When you are ready to "strike", what should you do if "bald" suddenly attacks?

Because of the unknown, there is fear. Correct understanding and scientific prevention and control.

Written by | Ji Sheng

At the Oscars ceremony in March this year, Will Smith was unhappy with the jokes about his wife's hair loss and slapped the host hard on the stage. This slap caused the Oscars ratings to soar and also brought the word "alopecia areata" into the eyes of netizens around the world.

In fact, many people have suffered from alopecia areata, such as Shen Mengchen, the host of Mango TV, and Guixiang in the movie "Hello, Li Huanying". According to statistics, nearly 150 million people in the world are affected by alopecia areata. So what exactly is alopecia areata?

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What is alopecia areata?

Alopecia areata is a type of hair loss. The specific symptom is that a round or oval hairless area with clear boundaries suddenly appears on the scalp, just like a piece or several pieces of coin-sized hair have been shaved off out of thin air. The skin in the hair loss area is smooth, without inflammation, scaling and scars. In addition to alopecia areata, the hair loss we see in daily life also includes androgenic alopecia (abbreviated as "male alopecia"), or hair loss caused by drugs or inflammation. But alopecia areata has its own unique features: male alopecia generally has genetic factors and develops gradually, and drug-induced hair loss also has a development process; while alopecia areata often comes "bald" suddenly, and patients often do not have special feelings when alopecia areata occurs. Many patients suddenly find that they have lost a piece of hair, and even suspect that someone shaved their hair while they were sleeping at night. For this reason, alopecia areata is commonly known as "ghost hair loss". In the Western world, the ancient Greeks first used the word "alopekia" to describe alopecia areata. The word originally meant fox scabies - when a fox gets scabies, the hair on its head falls off, and human alopecia areata looks similar to fox scabies.

There are many types of alopecia areata according to clinical manifestations, among which three are the most common, namely localized alopecia areata, total alopecia and universal alopecia according to the severity of symptoms. If a small piece or several small pieces of scalp fall off, it is a mild case, which is the classic alopecia areata (alopecia areata, often referred to as AA). About 5% to 10% of alopecia areata can gradually develop or rapidly develop into severe alopecia areata. The situation where all hair falls off is called total alopecia (alopecia totalis). In more serious cases, in addition to the hair, eyebrows, eyelashes, pubic hair, armpit hair, etc. also fall off, which is universal alopecia (alopecia universalis).

There are three types of alopecia areata: classic alopecia areata, alopecia totalis, and alopecia universalis.
https://www.healthywomen.org/created-with-support/alopecia-areata)

According to the stage of the disease, alopecia areata can be divided into progressive stage, quiescent stage and recovery stage. In the progressive stage, the hair at the edge of the hair loss area is loose and will fall off with a slight pull; in the quiescent stage, the hair at the edge of the hair loss area is no longer loose; most patients enter the recovery stage after 3 to 4 months of quiescence, and new hair will grow. At first, it is fine and light-colored hair, which gradually becomes thicker and darker in color, and finally completely returns to normal.

Alopecia areata can occur at any age, but is more common in young and middle-aged people, with no obvious gender difference. About half of patients will have recurrent alopecia areata, which can last for years or decades. Epidemiological studies show that the prevalence of alopecia areata in my country is 0.27%. Foreign studies show that the risk of alopecia areata worldwide is about 2%, which means that about 2 out of every 100 people will suffer from alopecia areata at some time in their lives. [J Invest Dermatol. 2014 Apr; 134(4): 1141–1142.]. Alopecia areata is not contagious or fatal, but it affects the external image and can cause great mental stress to patients, which has a negative impact on mental health and quality of life. Many public figures are willing to bravely talk about their alopecia areata symptoms in public and encourage alopecia areata patients to embrace life, but this does not mean that they themselves do not feel pain as patients. Therefore, it is very important to understand the pathogenesis of alopecia areata, develop effective treatment drugs, and provide psychological counseling for patients.

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How does alopecia areata come about?

We don't know the exact cause of alopecia areata, but existing medical research generally shows that alopecia areata is an autoimmune disease. As the immune system attacks the hair follicles, the patient gradually loses hair on the scalp, face, and even the whole body.

Most cases of alopecia areata are caused by a combination of genetic and environmental factors. About 1/3 of patients with alopecia areata have a family history of alopecia areata, and the common prevalence of identical twins is about 55%. If alopecia areata occurs in childhood, the probability of it being inherited from the family is greater. In addition to family inheritance, alopecia areata may also be caused by a person having some immune-related diseases, such as hyperthyroidism or vitiligo, which are immune-related hair loss diseases. In addition, nervous and anxious emotional stress, physical fatigue, poor sleep, etc. may all cause alopecia areata.

As mentioned earlier, people have noticed and recorded the symptoms of alopecia areata very early, so there are some cognitions and interpretations of alopecia areata in traditional medicine. For example, Chinese medicine believes that "the liver stores blood, the kidneys store essence" and "hair is the surplus of blood". Insufficient qi and blood will cause hair loss and form alopecia areata; alopecia areata is also related to internal dampness and heat, wind caused by blood heat, liver stasis, spleen deficiency and deficiency of qi and blood. When people are under great mental stress, anxious, or angry, their endocrine system is out of balance, their metabolism is abnormal, and their skin may become abnormal. Modern medical researchers have successively proposed theories such as infection, neurological disease, endocrine disorder and autoimmune hypothesis to explain the cause of alopecia areata. Although both Chinese and Western medicine have their own theories on the cause and pathogenesis of alopecia areata, traditional Chinese medicine and Western modern medicine generally agree on the pathogenesis and treatment direction of alopecia areata, and most of them use methods such as regulating immunity and neuropsychiatric factors for treatment.

Schematic diagram of hair follicles and immune cells (from Nature Reviews Disease Primers 2017:17012)

There are also different hypotheses and theories about how autoimmune disorders cause alopecia areata symptoms at the microscopic molecular level. Under normal circumstances, hair follicles are immune-privileged organs, that is, the immune system does not monitor hair follicle cells, and specific antigenic proteins expressed in hair follicles do not cause immune responses. This immune privilege ensures the continued growth of hair and the periodic regeneration of the lower part of the hair follicle. However, under the conditions of genetic factors or external pathological stimulation, specific types of immune cells such as T cells and NK cells (Nature Killer) begin to gather around the hair follicles and attack the hair follicles. The cytokine IL-15 (Interleukin-15) secreted by the hair follicles binds to two JAK kinases (JAK1 and JAK3) to activate T cells, thereby increasing the secretion of interferon IFN-γ. After interferon IFN-γ binds to the IFN-γ receptor protein on the surface of hair follicle cells, it can activate the secretion of more cytokines IL-15, forming a continuous stimulation circuit, which also causes continuous damage to the hair follicles. In this process, JAK kinase is the core signaling molecule, so JAK inhibitors have become a popular research and development direction for alopecia areata drugs. The research and development progress in this area will be introduced later.

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How to prevent and treat alopecia areata?

We cannot control genes and autoimmune factors, but in daily life, paying attention to adjusting diet and sleep, learning to relieve mental stress, avoiding staying up late and irregular work and rest, all help prevent alopecia areata. If you really have alopecia areata, you don't need to worry too much. The treatment effect of alopecia areata is mostly very good, and it has no effect on physiological functions. You only need to conduct necessary examinations under the guidance of a doctor to rule out the possibility of other diseases. During the treatment process, you should relax, adjust your mentality, actively cooperate with the doctor, closely observe changes in the condition, and have regular checkups. Usually, more than half of the patients' hair can grow back in 6 to 12 months through normal treatment. Milder alopecia areata can even heal itself, but this takes time, because the hair needs to go through a 3-4 month rest period before entering the next growth cycle, after which new hair will gradually grow again.

It should be noted that alopecia areata is prone to recurrence. If early treatment is not thorough or the cause is not completely removed, alopecia areata is likely to come back. Patients with recurring hair loss, patients with a larger area of ​​hair loss, and patients with a young age of onset may need longer to recover.

As far as alopecia areata is concerned, almost all patients do not require surgical treatment. In order to achieve better results in stopping hair loss and promoting hair growth, patients can be given topical application of some hormone-containing ointments such as halometasone cream, or local injection of some hormone-containing solutions such as depoxetine or triamcinolone solution. If the alopecia areata is severe, patients may need to take oral glucocorticoids for a short period of time, or use JAK inhibitors to achieve the effect of hair growth. Severe alopecia areata and total alopecia areata are usually more difficult to treat, and the treatment cycle is also longer, mostly for more than one year.

There is a saying among the people that folk remedies can cure serious diseases. Some folk remedies suggest applying ginger to the areas of hair loss, and some patients' alopecia areata symptoms have indeed improved after applying ginger. Applying ginger on the scalp can make the local skin warm, and has a certain stimulation and circulation improvement effect. However, there is no standard for the use of ginger. The main ingredient of ginger, 6-gingerol, can easily cause side effects such as contact dermatitis, which may cause hair loss. Therefore, there are thousands of folk remedies, but science is the first. If the treatment is not standardized, the hair will continue to fall out. Fortunately, in recent years, the research and development of specific drugs for alopecia areata has made certain progress, and new treatment strategies such as immunotherapy and stem cell therapy are also in active clinical trials. Patients with alopecia areata are reminded to pay attention to the latest clinical diagnosis and treatment guidelines and cooperate with doctors for active treatment.

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Good news for severe alopecia areata: JAK inhibitor approved

The JAK mentioned above is a non-receptor tyrosine protein kinase that can mediate the signals produced by cytokines and transmit them through the JAK-STAT signaling pathway. There are four subtypes of JAK: JAK1, JAK2, JAK3, and TYK2. At present, JAK1 has become a target for diseases such as inflammation, cancer, and immunity; JAK2 has become a target for blood system-related diseases; and JAK3 has become a hot target for autoimmune diseases. Therefore, members of the JAK family have always been a hot spot for drug research and development. In fact, in the past decade, nearly 10 JAK inhibitors have been approved for marketing worldwide, but most of the approved indications are not related to alopecia areata. In recent years, with the confirmation of JAK as an important therapeutic target for alopecia areata, research on the use of JAK inhibitors to solve alopecia areata has gradually emerged, and Chinese and foreign pharmaceutical companies have entered the market.

Representative drugs currently entering clinical trials for alopecia areata include Olumiant (baricitinib) developed in collaboration between Eli Lilly and Incyte, Ritlecitinib (PF-06651600) from Pfizer, and deuruxolitinib (CTP-543) from Concert Pharmaceuticals. So far, the only drug officially approved for the treatment of alopecia areata is baricitinib. On June 13, 2022, the U.S. Food and Drug Administration (FDA) approved baricitinib as an oral medication for the treatment of severe alopecia areata. This is the first FDA-approved systemic therapy for alopecia areata. Previously, baricitinib received FDA breakthrough therapy designation in 2020 for the treatment of alopecia areata.

Eli Lilly's drug introduction

my country's pharmaceutical companies have also achieved good results in this JAK competition, such as Zejing Pharmaceutical's Jaktinib and Ruishi Biopharma's SHR0302. Currently, these two drugs, Eli Lilly's baricitinib and Pfizer's ritlecitinib have entered the domestic Phase III clinical trial stage.

According to public industry research reports, there are currently 173 JAK inhibitors under global drug development and 460 clinical trials are being conducted worldwide. Although not all of these clinical trials are related to alopecia areata, the successful development of these drugs will undoubtedly bring new hope for the recovery of alopecia areata patients. It is hoped that in the near future, alopecia areata patients in China will be able to use drugs and say goodbye to the suffering of hair loss.

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No longer alone: ​​social forces support patients with alopecia areata

Supporting patients with alopecia areata requires the joint efforts of family members, friends, drug development institutions and even the entire society.

First of all, the popularization of alopecia areata needs to be strengthened. There is still very limited information on alopecia areata on the Chinese Internet, with only a few popular science articles produced by well-known medical media such as the Chinese Medical Association and Dingxiangyuan. It should be known that alopecia areata is just one of many common diseases, not contagious and not fatal. The social and psychological pressures faced by patients with alopecia areata are largely due to our lack of understanding of this disease. Because of the unknown, there is fear. Correct understanding and scientific prevention and treatment can allow many patients to live a normal life.

Secondly, we should actively promote the linkage between patients and scientific research institutions, and support the research on the pathogenesis of alopecia areata and specific drugs. In 2017, the US FDA held a "Listen to the Voice of Patients" exchange meeting on alopecia areata (FDA has similar theme meetings for many diseases) to listen to the feedback of alopecia areata patients or family representatives on the treatment plan for alopecia areata at that time. At the meeting, a large number of patients reported the off-label use of JAK inhibitors such as tofacitinib (that is, these drugs have been approved but the designated use is not alopecia areata, and they have begun to use these drugs to treat alopecia areata), urging the FDA to speed up the approval of JAK inhibitors for alopecia areata indications. This meeting, to some extent, contributed to the FDA's breakthrough therapy recognition of baricitinib and CTP-543 in 2020, and even the official approval of baricitinib in 2022. The approval of new drugs for alopecia areata is a win-win situation for patients, drug development institutions and review institutions. It can be seen that patients should actively speak up and let official institutions hear everyone's voice.

The last and most important point is that social group support for patients with alopecia areata is crucial. We need to create a social atmosphere in which patients with alopecia areata feel safe, and also set up some platforms for them to gather together for warmth, communication and sharing, so as to reduce their social pressure. The practices of Western countries are worth learning from in this regard. European and American countries have officially certified alopecia areata foundations, alopecia areata information release platforms, and officially supported publicity festivals. The Canadian Alopecia Areata Foundation once published an initiative on its official website entitled "Five Do's and Five Don'ts in the Face of Alopecia Areata", which lists some behavioral norms that we can follow in our daily lives to respect and protect the mental health of patients with alopecia areata.

Translated from the official website of Canadian Alopecia Areata Foundation (CANAAF)

The American Alopecia Areata Foundation holds the Alopecia Areata Awareness Month in September every year. During this month, celebrities and patients launch public initiatives and fundraising, calling on everyone to understand and pay attention to alopecia areata and support alopecia areata patients.

The first Saturday of August every year is International Alopecia Areata Day. This "folk" memorial day was initiated by Mary Marshall, an alopecia areata patient in San Diego, California, and has now been supported by many countries. On this day, a large number of alopecia areata patients share their life photos on social media, in which they generously show their bald heads and smiles, which is very contagious. There is even a term called bald for beautiful. Be brave to be bald and bloom beautifully. In recent years, under the initiative of people of insight, Children's Alopecia Areata Day (April 14th every year) has also been successfully established. It should be noted that the incidence of alopecia areata in children is not low, and children with alopecia areata may face greater peer pressure than adults, and they need more care from their family and society.

Left: Promotional image from the website of the American Alopecia Areata Association: "25 years of alopecia areata, better understanding of yourself and others." Right: Promotional image from the website of the Canadian Alopecia Areata Association: "No hair, no problem."

I sincerely hope that all patients with alopecia areata can get rid of the pain of hair loss as soon as possible and embrace life!

References

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Chinese Alopecia Areata Diagnosis and Treatment Guidelines 2019 Edition.

https://www.prnewswire.com/news-releases/olumiant-significantly-improved-hair-regrowth-to-at-least-80-scalp-coverage-as-early-as-24-weeks-across-first-completed-phase-3-studies-for-alopecia-areata-301388398.html

Produced by: Science Popularization China