Acne

ACNE By Daphne Gima 18th 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 foulsmelling 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 antiinflammatory and slight anticomedogenic effects  Reduces P. acnes colonization by releasing freeradical 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 antiandrogens 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 Non-inflammatory comedonal acne

TREATMENT Topical retinoids

Mild to moderate inflammatory Benzoyl peroxide + a topical acne antibiotic or combination of both Moderate to severe inflammatory acne

Benzoyl peroxide + topical/oral antibiotics + topical retinoids

Severe nodulocystic acne

Benzoyl peroxide + oral isotretinoin

REFERENCES 1.

P. Rutter, Community Pharmacy: Symptoms, Diagnosis and Treatment. 1st edn, ChurchillLivingstone 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.