Preventing and Modifying the Aging Process skin is more prone to

THE

WESTERN

JOURNAL

OF

MEDICINE

*

DECEMBER

1989

*

151

*

6

653

Psychogenic

excoriators

often

are

found

to

produce

an

underlying

depression

or

obsessive-compulsive

disorder.

A

tricyclic

antidepressant,

doxepin

hydrochloride

(Sinequan,

Adapin),

is

useful

in

treating

those

patients

with

an

under-

lying

depression.

Doxepin

has

a

notable

antipruritic

effect,

as

well

as

an

antidepressant

effect.

The

major

side

effects

of

doxepin

are

sedation,

anticholinergic

symptoms

such

as

con-

stipation,

dry

mouth,

or

urinary

hesitations,

and

orthostatic

hypotension.

In

elderly

patients,

cardiac

side

effects

such

as

prolongation

of

the

QT

interval

need

to

be

monitored.

Both

pimozide

and

doxepin

reduce

the

seizure

threshold,

and

cau-

tion

must

be

exercised

in

using

them

to

treat

patients

with

epilepsy.

Antianxiety

agents

such

as

alprazolam

(Xanax)

are

helpful

in

managing

dermatologic

patients

with

symptoms

of

stress,

tension,

and

anxiety.

There

are

many

cutaneous

con-

ditions

that

can

be

exacerbated

by

stress

and

anxiety,

ranging

from

hyperhidrosis

(excessive

sweating)

to

psoriasis.

In

ad-

dition,

there

are

self-induced

skin

conditions

that

can

be

exacerbated

by

stress

and

anxiety

such

as

onychophagia

(nail

biting),

neurodermatitis

(lichen

simplex

chronicus),

and

prurigo

nodularis.

The

usual

starting

dose of

alprazolam

ranges

from

0.25

mg

to

0.5

mg

taken

orally

four

times

a

day

as

needed.

The

short-term

side

effect

is

usually

limited

to

sedation.

Long-term

use

of

alprazolam

should

be

supervised

by

a

psychiatrist.

Because

alprazolam

was

found

to

have

a

notable

antidepressant

effect,

it

is

sometimes

used

as

a

substi-

tute

for

an

antidepressant

when

the

cardiac

and

anticholin-

ergic

side

effects

of

a

tricyclic

or

other

"classic"

antidepres-

sants

pose

substantial

risk

to

the

patient.

Anticompulsive

agents

may

be

useful

in

treating

patients

with

obsessive-compulsive

disorders

seen

in

a

dermatologic

practice,

such

as

hand

eczema

resulting

from

obsessive

hand

washing,

trichotillomania,

and

acne

excoriee.

The

prototyp-

ical

medication

with

anticompulsive

effect,

clomipratnine

hydrochloride

(Anafranil),

is

expected

to

become

available

in

the

United

States

in

the

near

future.

JOHN

Y.

M.

KOO,

MD

San

Francisco

REFERENCES

Koo

JYM,

Strauss

GD:

Psychopharmacologic

treatment

of

psychocutaneous

disorders:

A

practical

guide.

Semin

Dermatol

1987;

6:83-93

Panconesi

E:

Psychosomatic

dermatology.

Clin

Dermatol

1984;

2:94-179

Robinson

DS,

Kayser

A,

Bennette

B:

Alprazolam:

An

antidepressant.

Alpra-

zolam,

desipramine,

and

an

alprazolam-desipramine

combination

in

the

treatment

of

adult

depressed

outpatients.

J

Clin

Psychopharmacol

1987;

7:295-3

10

Preventing

and

Modifying

the

Aging

Process

SKIN

CHANGES

in

the

elderly

have

been

considered

an

inevi-

table

and

irreversible

part

of

the

aging

process,

with

the

undesirable

texture

and

appearance

masked

with

the

use

of

cosmetics.

Recently,

however,

there

has

emerged

a

clearer

understanding

that

aging

of

the

skin

is

the

total

of

two

pro-

cesses:

intrinsic

changes

associated

with

aging

and

extrinsic

damage,

particularly

the

accumulative

effects

of

repeated

exposure

to

actinic

radiation,

referred

to

as

photoaging.

In

many

instances,

the

cumulative

actinic

damage

has

been

the

major

contributing

factor

to

the

changes

observed

in

the

skin

of

the

elderly,

including

various

degrees

of

wrinkling,

laxity,

pebbliness,

roughness,

leathery

appearance,

telangiectasias,

in

fair-skinned

persons

of

Celtic

background

and

others

who

have

poor

natural

defenses

against

actinic

radiation.

The

photodamaging

effects

on

the

skin also

have

been

implicated

in

the

development

of

the

commonest

malignant

neoplasms:

basal

cell

and

squamous

cell

carcinomas

of

the

skin.

These

malignant

neoplasms

are

occurring

in

epidemic

proportions.

The

most

damaging

segment

of

the

sun's

rays

has

been

identified

as

those

in

the

ultraviolet

B

band

of

the

ultraviolet

light.

A

large

number

of

topical

sunscreening

agents

have

been

developed

that

if

properly

used

will

effectively

screen

out

such

rays.

More

recently,

ultraviolet

A

and

even

rays

in

the

infrared

band

also

have

been

incriminated

as

contributing

to

the

total

photodamage

of

the

skin,

and

some

of

the

new

sun

shields

have

desirable

ultraviolet

A

absorbers,

as

well.

Simple,

effective

measures

have

been

proposed

to

mini-

mize

the

photoaging

effects

of

actinic

radiation:

avoiding

sun

bathing,

both

outdoors

and

in

tanning

parlors;

wearing

ap-

propriate

protective

clothing

when

outdoors;

applying

sun-

screen

to

exposed

portions

of

the

body;

and

choosing,

when-

ever

possible,

to

engage

in

outdoor

activities

before

10

AM

or

after

4

PM,

when

photodamaging

rays

are

less

intense.

These

measures

should

apply

particularly

to

children,

as

mounting

evidence

suggests

that

50

%

to

80

%

of

the

total

accumulative

photodamage

occurs

during

the

first

20

years

of

life.

Further,

it

has

been

predicted

that

the

regular

use

during

childhood

and

adolescence

of

sunscreens

with

a

sun-protective

factor

of

15

or

greater

would

reduce

the

lifetime

incidence

of

nonme-

lanoma

skin

cancer

by

as

much

as

70

%

to

80

%.

Even

the

concept

of

the

irreversibility

of

acquired

photo-

damage

is

no

longer

tenable.

It

is

now

known

that

the

body's

own

reparative

mechanisms

will

partially

correct

the

photo-

damaging

aspect

of

the

skin

over

a

period

oftime

if

a

person

will

remain

out

of

the

sun's

harmful

rays

or

if

appropriate

measures

are

taken

to

minimize

exposure.

Destruction

and

repair

go

on

simultaneously

under

continued

assault

by

ac-

tinic

radiation;

the

balance

is

shifted

toward

repair

when

radiation

stress

is

reduced.

Considerable

scientific

and

public

interest

has

been

gen-

erated

regarding

the

recent

clinical

and

laboratory

evidence

that

topically

applied

tretinoin

(Retin-A)

can

accelerate

the

reversal

of

the

skin

damage

due

to

excessive

sun

exposure

and

possibly

intrinsic

aging

as

well.

The

application

of

treti-

noin

decreases

the

cohesiveness

of

the

corneocytes

and

pro-

motes

their

shedding,

so

that

there

is

a

thinner,

more

uniform

horny

layer.

Epidermopoiesis

is

enhanced,

leading

to

a

greater

thickness

of

the

epidermis

with

some

correction

of

cytologic

atypia,

variability,

and

polarity.

Blood

flow

is

in-

creased,

and

angiogenesis

is

stimulated,

improving

oxygen-

ation

as

well

as

nutrient

transfer

to

the

skin.

Fibroplasia

is

stimulated

with

the

laying

down

of

new

collagen,

leading

to

some

improvement

in

skin

turgor

and

a

possible

reduction

of

wrinkles.

The

accumulation

of

melanin

granules

is

pre-

vented,

thus

leading

to

a

more

uniform

pigmentation.

Fi-

nally,

tretinoin

has

a

redifferentiation,

antitumor

effect

that

causes

some

of

the

atypical

cell

clones

of

actinic

keratoses

to

regress

and

disappear.

Tretinoin

therapy

is

to

be

used

indefinitely,

starting

with

daily

application

for

from

eight

months

to

a

year,

and

then

twice-weekly

application

thereafter.

The

use

of

tretinoin

has

certain

drawbacks.

In

some

patients,

the

changes

are

only

slight,

while

in

others

the

treatment

is

too

irritating.

Treated

and

spotty

hypo-

or

hyperpigmentation

of

the

skin.

This

has

been

particularly

true

where

exposure

has

been

excessive,

or

THE

WESTERN

JOURNAL

OF

MEDICINE

-

DECEMBER

1989

-

151

-

6

653

skin

is

more

prone

to

sunburn,

necessitating

the

use

of

a

sunscreen.

All

current

information

about

tretinoin

is

still

of

a

short-

term

nature,

and

considerable

additional

data

will

be

re-

quired

before

its

exact

effectiveness

and

any

additional

side

effects

can

be

determined.

For

the

purpose

of

evaluating

the

effects

of

sunlight

and

artificial

ultraviolet

radiation

on

the

skin,

a

recently

convened

14-member

panel

of

the

National

Institutes

of

Health

found

that

available

evidence

was

insuffi-

cient

to

recommend

the

use

of

tretinoin

and

similar

com-

pounds

for

the

treatment

of

sun-induced

wrinkles.

VICTOR

D.

NEWCOMER,

MD

Santa

Monica,

California

REFERENCES

Gilchrest

BA:

Skin

and

Aging

Processes.

Boca

Raton,

Fla,

CRC

Press,

1984

Kligman

LH,

Akin

EJ,

Kligman

AM:

The

contributions

of

UVA

and

UVB

to

connective

tissue

damage

in

the

hairless

mice.

J

Invest

Dermatol

1985;

84:272

Stern

RS,

Weinstock

MC,

Baker

SG:

Risk

reduction

for

non-melanoma

skin

cancer

with

childhood

sunscreen

use.

Arch

Dermatol

1986;

122:537-545

Weiss

JS,

Ellis

CN,

Headington

JT:

Topical

tretinoin

improves

photoaged

skin:

A

double-blind

vehicle-controlled

study.

JAMA

1988;

259:527-532

Scierotherapy-Treating

the

Small

Vessels

IN

AMERICA

the

treatment

of

"spider"

veins-vessels

less

than

1

mm

in

diameter-was

pioneered

by

Biegeleisen,

who

coined

the

term

sclerotherapy

in

the

1930s.

Sclerotherapy

is

now

routinely

carried

out

by

dermatologists

who

received

training

during

their

residencies

or

acquired

it

as

postgradu-

ates.

Of

patients

treated,

90%

are

pleased

with

the

results,

and

many.note

a

reduction

in

leg

discomfort

and

fatigue.

Spider

veins

are

not

a

purely

cosmetic

problem.

There

is

no

perfect

sclerosing

agent.

All

work

by

initi-

ating

destruction

of

endothelium

followed

by

thrombus

for-

mation

and

fibrosis.

Sodium

tetradecyl

sulfate

(Sotradecol)

and

morrhuate

sodium

were

approved

by

the

Food

and

Drug

Administration

decades

ago

during

an

era

when

such

ap-

proval

was

easily

obtained.

Neither

is

more

efficacious,

and

both

are

far

more

toxic

than

hydroxypolyethoxydodecane

(Polidocanal,

Aethoxysclerol),

a

chemical

analog

of

xylo-

caine

not

approved

by

the

Food

and

Drug

Administration

but

widely

and

successfully

used

in

Europe

and

Canada.

Hyper-

tonic

saline

also

works

well

in

treating

spider

and

small

varicose

veins.

Compression

dressings

and

hosiery,

which

are

commonly

used

after

treating

larger

varicose

veins

and

which

can

help

reduce

their

recurrence,

do

not

appear

to

be

as

important

in

treating

most

spider

veins.

Side

effects

following

treatment

include

streak-like

pig-

mentation,

which

occurs

when

treatment-damaged

vessels

leak

red

blood

cells

into

the

surrounding

skin.

This

phenom-

enon

is

not

associated

with

the

use

of

any

one

type

of

solution

and

is

probably

caused

by

vascular

fragility.

Tissue

necrosis

and

ulcerations

can

follow

treatment,

particularly

when

so-

dium

tetradecyl,

morrhuate,

and

hypertonic

saline

are

used.

Extremely

tiny

vessels

can

appear

in

a

bruise-like

cloud

mat-

ting,

as

post-treatment

neovascularization,

or

as

blush

areas

on

the

skin

surrounding

the

treated

areas.

High

cumulative

doses

of

estrogen

seem

to

intensify

this

phenomenon

but

have

not

produced

a

higher

than

expecte4

incidence

of

more

dan-

gerous

side

effects.

The

uncommon

but

often

unpredictable

occurrence

of

severe

and

sometimes

fatal

side

effects-deep

thrombophlebitis,

pulmonary

emboli,

and

anaphylaxis-

must

be

kept

in

mind.

Proper

patient

selection,

ambulation,

and

compression

can

almost

eliminate

these

problems.

It

should

also

be

remembered

that

there

are

real

disadvantages

when

viable

veins

that

could

be

used

to

repair

an

ailing

heart

are

destroyed.

To

further

confuse

the

situation,

serious

side

effects

are

decidedly

rarer

with

solutions

not

approved

by

the

Food

and

Drug

Administration,

but

physicians

who

use

them

may

be

at

legal

risk

for

doing

so.

In

the

future,

sclerotherapy

may

be

more

widely

used

to

treat

esophageal

varices,

hemorrhoids,

and

other

vascular

lesions.

A

better

understanding

of

the

etiology

of

spider

and

varicose

veins

may

provide

insights

into

the

mechanisms

of

underlying

diseases

in

which

vascular

growth

plays

a

domi-

nant

role.

DAVID

M.

DUFFY,

MD

Torrance,

California

REFERENCES

Bodian

EL,

Goldman

MP

(Eds):

Sclerotherapy

(special

issue).

J

Dermatol

Surg

Oncol

1989

Feb;

15:131-225

Duffy

DM:

Small

vessel

sclerotherapy:

An

overview.

In

Advances

in

Derma-

tology,

Vol

3.

Chicago,

Year

Book

Medical,

1988,

pp 221-242

FolkmanJ,

Klagsbrun

M:

Angiogenic

factors.

Science

1987;

235:442-447

Treatment

of

Androgenetic

Alopecia

ANDROGENETIC

ALOPECIA

or

common

hereditary

balding

af-

fects

both

men

and

women.

The

difference

between

the

sexes

is

that

women's

hair

becomes

diffusely

thin

but

they

do

not

become

bald.

Thinning

hair

begins

in

the

teens,

20s,

and

30s

in

both

sexes

and

is

usually

completely

expressed

by

the

age

of

40.

Androgenetic

alopecia

has

a

polygenic

inheritance

pattern

and

is

caused

by

the

influence

of

normal

androgens

on

genetically

marked

scalp

follicles.

This

results

in

a

gradual

miniaturization

of

affected

follicles

over

several

years.

Because

all

the

follicles

are

still

present,

it

is

possible

to

reverse

this

process

and

re-enlarge

the

follicles.

On

the

other

hand,

involutional

alopecia,

or

hair

thinning

in

the

later

decades

associated

with

the

aging

process,

results

in

the

loss

of

follicles,

is

probably

not

androgen-mediated,

and

is

not

expected

to

respond

to

hair

growth-promoting

agents.

Topical

minoxidil

is

the

first

approved

agent

for

pro-

moting

hair

growth

and

represents

a

major

medical

advance.

Though

not

very

strong,

its

limited

effect

is

real.

Its

suc-

cessful

use

in

androgenetic

alopecia

depends

on

careful

pa-

tient

selection

and

realistic

expectations

on

the

part

of

both

patient

and

physician.

Minoxidil

causes

partial

enlargement

of

the

miniaturized

follicles,

which

in

turn

produce

longer,

coarser,

and

darker

hairs-about

3

to

5

cm

long.

These

hairs

increase

the

coverage

of

the

scalp.

The

increase

in

scalp

coverage

produced

by

topical

mi-

noxidil

is

easily

seen

in

men

and

women

if

the

scalp

is

clearly

visible

before

treatment

and

then

is

more

covered,

but

not

usually

totally

covered,

after

treatment.

Men

and

women

with

androgenetic

alopecia

who

still

have

adequate

density

to

cover

the

scalp

also

respond

to

minoxidil,

but

they

may

not

perceive

the

increase

in

partially

enlarged

hairs;

they

will

primarily

perceive

that

the

hair

thinning

is

stabilized

and

not

progressing.

With

a

quantitative

method

of

hair

growth

assessment

that

measures

total

hair

mass

in

a

permanently

marked

scalp

area,

studies

have

shown

that

virtually

all

subjects

using

topical

minoxidil

respond

with

some

growth-with

an

average

total

weight

increase

of

40%

in

women

and

46

%

in

men.

These

subjects

could

be

easily

differentiated

from

those

who

were

using

a

placebo-average

total

weight

increase

of

4

%

in

women

and

11

%

in

men.

Not

all

subjects

perceived

the

increase,

however.

Primarily,

those

subjects

whose

scalp

was

visible

before

treatment

perceived

the

increase

in

hair

mass

as

improved

coverage

of

their

scalp.

Key

factors

to

successful

treatment

with

topical

minoxidil

654

EPITOMES-DERMATOLOGY