© Springer International Publishing Switzerland 2017Katlein França and Mohammad Jafferany (eds.)Stress and Skin Disorders10.1007/978-3-319-46352-0_16
16. Stress Related Hair Disorders
Department of Dermatology, Medical University of Warsaw, Warszawa, Poland
KeywordsStressHair LossHair CycleTelogen EffluviumAlopecia Areata
Stress is an established and proven trigger of mental illness’ development and stress-related disorders. It also provokes various skin and hair changes. The mechanisms are still not entirely discovered. Stress is a common possible cause of hair loss and other hair disorders. There have been published studies proving that stress alters hair growth and cycling in vivo in a murine model  confirmed by clinical observations of those disruptions in people.
Historically, samples of serum, saliva, and urine were used to measure cortisol levels . Hair cortisol analysis is a new, non-invasive method providing an information about a previous cortisol secretion in response to stress [3, 4]. This innovative method could be useful primarily in the field of psychiatry, however it reflects a chronic stress, that commonly results in hair disorders, like alopecia, greying, trichotillomania or alopecia areata.
The existence of a ‘brain-hair follicle axis’ (BHA) has been postulated in recent years as the patomechanism of various skin changes triggered by a stress stimulus. It consists of a chain of stimulatory hormones and feedback loops under the control of higher cerebral centres determining its overall activity . Cortisol is at the centre of a pathophysiological stress response. The brain-follicle axis explains the patomechanism of hair changes in case of stress-triggered hormonal changes, like hypercortisolism and up-regulation of CRH. Widely used topically active hair growth stimulator- minoxidil prevents a stress-triggered hair growth by down-regulation of the BHA . As a result, it has been proven that minoxidil is not only effective in female androgenetic alopecia but, what is clinically often observed it helps numbers of patients with stress-induced hair loss.
For years stress has been suspected as a possible cause of hair loss , especially through an impact on hair follicle cycle.
The hair growth cycle consists of three main phases: anagen (growth phase), catagen (regression phase) and telogen (resting phase). Catagen is related to cessation of protein and pigment production, involution of the hair follicle and restructuring of the extracellular matrix. It precedes a telogen resting phase, when the hair follicle regresses. Increased telogen hairs ratio clinally cause hair loss [7, 8].
There is a great number of factors which have an impact on hair follicle cycle. A fascinating and composed pilo–neural–immune interactions and immune cells cross-react during the hair cycle. Numerous growth factors, cytokines, hormones and neuropeptides involved in a systemic stress response also act directly on hair cycle [9–11]. Stress causes a cascade of hormonal changes in the organism. Hormones affect follicular mesenchymal-epithelial interactions altering growing time, dermal papilla size and dermal papilla cell, keratinocyte and melanocyte activity . Highly stress-vulnerable areas of the hair follicle are stem cells in the bulge region. Stress -changes could have wide-ranging consequences. This direct impact of stress and hormonally driven changes in hair cycle are explained by novel data indicating the existence of a ‘brain-hair follicle axis’ (BHA) . It has been proven that there are hormones produced locally in the skin, where adequate receptors are also located. Cortisol and corticotropin-releasing hormone (CRH), the main hormones of the stress, are upregulated by stress, being released directly in the skin as a part of the BHA . This causes a direct proinflammatory effect or activates mast cells. Among the neuromediators neuropeptide substance P (SP) is proposed to be a potential mediator by which stress exerts its inhibitory influence on hair growth [14, 15]. Stress-induced hair follicle apoptosis could also be driven by activated perifollicular macrophages and through a degranulation of mast cells which leads to an intense local inflammation. That results in destruction of the hair root as a consequence of stress-mediated mast cells degranulation . Recently, it has been proven that exposure to an experimental psychoemotional stressor provokes a premature catagen and results in excessive telogen hairs ratio . Changes of the hair growth cycle therefore result in alopecia. Telogen effluvium and alopecia areata are the most tightly associated with stress due to pathogenesis. However every type of hair loss results in a psychological impact that lowers quality of life and aggravates the stress.
Telogen effluvium (TE) was first described by Kligman in 1961. It is a most common cause of diffuse hair loss. There is a wide variety of potential triggers evoking telogen effluvium hair loss. Stress is one of them. Diffuse shedding of telogen hair takes place 3–4 months after a triggering, stressful event. It is diagnosed when the hair loss refers to changes in trichogram with anagen to telogen ratio less than 70:30 % of hairs . Telogen effluvium could occur as an acute (ATE) and chronic telogen effluvium (CTE). When acute telogen effluvium is related do stressful events, chronic TE is rather accompanying chronic illnesses. A sudden onset and great amounts of shedding hairs could bring some fear and upregulate existing psychological problems. The triggering factors are numerous. It could be a stress, an illness, metabolic changes, hormonal fluctuations, diet and malnutrition, vitamins and minerals deficiencies . However, the severity of the hair loss here depends on the intensity and duration of exposure, rather than on the type of a trigger . It also should be noticed that psychological stressful event and chronic imflammatory illnesses which cause a medical stress to organism result in the same hormonal and BHA changes in hair follicle cycling.
Despite the diagnostic process, the trigger in telogen effluvium (especially in its chronic type) often cannot be clearly defined. Also the real frequency of TE in the population seems to be underestimated as some part of the cases, especially those of chronic telogen effluvium are subclinical . The most typical target group of acute TE are women after the childbirth (30–50 % of women have postpartum TE). However, in repeated studies women, especially older in age, seem to be more susceptible to acute form of telogen effluvium . According to Whiting chronic telogen effluvium probably affects only women . The most frequently it affects women aged 30–60 years and starts abruptly with or without a recognizable initiating factor. CTE is in fact considered as an age-related problem in women . In TE a normal thickness of hairs and characteristic shorter regrowing hairs especially in the frontal and bitemporal areas could be observed in trichoscopy. Few patients may have a marked bitemporal recession. Hair pull test is commonly positive. However, a diagnosis of TE is always out of the exclusion of other causes of chronic diffuse hair loss .
Alopecia areata (AA) is a nonscarring loss of hair on the skin of the head with possible affecting the entire skin of the head (alopecia totalis) or the entire body (alopecia universalis). The frequency in general population is estimated to be 0.2 and 2.1 % amongst dermatological ambulatory patients (Rochester Epidemiology Project, 1990–2009) . Alopecia areata frequently starts in childhood, and, 60 % of patients with AA are younger than 20 . The occurrence of the disease depends on the interaction between genetic factors, autoimmune and hormonal changes, psychological factors and disorders of the nervous system. The role of psychological factors, like acute or chronic stress in the course of AA is especially important [26, 27]. An emotional trauma associated with actual or symbolic loss, like death of a close individual, divorce, loss of job etc., commonly occurred prior to the first episode of the disease in 66 % of patients . Other disorders that can also be triggered by a stress and/or commonly coexist with AA are: diabetes, Hashimoto disease, psoriasis, atopic dermatitis, urticaria, angioedema. As it has been proven exposure to chronic stress induce a chronic course of alopecia areata. It is at least partly explained by a correlation of stress and changes in brain-hypothalamic-pituitaryadrenal axis (BHA), or immune and endocrine systems. However the exact patomechanism is still under investigation .
Trichotillomania is a form of traction alopecia resulting from habitual, repetitive removal of one’s own hair [29–31]. From a psychiatric point of view, this term encompasses an entire syndrome of pathologic hair pulling. According to the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), the diagnostic criteria for trichotillomania are (a) the recurrent pulling out of one’s own hair, resulting in noticeable hair loss; (b) an increasing sense of tension immediately before pulling out the hair or when attempting to resist the behavior; (c) pleasure, gratification, or relief when pulling out the hair; (d) hair pulling that cannot be better accounted for by another mental disorder; and (e) significant distress or impairment in social, occupational, or other important areas of functioning . This definition describes a mental disorder that perhaps should be called trichotillomania syndrome. Accordingly, the validity of the DSM-IV criteria recently was questioned by several authors [32, 33]. From a dermatologist’s point of view, trichotillomania is self-induced hair loss due to the repetitive pulling of one’s own hair [34, 35].
The condition is most frequently among children between the ages of 9 and 13 years and with a female predominance of 70–93 % . Adult-onset trichotillomania possibly reveal an underlying psychiatric disorder . Clinically, patients present patches of irregular-length hair or hairless areas. Commonly, the vertex is affected, what is characteristically named “tonsure trichotillomania,” or the “Friar Tuck sign”. Pull test is negative. Patients may pull hair at multiple sites, including the eyebrows, eyelashes, face, arms, legs, and pubic area [34, 35].
Trichotillomania is currently easily diagnosed by trichoscopy. The flame hairs, coiled hairs and presence of multiple broken hairs in a field of view are now considered the most typical trichoscopy signs of trichotillomania.
Stress and Chemotherapy Induced Alopecia
Chemotherapy-induced alopecia (CIA) is almost a constant side effect of chemotherapy . The incidence and severity of CIA could by various and dependent on the chemotherapy protocol, but general prevalence of CIA is estimated to range from 65 to 85 % of chemotherapy patients . Hair loss in this condition is associated with impaired regrowth of hair that are shorter, thinner and more fragile. Mechanisms connected to this process are multiple and depending on the type of chemotherapeutic agent. CIA is usually linked to apoptosis-related damage to the hair follicle . It affects mainly scalp hair causing widespread alopecia especially in women and affecting the most intensely frontal and occipital hairlines [37, 39, 40]. It starts as anagen effluvium or rarely as telogen effluvium  in the first weeks after the initiation of the therapy . The severity and the exact mechanism depends on the agent. Reversibility of alopecia is typical. Coping with cancer and with chemotherapy is a highly stressful situation. Associated telogen effluvium starting with a delay after anagen hair loss commonly takes part in a burden of alopecia.
The psychosocial impact of CIA is problematic, especially in women. Chemotherapy-induced alopecia stigmatizes patients and isolates them from the society. For women it is even more traumatic than losing breast [43, 44]). In a study with 638 cancer patients receiving chemotherapy, 86.6 % of women were worried about changes in their appearance and hair loss . Although chemotherapy-induced hair loss is a stressor for both women and men, existing studies confirm that female patients concern hair loss as a more severe stressor than it is concerned among male cancer patients . Among 47 % of female cancer patients who considered hair loss to be the most traumatic aspect of chemotherapy, 8 % consider a decision about a withdrawal of the chemotherapy because of the expected hair loss . A treatment of chemotherapy induced alopecia is highly needed, but still there are no recommended models of prevention and therapy. As there is still no approved treatment for patients with CIA, the research seeking for the drug, especially topical is highly needed. There are numbers of ongoing studies, however more studies must be performed to find the way out of this problem.
Cicatricial alopecia (CA) term refers to scarring hair loss. The prevalence according to different studies ranges from 2 to 7 % of he hair loss causes . The causes of CA could be classified as primary (PCA, primary cicatricial alopecias), secondary to various factors or hereditary/developmental defects [47, 48]. Cicatricial alopecia may occur secondary to trauma (burns, radiation, traction), extensive infiltrative processes (morphea, scleroderma, sarcoidosis, carcinomas) or infections . In contrast, primary cicatricial alopecias (PCA) are a group of disorders, in which the hair follicle is the main target of destructive inflammation resulting in irreversible hair loss . Primary cicatricial alopecias (PCA) represent uncommon inflammatory disorders that result in permanent loss of scalp hair. According to hormonal and neurophysiological changes during stressfull events, stress could be placed among factors which trigger or aggravate primary cicatricial alopecias.
Greying as a Result of Oxidative Stress
The perception of the grey hair is derived from the mixture of white non-pigmented and pigmented scalp hairs and it is called canities/or greying.
A relatively small number of melanocytes is capable to produce long pigmented hair shaft  however this enourmous capacity of melanocytes activity is greatest in the first few hair cycles and decreases with time as the cessation of melanogenesis seems to be genetically programmed. In certain situations triggered by a psychological stressor or resulting in a metabolic stress a premature or increased greying process could be observed . The underlying causes of this phenomenon are genetic and hormonal changes that come along with age and other possible coexisting factors. The cessation of melanogenesis resulting in a clinically grey hair shaft correlates with a reduction in tyrosinase activity of hair bulbar melanocytes . It is also thought that canities could be correlated with changes in innervation and neuropeptide stimulation, what could possibly refer to premature greying in some metabolic disturbances [53, 54]. Grey hair include only few melanocytes, highly vacuolated, defective as a result of oxidative stress [50, 55]. Metabolic and nutritional status, racial and gender differences, hormones, genes and age-related changes all impact on the regulation of hair pigmentation.
Coping with Stress Induced Hair Loss
Stress and hair loss are tightly associated. However, up to date, no specific medical intervention is available to manage stress-induced hair loss. On the other hand, stress-induced hair loss reduces the quality of life of affected patients and so, effective treatment of alopecia is more and more needed among patients who seek for help.
Minoxidil (MXL) was developed to treat hypertension. This ATP-sensitive potassium channel opener, has next been discovered as a topically applied stimulator of hair regrowth in androgenetic alopecia (AGA) [56–58] prolonging the anagen . In that mechanism stress-induced hair follicle changes can be prevented by MXL. Application of 5 % MXL results in a significant increase of Ki67p, marker of proliferating intrafollicular cells in the bulb, bulge and infundibulum. In addition MXL treatment had been demonstrated to cause an early initiation of anagen, decreasing period of kenogen with lack of hair .
Minoxidil then reverts stress-driven changes in hair follicle cycle and stress-induced hair loss (e.g. in patients with alopecia areata (AA) or telogen effluvium) [1, 6]. Its mechanism of action with respect to the stimulation of hair growth is unknown, but it appears to be independent of vasodilatation .