Alopecia Areata: Treatment Options and Etiology

Alopecia areata: treatment options and etiology

Alopecia areata is an autoimmune disorder that causes hair loss which can be relapsing, remitting, or persistent. Hair loss can occur in patches or be totally lost. The most common type of alopecia is patchy losses of hair on the scalp that can progress to total loss on the scalp or on the body. There is increased occurrence between twins, siblings, and families indicating a genetic basis for disease. Alopecia areata increases the likelihood of comorbidities like depression, anxiety, and other autoimmune diseases like psoriasis, inflammatory bowel disease, and thyroid diseases.

In patients with alopecia areata, there is increased fragility of the hair shaft leading to breakage. Hairs are normally in the anagen phase which is when the hair follicle is growing. In alopecia areata, there is an increase of hairs prematurely entering the telogen phase. Patients with alopecia have exclamation point hairs which have a normal club root, but it is more narrowed and falls out easier. The hairs do not anchor themselves properly into the hair follicle. These hairs have degenerative changes that cause intra-cytoplasmic vacuoles in the hair follicles leading to weakness. Biopsies of bald patches have shown that there are follicles that were halted in the anagen III/IV phase (Pratt, C. H. et al.). There is a lymphocytic infiltrate around the bulb area of the hair follicles in the anagen phase. The breakdown of immune privilege in the hair follicle is a mechanism of alopecia areata. Normal hairs have low MHC class I and II expression and high macrophage migration inhibitory factor expression which prevents the infiltration of T lymphocytes. They are naturally able to escape autoimmune reactions. Furthermore, polymorphisms of ULBP genes and defects in VIPR-mediated signaling increase susceptibility to alopecia areata.

Alopecia areata can be triggered by emotional or physical stress. Other possible lifestyle factors include smoking, alcohol, sleep disorders, obesity, intake of fatty acids, and gluten (Minokawa, Y., Sawada, Y., & Nakamura, M.). Alopecia areata is most commonly diagnosed on the scalp. It can also be seen in the beard of men, or loss of eyebrows and eyelashes. There is always potential for the regrowth of hair since the hair follicles are preserved in alopecia areata. There are no treatments approved by the FDA for alopecia areata. There are many treatments that can help with hair growth, but not enough research has been done on them. Treatment is not always required since people can go into remission spontaneously. The more extensive the diagnosis, the less favorable regrowth is. Local corticosteroids may be used to speed regrowth of hair in mild patchy alopecia areata. This should be tried for at least 3 months to see an effect, but no longer than 6 months with no response. Intralesional steroids is another effective treatment. Steroid is administered into the upper subcutaneous tissue by a needle to stimulate hair growth. This is only suitable for patchy alopecia areata. It will not help prevent alopecia at other parts of the body or with total hair loss. Other medications include topical minoxidil and anthralin, but there is still uncertainty around the benefit of these. Systemic corticosteroids can be used to successfully regrow hair, but they must be continued to maintain the hair growth. Ma\ost patients discontinue treatment due to side effects of corticosteroids. Contact immunotherapy is another treatment for patchy alopecia areata. A possible mechanism is competition to attract CD4 T cells away from the follicle (Pratt, C. H. et al.).

There is not a treatment to cure alopecia areata, but there is hope for the regrowth of hair. There are some treatments that can be tried by patients, but efficacy compared to risks sometimes does not justify their use. Adjusting some lifestyle factors may have a role in the course of this disease.

Resources

Minokawa, Y., Sawada, Y., & Nakamura, M. (2022). Lifestyle Factors Involved in the Pathogenesis of Alopecia Areata. International journal of molecular sciences, 23(3), 1038. https://doi.org/10.3390/ijms23031038

Pratt, C. H., King, L. E., Jr, Messenger, A. G., Christiano, A. M., & Sundberg, J. P. (2017). Alopecia areata. Nature reviews. Disease primers, 3, 17011. https://doi.org/10.1038/nrdp.2017.11

Alopecia

Alopecia, known as hair loss, is a class of conditions which may affect people of any age or gender. The hair loss may be obvious or subtle but if the patient is seeking medical treatment, it is most likely affecting their quality of life. When examining a patient with hair loss, providers must look at the whole picture in order to determine the cause and then the treatment. If patients have systemic symptoms like fatigue and weight gain, the provider should suspect hypothyroidism as the cause and obtain further laboratory tests to confirm. If the patient recently experienced a febrile illness, stressful event, or pregnancy, they can assume the hair loss is due to telogen effluvium. Family history is also important to obtain from the patient as a family history of hair loss would suggest androgenetic alopecia.

The different types of alopecia include alopecia areata, anagen effluvium, androgenetic alopecia, telogen effluvium, tinea capitis, trichorrhexis nodosa, and trichotillomania. Alopecia areata is an acute, patchy hair loss that affects about 2% of the population. It occurs equally among males and females. The cause is likely autoimmune but the exact mechanism is unknown. There are 3 different patterns of alopecia areata: patchy alopecia, which occurs in oval-shaped patches on any part of the body; alopecia totalis which involves the entire scalp; and alopecia universalis which affects the whole body. Treatment of this type is triamcinolone acetonide injected intradermally. The treatment can be repeated every 4-6 weeks for a maximum of 6 months. This treatment does not always produce satisfactory results so many times patients opt to use a hairpiece or a wig.

Anagen effluvium is identified by diffuse hair loss days to weeks after exposure to a chemotherapeutic agent. It affects around 65% of patients on chemotherapy. There is no pharmacologic therapy that is effective for this type of alopecia. Androgenetic alopecia is characterized by a gradually progressive course of hair loss. Men experience bitemporal thinning of the frontal and vertex scalp while women experience diffuse hair thinning of the vertex with sparing of the frontal hairline. Treatment of this type of alopecia includes topical minoxidil or finasteride. Topical minoxidil comes in 2% and 5% strength solutions and is approved for androgenetic alopecia in men and women. The 2% strength is indicated for women and the 2% or 5% may be used in men. The treatment should be continued indefinitely to maintain results. Finasteride at a dose of 1 mg orally daily is the second option for androgenetic alopecia in men who have failed treatment with minoxidil. Finasteride has a higher side effect profile with decreased libido, erectile dysfunction, and gynecomastia being reported.

Telogen effluvium is a type of alopecia which occurs suddenly, happening when more hairs enter the telogen phase than normal. The hair loss occurs usually 3-5 months after an emotional or physiologic stressor. It can also be caused from medications like retinoids, anticoagulants, anticonvulsants, and antithyroid medications. This type of alopecia is not treated with medications because it often resolves by itself within 2-6 months. Trichotillomania is a psychological disorder in which patients pull or twist their hair so frequently that it falls out. Treatment for trichotillomania would be cognitive behavioral therapy or treatment with an SSRI.

Resources:

Phillips TG, Slomiany WP, Robert Allison II. Hair loss: Common causes and treatment. American Family Physician. https://www.aafp.org/afp/2017/0915/p371.html. Published September 15, 2017. Accessed March 24, 2022.

Hair loss types: Alopecia areata diagnosis and treatment. American Academy of Dermatology. https://www.aad.org/public/diseases/hair-loss/types/alopecia/treatment. Accessed March 24, 2022.

Alopecia Areata is an autoimmune disease that causes hair loss. It is common to notice hair being lost in circular patches ranging from small to large areas. This condition affects two out of every hundred people. In patients with this condition, the hair follicles release a chemical that causes the immune system to attack them. As long as the immune system is attacking the follicle, new hair will be unable to grow. This is a genetic condition involving multiple genes. This also affects men and women similarly. The only symptom of this condition is sudden hair-loss in patches and could affect larger portions of the scalp or other parts of the body.

Alopecia Areata can be diagnosed by a doctor through the examination of the hair loss and discussing the patient’s history. In some cases, they can also look for a pattern of immune cells that are around the hair follicle in the skin through a biopsy. Many cases of alopecia areata will resolve without treatment and the condition can reappear over a patient’s lifetime. There are also steroid injections that can be given in the areas here hair loss is occurring. The steroids suppress the immune system cells so hair can regrow. Another approach is the topical application of an irritant such as squaric acid. This can create a poison ivy-like reaction which seems to distort the immune system’s attack on hair follicles. Recently, there has been studies showing the benefits of janus kinase inhibitors that help with this condition. This condition can be very unexpected and have a huge impact on a patient’s quality of life and confidence. I hope further research and more reliable treatment options are discovered in the future.

References:

1. “Alopecia Areata.” Yale Medicine, Yale Medicine, 23 Oct. 2019, https://www.yalemedicine.org/conditions/alopecia-areata.

2. “Hair Loss Types: Alopecia Areata Overview.” American Academy of Dermatology, https://www.aad.org/public/diseases/hair-loss/types/alopecia.

Chemotherapy-induced Alopecia

Written by: Jae Chang and Hillary Pham

Although chemotherapy has been proven to be safe and effective treatment for various kinds of cancer, there are many side effects that come along with this therapy. Some of the most common side effects from chemotherapy are fatigue, nausea, hair loss, mucositis, and much more. This is most seen when patients are taking the chemotherapy intravenously rather than orally. Regardless, the effects of the chemotherapy can take a toll on patients, physically, mentally and emotionally.

Alopecia areata, commonly known as hair loss, is one of the most common side effects that is seen with chemotherapy. This can be seen most in a class of chemotherapy medications called the alkylating agents. Alkylating agents are one of the most known chemotherapy drugs, that includes medication therapy such as Cytoxan, Ifex, or even Thioplex.

Alopecia can occur from days to weeks after the initiation of chemotherapy and may involve different shedding types such as dystrophic anagen effluvium and telogen effluvium. Hair loss from chemotherapy occurs because the main targets for chemotherapy medications are the matrix keratinocytes. Matrix keratinocytes are highly proliferative during anagen phase, which is the active phase of the hair, involving the rapid dividing of the cells in the root of the hair. Anti-cancer medications accelerate the normal transition of the hair from anagen phase to telogen phase, which is a mitotically inactive phase. Because 90% of the hair on our scalp are known to be in anagen phase, the scalp is the most frequently affected area. The hairs of the beard, eyebrows, and other areas are affected based on the percentage of hairs in anagen phase. While these kinds of alopecia are generally temporary and reversible with hair regrowth seen after 3-6 months, there are reports of permanent alopecia that is caused by high dose chemotherapy or by busulfan and cyclophosphamide administration. The exact cause of permanent alopecia is not exactly known, but is thought to be the consequence of a damage to the hair-follicle stem cells.

Cyclophosphamide is an example of an alkylating agent. It is especially known for its nitrogen mustard chemical structure. The mechanism of action for this drug is that the activated form of cyclophosphamide, the phosphoramide mustard will alkylate or bind to DNA. By doing so, this will cause a cytotoxic effect due to the cross-linking of strands of DNA and RNA. Furthermore, this will allow for the inhibition of protein synthesis which will ultimately, further prevent the growth of the cancer cells.

Although the cyclophosphamide treatment is well studied and used in cancer therapy, the side effects along with this chemotherapy is what is most worrisome for some patients. A study that was conducted used the medication, Cytoxan or cyclophosphamide, to study the effects of the chemotherapy-induced alopecia on mice. The study showed that with just one injection of the cyclophosphamide to the mice’s back skin follicle caused severe alopecia.

During chemotherapy, gentle hair care strategies should be implemented to prevent further hair loss. This includes using soft brushes, washing hair with gentle shampoo, and possibly cutting hair short for better comfort. Scalp cooling may also be recommended as preventative therapy for alopecia. The mechanism of action is unclear, but scalp cooling is proposed to cause vasoconstriction in the vessels of the scalp to reduce local concentration of chemotherapy and cellular uptake at the hair follicle and reducing metabolic uptake. A meta-analysis has shown that scalp cooling reduces chemotherapy induced alopecia, although it may cause headaches and discomfort. Scalp cooling has been most effective in alopecia induced by doxorubicin, epirubicin and docetaxel. Unfortunately, there are currently no approved drugs to be used for alopecia treatment.

As future healthcare professionals, we must study and explore the possible treatments or remedies that can help patients with the effects of alopecia due to chemotherapy. For instance, understanding the use and benefits of medications like corticosteroids or Minoxidil therapy that can be useful for some patients. Alopecia does not only cause a physical change of appearance but also can cause an emotional and self esteem issues to patients that some may struggle with. Of many helpful resources to explore, Wigs for Kids or Locks of Love are excellent organizations that have been created for everyone around the world to donate locks of hair to. These organizations will then collect, sort, and create beautiful wigs for patients to wear. We must be aware, as providers, of these different therapies and resources to help patients during a difficult phase of life.

References:

Dechant, K.L., Brogden, R.N., Pilkington, T. et al. Ifosfamide/Mesna. Drugs 42, 428–467 (1991). https://doi-org.jerome.stjohns.edu/10.2165/00003495-199142030-00006

Paus, R., Handjiski, B., Eichmüller, S., & Czarnetzki, B. M. (1994). Chemotherapy-induced alopecia in mice. Induction by cyclophosphamide, inhibition by cyclosporine A, and modulation by dexamethasone. The American journal of pathology, 144(4), 719.

Rossi, A., Fortuna, M. C., Caro, G., Pranteda, G., Garelli, V., Pompili, U., & Carlesimo, M. (2017). Chemotherapy-induced alopecia management: Clinical experience and practical advice. Journal of cosmetic dermatology, 16(4), 537–541. https://doi.org/10.1111/jocd.12308

Alopecia Areata: Here is what we know! Alopecia Areata literally translates to bald patches. It is a condition that causes hair loss at various areas on the body. It is mostly associated with hair loss on the scalp because that is the most prominent place in which the effects of alopecia areata is visible but it can actually also occur on other areas such as the beards, eyebrows, eyelashes, anywhere in which there is hair growth then there is a possibility for hair loss. Alopecia Areata can also affect the nails and making them appear brittle, with dents as well as ridges. This disease is classified as an autoimmune disease meaning that the immune system attacks a part of the body by accident because it thinks that a specific part of a body is a foreign substance therefore it attacks the body in order to try and protect it which yields to hair loss and at times brittle nails.

Alopecia can begin at any age but it is mostly developed during the childhood or teenage years. There is a risk that if a parent or a relative have had alopecia then the child might also develop the disease but it will not necessarily occur. People who also have asthma, atopic dermatitis, thyroid disease, as well as other conditions might be more prone to having alopecia areata. People who are also treated for lung cancer and melanoma with a drug called Nivolumab might develop alopecia areata but in this case, if alopecia occurs then it is a good sign meaning that the cancer treatment is working.

People with alopecia may lose hair in certain spots and then gain it back within 12 months without any treatment. The hair that grows back might never fall out again. There are different types of alopecia areata that a person may be diagnosed with by the dermatologist. The main types include alopecia areata, alopecia totalis, and alopecia universalis. Alopecia areata is, as mentioned earlier, a patchy baldness that can develop anywhere on the body. it can occur on the scalp, beard area, eyebrows, armpits, eyelashes, the hair inside the nose as well as the hair inside the ear. Alopecia totalis is when the person loses all hair on the scalp. Alopecia universalis is when the person loses all hair which makes the entire body hairless but this is a rare form.

There are studies that show the different types of alopecia areata might be triggered by the cold. It has been shown to occur mostly in the months of October, November, as well as January. There are no FDA approved medications for the treatment of alopecia but there are a few medications that are for off-label use. For patchiness symptoms, treatment includes corticosteroid injections every 4 to 8 weeks as needed. Studies have shown that at least half of the hair regrows within 12 weeks. Another treatment is Minoxidil which can help with hair regrow on the scalp, beard area as well as eyebrows. It is applied 2 to 3 times daily. For the eyelashes, there is a medication called Bimatoprost which is approved to treat glaucoma but it has an effect to make eyelashes grow longer.

It is important to note that with alopecia when there is hair loss on the eyebrows or eyelashes then there are precautions that must be followed in order to protect the eyes. It is important to wear glasses, wear false eyelashes as well as applying stick-on eyebrows. There are all great steps to take to protect the eyes. In order to protect your scalp, it is important to wear sunscreen and a hat to reduce the risk of sunburn. If you or someone you know has alopecia then make sure to follow-up with a dermatologist for the safest and most effective therapies.

“Hair Loss Types: Alopecia Areata Overview.” American Academy of Dermatology, www.aad.org/public/diseases/hair-loss/types/alopecia.

The Psychological Impact of Alopecia Areata in Adult Patients

"For patients who suffer from alopecia areata, it is not a cosmetic condition, it is a devastating autoimmune disease that can have significant psychological effects. They lose much more than just hair." (Lotus Mallbris, M.D., Ph.D.)

There is a lack of information concerning the prevalence of mental disorder symptoms and QoL in AA patients in our country. Despite the fact that AA is considered a benign disease (does not cause harm), it highly influences the QoL and psychosocial wellbeing of patients, affecting their functional, work, and social capacities. The aim of this study was to determine the prevalence of mental disorder symptoms and QoL among Mexican patients with mild and severe forms of AA.

Previous studies have found a prevalence of psychiatric disorders in 22-70% AA patients. The most frequent diagnoses were depression, generalized anxiety disorder, and social phobia. Although depression is frequently seen in AA patients, no increase in suicide risk has been documented in patients with AA.

A total of 126 patients (56% females and 41% males) participated in this cross-sectional study during the 1-year period of enrollment. The mean age of AA onset was 25 years (SD 5.3 years), and the mean duration of the disease was 3.6 years (SD 6.4 years). Most of the patients had patchy AA (92.9%), 3.2% total AA, 1.6% ophiasis, and 1.6% universal AA. Thirty-nine out of 126 (31%) patients had multiple episodes of AA.

Three quarters of the studied adults with AA (71.2%) had some degree of depression or anxiety according to the HADS scale, and 60% of them initiated pharmacological treatment due to their symptoms. These results agree with those reported by Baghestani et al. who found that in a cohort of 68 AA patients, 47% of the patients showed anxiety signs and 56% of the patients experienced some degree of depression. They concluded that AA patients have a 5 times greater risk of developing depression than their healthy counterparts do. The prevalence of depression and anxiety is higher in women because they could be pressured by the beauty standards expected for their gender.

This study is useful because it highlights the correlation between alopecia areata and a deterioration in patients' quality of life and mental health. Many adult patients show depression and anxiety symptoms that could be related to negative self-perception symptoms. Since quality of life impairment in adults was related to the presence of signs and symptoms of anxiety and depression, it is recommended to screen AA patients for mental disorders including anxiety, depression, and suicidality.

Resources:

1. Vélez-Muñiz RDC, Peralta-Pedrero ML, Jurado-Santa Cruz F, Morales-Sánchez MA. Psychological Profile and Quality of Life of Patients with Alopecia Areata. Skin Appendage Disord. 2019;5(5):293-298. doi:10.1159/000497166

Seeking FDA Approval: Olumiant (baricitinib) for AA

There are currently no FDA-approved treatments for alopecia areata (AA). Although we have drugs such as finasteride and minoxidil, which have shown efficacy in treatment of AA, there are no long-term therapies available for those with severe, treatment refractory alopecia areata. There is no cure for AA, and the psychosocial stigmatization associated with hair loss drives the desire to find a long-term therapy for severe cases.

"For patients who suffer from alopecia areata, it is not a cosmetic condition, it is a devastating autoimmune disease that can have significant psychological effects. They lose much more than just hair." (Lotus Mallbris, M.D., Ph.D., vice president of immunology development at Lilly)

On March 3, 2021 Eli Lilly and Company and Incyte released preliminary results from BRAVE-AA2, a Phase 3 study evaluating the efficacy and safety of once-daily baricitinib 2 mg and 4 mg in adults with severe alopecia areata. Baricitinib has received “Breakthrough Therapy” designation from the U.S. Food and Drug Administration (FDA) for the treatment of AA. The “Breakthrough Therapy” designation aims to expedite the development and review of drugs that are intended to treat a serious condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over already available therapies on a clinically significant endpoint.

BRAVE-AA2 is the first Phase 3 study with positive results in patients with AA. This multicenter, randomized, double-blind, placebo-controlled study included 546 adults with a Severity of Alopecia Tool (SALT) score ≥ 50 (i.e., who had ≥50% scalp hair loss) and a current episode of severe AA lasting between 6 months - 8 years. Both doses of baricitinib met the primary efficacy endpoint at Week 36, demonstrating a statistically significant improvement in scalp hair regrowth compared to those randomized to placebo. Safety outcomes of baricitinib in BRAVE-AA2 were consistent with its established safety profile in patients with rheumatoid arthritis and atopic dermatitis. No deaths, major adverse CV events, or VTEs were reported in the study. Data from an additional Phase 3 study of baricitinib in AA will be available in the first half of 2021. AA is the second potential treatment indication in dermatology for baricitinib after atopic dermatitis.

WARNINGS: SERIOUS INFECTIONS, MALIGNANCY, AND THROMBOSIS

1. SERIOUS INFECTIONS: Patients treated with Olumiant are at risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt Olumiant until the infection is controlled.

2. MALIGNANCIES: Lymphoma and other malignancies have been observed in patients treated with Olumiant.

3. THROMBOSIS: Thrombosis, including deep venous thrombosis (DVT) and pulmonary embolism (PE), has been observed at an increased incidence in patients treated with Olumiant compared to placebo. In addition, there were cases of arterial thrombosis. Many of these adverse events were serious and some resulted in death. Patients with symptoms of thrombosis should be promptly evaluated.

Resources:

1. Eli Lilly and Company. Baricitinib is First JAK-Inhibitor to Demonstrate Hair Regrowth in Phase 3 Alopecia Areata (AA) Trial. Lilly. https://investor.lilly.com/node/44706/pdf. Published 03/03/2021.