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.
DIAGNOSING HAIR LOSS
During his lecture, Dr. Shapiro reviewed treatment algorithms he uses for the variety of hair loss conditions he sees in his clinic. Following is a brief overview of some of conditions he sees and tips and pearls for making a diagnosis.
By definition, cicatricial alopecias are, “A group of disorders characterized by a final common pathway of replacement of follicular structure by fibrous tissue,” Dr. Shapiro says. Within the family are primary cicatricial alopecias that exhibit, “preferential destruction of follicular epithelium and sparing of the interfollicular dermis.”
Clinically, there is loss of follicular ostia, and histopathology demonstrates obliteration of the hair follicle. The primary cicatricial alopecias may then be further divided into lymphocytic, neutrophilic, and mixed. Because there are no data on treatment from randomized clinical trials, treatment is frequently guided based on the infiltrate, which is determined by biopsy. Another way to direct therapy, Dr. Shapiro said, is based on disease activity, which is assessed using four criteria: level of hyperkeratosis, level of erythema, pull test positivity, and presence of symptoms (i.e., burn, itch, and pain).
Lupus. Discoid lupus erythematosus (DLE) has a distinct appearance that is familiar to many dermatologists, although in its early stages, it can mimic psoriasis: scaly, but with pigmentary changes and atrophy. Dr. Shapiro always looks around the ears, because, “frequently if it’s on the scalp, it’s on the ears as well.” While the diagnosis is frequently made upon clinical evaluation, Dr. Shapiro said he also uses the Folliscope at 70X magnification to look for certain hallmark characteristics: large yellow dots, keratotic plugs, and a “strawberry ice cream color” that is suggestive of fibrosis.
“Sometimes you can save hairs,” Dr. Shapiro said, but “these are trichologic emergencies, because every hair the patient loses to lupus will be lost forever, so you really want to get on top of them.”
Lichen Planopilaris. Lichen planopilaris (LP) is characterized by perifollicular scaling with scales that migrate along the shaft forming tubular scales, as well as fibrotic white dots on trichoscopy. It has many similar features to pseudopelade (Brocq), and in fact, Dr. Shapiro says he considers pseudopelade (Brocq) a form of LP. In cases of suspected LP, dermoscopy or trichoscopy enhances the ability to characterize clinical features, including erythema and hyperkeratosis.
For patients with extent of disease < 10 percent, Dr. Shapiro starts the treatment plan with an ultra potent topical steroid and may consider also treating with intralesional tramcinalone acetonide (IL-TAC). If the patient improves, he recommends continuing the treatment as needed. If no improvement is seen, next steps include treating with hydroxychloroquine ± isotretinoin, and ± tacrolimus 0.3% BID plus coricosteroid BID plus 5% minoxidil solution BID (TCM). For patietns with extent of disease ≥ 10 percent, treatment considerations include with hydroxychloroquine 200mg BID ± ultra potent topical steroid ± IL-TAC monthly ± prednisone (bridge). If the condition improves, Dr. Shapiro recommends tapering treatment to lowest effective dose. If no imporvent is seen, additional options include isotretinoin and TCM. Beyond his treamtent algorithm described above, Dr. Shapiro said other options may include pioglitazone, naltrexone, and excimer laser.
Frontal Fibrosing Alopecia. In reviewing the distribution of hair loss in his practice, Dr. Shapiro found that about 23 percent are due to frontal fibrosing alopecia (FFA)—and the prevalence appears to be rising. While FFA typically affects the frontotemporal region of the scalp, upper periocular and occipital localization are not uncommon. It is most typically diagnosed in postmenopausal women, with onset between 55 and 65 years of age. A potential association with sunscreen and facial moisturizes and FFA has been suggested by some authors, specifically with formulations containing oxybenzone or avobenzone. However, other studies have not found any association. In addition to environmental causes, genome analysis studies have identified at least three genetic variants that are linked to FFA. Clinically, the eyebrows are frequently involved and facial papules indicate vellus hair involvement.
“Sometimes eyebrow involvement is the first sign and patients are misdiagnosed as alopecia areata, so always keep in the back of your mind that if there is eyebrow involvement, there may be some FFA,” Dr. Shapiro says.
Other parts of the evaluation are directed to documenting the extent and patterns of hair loss, particularly during the baseline evaluation, and for monitoring change over time.
“Frontal recession can be measured, and it is important that you measure it every time [patients] come in so you know how seriously its developing over time,” Dr. Shapiro says. “It’s important that you photograph everything on these patients, so we can monitor. We measure the glabella to hairline, the right canthus to the hairline, left canthus to hairline, as well as the sideburn area.”
Neutrophilic Primary Cicatricial Alopecias
Folliculitis Decalavans is a neutrophilic primary cicatricial alopecia, “where we see a lot of hairs coming out of one follicle. It can be very painful, very itchy. We see a lot of polytrichia, or tufting,” Dr. Shapiro says.
Dissecting cellulitis is a rare, chronic inflammatory disorder that is characterized by follicular occlusion. It often occurs in association with other follicular occlusive disorders, including acne conglobata, hidradenitis suppurativa, and pilonidal cysts.
“Dissecting cellulitis can be a very painful condition, with huge cystic, boggy lesions,” Dr. Shapiro says.
Due largely to it’s rarity, there are currently no guidelines to support treatment in clinical practice. Correspindingly, there is limited data on the effectiveness of treatment.
In women, androgenetic alopecia (AGA) is sometimes referred to as female pattern hair loss, and it is classically divided into three stages on the basis of scalp involvement. Additional laboratory studies may be needed to confirm the diagnosis, including levels of TSH, ferritin, vitamin D, and zinc. Workup for androgens may be indicated in women reporting irregular periods, in which case testing for free and total testosterone, DHEA-S, and 17-OH-progresterone may be helpful.
Use of birth control measures should be carefully monitored in women of childbearing age and a diagnosis of AGA. With several different types available on the market, there are several potential options, although Dr. Shapiro said that norgesterol and norethindrone should be avoided, as they contain higher levels of androgen. Importantly, every time there is a change in agent, patients will experience telogen effluvium—and the same holds true for intrauterine devices (IUD) that contain hormones, especially levonogesterol. Fortunately, there are several effective options for treatment, which is typically guided by the extent of scalp involvement.
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.