What is acne?

 Acne vulgaris: a chronic condition linked

to the onset of puberty
 Not a physical threat;
 acne may have a significant negative
psychological effect: low self esteem,
social phobia and depression.
Etiology of Acne

1. Abnormal keratinization of the

epithelial cells;
2. An increase in sebum production;
3. An accelerated growth of
Propiobacterium acnes.
4. The occurrence of inflammation;
Pathophysiology of Acne

 Abnormal keratinization of the cells in

obstruction of the follicle with impacted
cells and sebum to form a plug;
 This plug will distend the follicle and form
a microcomedone
 Microcomedone is the initial pathologic
lesion of acne
Pathophysiology of Acne
 As more sebum accumulate, the
microcomedone enlarges and becomes visible
as a closed comedo, or white head
 The whitehead: is a small pale nodule just
beneath the skin surface that may form a
precursor for other acne lesions
 An open comedo (blackhead) occurs: when
the peeled off epithelial cells and sebum
accumulate behind the plug and the orifice of the
follicular canal becomes distended, allowing the
plug to bulge. The tip of the plug may darken
because of melanin NOT dirt;
Pathophysiology of Acne
Pathophysiology of Acne
 Inflammatory acne begins with closed
comedones that distend the follicle, causing the
cellular lining of the walls to spread and become
thin;
 Primary inflammation results from disruption of
the epithelial lining + lymphocyte infiltration
 A severe inflammatory reaction happens if the
follicle wall ruptures spontaneously or is
ruptured by picking, squeezing, or attempted
expression with a comedo extractor
Pathophysiology of Acne

 Contents are discharged into surrounding

tissue: abscesses scars or pits after
healing

 Pustules or purulent nodules of

inflammatory acne are more likely to
cause scarring than those of non-
inflammatory acne
Exacerbating Factors for Acne

 Several factors are known to exacerbate

existing acne or cause periodic flare-ups
of acne in some patients;
 Some may have control over, while others
not (e.g. heredity);
 Factors: environmental and physical
factors, cosmetic use, hormonal factors
and medication use
Environmental & Physical
1. Hydration: decreases size of duct and prevents
loosening of comedone. e.g. high humidity
environment or prolonged sweating and occlusive
clothing
2. Irritation and friction (acne mechanica): may
increase symptoms of acne. E.g. occlusive
clothing, headbands, helmets, resting chin or
cheek on hand
3. Occupational acne: exposure to dirt, vaporized
cooking oils, or certain industrial chemicals
Cosmetic Use
 Acne cosmetica: mild form of acne on the face,
cheek and chin;
 Typically: closed, non-inflammatory comedones;
 Occurs as a result of using oil-based products
on the skin that causes occlusion of the
pilosebaceous unit;
 Oil-based cosmetics may exacerbate acne or
even induce it;
 Moisturizers or tanning oils may contain
comedogenic oils (e.g. lanolin, mineral oil, cocoa
butter)
Emotional Factors
 Severe or prolonged periods of stress may
exacerbate acne; however they do not
induce acne!
 Mechanism!

Hormonal Factors
 Many women with acne experience a premenstrual
flare-up of symptoms (i.e. ovulation, pregnancy).
 OCP with high androgenic progestin are implicated
in the production of acne
Unsubstantiated Etiologic Factors

 Little evidence supports link between: diet

and acne;
 A rule of thumb: people should be advised
to avoid any particular food that seems to
exacerbate their acne;
 Excessive scrubbing in attempt to open
blocked pores may exacerbate rather than
improve acne
Can I pop a pimple?

 Opinion differs (Some say popping a

pimple can scar, others say it can't scar)
 Most: lancing and gently squeezing
pimples that are at the surface and
white will usually not lead to
scarring.
 However, trying to squeeze and pop
a pimple which is still below the
surface may lead to major problems.
Signs and Symptoms of Acne
 Non-inflammatory acne is characterized by
whiteheads or blackheads
 Inflammatory acne is characterized by pimples
(i.e. small, prominent inflamed elevations of the
skin) which may rupture to form a papule
 Papules are inflammatory lesions appearing as
raised, reddened areas on the skin, which may
enlarge to form pustules
 Pustules appear as raised reddened areas filled
with pus
Signs and Symptoms of Acne
 More extensive penetration into surrounding and
underlying tissue produces necrotic purulent
nodular lesions (previously designated as
cysts), and may lead to pitting or scarring if
untreated
 Typical acne patient presents with a combination
of lesions: comedones (open and closed),
papules and pustules
 Usually found on the face, chest and back
(sometimes on neck and upper arms too)
Classification of Acne
Grade Qualitative Quantitative Description
of Description
Acne
I Comedonal acne Comedones only, < 10 lesions on face, none
on trunk, no scars, noninflammatory lesions
only
II Papular acne 10-25 papules on face and trunk, mild
scarring, inflammatory lesions < 5 mm in
diameter
III Pustular acne More than 25 pustules, moderate scarring,
size similar to papules but with visible
purulent core
IV Severe persistent Nodules or cysts, extensive scarring,
pustulocyctis inflammatory lesions > 5 mm in diameter
acne
- Recalcitrant Extensive nodules/cysts
severe cystic
acne
Pharmacologic Therapy

Benzoyl Peroxide
Salicylic acid
Sulfur
Sulfur-Resorcinol combination
products
Alpha-hydroxy acids
Benzoyl Peroxide
 Available in variety of concentrations
(2.5%, 5% and 10%) and dosage forms
(lotions, gels, creams, cleansers, masks
and soaps);
 MOA: (1) irritation & desquamation-
prevents closure of pilosebaceous duct.
Increase turnover rate of epithelial cells.
(2) Oxidizing potential-antibacterial activity,
decreasing P.acnes
 Safety studies are ongoing
Benzoyl Peroxide
 The most effective and widely used OTC
drug for non-inflammatory acne;
 Clinical response to all concentrations is
similar in reducing the number of
inflammatory lesions
 Different formulations are not equivalent:
alcohol gel is superior to lotion of the same
concentration;
 Washes and cleansers: have little or no
comedolytic effect
Benzoyl Peroxide
 Adverse Effects: excessive dryness,
peeling, some skin sloughing, erythema or
edema lower concentrations must be
used for shorter duration
 Stinging/burning: non alarming unless
persist or worsen
 Precautions: (1) bleach hair, clothes, bed
linens, (2)avoid excessive sun or sunlamps,
(3) alcohol-based products (e.g. after shave
lotion)( may exacerbate stinging/burning
Salicylic Acid

 Available in wide range: 0.5%-2%

 A milder, less effective alternative for
teretoin
 MOA: acts as a surface keratolytic, mild
comedolytic agent
 When used in cleansing preparations:
adjunctive treatment
Sulfur
 Keratolytic and antibacterial (precipitated or
colloidal) 3%-10%
 Generally: accepted as effective in promoting the
resolution of existing comedones, but, on
continued use, may have a comedogenic effect
 Alternative forms of sulfur: Na thiosulfate, Zn
sulfate, Zn sulfide
 Applied in thin film to skin 3 times daily
 Have noticeable color and odor
Sulfur-Resorcinol combination

 3-8% sulfur with resorcinol 2% (enhances

the effect of sulfur)
 MOA: keratolytics, fostering cell turnover
and desquamation
 Resorcinol produces a reversible dark
brown scale on some darker-skinned
individuals
Alpha-hyrdoxy Acids

 They occur naturally in sugar cane, fruits

and milk products;
 The most useful AHAs in dermatologic
practice are glycolic acid, lactic acid and
gluconic acid
 MOA: facilitate desquamation of the
stratum corneum.
 Effective in treatment of comedonal acne
Therapeutic Comparison
Benzoyl Peroxide Salicylic Acid Sulfur

Concentration 2.5%-20% 0.5%-2% 2%-10%

Frequency of use 1-2 times daily Used mainly as 1-3 times daily
cleanser, then
rinsed off

Adverse effects Bleached hair and Potent keratolytic Color, unpleasant

clothing at high odor
concentration
Product Selection Guidelines
 Cosmetic appearance may influence
compliance
 Cleansers (bars, liquids, suspensions,
lotions, creams, gels, and pads/wipes) are
not of much value?
 Lotions & creams with low fat content are
intended to counteract drying (astringent
effect) and peeling (keratolytic effect):
alternative to more effective gels for dry
sensitive skin or during winter weather
Patient Education:
 Cleanse skin thoroughly but gently at least
twice daily to produce a mild drying effect
that loosens comedones, using soft wash
cloth, warm water and facial soap without
moisturizing oils
 To prevent or minimize acne flare-ups,
avoid or reduce exposure to environmental
factors, such as dirt, dust, petroleum
products, cooking oils or chemical irritants
Patient Education:

 To prevent friction or irritation that may

cause acne flare-ups, do not wear tight-
fitting clothes, headbands, or helmets,
avoid resting the chin on the hand;
 To minimise acne related to cosmetic use,
do not use oil based cosmetics and
shampoos
Patient Education:
 To prevent excessive hydration of the skin,
which can cause flare-ups, avoid areas of
high humidity and do not wear tight fitting
clothes that restrict air movement;
 Try to maintain proper diet, although a link
between diet and acne is not found;
 Avoid stressful situations. Stress may play
a role in acne flare-ups but it does not
cause acne
 Comedo: A plug of keratin and sebum within the
dilated orifice of a hair follicle, frequently
containing the bacteria Propionibacterium acnes,
Staphylococcus albus, also called blackhead.
 Propiobacterium acnes: a gram positive
anearobic rod found on the skin
 Pustule: a vesicle or an elevation of the
cuticle with an inflamed base, containing
pus.
 Blemish: Any mark of deformity or injury,
whether physical or moral; anything; that
diminishes beauty, or renders imperfect that
which is otherwise well formed
 Pimple: Any small acuminated elevation of the
cuticle, whether going on to suppuration or not
 Papule: A small circumscribed, superficial, solid
elevation of the skin
Important points to
remember!
 Self-treatment of acne is effective in patients
mature enough to understand that acne can be
controlled but not cured;
 Treatment of noninflammatory acne:
pharmacologic agents + nonpharmacologic
measures;
 Self treatment is appropriate only for grade I
acne (i.e. noninflammatory acne of mild to
moderate severity), presenting with open or
closed comedones
Classification of Acne
Grade Qualitative Quantitative Description
of Description
Acne
I Comedonal acne Comedones only, < 10 on face, none on
trunk, no scars, noninflammatory lesions only
II Papular acne 10-25 papules on face and trunk, mild
scarring, inflammatory lesions < 5 mm in
diameter
III Pustular acne More than 25 pustules, moderate scarring,
size similar to papules but with visible
purulent core
IV Severe persistent Nodules or cysts, extensive scarring,
pustulocyctis inflammatory lesions > 5 mm in diameter
acne
- Recalcitrant Extensive nodules/cysts
severe cystic
acne
Exclusion for Self-Treatment
 Grades II-IV acne: papules, pustules,
nodules, cysts and/or scarring
 Severe, recalcitrant acne (extensive
nodules/cysts)
 Exacerbating factors (e.g. comedogenic
drugs)
 Possible rosacea
(If acne lesions persist beyond mid-20s or develop in the
mid-20s or later, the symptoms may signal rosacea
rather than acne vulgaris)
Prescription Medication for
acne:
 Retinoic acid & Derivatives
 Isotretinoin
 Azelaic Acid
 Antibiotics (topical or systemic)
 Hormonal therapy
Retinoic Acid & Derivatives
 Retinoic acid (tretinoin) is the acid form of
vitamin A
 13-cis-retinoic acid (isotretinoin) is analog of
retinoic acid effective when given orally
 Retinoic acid insoluble in water; susceptible
to oxidation and ester formation particularly
when exposed to light;
 Topically applied retinoic acid remains chiefly
in the epidermis (< 10% absorbed)
Retinoic Acid & Derivatives
 The small quantities absorbed following a topical
application are metabolized by the liver and
excreted in bile and urine;
 Retinoic acid has several effects on epithelial
tissues (lysosomes, PG-E2, cAMP, cGMP and
RNA polymerase)
 Action in acne: (1) decreased cohesion between
epidermal cells (2) increased epidermal cell
turnover.
 This results in expulsion of open comedones
and transformation of closed comedones into
open ones
 Retinoic Acid & Derivatives
 Retinoic acid is applied initially in a concentration
sufficient to induce slight erythema with mild
peeling
 If too much irritaion is produced, decrease
concentration or frequency of application;
 During the first 4-6 weeks of therapy, comedones
not previously evident may appear
 However, with continued therapy, the lesions will
clear, and in 8-12 weeks optimal clinical
improvement should occur
 (Retin-A Micro): timed release formulation with
tretinoin containing microspheres. Less irritating
Retinoic Acid & Derivatives
 Prolonged use of tretinoin promotes :
(1) dermal collagen synthesis
(2) new blood vessel formation
(3) thickening of the epidermis
Which helps diminish fine lines and wrinkles

 Renova (0.05% cream): specially

formulated for this purpose
Retinoic Acid & Derivatives

The most common adverse effects (topical):

1. erythema, dryness: first few weeks of use,
but resolve with continued therapy;
2. May increase tumerogenic potential of UV
radiation (in animals). Thus, patients are
advised to minimize or avoid sun exposure
and use protective sunscreen
3. Allergic contact dermatitis: rare
Adapalene (Differin)
 A derivative of naphathoic acid that
resembles retinoic acid in structure and
effects
 Applied 0.1% gel once daily
 Unlike tretinoin:
1. photochemically stable
2. less irritating
 Most effective: mild to moderate acne
vulgaris
Tazarotene (Tazorac)
 Acetylenic retinoid
 0.1% gel
 Treatment of mild to moderately severe
facial acne
 Should not be used by pregnant women
(pregnancy risk factor=X)
 Contraceptive counseling in women of
childbearing age.
Isotretinoin (Accutane)
 A synthetic retinoid currently restricted to
the treatment of severe cystic acne that is
recalcitrant to standard therapies;
 Well absorbed to circulation, extensively
bound to plasma albumin,
 elimination half-life of 21 hrs (parent drug),
21-24 hrs (metabolite)
 MOA: inhibits sebaceous gland size and
function
MOA- isotretenoin:
 Isotretinoin prevents the formation of new
comedos and resultant inflammatory lesions by:
1. decreasing the size and secretions of the
sebaceous glands,
2. normalizing follicular keratinization, and
3. exerting anti-inflammatory effects.
 Sebum production is reduced by at least 90%
through competitive inhibition of retinol
dehydrogenase-4, the enzyme that mediates the
skin's production of dihydrotestosterone and
androstenedione.
 Isotretinoin (Accutane)
Dose:
 0.5-2 mg/kg/day, given orally in two divided doses
daily for 4-5 months;
 If severe cystic acne persists following this initial
treatment, a second course of therapy may be
initiated after 2 months;
 The skin would be sensitive during treatment.
Patient is at high risk for abnormal healing and
development of excessive granulation following
procedures (e.g. piercing, tatoos, epilation)
•Isotretinoin is available in 10-, 20-, and 40-mg soft gelatin capsules for oral
administration.
• Isotretinoin capsules should always be taken with food to maximize absorption
Isotretinoin (Accutane)
Adverse Effects
Common adverse effects (resemble
hypervitaminosis A):
 Dryness and itching of skin and mucous
membranes
 Less common: Headache, corneal opacities,
pseudotumpr cerebri inflammatory bowel
disease, anorexia, alopecia, muscle and joint
pains
 These effects are all reversible on
discontinuation of therapy.
Isotretinoin (Accutane)
Adverse Effects
 Skeletal hyperostosis has been observed in
patients receiving isotretinoin
 Premature closure of epiphyses noted in
children treated with this medication
 Lipid abnormalities (triglycerides, HDL) are
frequent
 Depression, psychosis, aggressiveness or violent
behavior & rarely suicidal thoughts (discontinuation MAY
NOT be sufficient)
 Teratogenecity
Teratogenecity
 the skull, ears, and eyes and include facial
dysmorphia and cleft palate.
 Internal abnormalities affecting the thymus
gland, central nervous system, cardiovascular
system, and parathyroid gland (hormone
deficiency) are recognized.
 In some cases, these abnormalities have
resulted in fetal death.
 Nursing mothers should not receive isotretinoin.
Isotretinoin (Accutane)
Teratogenecity
1. Women of childbearing age must use an
effective form of contraception for at least 1
month before; throughout isotretinoin therapy,
and for one or more menstrual cycles following
discontinuance of therapy
2. A serum pregnancy test must be obtained
within 2 weeks before starting therapy
3. Therapy should be initiated only on the second
or third day after the next normal menstrual
period
Isotretinoin (Accutane)
Monitoring parameters:
1. CBC with differential & platelet count, baseline
sed. rate, glucose,
2. Pregnancy tests
3. Lipids: prior to treatment & at weekly or
biweekly intervals until response to treatment
is established
4. Liver function tests: prior to treatment & at
weekly or biweekly intervals until response to
treatment is established
5. Creatine Phosphokinase
6. Blood Glucose
Azelaic Acid
 Straight chain saturated dicarboxylic acid; effective in the
treatment of acne vulgaris;
 Its mechanism of action not fully determined.
However, studies shown:
1. Antimicrobial activity against P acnes
2. In vitro inhibition of the conversion of testosterone to
dihydrotestosterone
 Initial therapy: once daily application of 20% cream to
affected areas for 1 week. Then twice daily thereafter
 Mild irritation with redness and dryness of the skin during
the first week of treatment
 Clinical improvement 6-8 weeks of continuous therapy
Topical Antibiotics
 Commonly prescribed: erythromycin and
clindamycin alone or in combination with benzoyl
peroxide
 MOA: (1) bactericidal activity against P acnes.
(2) may also have anti-inflammatory effect
 Topical antibiotics are not comedolytic,
 Bacterial resistance may develop to any of these
agents.
 The development of resistance is lessened if
topical antibiotics are used in combination with
benzoyl peroxide
Systemic Antibiotics
 Tetracycline and congeners (minocycline
and doxycycline*)
 Erythromycin, azithromycin
 Trimethoprim alone or in combination with
sulfamethoxazole
 MOA: (1) P acnes; (2) Anti-inflammatory
 Minocycline is more effective than
tetracycline and bacteria has less
resistance to this agent
Systemic Antibiotics
 Bacterial resistance to these agents may be
reduced by combining them with topical retinoids
and/or topical benzoyl peroxide
Most common side effects:
 phototoxicity from tetracycline group, especially
doxycycline
 Vertigo-like dizziness>> minocycline
 Stevens-Johnson syndrome>> trimethoprim-
sulfamethoxazole
 All oral antibiotics predispose to Candida
infections, particularly vaginitis
Hormonal Therapy
 MOA: estrogens are responsible for
maintenance of the normal structure and
function of the skin and blood vessels.

 Acne may be exacerbated by agents containing

androgen-like progestins (e.g. norethindrone,
lynestrenol, norethynodrel), whereas agents
containing large amounts of estrogen usually
cause marked improvement in acne
Hormonal Therapy

 FDA approved a triphasic, combination

OCP:
 Ortho-Tri-Cyclen: Ethinyl estradiol (0.035
mg) + Norgestimate:
Days 1-7 ………. 0.18 mg
Days 8-14……….0.215 mg
Days 15-21………0.25 mg
Hormonal Therapy
 A study showed that this OC reduced acne lesion
counts by more than 50% in female subjects,
compared with lesion reductions of about 26% in
controls
 Acne improvement during treatment with Ortho-
Tri Cyclen may take 3-4 months to become
apparent;
 Main limitation of anti-androgen therapy for acne
is that it cannot be used with male patients