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Acne Vulgaris: Pathophysiology, diagnosis, and treatment of a common dermatologic condition

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(1)

Acne Vulgaris:

Pathophysiology, diagnosis, and treatment

of a common

dermatologic condition

Dr. Mohamed Emam

Lecturer in

Clinical Pharmacy Department

(2)

Hair

(3)

What is Acne?

• Acne vulgaris is a chronic, inflammatory

disorder of the pilosebaceous units of the

skin.

• Sebaceous gland found in hair-covered

areas

• Functions to secrete sebum which is an

oily substance that acts to protect and

waterproof skin and hair and keep it from

being dry, brittle, and cracked

(4)

Epidemiology

• Age

Acne can present at any point during a person’s

life but 85% is between 12-24 years old

 Adolescent acne usually presents prior to the

onset of puberty

• Sex

 During adolescence, acne is more common in

males than females

 During adulthood, acne is more common in

females than males

(5)

Psychosocial impact

• Social, psychological and emotional

impairment

• Patients are prone to depression, social

withdrawal, anxiety and anger

• Scarring associated with acne can lead to

lifelong problems with regards to self

(6)

Pathophysiology

Primary Causes

Increased sebum production

Abnormal epithelial desquamation Bacterial growth

Inflammation Secondary Triggers

Mechanical obstruction (e.g., helmets, shirt collars)

Increased hormonal activity (e.g., menstrual cycles, puberty)

Stress (due to increased output of hormones from the adrenal gland) Cosmetics and emollients (occlude follicles and cause an acneiform eruption)

Medications with halogens (iodine, chlorine, bromine), Lithium, barbiturates, androgens, topical coal tar, phenytoin

Anabolic steroids

Diet (no proven effect but patient should eat well balanced diet and excess fat and carbohydrate should be avoided)

(7)

1. Increased Sebum Production

Maturation of the adrenal gland or an increase in

the number of cells of the sebaceous gland can

lead to excess sebum production

Caused mainly by androgens in both sexes e.g.

testosterone which is converted to

Dihydrotestosterone (DHT)

DHT increase size and activity of sebaceous

gland resulting in increase in sebum

(8)

2. Abnormal Epithelial

Desquamation

• Abnormal clumping of horny cells in pilosebaceous

unit

• Hyperkeratinization of the hair follicle prevents the

normal shedding of follicular keratinocytes

• This results in follicular canal widening and

increased cell production

• Sebum mixes with excess loose cells in the follicular

canal to form a keratinous plug, or microcomedo

- “Blackhead” – aka, open comedo; color due to the

oxidation of tyrosine to melanin upon exposure to air

- “Whitehead” – aka, closed comedo; due to

(9)

3. Bacterial Growth

• The occluded follicle is rich in lipids as this

is a major component of sebum

• This environment encourages the growth

of Propionibacterium acnes (P. acnes), a

bacteria that is part of the normal flora of

the skin

(10)

4. Inflammation

• P. acnes provokes an inflammatory

response by breaking down triglycerides

found in sebum to free fatty acids and

glycerol, and these compounds are

proinflammatory

• P. acnes leads to further inflammation by

releasing chemotactic factors that result in

white blood cells (WBC) activity.

(11)

Clinical Presentation

• Acne may present on the face, neck,

chest, back, shoulders, or upper arms

• Acne can be described in terms of:

– Type of lesion

– Classification of severity

• Lesions can take months to heal

completely and fibrosis associated with

healing may lead to permanent scarring

(12)
(13)

Type of Lesion

• Non-Inflammatory

Comedonal acne: Whitehead and Blackhead

less than 10 in the face

• Inflammatory

Papular: small bumps less than 5mm in diameter

10-25 in the face

Pustular– small bump with a visible central core

of purulent material more than 25 in the face

Pustulcystic acne or Nodulocystic: Nodule –

(14)

Comedonal Lesions and

papular acne

(15)

Pustular acne or Inflammatory

Lesions

(16)

Pustulocystic acne or

Nodulocystic Lesions

(17)
(18)

Therapeutic Objectives

• To prevent the formation of new acne

lesions

• To heal existing lesions

(19)

Treatment Options

• Non-pharmacologic

Surface skin cleansing

• Pharmacologic

Topical products

Oral products

(20)

Non-Pharmacologic Treatment

• Surface skin cleansing with soap and water has

a relatively small effect on acne because it has

minimal impact within follicle

• Skin scrubbing or excessive face washing does

not necessarily open or cleanse pores and may

lead to skin irritation

• Use of gentle, nondrying cleansing agents is

important to avoid skin irritation and dryness

during some acne therapies

(21)

Pharmacologic Treatment:

• Topical Products

Benzoyl peroxide

Retinoid analogues

Topical antibiotics

Azelaic acid

• Oral products

Oral Antibiotics

Isotretinoin

(22)

Topical Products

• Treatment Vehicle

– cream 

sensitive or dry skin

– lotion  any skin type

– gel 

oily skin

(23)

Benzoyl Peroxide

• e.g. Panoxyl 5 or 10 acne gel and cream or

Akneroxid 5 gel

• Role in Acne Treatment:

– Non-antibiotic bacteriostatic agent against

Propionibacterium acnes

– Increases the removal rate of epithelial cells and

loosens the follicular plug structure

– Proven effective in the treatment of acne

• Availability

– Available in a wide variety of dosage forms (e.g.,

soaps, lotions, creams, washes, and gels) and

dosages (e.g., 2.5% to 10%)

(24)

Benzoyl Peroxide

cont…

• Dosing

– To limit irritation and increase tolerability,

begin with lowest concentration and increase

either the strength or application frequency

– Patients should apply the product to cool,

clean, dry skin no more than twice daily

• Common Side Effects

– Dryness and irritation

(25)

Retinoid Analogues

Role in Acne Treatment

• Increases cell turnover in the follicular wall

• Decreases cohesiveness of cells, leading

to extrusion of the comedones and

inhibition of new comedo formation

• Effectiveness in the treatment of acne is

well documented

(26)

Retinoid Analogues

cont…

Examples

• Tretinoin (topical vitamin A acid e.g. Retin A gel or cream)

Availability – wide variety of dosage forms and concentrations Dosing – applied once nightly

Side Effects – skin irritation, erythema, peeling, increased sensitivity to sun exposure, wind, or cold

• Adapalene (Differin)

Availability – 0.1% gel, cream and alcoholic solution Dosing - applied once daily at night or in the morning Side Effects – minimal irritation

• Tazarotene (Acnee free gel, cream and lotion) Availability – 0.05% and 0.1% gel or cream Dosing – applied once nightly

(27)

Topical Antibiotics

• Role in Acne Treatment

- Both erythromycin and clindamycin have demonstrated efficacy and are well tolerated

• Availability

- Wide variety of dosage forms and concentrations - Also available in combination with benzoyl peroxide • Dosing

- Erythromycin – applied once or twice daily

- Clindamycin (e.g. Dalacin T lotion) – applied once or twice daily - In combination with benzoyl peroxide – applied once or twice daily • Common Side Effects

(28)

Azaleic Acid

• Role in Acne Treatment

Reported to possess comedolytic,

anti-inflammatory and antibacterial properties

• Availability

20% cream e.g. Skinoren or Azaderm cream

• Dosing

Applied twice daily on clean, dry skin

• Side Effects

Mild transient burning, pruritus, stinging and

tingling

(29)

Other topical Products

• Salicylic Acid 0.5 - 2%

– Irritant keratolytic agent – applied twice daily

– skin dryness and irritation

• Sulfur 3 - 8%

– Keratolytic agent and antibacterial – offensive color and odor

• Resorcinol

– Keratolytic agent

– more effective when combined with sulfur

• Example of the above three in combination

(30)

Oral therapy (Indications)

Moderate inflammatory acne non responsive to

topical therapy

(31)

Oral Antibiotic

Role in Acne Treatment

Standard of care in the management of moderate and severe acne as well as in treatment-resistant forms of inflammatory acne

Examples

• Tetracycline – least expensive and most often prescribed for initial therapy

• Doxycycline (vibramycin)– more effective than tetracycline

• Minocycline (minocin)– reserved for patients who do not respond to other oral antibiotics or topical products; superior to doxycycline in reducing P. acnes

• Erythromycin – effective, but use is limited to those who cannot use the tetracyclines (e.g. pregnant women or children under 8 y.o.) • Trimethoprim-Sulfamethoxazole (Septazol and sutrim)– effective,

but use is limited to those who cannot use the tetracyclines or erythromycin, or in case of resistance to these antibiotics

• Clindamycin (Dalacin C Cap.) – use is limited because it causes diarrhea

(32)

Oral Antibiotics

cont…

• Dosing

- Tetracycline – 250-500mg twice to four times daily

- Doxycycline– 50-100mg once to twice daily

- Minocycline – 50-100mg once to twice daily

- Erythromycin – 250-500mg twice daily

- Trimethoprim-Sulfamethoxazole – 160/800mg twice

daily

- Clindamycin – use is limited by diarrhea

- Combined with topical therapy

• Common Side Effects

(33)

Isotretinoin (e.g. Roaccutan10 or

20 mg Cap.)

• Role in Acne Treatment

- Indicated for severe nodular or inflammatory acne in patients unresponsive to conventional therapies, for scarring, for those with chronic relapsing acne and for acne associated with severe psychological distress

- Decreases sebum production, changes in sebum composition, inhibits

P.acnes growth within follicles, inhibits inflammation

• iPLEDGE program

- Isotretinoin is a potent teratogen, and thus should only be prescribed by physicians knowledgeable in its appropriate administration and monitoring - iPLEDGE is a mandatory distribution program in the United States for isotretinoin

- Female patients of child-bearing potential must only be treated with this agent if they are participating in iPLEDGE

- Physician enters the patient’s information into the iPLEDGE website

- Dispensing pharmacist interviews patient and verifies patient information on website

(34)

Isotretinoin

cont…

• Dosing

- 0.5-2.0 mg/kg/day

- Drug is usually given for a 20 week course of therapy

- Lower doses can be used for a longer time period, with

a total cumulative dose of 120-150 mg/kg

• Common side effects

- Teratogenicity, Dry mouth, nose and eyes

- Increases in cholesterol, triglycerides and glucose

- Mood disorders, depression and suicidal ideation.

(35)

Antiandrogens and Hormones

• Role of hormones (e.g. Diane 35 tab.) in Acne Treatment

- Acne associated with hirsutism, menstrual irregularity and

alopecia as well as women desiring contraception

- Estrogen-containing oral contraceptives can be useful in the

treatment of acne in some women

- Currently FDA-approved products for the treatment of acne

include Ortho Tri-Cyclen (norgestimate with ethinyl estradiol)

and Estrostep (norethindrone acetate with ethinyl estradiol) as

both show to be equally efficacious

- The effect of other estrogen-containing contraceptives (e.g.,

transdermal patches, vaginal rings) has not been studied

(36)

Antiandrogens and Hormons

cont…

• Spironolactone (Aldactone) can be used

as an androgen antagonist

• Oral corticosteroids (e.g. Prednisone in 20

mg/day or its equivalent) can be used to

treat severe acne.

• Oral corticosteroids provide quick

improvement for important events like

wedding.

(37)

Acne Treatment and Therapeutic Strategies

Comedonal lesions Topical retinoid Azelaic acid Salicylic acid If results unsatisfactory Increase strength or change medications Papules and pustules Benzoyl peroxide If results unsatisfactory switch to or add topical antibiotics If results unsatisfactory add course of oral antibiotics Cystic lesions Prescribe course of oral antibiotics + mixed comedonal- papulopustular topical therapy If results unsatisfactory consider referral to dermatologist for oral isotretinoin therapy Mixed comedonal lesions

and papulopustules Retinoid+topical antibiotics Retinoid+benzoyl peroxide Retinoid+benzoyl peroxide+topical antibiotics Azelaic acid+benzoyl peroxide Azelaic acid+topical antibiotics If results unsatisfactory prescribe topical retinoid+

References

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