Recent Advances in Hair Restoration

Trichoscopy, coupled with a thorough evaluation of the scalp, forms the basis for diagnosing the cause of hair loss, and it may have utility for directing the type and site of biopsy, as well as for informing the ideal treatment approach, says Jerry Shapiro, MD, who presented at the recent Maui Derm for Dermatologists meeting.

Dr. Shapiro delivered the Stuart Maddin Memorial Lecture at the meeting, during which he reviewed recent advances in evaluating hair loss etiology, new understandings in the mechanism of action of platelet rich plasma (PRP), and the potential for using Janus kinase (JAK) inhibitors in treatment of alopecia areata.

Recent Advances in Trichoscopy

Conditions that are associated with hair loss have historically been diagnosed and classified according to severity based on subjective clinical evaluation. Over the past two decades, the expanded use of trichoscopy, which is based on principles of dermoscopy, has facilitated the development of more objective standards for diagnosis, classification, and response to treatment of hair disorders. Moreover, it is noninvasive and does not require plucking or biopsy. Some companies that offer devices in the fast-growing market even offer the option of sending exam results for an independent assessment with results provided in the form of a detailed report.

While trichoscopy is a relatively recent advance in diagnosing and measuring hair loss conditions—the term was first introduced at the First World Congress of the International Dermoscopy Society in 2006—Dr. Shapiro believes it is becoming an indispensable tool for use in clinical practice and research.

“We need to know hair density and we need to know hair calibers every time the patient comes in,” says Dr. Shapiro.

Dr. Shapiro uses the Folliscope (Lead M) for consultations in his clinic, which has magnification ranging from 50X to 100X; the FotoFinder device (FotoFinder Systems, Inc) has a similar functionality. Different magnifications are used for different purposes. The 50X magnification is useful, for example, for general quantification of hair density and count, as well as for determining whether hairs are terminal or vellus. The 100X magnification allows a much more detailed look at individual follicles, useful for determining width of follicles and change over time and in response to treatment.

As an example of how he uses Folliscope in practice, Dr. Shapiro says that hair quantity and quality are assessed during each visit in every patient with androgenetic alopecia (AGA): in usual distribution, measurements are taken from 12cm from glabella to hair line to assess density and caliber; in temporal thinning, 10cm from outer canthi; and in vertex thinning, 24cm from the glabella. Of note, it is not necessary to tattoo the patient’s scalp and measure precisely the same area during each visit. Returning to approximately the same area is usually sufficient, he says.

Dr. Shapiro recently gained access to a new trichoscopy device powered by artificial intelligence platform called HairMetrix (Canfield Scientific). In his experience with the platform, he says, imaging takes less than a minute and produces a number of graphs and reports useful for quantification and qualification of hair loss patterns.

Update on PRP

PRP is a much-discussed treatment for hair loss, although there are conflicting reports regarding its efficacy and variability in clinical approach. Theoretically, upon injection, the platelet opens up to release a number of growth factors that bind to receptors on hair follicle bulge stem cells to stimulate hair growth. Of note, while PRP has approval for use in joint repair surgery, its use for facial rejuvenation or hair loss is off-label.

In a study soon to be published, Dr. Shapiro and his group assessed changes in serum levels of growth factors following application of PRP in 10 patients. In the study, both glial cell derived neurotrophic growth factor (GDNF) and vascular endothelial growth factor (VEGF) were found to significantly increase among patients who responded to PRP. The exact mechanism by which GDNF contributes to hair growth is not fully known, but studies suggest that it promotes hair follicle cell proliferation and slows hair follicle catagen regression. VEGF, as its name implies, stimulates angiogenesis, thus supporting growth of new follicles by facilitating a supply of nutrients. However, high concentrations of VEGF may be toxic, indicating there might be an optimal concentration for promoting hair growth.

Nevertheless, PRP can be an effective adjunctive modality for AGA and other hair loss conditions in select patients. Dr. Shapiro’s protocol for using PRP is to provide 50 injections; local anesthesia may be used to numb the scalp, although an ice pack applied to the treatment area beforehand is usually sufficient. The treatment is repeated twice before assessment. If there are fewer than 10 newly grown hairs per cm², treatment is discontinued. However, more than 10 newly grown hairs/cm² suggests a treatment response, and PRP is repeated for another four treatments, following by injections every three to six months for life.

Dr. Shapiro said the rationale for this protocol derives from a study he conducted in 24 patients treated with PRP. Among 17 responders, mean follicle count was 163 hairs/cm² at baseline and 198 hairs/cm² after two treatments, whereas among nonresponders, mean follicle count was 135 hairs/cm² at baseline and 133 hairs/cm² after two treatments. The study found that response after two treatments was indicative of long-term benefit, with an average increase of 35 hairs/cm² after about two to four months in responders. Generally, patients with earlier onset hair loss and those with lower density at the start of treatment did not respond as robustly or at all.

Other studies that Dr. Shapiro has participated in have shown conflicting results, although study design may explain some of the discrepancies. For instance, in a split-head study in which PRP was injected in half the scalp and saline solution (as placebo) was injected in the other half, there was statistically significant growth of hair in both PRP and placebo treated areas, compared to baseline, and the intergroup difference between the two was not statistically significant. It may be the case that diffusion of PRP to the nontreated side confounded the results, Dr. Shapiro says.

Future studies, he says, should randomize patients to whole-scalp treatment with either PRP or placebo. Additionally, Dr. Shapiro says, such studies would benefit from a standardized PRP preparation method and administration protocol, as well as objective criteria for documentation and evaluation.

“We need a better understanding, we need more randomized controlled studies, and we need more long-term follow-up,” Dr. Shapiro says. “We don’t even know how often PRP has to be done.”

JAK Inhibitors in Alopecia Areata

Alopecia areata is the second leading cause of hair loss in men and women, affecting as many as 6.8 million people in the United States, but to date, there are no approved therapies for the condition. Immunosuppressive treatments, specifically topical corticosteroids, often for the basis for treatment. More recently, interest has grown around the use of JAK inhibitors, either in oral form or in topical applications.

Several promising case studies and early-stage clinical trials, mostly conducted in patients with severe manifestations, have demonstrated benefit. According to Dr. Shapiro, oral JAK inhibitors, including tofacitinib, baricitinib, and ruxolitinib, have been shown to be efficacious, although long-term benefit is questionable, with most patients experiencing hair loss after discontinuation. Topical JAK inhibitors have also been shown to be effective, he said, but have not been fully evaluated.

However, Dr. Shapiro adds that the high cost associated with JAK inhibitors, as well as safety concerns, are potential limiting factors in their development for alopecia areata. In clinical trials in other disease states, JAK inhibitors have been associated with a range of common and rare side effects, and some on-market JAK inhibitors carry safety warnings due to the theoretical risk of blood clot development. Beyond the tolerability profile, the annual cost of JAK therapy might be prohibitive for many patients.

Still, there may be reason for guarded optimism with respect to JAK inhibitors for treatment of alopecia areata. For one, the suggested efficacy of JAK inhibitors appears to be far more robust than currently used therapies. In one recently completed open-label study, about a third of patients taking 5mg tofacitinib twice daily experienced a 50 percent reduction in scores on the Severity of Alopecia Tool. Secondly, ongoing drug development efforts offer promise to answer questions about the risk-benefit profile. Eli Lilly (baricitinib), Pfizer (PF-06651600), and Concert Pharmaceuticals (CTP-543) have all announced Phase 3 trials of JAK inhibitors for alopecia areata.