1. Dr. Abdulaziz Saeedan PhD, Pharmacology a.binsaeedan@psau.edu.sa
Acne Vulgaris Drugs Pharmacology IV (PHL 425)
Dr. Abdulaziz Saeedan
PhD, Pharmacology

2. Acne, Epidemiology & Etiology
Acne vulgaris is the most common of all cutaneous disorders and occurs in more than 85% of adolescents. It is more severe in males than in females. Genetic background plays a role in the incidence of this disorder
Commonly involved areas are those with the highest concentration of sebaceous glands, that is the face, neck, chest, shoulders, and upper back.
The most common trigger is puberty, when surges in androgen stimulate sebum production and hyperproliferation of keratinocytes
Other triggers include hormonal changes that occur with pregnancy or throughout the menstrual cycle; some cosmetics, humidity and sweating
Acne may improve in summer months because of sunlight's anti-inflammatory effects
Drugs such as lithium, glucocorticoids, oral contraceptives, androgens (e.g., testosterone), iodides, and bromides are contributory factors
Others Emotional stress can definitely cause exacerbations
Occlusion and pressure on the skin, such as by leaning face on hands, very important and often unrecognized exacerbating factor (acne mechanica)
Acne is not caused by chocolate or fatty foods or, in fact, by any kind of food
sebaceous glands: a small gland in the skin which secretes a lubricating oily matter (sebum) into the hair follicles to lubricate the skin and hair

3. Acne Vulgaris (Acne): Overview & Pathogenesis
Acne is the formation of comedones, papules, pustules, nodules, and/or cysts as a result of obstruction and inflammation of pilosebaceous units (hair follicles and their accompanying sebaceous gland)

6. Acne, Pathogenesis sebaceous follicle Micro comedo
Acne occurs when pilosebaceous units become obstructed with plugs of sebum and desquamated keratinocytes, then sometimes infected with the normal skin anaerobe Propionibacterium acnes
Manifestations differ depending on whether Propionibacterium acnes stimulates inflammation in the follicle
Thus, acne can be inflammatory or non-inflammatory, depending on whether P. acnes stimulates inflammation in the follicle or not
Non-inflammatory acne is characterized by comedones; uninfected sebaceous plugs “a plug of keratin and sebum” impacted within follicles
Comedones are termed closed (whiteheads) or open (blackheads) depending on whether the follicle is closed or dilated at the skin surface
sebaceous follicle Micro comedo
closed comedo open comedo

7. Acne, Pathogenesis
Inflammatory acne comprises papules, pustules, nodules and cysts
Papules appear when lipases from P. acnes metabolize triglycerides into free fatty acids (FFA), which irritate the follicular wall
Pustules occur when active P. acnes infection causes inflammation within the follicle
Nodules and cysts occur when rupture of follicles due to inflammation, physical manipulation, or harsh scrubbing releases FFAs, bacteria and keratin into tissues, triggering soft-tissue inflammation

8. Severity rating for acne
Type 1: Comedones only, fewer than 10 lesions on the face, no lesions on the trunk and no scarring
Type 2: Papules, 10 to 25 lesions on the face and trunk, mild scarring
Type 3: Pustules, more than 25 lesions, moderate scarring
Type 4: nodules or cysts, extensive scarring

9. Another severity rating for acne

10. Management of Acne
The withdrawal of aggravating factors such as cosmetics and drugs is paramount where they appear to be involved in the etiology of acne. Trauma, such as picking and vigorously squeezing acne lesions, can aggravate the condition
Affected areas should be cleansed daily
Extra washing, use of antibacterial soaps, and scrubbing confer no added benefit
Changes in diet are also unnecessary and ineffective
Treatments are directed at reducing sebum production, comedones formation, inflammation and infection
Selection of treatment is generally based on severity

11. Treatment Mild and mild to moderate acne:
Single-agent therapy is generally sufficient for comedonal acne
a mainstay of treatment for comedones is daily topical tretinoin in escalating concentrations as tolerated.
Azelaic acid has comedolytic and antibacterial properties and may be synergistic with retinoids
Papulopustular acne generally requires dual therapy
The combination of tretinoin with benzoyl peroxide or topical antibiotics (e.g., erythromycin, clindamycin) and/or glycolic acid
Daily adapalene gel and tazarotene cream or gel are alternatives for patients who cannot tolerate topical tretinoin
Treatment should be continued for 6 week or until lesions respond. Maintenance treatment may be necessary to maintain control.
Oral antibiotics (e.g., tetracycline, minocycline, doxycycline, erythromycin) can be used when wide distribution of lesions makes topical therapy impractical

12. Treatment Moderate acne:
Moderate acne responds best to oral systemic therapy with antibiotics. Antibiotics effective for acne include tetracycline, minocycline, doxycycline and erythromycin. Full benefit takes ≥ 12 wk
Tetracycline is usually a first choice: 250 or 500 mg bid (between meals and at bedtime) for 4 wk or until lesions respond, after which it may be reduced to the lowest effective dose
Because relapse ordinarily follows short-term treatment, therapy must be continued for months to years, although for maintenance tetracycline 250 or 500 mg once/day is often sufficient
Minocycline 50 or 100 mg bid causes fewer GI adverse effects, is easier to take, is less likely to cause photosensitization
Erythromycin and doxycycline are considered 2nd-line agents because both can cause GI adverse effects, and doxycycline is a frequent photosensitizer
In women, prolonged antibiotic use can cause candidal vaginitis; if local and systemic therapy does not eradicate this problem, antibiotic therapy for acne must be stopped

13. Treatment Severe acne:
Oral Isotretinoin is nearly always effective. It is also the best treatment for patients with moderate acne in whom antibiotics are unsuccessful and for those with severe inflammatory acne.
It is limited by adverse effects, including dryness of conjunctiva and genital mucosa, chapped lips, depression, elevated lipids and birth defects.
CBC, liver function, and fasting glucose, triglyceride, and cholesterol levels should be determined before treatment. Each should be re-assessed at 4 wk and, unless abnormalities are noted, need not be repeated until the end of treatment
CBC = complete blood count

14. Thanks