284 Academy DOI: 10.1111/j.1610-0387.2010.07261.

CME

Systematic approach to hair loss in women

Ralph M. Trüeb
Department of Dermatology, University Hospital of Zurich
Lecture presented by RMT on the occasion of the 17th EADV Meeting in Paris, 17–20 September 2008

Section Editor
Prof. Dr. Jan C. Simon,
JDDG; 2010 • 8:284–297 Submitted: 9. 6. 2009 | Accepted: 1. 8. 2009 Leipzig

Keywords Summary
• women Diffuse hair loss is a common complaint and cause of significant emotional dis-
• telogen effluvium tress particularly in women. The best way to alleviate the anxiety is to effectively
• seasonality treat the hair loss. It is paramount to address the symptom systematically. In
• minoxidil addition to its psychological impact, hair loss may be a manifestation of a more
• oral supplementation general medical problem. The diagnosis can be established with a detailed
• psychological counseling patient history focussing on chronology of events, examination of the scalp
and pattern of hair loss, a pull test with examination of bulbs of shed hairs, tri-
choscopy, and few pertinent screening blood tests. In selected cases a scalp
biopsy may be required. The most important differential diagnoses include
acute and chronic telogen effluvium, female pattern hair loss, and diffuse
alopecia areata. Occasionally, patients seeking advice are not necessarily losing
hair. In the absence of convincing evidence of hair loss, they are suffering of
psychogenic pseudoeffluvium, and thought should be given to an underlying
psychological disorder. Once the diagnosis is established, treatment appropri-
ate for that diagnosis is likely to control the hair loss. Finally, appropriate psy-
chological support and education about the basics of the hair cycle, and why
considerable patience is required for effective cosmetic recovery, are essential
to help limit patient anxiety.

Introduction
Few dermatologic complaints carry as much emotional overtones as hair loss, and in
some cases they seem disproportionate to the extent of hair loss, especially in the
adult female patient presenting with diffuse hair loss. Adding to the patient’s worry
may be prior negative experiences with physicians, who tend to trivialize complaints
of hair loss. This attitude on the part of physicians may result from lack of familiar-
ity with the management of hair loss, thereby making them feel uncomfortable deal-
ing with such patients. However, comprehension of the main types of hair loss and
their causes is prerequisite to meeting patients’ expectations and providing appropri-
ate patient management. Finally, in addition to its obvious psychological impact, hair
loss may also be a manifestation of a more general medical problem.
In 1932, Sabouraud originally coined the term “defluvium capillorum” to character-
ize a sudden type of diffuse hair loss following shortly after a severe emotional shock,
while others later applied it to all forms of alopecia. In the late 1950’s, Sulzberger dif-
ferentiated a chronic type of diffuse alopecia in women from acute and reversible hair
loss that is attributable to a readily identifiable cause [1]. However, a majority of
these patients later turned out to be women with female pattern hair loss or diffuse
hair loss of unexplored etiology, such as thyroid dysfunction, or malnutrition. In
1960, Guy and Edmundson described a form of “diffuse cyclic hair loss in women”
in which no specific trigger was evident [2].

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Figure 1: Hair follicle cycle.

Whatever the cause, the follicle tends to behave in a similar way. To grasp the meaning
of this generalization, requires understanding of the hair cycle and its derangements.

Pathologic dynamics of hair loss

Hair follicle cycling
The hair follicle is subject to constant turnover in the course of perpetual cycles The hair follicle is subject to constant
through phases of proliferation (anagen), involution (catagen), and resting turnover.
(telogen), with regeneration in the successive hair cycle (Figure 1): It is a major
characteristic of anagen that not only the hair shaft is growing but that most
epithelial hair follicle compartments undergo proliferation, with the hair matrix
keratinocytes showing the highest proliferative activity. During catagen, hair folli-
cles enter a process of involution that is characterized by a burst of programmed
cell death (apoptosis) in follicular keratinocytes. The resulting shortening of the
regressing epithelial strand is associated with an upwards movement of the folli-
cle. In telogen, the hair shaft matures into a club hair, which is held in the base of
the follicular epithelium, before it is eventually shed. It is still unresolved whether
shedding of the telogen hair (teloptosis) is an active, regulated process or repre-
sents a passive event that occurs at the onset of subsequent anagen, as the new hair Cyclic hair growth activity occurs in a
grows in. random mosaic pattern with each fol-
Cyclic hair growth activity occurs in a random mosaic pattern with each follicle pos- licle possessing its own individual
sessing its own individual control mechanism over the evolution and triggering of the control mechanism, though hormones,
successive phases, though systemic factors, such as hormones, cytokines and growth cytokines and growth factors, as well
factors, as well as external factors linked to the environment, such as toxins, and defi- as toxins, and deficiencies of nutrient,
ciencies of nutrient, vitamins and energy, have influence. vitamins and energy, have influence.

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Except for the scarring alopecias, hair
loss represents a disorder of hair folli-
cle cycling.
Dystrophic anagen effluvium results
from a direct insult to the rapidly di-
viding bulb matrix cells.
Telogen effluvium results from the in-
creased shedding of hairs from the
telogen phase of growth.
A short anagen phase results in a slight
but persistent telogen effluvium.
In diffuse hair loss the hair pull test is
positive in both the vertex area and
margins of the scalp.
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Finally, there are considerable variations in length of these phases depending on the
body site location, with the duration of anagen determining the type of hair pro-
duced, particularly its length. On the scalp, hairs remain in anagen for a 2- to 6-year
period of time, whereas that of telogen is approximately 100 days, resulting in a ratio
of anagen to telogen hairs of 9 : 1. On average, the amount of new scalp hair forma-
tion matches the amount that is shed, thereby maintaining a consistent covering.
With a range of 75 000 to 150 000 hairs on the head, the reported average daily tel-
ogen hair shedding varies from under 50 to over 100.
Disorders of hair follicle cycling
Many factors can lead to pathologically increased hair loss. Disease states that cause
hair loss are categorized according to whether the hair loss is diffuse or localized, and
to whether the follicle remains intact or is destroyed and replaced by scar. Except for
the scarring alopecias, hair loss represents a disorder of hair follicle cycling [3].
Dystrophic anagen effluvium results from a direct insult to the rapidly dividing bulb
matrix cells. The abrupt cessation of mitotic activity leads to the weakening of the
partially keratinized, proximal portion of the hair shaft, its narrowing and subsequent
breakage within the hair canal and shedding of hairs from the anagen phase of
growth. The morphological consequence is dystrophic anagen hair with a tapered
proximal end and lack of root sheath.
Telogen effluvium results from the increased shedding of hairs from the telogen phase
of growth. As telogen hairs have a depigmented bulb, examination of shed or pulled
hairs with the naked eye will usually clarify this. In 1961 Kligman [4] revealed the
pathodynamics of one common pattern of response of hair follicles to a variety of
insults and named it telogen effluvium. On the basis of changes in different phases
of the follicular cycle, Headington [5] proposed classification of telogen effluvium
into five functional types:
In immediate anagen release, follicles that would normally complete a longer cycle by
remaining in anagen prematurely enter telogen. It is a very common form of
telogen effluvium, typically occurring after periods of physiologic stress including
episodes of high fever. In fever, the pyrogens, basically circulating cytokines, drive the
hair follicle keratinocytes into apoptosis initiating catagen with following telogen.
Because the shedding is dependent on transition from anagen through catagen and
telogen with subsequent release of telogen hairs, hair loss occurs 3 to 4 months after
the inciting event.
In delayed anagen release, hair follicles remain in prolonged anagen rather than
cycling into telogen. When finally released from anagen, the clinical sign of
increased shedding of telogen hair will be found. This type underlies post partum
hair loss.
In immediate telogen release, hair follicles normally programmed for release of the
club hair after an interval of usually 100 days after the end of anagen, are prema-
turely stimulated to cycle into anagen. There is premature teloptosis. This type
underlies the shedding of hair upon initiation of therapy with topical minoxidil
(shedding phase).
In delayed telogen release, hair follicles remain in prolonged telogen rather than being
shed and recycling into anagen. When finally teloptosis sets in, again increased
shedding of club hairs is observed. This process underlies moulting in mammals and
possibly mild telogen effluvia following travel from low-daylight to high-daylight
conditions.
Finally, a short anagen phase results in a slight but persistent telogen effluvium in
association with decreased hair length: This occurs in the course of androgenetic
alopecia or female pattern hair loss.
Etiologies and clinical presentations
A simple office technique for evaluation of hair loss is to pull gently on the patient’s
hair (hair pull test). Normally, one can come away with up to five hairs, but with
pathologic hair loss this number is increased (positive hair pull). In diffuse hair loss
the hair pull test is positive in both the vertex area and margins of the scalp. Diffuse
hair loss is further classified whether the hairs shed are anagen hairs (anagen effluvi-
um) or telogen hairs (telogen effluvium).
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Figure 2: Chemotherapy-induced alopecia (dystrophic anagen effluvium).

Dystrophic anagen effluvium

While antineoplastic drugs (chemotherapy-induced alopecia) and radiation (radia-
tion-induced alopecia) are obvious from the patient’s history, environmental or occu-
pational exposure to toxins (toxic alopecia) and alopecia areata (see differential diag-
nosis) should be taken into account in cases of dystrophic anagen effluvium without
a history of chemotherapy, therapeutic or accidental radiation exposure.
Chemotherapy-induced alopecia usually begins at 1–3 weeks and is complete at 1–2
months after initiation of chemotherapy. Since normally up to 90 % of scalp hairs
are in anagen, hair loss is usually copious and the resulting alopecia is quite obvious
(Figure 2). The incidence and severity of the hair loss are variable and related to the
particular chemotherapeutic protocol. Multiple classes of anticancer drugs induce
alopecia with frequencies of chemotherapy-induced alopecia differing for the four
major drug classes: over 80 % for antimicrotubule agents, e. g. paclitaxel, 60–100 %
for topoisomerase inhibitors, e. g. doxorubicin, over 60 % for alkylators, e. g.
cyclophosphamide, and 10–50 % for antimetabolites, e. g. 5-fluorouracil plus leu-
covorin. Combination therapy consisting of two or more agents usually produces
higher incidences of a more severe chemotherapy-induced alopecia compared to
single agent therapy. Chemotherapy-induced alopecia is usually reversible with hair
regrowth typically occurring after a delay of 3–6 months. In some patients, the
regrown hair shows changes in color and/or structure and texture, in others the hair
growth may remain reduced [6].
Radiation-induced alopecia may either be reversible or permanent. Permanent alope-
cia occurs with > 30 Gy of deep x-rays, or > 50 Gy of soft x-rays.
Toxic alopecia from occupational exposure to hazardous chemicals has decreased
over the years due to more stringent government regulations. More recently, inter-
est has focussed on mild aggressions from toxic metals of the environment. Many
heavy metals are capable of disrupting the formation of the hair shaft through
covalent binding with the sulfhydryl groups in keratin: thallium, mercury, arsenic,
copper, cadmium, and bismuth. A study conducted 1979 in Belgium reported dif-
fuse alopecia related to ingestion of toxic metals in 36 of 78 patients with diffuse
alopecia: Copper was involved in 17 alopecias, arsenic in 12, mercury in 5, and
cadmium in 2.
Toxic metals in abnormal amount in blood and urine were observed only when Toxic metals in abnormal amount in
> 10 % of hair bulbs were dystrophic [7]. blood and urine were observed only
Adverse effects related to dental amalgam, including hair loss, have also been the sub- when >10% of hair bulbs were dys-
ject of recent attention. In a study, assays of mercury in urine samples of patients with trophic.
“amalgam illness” indicated that the exposure was far below the levels at which symp-
toms could be indicated by psychometric tests. Psychologic investigation indicated
that the symptoms were psychosomatic [8].

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Alopecia areata represents the most
frequent cause of anagen dystrophic
effluvium occurring in the otherwise
healthy child or adult.
Most patients with hair loss seen in
clinical practice present with telogen
effluvium.
Women who experience high stress
are more likely to experience hair loss.
Chronic telogen effluvium is defined as
diffuse telogen hair loss that persists
> 6 months.
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Figure 3: Temporal hair thinning in telogen effluvium.
Alopecia areata represents the most frequent cause of anagen dystrophic effluvium
occurring in the otherwise healthy child or adult. It is regarded to be an organ-
specific autoimmune disease, with the hair follicle being the target of autoimmunity.
The cytokines generated by a peripulbar lymphocytic infiltrate cause apoptosis of
hair follicle keratinocytes.
Telogen effluvium
Most patients with hair loss seen in clinical practice present with telogen effluvium.
Hair loss is usually < 50 % of scalp hair. The diffuse hair loss from the scalp may pro-
duce thinning of hair all over the scalp, but frequently manifests with bitemporal hair
thinning (Figure 3).
Acute telogen effluvium presents as a diffuse, non-patterned hair loss from the scalp
that occurs around 3 months after a triggering event, and is usually self-limiting
within 6 months by definition. A host of different triggers has been implicated:
Severe febrile illness, childbirth, accidental trauma or surgical operations with a large
hemorrhage, a crash diet, or severe emotional distress are among the most common
causes.
The literature on the subject of psychogenic hair loss has been more confounding than
helpful. The presence of emotional stress is not indisputable proof of its having incit-
ed the patient’s hair loss. The relationship may also be the inverse. Nevertheless,
recent studies suggest that women who experience high stress are more likely to expe-
rience hair loss [9].
Chronic telogen effluvium is defined as diffuse telogen hair loss that persists > 6
months. It either represents a primary disorder and is a diagnosis of exclusion, or it
is secondary to a variety of systemic disorders: iron deficiency, other dietary deficien-
cies (protein-calorie malnutrition, zinc deficiency), thyroid disease, other metabolic
diseases (chronic renal or liver failure, advanced malignancy, pancreatic disease and
upper gastrointestinal disorder with malabsorption), systemic lupus erythematosus,
other connective tissue disorders (dermatomyositis), HIV infection, and drug-
induced telogen hair loss.
Apart from iron deficiency as cause of diffuse hair loss, all others are less common.
Although nonanemic iron deficiency as an etiologic factor for diffuse hair loss in
women was postulated by Hard in 1963 [10], it is not until recently that the signif-
icance of iron stores as assessed by serum ferritin levels in women with hair loss has
been systematically studied [11]. Various observational studies have evaluated the
association between decreased ferritin levels and hair loss and resulted in opposing
conclusions [12–18]. Our own data suggest that in most women with chronic telo-
gen effluvium no direct relationship between serum ferritin levels within the lower
normal range (i. e. above 10 microgram/Liter) and hair loss exists [19].
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While chronic telogen effluvium may be triggered by an acute telogen effluvium, in In primary chronic telogen effluvium
primary chronic telogen effluvium no specific trigger is evident. The presentation of no specific trigger is evident.
this type of diffuse hair loss tends to be distinctive, and was first described in detail
by Guy and Edmundson [2] as “diffuse cyclic hair loss in women”, and revived by
Whiting in 1996 [20], who additionally characterized the histopathologic features. It
is has been proposed that this disorder may be due to synchronization phenomena of
the hair cycle [2], shortening of the anagen phase [4], or premature teloptosis. The
typical patient is a vigorous otherwise healthy woman between 30 and 60 with a full,
thick head of hair. On examination there is some bitemporal recession and a positive
hair pull test equally over the vertex and occiput. There is no widening of the central
part, as is common in female pattern hair loss. Many frequently bring large balls of
hair for inspection (Figure 4), but despite this do not show any obvious balding. The
condition tends to run a fluctuating course, in the long run the disorder appears to
be self-limiting. Nevertheless, patients are adamant that they previously had more
hair and are distressed by the prospect of going bald. Therefore, it is important to
reassure patients that primary chronic telogen effluvium condition represents exag-
gerated shedding rather than actual hair loss.

Quantitating hair loss

Reliably assessing the actual shedding of hair is a crucial diagnostic point in tricho-
logical practice. To fulfill office requirements, the test should be easy, non-invasive
and not time-consuming. Many methods have been proposed, but all need standard-
ization.
The hair pull test has been found to be a poorly sensitive method, while telogen Figure 4: Hair ball brought in by patient with
percentage in the trichogram did not correlate with severity of hair loss. While the chronic telogen effluvium.
daily hair count is a cumbersome procedure, it has been proposed that the wash test
is probably the best method to adopt [21]: In the wash test, the patient, five days Reliably assessing the actual shed-
after the last shampoo, washes the hair in the sink with its drain covered by gauze. ding of hair is a crucial diagnostic
The hairs entrapped in the gauze are then counted. point in trichological practice.
More so, measurement of the effects of treatment needs to be quantified reliably. The More so, measurement of the effects
method should be capable of analyzing relevant parameters of hair growth, which are: of treatment needs to be quantified
hair density, hair diameter, hair growth rate, and anagen/telogen ratio. For this pur- reliably.
pose, a technique has been developed that combines epiluminiscence microscopy
with automatic digital image analysis (TrichoScan) [22].

Seasonality of hair growth and shedding

A number of otherwise healthy women with or without clinical alopecia complain of
recurrent hair loss, despite at times successful therapy. To test the hypothesis that
periodicity in shedding of hair reflects seasonal changes in human hair growth, we
performed a retrospective study in otherwise healthy women with telogen effluvium
and demonstrated the existence of an overall annual periodicity in the growth and
shedding of hair (Figure 5 a–c), manifested by a maximal proportion of telogen hairs
in July [23]. A second peak seems to exist, although less pronounced, in April. The
telogen rate was lowest towards the beginning of February. These results confirm the
findings of former authors who have demonstrated seasonal changes in human hair
growth [24, 25], though this is the first study performed systematically in a represen-
tative number women. The existence of seasonal fluctuations in hair growth and The existence of seasonal fluctuations
shedding complicates the assessment of pharmacological effects. Awareness of these in hair growth and shedding compli-
fluctuations is prerequisite to providing the correct cause and prognosis to the cates the assessment of pharmaco-
patient, ensuring patient compliance with therapy. logical effects.

Differential diagnosis
The most important differential diagnoses of diffuse telogen hair loss include female The most important differential diag-
pattern hair loss and psychogenic pseudoeffluvium. Between these, considerable noses of diffuse telogen hair loss in-
overlap exists further complicating differential diagnosis, especially in women. Far clude female pattern hair loss and
less common is diffuse alopecia areata. psychogenic pseudoeffluvium.

Female pattern hair loss Female pattern hair loss is by far the
Female pattern hair loss is by far the most common cause of hair loss in otherwise most common cause of hair loss in
healthy women. In the early stages the pattern may not be apparent, and patients otherwise healthy women.

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Figure 5: Seasonality of hair growth and shedding. January 2007 (a), July 2007 (b), February 2008 (c) (from: Kunz et al. [23]).
Figure 6: Differential diagnosis: Female pattern
hair loss.
Female pattern hair loss is usually
successfully treated with topical
Minoxidil.
Special attention is given to the use
of a contraceptive pill or hormonal re-
placement therapy, since gestagens
with proandrogenic effect (norethis-
terone, levonorgestrel, tibolon) may
exacerbate hair loss.
It is important to question women who
complain of excessive hair loss while no
evidence of alopecia is evident on ex-
amination about depression and mari-
tal difficulties.
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may complain of diffuse hair loss. Eventually, hair thinning becomes obvious on top
of the scalp (Figure 6), in some women there may be a triangular diminution in hair
density in the frontal scalp immediately behind a preserved frontal fringe.
Recent literature suggests that patterned hair loss may have different mechanisms in
men and in women. Because the androgen dependence of hair loss in all women with
this type of alopecia has not been sufficiently demonstrated, and it has been observed
in the absence of circulating androgens [26], the term female pattern hair loss has
been proposed to replace androgenetic alopecia when applied in women.
Nevertheless, female pattern hair loss and androgenetic alopecia share the same his-
tolopathologic feature of hair follicle miniaturization.
Female pattern hair loss is usually successfully treated with topical minoxidil [27],
unless it is coincident with another cause of telogen effluvium, that needs to be
addressed. A special attention is also given to the use of a contraceptive pill or
hormonal replacement therapy, since gestagens with proandrogenic effect (norethis-
terone, levonorgestrel, tibolon) may exacerbate hair loss and are consequently
contraindicated in these women. Some authors eventually recommend the use of
antiandrogen therapy, such as cyproterone acetate, spironolactone, or finasteride,
though there exists controversy on this issue [27, 28].
Psychogenic pseudoeffluvium
Patients seeking advice for hair loss are not necessarily balding. When they have nor-
mally dense scalp hair, and absence of any convincing evidence of hair loss, they are
regarded as suffering of “imaginary hair loss” or psychogenic pseudoeffluvium. In
these cases thought should be given to underlying psychological disorders: Mild
instances of “alopeciaphobia” [4] are common in connection with depressive or anx-
iety disorders (Figure 7). Therefore, it is important to question women who complain
of excessive hair loss while no evidence of alopecia is evident on examination about
depression and marital difficulties. Finally, the physician should be aware of the
potential seriousness of body dysmorphic disorder and delusion of alopecia, both near-
ly psychotic states. In addition to the relentless complaint of hair loss, patients suf-
fering from body dysmorphic disorder adopt obsessional, repetitive ritualistic
behavior, and may come to spend the majority of the day in front of a mirror,
repeatedly checking their hair. Another aspect of this behavior is a constant need for
reassurance about the hair, not only from the immediate family but also from the
medical profession and from dermatologists in particular. These patients may
become the most demanding types of patient to try to manage.
Alopecia areata incognita
Alopecia areata is an immune-mediated form of hair loss, which commonly presents
as localized patches of bald scalp. An as yet unidentified trigger stimulates an autoimmune
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Figure 7: Differential diagnosis: Psychogenic pseudoeffluvium. Patient letter.

lymphocytic attack on the hair bulb. The inflammation is specific for anagen hairs and
causes anagen arrest. Alopecia areata incognita is an uncommon variety of alopecia area- Alopecia areata incognita is an un-
ta characterized by diffuse hair shedding in the absence of typical patches. The condi- common variety of alopecia areata
tion usually affects women over 40 years of age, who complain of acute diffuse alopecia characterized by diffuse hair shedding
and are often misdiagnosed as having telogen effluvium. Where no patch of alopecia in the absence of typical patches.
coexists as a clue to the diagnosis, a biopsy is usually required to establish the diagnosis.
Optimal specimens include two 4-mm punch biopsy specimens from the vertex submit-
ted for horizontal and vertical embedding. The histologic features depend on the stage A response with hair regrowth to a
of the disease, and biopsy specimens of clinically active alopecia areata show peribulbar trial of oral prednisolone in doses > 0.5
lymphocytic infiltrates around anagen follicles. Alternatively, a response with hair mg/kg for 3–4 weeks with subsequent
regrowth to a trial of oral prednisolone in doses > 0.5 mg/kg for 3–4 weeks with subse- tapering is sometimes required to es-
quent tapering is sometimes required to establish the diagnosis (Figure 8 a, b). tablish the diagnosis.

Value of trichoscopy for differential diagnosis

While the standard methods used to diagnose hair and scalp disorders (clinical
inspection, pull test, trichogram, and biopsy) vary in sensitivity, reproducibility, and
invasiveness, recent studies suggest that the use of dermoscopy in the clinical evalu- The use of dermoscopy in the clinical
ation of hair and scalp disorders improves diagnostic capability beyond simple clini- evaluation of hair and scalp disorders
cal inspection [29]. In daily clinical practice a simple dermatoscope (Heine Delta 20® improves diagnostic capability be-
or DermoGenius®) can be used, with alcohol as the interface solution (Kodan® spray, yond simple clinical inspection.
Schulke & Mayr, Vienna, Austria). This method allows viewing of the hair and scalp

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Figure 9: Trichoscopy for differentiation of dif-
fuse telogen effluvium from female pattern hair
loss and diffuse alopecia areata: diffuse telogen
effluvium: normal trichoscopy (a); female pat-
tern hair loss: diversity of hair shaft diameter
(anisotrichosis) (b); diffuse alopecia areata: yel-
low dots (c).
Management and prognosis of dif-
fuse hair loss depend on the cause
and underlying pathomechanism in
its relation to the hair growth cycle.
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Figure 8: Diffuse alopecia areata, before (a) and after (b) systemic corticosteroid treatment.
at high magnifications, and is especially helpful in differentiating diffuse telogen
effluvium from female pattern hair loss or alopecia areata (Figure 9 a–c).
Dermoscopic features of female pattern hair loss are: hair diameter diversity, peripi-
lar signs, and empty follicles. Hair diameter diversity or anisotrichosis relates to the
presence of hairs with different caliber. This finding reflects progressive hair follicle
miniaturization due to this condition. Peripilar signs (peripilar cupular atrophy) are
characterized by the presence of a brown halo, roughly 1 mm in diameter, at the fol-
licular ostium around the emerging hair shaft. This finding has been found to be
linked to superficial perifollicular lymphocytic infiltrates. Empty follicles are charac-
terized by empty follicular ostia. They represent the physiological interval of the hair
cycle in which the hair follicle remains empty after the telogen hair has been extrud-
ed and before a new anagen hair emerges (lag phase or kenogen). During kenogen,
the hair follicle rests physiologically, but duration and frequency are greater in female
pattern hair loss, possibly accounting for hair thinning.
Dermoscopic features of alopecia areata are: yellow dots, dystrophic hairs, and short
regrowing miniaturized hairs. Yellow dots are characterized by an array of quite
monomorphous, though variably sized, yellow to yellow-pink, round or polycyclic
dots that are devoid of hair or contain dystrophic or vellus hair. They correspond to
dilated follicular infundibula that contain sebaceous and keratinous material.
Dystrophic hairs represent hairs that have fractured tips due to any process inhibiting
cell division in the hair matrix. The hair shaft may be fractured before emergence
from the scalp and then appears as cadaverized hair, or then appears as short excla-
mation mark hair. Dystrophic hairs are typically seen in acute alopecia areata at the
active margin, where all types are usually numerous. Short regrowing miniaturized
hairs are a common feature seen in both acute and chronic alopecia areata.
Treatment
Management and prognosis of diffuse hair loss depend on the cause and underlying
pathomechanism in its relation to the hair growth cycle. Once the diagnosis is estab-
lished, treatment appropriate for that diagnosis is likely to control the hair loss. While
most acute telogen effluvia, particularly those due to acute-onset physiologic events,
e. g. postfebrile, postpartum, as well as seasonal telogen effluvium, and the shedding
phase upon initiation of topical minoxidil treatment are self-limiting and will undergo
normal reversal, the cause of chronic telogen effluvium may be multifactorial and dif-
ficult to establish. Differential diagnosis may be complicated through considerable
overlap, especially with female pattern hair loss, for instance in postpartum effluvium
that does not necessarily return to the same antepartum texture and length of hair. In
these cases the addition of topical minoxidil to the treatment regimen is usually help-
ful. Synchronization phenomena of hair cycling, also on a seasonal basis, seem to be
more pronounced in patients with female pattern hair loss, since with a shorter anagen
phase a greater proportion of hair follicles will synchronize.
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Figure 10: Telogen effluvium before (a) and after 6 months (b) of oral supplementation therapy with
L-cystine, medicinal yeast, and B-complex vitamins (from: Lengg et al. [34]).

Recommendations for treatment of primary chronic telogen effluvium are scanty,

and include topical or systemic corticosteroids [2], topical minoxidil, and dietary
supplements.

Value of oral supplementation therapy

The quantity and quality of hair are closely related the nutritional state of an indi- The quantity and quality of hair are
vidual. Normal supply, uptake, and transport of proteins, calories, trace elements, closely related the nutritional state of
and vitamins are of fundamental importance in tissues with a high biosynthetic activ- an individual.
ity such as the hair follicle. Because hair shaft is composed almost entirely of protein,
protein component of diet is critical for production of normal healthy hair. The rate
of mitosis is sensitive to the calorific value of diet, provided mainly by carbohydrates
stored as glycogen in the outer hair root sheath of the follicle. Finally, a sufficient sup-
ply of vitamins and trace metals is essential for the biosynthetic and energetic metab-
olism of the follicle. The effects of nutrition on hair growth have been recognized
from observations in inborn errors of metabolism, in deficiency disorders, and from
supplementation studies in animals and humans.
The rationale for the use of a dietary supplement based on L-cystine, usually in The rationale for the use of a dietary
combination with B vitamins, for treatment of hair loss is based on the biochemistry supplement based on L-cystine, usually
of cystine metabolism, clinical observations in disorders of cystine metabolism and in combination with B vitamins, for
deficiency, and results of supplementation studies. In the 1960s, the role of L-cystine treatment of hair loss is based on the
in the production of wool proteins was investigated, and it was found that enrich- biochemistry of cystine metabolism,
ment of even what appeared to be a normal diet with sulfur-containing amino acids clinical observations in disorders of
increased wool production in sheep. In the early 1990s, human studies on the effect cystine metabolism and deficiency, and
of dietary supplements containing L-cystine, usually in combination with B-complex results of supplementation studies.
vitamins or medicinal yeast that is rich in B-complex vitamins, have been published,
exclusively in German language, showing improvements in the trichogram (hair
pluck test), in hair swelling as a criterion for hair quality, and in the tensile strength
of the hair fiber, and in the phototrichogram [30–33]. We performed a study com-
bining epiluminiscence microscopy with digital image analysis (TrichoScan) to
demonstrate that a L-cystine-, medicinal yeast- and B-complex vitamin-based nutri-
ent influences hair growth in otherwise healthy women between 25 and 65 years
of age with telogen effluvium [34]: After 6 months of treatment the active com-
pound group showed a statistical significant improvement and normalization of
the anagen hair rate, while the placebo group did not. The hair count, hair densi-
ty, and cumulative hair shaft diameter did not show any changes from the baseline
values. Nevertheless, the change in anagen hair rate was sufficient to reflect in clin-
ical outcome, since the appearance of hair growth in the global photographic
assessment was judged better, probably due to the increase of the proportion of
actively growing hairs in anagen (Figure 10 a, b). The mechanism of action is not

© The Author • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010/0804 JDDG | 4 ˙2010 (Band 8)
294 Academy

Pulltest negative

positive Trichogram

LM
Dystrophic anagen effluvium Telogen effluvium

Patient history < 6 months: > 6 months:

Acute telogen effluvium Chronic telogen effluvium (CTE)

Chemotherapy Negative Patient history: Patient history and laboratory

Radiation exposure • Fever investigations
• Postpartum
• Crash diet

Occupational exposure Negative Negative: Secondary CTE:

Environmental exposure
Toxicologica l studies:
• Heavy metals
• Plant toxins
Primary CTE • Drugs
• Iron deficiency
• Thyroid dysfunction
• Other
Dermoscopy and/or biopsy for differential diagnosis:
• Diffuse alopecia areata
• Androgenetic alopecia

Figure 11: Scheme of systematic approach to diffuse hair loss.

known. Nevertheless, it recently was shown that the noxious effect of cigarette
smoke in exposed C57BL/6 mice could be abrogated by the oral administration of
N-acetylcysteine, an analogue and precursor of L-cysteine and reduced glu-
tathione, as well as by L-cystine, the oxidized form of L-cysteine, which is a key
hair component, in combination with vitamin B6, which plays a role in L-cystine
incorporation in hair cells [35]. The effect may be related to the glutathione-related
detoxification system.

It is important to control stress as a
complication of hair loss or fear of hair
loss.
Patients need to be educated about
the basics of the hair cycle, and why
usually considerable patience is re-
quired for effective cosmetic recovery.
Psychological counseling
Finally, the issue of psychogenic effluvium or of overvalued ideas in relation to the
condition of the hair is not always easy to resolve, however it is important to control
stress as a complication of hair loss or fear of hair loss. In general, the best way to alle-
viate the emotional distress caused by a hair disorder is to effectively treat it.
Psychotherapy is aimed at any associated symptomatology of depression, regardless
of whether there is a causal relationship between the psychiatric findings, hair loss or
fear of hair loss, because it is possible that patients who are depressed perceive even
normal hair shedding in an exaggerated manner. Patients with anxiety related to the
fear of hair loss may also benefit from anxiolytic therapy. In addition, appropriate
psychological support is essential to help limit patient anxiety. Patients need to be
educated about the basics of the hair cycle, and why usually considerable patience is
required for effective cosmetic recovery.

Concluding remark
Diffuse hair loss is a common complaint in women. It is paramount to address the
symptom systematically (Figure 11). The diagnosis can be established with a
detailed patient history, examination of the scalp and pattern of hair loss, a pull test
with examination of bulbs of shed hairs, trichoscopy, and few pertinent screening
blood tests. In selected cases a scalp biopsy may be required. Once the diagnosis is
established, treatment appropriate for that diagnosis is likely to control the hair
loss. The best way to alleviate the anxiety associated with hair loss is to effectively
treat it appropriately, and at the same time to educate the patient about the basics
of the hair cycle, and why considerable patience is required for effective cosmetic
recovery. <<<

Conflicts of interest
RMT has conducted clinical trials for Merz Pharma, and has had consultant activi-
ties for Asatona, Johnson & Johnson, MSD, and Procter & Gamble.

JDDG | 4 ˙2010 (Band 8) © The Author • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010/0804
 Academy 295

Correspondence to
Prof. Dr. med. Ralph M. Trüeb
Dermatologische Klinik, Universitätsspital Zürich
Gloriastrasse 31
CH-8901 Zürich, Switzerland
E-Mail: ralph.trueeb@usz.ch

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Fragen zur Zertifizierung durch die DDA

1. Welche der folgenden Aussagen c) Androgenetische Alopezie b) Diffuser telogener Haarausfall bei
zum Haarzyklus ist falsch? d) Postpartum dem kein spezifischer Auslöser
a) Der Follikel unterliegt einem e) Fieber nachweisbar ist.
ständigem Umsatz. c) Ausdünnung der zentralen
b) Jeder Follikel verfügt über seine 4. Was führt zu einem anagen- Kopfpartie bei Frauen infolge
individuelle Kontrolle über das dystrophischen Effluvium? telogenen Haarausfalls.
Durchlaufen der Haarzyklusphasen a) Chemotherapie d) Durch Frauen beklagter
c) Die zyklische Haarwachstumsak- b) Röntgenstrahlung Haarausfall ohne Nachweis
tivität unterliegt einem synchro- c) Alopecia areata eines Haarausfalls.
nisierten Muster. d) Alle genannten e) Keine Aussage trifft zu.
d) Es existiert eine allgemeine e) Alle außer c)
jährliche Periodizität von 8. Das verlässlichste Werkzeug zur
Haarwachstum und Haarausfall. 5. Welche der folgenden Bestimmung des Haarausfalls:
e) Nicht vernarbende Alopezie stellt Schwermetallexpositionen führt a) Trichoscan
eine Störung des Haarzyklus dar. nicht zu toxischer Alopezie? b) Haarzugtest
a) Kupfer c) Haarwaschtest
2. Welche dieser Aussagen trifft b) Amalgam d) Dermatoskopie
nicht für das Kopfhaar zu? c) Arsen e) Haarkalender
a) Kopfhaar verbleibt für 2–6 Jahre d) Quecksilber
in der Anagenphase. e) Cadmium 9. Dermatoskopische Hinweise auf
b) Die Dauer von Telogen ist etwa die Diagnose der diffusen Alopecia
100 Tage. 6. Welche sind typische areata:
c) In etwa deckt die Anzahl der Charakteristika des diffusen a) Anisotrichose
neuen Kopfhaare die der Telogeneffluviums? b) Leere Follikel
ausgefallenen Haare. a) Der diffuse Haarausfall führt zu c) Peripiläre Höfe
d) Die Relation von Anagen- zu Telo- einer gleichmäßigen Ausdünnung d) Yellow dots
genhaaren ist normalerweise 6 : 1. der Kopfhaare. e) Keiner der genannten
e) Die tägliche Anzahl ausgefallener b) Er beträgt üblicherweise
Telogenhaare liegt, abhängig von > 50 %. 10. Die zuverlässigste Behandlung
der Anzahl der Kopfhaare, zwischen c) Der Haarverlust manifestiert des chronischen
unter 50 bis über 100 Haare. sich häufig mit bitemporaler Telogeneffluviums:
Ausdünnung. a) Topisches Minoxidil
3. Welche der Folgenden ist eine d) Alle genannten. b) Eisenergänzung
typische Ursache des Telogenefflu- e) Alle außer b). c) Andere Diätergänzungen
viums infolge vorzeitiger Anagen- d) Behandlung der Ursache
abschaltung? 7. Chronisches Telogeneffluvium ist e) Versuch der Therapie mit
a) Chemotherapie definiert als: oralem Prednisolon in Dosen
b) Haarausfall infolge Beginn einer a) Diffuser telogener Haarausfall > 0,5 mg/kg
topischen Minoxidiltherapie über > 6 Monate Dauer.

Liebe Leserinnen und Leser,

der Einsendeschluss an die DDA für diese Ausgabe ist der 21. Mai 2010.
Die richtige Lösung zum Thema „Therapie des Basalzellkarzinoms“ in Heft 12 (Dezember 2009) ist: 1c, 2b, 3a, 4a, 5c, 6a, 7c,
8d, 9a, 10d.
Bitte verwenden Sie für Ihre Einsendung das aktuelle Formblatt auf der folgenden Seite oder aber geben Sie Ihre Lösung online
unter http://jddg.akademie-dda.de ein.

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