ACNEBy Daphne Gima18th February 2009

OUTLINE

Introduction Pathogenesis of Acne Classification of Acne Management of Acne Summary References

INTRODUCTION

Inflammatory disease of the pilosebaceous follicles marked by comedones, papules or pustules on the face, chest and upper back.

Has high prevalence, particularly in adolescence, but can occasionally occur even until 4th decade of life.

Affects more males than females Although not fatal, produces physical

scarring as well as psychological stress.

PATHOGENESIS OF ACNE VULGARIS

Four main pathogenetic factors:

(i) Increased sebum production(ii) Follicular hyperkeratinization, leading to

hyperkeratotic plug of sebum and keratin (microcomedone)

(iii) Follicular colonization with anaerobe Propionibacterium acnes

(iv) Inflammation

PATHOGENESIS OF ACNE (2)

Depending on degree of the factors, the microcomedone will form

- Closed comedone (whitehead) with further accumulation of sebum

- Open comedone (blackhead) with further follicular orifice distension, and oxidized lipids.

- Inflammatory lesions (cysts) develop when follicular contents rupture, forming superficial pustule, deeper papule and even deeper nodule.

PATHOGENESIS OF ACNE (3)

PATHOGENESIS OF ACNE (4)

External factors that may also contribute to acne:

(i) Cosmetics(ii)Diet(iii)Stress(iv)Medications- azathioprine, barbiturates, corticosteroids,

cyclosporin, isoniazid, lithium etc

CLASSIFICATION OF ACNE

Generally divided into 4: Type 1: Mainly comedones with occasional

small inflamed papule or pustule, no scarring Type 2: Comedones and more facial papules

and pustules; mild scarring Type 3: Numerous comedones, papules and

pustules, spreading to back, chest and shoulders, with occasional cyst and nodule; moderate scarring

Type 4: Numerous large cysts on the face, neck and upper trunk; severe scarring

CLASSIFICATION OF ACNE

DIFFERENTIAL DIAGNOSIS: ACNE FULMINANS

Rare form of severe cystic acne usually seen in young males age 12 to 17.

Onset of severe cystic involvement and concomitant ulceration is acute.

Besides cysts, patients also usually presents with fever, malaise, fatigue and arthralgias.

Ulcerations have a characteristic overhanging, ragged border which surrounds an exudative necrotic plaque.

DIFFERENTIAL DIAGNOSIS: ACNE CONGLOBATA

Severe form of acne that is uncommon and produces disfigurement.

Characterized by paired and grouped comedones, primarily seen on neck and trunk.

Nodules can increase in size or coalesce to eventually degenerate to discharge foul-smelling pus and ulcerate.

As cyst or nodule breaks down, crusts can form over deep ulcers which are very slow to heal.

MANAGEMENT OF ACNE

Acne treatment involves targeting of the 4 factors involved in the pathogenesis of acne

Aim: Reduce/eliminate microcomedones Treatment is based on severity of acne and

the agents used include the retinoids, antibiotics & anti-inflammatory agents.

Given either topically or orally. Acne lesions take at least 2 months to

mature, so any treatment should be given for 2-3 months.

TOPICAL TREATMENT: BENZOYL PEROXIDE Preparations available in 2.5%, 5% & 10%,

Use OD or BD. Strong antibacterial effects, moderate anti-

inflammatory and slight anticomedogenic effects

Reduces P. acnes colonization by releasing free-radical oxygen that oxidizes bacterial proteins in the sebaceous follicles

Most common SE is skin irritation, also can bleach hair and clothing.

Combination with topical antibiotic or retinoid more effective than benzoyl peroxide alone.

Advantage: Does not cause bacterial resistance, as seen with antibiotics

TOPICAL TREATMENT: RETINOIDS

Topical preparations of retinoids include tretinoin, adapalene and tazarotene.

Chemically related to vitamin A and exerts function via the retinoic acid receptor and the retinoid receptor, exact MOA unknown.

Effects include:- Normalization of desquamation to decrease

microcomedones formation.- Anti-inflammatory effects by inhibiting

activity of leukocytes, release of pro-inflammatory cytokines and other mediators.

- Helps penetration of other active agents.

TOPICAL TREATMENT: RETINOIDS (2)

Potential SE include excessive desquamation, burning, increased photosensitivity, erythema, irritation, abnormal pigmentation and teratogenicity.

3rd generation retinoids e.g. adapalene produces less irritation and has faster onset of action than older generations retinoids.

Topical retinoids can be used OD or BD. In OD regimens, preparation should be applied at bedtime with concurrent use of sunscreen during daytime.

TOPICAL TREATMENT: ANTIBIOTICS

Act as bacteriostatic and specifically reduce P. acnes growth and decrease percentage of pro-inflammatory free fatty acids in surface lipids.

Most frequently used are clindamycin, erythromycin and occasionally metronidazole, all used BD.

Most common SE are irritation with erythema, itching, peeling, dryness and burning.

Also risk of pseudomembranous colitis in clindamycin use.

SYSTEMIC TREATMENT: ANTIBIOTICS For management of moderate and severe

acne, particularly in pustular acne. Oral antibiotics produce more rapid clinical

improvement than topical preps, but also associated with GI upset, vaginal candidiasis, and also decrease efficacy of oral contraceptives.

Normal regimens include:- Tetracycline 500-1000mg in 2 divided doses.- Erythromycin 250-750mg BD.- Doxycyline 100mg BD.- Minocycline 50-100mg BD.- Azithromycin 250mg 3 times/week

SYSTEMIC TREATMENT: ANTIBIOTICS (2)

Resistance of P. acnes is problem, erythromycin most common, followed by tetracycline and doxycyline.

Recommendations to limit resistance:- Avoid antibiotics if nonantibiotic agents eg.

benzoyl peroxide are effective.- Antibiotics should be prescribed for a

minimum of 2 months and max 6 months.- Avoid concomitant use of topical and oral

antibiotics.- Educate patient on compliance.

SYSTEMIC TREATMENT: ISOTRETINOIN

Only treatment that targets all 4 pathogenic factors leading to acne, so indicated for severe recalcitrant nodular acne.

Dose (adults) : 0.5-1mg/kg/day in 2 divided doses for 15 to 20 weeks

However, highly teratogenic and is contraindicated in pregnancy, lactation and severe hepatic and renal dysfunction.

Also causes hypertriglyceridemia, linked to suicide & depression, possibly due to decreased brain metabolism in the orbitofrontal cortex.

SYSTEMIC TREATMENT: ISOTRETINOIN (2)

Patients should be counselled to use two forms of contraception due to teratogenic risk.

Monitoring parameters:- Monthly pregnancy tests- Lipids (particularly triglycerides)- Liver function tests

MISCELLANEOUS TREATMENT

Patients may also benefit from oral anti-androgens that act at peripheral receptor level to reduce sebum production.

- Spironolactone 50-150mg daily.- Flutamide 125mg OD. Estrogen-containing oral contraceptives are

also useful.- Diane 35 (Cyproterone acetate 2mg &

ethinyloestradiol 0.035mg) Salicylic acid preparations (including facial

wash) may also be used though they are moderately effective.

SUMMARY

Acne is an inflammatory disease of the pilosebaceous follicles caused by abnormal keratinization, increased sebum production, P. acnes colonisation and inflammation.

Classified into 4 types depending on clinical presentation of lesions.

Treatment includes benzoyl peroxide, topical and oral preparations of retinoids and antibiotics.

SUMMARY (2)

ACNE SEVERITY TREATMENT

Non-inflammatory comedonal acne

Topical retinoids

Mild to moderate inflammatory acne

Benzoyl peroxide + a topical antibiotic or combination of both

Moderate to severe inflammatory acne

Benzoyl peroxide + topical/oral antibiotics + topical retinoids

Severe nodulocystic acne Benzoyl peroxide + oral isotretinoin

REFERENCES1. P. Rutter, Community Pharmacy: Symptoms, Diagnosis and Treatment. 1st edn, Churchill-

Livingstone 2004.

2. UpToDate: Approach to Acne Vulgaris

3. Lacy et al. Drug Information Handbook, 17th edn, Lexi-Comp. 2008.

4. Kumar A. et al. Treatment of acne with special emphasis on herbal remedies. Expert Rev Dermatol. 2008;3(1):111-122

5. Piskin S. & Uzunali E. A review of the use of adapalene for the treatment of acne vulgaris. Therapeutics & Clinical Risk Management 2007:3(4) 621-624

6. Bardazzi et al. Azithromycin: A new therapeutical strategy for acne in adolescents. Dermatol Online J. 2007; 13(4):4

7. Swanson J. Antibiotic resistance of Propionibacterium acnes in acne vulgaris. Dermatol Nurs 2003; 15(4): 359-362

8. National Guideline Clearinghouse. Guidelines of care for acne vulgaris management. From www.guideline.gov.

9. Woodard I. Adolescent acne: a stepwise approach to management. Topics in Advanced Practise Nursing eJournal. 2002;2:2.