complementary and alternative medicine in alopecia areata

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Complementary and Alternative Medicinein Alopecia AreataFrank J.H.M. van den Biggelaar,1,2 Joost Smolders3 and Jacobus F.A. Jansen2,3,4

1 Alopecia Areata Patient Organization, Utrecht, The Netherlands

2 Department of Radiology, Maastricht University Medical Center, Maastricht, The Netherlands

3 School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands

4 Department of Medical Physics and Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

Contents

Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

2. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

2.1 Whole Medical Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

2.2 Mind-Body Medicine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

2.3 Biologically Based Practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

2.4 Manipulative and Body-Based Practices. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

2.5 Energy Healing Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

2.6 Animal and In Vitro Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

3. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

3.1 Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Abstract Alopecia areata is an unpredictable hair-loss condition. As there is no cure for alopecia areata and no

effective conventional therapy, a substantial number of alopecia areata patients resort to complementary

and alternative medical remedies and therapies (CAM). This review on the application of CAM in alopecia

areata addresses two pertinent aspects. First, it provides a current overview of the published medical liter-

ature on CAM used in alopecia areata, and alopecia areata-related studies. Second, it presents a thorough

assessment of the considerations and limitations of the use of CAM for the treatment of alopecia areata.

A systematic MEDLINE search yielded 13 studies of the clinical use of CAM in the management of

alopecia areata, all belonging to one of the five main categories of CAM. Methodological quality was

analyzed using objective assessment scores (Wilson and Lawrence scores). Unfortunately, no study was of

sufficient internal validity to provide robust evidence of the benefit of CAM. This might be attributable to

several specific disease characteristics of alopecia areata, which require an especially solid trial design to

properly assess the therapeutic effects of CAM. The review concludes with some recommendations for

improving the quality of trials incorporating CAM in the treatment of alopecia areata.

Alopecia areata is an unpredictable, usually patchy, non-

scarring, autoimmune, inflammatory hair-loss condition.[1] It is

a relatively common condition, with a reported incidence of

0.15% of the population,[2] and it accounts for approximately

2% of new patients attending dermatology outpatient centers in

the UK and theUS.[3,4] The severity and pattern of hair loss can

vary substantially between individuals, for example, from

small, hardly visible spots that often regenerate spontaneously,

Approval for publication Signed Date Number of amended pages returned

REVIEW ARTICLEAm J Clin Dermatol 2010; 11 (1): 1-10

1175-0561/10/0001-0001/$49.95/0

ª 2010 Adis Data Information BV. All rights reserved.

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to long-term forms of complete hair loss. Extensive hair loss is

experienced by about 30% of people with alopecia areata.[2] The

condition can affect the entire scalp (alopecia totalis) or can

even cause loss of all body and scalp hair (alopecia uni-

versalis).[4] The majority of people with alopecia areata ex-

perience only the occasional bald area, which spontaneously

resolves within a year, but most will experience a relapse at

some stage in their life. Factors associated with a less favorable

prognosis are a family history of alopecia areata, childhood

onset, severe hair loss, and a history of atopic diseases or auto-

immune conditions, particularly thyroid disease.[3] Although

the exact pathogenesis of alopecia areata is unknown, an auto-

immune basis is assumed.[5] A combination of a genetic sus-

ceptibility and as yet largely undefined environmental factors is

believed to trigger alopecia areata development. These en-

vironmental factors include physical stress, trauma, or a major

life crisis,[3] but often a specific trigger cannot be identified.[2]

There is no cure for alopecia areata and no effective con-

ventional therapy to induce hair regrowth and sustain remis-

sion.[2] Conventional treatment options most often used, albeit

with a disappointing success rate, are glucocorticoids and

minoxidil.[6] Alopecia areata is associated with significant

psychosocial problems, such as reduced self-esteem, and may

negatively affect quality of life.[7] As the psychologically de-

bilitating nature of alopecia areata and the possibility of long-

term hair loss are rather unpleasant for many alopecia areata

patients, a substantial number of them resort to complementary

and alternative medical remedies and therapies (CAM).[8] This

interest in CAM can be clearly noted through the numerous

threads on alternative therapy on the message boards for

patients with hair problems,[9] blogs reporting on CAM,[10]

and the patients’ questions on CAM for medical specialists

associated with the National Alopecia Areata Foundation.[11]

On the whole, a dramatic increase in the use of CAM by

the public has been reported in recent years.[12] Consumers

find CAM attractive as they perceive many modalities to be

based on what they regard to be a more holistic approach,

which allows patients to feel they are more actively partici-

pating in their own healthcare. In addition, there is the belief

that natural therapies will be safer and more effective than

synthetic pharmaceuticals. On the other hand, healthcare

professionals often dismiss CAM, based on what they believe

to be a lack of sufficient scientific evidence to support their

effectiveness, and attribute their perceived efficacy, by pa-

tients, to the high placebo response rates associated with

many of the disorders for which CAM are most commonly

employed. However, since alternative medicine is becoming

increasingly popular with the public worldwide, it is also

starting to receive more attention in systematic studies and

experimental research.

CAM is defined by the National Center for Complementary

and Alternative Medicine (NCCAM) of the National Institute

of Health (Bethesda, MD, USA) as medical practices that are

not currently considered to be a part of conventional medi-

cine.[13] Complementary medicines or medical practices are

taken or used in conjunction with conventional medicines,

whereas alternative medicines or medical practices are taken or

used in place of conventional medicines or practices. CAM are

usually divided into five main categories: (i) whole medical

systems; (ii) mind-body medicine; (iii) biologically based prac-

tices; (iv) manipulative and body-based practices; and (v) en-

ergy healing therapies.[13]

Individual physicians are currently confronted with ques-

tions from patients regarding all these therapies. Therefore, it

would be beneficial to have a comprehensive review that covers

the evidence for the efficacy of different CAM that have been

published so far. Numerous reports on CAM and their effects

on hair growth in the form of case reports, patient series, animal

studies, and in vitro cellular studies have been published.

However, the number of CAM that have been submitted to

scientific study in the form of randomized controlled trials

(RCTs) in alopecia areata populations is rather limited.

This review on the application of CAM in alopecia areata

addresses two pertinent aspects of CAM and its application to

alopecia areata. First, it provides a current overview of the

literature on all CAM used in alopecia areata, and alopecia

areata-related studies (animal or in vitro). Second, it presents a

thorough assessment of the considerations and limitations of

CAM and their application to alopecia areata.

1. Methods

A systematic MEDLINE search was performed to identify

alternative medications and their potential clinical uses from

human, animal, and in vitro studies. Review articles were also

searched for additional references. No restrictions were placed

on the search by type of publication, publication date, or

country. The search was restricted to publications in English,

French, and German.

All papers evaluating CAM in the management of patients

categorized as having alopecia areata, irrespective of the cri-

teria for diagnosis, were included. Multiple component thera-

pies were excluded. Any patient-related outcome measure was

deemed eligible for inclusion. All study designs were included in

an attempt to capture all the available data.

2 van den Biggelaar et al.

ª 2010 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2010; 11 (1)

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A scoring system was used to assess the internal validity for

non-randomized trials.[14] Uncontrolled studies are recognized

to be methodologically weaker than RCTs. We assessed the

quality of the uncontrolled trials by extracting data according

to a four-point scoring system (Wilson score) that took into

account the availability of before and after data (one point),

assessment of confounders (one point), and dropouts (two

points). The quality of trials to a randomized standard was

assessed by a three-point scoring systemdefinedby theCanadian

Task Force on the Periodic Health Examination[15] as im-

plemented by Lawrence and Mickalide[16] (Lawrence score).

This score ranks grades of evidence as: (I) evidence obtained

from at least one properly conductedRCT; (II-1) evidence from

well designed, controlled trials without randomization; (II-2)

evidence from well designed cohort (prospective or retro-

spective) or case-controlled studies, preferably from more than

one center or research group; (II-3) evidence obtained from

comparisons between times or places with or without inter-

vention; and (III) opinions of respected authorities, based on

clinical experience, descriptive studies, or reports of expert

committees. Data extraction aimed to establish the study size,

patient demographics, details of interventions, outcome mea-

sures, duration of follow-up, and results. Final searches of the

literature were undertaken in January 2008.

2. Results

A systematic MEDLINE search yielded 13 studies of the

clinical use of CAM in the management of alopecia areata, all

belonging to one of the five main categories of CAM. The

studies are summarized in table I. The quality and validity of

the studies are expressed as the Wilson and the Lawrence

scores.

2.1 Whole Medical Systems

‘Whole medical systems’ is the NCCAM classification for

those forms of alternative medicine that are built upon a

complete system of theory and practice. Of these approaches,

homeopathy has been applied by Itamura.[17] Homeopathy is a

form of alternative medicine in which a dilution of a certain

substance (pathogenic or non-pathogenic) to a non-detectable

low concentration is claimed to have a therapeutic effect on

consumers.[31] In a case report, Itamura[17] describes the treat-

ment of a 20-year-old woman, who had alopecia universalis for

7 years, with the homeopathic medicineMercurius. The patient

was treated for 3months, and effectiveness of the treatment was

evaluated using the patient’s own assessment of overall im-

pression. According to the patient, the homeopathic treatment

yielded a ‘significant improvement.’

2.2 Mind-Body Medicine

Mind-body interventions are alternative therapies that cover

a variety of techniques designed to enhance the mind’s capacity

to affect bodily function and symptoms.[13]

Two studies have evaluated the effect of hypnotherapy for the

treatment of alopecia areata.[18,19] In hypnotherapy, the subject

is brought into a trance-like state (hypnosis) of inner absorp-

tion, concentration, and focused attention that is induced by a

therapist, whose suggestions are readily accepted by the subject.[19]

Harrison and Stepanek[18] treated patients with extensive alo-

pecia areata using hypnotherapy. They included 12 patients in

the study, of whom five completed the protocol. During this

therapy, techniques were used such as direct and indirect sug-

gestions, and ego strengthening. Afterwards, the patients who

completed the protocol reported a feeling of general well-being.

However, cosmetic hair growth was seen in only one patient.

Recently, Willemsen et al.[19] used hypnosis to treat 28 alopecia

areata patients who were refractory to previous conventional

treatments. Hypnotherapy was either applied in an alterna-

tive or complementary fashion. Of the 28 patients included, 21

patients completed the treatment and seven withdrew because

of lack of motivation. The 21 patients who completed the study

were comprised of nine with alopecia totalis or alopecia uni-

versalis and 12 with extensive alopecia areata, with a disease

course varying from 6 weeks to 4 years. After treatment, all pa-

tients who completed the protocol had a significantly lower score

for anxiety and depression. Significant hair growth was found in

12patients after three to eight sessions, with total hair regrowth in

nine patients. Of these responders, three used no additional

conventional therapies, whereas eight used conventional therapy

including corticosteroids and immunotherapy. In five patients, a

significant relapse occurred when treatment ended.

Psychotherapy and administration of immunosuppressants

(2 months of monotherapy with prednisolone 5–10mg/day,followed by 4–5 months of combination therapy with cyclo-

sporine [ciclosporin] 2.5mg/kg) was used by Teshima et al.[20]

for the treatment of alopecia areata. Eleven patients with re-

fractory alopecia universalis were included in this study: six

patients received psychotherapy and immunotherapy, whereas

five patients received only immunotherapy. Psychotherapy in-

cluded relaxation and image therapy and was conducted for

30 minutes once a week for a 2-month period. Hair regrowth

and stress relief were observed in five of six patients treated with

Alternative Medicine in Alopecia Areata 3


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Tab

leI.

Com

ple

menta

ryand

altern

ative

medic

alre

medie

sand

thera

pie

s(C

AM

)in

alo

pecia

are

ata

Stu

dy,year,

location

CA

Ma

Desig

n(n

o.of

pts

;sex)

Age

(y)

Dura

tion

of

alo

pecia

are

ata

Inte

rvention/A

LT

or

CO

MP

Contr

ol

treatm

ent

Outc

om

es

Trial

dura

tion

Follo

w-u

p

period

Results

Wils

on

score

b

Law

rence

score

c

Itam

ura

,[17]2007,

Japan

IC

ase

report

(1F

)

20

7y

Hom

eopath

y/A

LT

NR

Well-

bein

g3

mo

NR

Sig

nific

ant

impro

vem

ent

0II

I

Harr

ison

and

Ste

panek,[1

8]

1991,U

K

IIP

atientseries

(12;4

M,8

F)

19–64

>5y

Hypnoth

era

py/A

LT

NR

Hair

gro

wth

3m

oN

RS

lightim

pro

vem

ent

2II

I

Will

em

sen

etal.,[1

9]2006,

Belg

ium

IIP

atientseries

(21;5

M,16

F)

15–68

6w

kto

4y

Hypnoth

era

py/C

OM

P+

ALT

NR

Well-

bein

g,

hair

gro

wth

5y

4m

oto

4y

Bett

er

well-

bein

g;

regro

wth

in12/2

1,

with

rela

pse

in5

pts

2II

I

Teshim

a

etal.,[2

0]1991,

Japan

IIP

atientseries

(11;6

M,5

F)

9–28

1–10

yP

sychoth

era

py/C

OM

P

(n=

6)

Imm

unoth

era

py

(n=

5)

Hair

gro

wth

2m

oN

RF

ull

regro

wth

(5/6

pts

receiv

ing

psychoth

era

py

plu

s

imm

unoth

era

py)

1II

I

Hay

etal.,[2

1]

1998,U

K

IIrc

t

(84)

39

–15

0to

>9y

Aro

math

era

py/A

LT

(n=

43)

Carr

ier

oils

(n=

41)

Hair

gro

wth

7m

o7

mo

Sig

nific

ant

impro

vem

ent

(54

%of

pts

inactive

treatm

ent

gro

up

impro

ved

vs

21

%in

contr

olg

roup)

2I

Sharq

uie

and

Al-O

baid

i,[2

2]

2002,Ir

aq

III

sb,pc

stu

dy

(62;40

M,22

F)

3–50

Recent

Onio

nju

ice/C

OM

P

(n=

45)

Wate

r(n

=17)

Hair

gro

wth

8w

kN

RS

ignific

ant

impro

vem

ent

(hair

regro

wth

in87

%ofpts

treate

dw

ith

onio

n

juic

evs

13

%ofcontr

ol

pts

)

1II

-1

Hajh

eydari

etal.,[2

3]2007,

Iran

III

db,rc

t

(40;22

M,18

F)

25

–16

<1m

oG

arlic

gel/C

OM

P

(n=

20)

Pla

cebo

gel

(n=

20)

Hair

gro

wth

3m

oN

RS

ignific

ant

impro

vem

ent

2I

Much,[2

4]

1976,S

witzerland

III

Com

para

tive

stu

dy

(66)

NR

NR

Vitam

inA

acid

(tre

tinoin

)/ALT

(n=

30)

Topic

al

cort

icoste

roid

s

(n=

36)

Hair

gro

wth

3m

o8

wk

Impro

vem

ent(h

air

regro

wth

in70

%ofpts

treate

dw

ith

vitam

inA

acid

vs

47

%ofcontr

ol

pts

)

1II

-2

Xie

,[25]2005,

Chin

a

III

Case

report

(1F

)

11

1.5

yT

CM

concoction/A

LT

NR

Well-

bein

g,

hair

gro

wth

3m

oN

RIm

pro

vem

ent

0II

I

Hofe

r

etal.,

[26]1969,

Germ

any

IVC

om

para

tive

stu

dy

(130;

56

M,74

F)

6–69

NR

Segm

enta

l

massage/C

OM

P

Ora

l

cort

icoste

roid

s

Hair

gro

wth

3–5

wk

NR

Cle

ar

reduction

in

gro

wth

tim

e

0II-2

Continued

nextpage



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psychotherapy, whereas hair regrowth was observed in one

of five patients treated with immunosuppressants alone. The

authors suggested that alleviating stress facilitates recovery of

immunologic competence.

Aromatherapy is the use of essential oils from plants to

support and balance themind, body, and spirit. Alopecia areata

was treated with 7 months of aromatherapy by Hay et al.[21,32]

A mixture of thyme, rosemary, lavender, and cedarwood es-

sential oils in jojoba and grape seed carrier oils massaged into

patients’ scalps significantly improved the alopecia areata when

compared with the carrier oils alone (improvement in 54% and

21% of patients, respectively). The efficacy of the treatment was

evaluated at initial assessment and 3 and 7 months after treat-

ment by dermatologists’ visual scoring of photographs and

a computerized analysis of traced areas of alopecia. The

distribution of several prognostic factors in the cohorts was

described, but the distribution between the treatment arms of

disease duration and the extent and severity of the alopecia

areata were not mentioned.

2.3 Biologically Based Practices

Biologically based practices in CAMuse substances found in

nature, such as herbs, foods, and vitamins that are not part of

conventional medicine.[13] Several researchers have used bio-

logic compounds to treat alopecia areata patients. Sharquie and

Al-Obaidi[22] investigated the effectiveness of topical crude

onion juice in the treatment of patchy alopecia areata in com-

parison with tap water. Sixty-two patients were enrolled in

a single-blind, placebo-controlled clinical study of 8 weeks

duration. Forty-five patients underwent the onion juice treat-

ment, and 17 patients underwent the control treatment with tap

water. All patients had recently developed alopecia areata, and

severe cases (alopecia universalis and alopecia totalis) were

excluded. Hair regrowth was observed in 87% of patients

treated with onion juice, whereas only 13% of the control group

displayed hair regrowth.

An Iranian research group investigated the effectiveness of

topical garlic gel as complementary medicine in the treatment

of alopecia areata.[23] A group of 40 patients with alopecia

areata received topical application of corticosteroid twice daily.

Patients had up to three hairless patches, and a disease duration

of <1 month. Using a randomized, double-blind, controlled

design, the patients were divided into two groups: a group of 20

patients treated with garlic gel, and a control group of 20 pa-

tients receiving a placebo treatment for 3 months. Effectiveness

was assessed by a dermatologist, blinded to the treatment

status. A beneficial effect of garlic gel on the therapeutic efficacyTab

leI.

Contd

Stu

dy,year,

location

CA

Ma

Desig

n(n

o.of

pts

;sex)

Age

(y)

Dura

tion

of

alo

pecia

are

ata

Inte

rvention/A

LT

or

CO

MP

Contr

ol

treatm

ent

Outc

om

es

Trial

dura

tion

Follo

w-u

p

period

Results

Wils

on

score

b

Law

rence

score

c

Putt

etal.,[2

7]

1994,U

S

IVC

ase

report

(1M

)

16

5y

Massage,re

laxation

and

rew

ard/A

LT

NR

Patc

hsiz

e149

d14

mo

Full

regro

wth

1II

I

Ge,[2

8]1990,

Chin

a

VC

ase

report

s(9

)55

(mean)

3m

oA

cupunctu

re/A

LT

NR

Hair

gro

wth

NR

1y

Com

ple

tere

gro

wth

in8

pts

0II

I

Annin

os

etal.,[2

9,3

0]

2002,2004,

Gre

ece

VC

ase

report

s

(6;5F

,1

M)

6–23

1–8

yT

MS/A

LT

(n=

3)

Regula

r

thera

py

(n=

3)

Hair

gro

wth

14

mo

2y

Sig

nific

ant

impro

vem

ent

1II

I

aC

AM

cate

gories:(I

)w

hole

medic

als

yste

m;(I

I)m

ind-b

ody

inte

rvention;(I

II)

bio

logic

ally

based

pra

ctice;(I

V)

manip

ula

tive

and

body-b

ased

pra

ctices;(V

)energ

yhealin

gth

era

pie

s.

bW

ilson

score

:befo

reand

aft

er

data

availa

ble

(one

poin

t);asse

ssm

entofconfo

unders

(one

poin

t);dro

pouts

record

ed

(one

poin

t);fo

llow

-up

ofth

edro

pouts

(one

poin

t).[1

4]

cLaw

rence

score

:(I

)evid

ence

obta

ined

from

at

least

one

pro

perly

conducte

drc

t;(I

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of topical corticosteroid therapy in patients with alopecia

areata was observed.

The treatment of alopecia areata with vitamin A acid

(tretinoin 0.05% gel) was described by Much.[24] In this study,

30 patients with alopecia areata were treated with vitamin A

acid and 36 patients were treated with a topical corticosteroid

or hyperemia-producing gel. Patients with patches on the

head, excluding patients with alopecia totalis, were treated for

12 weeks. The efficacy of the treatment was evaluated by a

dermatologist 8 weeks after termination of therapy, who in-

dicated a successful treatment when hair was fully regrown, or

when an obvious improvement of the clinical status by >50%had occurred. Hair regrowth was observed in 70% of patients

treated with vitamin A acid, whereas only 47% of the control

group displayed hair regrowth.

Xie[25] described a case report of an 11-year-old girl with a

1.5-year history of alopecia areata, who was treated with a

traditional Chinese medicine concoction. The concoction,

mostly consisting of roots of various origins, was taken orally

and applied to the scalp. After treatment for 3 months, hair re-

growth occurred and an improvement inwell-beingwas observed.

2.4 Manipulative and Body-Based Practices

This form of alternative therapy is based uponmanipulation

and/or movement of one or more parts of the human body.[13]

In the literature, massage for the treatment of alopecia areata

has been described by two research groups.

Hofer et al.[26] described an investigation of the efficacy of

segmental massage for the treatment of alopecia areata. A total

of 130 patients were divided into four groups: (I) local treat-

ment with propyl niacin (pyridine-3-carboxylate; a nicotinic

acid propylester, also used as a hyperemia-inducing substance);

(II) local treatment with propyl niacin and segmental massage;

(III) local treatment with propyl niacin and oral prednisone

30mg/day; and (IV) local treatment with propyl niacin, oral

prednisone 30mg/day, and segmental massage. Groups I and II

included milder forms of alopecia areata, whereas III and IV

included more severe forms of alopecia areata. Patients with

alopecia areata totalis were excluded. Efficacy of treatment was

evaluated by measuring the time to grow hairs with a length of

0.5–1.0 cm in all areas. A total of 12–24 segmental massages

were applied by an experienced physiotherapist. Segmental

massage significantly reduced the time for hair regrowth by

34% compared with propyl niacin therapy alone, and 75%compared with propyl niacin and prednisone therapy.

In a case report described by Putt et al.,[27] three treatment

techniques (hair massage, relaxation procedures, and monetary

reward) were applied to a 16-year-old male patient with a 5-year

history of alopecia areata. During the 7-month treatment period,

disease went into remission and hair loss was reduced.During the

last 4 months of the study, new hair growth was observed.

2.5 Energy Healing Therapies

In energy healing therapies, energy is applied during treat-

ment. Two types of energy exist: (i) veritable, which can be

measured; and (ii) putative, which has yet to be measured.[13]

Transcranial magnetic stimulation (TMS) is a form of veri-

table energy therapy. Neurons in the brain are believed to be

excited byweak electric currents induced in the tissue by rapidly

changing magnetic fields.[29] TMS was recently applied by

Anninos et al.[29,30] for the treatment of alopecia areata. In

total, three patients with alopecia areata (duration 1–8 years)

were treated with TMS, with a therapeutic protocol consisting

of a low-intensity external magnetic field (five sessions per

week). All patients displayed an improvement in hair regrowth

during the treatment period.

Another form of energy healing therapy is acupuncture. This

putative form of energy therapy is a technique of inserting and

manipulating needles into points on the body with the aim of

restoring health and well-being. Ge[28] described nine patients

with alopecia areata who were treated with acupuncture. Full

hair regrowth was reported in eight patients, and marked im-

provement in one patient.

2.6 Animal and In Vitro Studies

A vast amount of literature exists where CAM have been

applied to promote hair growth in non-human subjects. The

examined populations vary from shaved mice,[33-37] Wistar al-

bino rats,[38] and cats[39] to human hair follicles.[37,40] One case

report describes the successful application of acupuncture to a

cat with alopecia due to extensive licking.[39] Most of these

therapies belong to CAM category III – biologically based

practices. Root[34,36] and plant worm[35] extracts are especially

popular, in addition to polyphenolic compounds present in

green tea.[33,40] Often, these compounds are traditionally ac-

claimed for their hair growth-promoting potential. However,

the clinical relevance of these studies is limited. The evidence

that a certain natural compound is beneficial with respect to

hair growth on shavedmice has little relevance for patients with

alopecia areata. The in vitro application of certain compounds

on cultures of human dermal papilla cells might be more re-

levant,[37,40] although the cells used usually originate from men

with alopecia androgenetica, a condition where other cellular

and molecular mechanisms are involved.[41]



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Another approach for understanding, implementing, and

refining new therapies for alopecia areata is the use of rodent

models. Two established rodent models for alopecia areata are

the C3H/HeJ mouse[42] and the DEBR (Dundee Experimental

Bald Rat).[43] These models display a patchy alopecia that is

clinically and histopathologically similar to human alopecia

areata.

C3H/HeJ mice display a diffuse non-scarring alopecia with

clinical and pathologic features similar to alopecia areata.[42]

On the dorsal skin, the alopecia develops in circular areas with

disease involvement restricted to anagen follicles.

The DEBR arose as a spontaneous mutation at the Uni-

versity of Dundee, Scotland.[43] These animals grow a normal

first coat of hair but then become progressively hairless. His-

tology of the skin confirms the persistence of hair follicles in a

pattern similar to that observed in human alopecia areata. Thus

far, mostly traditional topical sensitizers such as diphencyprone

have been applied on these rodent models, yielding convincing

hair growth on the treated portions of the animals.[44] In future

CAM studies, it might be interesting to apply the therapy to one

of the established rodent models for alopecia areata, instead of

shaven mice or rats.

3. Discussion

All of the published trials identified by this comprehensive

systematic review provided evidence to suggest that CAM are

effective in the management of alopecia areata, with the main

measured effects being substantial hair regrowth and improved

well-being. This is remarkable, as of the 13 studies identified,

approximately one negative result would be expected by chance

alone. These unanimous positive results hint at a publication

bias.[45]

However, despite all the positive results, unfortunately no

study was of sufficient internal validity to provide robust evi-

dence of the benefit of CAM in alopecia areata. Even the RCTs

(of Hay et al.[21] and Hajhydari et al.[23]) and controlled studies

(Sharquie and Al-Obaidi,[22] Much,[24] and Hofer et al.[26]) in-

cluded in this review did not satisfy objective quality require-

ments. This might be attributable to several specific disease

characteristics of alopecia areata, which require an especially

solid trial design to assess the therapeutic effects of CAM

properly. In this regard, the development of alopecia areata and

its evolution over time is relevant.Madani and Shapiro[3] stated

that: ‘‘the only predictable thing about the progress of the

alopecia areata is that it is unpredictable.’’ An evaluation of 230

patients by Walker and Rothman[46] showed that the duration

of the initial attack was <6months in 33% and <1 year in 50% of

patients. This indicates that results from studies that include

patients who have had alopecia areata for <1 year should be

interpreted with caution. Furthermore, Walker and Rothman[46]

reported that relapse occurred in 86% of the patients. Vestey

and Savin[47] included 50 patients with extensive alopecia areata

(>40% hair loss). Twenty-four percent of these patients ex-

perienced spontaneous complete or nearly complete regrowth

in a follow-up period of 3–3.5 years. Tosti et al.[48] followed

191 patients who hadmild and severe alopecia areata for <2 yearsat the first consultation for a mean of 17.7 years. In patients

with mild alopecia areata, about 50% were free of disease after

long-term follow-up. These studies show that regrowth can

occur at any time, which makes it very difficult to draw con-

clusions when only a few patients are included in a trial and

when no solid randomization has been applied.

Furthermore, alopecia areata is a disease of great hetero-

geneity in which the severity and extent can vary from a

few patches to alopecia universalis. A trial should either con-

tain enough patients to assess the effect of treatment in

each specific subgroup, or be confined to an individual group.

There are several factors that affect the disease course, includ-

ing family history and the presence of other autoimmune dis-

eases. Treatment and placebo arms should therefore be well

matched and these factors should be taken into account in

appropriate statistical methods to correct for the multiple

comparisons.

There are also some CAM-specific pitfalls that should be

taken into account when assessing therapeutic effects. The lay

literature and the Internet continue to maintain the perception

that natural therapies and products such as herbs tend to be

safer than conventional medicines. Modern medical practice

relies heavily on the use of highly purified pharmaceutical

compounds whose purity, efficacy, and toxicity can be easily

assessed. In contrast, for many CAM, such as herbal medicines,

there are different manufacturing standards and criteria of

purity, and these herbs contain mixtures of natural compounds

that have not undergone detailed analyses and whose mecha-

nism of action is not known.[49] Therefore, safety and adverse

effects are important issues when considering CAM strate-

gies.[31] Translating traditional CAM practices into acceptable

evidence-based Western therapies can be challenging.[50] For

example, the medicinal role of herb extracts may lie in the

synergistic interaction of the many constituents. When such a

complex mixture is fractioned, the active ingredients are sepa-

rated and efficacy may be lost. Similarly, therapies such as

acupuncture, hypnotherapy, and aromatherapy require well

trained therapists, whose professional training has unfortu-

nately not been standardized.



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3.1 Recommendations

It is essential that, in a similar fashion as for conventional

therapies, alternative therapies are evaluated using rigorously

conducted scientific tests of efficacy based on accepted rules

of evidence. The lack of properly designed and conducted

RCTs is a major deficiency. The current evidence is inadequate

for development of practice guidelines for alternative thera-

pies, largely because of a lack of relevant outcomes data from

high-quality clinical trials. We recommend adhering to the

CONSORT statement,[51] which is intended to improve the

reporting of RCTs, enabling readers to understand the design,

method, analysis, and interpretation of a trial, and to assess the

validity of its results. It emphasizes that this can only be

achieved through complete transparency from authors.

However, some supporters of alternative medicine might

argue that many alternative therapies can not be subjected to

the standard scientific method and, thus, instead must rely on

anecdotes, beliefs, theories, testimonials, and opinions to sup-

port effectiveness and justify continued use. Regardless of the

origin or type of therapy, the theoretical underpinnings of its

mechanism of action, or the practitioner who delivers it, the

critical questions are the same.[52] For virtually all medical

therapies and interventions, whether conventional or alter-

native, determination of effectiveness and recommendations

for clinical application should be based on the strength of the

scientific evidence using explicit criteria for grading the quality

of evidence.

Additionally, alternative medicine comprises a large and

heterogeneous group of treatments, many of which are proce-

dures that are not readily testable under blinded conditions and

for which the choice of appropriate control conditions is by no

means straightforward. Sometimes, it is nearly impossible to

conduct studies under conditions inwhich both the patients and

practitioners are blinded.[53] Training and competency are a

prerequisite to providing the treatments, and experienced

practitioners will know which treatment is hypothesized to be

active. Unlike pharmacotherapy studies in which the active

medication and the pill placebo can be made to be identical in

appearance, procedures are observably different to all of the

participants in the study. For example, acupuncture RCTs may

need to be conducted unblinded, with multiple checks on bias.[53]

Nevertheless, a proper, well considered design will yield

more scientific evidence than studies of inferior quality. In cases

where it is hard to use therapeutic procedures under fully

blinded conditions, it should always be possible to rely on ob-

jective assessment of (successful) treatment. Studies will hugely

benefit when the assessment of hair regrowth is performed

using objective criteria. In this regard, the objective four-point

scale as described by Hull and Norris[54] is highly recom-

mended. Hay et al.[21] also describe an additional standardized

professional photographic assessment performed by two in-

dependent observers and a computerized patch size analyzer

using transparent films. In addition to hair regrowth, the

patient’s well-being is a valuable outcome measure to incor-

porate in an alopecia areata trial. After all, if the patient’s well-

being improves, even without any hair regrowth, the end result

can still be positive. For this outcome, a questionnaire such as

the Symptom Check List (SCL)-90,[55] which assesses eight

different psychological symptoms, can be advantageous.

Unfortunately, the studies presented in this review do not

satisfy objective quality requirements and should therefore be

interpreted with caution. Further investigation of these thera-

pies under accurate experimental conditions would better esti-

mate their true clinical benefit. Indeed, the lower cost, ample

accessibility, and potential clinical improvement with these

newer unconventional remedies is encouraging for continued

research.However, it remains to be seenwhich, if any, provide a

more advantageous therapeutic ratio than standard agents.

4. Conclusions

The recourse of alopecia areata patients to CAM is wide-

spread, and therefore doctors must be familiar with this practice.

Furthermore, it would be beneficial if physicians attempted to

understand their patients’ confidence in these therapies despite

a lack of scientific basis. It is important to realize that not all

CAM are identical, and that some, such as hypnotherapy or

forms of herbal therapy, may well find a place in the complete

armamentarium of a physician caring for alopecia areata pa-

tients. Nevertheless, more research in the form of controlled

studies is needed. These studies should not only assess hair

regrowth in an objective manner, but also look at the patients’

well-being. The lack of truly randomized, placebo-controlled

trials of high quality for CAM is rather disappointing.

Acknowledgments

No sources of funding were used to assist in the preparation of this

review. The authors have no conflicts of interest that are directly relevant

to the content of this review.

References1. Sehgal VN, Jain S. Alopecia areata: clinical perspective and an insight into

pathogenesis. J Dermatol 2003 Apr; 30 (4): 271-89

2. Sinclair RD. Alopecia areata. In: Sinclair RD, Banfield C, Dawber R, editors.

Handbook of diseases of the hair and scalp. Oxford: Blackwell Science Ltd,

1999: 75-84



AU

TH

OR

PR

OO

F

3. Madani S, Shapiro J. Alopecia areata update. J Am Acad Dermatol 2000 Apr;

42 (4): 549-66; quiz 67-70

4. Price VH. Treatment of hair loss. NewEngl JMed 1999 Sep 23; 341 (13): 964-73

5. Green J, Sinclair RD. Genetics of alopecia areata. Australas J Dermatol 2000

Nov; 41 (4): 213-8

6. Wasserman D, Guzman-Sanchez DA, Scott K, et al. Alopecia areata. Int J

Dermatol 2007 Feb; 46 (2): 121-31

7. McMichael A. Impact of hair disorders and pigment disorders on quality of

life. In:RajagopalanR, Sherertz E,AndersonR, editors. Caremanagement of

skin diseases, life quality and economic impact. New York: Marcel Dekker

Inc., 1998: 207-23

8. Levin C, Maibach H. Exploration of ‘‘alternative’’ and ‘‘natural’’ drugs in

dermatology. Arch Dermatol 2002 Feb; 138 (2): 207-11

9. Hairweb Forum. The support site for people with hair problems in The

Netherlands and Belgium [online; in Dutch]. Available from URL: http://

www.haarweb.nl/forum/index.php [Accessed 2007 Aug 1]

10. Russo J. Home remedies to treat alopecia areata: the CAM report.

Complementary and alternative medicine: fair, balanced, and to the point

2007 [online]. Available from URL: http://www.thecamreport.com/?p=744[Accessed 2008 Jan 1]

11. Shapiro J, Kalish RS, Mallory S, et al. Medical questions and answers: alter-

native treatments. 17th Annual National Alopecia Areata Foundation In-

ternational Conference; 2002 Jul 11-14; St. Louis (MO)

12. EisenbergDM,DavisRB, Ettner SL, et al. Trends in alternativemedicine use in

the United States, 1990-1997: results of a follow-up national survey. JAMA

1998 Nov 11; 280 (18): 1569-75

13. National Center for Complementary andAlternativeMedicine.What is CAM?

2007 [online]. Available from URL: http: //nccam.nih.gov/health/whatiscam/[Accessed 2007 Aug 1]

14. Wilson S, Maddison T, Roberts L, et al. Systematic review: the effectiveness of

hypnotherapy in the management of irritable bowel syndrome. Aliment

Pharmacol Ther 2006 Sep 1; 24 (5): 769-80

15. Canadian Task Force on the Periodic Health Examination. The periodic health

examination 2: 1987 update. CMAJ 1988 Apr 1; 138 (7): 618-26

16. Lawrence RS, Mickalide AD. Preventive services in clinical practice: designing

the periodic health examination. JAMA 1987 Apr 24; 257 (16): 2205-7

17. Itamura R. Effect of homeopathic treatment of 60 Japanese patients with

chronic skin disease. Complement Ther Med 2007 Jun; 15 (2): 115-20

18. Harrison PV, Stepanek P. Hypnotherapy for alopecia areata. Br J Dermatol

1991 May; 124 (5): 509-10

19. Willemsen R, Vanderlinden J, Deconinck A, et al. Hypnotherapeutic man-

agement of alopecia areata. J Am Acad Dermatol 2006 Aug; 55 (2): 233-7

20. Teshima H, Sogawa H, Mizobe K, et al. Application of psychoimmuno-

therapy in patients with alopecia universalis. Psychother Psychosom 1991;

56 (4): 235-41

21. Hay IC, Jamieson M, Ormerod AD. Randomized trial of aromatherapy: suc-

cessful treatment for alopecia areata.ArchDermatol 1998Nov; 134 (11): 1349-52

22. Sharquie KE, Al-Obaidi HK. Onion juice (Allium cepa L.), a new topical

treatment for alopecia areata. J Dermatol 2002 Jun; 29 (6): 343-6

23. Hajhydari Z, JamshidiM, Akbari J, et al. Combination of topical garlic gel and

betamethasone valerate cream in the treatment of localized alopecia areata:

a double-blind randomized controlled study. Indian J Dermatol Venereol

Leprol 2007 Jan-Feb; 73 (1): 29-32

24. Much T. Treatment of alopecia areata with vitamin A acid [in German].

Zeitschrift fur Hautkrankheiten 1976 Dec 1; 51 (23): 993-8

25. Xie S. Three typical dermatological cases treated by Dr. Li Yueping. J Tradit

Chin Med 2005 Jun; 25 (2): 129-31

26. Hofer W, Honemann W, Sierke ML. Treatment of alopecia areata with seg-

mental massage [in German]. Dermatol Monatsschr 1969; 155 (9): 724-9

27. Putt SC,Weinstein L,DzindoletMT.A case study:massage, relaxation, and re-

ward for treatment of alopecia areata. Psychol Rep 1994 Jun; 74 (3 Pt 2): 1315-8

28. Ge S. Treatment of alopecia areata with acupuncture. J Tradit Chin Med 1990

Sep; 10 (3): 199-200

29. Anninos P, Karpouzis A, Kotini A, et al. Exogenous magnetic stimulation in

therapeutic management of universalis alopecia areata. Gazzetta Medica

Italiana-Archivio per le Scienze Mediche 2004; 163: 281-4

30. Anninos PA, Karpouzis A, Kotini A, et al. Magnetoencephalography mea-

surements and exogenousmagnetic stimulation in therapeuticmanagement of

universalis alopecia areata: about three cases. 12th International Conference

on Mechanics and Medicine and Biology; 2002 Sep 9-13; Lemnos

31. Kirby BJ. Safety of homeopathic products. J R Soc Med 2002 May; 95 (5):

221-2

32. Kalish RS. Comment and author reply on: randomized trial of aromatherapy:

successful treatment for alopecia areata.ArchDermatol 1999May; 135 (5): 602-3

33. Esfandiari A, Kelly AP. The effects of tea polyphenolic compounds on hair loss

among rodents. J Natl Med Assoc 2005 Aug; 97 (8): 1165-9

34. Matsuda H, Yamazaki M, Asanuma Y, et al. Promotion of hair growth by

ginseng radix on cultured mouse vibrissal hair follicles. Phytother Res 2003

Aug; 17 (7): 797-800

35. OgawaH,OguraK, IshigouokaH, et al. Effect of plant worm extract onmouse

hair growth. J Dermatol 1986 Apr; 13 (2): 126-31

36. Rho SS, Park SJ,Hwang SL, et al. The hair growth promoting effect of Asiasari

radix extract and its molecular regulation. J Dermatol Sci 2005 May; 38 (2):

89-97

37. Roh SS, Kim CD, LeeMH, et al. The hair growth promoting effect of Sophora

flavescens extract and its molecular regulation. J Dermatol Sci 2002 Oct;

30 (1): 43-9

38. Adhirajan N, Ravi Kumar T, Shanmugasundaram N, et al. In vivo and in vitro

evaluation of hair growth potential of Hibiscus rosa-sinensis Linn. J Ethno-

pharmacol 2003 Oct; 88 (2-3): 235-9

39. Waters KC. Acupuncture for dermatologic disorders. Probl Vet Med 1992

Mar; 4 (1): 194-9

40. Kwon OS, Han JH, Yoo HG, et al. Human hair growth enhancement in vitro by

green tea epigallocatechin-3-gallate (EGCG). Phytomedicine 2007 Aug; 14 (7-8):

551-5

41. Meidan VM, Touitou E. Treatments for androgenetic alopecia and alopecia

areata: current options and future prospects. Drugs 2001; 61 (1): 53-69

42. Sundberg JP, Boggess D, Montagutelli X, et al. C3H/HeJ mouse model for

alopecia areata. J Invest Dermatol 1995 May; 104 (5 Suppl.): 16S-7S

43. Michie HJ, Jahoda CA, Oliver RF, et al. The DEBR rat: an animal model of

human alopecia areata. Br J Dermatol 1991 Aug; 125 (2): 94-100

44. Shapiro J, Sundberg JP, Bissonnette R, et al. Alopecia areata-like hair loss in

C3H/HeJ mice and DEBR rats can be reversed using topical diphencyprone.

J Investig Dermatol Symp Proc 1999 Dec; 4 (3): 239

45. Sterne JA, EggerM, SmithGD. Systematic reviews in health care: investigating

and dealing with publication and other biases in meta-analysis. BMJ 2001 Jul

14; 323 (7304): 101-5

46. Walker SA, Rothman S. A statistical study and consideration of endocrine

influences. J Invest Dermatol 1950 Jun; 14 (6): 403-13

47. Vestey JP, Savin JA. A trial of 1% minoxidil used topically for severe alopecia

areata. Acta Derm Venereol 1986; 66 (2): 179-80

48. Tosti A, Bellavista S, Iorizzo M. Alopecia areata: a long term follow-up study

of 191 patients. J Am Acad Dermatol 2006 Sep; 55 (3): 438-41

49. Singer AJ. Alternative medicine: why should we care? Acad Emerg Med 2001

Jan; 8 (1): 65-7

50. Sullivan R, Smith JE, Rowan NJ. Medicinal mushrooms and cancer therapy:

translating a traditional practice into Western medicine. Perspect Biol Med

2006 Spring; 49 (2): 159-70



AU

TH

OR

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OO

F

51. Begg C, Cho M, Eastwood S, et al. Improving the quality of reporting of

randomized controlled trials: the CONSORT statement. JAMA 1996Aug 28;

276 (8): 637-9

52. Fontanarosa PB, Lundberg GD. Alternative medicine meets science. JAMA

1998 Nov 11; 280 (18): 1618-9

53. Margolin A, Avants SK, Kleber HD. Investigating alternative medicine

therapies in randomized controlled trials. JAMA1998Nov 11; 280 (18): 1626-8

54. Hull SM, Norris JF. Diphencyprone in the treatment of long-standing alopecia

areata. Br J Dermatol 1988 Sep; 119 (3): 367-74

55. Derogatis LR. SCL-90: administration, scoring and procedures manual: I for

the revised version. Baltimore (MD): Johns Hopkins University School of

Medicine, Clinical Psychometrics Research Unit, 1977

Correspondence: Dr Jacobus F.A. Jansen, PhD, Department of Medical Physics

and Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue,

New York, NY 10021, USA.

Email: [email protected]



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