Acne vulgaris is a disorder of the pilosebaceous units and a chronic inflammatory dermatosis notable for open/closed comedones, papules, pustules, nodules.
Favre-Racouchot syndrome: comedones on face/head due to sun exposure
- May result in a flare or remission of acne
- Typically improves in 1st, may worsen in 3rd trimester
- Can use topical benzoyl peroxide, azelaic acid, erythromycin or clindamycin; oral erythromycin, azithromycin or cephalexin
- Avoid topical tretinoin and adapalene—may cause retinoid embryopathy; class C
- Contraindicated: isotretinoin (Category X), tazarotene, tetracycline, doxycycline, minocycline, sarecycline
- Neonatal acne (neonatal cephalic pustulosis)—newborn to 8 weeks; lesions limited to face; usually self-limited, Rx topical ketoconazole 2% cream
- Infantile acne—newborn to 1 year; lesions on face, neck, back, chest; topical/systemic Rx
- Early to middle childhood acne—1 to 7 years; rare; consider hyperandrogenism.
- Preadolescent acne—7 to 12 years; common, 47% of children, usually due to adrenal awakening, comedonal lesions
- Do not use tetracyclines in those <8 years old; other therapies similar to adolescent
- Predominant age: early to late puberty, may persist in 20–40% of affected individuals into 4th decade
- Male > female (teen), female > male (adult)
- 80–95% of adolescents affected; 8% of adults aged 25 to 34 years; 3% at 35 to 44 years
- African Americans 37%, Caucasians 24%
Etiology and Pathophysiology
- Androgens (testosterone and dehydroepiandrosterone sulfate [DHEA-S]) stimulate sebum production/qualitative sebum changes and proliferation of keratinocytes in follicles (1).
- Keratin plug obstructs follicle os, causing sebum accumulation and follicular distention.
- Cutibacterium acnes phylotype Ia, an anaerobe, colonizes and proliferates within a biofilm in the plugged follicle.
- C. acnes promote proinflammatory mediators, causing inflammation of follicle/dermis.
Familial association in 50%
- Increased endogenous androgenic effect
- Oily cosmetics, cocoa butter, polyvinyl chloride, chlorinated hydrocarbons, cutting oil
- Occluding skin surface (e.g., sports equipment such as helmets and shoulder pads), cell phones, hands against the skin, or pandemic masks (“maskne”—subset of acne mechanica)
- Numerous drugs, including androgenic steroids (e.g., steroid abuse, some birth control pills), lithium, phenytoin
- Endocrine disorders: PCOS, Cushing syndrome, congenital adrenal hyperplasia, androgen-secreting tumors, acromegaly
- High-glycemic load, possibly high-dairy diets (skim milk), and whey protein supplements may exacerbate acne (1).
- Severe acne may worsen with smoking.
Avoidance of risk factors
Commonly Associated Conditions
- 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)
- Dark-skinned patients: 50% keloidal scarring and 50% acne hyperpigmented macules
Ask about duration, relation to menses, medications, cleansing products, stress, smoking, exposures, diet, family history.
- Closed comedones (whiteheads), open comedones (blackheads)
- Nodules or papules, pustules, cysts
- Scars: ice pick, rolling, boxcar, atrophic macules, hypertrophic, depressed, sinus tracts
- Consistent grading is useful; no specific universal grading system is recommended per guidelines (2).
- Grading system (American Academy of Dermatology, 1990) (1)
- Mild: few papules/pustules; no nodules
- Moderate: some papules/pustules; few nodules
- Severe: many papules/pustules/nodules
- Very severe: acne conglobata, acne fulminans, acne inversa
- Most common areas affected are face, chest, back, and upper arms (greatest concentration of sebaceous glands) (1).
- Adult female—facial lesion distribution not limited to mandibular and perioral lesion location, similar to adolescents
Folliculitis: gram-negative and gram-positive, acne (rosacea, cosmetica, steroid induced), perioral dermatitis, pseudofolliculitis barbae, drug eruption, keratosis pilaris, sarcoidosis, seborrheic dermatitis, lupus erythematosus
Diagnostic Tests & Interpretation
Initial Tests (lab, imaging)
Only indicated if additional signs of androgen excess; if so, test for free and total testosterone and DHEA-S and consider LH and FSH (PCOS).
- Comedonal (grade 1): keratinolytic agent
- Mild inflammatory acne (grade 2): benzoyl peroxide +/− topical retinoid or benzoyl peroxide +/− topical antibiotic +/− topical retinoid
- Moderate inflammatory acne (grade 3): Add time-limited systemic antibiotic to grade 2 regimen.
- Severe inflammatory acne (grade 4): as in grade 3, or isotretinoin
- Topical retinoid plus a topical antimicrobial agent (such as BP) is first-line treatment for more than mild disease (3)[A].
- Topical retinoid + antibiotic (topical or PO) is better than either alone for mild/moderate.
- Topical retinoids are first-line agents for maintenance therapy (3)[A]. Avoid long-term antibiotics for maintenance.
- Avoid oral or topical antibiotics as monotherapy. Use with topical BP +/− topical retinoid (2)[C].
- Recommended vehicle type
- Dry or sensitive skin: cream, lotion, or ointment
- Oily skin, humid weather: gel, solution, 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; use gentle cleanser/noncomedogenic moisturizer to decrease irritation with keratinolytic agents.
Most prescription branded topical medications are very expensive.
- Keratinolytic agents (α-hydroxy acids, salicylic acid, topical retinoids, azelaic acid) (Side effects include dryness, erythema, and scaling; start with lower strength or alternate day Rx; increase as tolerated.)
- Tretinoin (Retin-A, Retin-A Micro, Avita, Atralin) varying strengths and formulations: wash skin; let skin dry 30 minutes before application to reduce irritation. Apply pea-sized dose at bedtime.
- Retin-A Micro, Atralin, and Avita are less irritating and stable with BP.
- May cause an initial flare of lesions; may be eased by every other day application for first 2 to 4 weeks
- Avoid in pregnant and lactating women.
- Cost varies based on formulation—$50 to $150 per tube for generic.
- Adapalene (Differin): 0.1%, apply topically HS
- Effective; less irritation than tretinoin or tazarotene (3)[A]
- May be combined with benzoyl peroxide (Epiduo) 0.1 or 0.3%/2.5%—very effective in skin of color
- Available over-the-counter (OTC); much less expensive than other Rx retinoids ($10–$15)
- Tazarotene (Tazorac): Apply at bedtime. Most effective and most irritating; teratogenic, $400 per tube
- Azelaic acid (Azelex, Finevin): 20% topical BID
- Keratinolytic, antibacterial, anti-inflammatory
- Reduces postinflammatory hyperpigmentation in dark-skinned individuals
- Side effects: erythema, dryness, scaling, hypopigmentation
- Effective in postadolescent acne
- Safe in pregnancy-risk Category B
- 20% Rx >$400 per tube; OTC 10% and 15% formulations cost $10 to $40 per tube.
- Salicylic acid: 2%, less effective and less irritating than tretinoin. α-Hydroxy acids: available OTC
- Topical benzoyl peroxide: no resistance in C. acnes
- 2.5% as effective as stronger preparations, gel penetrates better into follicles.
- When used with tretinoin, apply benzoyl peroxide in morning/tretinoin at night.
- Side effects: concentration dependent irritation; may bleach clothes; photosensitivity
- Topical antibiotics (other than benzoyl peroxide): Do not use as monotherapy due to antibiotic resistance (2)[A].
- Erythromycin 2%, clindamycin 1%, metronidazole gel or cream: once daily.
- 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: useful in adult females with inflammatory acne; may cause yellow/orange skin discoloration when mixed with BP; very rare methemoglobinemia, expensive—$350 per tube
- Oral antibiotics: Use for shortest possible period, generally 6 to 12 weeks of therapy, limit to 3 months, max 6 months if necessary (2); use when acne is more severe, trunk involvement, unresponsive to topical agents, or at greater risk for scarring; do not use as monotherapy.
- Tetracycline: 500 to 1,000 mg/day divided BID; high dose initially, taper in 6 months, less effective than doxycycline or minocycline (2), take fasting or without dairy, side effects: photosensitivity, esophagitis
- Minocycline: 100 to 200 mg/day, divided daily—BID; side effects include photosensitivity, urticaria, gray-blue skin, vertigo, autoimmune hepatitis, lupus; extended release preparation better tolerated
- Doxycycline: 20 to 200 mg/day, divided daily—BID; photosensitivity
- Sarecycline (Seysara): 60 to 150 mg (1.5 mg/kg) given once daily, narrow spectrum, $1,000/month
- Erythromycin: 500 to 1,000 mg/day; divided BID–QID; decreasing effectiveness due to C. acnes resistance
- Trimethoprim-sulfamethoxazole (Bactrim DS, Septra DS): QD 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 1.0 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 (1), 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, possible suicidal ideation, psychosis
- Avoid tetracyclines or vitamin A during isotretinoin.
- Monitor for pregnancy, psychiatric/mood changes, CBC, lipids, glucose, and LFTs at baseline and every month.
- Patient and provider must register with iPLEDGE program (www.ipledgeprogram.com), two forms of effective contraception required
- Medications for women only
- FDA-approved oral contraceptives (in order of possible effectiveness) (4)[B]
- Drospirenone/ethinyl estradiol (Yaz), or drospirenone/ethinyl estradiol/levomefolate (Beyaz) > norgestimate/ethinyl estradiol (Ortho Tri-Cyclen) > norethindrone acetate/ethinyl estradiol (Estrostep)
- Most combined contraceptives are also effective; may take 3 to 6 months
- Spironolactone (Aldactone); 25 to 200 mg/day; antiandrogen; reduces sebum production, not FDA-approved for acne Rx
Issues For Referral
Management of acne scars
- Acne hyperpigmented macules
- Topical hydroquinone (1.5–10%), azelaic acid (20%) topically, topical retinoids, corticosteroids: low dose, dapsone 5% gel (Aczone): topical, anti-inflammatory; use in patients >12 years, sunscreen
- Light-based treatment—ultraviolet A/ultraviolet B (UVA/UVB), blue or blue/red light; pulse dye, infrared laser; photodynamic therapy with 5-aminolevulinic acid has best evidence.
- Comedo extraction after incising the layer of epithelium over closed comedo
- Inject large cystic lesions with 0.05 to 0.30 mL triamcinolone (Kenalog 2 to 5 mg/mL); 30-gauge needle, inject through pore, slightly distend cyst.
- Acne scar treatment: retinoids, steroid injections, cryosurgery, electrodesiccation, micro-/dermabrasion, chemical peels, laser resurfacing, pulsed dye laser, microneedling, fillers, punch elevation
Complementary and Alternative Medicine
- Evidence suggests tea tree oil, seaweed extract, Kampo formulations, Ayurvedic formulations, rose extract, basil extract, epigallocatechin gallate, barberry extract, gluconolactone solution, and green tea extract may be useful (2).
- Dermocosmetics—limited data for acne Rx
Limit use of oral antibiotics to 3 months; taper topical antibiotic (5),(6) as lesions resolve.
High-glycemic index foods and skim milk may worsen acne (2)[B].
Lesions may worsen during first 2 weeks of treatment; improvement typically seen after a minimum of 4 weeks of treatment.
Gradual improvement over time (usually within 8 to 12 weeks after beginning therapy)
- Acne conglobata: severe confluent inflammatory acne with systemic symptoms. Facial scarring, psychological distress, including anxiety, depression, and suicidal ideation (1)
- Postinflammatory hyperpigmentation, keloids, scars—more common in skin of color
Acne Rosacea, Algorithm: Acne
- L70.0 Acne vulgaris
- L70.1 Acne conglobata
- L70.4 Infantile acne
- L70.8 Other acne
- 706.0 Acne varioliformis
- 706.1 Other acne
- 13277001 Cystic acne (disorder)
- 238744006 Comedonal acne
- 403359004 acne nodule (disorder)
- 42228007 Acne conglobata
- 88616000 Acne vulgaris (disorder)
- May need 8 to 12 weeks to see the effect of therapy
- Decrease topical frequency to every day or to every other day to lessen irritation.
- Use benzoyl peroxide every time a topical or oral antibiotic is used to reduce emergence of bacterial resistance.
Inflammatory acne lesions. Papules, pustules, and closed comedones are all present on this patient.
Severe cystic acne. This patient was subsequently treated with isotretinoin (Accutane).
- Dawson AL, Dellavalle RP. Acne vulgaris. BMJ. 2013;346:f2634. [PMID:23657180]
- Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945.e33–973.e33. [PMID:26897386]
- Kolli SS, Pecone D, Pona A, et al. Topical retinoids in acne vulgaris: a systematic review. Am J Clin Dermatol. 2019;20(3):345–365. [PMID:30674002]
- Lortscher D, Admani S, Satur N, et al. Hormonal contraceptives and acne: a retrospective analysis of 2147 patients. J Drugs Dermatol. 2016;15(6):670–674. [PMID:27272072]
- Marson JW, Baldwin HE. An overview of acne therapy, part 1: topical therapy, oral antibiotics, laser and light therapy, and dietary interventions. Dermatol Clin. 2019;37(2):183–193. [PMID:30850041]
- Marson JW, Baldwin HE. An overview of acne therapy, part 2: hormonal therapy and isotretinoin. Dermatol Clin. 2019;37(2):195–203. [PMID:30850042]
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