EADV Fostering Training Course in Hair & Scalp … Fostering Training Course in Hair & Scalp Bologna, Italy - 18-20 November 2011 1. A traditional sacred story, typically revolving

Professor Ralph M. Trüeb, M.D.

Center for Dermatology and Hair Diseases

Zentrum Wallisellen

Bahnhofplatz 1a

CH-8304 Wallisellen (Zurich)

Switzerland

Telogen Effluvium (Old Myths and New Insights into Hair Loss in Women)

EADV Fostering Training Course in Hair & Scalp

Bologna, Italy - 18-20 November 2011

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

A Definition of Myth

Religious Myth: The „Hair Miracle“ of St. Agnes of Rome

Trüeb RM. St. Agnes of Rome: Patron Saint for women with hair loss?

Dermatology 2009;219:97-8

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.

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

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

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)

The best way to treat the adjustment disorder is to effectively treat the

underlying hair disorder!

anagen (2-6 years)

catagen (2 weeks)

telogen (3 months)

teloptosis

empty hair follicle

Anagen

(2-6 years)

Catagen

(2 weeks)

Telogen

(3 months)

Teloptosis

Hair cycling in a random

mosaic pattern

Control of hair cycling within

the hair follicle itself

Influence of systemic and

external factors:

• hormones

• cytokines

• toxins

• deficiencies (nutrients,

vitamins, energy)

Daily telogen shedding: 35-100 depending on amount of

hair on the head!

Mildred Trotter

(1899-1991)

Hair Follicle Cycle

Diffuse Alopecia: Dystrophic Anagen Effluvium

anagen (2-6 years)

catagen (2 weeks)

telogen (3 months)

teloptosis

empty hair follicle

Direct insult to the rapidly dividing bulb matrix cells

LM: Tapered proximal end and lack of root sheath

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

anagen (2-6 years)

catagen (2 weeks)

telogen (3 months)

teloptosis

empty hair follicle

Kligman. Arch Dermatol 1961;83:175-198

Headington. Arch Dermatol 1993;129:356-363

Whiting. J Am Acad Dermatol 1996;35:899-906

Definition:

Disruption of the hair cycle resulting in increased

proportion (> 20%) and shedding of telogen hair

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

anagen (2-6 years)

catagen (2 weeks)

telogen (3 months)

teloptosis

empty hair follicle

Pathologic Dynamics of Telogen Effluvium

Headington JT. Telogen effluvium. New concepts and review.

Arch Dermatol 1993;129:356-363

With synchronization:

- Diffuse Telogen effluvium:

Immediate anagen release

Delayed anagen release

Immediate telogen release

Delayed telogen release

Without synchronization:

Short anagen:

- Androgenetic alopecia

- Senescent alopecia

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

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.

Seasonality of Hair Growth and Shedding in Women

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

Men: 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: 70% 80 - 89: 32% Hamilton-Norwood I-VII

Ludwig I-III

Genetically determined, androgen induced, age-dependent progressive

loss of hair with sex-dependent differences in pattern of alopecia

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

Hair follicle miniaturization/hair growth arrest

Increased shedding of hair:

Telogen effluvium

Decreased hair growth:

Terminal-to-vellus hair

transformation

Follicular microinflammation Perifollicular fibrosis

anagen (2-6 years)

catagen (2 weeks)

telogen (3 months)

teloptosis

empty hair follicle

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)

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

Tosti A. Dermoscopy of Hair and Scalp Disorders with clinical and

pathological correlations. Informa healthcare UK 2007

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

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

Follicular inflammation

and fibrosis

microscopic

localized

generalized

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

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

Efficacy of Topical Minoxidil in Androgenetic Alopecia/FPHL

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

From: Bregy and Trüeb. Dermatology 2008;217:1-6

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).

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

Personal observation

Efficacy of Topical Minoxidil in Senescent Alopecia

After 6 months of treatment Before 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

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

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.

Skin:

Vulnerability

Impaired wound healing

Decreased hydration

Pruritus

Eczema

Infections

Carcinogenesis

Hair:

Hair loss

Hair greying

Hair weathering

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

Nutritional Intervention?

Value of Nutritional Intervention in Aging Hair

65

70

75

80

85

0 3 6

Verum

Placebo

Normal range

months

An

ag

en

rate

(%

)

Verum 72.5 78.5 80.5 p = 0.003

Placebo 75.3 78.2 75.6 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)

(N=15)

(N=15)

Global photographic

assessment

Trichoscan

From:

Lengg et al. Therapy 2007;4:59

Double-Blinded, Placebo-Controlled Study in Healthy Women with Hair Loss

Using Oral Combination of Cystine and B-Vitamins

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

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

Trüeb RM. Systematic approach to hair loss in women. J Dtsch

Dermatol Ges 2010;8:284-7

www.derma-haarcenter.ch

Thank you

for your

attention!