Burden of Hair Loss: Stress and the Underestimated Psychosocial Impact of Telogen Effluvium and Androgenetic Alopecia
2004; Elsevier BV; Volume: 123; Issue: 3 Linguagem: Inglês
10.1111/j.0022-202x.2004.23237.x
ISSN1523-1747
AutoresIna M. Hadshiew, Kerstin Foitzik, Petra Arck, Ralf Paus,
Tópico(s)Hair Growth and Disorders
ResumoHair loss, as it occurs with telogen effluvium and androgenetic alopecia, provokes anxieties and distress more profound than its objective severity would appear to justify. This reflects the profound symbolic and psychosocial importance of hair. Stress has long been implicated as one of the causal factors involved in hair loss. Recently, in vivo studies in mice have substantiated the long-held popular belief that stress can exert profound hair growth-inhibitory catagen-inducing and hair-damaging pro-inflammatory effects. Insights into the negative impact of stress on hair growth and the integration of stress-coping strategies into the management of hair loss disorders as well as the development of new pharmacotherapeutic strategies might lead to enhanced therapeutic modalities with the alleviation of clinical symptoms as well as the concomitant psychological implications. Hair loss, as it occurs with telogen effluvium and androgenetic alopecia, provokes anxieties and distress more profound than its objective severity would appear to justify. This reflects the profound symbolic and psychosocial importance of hair. Stress has long been implicated as one of the causal factors involved in hair loss. Recently, in vivo studies in mice have substantiated the long-held popular belief that stress can exert profound hair growth-inhibitory catagen-inducing and hair-damaging pro-inflammatory effects. Insights into the negative impact of stress on hair growth and the integration of stress-coping strategies into the management of hair loss disorders as well as the development of new pharmacotherapeutic strategies might lead to enhanced therapeutic modalities with the alleviation of clinical symptoms as well as the concomitant psychological implications. Although a benign medical condition, affected individuals experience great psycho-emotional stress, often leading to a reduction of quality of life and secondary morbidity. Some patients' suffering can reach a level where the burden of hair loss is comparable with that caused by many more severe chronic or life-threatening diseases (de Koning et al., 1990de Koning E.B. Passchier J. Dekker F.W. Psychological problems with hair loss in general practice and the treatment policies of general practitioners.Psychol Rep. 1990; 67: 775-778Crossref PubMed Google Scholar;Cash, 2001Cash T.F. The psychology of hair loss and its implications for patient care.Clin Dermatol. 2001; 19: 161-166Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar). In recent years, correlations between specific coping strategies and quality of life have emerged. Particularly, the development of better instruments for assessing quality of life has allowed identification and intervention of coping patterns (Table II) (Schmidt et al., 2001Schmidt S. Fischer T.W. Chren M.M. Strauss B.M. Elsner P.E. Strategies of coping and quality of life in women with alopecia.Br J Dermatol. 2001; 144: 1038-1043Crossref PubMed Scopus (60) Google Scholar). Stress has long been implicated as one of the causal factors involved in hair loss (Bosse and Gieler, 1987Bosse K.A. Gieler U. Seelische Faktoren bei Haustkrankheiten: Beiträge zur psychosomatischen Dermatologie. Verlag Hans Huber, Bern1987Google Scholar;Paus, 2000Paus R. Stress, hair growth control and the neuro-endocrine immune connection.Allergo J. 2000; 9: 611-620Google Scholar;Botchkarev, 2003Botchkarev V.A. Stress and the hair follicle: Exploring the connections.Am J Pathol. 2003; 162: 709-712Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar). With respect to the connections between psycho-emotional stress and hair loss, several levels of interactions can be distinguished: (a) acute or chronic stress as a primary inducer of telogen effluvium, (b) acute or chronic stress as an aggravating factor in a hair loss disorder whose primary pathogenesis is of endocrine, toxic, metabolic or immunological nature (e.g. AGA, alopecia areata), and (c) stress as a secondary problem in response to prior hair loss. The latter might also contribute to the perpetuation or aggravation of hair loss and induce a self-perpetuating vicious circle (Figure 1).Table ITable IPatient-perceived negative effects of hair lossaModified after van der Donk et al (1991) Cash et al (1993), Franzol et al (1990), and Girman et al (1999)• Shame• Feeling uncomfortable• Anger• Dissatisfaction with body image• Embarrassment• Feeling of being older• Humiliation• Sense of inadequacy• Disgrace• Loss if self-confidence• Hate• Unhappy about appearance• Disgust• Reduced worth• Fright• Reduced social acceptance• Sadness• Feelings of helplessness• Depression• Self-consciousness• Worrying• Social stress• Frustration• Powerlessnessa Modified after van der Donk et al (1991) Cash et al (1993), Franzol et al (1990), and Girman et al (1999) Open table in a new tab Recent studies in mice have substantiated the long-held popular belief that stress can exert profound hair growth-inhibitory catagen-inducing and hair-damaging pro-inflammatory effects, with a likely key role for substance P (SP) (Arck et al., 2001Arck P.C. Handjiski B. Hagen E. Joachim R. Klapp B.F. Paus R. Indications for a “brain–hair follicle axis (BHA)”: Inhibition of keratinocyte proliferation and up-regulation of keratinocyte apoptosis in telogen hair follicles by stress and substance P.FASEB J. 2001; 15: 2536-2538PubMed Google Scholar, Arck et al., 2003bArck P.C. Handjiski B. Peters E.M. Stress inhibits hair growth in mice by induction of premature catagen development and deleterious perifollicular inflammatory events via neuropeptide substance P-dependent pathways.Am J Pathol. 2003; 162: 803-814Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar) (Fig S1, see full-text version online) and corticotrophin releasing hormone (Aoki et al., 2003Aoki E. Shibasaki T. Kawana S. Intermittent foot shock stress prolongs the telogen stage in the hair cycle of mice.Exp Dermatol. 2003; 12: 371-377Crossref PubMed Scopus (31) Google Scholar). If transferable to the human system, the stress effects elucidated for murine hair follicles would result in a marked telogen effluvium under clinical conditions. Administration of a specific SP receptor (NK 1) antagonist can abrogate the stress-induced hair-growth-inhibiting or hair follicle-damaging effects in mice (Arck et al., 2001Arck P.C. Handjiski B. Hagen E. Joachim R. Klapp B.F. Paus R. Indications for a “brain–hair follicle axis (BHA)”: Inhibition of keratinocyte proliferation and up-regulation of keratinocyte apoptosis in telogen hair follicles by stress and substance P.FASEB J. 2001; 15: 2536-2538PubMed Google Scholar, Arck et al., 2003bArck P.C. Handjiski B. Peters E.M. Stress inhibits hair growth in mice by induction of premature catagen development and deleterious perifollicular inflammatory events via neuropeptide substance P-dependent pathways.Am J Pathol. 2003; 162: 803-814Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar).Table IITable IICoping strategies for diffuse and androgenetic alopeciaaModified afterSchmidt et al, 2001Pro-adaptiveMal-adaptive• Flexible coping: positive and constructive• Hair focused coping (hair-specific dysmorphophobia): social withdrawal, anger towards others, aimless reflection on hair loss• Bother minimizing: diversion, optimism, denial, acceptance, stoicism• Negative emotional: resignation, brooding, anxiety, self-accusationa Modified afterSchmidt et al., 2001Schmidt S. Fischer T.W. Chren M.M. Strauss B.M. Elsner P.E. Strategies of coping and quality of life in women with alopecia.Br J Dermatol. 2001; 144: 1038-1043Crossref PubMed Scopus (60) Google Scholar Open table in a new tab Stress-induced hair growth inhibition is promoted by nervegrowth factor (NGF) which appears to be up-stream of SP (Peters et al., 2004Peters E.M.J. Handjiski B. Kuhlmann A. Neurogenic inflammation in stress-induced termination of murine hair growth is promoted by nerve growth factor.Am J Pathol. 2004Abstract Full Text Full Text PDF Scopus (98) Google Scholar). These findings are noteworthy in two respects: They have identified missing molecular links between psycho-emotional stressors and well-defined parameters that reflect hair follicle growth and function—the neuropeptide SP and the neurotrophin NGF. In addition, the finding that an NK1 antagonist could counteract most of the stress-induced negative effects on the hair follicle is particularly intriguing since NK1 antagonists are under clinical investigation as a potential new class of anti-depressive drugs (Rupniak and Kramer, 1999Rupniak N.M. Kramer M.S. Discovery of the antidepressant and anti-emetic efficacy of substance P receptor (NK1) antagonists.Trends Pharmacol Sci. 1999; 20: 485-490Abstract Full Text Full Text PDF PubMed Scopus (260) Google Scholar). Therefore, it is tempting to speculate that NK1 antagonists might be especially well-suited to inhibit the adverse hair growth effects of psycho-emotional stress at the basis of the underlying molecular pathogenesis chain, while at the same time offering helpful pharmacotherapeutic support to allow affected patients with hair loss to break away from the depressing pyscho- and socio-dynamic vicious circles of hair loss (Figure 1). Besides SP, a plethora of other stimuli and mediators (neurotransmitters, neuropeptides, neurohormones, neurotrophins, etc.) must now be considered as potential local or systemic mediators of stress-induced hair growth inhibition—not the least since the hair follicle has been identified as both a prominent peripheral target organ and a source for many bioregulatory molecules recognized as mediators of stress responses (Paus and Cotsarelis, 1999Paus R. Cotsarelis G. The biology of hair follicles.N Engl J Med. 1999; 341: 491-497Crossref PubMed Scopus (883) Google Scholar;Paus, 2001Paus R. Stress and the skin.Exp Dermatol. 2001; 10: 367Crossref PubMed Google Scholar;Arck et al., 2001Arck P.C. Handjiski B. Hagen E. Joachim R. Klapp B.F. Paus R. Indications for a “brain–hair follicle axis (BHA)”: Inhibition of keratinocyte proliferation and up-regulation of keratinocyte apoptosis in telogen hair follicles by stress and substance P.FASEB J. 2001; 15: 2536-2538PubMed Google Scholar, Arck et al., 2003bArck P.C. Handjiski B. Peters E.M. Stress inhibits hair growth in mice by induction of premature catagen development and deleterious perifollicular inflammatory events via neuropeptide substance P-dependent pathways.Am J Pathol. 2003; 162: 803-814Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar;Botchkarev, 2003Botchkarev V.A. Stress and the hair follicle: Exploring the connections.Am J Pathol. 2003; 162: 709-712Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar;Peters et al., 2004Peters E.M.J. Handjiski B. Kuhlmann A. Neurogenic inflammation in stress-induced termination of murine hair growth is promoted by nerve growth factor.Am J Pathol. 2004Abstract Full Text Full Text PDF Scopus (98) Google Scholar). For example, in mice and/or man, hair follicle cycling, whose alteration lies at the basis of telogen effluvium (Paus and Cotsarelis, 1999Paus R. Cotsarelis G. The biology of hair follicles.N Engl J Med. 1999; 341: 491-497Crossref PubMed Scopus (883) Google Scholar), is modulated by catecholamins, prolactin, and nerve growth factor, three classical bioregulators of systemic stress responses. Stress responses, mediated by typical stress hormones, like catecholamines, prolactin, ACTH, CRH, β-endorphins, glucocorticoids, and SP, directly and indirectly may alter hair growth by interacting and disturbing the release of the various neuropeptides (Paus, 1999Paus R. The skin POMC system (SPS).in: Slominski A.T. Cutaneous Neuroimmunomodulation: The Proopiomelanocortin System. The New York Academy of Sciences, New York1999: 350-363Google Scholar;Slominski, 1999Slominski A. Cutaneous expression of CRH and CRH-R: Is there a “skin stress response system?”.in: Luger T. Paus R. Lipton J. Slominski A. Cutaneous Neuroimmunomodulation: The Proopiomelanocortin System. The New York Academy of Sciences, New York1999: 287-311Crossref Scopus (116) Google Scholar, Slominski et al., 2000Slominski A. Wortsman J. Luger T. Paus R. Solomon S. Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress.Physiol Rev. 2000; 80: 979-1020Crossref PubMed Scopus (599) Google Scholar;Botchkarev, 2003Botchkarev V.A. Stress and the hair follicle: Exploring the connections.Am J Pathol. 2003; 162: 709-712Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar). Also, the hair follicle itself can generate an abundance of stress mediators and expresses cognate receptors and thus may directly be involved in the modulation of stress responses at the local level, possibly as part of a “skin stress system” (Slominski et al., 2000Slominski A. Wortsman J. Luger T. Paus R. Solomon S. Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress.Physiol Rev. 2000; 80: 979-1020Crossref PubMed Scopus (599) Google Scholar). Recently, it has also become apparent that inflammatory stimuli, especially agents involved in neurogenic inflammation, may play an important role in hair growth modulation (Paus, 1999Paus R. The skin POMC system (SPS).in: Slominski A.T. Cutaneous Neuroimmunomodulation: The Proopiomelanocortin System. The New York Academy of Sciences, New York1999: 350-363Google Scholar;Rückert et al., 2000Rückert R. Lindner G. Bulfone-Paus S. Paus R. High-dose proinflammatory cytokines induce apoptosis of hair bulb keratinocytes in vivo.Br J Dermatol. 2000; 143: 1036-1039Crossref PubMed Scopus (65) Google Scholar;Arck et al., 2001Arck P.C. Handjiski B. Hagen E. Joachim R. Klapp B.F. Paus R. Indications for a “brain–hair follicle axis (BHA)”: Inhibition of keratinocyte proliferation and up-regulation of keratinocyte apoptosis in telogen hair follicles by stress and substance P.FASEB J. 2001; 15: 2536-2538PubMed Google Scholar, Arck et al., 2003bArck P.C. Handjiski B. Peters E.M. Stress inhibits hair growth in mice by induction of premature catagen development and deleterious perifollicular inflammatory events via neuropeptide substance P-dependent pathways.Am J Pathol. 2003; 162: 803-814Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar;Botchkarev, 2003Botchkarev V.A. Stress and the hair follicle: Exploring the connections.Am J Pathol. 2003; 162: 709-712Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar). Although further investigation is required to fully elucidate the interactions of these factors in human hair follicle biology, as well as the impact of psycho-emotional stress (acute and chronic) on the release of neuropeptides and their effects on human hair growth, these stimuli should now be considered when discussing strategies for the management of hair loss. No specific pharmacological intervention is currently available to manage stress-induced hair loss in man. An effective therapeutic intervention in this respect would have to prolong the anagen phase of the hair cycle, thus preventing the premature onset of catagen, which forms the basis of stress-induced telogen effluvium (Paus and Cotsarelis, 1999Paus R. Cotsarelis G. The biology of hair follicles.N Engl J Med. 1999; 341: 491-497Crossref PubMed Scopus (883) Google Scholar). Topical minoxidil (MXL) may be considered a reasonable candidate drug for the management of stress-related hair loss since it is known to prolong anagen (Buhl, 1989Buhl A.E. Minoxidil's action in hair follicles.J Invest Dermatol. 1989; 92: 315-320Crossref PubMed Scopus (114) Google Scholar). Also, recent results from a well-established mouse model on stress-induced hair loss demonstrate that most of the stress-induced hair growth-inhibitory changes along the “brain–hair axis” (Arck et al., 2001Arck P.C. Handjiski B. Hagen E. Joachim R. Klapp B.F. Paus R. Indications for a “brain–hair follicle axis (BHA)”: Inhibition of keratinocyte proliferation and up-regulation of keratinocyte apoptosis in telogen hair follicles by stress and substance P.FASEB J. 2001; 15: 2536-2538PubMed Google Scholar), including premature hair cycle progression towards catagen, could be downregulated by topical MXL application (Arck et al., 2003aArck P.C. Handjiski B. Peters E.M.J. Hagen E. Klapp B.F. Paus R. Topical minoxidil counteracts stress-induced hair growth inhibition in mice.Exp Dermatol. 2003; 11: 1-11Google Scholar). Whether MXL is also capable of counteracting negative effects of “stress” on human hair growth remains to be investigated. Insights into the negative impact of stress on hair growth particularly encourage one to integrate stress-coping strategies into the management of hair loss disorders and to therapeutically interfere with the stress-aggravating factors indicated in Figure 1. Hair loss patients, therefore, require complex, comprehensive and careful management beyond drug prescription in order to alleviate their clinical symptoms and the concomitant psychological implications. The following material is available from http://www.blackwellpublishing.com/products/journals/suppmat/JID/JID23237/JID23237sm.htmFigure S1 Download .jpg (.06 MB) Help with files Figure S1 Download .jpg (.05 MB) Help with files Figure S2
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