ACNE VULGARIS

ACNE VULGARIS - Katrina Miller, MD
BASICS
DESCRIPTION
• Acne vulgaris is a disorder of the pilosebaceous units (PSU), caused by androgen-mediated hyperkeratinization and increased sebum production, resulting in plugging of the follicles and formation of comedones. When further inflammation occurs, lesions include papules, inflammatory pustules, nodules, and scarring.
• System(s) Affected: Skin/exocrine
ALERT
Geriatric Considerations
Favre-Racouchot syndrome
Isotretinoin is a teratogenic; Pregnancy Class X
Pregnancy Considerations
• May result in a flare, or remission, of acne
• Erythromycin can be used in pregnancy; use topical agents when possible
• Avoid topical tretinoin, although no good evidence exists that its use is teratogenic.
• Contraindicated: Isotretinoin, tazarotene, tetracycline, doxycycline, minocycline
Pediatric Considerations
• Neonatal acne
• Infantile acne: Increased risk for severe teenage acne vulgaris.
• Rare in ages 1-7 years
- Check for hyperandrogenemia of adrenal or ovarian origin
- Do not use tetracyclines 8 years of age
• Adolescent acne
- Often very significant to adolescent patient
- Often an "entry ticket" for advice on lifestyle, contraception, physiology, etc.
EPIDEMIOLOGY
• Predominant age
- Primarily early to late puberty, may persist into 3rd to 4th decades
- Affected ages: All
• Predominant sex
- Male > Female (adolescence)
- Female > Male (adult)
Prevalence
• 17-50 million in the U.S. Varies geographically.
• Nearly 100% of adolescents affected. A smaller percentage will seek medical advice.
• 8% of 25-34 year olds, 3% of 35-44 year olds
RISK FACTORS
• Adolescence
• Increased endogenous androgenic effect
• Androgenic steroids (e.g., steroid abuse, some birth control pills)
• Possibly stress
• Oily cosmetics: Cleansing creams, moisturizers, and oil-based foundations; pomade
• Rubbing or occluding skin surface (e.g., sports equipment such as helmets and shoulder pads), telephone or hands against the skin
• Drugs
- Androgens and androgenic stimulants
- Anabolic steroids
- Systemic corticosteroids
- Long-acting progestins
- Lithium, phenytoin, isoniazid, phenobarbital, ethionamide, azathioprine, disulfiram, cyclosporine, quinine, thiourea, and thiouracil
• Virilization disorders: PCOS
• Hot, humid climate
Genetics
• Familial association.
• If a family history exists, the acne may be more severe and occur earlier.
PATHOPHYSIOLOGY
• Androgens (testosterone and DHEA)
- Stimulate sebum production and proliferation of keratinocytes in hair follicles
• Keratin plug obstructs follicle os, causing sebum accumulation and follicular distention
• Propionibacterium acnes, an anaerobe, colonizes and proliferates in the plugged follicle.
- P. acnes promotes chemotactic factors and proinflammatory mediators, causing inflammation of follicle and dermis.
ETIOLOGY
Androgens, inflammation, and P. acnes
ASSOCIATED CONDITIONS
• Acne fulminans
• Pyoderma faciale
• Acne conglobata
• Hidradenitis suppurativa
• Pomade acne
• SAPHO syndrome: Synovitis, acne, pustulosis, hyperostosis, osteitis
• PAPA syndrome: Pyogenic sterile arthritis, pyoderma gangrenosum, cystic acne
• Dark-skinned patients: 50% keloidal scarring and 50% acne hyperpigmented macules (AHMs)

DIAGNOSIS
SIGNS AND SYMPTOMS
• Closed comedones (whiteheads)
• Open comedones (blackheads)
• Nodules or papules
• Pustules ("cysts")
• Scars: Ice pick, rolling, boxcar, atrophic macules, hypertrophic, depressed, sinus tracts
• Most common areas affected are: face, chest, back, and upper arms (areas of greatest concentration of sebaceous glands)
• Factors influencing symptomatology
- Males later onset, greater severity
- Females may worsen immediately prior to menses
• Grading system (American Academy of Dermatology, 1990)
- Mild: Few papules/pustules; no nodules
- Moderate: Some papules/pustules; few nodules
- Severe: Numerous papules/pustules; many nodules
- Very severe: Acne conglobata, acne fulminans, acne inversa
History
Duration, medications, cleansing products, stress, smoking, exposures, family history
Physical Exam
Type of lesions, number, location
TESTS
Lab
Testosterone, dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) measure in rare cases when acne arises de novo in previously unaffected adult. High levels or LH:FSH ratio >2.5 suggests PCOS.
Pathological Findings
• Oiliness, thickening of the skin
• Hypertrophy of the sebaceous glands
• Perifolliculitis
• Scarring
DIFFERENTIAL DIAGNOSIS
• Folliculitis
• Acne (rosacea, cosmetica, steroid induced)
• Perioral dermatitis
• Chloracne
• Pseudofolliculitis barbae
• Drug eruption
• Verruca vulgaris and plana
• Keratosis pilaris
• Molluscum contagiosum
TREATMENT
GENERAL MEASURES
• Therapy goals
- Lessen physical discomfort
- Minimize scarring
- Improve appearance
- Avoid adverse psychologic impact
• Cleansing
- Use mild soap, once or twice a day to control surface oiliness (frequent washing and abrasives can irritate the skin and increase sebum production and inflammation).
• Comedonal acne (grade 1): Keratinolytic agent preferred (1,3)[A]
• Mild inflammatory acne (grade 2): Topical antibiotic with benzoyl peroxide. Add keratinolytic agent if needed and tolerated (2,3)[A].
• Moderate inflammatory acne (grade 3): Systemic antibiotic added to regimen above for grade 2, or systemic antibiotic substituted for the topical treatment of benzoyl peroxide or topical antibiotic. Continue keratinolytic agent after completion of antibiotic for maintenance.
• Severe inflammatory acne (grade 4): As in Grade 3, or isotretinoin (1,3)[A]
• Apply topical agents to both lesions and surrounding area of affected skin.
• Topical retinoid plus antibiotic (topical or PO) is better than either alone (1,3)[A].
• Antibiotic therapy should be stopped after inflammatory lesions resolve.
• Oral antibiotics should generally be used for 6 months to prevent development of resistance. Topical antibiotic use should generally be limited to 3 months. Topical and oral antibiotics should not be used in combination.
• Recommended vehicle type
- Cream: Dry or sensitive skin, better in cold, dry weather
- Gel or solution: Oily skin, warmer, humid weather
- Lotion: Hair bearing areas
• Avoid use of drying agents in combination with keratinolytic agents.
• Oilfree, noncomedogenic sun screens
- Although UV light results in some improvement in untreated acne, it will react adversely with retinoids and tetracyclines.
• Stress management if acne flares with stress
Diet
• Good nutrition and hydration preferable
• Special diets do not diminish acne.
Activity
Cleansing after sweating
SPECIAL THERAPY
Phototherapy is effective for inflammatory lesions.
Complementary and Alternative Medicine
Zinc gluconate 30 mg/d may reduce inflammatory lesions (1)[B]
MEDICATION (DRUGS)
• Keratinolytic agents (1)[A]
- Side effects include dryness, erythema, scaling, and photosensitivity, which are dose related. Start with lower strength or frequency and increase as tolerated.
• Tretinoin (Retin-A, Retin A micro, Avita): Apply at bedtime; wash skin and let skin dry 30 minutes before topical application
- Retin-A Micro and Avita are less irritating, less phototoxicity.
- May cause an initial flare of lesions, which indicates a good initial response to treatment. May be eased by 14-day course of oral antibiotics
• Adapalene (Differin): Apply topically at night.
- As effective and better tolerated than tretinoin (1,2)[A]
• Tazarotene (Tazorac): Apply at bedtime.
- Highly effective
• Azelaic acid (Azelex): 20% topically, b.i.d.
- Keratinolytic, antibacterial, and antiinflammatory
- Reduces postinflammatory hyperpigmentation in dark-skinned individuals
- Side effects: Erythema, dryness, scaling, hypopigmentation
• Salicylic acid: Less effective than tretinoin
• Alpha-hydroxy acids: Available OTC
• Antibiotics and anti-inflammatories (1)[A]
- Daily to b.i.d. usage
• Topical benzoyl peroxide
- Bactericidal through direct toxic effect
- No P. acnes resistance noted
- Benzoyl peroxide 2.5% as effective as stronger preparations
- When used with tretinoin, apply benzoyl peroxide in morning and tretinoin at night
- Side effects: Irritation; may bleach clothes
• Topical antibiotics (1)[A]
- Erythromycin
- Clindamycin
- Metronidazole gel: Apply once daily
- Azelaic acid (Azelex): 20% cream: Enhanced bactericidal effect and decreased risk of resistant P. acnes when used with zinc and benzoyl peroxide
- Benzoyl peroxide-erythromycin (Benzamycin): Probably most effective topical antibiotic; especially effective with azelaic acid
- Benzoyl peroxide-clindamycin (BenzaClin, DUAC, Clindoxyl): Better than either alone (2)[A]
- Sodium sulfacetamide (Sulfacet-R, Novacet, Klaron): Useful in acne with seborrheic dermatitis or rosacea
• Systemic antibiotics (1)[A]
• Tetracycline: 500-2,000 mg/d, given b.i.d.-q.i.d.; begin at high dose, then taper in 4-6 months if good response; side effects include photosensitivity and esophagitis
- Avoid use with antacids, iron
• Minocycline 50-200 mg/d, q.i.d.-b.i.d.; side effects include photosensitivity, urticaria, gray-blue skin color, vertigo, autoimmune hepatitis, pseudotumor cerebri, and lupus-like syndrome
• Doxycycline 50-200 mg/d, given b.i.d.-q.i.d.; side effects include photosensitivity
• Erythromycin: 500-1,000 mg/d; given b.i.d.-q.i.d.; decreasing effectiveness as a result of increasing P. acnes resistance
• Trimethoprim-sulfamethoxazole (Bactrim DS)
• Isotretinoin (Accutane) (1)[A]: 0.5-1.0 mg/kg/d b.i.d. PO; 60-90% cure rate; usually given for 12-20 weeks, 20% of patients relapse and require retreatment.
- Side effects: Cheilitis, arthralgias, tendinitis, hyperlipidemia, pseudotumor cerebri, poor wound healing, highly teratogenic (severe central nervous system and cardiovascular anomalies and facial deformities)
- Avoid tetracyclines or vitamin A preparations during isotretinoin therapy
- Monitor for pregnancy, lipids and liver function tests at baseline, and every month.
- Should be registered member of manufacturer's iPLEDGE program
• Acne hyperpigmented macules
- Topical hydroquinones (1.5-10%)
- Azelaic acid (20%) topically
- Topical retinoids as above
• Other medications for women only
- Oral contraceptives (1)[A]: More improvement with 35 mcg estradiol than lower dose.
- Spironolactone (Aldactone); 25-200 mg/d; antiandrogen; reduces sebum production
- Flutamide (Eulexin) 250-500 mg/d
- Corticosteroids: Low dose, suppresses adrenal androgens. May be used in males with high-grade acne as well.
SURGERY
• Comedo extraction: Use a comedom extractor after incising the layer of epithelium over comedo
• Incision and drainage may be needed for abscesses
• Injection of large cystic lesions with 0.05-0.3 mL triamcinolone (Kenalog 2-5 mg/mL), use 30-gauge needle to inject and slightly distend cyst
• Acne scar treatment: Dermabrasion, chemical peels, laser resurfacing, grafting, subcutaneous incision, punch excision, punch elevation, tissue augmentation injections
FOLLOW-UP
DISPOSITION
Issues for Referral
Dermatology consultation recommended for the following: Refractory lesions despite appropriate therapy, consideration of isotretinoin therapy, management of acne scars
PROGNOSIS
Gradual improvement over time (usually within 8-12 weeks after beginning therapy)
COMPLICATIONS
• Acne conglobata: Severe confluent inflammatory acne with systemic symptoms
• Facial and psychological scarring
• Gram-negative folliculitis: Superinfection due to long-term oral antibiotic use, treatment with ampicillin, trimethoprim-sulfa, or isotretinoin
PATIENT MONITORING
• Monthly visits until adequate response
• Pretreatment and monthly lipids, liver function tests, and pregnancy tests when on isotretinoin
• Consider antibiotic resistance (60% overall) or gram-negative folliculitis if treatment fails
REFERENCES
1. Feldman S, Careccia RE, Barham KL, et al. Diagnosis and treatment of acne. Am Fam Physician. 2004;69(9):2123-2130.
2. Haider A, Shaw JC. Treatment of acne vulgaris. JAMA. 2004;292(6):726-735.
3. Webster G. Mechanism-based treatment of acne vulgaris: the value of combination therapy. J Drugs and Dermatol. 2005;4(3):281-288.