Alopecia Areata: Treatment Options and Etiology

Chemotherapy-induced alopecia refers to the temporary loss of hair resulting from systemic cancer treatment. It affects approximately 65% of patients undergoing cytotoxic therapy and significantly impacts their quality of life, adding to the burden of cancer diagnosis and treatment. The psychological toll can be severe, potentially leading to treatment avoidance or delays.

The mechanism behind chemotherapy-induced alopecia involves damage to rapidly dividing hair follicle cells by cytotoxic drugs. Hair follicles cycle through stages of growth (anagen), regression (catagen), and rest (telogen), with most scalp follicles in the growth phase at any time. Chemotherapy agents interfere with the highly proliferative keratinocytes in the hair follicle matrix during the anagen phase, causing anagen effluvium. The likelihood and severity of alopecia depend on factors such as the specific drug, its route of administration, dosage, and treatment schedule. High-dose, intravenous, and combination chemotherapy regimens are associated with a higher incidence of complete or near-complete alopecia. Drugs like cyclophosphamide, paclitaxel, docetaxel, doxorubicin, and etoposide are particularly notorious for causing significant hair loss.

Chemotherapy-induced alopecia manifests as partial or complete loss of hair from areas with normal hair growth, most prominently on the scalp, including the crown and frontal regions. Eyebrows, eyelashes, and body hair may also be affected but often regrow faster than scalp hair after treatment cessation. While most cases of alopecia are reversible within three to six months post-therapy, certain chemotherapy drugs, such as high-dose docetaxel, may lead to prolonged or permanent hair loss in some patients. Studies have shown significant rates of persistent alopecia in breast cancer patients even years after treatment completion, highlighting its lasting impact on quality of life.

Managing chemotherapy-induced alopecia involves preventive measures and supportive care. Scalp cooling, or scalp hypothermia, is used in patients undergoing chemotherapy for solid tumors to reduce hair loss. It works by constricting blood vessels in the scalp, thereby reducing the delivery of chemotherapy drugs to hair follicles. However, its effectiveness varies depending on the chemotherapy regimen used, with anthracycline-based therapies showing less preservation of hair. Scalp cooling may cause discomfort, cold intolerance, and headaches and comes with financial costs ranging from $1500 to $3000 per patient, depending on the treatment duration and equipment used.

Ongoing research explores pharmacological interventions like minoxidil, finasteride, spironolactone, and calcitriol for preventing or minimizing chemotherapy-induced alopecia. These treatments, although promising, lack regulatory approval for this specific indication and require further validation of their efficacy and safety profiles.

In addition to medical interventions, nonpharmacological strategies such as wigs, head coverings, and psychosocial support play crucial roles in helping patients cope with the cosmetic and emotional aspects of hair loss during chemotherapy. It is essential for healthcare providers to discuss the potential for alopecia before initiating treatment and explore alternatives when feasible, ensuring comprehensive support for patients facing this challenging side effect of cancer therapy.

Wikramanayake, T. C., Haberland, N. I., Akhundlu, A., Laboy Nieves, A., & Miteva, M. (2023). Prevention and Treatment of Chemotherapy-Induced Alopecia: What Is Available and What Is Coming?. Current oncology (Toronto, Ont.), 30(4), 3609–3626. https://doi.org/10.3390/curroncol30040275

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 (AA) is a chronic, immune-mediated autoimmune disorder that affects hair follicles, nails, and on occasion the retinal pigment epithelium. This condition affects the anagen phase hair follicles in individuals, resulting in hair loss without causing damage to the follicles. AA can be classified in several ways, depending on the extent and location of hair loss on the body. Alopecia areata totalis involves complete hair loss on the scalp. Alopecia areata universalis results in complete hair loss on both the scalp and body. Diffuse alopecia areata is characterized by general hair thinning rather than patchy hair loss. Ophiasis alopecia areata causes hair loss in a band along the lower back and sides of the scalp (occipitotemporal region).

Alopecia areata typically manifests as sudden, patchy hair loss, characterized by well-defined single or multiple patches. Although it most frequently occurs on the scalp, it can affect other parts of the body as well. Patches up to 2 cm (approximately 0.8 inches) in diameter can appear overnight and expand at a rate of around 1 cm (0.4 inches) per week. The hair loss often involves hair breakage near or just below the skin's surface. The diagnosis is generally made through clinical evaluation, supported by indicators like a positive hair pull test or trichoscopy results. During trichoscopy, active disease is marked by the presence of yellow dots, black dots, “exclamation mark” hairs, tapering hairs, and broken hairs. The presence of vellus hair in lesions is another sign of alopecia areata (AA) and may suggest late-stage or inactive disease.

Understanding the pathophysiology of alopecia areata is complex and challenging. Current evidence indicates that the condition is autoimmune in nature, with a significant genetic component and additional influence from unidentified environmental factors. Reported triggers include emotional or physical stress, vaccinations, viral infections, and medications. These triggers initiate hair loss by inhibiting the production of two anti-inflammatory cytokines, transforming growth factor-β (TGF-β) and α-melanocyte–stimulating hormone (α-MSH), and by stimulating the expression of major histocompatibility complex class I (MHC-I) polypeptide-related sequence A (MICA) on hair follicles. This process activates natural killer (NK) cells, leading to the secretion of interferon-y (IFN-γ) and interleukin-15 (IL-15) FN-γ promotes the expression of MHC-I proteins on hair follicle cells, exposing previously hidden antigens to T cells, while IL-15 inhibits regulatory T cells. Both IFN-γ and IL-15 activate immune cells via the JAK-STAT signaling pathway, causing inflammatory cells to target the hair follicle matrix epithelium undergoing early cortical differentiation or anagen hair follicles, and prematurely pushing them into the catagen or telogen phase.

Alopecia areata can be managed with various treatment options, including corticosteroids, minoxidil, phototherapy, platelet-rich plasma, and topical immunotherapy. Triamcinolone acetonide is a common treatment for alopecia areata, administered at concentrations of 5 to 10 mg/mL every 4 to 6 weeks on the scalp. This regimen promotes localized hair regrowth in 60% to 67% of patients. Typically, around 0.1 mL of triamcinolone acetonide is injected into the affected area at intervals of 1 cm apart. Another effective treatment for alopecia areata is betamethasone dipropionate 0.05% cream, lotion, or ointment, a potent topical glucocorticoid. This option is often preferred for children and individuals who prefer to avoid frequent injections. Patients typically apply betamethasone to the affected area daily, extending 1 cm beyond the border of hair loss. Patients experiencing widespread disease, often characterized by hair loss exceeding 50% on the scalp, may explore alternative treatments such as topical immunotherapy or oral JAK inhibitors like ritlecitinib and baricitinib. These options aim to reduce the necessity of frequent injections associated with intralesional corticosteroids, offering effective management strategies for alopecia areata.

Living with alopecia areata can be emotionally challenging for patients, given the unpredictable nature of hair loss. To manage the condition and support overall well-being, patients should prioritize skin protection, minimize stress, and avoid hair products containing harsh chemicals. There are various methods of concealing hair loss available to patients with alopecia areata. These include hairpieces such as wigs, as well as hair thickening fibers and concealing powders. Microblading has also gained popularity as a method to add pigment to the skin, often used to recreate eyebrow appearance. These approaches can provide cosmetic relief and enhance self-confidence for individuals affected by alopecia areata. In addition to managing the physical aspects of the condition, addressing emotional well-being through appropriate psychosocial support can greatly benefit individuals affected by alopecia areata.

References:

1. Law, R. M., Do, L. H. D., & Maibach, H. I. (n.d.). Chapter 120: Alopecia . Shibboleth authentication request. https://accesspharmacy-mhmedical-com.jerome.stjohns.edu/content.aspx?sectionid=272008034&bookid=3097#1197559396 

2. professional, C. C. medical. (n.d.-a). Alopecia areata. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/12423-alopecia-areata 

3. Sibbald, C. (2023). Alopecia areata: An updated review for 2023. Journal of cutaneous medicine and surgery. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291119/ 

Lepe, K. (2024, February 8). Alopecia areata. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK537000/

Alopecia areata is a chronic, immune-mediated disorder that primarily affects anagen hair follicles and results in non-scarring hair loss. Typically, alopecia areata manifests as distinct, smooth patches of hair loss/baldness on the scalp, although it can still affect other areas with hair such as the eyebrows, eyelashes, beard and limbs. In the most severe cases, individuals may undergo complete loss of scalp or body hair. There are three primary types of alopecia areata patients may be diagnosed with: 

• Patchy alopecia areata: the most common type, results in hair loss of one or multiple coin-sized patches on the scalp or various regions of the body 

• Alopecia totalis: loss of all or most of the hair on the scalp 

• Alopecia universalis: the rarest form of the disorder, is a complete or nearly complete loss of hair on the scalp, face and the rest of the body.

Alopecia areata is a global disorder, with an approximate prevalence of around 1 in 1000 individuals and a lifetime risk of about 2%. This condition can affect both children and adults and occurs at about the same rate in males and females. An analysis of clinical records from Minnesota spanning from 1990 to 2009 showed that the average age at diagnosis for alopecia areata was 32 years old for males and 36 years old for females. 

As aforementioned, alopecia areata is an autoimmune disorder whereby the “hair follicles in the growth phase (anagen) prematurely transition to the nonproliferative involution (catagen) and resting (telogen) phases, leading to sudden hair shedding and inhibition of hair regrowth.” However, the precise mechanisms behind the onset of alopecia areata remain not fully understood. It has been theorized that critical factors for the development of this order may involve the breakdown of follicular immune protection and the emergence of a T-cell mediated immune assault on cells within the hair bulb. Additionally, genetic predisposition contributes significantly to the susceptibility of contracting alopecia areata. 

In order to diagnose a patient with alopecia areata, patient history and physical evaluation are usually adequate. When gathering patient history, it is crucial to investigate the onset and duration of hair loss alongside any accompanying symptoms. Although alopecia areata typically manifests as a sudden, symptom-free hair loss, there is a possibility of spontaneous resolution so it is important to ask patients about previous instances of hair loss as well. In terms of the physical exam, the provider should ensure to thoroughly evaluate the hair, scalp and other regions with hair to analyze the pattern and extent of hair loss and to identify indications suggestive of other scalp or hair disorders. Careful physical examination of patients with alopecia areata may also reveal “exclamation point” hairs, which is a characteristic sign of the disorder. Furthermore, when examining the scalp, it is also important to check for follicular openings within areas of hair loss as the absence of these indicates scarring alopecia. 

Treatment for alopecia areata consists of pharmacological therapies, cosmetic options and psychosocial support. The choice of initial pharmacological treatment is dependent upon the severity of hair loss in the patient. While there are no strictly defined criteria for disease severity, the two commonly recognized categories include: limited, patchy hair loss and extensive hair loss. For limited, patchy hair loss, the first-line option for treatment is intralesional corticosteroids. A common example is Triamcinolone acetonide, which is injected into the upper subcutis of the scalp at a dose ranging from 2.5 to 10 mg/mL. When intralesional corticosteroids are administered on both existing and newly forming patches of hair loss, they are able to promote regrowth and limit the amount of hair loss. Another first-line treatment option for patients who are not able to tolerate or are not willing to receive intralesional corticosteroids is topical corticosteroids. Typically, a high-dose corticosteroid such as Betamethasone dipropionate 0.05% is necessary in this disorder. On the other hand, in cases of extensive hair loss, there are other treatment options available. First-line options in patients with extensive hair loss include baricitinib (Olumiant), ritlectinib (Litfulo) and topical immunotherapy. Olumiant is an oral, JAK1 and JAK2 inhibitor (intracellular enzymes responsible for stimulating hematopoiesis and immune cell function through a signaling pathway) and was approved by the FDA in 2022 for the treatment of alopecia areata. The standard adult dosing for this medication is 2 mg once daily, which may be increased to 4 mg once daily depending upon patient response. Litfulo, an alternative option for Olumiant, is an irreversible inhibitor of JAK3 and the tyrosine kinase which is found in hepatocellular carcinoma kinase family, consequently resulting in inhibition of T-cell activation. The recommended adult dosing for this medication is 50 mg once daily. Common adverse effects of both JAK inhibitors include acne vulgaris, diarrhea, urticaria, infection and hyperlipidemia. 

Resources: 

Messenger A. Alopecia areata: Clinical manifestations and diagnosis. UpToDate. April 5, 2021. Accessed April 23, 2024. https://www-uptodate-com.jerome.stjohns.edu/contents/alopecia-areata-clinical-manifestations-and-diagnosis?search=alopecia+areata+&source=search_result&selectedTitle=2~79&usage_type=default&display_rank=2. 

Alopecia Areata. National Institute of Arthritis and Musculoskeletal and Skin Diseases. July 27, 2023. Accessed April 23, 2024. https://www.niams.nih.gov/health-topics/alopecia-areata#:~:text=Causes%20of%20Alopecia%20Areata,genetic. 

Baricitinib (Lexi-Drugs). Lexicomp. Accessed April 23, 2024. https://online-lexi-com.jerome.stjohns.edu/lco/action/doc/retrieve/docid/patch_f/6653506?cesid=7WIK4zRz1Xx&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dolumiant%26t%3Dname%26acs%3Dfalse%26acq%3Dolumiant#. 

Ritlecitinib (Lexi-Drugs). Lexicomp. Accessed April 23, 2024. https://online-lexi-com.jerome.stjohns.edu/lco/action/doc/retrieve/docid/patch_f/7353031?cesid=5laxa31uePu&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dlitfulo%26t%3Dname%26acs%3Dfalse%26acq%3Dlitfulo. 

Messenger A. Alopecia areata: Management. UpToDate. November 2, 2023. Accessed April 23, 2024. https://www-uptodate-com.jerome.stjohns.edu/contents/alopecia-areata-management?search=alopecia+areata+treatment&source=search_result&selectedTitle=1~80&usage_type=default&display_rank=1#H3. 

Alopecia is a medical condition involving the loss of hair on varying parts of the body including eyebrows, eyelashes, and primarily the scalp. This can be the result of aging, hormones, stress, medical conditions, medications, anemia, infections, and various other conditions. It can affect any gender temporarily or permanently, reducing the individual’s quality of life. It is important to assess for any risk factors or lifestyle behaviors that may induce alopecia. Recognizing the cause allows us to directly treat it, otherwise, patients are left with an array of treatment options. 

In alopecia, the hair follicles may be preserved, allowing for regrowth and reversal of the loss. There are many types of alopecia such as alopecia areata, androgenetic alopecia, chemotherapy-induced alopecia, frontal fibrosing alopecia, trichotillomania alopecia, etc. Androgenetic alopecia is hereditary alopecia in which we can see male-pattern baldness or female-pattern baldness. This is the most common type of alopecia, with a 2019 multicenter retrospective study reporting a frequency of 37.7% of androgenetic alopecia. Alopecia areata is a chronic immune-mediated disease resulting in patchy hair loss on the scalp, affecting children and adults of all ages. That same study respectively reported an 18.2% frequency.

The Severity of Alopecia Tool (SALT) score guides providers in therapeutic decision-making in alopecia areata patients. After dividing the scalp into four quadrants, the percentage of hair loss is estimated, allowing provides to monitor therapeutic response. Laboratory testing should be performed to find underlying causes or comorbidities. Tests may include a CBC, CMP, iron panel, and TSH levels. Many patients are referred to specialists such as dermatologists to further inquire into the cause of the hair loss. 

In the case of androgenetic alopecia, treatments target hair loss prevention as opposed to regrowth. First-line treatments include oral finasteride and/or topical minoxidil. Minoxidil is available over the counter as a generic product or popular topical Rogaine in drugstores. it is important to note that results are not seen immediately and may take 2-3 months to be seen. Patients can opt for other treatments offered in dermatology clinics that are not covered by insurance. Laser therapy, micro-needling, and platelet-rich plasma injections have shown efficient results. A popular cosmetic trend on the rise at the moment is hair transplants. Many countries offer affordable prices and are both reputable and successful, showing promising results. An overlooked treatment option is ensuring patients are receiving nutritious diets. Nutritional deficiencies are a common cause of hair loss.

Alopecia has no negative harm to the body physically, however, the emotional and psychological effects make all parties vulnerable to society’s eyes. People become more self-conscious and anxious, lowering their self-esteem. For patients unable to afford the stated treatment methods, an Ayurvedic approach may be more feasible. With the rising trends seen online and passed down generations, rosemary oil, and castor oil have been sold religiously on various sites and shops. Beauty and Ayurvedic companies have released serums and supplements that encourage hair regrowth. It is both the provider's and the patient’s responsibility to see what treatment options best work for the patient.

References

1. https://www.ncbi.nlm.nih.gov/books/NBK538178/

2. https://my.clevelandclinic.org/health/diseases/12423-alopecia-areata

3. https://www.niams.nih.gov/health-topics/alopecia-areata

4. https://www.aad.org/public/diseases/hair-loss/types/alopecia

Alopecia areata is a disease that happens when the immune system attacks hair follicles and causes hair loss. While hair can be lost from any part of the body, alopecia areata usually affects the head and face. Hair will typically fall out in small, round patches about the size of a quarter. Researchers do not fully understand what causes the immune attack on the hair follicles, but it is believed that both genetic and environmental factors play a role. In some more severe cases, hair loss is more extensive. Most people with the disease are healthy and have no other symptoms but the loss of hair. Alopecia areata is not the same for every person who suffer from the disease. Some will have hair loss throughout their lives while others may only have a few episodes of it and it will all grow back. There is no define cure for alopecia areata but there are treatments to help the unwanted side effects of hair loss, by helping the hair grow back quicker.

Alopecia areata equally effects men and women, as well as all racial and ethnic groups. The onset of the disease can be any age, but most people experience it in their teens, twenties and thirties. Having family with the disease presents you to have a higher risk of getting alopecia areata. People with certain autoimmune disease like psoriasis, thyroid disease or vitiligo are more likely to get alopecia areata.

Alopecia areata usually presents in three types of clinical presentations. Patchy alopecia, this type is the most common, hair loss happens in one or more coin-sized patches on the scalp or other parts of the body. Alopecia totalis, is when people lose all or nearly all of the hair on their scalp. Lastly, Alopecia universalis, in this type which is the most rara form of alopecia, there is a complete or nearly complete loss of hair on the scalp, face and rest of the body. Overall, alopecia areata primarily effects the hair. It begins with a sudden loss of round or oval patches on the scalp, but any part of the body may be affected such as the bear area in men. Around the edges of the patch there are often short or broken hairs or “exclamation point” hairs that are narrow at their base than their tip. There are some cases, where alopecia areata is said to change people’s nails as well.

There is no cure for alopecia but managing the symptoms to regrow hair is important. A lot of the times, hair grows back without any type of treatment. For people with less severe cases, no treatment may be needed. A lot of people will decide to not have medical treatment or procedures but instead cosmetic products such as hair pieces or wigs. If choses to use medication in treating hair regrowth the regimen is based on the patient’s demographics. Overall, alopecia areata is a immune disease that doesn’t have a solidified cure. It does not have many symptoms other than hair loss, however, this can be very emotionally painful.

References:

https://www.niams.nih.gov/health-topics/alopecia-areata/diagnosis-treatment-and-steps-to-take

https://www.mdpi.com/1422-0067/23/3/1038

General overview of alopecia

Alopecia, characterized by the absence or loss of hair in expected areas, can manifest in various forms affecting individuals across age groups and genders. Patients often experience distress, impacting their quality of life. Effective management relies on identifying the underlying cause through thorough history, examination, and evaluation.

Nonscarring alopecias, where hair follicles are retained, include androgenetic alopecia. It is prevalent in men and women, and it stems from altered follicle cycling, driven by genetic and hormonal influences. Alopecia areata, an immune-mediated disease, presents as patchy hair loss, with an unpredictable, relapsing-remitting course. Telogen effluvium, triggered by various factors, results in reversible hair shedding.

In contrast, scarring alopecias, where hair follicles are permanently damaged, predominantly affects postmenopausal women, showcasing a band of frontal hairline alopecia. It presents with patches of irregular alopecia on the scalp vertex. Secondary cicatricial alopecias have diverse causes, including scleroderma and neoplasms.

Diagnosis relies on a detailed history and physical examination. Dermoscopy aids in visualizing structures, and the hair pull test evaluates shedding. Laboratory tests, including a complete blood count and scalp biopsy, may be necessary for rare cases. 

Topical therapies, especially for early or mild-to-moderate hair loss, offer a potential solution for individuals averse to systemic side effects associated with oral medications. Topical minoxidil is among the three FDA-approved treatments for androgenetic alopecia (AGA). Available in 2% and 5% foam and liquid formulations, minoxidil's efficacy lies in its ability to prolong the anagen phase, increase hair diameter and density, and stimulate cutaneous blood flow. 

Side effects of topical minoxidil are generally low, with irritant and allergic reactions more common in 5% solutions. The foam variant, lacking propylene glycol, minimizes skin irritation. Application frequency is crucial, requiring once or twice daily use for 4–8 months to observe hair growth, stabilizing after 12–18 months. Discontinuation may lead to progressive hair loss within 12–24 weeks.

Topical finasteride, a Type II 5-alpha-reductase inhibitor, is available through compounding pharmacies. While studies indicate its efficacy in reducing plasma and scalp DHT levels, formulations vary, making it challenging to determine overall efficacy. Potential side effects include skin erythema, contact dermatitis, and increased liver enzymes. Its once-daily regimen requires chronic use, with limited data on patient compliance.

Oral therapies, often favored for moderate AGA, come with more side effects. Oral finasteride, approved since 1997, inhibits Type II 5-alpha-reductase, with 1 mg tablets indicated for male pattern baldness. Long-term use has shown significant hair growth, but side effects include orthostatic hypotension, erectile dysfunction, and ejaculatory dysfunction. Persistent sexual side effects raise concerns, and patients need screening.

Oral dutasteride, a second-generation 5-alpha-reductase inhibitor, is three times more potent than finasteride. Studies show superior efficacy, blocking 98.4% of DHT. Side effects, including decreased libido and erectile dysfunction, parallel those of finasteride. Once-daily oral use ensures patient compliance.

Oral minoxidil, though not FDA-approved, shows promise, especially for female AGA. Studies suggest effectiveness at low doses, with systemic side effects like increased heart rate and weight gain. Despite being convenient, its side effects make it less favorable than topical minoxidil.

Spironolactone, a widely used antiandrogen, has shown efficacy in female pattern hair loss. Flutamide and bicalutamide, though effective, carry risks of hepatic injury

Microneedling, as a safe and effective adjuvant therapy, stimulates growth factors and dermal papilla-associated stem cells, leading to collagen formation and wound regeneration. Combining microneedling with 5% minoxidil lotion has shown significant improvements in hair density and thickness. Common side effects include pain, bruising, and folliculitis, and patient compliance is crucial due to the procedure's cost and discomfort.

Hair transplantation, considered for patients who have failed medical therapy or have significant hair loss, induces a natural-looking appearance that lasts permanently. The procedure, performed in-office, comes with potential side effects and a significant cost for a single treatment, with an uncertain cost over five years.

References:

Al Aboud AM, Zito PM. Alopecia. [Updated 2023 Apr 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-

Caserini M, Radicioni M, Leuratti C, Terragni E, Iorizzo M, Palmieri R. Effects of a novel finasteride 0.25% topical solution on scalp and serum dihydrotestosterone in healthy men with androgenetic alopecia. Int J Clin Pharmacol Ther. 2016;54(1):19‐27

Dhurat R, Sukesh M, Avhad G, Dandale A, Pal A, Pund P. A randomized evaluator blinded study of effect of microneedling in androgenetic alopecia: a pilot study. Int J Trichology. 2013;5(1):6‐11

Dinh QQ, Sinclair R. Female pattern hair loss: current treatment concepts. Clin Interv Aging. 2007;2(2):189‐199

Nestor MS, Ablon G, Gade A, Han H, Fischer DL. Treatment options for androgenetic alopecia: Efficacy, side effects, compliance, financial considerations, and ethics. J Cosmet Dermatol. 2021 Dec;20(12):3759-3781

Olsen EA, Whiting D, Bergfeld W, et al. A multicenter, randomized, placebo‐controlled, double‐blind clinical trial of a novel formulation of 5% minoxidil topical foam versus placebo in the treatment of androgenetic alopecia in men. J Am Acad Dermatol. 2007;57(5):767‐774

Chemotherapy-induced alopecia refers to the transient loss of hair as a consequence of systemic cancer therapy. Alopecia is a distressing condition that occurs in approximately 65% of patients receiving cytotoxic agents. The condition significantly impacts the quality of life of patients, adding to the overall burden of cancer diagnosis and chemotherapy. The psychological impact on patients may be severe, leading to suboptimal therapy, refusal, or delay of therapy.

            The pathophysiology of chemotherapy-induced alopecia involves damage to rapidly dividing hair follicle cells by chemotherapeutic agents. Hair follicles continuously cycle through three stages – anagen (growth), catagen (regression), and telogen (rest) – with approximately 90% of scalp hair follicles in the anagen stage (differentiating and dividing) at any given time. Keratinocytes of the hair follicle matrix are highly proliferative during the anagen stage and highly sensitive to toxins and medications; inhibition of these keratinocytes leads to anagen effluvium. The risk of alopecia depends on the specific agent, route of administration, dose, and schedule of chemotherapy. High-dose, intermittent, intravenous, and combination regimens are associated with a high incidence of complete or total alopecia. Cytotoxic agents with the highest risk include alkylating agents such as intravenous cyclophosphamide and ifosfamide (>60%); anti-microtubule agents such as paclitaxel, docetaxel, and doxorubicin (80%); and topoisomerase inhibitors such as etoposide (60% to 100%).

            The manifestations of chemotherapy-induced alopecia involve partial or complete absence of hair from any area with normal hair growth on the body. Alopecia is most prominent on the scalp (particularly the crown and frontal areas); total scalp alopecia is common but can appear patchy. Loss of eyebrows and eyelashes, extremity and pubic hair is variable and typically regrows faster than scalp hair. Alopecia is usually reversible within three to six months after therapy cessation, as chemotherapy specifically targets proliferating cells and spares those responsible for follicle growth initiation. In some cases, specifically with docetaxel doses of 75 mg/m2 or higher per cycle, patients may experience prolonged or permanent alopecia. In one prospective study of breast cancer patients, prolonged chemotherapy-induced alopecia was assessed at six months and three years at 39.5% and 42.3%, respectively. Complications of alopecia are largely psychological, contributing to emotional distress and decreased self-esteem and quality of life.

            Management of chemotherapy-induced alopecia includes preventive measures and supportive care. Scalp hypothermia (scalp cooling) may be offered to patients with solid tumors, receiving bolus or short-term infusion chemotherapy regimens associated with moderate or high risk of alopecia. The mechanism of scalp hypothermia involves local vasoconstriction of blood vessels, resulting in reduced delivery of chemotherapy to hair follicles in the scalp. Efficacy of scalp hypothermia depends on the type and intensity of planned chemotherapy, with less preservation in patients receiving anthracycline regimens. The decision to pursue therapy should be individualized based on contraindications/precautions, potential side effects (such as discomfort, cold intolerance, and headache), time requirements, and cost. Cost depends on the number of cycles and cooling device used but is estimated to range between $1500 and $3000 per patient.

            Research into potential pharmacological interventions for preventing or minimizing chemotherapy-induced alopecia is ongoing. The interventions with supporting evidence include topical and oral minoxidil, oral finasteride, spironolactone, and topical calcitriol. However, the mentioned interventions have not been approved by regulatory agencies for this indication and require further efficacy and safety data. In the meantime, it is essential to discuss the potential of alopecia before chemotherapy and consider alternatives, if medically feasible. Nonpharmacological options such as wigs and head coverings aid in cosmetic coping, while psychosocial support is crucial for emotional well-being.  

References

Chon SY, Champion RW, Geddes ER, Rashid RM. Chemotherapy-induced alopecia. J Am Acad Dermatol. 2012 Jul;67(1):e37-47. https://www-sciencedirect-com.jerome.stjohns.edu/science/article/pii/S0190962211003124

Rossi A, Fortuna MC, Caro G, et al. Chemotherapy-induced alopecia management: clinical experience and practical advice. J Cosmet Dermatol. 2017 Dec;16(4):537-41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540831/

Rugo HS, van den Hurk C. Alopecia related to systemic cancer therapy. Wolters Kluwer: UpToDate. 2023 Aug. https://www-uptodate-com.jerome.stjohns.edu/contents/alopecia-related-to-systemic-cancer-therapy#H1

Wikramanayake TC, Haberland HI, Akhundlu A, et al. Prevention and treatment of chemotherapy-induced alopecia: what is available and what is coming? Curr Oncol. 2023 Mar;30(4):3609-26. https://www.mdpi.com/1718-7729/30/4/275

Alopecia Areata

          Alopecia Areata (AA) is an autoimmune inflammatory disease that causes nonscarring hair loss. It can affect any gender or age, prevalent in about 2% of the population. AA is shown in patients with round or oval patches. The patches can be seen in any area that has hair including the scalp. body, or eyebrows. The hair follicle goes through three life stages. When a patient has Alopecia Areata, the phases of the hair follicle are disrupted. AA incidence is higher in patients with a family history of the disease. Alopecia Areata is linked to HLA genes, such as HLA-DQB1*03, HLA-C*04:01, and HLA-DR. There is also an increased prevalence of Alopecia Areata in monozygotic twins. The reason for the connection is unknown, however, there is a connection.  It is induced by the JAK pathway, involving type 1 cytokines, specifically CD4+ and CD8+. These lymphocytes attack the hair follicle, causing inflammation, inhibiting growth, and changing the follicle’s life cycle.  Environmental factors, such as stress, can contribute to the hair loss. Many patients experience hair loss without symptoms. Some may experience tingling, itching, or sensations in the area they are losing hair. Other symptoms include nail changes, such as brittle nails, striations, and pitting.

           When treating Alopecia Areata, one must take into consideration the age of the patient, the severity of the disease, and the disease phase (acute or chronic). The first line treatment of Alopecia is topical immunotherapy. These include squaric acid dibutylester (SADBE) and diphenylcyclopropenone (DPCP). It is recommended in patients with moderate to severe AA, regardless of age. Intralesional corticosteroid injection has been analyzed in an open-label randomized study. In this study, the triamcinolone acetonide injection increased hair growth in patients with localized AA. These patients experienced a decrease in type 1 and 2 cytokines and IL-23. However, pediatric patients should avoid the injection. Topical corticosteroids were shown to have the benefits of regrowing hair in patients with moderate or severe AA. Some side effects are experienced which are folliculitis and skin atrophy. Studies showed the benefits of oral corticosteroids, however, relapse occurred after discontinuation. Other treatments include cyclosporine, methotrexate, sulfasalazine, and minoxidil.

              Hair loss impacts the social and mental life of people of all ages. It can lead to low self-esteem, depression, and a low quality of life. Treatment plans can vary, and so can the success rate. There are many treatments that fail for some but work for others. In addition, the risk of relapse is always a threat. However, it is key to have hope and never give up.

Juárez-Rendón KJ, Rivera Sánchez G, Reyes-López MÁ, García-Ortiz JE, Bocanegra-García V, Guardiola-Avila I, Altamirano-García ML. Alopecia Areata. Current situation and perspectives. Arch Argent Pediatr. 2017 Dec 1;115(6):e404-e411. English, Spanish. doi: 10.5546/aap.2017.eng.e404. PMID: 29087123.

Strazzulla LC, Wang EHC, Avila L, Lo Sicco K, Brinster N, Christiano AM, Shapiro J. Alopecia areata: Disease characteristics, clinical evaluation, and new perspectives on pathogenesis. J Am Acad Dermatol. 2018 Jan;78(1):1-12. doi: 10.1016/j.jaad.2017.04.1141. PMID: 29241771.

Zhou C, Li X, Wang C, Zhang J. Alopecia Areata: an Update on Etiopathogenesis, Diagnosis, and Management. Clin Rev Allergy Immunol. 2021 Dec;61(3):403-423. doi: 10.1007/s12016-021-08883-0. Epub 2021 Aug 17. PMID: 34403083.

Alopecia, or hair loss, is a common concern for many individuals, and it can also occur during pregnancy. Pregnancy triggers significant hormonal fluctuations in the body, particularly an increase in estrogen levels. While estrogen is known to promote hair growth, the hormonal changes during pregnancy can disrupt the normal hair growth cycle. This disruption can lead to excessive shedding and hair loss in some pregnant women. Telogen effluvium is a common type of hair loss characterized by the premature entry of hair follicles into the resting (telogen) phase. Pregnancy-related factors such as hormonal changes, physical stress, or nutritional deficiencies can trigger telogen effluvium, resulting in noticeable hair shedding.

Hair loss can have a profound psychological impact on pregnant women, affecting their self-esteem and body image. Pregnancy itself brings about various physical and emotional changes, and experiencing hair loss during this time can add to feelings of distress and insecurity. Expectant mothers may feel anxious or concerned about the underlying cause of their hair loss and its potential impact on their overall health or the health of their baby. These emotional burdens can contribute to heightened stress levels, which may further exacerbate the condition. Consuming a well-balanced diet rich in essential nutrients can support hair health during pregnancy. Foods containing vitamins, minerals, and proteins, such as leafy greens, eggs, nuts, and fish, can provide the necessary building blocks for healthy hair growth. Adopting gentle hair care practices can help minimize hair loss and damage. This includes avoiding excessive heat styling, minimizing the use of chemical treatments, and using a wide-toothed comb or brush to prevent hair breakage. Engaging in stress-reducing activities, such as meditation, yoga, or prenatal exercise, can help manage stress levels and potentially reduce hair loss associated with pregnancy. Seeking support from loved ones or joining support groups can also provide emotional comfort during this time. If hair loss persists or becomes excessive, it is advisable to consult a healthcare professional, such as a dermatologist or obstetrician/gynecologist. They can assess the underlying cause of the alopecia and provide appropriate guidance and treatment options tailored to the individual's needs. It is important to note that most cases of alopecia during pregnancy are temporary, and hair regrowth typically occurs naturally after childbirth. However, if hair loss continues or worsens after delivery, further evaluation may be necessary to rule out other underlying causes.

Alopecia during pregnancy, though distressing, is often a temporary condition attributed to hormonal changes and the body's response to pregnancy-related factors. Managing hair loss during this time involves adopting healthy lifestyle practices, seeking emotional support, and consulting healthcare professionals when needed. It is crucial for expectant mothers to remember that hair regrowth commonly occurs after childbirth. By addressing the psychological impact, practicing self-care, and seeking appropriate medical guidance, pregnant women experiencing alopecia can navigate this condition with support and confidence.

Hair Loss During Pregnancy. (n.d.). American Pregnancy Association. https://americanpregnancy.org/healthy-pregnancy/pregnancy-health-wellness/hair-loss-during-pregnancy/

Alopecia Areata

Alopecia areata is an autoimmune condition that manifests as non-scarring hair loss. It is a form of alopecia that affects the hair follicles, nails, and in rare cases, the retinal pigment epithelium. Symptoms include distinguished smooth, round patches of hair loss without atrophy. Further, one can expect nail abnormalities— the most common form is nail pitting, although other nail abnormalities include trachyonychia, Beau’s lines, onychorrhexis, nail thinning or thickening, and others. Thyroid disease, vitiligo, and atopy are associated conditions with alopecia areata. According to a systematic review, alopecia areata has a global incidence of around 2%. This condition can occur at any age, however 33 is the median diagnosed age. It is found that male patients are more likely to be diagnosed in childhood while females are diagnosed in adolescence with nail involvement or concomitant autoimmune diseases. A positive hair pull test or trichoscopy are assessments used to determine alopecia areata diagnosis. Trichoscopy is the process of examining the scalp and hair using a video dermoscopy device. Findings are characterized by yellow dots, black dots, “exclamation marks” or tapering hairs, and broken hairs. In uncertain situations, a biopsy may be performed.

The exact mechanism of alopecia areata is unclear. There is evidence that genetic and environmental factors may trigger an autoimmune reaction against the hair follicles. The hair follicle-cycling process is impaired as a result of inflammatory cells attacking the hair follicle matrix epithelium. The hair follicles are able to re-enter the anagen phase (growth phase where the hair follicle forms a new hair shaft), but cannot progress past the anagen III/IV stage. Likewise, those with a family history of alopecia areata are more likely to develop this condition. According to a meta-analysis, one of the biggest risk factors are individuals who have the human leukocyte antigen-DR (HLA-DR) on chromosome 6. This gene belongs to the HLA class II gene and is associated with effector cells, CD4+ and CD8+ T-cells, involved in alopecia areata. Moreover, the protein BCL2-like protein 11 (BIM) responsible for regulation of autophagy, plays a role in the pathogenesis of alopecia areata. Stress may worsen or induce alopecia areata. Based on a mouse model, it was found that there was higher activity of the central and peripheral hypothalamus pituitary adrenal axis compared to the normal mice. Elevated levels of the adrenocorticotropic hormone, corticosterone, and estradiol are linked to high pro-inflammatory cytokine levels in the skin, all of which contribute to alopecia areata. Additionally, infections, vaccinations, hormonal fluctuations, and diet are potential factors.

Treatment involves the use of corticosteroids, immunotherapy, or light therapy. Intralesional and topical corticosteroids are considered first-line treatment. Corticosteroids work by reducing inflammation and quickens the recovery of damaged hair follicles. During topical corticosteroid treatment, about 57% of patients showed complete hair regrowth. On the other hand, the use of intralesional corticosteroids showed 63% complete hair regrowth within 4 months. One of the main side effects if corticosteroid therapy is used is an increased risk of cutaneous atrophy at the site of treatment. In refractory cases, systemic corticosteroids are used, which showed 62% of patients having full hair regrowth. It is shown that triamcinolone acetonide dosed 5-10 mg per mL given every 2-6 weeks stimulates localized regrowth in 60-67% of cases. In one study, intralesional triamcinolone acetonide with varying concentrations – 2.5 mg/mL, 5 mg/mL, and 10 mg/mL showed similar rates of hair regrowth irrespective of concentration. It is important to note that a higher concentration of triamcinolone acetonide, 10 mg/mL, is associated with the risk of cutaneous atrophy. Regardless of therapy, there are high relapse rates in alopecia areata. Further, topical immunotherapy may be a treatment option for those who experience greater than 50% scalp hair loss, and is also optimal for those who do not want injection therapy with intralesional corticosteroids. To precipitate hair growth, the contact allergen, diphenylcyclopropenone (DPCP) or squaric acid dibutyl ester (SADBE) is applied weekly to the scalp. A meta-analysis showed 74.6% of hair regrowth in those experiencing patchy alopecia.

Although alopecia areata is not harmful or affects mortality, it may lead to lack of self-confidence, social anxiety, and depression in affected individuals. Thus, it is important to identify and address patient concerns when discussing the most optimal treatment option.

References

“Alopecia Areata.” National Institute of Arthritis and Musculoskeletal and Skin Diseases, 14 June 2022, www.niams.nih.gov/health-topics/alopecia-areata/diagnosis-treatment-and-steps-to-take.

Darwin, Evan, et al. “Alopecia Areata: Review of Epidemiology, Clinical Features, Pathogenesis, and New Treatment Options.” International Journal of Trichology, Apr. 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC5939003/.

Lepe, Kenia, and Patrick M Zito. “Alopecia Areata - Statpearls - NCBI Bookshelf.” Alopecia Areata, www.ncbi.nlm.nih.gov/books/NBK537000/. Accessed 12 June 2023.

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.