Description

Acne vulgaris is a disorder of the pilosebaceous units and a chronic inflammatory dermatosis notable for open/closed comedones, papules, pustules, nodules.

Geriatric Considerations
Favre-Racouchot syndrome: comedones on face/head due to sun exposure

Pregnancy Considerations

• 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

Pediatric Considerations

• 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

Epidemiology

• Predominant age: early to late puberty, may persist in 20–40% of affected individuals into 4th decade
• Male > female (teen), female > male (adult)

Prevalence

• 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.

Genetics
Familial association in 50%

Risk Factors

• 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
• Stress
• High-glycemic load, possibly high-dairy diets (skim milk), and whey protein supplements may exacerbate acne (1).
• Severe acne may worsen with smoking.

General Prevention

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

History

Ask about duration, relation to menses, medications, cleansing products, stress, smoking, exposures, diet, family history.

Physical Exam

• 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

Differential Diagnosis

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).

Medication

• 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

Additional Therapies

• 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.

Surgery/Other Procedures

• 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

Follow-up Recommendations

Limit use of oral antibiotics to 3 months; taper topical antibiotic (5),(6) as lesions resolve.

Diet

Patient Education

Lesions may worsen during first 2 weeks of treatment; improvement typically seen after a minimum of 4 weeks of treatment.

Prognosis

Gradual improvement over time (usually within 8 to 12 weeks after beginning therapy)

Complications

• 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

See Also

Acne Rosacea, Algorithm: Acne

ICD-10

• L70.0 Acne vulgaris
• L70.1 Acne conglobata
• L70.4 Infantile acne
• L70.8 Other acne

ICD-9

• 706.0 Acne varioliformis
• 706.1 Other acne

SNOMED

• 13277001 Cystic acne (disorder)
• 238744006 Comedonal acne
• 403359004 acne nodule (disorder)
• 42228007 Acne conglobata
• 88616000 Acne vulgaris (disorder)