory behind using PRP for dermatologic procedures is not unlike that for orthopedic procedures, says Joshua Zeichner, MD, assistant professor of dermatology at Mount Sinai. “The plasma contains white blood cells and platelets, and platelets contain high levels of growth factors. Growth factors are messengers that tell our skin cells and our hair cells to function optimally. It’s a signal to rev up their activity.” To obtain PRP, the patient’s blood is spun down using a centrifuge so the platelets can be collected and used in high concentration either topically or via injection. In dermatology, it is most commonly being tested for alopecia, facial rejuvenation, and/or for its healing properties.

“I think that the use of PRP is the hottest topic right now in treatment of hair thinning,” said Dr. Zeichner. “When it comes to the hair, the idea is that it can make lazy hair cells behave more like young healthy hair cells to produce not only more hair, but perhaps thicker hair.” Dr. Khetarpal is currently running a program at the Cleveland Clinic testing the use of PRP for multiple types of alopecia. “Originally, when we were thinking of bringing PRP on board, our goal was to treat androgenetic alopecia. There was a lack of effective therapies for male and female pattern hair loss.” After several months of treating non-scarring types of alopecia with PRP, patients were experiencing 20 to 40% regrowth of the hair, so Dr. Khetarpal is also testing PRP with other types of alopecia. “We thought if it’s working for pattern hair loss, why don’t we try it with other types of hair loss like alopecia areata and some of our burnt out scarring alopecias — people who are no longer actively inflamed?”

In addition to its use as a treatment for alopecia, Matthew Kelleher, MD, from Premier Dermatology in the southwest suburbs of Chicago, uses PRP for facial rejuvenation, also known as the ‘vampire facial.’ Despite its colloquial nickname, Dr. Kelleher maintains that the theory behind PRP for facial rejuvenation is quite complex. “The growth factors in PRP lead to skin rejuvenation and healthier and younger skin by various mechanisms: increased extracellular matrix accumulation; improved cell proliferation, cellular differentiation and migration; increased collagen synthesis and diameter; and increased hyaluronic acid synthesis, producing better tissue turgor and skin elasticity.”

Dr. Khetarpal uses PRP for facial rejuvenation as well, but also after ablative laser procedures. “The principle of microneedling or ablative lasers is that you’re creating a tiny channel in the skin to allow the delivery of these growth factors from the PRP to the deeper portions of the skin that you would have to inject.” Dr. Khetarpal’s findings are twofold. “The healing time is reduced significantly — by around half. We attribute that to all of the growth factors that are speeding up the normal wound-healing process.” Dr. Khetarpal is also finding that patient satisfaction after the treatment is increased. “If you compare satisfaction after the treatment by itself and then that treatment with the PRP, the results are enhanced for whatever procedure patients were getting after the PRP.”

Joel L. Cohen, MD, from AboutSkin Dermatology and DermSurgery in metropolitan Denver, primarily uses PRP in interested patients to try to speed up the healing process on the face after full-field erbium resurfacing patients as well as some heavier fractional ablative laser treatments. “For full-field erbium, the healing time for many of these patients to re-epithelialize is about 10 to 12 days. For fractional CO₂ and fractional erbium, typically the healing time would be about six or seven days. In both camps, people tend to be red or at least pink for a period of time, but that time interval is much longer with full-field erbium than fractional treatments.” According to Dr. Cohen, he became interested in PRP after reviewing the literature on using PRP as an adjunct to ablative laser resurfacing. “At this point, there are a few studies, like one by Hui from China (Rejuvenation Res. 2017; 20(1):25-31), that appear to show about a 15%+ reduction in the total duration of erythema, edema and crusting by incorporating PRP with ablative laser resurfacing — and this study showed a synergistic overall result with PRP in terms of wrinkles, texture and tightness as well,” Dr. Cohen said. In a 2017 split-face study on acne scars by Kar, ablative fractional CO₂ plus topical PRP showed less redness, edema, and pain than fractional CO₂ alone (J Cutan Aesthet Surg. 2017 Jul-Sep;10(3):136-144), he noted. Dr. Cohen pointed out that these studies are few in number and small at this point, but they are showing up in core dermatology journals – such as one in Dermatologic Surgery of 30 acne scar patients treated with fractional ablative resurfacing that indicated “both topical and intradermal PRP after fractional ablative resurfacing led to shorter downtime than the control group of laser alone without PRP, and further topical PRP showed the additional benefit of lower pain scores” (Dermatol Surg. 2014 Feb;40(2):152-61).

Treatment regimens

At Cleveland Clinic, Dr. Khetarpal is in the midst of a large-scale study of the duration and frequency of treatment for both scarring and non-scarring alopecia patients. After spinning down 20 ml of the patient’s blood for 10 minutes, patients are injected with PRP on a monthly basis for the first three months. Each session includes 10 to 20 injections depending on the size of the area being treated. Then after those three months, patients will have a session every three months for the first year. “What we’re finding is that during those three monthly sessions we’re delivering a high amount of growth factors causing all of the hairs to grow, and then every three months we’re keeping and maintaining what we grow. We have followed patients who finished their one-year therapy for six months now and they’re still holding on to the hair, even though they haven’t been doing treatments in the past six months. We do know that the effects of PRP are not permanent.” Dr. Khetarpal’s group has a professional photographer who takes serial photographs of all of the patients with the same lighting and from the same distance so everything is standardized. “Ultimately we’re looking for regrowth. Our endpoints are twofold. One, when the patients are happy we are essentially happy with the results. The other endpoint is either time — when that year comes to an end — or it would be earlier than that if the patient has results that they’re happy with.”

For facial rejuvenation, Dr. Kelleher uses PRP with five times the concentration of platelets compared to regular blood through intradermal injections and transcutaneous PRP with microneedling. Patients are treated every four weeks until the desired outcome is achieved. “Therapeutic efficiency is measured and tracked three ways,” said Dr. Kelleher. “The patients’ subjective satisfaction; my objective opinion on exam; and serial photographs taken before every treatment.” Similarly, Dr. Khetarpal’s facial rejuvenation patients receive four to six treatments. Her group will spin down 10 ml of blood as less is needed on the face than on the scalp for alopecia. “We do find that those who are doing the treatments monthly do better than those who are treated every other month or every three months just because that collagen remolding is going on constantly and providing consistent growth factors versus a start-stop, start-stop approach to the collagen remodeling.”

Using PRP for healing after ablative laser procedures is a relatively simple process, says Dr. Cohen. “The patient comes in for the procedure, we take some photos, we draw the blood in a tube with the patients name on it, the blood is spun down, and by the time I’m done with the procedure, my nurse walks into the room and she has the test tube labeled with the patient’s name on it. The PRP is drawn-up so that the patient sees what it is.” Dr. Cohen will then slowly drip the PRP from the syringe over the treatments regions, and gently rub this viscous liquid to cover the entire area treated.

LIMITATIONS

While the theories that support PRP use in alopecia, facial rejuvenation, and healing seem logical, why hasn’t PRP taken hold as quickly in dermatology as it did in orthopedics? According to Dr. Khetarpal, the appropriate technology simply hasn’t been available for dermatologic purposes. “About five years ago there were no centrifuge systems that were geared toward dermatologic use toward skin and hair. The orthopedic surgeons tend to use a double-spin system where the blood is spun twice and that tends to give a much higher yield of platelets but it also gives higher inflammatory cells like white blood cells and red blood cells. I think dermatologists weren’t so keen on it because we know for the skin and hair, you want the good stuff but you also don’t want to deliver those inflammatory components.” However, according to Dr. Khetarpal, within the last five years, several companies have developed PRP systems that are more geared toward dermatologic procedures — offering lower platelet concentration with few or no inflammatory cells.

In addition to the technologic delays, the treatment regimens and the efficacy endpoints have yet to be clearly standardized, says Jeffrey Dover, MD, from SkinCare Physicians in Chestnut Hill, Massachusetts. “Just because it makes sense, doesn’t mean it works,” Dr. Dover said. “The problem is that most of the studies that have been done are small, they have not been very well funded, or not particularly well done. In fact, we had a study that was planned for PRP and androgenetic alopecia that was actually stopped by the sponsor when a study came out showing that it didn’t work very well.” Dr. Cohen adds, “I think one of the issues is that it’s very difficult to do a clinical trial on this type of process because it’s obviously not a drug and there’s no single company behind developing it. Often, people end up doing studies on their own.”

For Dr. Zeichner, many questions remain about PRP. “We only have anecdotal reports from key opinion leaders. There are many different types of algorithms. How often do you need treatment? Can you space treatments out longer? For alopecia, if you stop, will the improvement go away? These are questions that we just don’t know the answers to.” Armand Keating, MD, spokesperson for the American Society of Hematology and professor of medicine at the University of Toronto, adds that there are a number of variables that could affect PRP efficacy. “We’re dealing with a host of different cytokines and growth factors, and it would be important to know which are playing a role and what the specific mechanisms are,” Dr. Keating said. “There are many other variables like platelet concentration, and other factors in patient plasma that could play other roles.”

SAFETY AND PATIENT CONSIDERATIONS

In addition to the need for more studies and standardized methodology, are there any safety issues or patient contraindications to consider prior to utilizing PRP? “I think the sense is that it’s safe and unlikely to cause major issues,” said Dr. Keating. “This really goes back to the whole issue of methodology. There don’t appear to be data to indicate that it’s unsafe.”

Yet, Dr. Keating warns that there are some basic safety considerations that physicians should take note of prior to tapping into this modality. “The safety issues are the obvious ones. The first thing is you need to be absolutely sure that it’s sterile, otherwise there could be infections. The second is: all autologous blood products really need to be treated in the same way as blood products are treated in blood transfusion centers.” According to Dr. Keating this means that physicians need to ensure appropriate documentation of samples, particularly for PRP injections. “The reason for that is that there is a risk — even though it might be very low — in practices that do a lot of this. What you wouldn’t want to see is the wrong PRP given to a patient — essentially the possibility of injecting someone else’s cells. If you have white cells and lymphocytes in the PRP from someone else that get into the blood stream, there is a theoretical risk of a transfusion type of acute graft versus host disease which can be very serious or even fatal.”

In addition to sterility concerns, Dr. Khetarpal cautions that PRP will not be appropriate for all patients. “There are certain situations where we want to be careful. If patients have underlying health problems like Hepatitis C and HIV we know that their platelets aren’t going to function the same way.” Additionally, Dr. Khetarpal warns that if the patient has a blood-related cancer, PRP will not be for them. “We obviously don’t want to take those cancer cells and deliver them into the scalp, for example. Also, if there’s any kind of malignancy like skin cancer in the area we’re treating, we obviously want to wait until that’s treated before we deliver growth factors there.” Finally, if the patient is on blood thinners they are not a candidate for PRP, says Dr. Khetarpal. “Blood thinners can actually change the quality of the platelets and make the treatments not as effective. We also ask that they avoid any kind of NSAIDs one week before just so the platelets aren’t altered in any way.”

Finally, the out-of-pocket costs of these treatments are a key consideration as well. According to Dr. Kelleher, the cost depends on a number of factors. “The costs for PRP treatment vary widely depending on: what is being treated, what is the delivery mechanism, scale of treatment, and any other combined therapies. This range would be roughly $250 to $2,500.”

THE FUTURE OF PRP

When it comes to patient demand, Dr. Cohen explained that sometimes PRP is a treatment that patients actually ask for themselves — especially those that have already used it for orthopaedic procedures. “I practice near the Denver-Boulder corridor, where many patients are already interested in natural products — so incorporating PRP from their own blood that seems to be packed with natural growth factors and cytokines is not a huge stretch.” Dr. Zeichner adds, “This is just about as natural as it gets.” Additionally, for alopecia patients, PRP may represent a last-ditch effort to treat what may sometimes feel like an untreatable condition. “On a weekly basis I get asked about PRP from our female androgenetic alopecia patients, because AGA is so devastating for women. Propecia doesn’t work well in women, and the results with Rogaine are so modest,” said Dr. Dover. “As a result, patients may go to these hair clinics which are not run by dermatologists and often are not even staffed by physicians for PRP. I think dermatologists need to do proper studies on PRP so we can put this on the map and control the dialogue. It needs to be done properly by experts who make the right diagnoses.”

Dr. Kelleher agrees and adds, “Given that dermatologists are the only physicians that are experts in hair loss and that 50% of all men suffer from androgenetic alopecia by the age of 50 and 40% of women by the age of 70, we should absolutely be the leaders in PRP for hair restoration. Given the tremendous potential of PRP in scar correction and skin rejuvenation, dermatologists should also be leading the way forward in using this tremendous tool to help our patients.”

While some physicians are fully embracing the use of PRP in dermatology, others remain on the fence. “I would say it’s a technique still in its infancy,” said Dr. Dover. “I believe that there probably is something there and that the basic mechanism of action — the biology of PRP — does make sense, but there are so few well-done studies and the results of studies are so unimpressive that until such time as really well-done studies are conducted to show conclusive evidence that it works in certain conditions, I think the jury is still out.”

Yet, given her research — particularly with regard to alopecia — Dr. Khetarpal is optimistic about the future of PRP. “I think people are skeptical because just like anything in medicine, they want concrete evidence that it actually works. I think with any of these procedures, when something new comes out, it just takes time to do the study and follow the patients out. In our clinical experiences, we’ve had high volumes, a lot of success, and it’s a very safe procedure so I think it’s just a matter of time before we will have a standardized protocol about how we treat these conditions, and know exactly what concentration of platelets, how often to do treatments, and how we can manage patient expectations.”