Current Treatment of Alopecia Areata

Abstract

The number of alopecia areata clinical trials with Janus kinase (JAK) inhibitors of cytoplasmic tyrosine kinases including JAK1, JAK2, JAK 3 and tyrosine-protein kinase (TYK2) has increased significantly since the last Research Summit. This means that the conversation about current treatments for alopecia areata now also needs to include a discussion of traditionally used off- label therapies as well as evolving therapies as with JAK inhibitors.

INTRODUCTION

The first step in selecting a treatment for a patient with alopecia areata is to ascertain what bothers the patient or the patient’s parents. Is it scalp hair loss or is it eyebrow, eyelash, or beard hair loss? For some patients who have adapted to scalp hair loss, the primary reason for requesting a treatment may be that the hair loss he or she is experiencing in a non-scalp area is what is most bothersome. For other patients, it may be the nail involvement and dealing with fragile, brittle nails or when seeing hair falling out and present everywhere, developing anxiety or depression. Dealing with the unpredictability of alopecia areata, whether it be recurrent episodes, lack of responsiveness to prescribed treatments or ongoing hair loss despite a commitment to a treatment plan, is challenging. This unpredictability needs to be discussed in the context of the pathophysiology of alopecia areata when developing treatment plans.

MEDICAL AND SOCIAL HISTORY

Before prescribing a treatment plan to a patient with alopecia areata, a thorough medical history, including medication and supplement use, as well as current and past treatments of his/her alopecia areata, need to be recorded. Scalp and hair care habits including use of cosmetic camouflage techniques, and scalp or eyebrow prostheses, should be noted as many patients with extensive scalp hair loss discontinue shampooing their scalp and only use “bar soap” or nothing. This may result in compromised scalp health and a scalp folliculitis which could impact the success of prescribed topical or oral therapies. Supplement use is common and when patients develop hair loss, it is not uncommon for patients to take even more supplements, and in particular biotin, despite its use not having been shown to be beneficial for normal, healthy hair or in individuals with no biotin deficiency (Lipner, 2018; Walth et al., 2018).

Discussing how alopecia areata affects the patient in their social/home environment is also an integral part of the treatment of this disease. In a recent survey by the National Alopecia Areata Foundation of 641 subjects, just over 50% reported that having alopecia areata impacted their physical activities and 20% felt that having alopecia areata impacted their relationships and social activities.

CLINICAL EXAMINATION

The examination should include an assessment of all hair bearing areas as well as both finger and toenails. Scalp vellus, indeterminate and terminal fibers and the presence or absence of scale, erythema, folliculitis or atrophy should be noted. Photography can be used to document disease extent and the Severity of Alopecia Tool or SALT score can be used as a tool to objectively measure scalp hair loss and treatment outcomes. (Olsen et al., 2018). Disease activity at the time of the clinical examination can be ascertained by the presence or absence of positive hair pull tests. Both finger and toenails should be examined and abnormalities such as pitting, dystrophy, onycholysis noted.

After the medical history, medication and supplement use, disease extent and activity have been ascertained, the conversation can turn to a discussion about autoimmune diseases with a focus on alopecia areata. It is important for patients and family members to understand alopecia areata is an autoimmune disease and that this disease can spontaneously resolve, persist, reoccur or progress, even in some situations while on therapy. There are currently no clinically significant biomarkers to predict when AA may flare but finding biomarkers is a subject of current research (Jabbari et al., 2016). Before proceeding to specific treatment recommendations, this is a good point in the visit to review the basics of what we know about alopecia areata (Table 1) and to introduce the patient and his/her family to the National Alopecia Areata Foundation.

Table 1.

Basic Facts about Alopecia Areata to Share with Patients

• Affects 1.7–2.1% of the population.

• 50–80% of cases are sporadic.

• Both males and females of all ages and races can be affected.

• Alopecia areata is immune mediated and is characterized by an attack on the anagen phase of the hair cycle.

• Disease associations may vary around the world and include vitiligo, thyroid disease, atopy (allergic rhinitis, asthma, atopic dermatitis).

• Current genetic research suggests the same genes involved in alopecia areata also play a role in rheumatoid arthritis, type 1 diabetes, celiac disease.

• Alopecia areata is a multifactorial condition with a concordance rate of 42–55% for monozygotic twins and 0–10% for dyzogotic or fraternal twins.

LABORATORY TESTING

Laboratory testing is not mandatory but may be helpful based on the results of the history and physical examination. If the patient is prescribed a systemic medication, then safety monitoring laboratory studies may be indicated. To insure the absence of other easily treated medical conditions commonly associated with hair loss, thyroid function studies, hematologic and iron profiles as well as Vitamin D levels are commonly checked.

CHOOSING A TREATMENT FOR ALOPECIA AREATA

There are several non -Food and Drug Administration (FDA) approved treatments used to treat alopecia areata. Treatment recommendations should take into account the patient’s age, location of the hair loss, disease extent and activity, presence of other medical or psychological problems, and in some cases, the results of a scalp biopsy. (Hordinsky, 2013). As many new therapies are currently being evaluated, alopecia areata patients should be updated about not only traditionally used therapies but also about ongoing clinical trials and the off label use of Janus kinase inhibitors and in particular, oral tofacitinib.

Since the last Alopecia Areata Summit in 2016, the treatment of stable patchy alopecia areata continues to commonly include the use of topical or intralesional corticosteroids, 2% or 5% topical minoxidil when there is fine vellus or indeterminate hair growth present, anthralin, topical immunotherapy or combinations such as a topical steroid with topical minoxidil. Local injections of intralesional triamcinolone acetonide ranging in concentrations from 3 to 10 mg/cc is still a preferred treatment for scalp and eyebrow alopecia areata. Topical immunotherapy with diphenylcyclopropenone (DPCP) or squaric acid dibutylester (SADBE) also continues to be another accepted therapy for AA.

In addition to the treatments already mentioned, oral immunosuppressive agents such as prednisone, methotrexate, cyclosporine or intravenous solumedrol or immunoglobulin are sometimes prescribed for patients with alopecia totalis or alopecia universalis. For those patients with active hair shedding, oral prednisone may be prescribed to try to turn off disease activity.

For those experiencing eyelash loss, there are again no established treatments. Topical prostaglandin analogues have been studied but this approach has not been popularized and the presence of some hair growth is probably needed to have a successful clinical outcome (Roseborough, et al., 2009).

Selection of the best treatment for the alopecia areata patient can be challenging. A review of randomized controlled trials in alopecia areata was published in 2014. (Hordinsky and Donati, 2014). A review of 29 trials using the American College of Physicians Guideline grading system, found that the studies were of moderate quality overall and that a number of treatments were effective, particularly the use of topical and oral corticosteroids and the sensitizing agents. The majority of these studies involved adult patients. Treatment studies of pediatric alopecia areata are limited, but of the studies available for review, the use of potent topical steroids such as clobetasol propionate cream 0.05% has been found to be more effective than a lower potency topical steroid such as 1% hydrocortisone (Lenane et al., 2014). The use of immunotherapy in children particularly in those with chronic and extensive alopecia areata is supported as is the use of pulsed high dose systemic corticosteroids particularly in the setting of acute hair loss.

Since the last Summit in 2016 where the use of JAK inhibitors was introduced and study results on adult patients were presented from Columbia University, Cleveland Clinic, Stanford and Yale Universities, there has been a surge in off label use of oral tofacitinib, currently approved in the United States for the treatment of rheumatoid arthritis. There has also been an increase in the use of compounded formulations of topical tofacitinib and ruxolitinib, as well as opportunities for alopecia areata patients to participate in several industry sponsored clinical trials assessing the efficacy of both topical and oral JAK inhibitors for the treatment of alopecia areata Overall treatment response rates reported at the 2016 Summit with oral tofacitinib or ruxolitinib ranged from 54% to 75% (Liu et al., 2017; Craiglow et al., 2017; Craiglow, et al.; 2016; Mackay-Wiggan, et al., 2016). The treatment response in 13 adolescents treated at Yale University was noted to be 75%. This group also reported no positive results with a compounded topical tofacitinib inhibitor.

With this surge in the use of JAK inhibitors to treat alopecia areata, part of the treatment visit needs to include a discussion of JAK inhibitors. As alopecia areata patients learn more about JAK inhibitors, they in turn ask their physicians and advanced health care providers about this new potential approach. Providers concurrently need to learn about JAK inhibitors and be able to share this information with their patients. Physicians and mid-level providers need to know that the JAK family includes JAK1, JAK2, JAK 3 and tyrosine-protein kinase (TYK2) and that this is a group of cytoplasmic tyrosine kinases which mediates signal transduction via interactions with Type 1 and Type 2 cytokine receptors that are critical for leukocyte activation, proliferation, survival and function.

Finally, there can be a discussion about cosmetic camouflage with wigs or “scalp prostheses.”. Patients can also be referred to Locks of Love, a non-profit organization that provides hair prostheses for children younger than age 18.

SUMMARY

Physicians and mid-level providers generally prefer topical or intralesional steroid therapy for the treatment of alopecia areata. However, following the recently published studies in which the systemic JAK inhibitors (e.g., tofacitinib or ruxolitinib) were shown to reverse the alopecia areata process, there is currently a surge of clinical trials and interest in treating alopecia areata patients with JAK inhibitors. Concurrently, more attention is being focused on the psychological needs of patients with alopecia areata. In the meantime, other therapeutic approaches are also being examined. Some of these treatments include the use of low dose interleukin-2 and simvastatin/ezetimibe (Castela et al., 2014; Lattoug, et al., 2015), administration of platelet rich plasma (Trink et al., 2013), use of oral antihistamines and the addition of photobiomodulation. With all the ongoing clinical research activities in alopecia areata, the future is looking up for both children, adolescents and adults who have this common autoimmune disease that currently has no FDA approved therapy.

Abbreviations:

AA

alopecia areata

DNCB

dinitrochlorobenzene

DPCP

diphenylcyclopropenone

FDA

Food and Drug Administration

JAK

Janus kinase

SADBE

squaric acid dibutylester

DATA AVAILABILITY

N/A