EADV Fostering Training Course in Hair & Scalp Bologna, Italy - 18-20 November 2011 Telogen Effluvium (Old Myths and New Insights into Hair Loss in Women) Professor Ralph M. Trüeb, M.D. Center for Dermatology and Hair Diseases Zentrum Wallisellen Bahnhofplatz 1a CH-8304 Wallisellen (Zurich) Switzerland A Definition of Myth 1. A traditional sacred story, typically revolving around the activities of gods and heroes, which purports to explain a natural phenomenon or cultural practice. 2. A fiction or half-truth, especially one that forms part of an ideology: Religious myth Historical myth Popular (layman„s) myths Physician„s myths Religious Myth: The „Hair Miracle“ of St. Agnes of Rome According to tradition, St. Agnes was a member of the Roman nobility and raised in a Christian family. She suffered martyrdom at the age of 12 during the reign of Roman Emperor Diocletian in 304. The Prefect Sempronius wished Agnes to marry his son, and on Agnes' refusal he condemned her to death. As Roman law did not permit the execution of virgins, Sempronius had a naked Agnes dragged through the streets to a brothel. Various versions of the legend give different methods of escape from this predicament. In one, as she prayed, her hair grew and covered her body. Trüeb RM. St. Agnes of Rome: Patron Saint for women with hair loss? Dermatology 2009;219:97-8 Historical Myths: Experiments on Hair Loss Cures Hair loss cures have been experimented for centuries: The great Greek doctor Hippocrates handled his patients‟ yearning for hair loss cures by applying pigeon droppings on their head. Renowned bald philosopher Aristotle used goat‟s urine to cure baldness. Cleopatra applied a mixture of ground horse teeth and deer marrow to help out Julius Caesar‟s receding hairline. She did this to save her beloved from being ridiculed since his name “Caesar” means “abundant hair” in Latin. Age Old Myths: Popular or Layman„s Myths Wearing hats causes hair loss Frequent washing and blow drying can lead to hair loss Hair styling products and dyes cause hair loss Brushing your hair can make it stronger and more resistant to hair loss Cutting your hair will make it grow back thicker Hair loss can't be stopped or helped Don‘t Believe Everything You Hear About Hair: Physician‘s Myths The majority of women complaining of hair loss are suffering of imaginary hair loss Losing 100 strands of hair per day is normal The most frequent disorder associated with hair loss in women is iron deficiency The first line treatment for androgenetic alopecia in women are antiandrogens Nutritional supplements have no significant effect on hair growth Ageing of hair and androgenetic alopecia are basically the same Starting Position Hair loss is frequent Norwood. South Med J 1975;68:1359-1365 Norwood. Dermatol Surg 2001;27:53-54 Hair loss causes considerable distress Cash. Br J Dermatol 1999 141:398-405 Treament options are available, though limited, both in terms of indications and of efficacy Ross and Shapiro. Dermatol Clin 2005;23:227-43 Success depends on unpatronizing sympathy from the side of the physician and comprehension of the underlying pathology Treatment must meet patients‘ expectations, otherwise patients must be informed on what to expect Psychocutaneous Disorders Related to the Hair Imaginary Hair Loss (Psychogenic Pseudoeffluvium) Adjustment Disorders Feeling of Disfigurement (Body Dysmorphic Syndrome) Abnormal Scalp Sensations (Cutaneous Sensory Disorder) Self-Induced Injury (Trichotillomania, Factitious Disorder) Trüeb RM, Gieler U. Psychocutaneous disorders of hair and scalp. In: Blume-Peytavi U, Tosti A, Whiting DA, Trüeb RM (eds.) Hair Growth and Disorders, Springer Berlin Heidelberg 2008: pp. 407-426 Adjustment Disorders to Hair Loss Prolonged depressive reaction (ICD-10 F43.21) Mixed anxiety and depressive reaction (ICD-10 F43.22) With predominant disturbance of conduct (ICD-10 F43.24) With mixed disturbance of emotions and conduct (ICD-10 F43.25) Cash TF. J Am Acad Dermatol 1992;26:926-931 Cash et al. J Am Acad Dermatol 1993;29:569-575 Maffei C et al. Arch Dermatol 1994;130:868-872 Panconesi E et al. Dermatol Clin 1996;14:399-422 The best way to treat the adjustment disorder is to effectively treat the underlying hair disorder! Hair Follicle Cycle Hair cycling in a random catagen mosaic pattern (2 weeks) Mildred Trotter (1899-1991) Control of hair cycling within the hair follicle itself anagen (2-6 years) Anagen (2-6 years) teloptosis Influence of systemic and external factors: • hormones telogen • cytokines (3 months) • toxins • deficiencies (nutrients, vitamins, energy) empty hair follicle Teloptosis Daily telogen shedding: 35-100 depending on amount of hair on the head! Catagen (2 weeks) Telogen (3 months) Diffuse Alopecia: Dystrophic Anagen Effluvium catagen (2 weeks) Direct insult to the rapidly dividing bulb matrix cells anagen (2-6 years) telogen (3 months) LM: Tapered proximal end and lack of root sheath teloptosis empty hair follicle Within days to few weeks loss of 90% of scalp hair antineoplastic drugs: chemotherapy-induced alopecia x-ray: radiation-induced alopecia: temporary > 3-4 Gy Krasovec, Trüeb. Hautarzt 1998;49:307-309 permanent > 30 Gy deep x-rays, > 50 Gy soft x-rays environmental or occupational toxin exposure: toxic alopecia immunologic injury: alopecia areata Alopecia Areata Most frequent cause of hair loss in childhood. Before age 2 <2%, before age 20 32,5-63 %, and after age 40 20% of cases May cause diffuse hair loss (2% of patients, women > 40 years)! Organ specific autoimmune disease of hair follicle with usually focal alopecia and unpredictable course with tendency to recurrence or chronicity, depending on age of onset, disease associations, duration of disease, and extent of hair loss Diagnosis: • Non-cicatrizing alopecia with dystrophic hairs and empty follicles: typical dermascopic findings • Nail changes in 20-40% (more frequent in children) • Trichogram: telogen or dystrophic anagen effluvium • Histology: peribulbar lymphocytic infiltration • Immune serology: Frequently circulating autoantibodies (thyroid, intrinsic factor) Telogen Effluvium catagen (2 weeks) anagen (2-6 years) telogen (3 months) teloptosis Definition: Disruption of the hair cycle resulting in increased proportion (> 20%) and shedding of telogen hair empty hair follicle Hair loss < 50% of scalp hair: Diffuse thinning of hair, most conspicuous at the temples Positive pull test of telogen club hairs < 6 months: acute telogen effluvium: Fever: postfebrile telogen effluvium Childbirth: postpartum telogen effluvium etc. > 6 months: chronic telogen effluvium: Primary disorder Secondary to a variety of systemic disorders Kligman. Arch Dermatol 1961;83:175-198 Headington. Arch Dermatol 1993;129:356-363 Whiting. J Am Acad Dermatol 1996;35:899-906 Pathologic Dynamics of Telogen Effluvium With synchronization: catagen (2 weeks) anagen (2-6 years) telogen (3 months) - Diffuse Telogen effluvium: Immediate anagen release Delayed anagen release Immediate telogen release Delayed telogen release teloptosis empty hair follicle Without synchronization: Short anagen: - Androgenetic alopecia - Senescent alopecia Headington JT. Telogen effluvium. New concepts and review. Arch Dermatol 1993;129:356-363 Seasonality of Hair Growth and Shedding Reports 3 women in New York who experienced maximum hair loss in November Orentreich N. Scalp replacement in man. In: Advances in Biology of Skin. Vol IX: Hair Growth. (Montagna W, Bobson RL., eds.). Oxford: Pergamon. 1969:99-108 Demonstrate in 14 men over a period of 18 months that the proportion of telogen hair and of hair shedding were maximal in September Randall VA, Ebling FJG. Seasonal changes in human hair growth. Br J Dermatol 1991;124:146-51 Demonstrate in 10 men with or without alopecia during a period of 8-14years a maximal proportion of telogen hairs at the end of summer Courtois M, Loussouarn G, Hourseau S, Grollier JF. Periodicity in the growth and shedding of hair. Br J Dermatol 1996;134:47-54 Seasonality of Hair Growth and Shedding in Women Fluctuations in frontal telogen rates (n = 823) in relation to the day of the year: Telogen rates showed an overall annual periodicity, manifested by a maximal proportion of telogen hair in July. A second telogen peak seems to exist, although less pronounced, in April. From: Kunz M, Seifert B, Trüeb RM. Dermatology 2009;219(2):105-10. Chronic Telogen Effluvium Diffuse shedding of telogen hair > 6 months Secondary to a variety of systemic disorders: iron deficiency, other dietary deficiencies thyroid disease, other metabolic diseases systemic lupus erythematosus, other connective tissue disorders syphilis, HIV drug-induced hair loss Primary disorder: First described 1960 as „Diffuse cyclic hair loss in women“ Guy and Edmundson. Arch Dermatol 1960;81:205-227 Revived in 1996, since then focus of interest again Whiting. J Am Acad Dermatol 1996;35:899-906 Diagnosis of exclusion! Differential diagnosis: Diffuse alopecia areata („alopecia areata incognita“) Androgenetic alopecia/Female pattern hair loss (FPHL) Androgenetic Alopecia Genetically determined, androgen induced, age-dependent progressive loss of hair with sex-dependent differences in pattern of alopecia Men: Hamilton-Norwood I-VII 18 - 29: 12% Women: 20 - 29: 3% 30 - 39: 38% 30 - 39: 17% 40 - 49: 45% 40 - 49: 16% 50 - 59: 52% 50 - 59: 23% 60 - 69: 65% 60 - 69: 25% 70 - 79: 64% 70 - 79: 28% > 80: 80 - 89: 32% 70% Ludwig I-III Norwood. South Med J 1975;68:1359-1365 Norwood. Dermatol Surg 2001;27:53-54 Androgens + Androgen metabolism Genetics Progressive shortening of anagen phase + Reduction of volume of dermal papilla Follicular microinflammation catagen (2 weeks) anagen (2-6 years) telogen (3 months) teloptosis empty hair follicle Perifollicular fibrosis Hair follicle miniaturization/hair growth arrest Increased shedding of hair: Telogen effluvium Decreased hair growth: Terminal-to-vellus hair transformation Value of Scalp Dermoscopy (Trichoscopy) Normal finding Diversity of hair shaft diameter > 20% in androgenetic alopecia de Lacharrière O, Deloche C, Misciali C, Piraccini BM, Vincenzi C, Bastien P, Tardy I, Bernard BA, Tosti A. Hair diameter diversity: a clinical sign reflecting the follicle miniaturization. Arch Dermatol 2001;137:641-6 Yellow dots typical for alopecia areata Lacarrubba F,Dall’Oglio F,Nasca MR, Micali G. Videodermoscopy enhances diagnostic capability in some forms of hair loss. Am J Clin Dermatol 2004;5:205-8 Dermoscopy of Scalp (Trichoscopy) Tosti A. Dermoscopy of Hair and Scalp Disorders with clinical and pathological correlations. Informa healthcare UK 2007 de Lacharrière et al. Hair diameter diversity: a clinical sign reflecting the follicle miniaturization. Arch Dermatol 2001;137:641-6 Zinkernagel MS, Trüeb RM. Fibrosing alopecia in a pattern distribution: patterned lichen planopilaris or androgenetic alopecia with a lichenoid tissue reaction pattern? Arch Dermatol 2000;136:205-11 Inflammatory Phenomena and Fibrosis Follicular microinflammation and fibrosis: Whiting D. Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia. JAAD 1993;28:755-763 microscopic Kossard S. Postmenopausal frontal fibrosing alopecia. Scarring alopecia in a pattern distribution. Arch Dermatol. 1994;130:770-4 Kossard S, Lee MS, Wilkinson B. Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen planopilaris. J Am Acad Dermatol 1997;36:59-66 Zinkernagel MS, Trüeb RM. Fibrosing alopecia in a pattern distribution: patterned lichen planopilaris or androgenetic alopecia with a lichenoid tissue reaction pattern? Arch Dermatol 2000;136:205-11 localized generalized Follicular inflammation and fibrosis Investigating Diffuse Hair Loss Family history of hair loss Personal history: • of hair loss • of medical problems and drug intake • of diet habits Clinical examination: • hair loss pattern • hair loss activity (pull test) • dermoscopy Biochemical investigations: • for hematinic deficiencies (CRP, ferritin, vitamin B12, folic acid) • thyroid stimulating hormone • estradiol (in menopausal), extended hormonal studies as indicated • extended biochemical studies as indicated Trichogram and scalp biopsy as indicated: • CTE versus FPHL (trichogram) • Loss of follicular orifices (biopsy) Managing Diffuse Hair Loss Trichological and biochemical characterization of hair loss Quantitating hair loss: • Daily count • Wash test • Combining epiluminiscence microscopy with digital imaging (TrichoScan) Causal treatment, wherever possible! Specific treatments for the scarring alopecias Specific treatments for alopecia areata: • Acute: Corticosteroids (pulse therapy, intralesional) • Chronic: Topical immunotherapy Specific treatments for androgenetic alopecia: • Topical 2-5% minoxidil • 5-alpha reductase inhibition Role for hormonal and nutritional treatments? Efficacy of Corticosteroid Pulse Therapy in Diffuse Alopecia Areata 3 x 500 mg i.v. methylprednisolone on 3 consecutive days Sato-Kawamura M, Aiba S, Tagami H. Acute diffuse and total alopecia of the female scalp. A new subtype of diffuse alopecia areata that has a favorable prognosis. Dermatology. 2002;205(4):367-73 Nakjima et al. Pulse corticosteroid therapy for alopecia areata: study of 139 patients. Dermatology 2007;215:320-324 Efficacy of Topical Minoxidil in Androgenetic Alopecia/FPHL Male Female Price et al. Changes in hair weight and hair count in men with androgenetic alopecia, after application of 5% and 2% topical minoxidil, placebo, or no treatment. J Am Acad Dermatol 1999;41:717-21 Role for Hormonal Treatments (in FPHL) ? Effect of estrogen therapy on postmenopausal women? Antiandrogen therapy not effective in normoandrogenic women Vexiau et al. Br J Dermatol 2002;146:992-999 Gestagens with androgenic action may precipitate hair loss in women: norethisterone, levonorgestrel, tibolone contraindicated! DHEA may cause hair loss in women in a dose-dependent manner! Finasteride in Postmenopausal Women Randomized, double-blind, placebo-controlled study with 1 mg oral finasteride during 12 months in137 postmenopausal age 41-60 Y. Study endpoints: Hair count Global photographic assessment Biopsy (morphometric) Results: For all endpoints no difference in comparison to placebo Price et al. J Am Acad Dermatol 2000;43:768-776 5 normoandrogenic postmenopausal women treated with 2.5 – 5 mg oral finasteride for up to 18 months showed improvement on global photographic assessments. Trüeb et al. Dermatology 2004;209:202-207 Iorizzo et al. Arch Dermatol 2006;142:298-302 Role for Nutritional Treatments in Diffuse Hair Loss Pharmacy aisles and Internet drugstores are full of nutrients promising full, thick, luscious hair -- for prices that range from suspiciously cheap to dishearteningly exorbitant. What are the facts? Unless the hair is falling out due to a nutritional deficiency, there's only so much that nutrients can do to increase the size of individual hairs. This is because hair thickness is largely genetic. Nevertheless, there are external factors that influence hair health to a great degree, and nutritients can boost hair that's suffering from these problems. Role of Nutritional Deficiency: Iron Iron deficiency most common nutritional deficiency: 12-16% prevalence in adolescent girls and women of childbearing age (16-49 years of age) and 6-9% in women 50 years of age and older in the USA Most laboratories use 10 - 15 µg/l as lower limit of normal for menstruating women, and 30 µg/l for children, men and non-menstruating women. In women of childbearing age, a cutoff of 10-15 µg/l yields a sensitivity of 75% and specificity of 98%, a cutoff of 30 µg/l yields a sensitivity of 92% and a specificity of 98% Most common causes of iron deficiency: in premenopausal women: menstrual blood loss, pregnancy and lactation in postmenopausal women: decreased absorption and gastrointestinal loss. Risk factors: heavy menstrual bleeding (> 80 ml per month), use of an IUD, history of iron deficiency anemia,insufficient dietary iron intake. From: Bregy and Trüeb.Dermatology 2008;217:1-6 Role for Iron Supplementation Decreased serum ferritin is associated with alopecia in women (“Rushtonians”): Hard S. Acta DermVenereol 1963;43:562-569 Rushton et al.Br J Dermatol 1990;123:187-197 Rushton et al. Clin Endocrinol 1992;36:421-427 Kantor et al. J Invest Dermatol 2003;121:985-988 There is no clear association between low serum ferritin and chronic diffuse telogen hair loss (“Sinclairians”): Aydingoz et al.1999;13:65-7 Sinclair R. Br J Dermatol 2002;147:982-4 No association between serum ferritin levels >10 microg/L and hair loss activity in women (trichogram). From: Bregy and Trüeb. Dermatology 2008;217:1-6 Androgenetic alopecia Senescent alopecia Onset Early (teens, twens) Late (60 years +) Distribution Patterned Diffuse Pathophyisology Increased activity of 5- reductase (DHT) in men Senescence (decreased activity of 5- reductase ) Genetics Polygenic Unknown Association or risk factor for other diseases Cardiovascular diseases Benign prostatic hyperplasia Prosate cancer Age-related disorders? Gene expression profiles Decreased expression of genes required for anagen onset and maintenance / increased expression of catagen and telogen inducers Increased expression of markers for mitochondrial dysfunction and oxidative stress Treatment Minoxidil Finasteride Estrogens (anecdotal) Minoxidil Nutritional supplements hGH (anecdotal) Mirmirani P,Karnik P. Compberative gene expression profiling of senescent and androgenetic alopecia using microarray analysis. In: Trüeb RM, Tobin DJ. Aging Hair. Springer, Berlin 2010: pp. 49 ff Efficacy of Topical Minoxidil in Senescent Alopecia Before treatment Personal observation After 6 months of treatment Biology of Hair Aging Intrinsic (Chronologic) Aging: Genetic: AGA, familial premature graysing (AD), progerias (rare) Hormones und hormone metabolism: AGA Replicative senescence: Graying, senescent alopecia? Oxidative metabolism (melanogenesis): Graying Extrinsic (Accelerated) Aging: Oxidative stress from UV-R Oxidative stress from tobacco smoking Others? Trüeb RM. Is androgenetic aopecia a photaggravated dermatosis? Dermatology 2003;207:343-348 Trüeb RM. Association between smoking and hair loss: another opportunity for health education against smoking? Dermatology 2003;206:189-191 Oxidative Stress from Smoking D'Agostini et al. Induction of alopecia in mice exposed to cigarette smoke. Toxicol Lett 2000; 3;114:117-23 D'Agostini et al. Chemoprevention of smoke-induced alopecia in mice by oral administration of L-cystine and vitamin B6. J Dermatol Sci 2007;46:189-98 Premature senescence of balding DPC in vitro in association with expression of p16(INK4a)/pRB suggests that balding DPC are sensitive to environmental stress and identifies alternative pathways that could lead to novel therapeutic strategies for treatment of AGA. Bahta AW, Farjo N, Farjo B, Philpott MP. Premature senescence of balding dermal papilla cells in vitro isassociated with p16(INK4a) expression. J Invest Dermatol 2008;128:1088–94 Value of Nutritional Intervention in Aging Hair Nutritional Intervention? Structural Ageing of Skin: Atrophy Degeneration Functional impairment Immune Ageing of Skin: Decrease in immunocompetence Photoageing of Skin: Cumulation of genotoxic and oxidative damage to Exhaustion of antioxidative defense network Skin: Vulnerability Impaired wound healing Decreased hydration Pruritus Eczema Infections Carcinogenesis Hair: Hair loss Hair greying Hair weathering Double-Blinded, Placebo-Controlled Study in Healthy Women with Hair Loss Using Oral Combination of Cystine and B-Vitamins Global photographic assessment 85 Anagen rate (%) Normal range Trichoscan 80 Verum Placebo 75 70 From: Lengg et al. Therapy 2007;4:59 65 0 Verum (N=15) 72.5 Placebo (N=15) 75.3 3 6 78.5 78.2 80.5 75.6 months p = 0.003 p = 0.85 Active compound led to statistically significant improvement and normalization of mean anagen hair rates within 6 monts of treatment, independent of age (smoking status not examined) Hair count and cumulative hair shaft diameter did not show any change in both groups (as opposed to studies with topical minoxidil) Summary and Conclusions The complaint of hair loss is frequent in women and causes considerable distress In a minority of patients hair loss is imaginary The number of hair lost per day depends on the amount of hair on the scalp and seasonal effects There are effective therapies of hair loss, though with limitations with respect to indications and efficacy Ther role of nutrition is overemphasized by the lay and underestimated by physicians Iron deficiency is overestimated as a single cause of hair loss in women, as well as the role of antiandrogens in the treatment of femal pattern hair loss Androgenetic alopecia and ageing of hair are two distinct entities, though with some common denominators Treatment should target multiple factors responsible for hair loss Treatment success depends on comprehension of the underlying pathology and unpatronizing sympathy on the part of the physician Thank you for your attention! References: Trüeb RM. Diffuse Hair Loss: pp. 259-272 In: Blume-Peytavi U, Tosti A, Whiting DA, Trüeb RM (eds.) Hair Growth and Disorders, Springer Berlin Heidelberg 2008 www.derma-haarcenter.ch Trüeb RM. Systematic approach to hair loss in women. J Dtsch Dermatol Ges 2010;8:284-7
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