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Acne Vulgaris
Gary I. Levine, MD
image BASICS
  • Acne vulgaris is a disorder of the pilosebaceous units. It is a chronic inflammatory dermatosis notable for open/closed comedones, papules, pustules, or nodules.
  • Systems affected: skin/exocrine
Geriatric Considerations
Favre-Racouchot syndrome: comedones on face and head due to sun exposure
Pregnancy Considerations
  • May result in a flare or remission of acne
  • Erythromycin can be used in pregnancy; use topical agents when possible.
  • Isotretinoin is teratogenic; pregnancy Category X
  • Avoid topical tretinoin as it may cause retinoid embryopathy; class C (1).
  • Contraindicated: isotretinoin, tazarotene, tetracycline, doxycycline, minocycline
Pediatric Considerations
  • Neonatal acne (neonatal cephalic pustulosis) (2)
    • Newborn to 8 weeks; lesions limited to face; responds to topical ketoconazole 2% cream (3)
  • Infantile acne
    • Newborn to 1 year; lesions on face, neck, back, and chest; no Rx required (3)
  • Early-mid childhood acne
    • 1 to 7 years; rare; consider hyperandrogenism (3)
  • Preadolescent acne
    • 7 to 11 years; common, 47% of children, usually due to adrenal awakening
  • Do not use tetracycline in those <8 years of age (2,3); other therapies similar to adolescent acne
  • Predominant age: early to late puberty, may persist in 20-40% of affected individuals into 4th decade
  • Predominant sex
    • Male > female (adolescence)
    • Female > male (adult)
  • 80-95% of adolescents affected. A smaller percentage will seek medical advice.
  • 8% of adults aged 25 to 34 years; 3% at 35 to 44 years
  • African-Americans 37%, Caucasians 24%
  • Androgens (testosterone and dehydroepiandros-terone sulfate [DHEA-S]) stimulate sebum production and proliferation of keratinocytes in hair follicles (4).
  • Keratin plug obstructs follicle os, causing sebum accumulation and follicular distention.
  • Propionibacterium acnes, an anaerobe, colonizes and proliferates in the plugged follicle.
  • P. acnes promote proinflammatory mediators, causing inflammation of follicle and dermis.
  • Familial association in 50%
  • If a family history exists, the acne may be more severe and occur earlier.
  • Increased endogenous androgenic effect
  • Oily cosmetics, cocoa butter
  • Rubbing or occluding skin surface (e.g., sports equipment such as helmets and shoulder pads), telephone, or hands against the skin
  • Polyvinyl chloride, chlorinated hydrocarbons, cutting oil, tars
  • Numerous drugs, including androgenic steroids (e.g., steroid abuse, some birth control pills)
  • Endocrine disorders: polycystic ovarian syndrome, Cushing syndrome, congenital adrenal hyperplasia, androgen-secreting tumors, acromegaly
  • Stress
  • High-glycemic load and possibly high-dairy diets may exacerbate acne (4,5).
  • Severe acne may worsen with smoking.
  • Acne fulminans, pyoderma faciale
  • Acne conglobata, hidradenitis suppurativa
  • Pomade acne
  • SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis)
  • Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) and seborrhea, acne, hirsutism, and alopecia (SAHA) syndromes
  • Behçet syndrome, Apert syndrome
  • Dark-skinned patients: 50% keloidal scarring and 50% acne hyperpigmented macules
  • Closed comedones (whiteheads)
  • Open comedones (blackheads)
  • Nodules or papules
  • Pustules (“cysts”)
  • Scars: ice pick, rolling, boxcar, atrophic macules, hypertrophic, depressed, sinus tracts
  • Grading system (American Academy of Dermatology, 1990) (4)
    • 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.
  • Most common areas affected are face, chest, back, and upper arms (areas of greatest concentration of sebaceous glands) (4).
  • Folliculitis: gram negative and gram positive
  • Acne (rosacea, cosmetica, steroid-induced)
  • Perioral dermatitis
  • Chloracne
  • Pseudofolliculitis barbae
  • Drug eruption
  • Verruca vulgaris and plana
  • Keratosis pilaris
  • Molluscum contagiosum
  • Sarcoidosis
  • Seborrheic dermatitis
  • Miliaria
Initial Tests (lab, imaging)
Only indicated if additional signs of androgen excess; if so, test for free and total testosterone, DHEA-S, LH, and FSH (6)
  • Comedonal (grade 1): keratinolytic agent (7)[A] (see as follows for specific agents)
  • Mild inflammatory acne (grade 2): benzoyl peroxide ± topical antibiotic + keratinolytic agent
  • Moderate inflammatory acne (grade 3): add systemic antibiotic to grade 2 regimen
  • Severe inflammatory acne (grade 4): as in grade 3, or isotretinoin (7)[A]
  • Topical retinoid plus a topical antimicrobial agent is 1st-line treatment for more than mild disease (8).
  • Topical retinoid + antibiotic (topical or PO) is better than either alone for mild/moderate acne (7)[A].
  • Topical retinoids are 1st-line agents for maintenance. Avoid long-term antibiotics for maintenance.
  • Avoid topical antibiotics as monotherapy.
  • Recommended vehicle type
    • Dry or sensitive skin: cream or ointment
    • Oily skin, humid weather: gel, solution, or wash
    • Hair-bearing areas: lotion, hydrogel, or foam
  • Apply topical agents to entire affected area, not just visible lesions.
  • Mild soap daily to control oiliness; avoid abrasives
  • Avoid drying agents with keratinolytic agents.
  • Gentle cleanser and noncomedogenic moisturizer help decrease irritation.
  • Oil-free, noncomedogenic sunscreens
  • Stress management if acne flares with stress
  • Keratinolytic agents (alpha-hydroxy acids, salicylic acid, azelaic acid) (side effects include dryness, erythema, and scaling; start with lower strength, increase as tolerated) (6,7)[A].
  • Tretinoin (Retin-A, Retin A Micro, Avita, Atralin) varying strengths and formulations: apply at bedtime; wash skin, let skin dry 30 minutes before application
    • Retin-A Micro, Atralin, and Avita are less irritating, and stable with BP
    • May cause an initial flare of lesions; may be eased by 14-day course of oral antibiotics
    • Avoid in pregnant and lactating women.
  • Adapalene (Differin): 0.1%, apply topically at night
    • Effective; less irritation than tretinoin or tazarotene (7)[A]
    • May be combined with benzoyl peroxide (Epiduo)—very effective in skin of color
  • Tazarotene (Tazorac): apply at bedtime
    • Most effective and most irritating; teratogenic
  • Azelaic acid (Azelex, Finevin): 20% topically, BID
    • Keratinolytic, antibacterial, anti-inflammatory
    • Reduces postinflammatory hyperpigmentation in dark-skinned individuals
    • Side effects: erythema, dryness, scaling, hypopigmentation
    • Less effective in clinical use than in studies
    • Effective in postadolescent acne
  • Salicylic acid: 2%, less effective and less irritating than tretinoin
  • Alpha-hydroxy acids: available over-the-counter
  • P.15

  • Topical antibiotics and anti-inflammatories
    • Topical benzoyl peroxide (6,7)[A]
      • 2.5% as effective as stronger preparations
      • Gel penetrates better into follicles
      • When used with tretinoin, apply benzoyl peroxide in morning and tretinoin at night
      • Side effects: irritation; may bleach clothes; photosensitivity
  • Topical antibiotics (6,7)[A]
    • Erythromycin 2%
    • Clindamycin 1%
    • Metronidazole gel or cream: apply once daily
    • Azelaic acid (Azelex, Finevin): 20% cream: enhanced effect and decreased risk of resistance when used with zinc and benzoyl peroxide
    • Benzoyl peroxide-erythromycin (Benzamycin): especially effective with azelaic acid
    • Benzoyl peroxide-clindamycin (BenzaClin, DUAC, Clindoxyl)
    • Benzoyl peroxide-salicylic acid (Cleanse & Treat, Inova): similar in effectiveness to benzoyl peroxide-clindamycin
    • Sodium sulfacetamide (Sulfacet-R, Novacet, Klaron): useful in acne with seborrheic dermatitis or rosacea
    • Dapsone (Aczone) 5% gel: may cause yellow/orange skin discoloration when mixed with benzoyl peroxide
  • Oral antibiotics: use for at least 6 to 8 weeks after initiation, discontinue after 12 to 18 weeks' duration; indicated when acne is more severe, trunk involvement, unresponsive to topical agents, or at greater risk for scarring (6,7,9)[A]
    • Tetracycline: 500 to 1,000 mg/day divided BID; high dose initially, taper in 6 months. Side effects: photosensitivity, esophagitis
    • Minocycline: 100 to 200 mg/day, divided daily—BID; side effects include photosensitivity, urticaria, grayblue skin, vertigo, hepatitis
    • Doxycycline: 50 to 200 mg/day, divided daily—BID; side effects include photosensitivity
    • Erythromycin: 500 to 1,000 mg/day; divided BID-QID; decreasing effectiveness as a result of increasing P. acnes resistance
    • Trimethoprim-sulfamethoxazole (Bactrim DS, Septra DS): 1 daily or BID
    • Azithromycin (Zithromax): 500 mg 3 days/week × 1 month, then 250 mg every other day × 2 months
  • Oral retinoids
    • Isotretinoin: 0.5 to 1 mg/kg/day divided BID to maximum 2 mg/kg/day divided BID for very severe disease; 60-90% cure rate; usually given for 12 to 20 weeks; maximum cumulative dose - 120 to 150 mg/kg; 20% of patients relapse and require retreatment (4,6,7)[A], 0.25 to 0.40 mg/kg/day in moderately severe acne
      • Side effects: teratogenic, pancreatitis, excessive drying of skin, hypertriglyceridemia, hepatitis, blood dyscrasias, hyperostosis, premature epiphyseal closure, night blindness, erythema multiforme, Stevens-Johnson syndrome, suicidal ideation, psychosis
      • Avoid tetracyclines or vitamin A preparations during isotretinoin therapy.
      • Monitor for pregnancy, psychiatric/mood changes, complete blood count (CBC), lipids, glucose, and liver function tests at baseline and every month.
      • Must be registered and adhere to manufacturer's iPLEDGE program (www.ipledgeprogram.com)
  • Medications for women only
    • Oral contraceptives (4,6,7)[A],(10)
      • Norgestimate/ethinyl estradiol (OrthoTricyclen), norethindrone acetate/ethinyl estradiol (Estrostep), drospirenone/ethinyl estradiol (Yaz, Yasmin) are USFDA approved.
      • Levonorgestrel/ethinyl estradiol (Alesse) and most combined contraceptives effective
      • Spironolactone (Aldactone); 25 to 200 mg/day; antiandrogen; reduces sebum production
Consider referral/consultation to dermatologist
  • Refractory lesions despite appropriate therapy
  • Consideration of isotretinoin therapy
  • Management of acne scars
  • Acne hyperpigmented macules (11)
    • Topical hydroquinones (1.5-10%)
    • Azelaic acid (20%) topically
    • Topical retinoids
    • Corticosteroids: low dose, suppresses adrenal androgens (6)[B]
    • Dapsone 5% gel (Aczone): topical, anti-inflammatory; use in patients over 12 years
    • Sunscreen for prevention
  • Light-based treatments
    • Ultraviolet A/ultraviolet B (UVA/UVB), blue or blue/red light; pulse dye, KTP, or infrared laser
    • Photodynamic therapy for 30 to 60 minutes with 5-aminolevulinic acid × 3 sessions is effective for inflammatory lesions.
      • Greatest use when used as adjunct to medications or if can't tolerate medications
  • Comedo extraction after incising the layer of epithelium over closed comedo (6)[C]
  • Inject large cystic lesions with 0.05 to 0.3 mL triamcinolone (Kenalog 2 to 5 mg/mL); use 30-gauge needle, inject through pore, slightly distend cyst (6)[C].
  • Acne scar treatment: retinoids, steroid injections, cryosurgery, electrodessication, micro/dermabrasion, chemical peels, laser resurfacing
Evidence suggests tea tree oil, seaweed extract, Kampo formulations, Ayurvedic formulations, rose extract, basil extract, epigallocatechin gallate, and tea extract may be useful (12).
Use oral or topical antibiotics for 3 months; taper as inflammatory lesions resolve. Do not use topical and oral antibiotic together.
Avoid high-glycemic index foods and milk (13)
  • There may be a worsening of acne during first 2 weeks of treatment.
  • Results are typically seen after a minimum of 4 weeks of treatment
Gradual improvement over time (usually within 8 to 12 weeks after beginning therapy)
1. Pugashetti R, Shinkai K. Treatment of acne vulgaris in pregnant patients. Dermatol Ther. 2013;26(4):302-311.
2. Friedlander SF, Baldwin HE, Mancini AJ, et al. The acne continuum: an age-based approach to therapy. Semin Cutan Med Surg. 2011;30(Suppl 3):S6-S11.
3. Admani S, Barrio VR. Evaluation and treatment of acne from infancy to preadolescence. Dermatol Ther. 2013;26(6):462-466.
4. Dawson AL, Dellavalle RP. Acne vulgaris. BMJ. 2013;346:f2634.
5. Burris J, Rietkerk W, Woolf K. Acne: the role of medical nutrition therapy. J Acad Nutr Diet. 2013;113(3):416-430.
6. Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol. 2007;56(4):651-663.
7. Feldman S, Careccia RE, Barham KL, et al. Diagnosis and treatment of acne. Am Fam Physician. 2004;69(9):2123-2130.
8. Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the management of acne: an update from the Global Alliance to improve outcomes in Acne group. J Am Acad Dermatol. 2009;60(5 Suppl):S1-S50.
9. Del Rosso JQ, Kim G. Optimizing use of oral antibiotics in acne vulgaris. Dermatol Clin. 2009;27(1):33-42.
10. Heymann WR. Oral contraceptives for the treatment of acne vulgaris. J Am Acad Dermatol. 2007;56(6):1056-1057.
11. Woolery-Lloyd HC, Keri J, Doig S. Retinoids and azelaic acid to treat acne and hyperpigmentation in skin of color. J Drugs Dermatol. 2013;12(4):434-437.
12. Fisk WA, Lev-Tov HA, Sivamani RK. Botanical and phytochemical therapy of acne: a systematic review. Phytother Res. 2014;28(8):1137-1152.
13. Mahmood SN, Bowe WP. Diet and acne update: carbohydrates emerge as the main culprit. J Drugs Dermatol. 2014;13(4):428-435.
See Also
  • Acne Rosacea
  • Algorithm: Acne
  • L70.0 Acne vulgaris
  • L70.4 Infantile acne
  • L70.1 Acne conglobata
Clinical Pearls
  • Expect worsening for the first 2 weeks of treatment. Full results for changes in therapy take 8 to 12 weeks.
  • Decrease topical frequency to every day or to every other day for irritation.
  • Use BP every time a topical or oral antibiotic is used.