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Prepared
by: Dr. Charlene DeHaven, Clinical Director
暗瘡肌膚 ©
Prevalence
About 17 million Americans have acne. It is the most common skin disease treated by physicians. Acne can appear at any age, although there are peaks of incidence in adolescence and again for females near the time of menopause. Acne and adolescence are so closely associated that 80-90% of all teenagers have at least some lesions at any given time. In adulthood, it is more common in women. In adult women, it occurs particularly near the time of menopause and, in pre-menopausal women, in the week or two before menses. In adolescence, it affects both males and females. Of the adolescents, boys tend to have more lesions and more severe disease than girls. This is probably due to the causal association with androgen (testosterone) levels. The occurrence in menopausal females is also related to relative androgen (testosterone) predominance in the face of declining estrogen levels seen with menopause. In menstruating females, the occurrence of lesions prior to menses is related to the increase in progesterone levels after ovulation and just before menses. Progesterone has androgenic (testosterone) effects and causes the increase in acne lesions during this time. Neonates (just-born babies) can present with acne because of the intra-uterine hormonal stimulation from maternal hormones.
People with acne, especially teenagers, tend to self-medicate. Each year in the US over $100 million is spent on over-the-counter products to treat acne.
Estimating Severity of Disease
The severity of acne is, unfortunately, often overlooked or minimized by the physician. Conversely, severity is often over-estimated by the patient, especially adolescents. Teenagers can experience quite severe social stigmata from even a few mild or moderate lesions. Since acne most commonly involves the face, lesions are readily obvious in the social setting. Individuals with deep inflammatory nodules and cysts may be scarred for life in more than one way.
Persons who had moderate to severe acne in youth frequently fail to realize their full potential in finding jobs or choosing careers suitable to their actual potential.
One system for grading acne divides the face into regions and then counts the number of lesions. The lesion count can further be divided by type into comedones, inflammatory lesions, and nodular and cystic lesions. This is quite time-consuming and is probably more useful in research studies than in the clinical setting. Clinically, it is probably more useful to classify the severity of acne according to the general severity of lesions.
This system must consider the progression of lesions from
slightly visible comedone to inflammatory lesions and
then to multiple severe pustular and cystic lesions. Thus,
mild or comedonal acne would involve
comedones (blackheads and whiteheads) only and be non-inflammatory.
Inflammatory acne has both comedones
and a substantial number of inflammatory lesions of pustules
and papules. Inflammatory lesions can leave permanent
scars. A mixture of both inflammatory
and non-inflammatory acne has all types of lesions including
severe inflammatory lesions (markedly reddened pustules)
and possibly cystic lesions (lesions over 0.5 cm in diameter
with a soft top that are losing their inflammation). It
is most common to have a mixture of lesions at any one
time. Treatment is chosen on the basis of severity of
disease, so this estimation is important.
 Steps
in Disease Progression and Causation
The basic skin structure affected by acne is the pilosebaceous
unit. This unit is composed of a sebaceous gland,
a vellus hair and the duct.
The function of the sebaceous gland is to produce sebum, an oily or lipid-based substance. We used to think that sebum had no particular function, although more recent research has focused on transport of the antioxidant Vitamin E to the skin surface by sebum. The duct (or pore) is the opening that carries the sebum to the epidermal surface and is lined with epidermal cells. Vellus hairs are rudimentary hairs and are found on all parts of the body except the palms and soles. They are the fine hairs found in all age groups. In contrast, hair found in the axillae (armpits), pubic areas and the male beard and chest is stimulated to grow at puberty and is of a different type. The density of pilosebaceous units is greatest on the face, upper neck and chest, at nine times the number found elsewhere on the body. These are also the areas most commonly affected by acne. The pilosebaceous unit is under stimulation at birth from maternal hormones, atrophies (becomes smaller and less active) during childhood and re-emerges during adolescence, again due to hormonal stimulation.
The triad of hormones, sebum
and bacteria contribute to acne development.
The primary cause of acne is obstruction of the
pilosebaceous unit related to several factors.
Higher androgen (male hormone or testosterone) levels
cause the over-production of sebum. This can occur during
direct elevation of androgens (during both male and female
puberty) or relatively higher androgen levels compared
to estrogen levels (during the pre-menstrual period, during
female menopause). Acne severity correlates with amount
of sebum secretion. Increased desquamation (shedding)
of the epithelial cells lining the duct (pore) also contributes
to the obstruction. Increased desquamation may be somewhat
under genetic influence, explaining why severe acne tends
to run in families, although may not be found in one or
both parents. The sebum in acne patients tends to be low
in certain lipids (fats) such as linoleic acid, although
it’s not really known if this is cause or effect. The
two factors of increased sebum production and desquamation
of epithelial lining cells contribute to obstruction of
the duct and lead to formation of the microcomedone.
The microcomedone is very small and cannot be seen. As
this process progresses, microcomedones increase in size
to form comedones. The comedone is the
essential focus lesion in acne. Comedones may be open
or closed. Open comedones are termed blackheads
because of their color.
In blackheads, the pore which has enlarged because of
the increased material within the duct, is open to the
surface and the black color is due to melanin pigment
in the cells that were shed and decomposed and also possibly
to some oxidized lipids (fats) in the shed sebum. In closed
comedones, a layer of epithelial cells covers the pore.
Closed comedones appear white and are termed whiteheads.
Whiteheads have a tiny microscopic opening to the skin
surface which is the pore or duct of the pilosebaceous
unit. The bacterial organism involves in the pathogenesis
(cause) of acne is Propionibacterium acnes (P.
acnes). Propionibacterium acnes is a normal inhabitant
of skin. However, the increased amount of sebum and obstruction
of the duct provide an environment conducive to proliferation
of P. acnes. As P. acnes increases in number, it uses
sebum as a nutritive source, causing sebum conversion
to free fatty acids which are very irritating. The immune
system is activated by both the free fatty acids and the
large amounts of P. acnes and inflammation thus ensues.
In the closed microcomedone or comedone, the epithelial
duct wall ruptures and the acne lesion progresses from
comedone to pustule or papule. The term
"cyst" is actually a misnomer and refers to large inflammatory
pus-filled nodules greater than 0.5 cm in diameter in
which the cell wall is composed of inflammatory cells
and scar tissue. A substantial number of severely inflammed
pustules or papules leading to cyst development can be
termed nodular cystic acne. The body
will repair severe inflammation with scarring.
Scars are permanent, can be deep or superficial, and will
persist throughout life.
Acne
lesions occur most commonly on the face, neck, chest and
back.
Hormonal influences are very important
in acne development and progression. Acne actually begins
to develop at age eight or nine when the adrenarche occurs.
Adrenarche is the activation of the adrenal gland occurring
before puberty and associated with increased DHEA levels.
DHEA is one of the hormones produced by the adrenal gland.
Some of the DHEA is converted to androgens by a metabolic
pathway, leading to microcomedone development. With puberty
in the female, DHEA is the primary source of androgens
(testosterone) since some of it is converted to androgens.
With female puberty, both estrogen and progesterone increase
as menarche (beginning of menses) occurs and the ovaries
begin to produce female hormones. Some of this ovarian
estrogen is converted to androgens as a byproduct. Progesterone
itself has androgenic effects. The increased severity
of acne in male adolescents is due to their higher androgen
secretion compared to females. As puberty passes, hormonal
levels decrease and acne resolves. However, in the female
adult, progesterone increases in the 2 weeks before menses,
causing more androgenic effects and leading to the spike
in acne lesions during this time. With female menopause,
estrogen and progesterone levels decrease as the ovaries
fail (stop hormone production). Now without the over-riding
effect of high estrogen and progesterone levels, DHEA
from the adrenals again becomes important.
The DHEA, which is androgenic because of its conversion to testosterone, causes the increase in acne seen with female menopause.
Other Causes of Acne
Some medicines can cause in acne. In adult females taking birth control pills (oral contraceptives), the choice of pill and medicine contained within it are most important in determining their effect on acne. Most oral contraceptives contain both estrogens and progestins (synthetic progesterone). Those containing progestins that are more androgenic (like testosterone) will contribute to acne. Pills containing relatively more estrogen and a progestin that is less androgenic do not contribute to acne development and are sometimes used to treat acne.
The ‘progesterone-only’ method of birth control (either by pill or injection) can contribute to acne progression via androgenic effects.
Other medicines that can be related to the development of acne include lithium, cortisone-type medicines, and anabolic (testosterone-type or androgenic) steroids.
Another rare but possible cause is endocrine disorders of various types which lead to over-production of androgenic substances.
Environmental factors occasionally play a role. Young people employed in auto repair shops or fast-food restaurants where they contact grease at work may experience a worsening of acne.
At the present time, we are unsure if stress can exacerbate acne or if the acne itself causes the increased stress. An increase in lesion number has been noted at exam time. This may relate to relative increases in cortisol, which is androgenic, with stress.
Patient
Education Facts and Myths
There are many public misconceptions about acne. Some of the important facts for general patient education are listed here.
Acne is not caused by dirty skin. Washing the skin more or more vigorously is not warranted, will not be helpful, and injury induced by vigorous washing may cause more inflammation and induce progression of lesions. The black visible part of the blackhead is not dirt—it is melanin and oxidized material and cannot be removed by washing.
Diet has no effect on acne. Many studies have been done regarding this and no foods have been shown to contribute to acne progression or development. Consequently, dietary modification will not help this disease. There is one exception to this regarding the individual patient. If any one individual notices the idiosyncratic relationship of a particular food to acne, they should avoid that food. But the association of a food substance with acne in one particular person cannot be generalized to the entire patient population with acne.
Therapy succeeds by preventing the formation of new acne lesions. Therefore, it is important to treat all acne-prone skin with topical agents and not just single acne lesions.
Any practice that further traumatizes (injures) acne lesions contributes to more inflammation and progression of disease. This includes picking at lesions and wearing athletic gear over lesions.
Some races use pomade on their hair. If this gets on the skin (as forehead and temples), it may plug the pilosebaceous gland, leading to acne development.
This can be avoided by being careful to avoid facial skin when placing these products on the hair.
Cosmetic substances, including makeup and moisturizers, containing large amounts of oil can worsen acne.
Acne is related to hormonal factors as explained above. Young women may experience flare-ups just prior to menses.
The treatment of acne requires some time. It will not go away overnight but requires persistence and consistent, effective treatment. Usually, weeks are required with any treatment before improvement is seen.
When treatment is stopped prematurely, the acne returns. It must be understood that, because of the hormonal influences occurring during adolescence, this entire period is an acne-prone time for the individual.
Scarring is permanent. The object of continuing treatment and being consistent with treatment is to avoid progression to severe lesions and scarring. Scars can only be removed or lessened via surgical procedures.
Treatment - General comments about treatment
will be made here and the specifics about every treatment
will not be discussed.
Some general concepts are very important. It is important to realize that severe inflammatory acne, with large pustules and cysts, cannot be treated by topical therapy alone. Topical therapy refers to putting a treatment on top of the skin. Topical treatment is appropriate for comedones and non-inflammatory acne. Topical treatment will not be effective for the severe inflammatory process because it cannot penetrate deep enough through the skin surface to treat the severely inflammed nodules and cysts. Severe acne requires systemic treatment, which refers to medicine taken orally.
Scars are permanent, persist into adulthood and can only be treated surgically. Sometimes the expression (removal) of comedones with a small instrument called a comedone-extractor may be done in the doctor’s office. Some medical literature terms this ‘surgery’, although it is not surgery in the traditional sense and cannot be used to treat scarring. Removal of comedone contents with a comedone-extractor in the doctor’s office is acceptable and helpful. It differs greatly from ‘picking at’ lesions at home which causes more inflammation and is harmful.
Non-inflammatory acne may be treated with a single agent applied topically. There are a variety of single agents available, which may have a variety of effects. These effects include antibacterial activity, mild anti-inflammatory activity, a lipid-dissolving cleansing action to remove lipid plugs from pores and desquamative activity to remove dead epithelial cells on the skin and pore surface and encourage epithelial cell turnover.
Two agents are required for non-inflammatory acne not responsive to a single agent or to inflammatory acne. If two different agents are chosen, they should have different mechanisms of action so as not to be redundant. Severe nodular cystic acne usually requires Accutane (13-cis-retinoic acid or isotretinoin). This is a pill with significant potential side effects and is reserved for the most severe acne cases. It causes drying of the skin, eyes, mouth, mucus membranes in all people as well as desquamation (flaking) of skin. Accutane is teratogenic (tumor-causing) and will cause malformations in 60% of exposed fetuses.
Therefore, doctors will never place a female patient on Accutane unless there is reliable pregnancy protection; all require oral contraceptive use, two negative pregnancy tests before beginning Accutane, a negative monthly pregnancy test while on Accutane, and some require oral contraceptives plus a second reliable contraceptive method (such as condom or diaphragm).
Common topical therapies include benzoyl peroxide, topical antibiotics (clindamycin topical marketed as Cleocin-T or erythromycin topical), topical retinoids (Retin-A, Renova, adapalene or Differin, tazarotene or Tazorac), azelaic acid (Azelex), salicylic acid, mild and fruit acids (also called AHAs, including glycolic acid, lactic acid, malic acid, citric acid, mixed fruit acids).
Systemic therapies cause distribution of the drug throughout the entire organism. Common systemic therapies include oral antibiotics (erythromycin and the tetracyclines including tetracycline, minocycline, doxycycline), hormonal therapy (oral contraceptives), and Accutane (isotretinoin, 13-cis-retinoic acid).
Each of these therapies, whether topical or systemic, has a list of advantages, disadvantages, potential toxicities and contraindications depending upon its own unique properties. Most of them may be used in combination, although Accutane, reserved for the most severe acne cases, is used alone as monotherapy. The topical agents may be used singly for comedonal non-inflammatory acne but if this type of acne is non-responsive to therapy with a single topical agent or is inflammatory, then therapy with more than one agent is required.
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