Description

• Acne vulgaris is a disorder of the pilosebaceous units. It is a chronic inflammatory dermatosis notable for open/closed comedones, papules, pustules, 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
• Typically improves in 1st trimester; may worsen in 3rd trimester
• Topical benzoyl peroxide, azelaic acid, erythromycin or clindamycin, and oral erythromycin, azithromycin or cephalexin can be used in pregnancy; use topical agents when possible.
• Isotretinoin is teratogenic; pregnancy Category X
• Avoid topical tretinoin and adapalene because they may cause retinoid embryopathy; class C
• Contraindicated: isotretinoin, tazarotene, tetracycline, doxycycline, minocycline, sarecycline

Pediatric Considerations

• Neonatal acne (neonatal cephalic pustulosis)
  • Newborn to 8 weeks; lesions limited to face; usually self-limited, may respond to topical ketoconazole 2% cream (1),(2)
• Infantile acne
  • Newborn to 1 year; lesions on face, neck, back, and chest; topical/systemic Rx (1)
• Early to middle childhood acne
  • 1 to 7 years; rare; consider hyperandrogenism (1).
• 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 of age (1); other therapies similar to adolescent acne

Epidemiology

• 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%

Etiology and Pathophysiology

• Androgens (testosterone and dehydroepiandrosterone sulfate [DHEA-S]) stimulate sebum production/qualitative sebum changes and proliferation of keratinocytes in hair follicles (3).
• Keratin plug obstructs follicle os, causing sebum accumulation and follicular distention.
• Cutibacterium acnes phylotype Ia (previously Propionibacterium acnes), an anaerobe, colonizes and proliferates within a biofilm in the plugged follicle.
• C. 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.

Risk Factors

• 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), lithium, phenytoin
• Endocrine disorders: polycystic ovarian syndrome, 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 (3).
• Severe acne may worsen with smoking.

General Prevention

Avoidance of risk factors

Commonly Associated Conditions

• 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

History

• Ask about duration, medications, cleansing products, stress, smoking, exposures, diet, and family history.
• Females may worsen 1 week prior to menses.

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 (4).
• Grading system (American Academy of Dermatology, 1990) (3)
  • Mild: few papules/pustules; no nodules
  • Moderate: some papules/pustules; few nodules
  • Severe: numerous 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) (3).
• 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
• Chloracne
• Pseudofolliculitis barbae
• Drug eruption
• Verruca vulgaris and plana
• Keratosis pilaris
• Molluscum contagiosum
• Sarcoidosis
• Seborrheic dermatitis
• Miliaria
• 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 luteinizing hormone and follicle-stimulating hormone (polycystic ovary syndrome).

Medication

ALERT
Most prescription branded topical medications are very expensive, costing from $100 to several hundred dollars per tube. OTC versions of azelaic acid and adapalene are now available and are much less 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 at night.
  • Effective; less irritation than tretinoin or tazarotene
  • May be combined with benzoyl peroxide (Epiduo) 0.1 or 0.3%/2.5%—very effective in skin of color
  • First FDA-approved over-the-counter (OTC) retinoid; much less expensive than other Rx retinoids ($10 to $15 per tube)
• Tazarotene (Tazorac): Apply at bedtime.
  • Most effective and most irritating; teratogenic, $400 per tube
• Azelaic acid (Azelex, Finevin): 20% topically, 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
  • 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 antibiotics and anti-inflammatories
  • 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 and tretinoin at night.
    • Side effects: concentration-dependent irritation; may bleach clothes; photosensitivity
• Topical antibiotics: Do not use as monotherapy due to antibiotic resistance (4)[A].
  • Erythromycin 2%
  • Clindamycin 1%
  • Metronidazole gel or cream: Apply 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 needs 6 to 12 weeks of therapy, limit to 3 months if possible, max 6 months if necessary (4); indicated 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 (4); side effects: photosensitivity, esophagitis
  • Minocycline: 100 to 200 mg/day, divided daily—BID; side effects include photosensitivity, urticaria, gray-blue skin, vertigo, hepatitis, lupus; extended release preparation better tolerated
  • Doxycycline: 20 to 200 mg/day, divided daily—BID; side effects include photosensitivity.
  • Sarecycline (Seysara): 60 to 150 mg (1.5 mg/kg) given once daily, narrow spectrum, FDA approved 2018, very expensive $1,000/month
  • 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): QD or BID
  • Azithromycin (Zithromax): 500 mg 3 days/week × 1 month and 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 (3), 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 iPLEDGE program (www.ipledgeprogram.com); two forms of effective contraception required
• Medications for women only
  • FDA-approved oral contraceptives (in order of possible effectiveness) (5)[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 also effective; all combined contraceptives may take 3 to 6 months to become effective.
• 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 hydroquinones (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 for prevention
• Light-based treatments
  • Ultraviolet A/ultraviolet B (UVA/UVB), blue or blue/red light; pulse dye, KTP, or 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); use 30-gauge needle, inject through pore, slightly distend cyst.
• Acne scar treatment: retinoids, steroid injections, cryosurgery, electrodessication, 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 (4).
• Limited data on use of dermocosmetics for acne Rx

Follow-up Recommendations

Limit use of oral antibiotics to 3 months; taper topical antibiotic (6),(7) as inflammatory lesions resolve.

Diet

Data suggest that high-glycemic index foods and skim milk may worsen acne (4)[B].

Patient Education

• 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.

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 (3)
• Postinflammatory hyperpigmentation, keloids, and scars are 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)