Description

Acne vulgaris is a disorder of the pilosebaceous units, and a chronic inflammatory dermatosis notable for open/closed comedones, papules, pustules, and/or 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 first trimester, may worsen in third trimester
• Can use topical benzoyl peroxide (BP), azelaic acid, erythromycin, or clindamycin; salicylic acid, oral erythromycin, azithromycin, cephalexin, or amoxicillin
• Avoid topical tretinoin, trifarotene, 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—6 weeks 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% 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 aged 35 to 44 years
• African Americans 37%, Hispanic 32%, Caucasians 24%

Etiology and Pathophysiology

• Androgens (testosterone and dehydroepiandrosterone sulfate [DHEA-S]) stimulate sebum production/qualitative sebum changes and proliferation of keratinocytes in follicles. Keratin plug obstructs follicle os, causing sebum accumulation and follicular distention.
• Cutibacterium acnes phylotype IA1, an anaerobe, colonizes and proliferates within a biofilm in the plugged follicle. C. acnes promote proinflammatory mediators/cytokines (IL-1), 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
• Psychological stress
• High-glycemic load, possibly high-dairy diets (skim milk), and whey protein supplements may exacerbate acne.
• Severe acne may worsen with smoking.

General Prevention

Avoidance of risk factors

Commonly Associated Conditions

• Acne conglobata, hidradenitis suppurativa
• Pomade acne—hair oils
• 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, and 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.
• Grading system (American Academy of Dermatology, 1990)
  • 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).
• Adult female—facial lesion distribution not limited to mandibular and perioral lesion location, similar to adolescents

Differential Diagnosis

Folliculitis: gram-negative, gram-positive, and pityrosporum; 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, Altreno), 1st generation, varying strengths and formulations: wash skin; let skin dry for 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 the 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, 3rd generation
  • Effective; less irritation than tretinoin or tazarotene (1)[A]
  • May be combined with BP (Epiduo) 0.1 or 0.3%/2.5%—very effective in skin of color
  • 0.1% gel is available over-the-counter (OTC); much less expensive than other Rx retinoids ($10 to $15)
• Tazarotene (Tazorac): Apply at bedtime; 3rd generation; most effective and most irritating; teratogenic, $400 per tube
• Trifarotene (Aklief): 0.005% cream, apply in PM, 4th-generation retinoid, greater selectivity, safer, $600
• Azelaic acid (Azelex): 20% topical cream BID, Finevin 15% gel
  • 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: 0.5–2%, less effective and less irritating than tretinoin; α-Hydroxy acids, can use with BP and OTC medications
• Topical BP: generates oxygen free radicals, no resistance in C. acnes
  • 2.5% as effective as stronger preparations (5% and 10%); gel penetrates better into follicles.
  • When used with tretinoin, apply BP in morning/tretinoin at night (tretinoin is photolabile).
  • Microencapsulated BP 3% and tretinoin 0.1% (Twyneo) are now FDA-approved (expensive).
  • Side effects: concentration dependent irritation; may bleach clothes; photosensitivity
• Topical antibiotics (other than BP): Do not use as monotherapy due to antibiotic resistance.
  • Erythromycin 2%, clindamycin 1%, minocycline 4% topical foam (Amzeeq), metronidazole gel or cream: once daily
  • BP–erythromycin (Benzamycin): especially effective with azelaic acid
  • BP–clindamycin (BenzaClin, DUAC, Clindoxyl)
  • Tretinoin 0.025% clindamycin 1.2% gel (Veltin); apply HS.
  • BP–salicylic acid (Cleanse & Treat, Inova): similar in effectiveness to BP–clindamycin
  • Sodium sulfacetamide (Sulfacet-R, Novacet, Klaron): useful in acne with seborrheic dermatitis or rosacea
  • Dapsone (Aczone) 5% or 7.5% gel: useful in adult females with inflammatory acne; may cause yellow/orange skin discoloration when mixed with BP; very rare methemoglobinemia; glucose 6 phosphate deficiency, expensive—$350 per tube
• Oral antibiotics: use for shortest possible period, generally 6 to 12 weeks of therapy, limit to 3 months, max of 6 months if necessary; 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, 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
  • 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 and then 250 mg every other day × 2 months
  • Amoxicillin: 1,000 to 1,500 mg/day
• Oral retinoids
  • Isotretinoin: 0.5 to 1 mg/kg/day divided BID to maximum of 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, 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 (https://www.ipledgeprogram.com), two forms of effective contraception required
  • Isotretinoin micronized (Absorica LD): 0.4 to 0.8 mg/kg/day BID × 15 to 20 weeks, may have fewer side effects, $1,100 per month
• Medications for women only
  • FDA-approved oral contraceptives (in order of possible effectiveness)
    • Drospirenone/ethinyl estradiol (Yaz), or drospirenone/ethinyl estradiol/levomefolate (Beyaz) > norgestimate/ethinyl estradiol > norethindrone acetate/ethinyl estradiol
    • 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
• Other agent: clascoterone topical (Winlevi): 1% cream, antiandrogen, can use in both sexes; no systemic side effects; expensive, $500 to $675

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): 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, can cause local atrophy.
• 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 that tea tree oil, some plant extracts, and green tea extract may be useful.

Follow-up Recommendations

Limit use of oral antibiotics to 3 months; taper topical antibiotic as lesions resolve (2).

Diet

High-glycemic index foods, milk chocolate, and skim milk may worsen acne; paleo diet and high omega-3 fatty acid foods are helpful.

Patient Education

Lesions may worsen initially; improvement is 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
• Postinflammatory hyperpigmentation, keloids, scars—more common in skin of color

See Also

Acne Rosacea Algorithm: Acne

ICD-10

• L70.0 Acne vulgaris

SNOMED

• 238744006 Comedonal acne
• 403347003 Superficial acne vulgaris
• 403348008 Superficial inflammatory acne vulgaris
• 403349000 Superficial mixed comedonal and inflammatory acne vulgaris
• 403359004 Acne nodule