Alopecia Totalis - Bernstein Medical - Center for Hair Restoration
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Two new studies researching a class of drugs called JAK inhibitors have shown that oral treatment results in significant hair regrowth in patients with alopecia areata, an autoimmune condition that causes non-scarring patches of localized hair loss. Currently there is no cure for alopecia areata, so the possibility of a safe, effective medication is welcome news for thousands of affected patients.

Background

Last year we wrote about how the two new FDA-approved drugs tofacitinib and ruxolitinib act as inhibitors of the family of enzymes called Janus kinase (JAK). ((Harel S, Higgins CA, Cerise JE, Dai Z, Chen JC, Clynes R, Christiano AM. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth. Sci Adv. 2015 Oct; 1(9): e1500973.)) By inhibiting the JAK enzymes, the drugs disrupt intracellular communication to white blood cells, called “T lymphocytes,” and are thus useful in treating alopecia areata. The JAK inhibitors prevented the onset of the disease and reversed the condition, enabling hair to regrow in areas previously devoid of hair.

The 2015 study we referenced – led by renowned alopecia areata researcher Dr. Angela Christiano – showed that topical application of tofacitinib and ruxolitinib in mice resulted in the rapid transition of hair follicles from the telogen (resting) phase of the hair cycle to the anagen (growth) phase. The same study found that tofacitinib encouraged hair follicle development in clumped human dermal papilla (DP) cells, stem cells that are critical in the development of hair follicles. [1]

The Studies

The two new studies were published in September 2016 in the journal JCI Insight, a peer-reviewed journal dedicated to biomedical research.

Tofacitinib

The study of oral tofacitinib – by Crispin, Ko, et al – was a 2-center, open-label, single-arm trial; the first to systematically examine the efficacy of JAK inhibitors as a treatment for alopecia areata. ((Crispin MK, Ko J, Craiglow BG, Li S, Shankar G, Urban JR, Chen JC, Cerise JE, Jabbari A, Winge MG, Marinkovich MP, Christiano AM, Oro AE, King BA. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight. 2016;1(15):e89776. doi:10.1172/jci.insight.89776.)) In addition to studying alopecia areata (AA) patients with greater than 50% scalp hair loss, they tested the drug on patients with alopecia totalis (AT), which is the complete loss of scalp hair; alopecia universalis (AU), the loss of scalp and body hair; and ophiasis pattern alopecia areata, hair loss localized to the temporal and occipital scalp. After three months on 5mg tofacitinib citrate, 32% showed up to 50% improvement, and 32% showed greater than 50% improvement. When broken down by subtype of the condition, those with AA improved by 70% on average, those with ophiasis improved by 68%, AT by 11.8%, and AU by 10.5%. They found that following cessation of the treatment, all patients experienced a recurrence of hair loss after an average of 8.5 weeks. Additional trials are necessary to determine the optimal dosage regimen for providing the most long-lasting response.

Ruxolitinib

The study of ruxolitinib – by Mackay-Wiggan, Jabbari, et al – was an open-label clinical trial of 12 patients with moderate to severe alopecia areata. ((Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise J, Clark C, Ulerio G, Furniss M, Vaughan R, Christiano AM, Clynes R. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight. 2016;1(15):e89790. doi:10.1172/jci.insight.89790.)) The pilot study tested the use of 20mg oral ruxolitinib twice a day for three to six months; this was followed by three months of monitoring the patients without treatment. Despite the small sample size, the results were striking in that 75% of patients showed a strong response to the medication, with hair regrowth over 50%. After treatment, those who responded to the treatment exhibited a 92% reduction in hair loss. Seven of the nine responders achieved greater than 95% hair regrowth. After stopping treatment hair loss resumed; however, it did not reach the level of hair loss that was present before treatment. This proof-of-concept pilot study showed that ruxolitinib is a safe and effective in reversing the balding effects of alopecia areata.

Conclusion

After showing promise in previous research, scientists have now shown that JAK inhibitors have strong potential to cause substantial hair regrowth in people with alopecia areata; a condition that causes hair loss that can be socially awkward at best and cosmetically disfiguring in severe cases. More studies need to go forward in order to determine which of the two drugs – tofacitinib or ruxolitinib – will be the most effective treatment, and what the proper dosage is for long-term treatment. However, we are hopeful that a medication will be developed for broad use in treating alopecia areata patients.

The other major point of interest following the publication of the series of studies is the potential for JAK inhibitors to treat androgenetic alopecia, or common genetic hair loss. One area that is being discussed is the potential for JAK inhibitors, perhaps in the form of a topical treatment, to stimulate the transition of hair follicles from the resting phase to the growth phase of the hair cycle. Christiano’s research is examining the effects of JAK inhibitors on cultured dermal papilla (DP) spheres. If JAK inhibitors can be used to stimulate DP spheres to grow into mature hair follicles, it may enable hair multiplication techniques to become a viable treatment for common baldness.

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According to an article published in the journal of Clinical Aesthetic, ((Rassman WR, Pak JP, Jino K, Estrin NF. Scalp Micro-Pigmentation, A Concealer for Hair and Scalp Deformities. Clinical Aesthetic, March 2015, 8(3): 35-42.)) scalp micropigmentation (SMP) is an effective cosmetic solution for millions of men and women who currently have significant scalp deformities for which there are few, if any, good medical treatment options.

Scalp Micro-Pigmentation is a Permanent Hair Loss and Scar Concealer

SMP is a permanent cosmetic tattoo of carefully selected pigments applied to the scalp in a stippling pattern to mimic closely cropped hair. This technique allows a physician skilled in SMP to effectively conceal a variety of alopecias and scars.

SMP can address the following situations:

  • Female hair loss not responsive to minoxidil or cannot be treated with a hair transplant
  • Hair loss due to chemotherapy
  • Deformities from autoimmune diseases, such as refractory alopecia areata or alopecia totalis
  • Scalp scars from scarring alopecias
  • Scars from neurosurgery or head trauma
  • A visible scar from a strip harvesting procedure or punctate scars from an FUE procedure
  • Visible open donor scars from older harvesting techniques – usually those from the 1950s through the early 1990s
  • A pluggy or corn-row look from older hair restoration procedures

Scalp micro-pigmentation can also create the appearance of fullness on an otherwise thinning or bald scalp with or without a shaved head.

The Scalp Micro-Pigmentation Process

The physician skilled in SMP has a variety of tools at hand, including pigments of different colors and viscosities. The pigments can be introduced into the skin using a number of different needle types and sizes.

The physician begins by taking a needle and inserting a tiny droplet of pigment through the top layer of the skin and into the upper dermis. Because the thickness of the top layer of the skin varies across the scalp, the doctor must judge the appropriate depth at each location by both “feel” and visual cues. For example, a portion of the outer skin layer that has more fat and hair follicles will have a different look and will produce a different feel when inserting a needle compared to a scarred or bald scalp.

To place the correct amount of pigment at the correct depth at a particular location on the scalp, the operator of the tattooing instrument must take into account the following variables:

  • The angle and depth of the needle
  • The time the needle is left in the scalp (in order to place the pigment into the upper dermis)
  • The resistance of the scalp, which varies locally across the scalp
  • The particular color and viscosity of the pigment
  • The size and shape of the particular needle

In order to produce the desired shading and create the desired illusion of texture and fullness, the doctor must vary the density of the stippling across the area of application. Because every patient is unique and every area of the scalp is different, the doctor must proceed carefully in order to achieve the desired aesthetic effect and to minimize the chances of the pigment bleeding into the area surrounding the point of application.

The complete SMP process usually takes two to four sessions.

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Hair restoration physicians William R. Rassman, Jae P. Pak, and Jino Kim have outlined a practical, permanent cosmetic treatment for hair loss, called scalp micro-pigmentation (SMP) in a paper published in the journal Hair Transplant Forum International. ((Pak JP, Rassman WR, and Kim J. Scalp micro pigmentation (SMP): novel application in hair loss. Hair Transplant Forum International, Vol. 21, No. 6, Nov./Dec. 2011, p. 1, 186-87. ))

Scalp micro-pigmentation, first described in the medical literature in 2001, ((Traquina AC. Micro-Pigmentation as an adjuvant in cosmetic surgery of the scalp. Dermatologic Surgery, Vol. 27(2) 2001: 123-8)) is a cosmetic tattoo that creates the appearance of the short hairs of a closely shaved head on an otherwise bald or thinning scalp. SMP (also referred to as ‘cosmetic transdermal hair replication,’ ‘scalp pigmentation,’ ‘cosmetic hair follicle replication,’ or ‘micro hair technique’) is an option for patients who are not candidates for a hair transplant and who are willing to keep their hair cut short or shaved. It is can also serve as a “filler” for those with longer hair.

The paper discussed case studies of six hair loss patients of varying age and hair loss condition who used SMP to camouflage scalp scars or areas of hair loss:

  1. A man in his mid-30s, who was diagnosed with scarring alopecia in his teens, used SMP to camouflage his scarring.
  2. A 30-year-old male, who had worn a hat continually since being diagnosed with alopecia totalis in his teens, used SMP to frame his face and re-build his self-esteem.
  3. A 55-year-old man, who had large-graft (“hair plug”) hair transplants and several scalp reductions, used SMP to fill in plug scars and re-define his hairline.
  4. A 32-year-old man used SMP to cover donor area scars from previous FUT procedures, fill in his thinning crown, and create a smooth hairline.
  5. A 22-year-old man filled in scars from a previous FUE hair transplant using scalp micro-pigmentation.
  6. A 45-year-old man, who had always shaved his head and refused hair transplantation, used SMP to create a hairline with an overall look of a clean-shaven head.

SMP can be applied to patients with alopecia areata, alopecia totalis, or pattern baldness. SMP can also help hide the scar tissue from several types of scarring alopecia. Finally, it can help to camouflage the scar tissue caused by large-graft “plug” transplants, scalp reduction procedures, or poorly performed or failed hair transplant procedures.

The authors note that adoption of SMP by physicians and potential patients has been slow because of the highly variable outcomes due to a lack of standardized SMP techniques and materials. However, the authors say a standardized SMP technique is being formalized that should support consistent high quality outcomes.

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Could a recently FDA-approved drug for rheumatoid arthritis also be a cure for a common type of hair loss called alopecia areata? The drug is called Xeljanz, and that’s what Dr. Brett King, assistant professor of dermatology at Yale, is hoping.

Dr. King’s patient, Kyle Rhodes, was diagnosed with alopecia totalis, the extensive variation of the auto-immune condition called alopecia areata that involves one’s entire scalp and body hair. By age 18, this condition had caused Kyle to lose all the hair on his head and body. He was also diagnosed with plaque psoriasis, a condition characterized by scaly red patches of skin.

While Dr. King was reviewing the research literature on tofacitinib citrate (Xeljanz), he discovered that the drug had been used to treat psoriasis in people and alopecia (hair loss) in mice, so he decided to try Xeljanz on Kyle’s condition.

The results were exactly what Dr. King hoped: after two months on the drug, Kyle’s psoriasis improved, and his hair started to return to his scalp and face. After five months, his scalp hair, eyebrows, eyelashes and facial hair were clearly visible. By eight months, his facial and scalp hair had fully returned.

Dr. King believes Xeljanz could be a major breakthrough in treating a disease that up till now has had few good treatment options.

This isn’t the first time a successful drug treatment for hair loss has been discovered serendipitously: oral minoxidil (later developed into the topical medication Rogaine) was first used as a treatment for high blood pressure, but it is now used as an FDA-approved topical treatment for androgenetic alopecia by both men and women.

Xeljanz, however, currently taken in pill form, isn’t an FDA-approved treatment for alopecia areata; further, it has some potentially serious side effects that could limit its use if it does become approved.

In order to reduce the possibility of those side effects, Dr. King is in the process of creating a topical form of Xeljanz a patient can use at the site of hair loss rather than take an oral medication. By applying a cream form of Xeljanz directly on the scalp, this would limit the drug from entering the blood stream in significant quantities and thus causing systemic side effects.

As a first step to getting FDA-approval, Dr. King has submitted a proposal to begin clinical trials that will use a cream form of Xeljanz.

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Q: Can a hair transplant into bald areas caused by alopecia areata ever be successful? — R.K., Providence, R.I.

A: Alopecia areata is an autoimmune disease in which the body attacks its own hair follicles. It generally appears as round patches of smooth bald areas scattered in the scalp or beard. Less commonly, it can involve the entire scalp (alopecia totalis) or all facial and body hair (alopecia universalis). Unless the condition is well localized and totally stable, hair transplantation is not likely to be effective because the transplanted hair would be subject to the same problem.

We prefer that one have no new lesions for a minimum of two years before considering surgical hair restoration, although this does not ensure that the procedure will be successful.

You may find more information on this relatively common condition at the National Alopecia Areata Foundation (NAAF). For more information, visit: www.naaf.org.

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