• Acne vulgaris is a disorder of the pilosebaceous units (PSU). It is a chronic inflammatory dermatosis notable for open/closed comedones and inflammmatory lesions, including papules, pustules, or nodules.
• System(s) affected: Skin/Exocrine

ALERT
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 a teratogenic; Class X
• Avoid topical tretinoin, although no good evidence exists that its use is teratogenic.
• Contraindicated: Isotretinoin, tazarotene, tetracycline, doxycycline, minocycline

Pediatric Considerations

• Neonatal acne
• Infantile acne: Increased risk for severe teenage acne vulgaris
• Rare in ages 1–7 years:
  • Check for hyperandrogenemia of adrenal or ovarian origin
  • Do not use tetracyclines < 8 years of age

• Predominant age: Early to late puberty, may persist into 4th decade
• Predominant sex:
  • Male > Female (adolescence)
  • Female > Male (adult)

Prevalence

• 17–50 million cases in the US
• Nearly 80–95% of adolescents affected. A smaller percentage will seek medical advice.
• 8% of adults aged 25–34 years, 3% of those aged 35–44 years

• Increased endogenous androgenic effect
• Oily cosmetics: Cleansing creams, moisturizers, and oil-based foundations; pomade
• Rubbing or occluding skin surface (e.g., sports equipment such as helmets and shoulder pads), telephone or hands against the skin
• Polyvinyl chloride
• Tars
• Drugs:
  • Androgenic steroids (e.g., steroid abuse, some birth control pills)
  • Systemic corticosteroids
  • Long-acting progestins
  • Lithium, phenytoin, isoniazid, phenobarbital, ethionamide, azathioprine, disulfiram, cyclosporine, quinine, thiourea, thiouracil, bromides, iodides, vitamin B12
• Virilization disorders: PCOS
• Stress

Genetics

• Familial association in 50%
• If a family history exists, the acne may be more severe and occur earlier.

• Androgens (testosterone and DHEA) stimulate sebum production and proliferation of keratinocytes in hair follicles.
• Keratin plug obstructs follicle os, causing sebum accumulation and follicular distention.
• Propionibacterium acnes, an anaerobe, colonizes and proliferates in the plugged follicle.
• P. acnes promotes chemotactic factors and proinflammatory mediators, causing inflammation of follicle and dermis.

• Acne fulminans
• Pyoderma faciale
• Acne conglobata
• Hidradenitis suppurativa
• Pomade acne
• SAPHO syndrome: Synovitis, acne, pustulosis, hyperostosis, osteitis
• PAPA syndrome: Pyogenic sterile arthritis, pyoderma gangrenosum, cystic acne
• Dark-skinned patients: 50% keloidal scarring and 50% acne hyperpigmented macules (AHMs)

Ask duration, medications, cleansing products, stress, smoking, exposures, family history. Factors influencing symptomatology:

• Males later onset, greater severity
• Females may worsen prior to menses

• 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):
  • 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)

Lab
Labs only indicated if there are additional signs of androgen excess; if so: Free testosterone, dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) (1)[A]

• 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
• Facial angifibromas
• Sarcoidosis

• Mild soap daily to control oiliness; avoid abrasives
• Comedonal acne (grade 1): Keratinolytic agent preferred (2,3)[A]
• Mild inflammatory acne (grade 2): Benzoyl peroxide +/- topical antibiotic. Add keratinolytic agent if needed (3,4)[A].
• Moderate inflammatory acne (grade 3): Add systemic antibiotic to grade 2 regimen, or substitute for the topical benzoyl peroxide or antibiotic. Continue keratinolytic agent.
• Severe inflammatory acne (grade 4): As in grade 3, or isotretinoin (2,3)[A]
• Topical retinoid plus antibiotic (topical or p.o.) is better than either alone (2,3)[A].
• Stop antibiotic if inflammatory lesions resolve.
• Use oral antibiotics for 6 months. Topicals generally limited to 3 months. Can switch abruptly from oral to topical antibiotics without taper. Do not use topical and oral antibiotics together.
• Recommended vehicle type:
  • Cream: Dry or sensitive skin
  • Gel or solution: Oily skin, humid weather
  • Lotion: Hair-bearing areas
• Avoid drying agents with keratinolytic agents.
• Oil-free, noncomedogenic sunscreens
• Stress management if acne flares with stress

Keratinolytic agents (side effects include dryness, erythema, scaling, and photosensitivity; start with lower strength; increase as tolerated) (1,2)[A]:

• Tretinoin (Retin-A, Retin A micro, Avita): Apply at bedtime; wash skin and let skin dry 30 minutes before topical application:
  • Retin-A Micro and Avita are less irritating, less phototoxicity
  • May cause an initial flare of lesions. May be eased by 14-day course of oral antibiotics
• Adapalene (Differin): 0.1%, Apply topically at night:
  • Effective; fewer problems than tretinoin (2,4)[A].
  • May be combined with benzoyl peroxide
• Tazarotene (Tazorac): Apply at bedtime
  • Most effective and most irritating
  • Teratogenic
• Azelaic acid (Azelex, Finevin): 20% topically, b.i.d:
  • 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
• Salicylic acid: Less effective than tretinoin
• Alpha-hydroxy acids: Available over-the-counter (OTC)
• Topical antibiotics and anti-inflammatories (2)[A]:
  • Topical benzoyl peroxide:
    • Bactericidal through direct toxic effect
    • No P. acnes resistance noted
    • 2.5% as effective as stronger preparations
    • When used with tretinoin, apply benzoyl peroxide in morning and tretinoin at night
    • Side effects: Irritation; may bleach clothes
• Topical antibiotics (1,2)[A]:
  • Erythromycin 2%
  • Clindamycin 1%
  • Metronidazole gel or cream: Apply once daily
  • Azelaic acid (Azelex, Finevin): 20% cream: Enhanced effect and decreased risk of resistant when used with zinc and benzoyl peroxide
  • Benzoyl peroxide-erythromycin (Benzamycin): Especially effective with azelaic acid
  • Benzoyl peroxide-clindamycin (BenzaClin, DUAC, Clindoxyl): Effective combined (4)[A]
  • Sodium sulfacetamide (Sulfacet-R, Novacet, Klaron): Useful in acne with seborrheic dermatitis or rosacea
• Oral antibiotics (1,2)[A]:
  • Tetracycline: 500–2,000 mg/d b.i.d.–q.i.d.; high dose initially, taper in 6 months, as tolerated. Side effects: Photosensitivity, esophagitis:
    • Avoid use with antacids, iron
  • Minocycline 50–200 mg/d, q.i.d.–b.i.d. Side effects: Photosensitivity, urticaria, gray-blue skin, vertigo, autoimmune hepatitis, pseudotumor cerebri, lupus-like syndrome. May be more effective than tetracycline (1)[A].
  • Doxycycline 50–200 mg/d, given b.i.d.–q.i.d.; side effects include photosensitivity
  • Erythromycin: 500–1,000 mg/d; given b.i.d.–q.i.d.; decreasing effectiveness as a result of increasing P. acnes resistance
  • Trimethoprim-sulfamethoxazole (Bactrim DS, Septra DS); 1 daily or b.i.d.
• Oral retinoids:
  • Isotretinoin (Accutane) (1,2)[A]: 0.5–2.0 mg/kg/d b.i.d.; 60–90% cure rate; usually given for 12–20 weeks, maximum cumulative dose = 120–150 mg/kg; 20% of patients relapse and require retreatment:
    • Side effects: Cheilitis, arthralgias, tendinitis, hyperlipidemia, pseudotumor cerebri, poor wound healing, highly teratogenic (severe central nervous system and cardiovascular anomalies and facial deformities), depression and suicidal ideation
    • Avoid tetracyclines or vitamin A preparations during isotretinoin therapy.
    • Monitor for pregnancy, complete blood count (CBC), lipids and liver function tests at baseline and every month.
    • Should be registered member of manufacturer’s iPLEDGE program

ALERT
Pregnancy Considerations

• Isotretinoin is a teratogenic; Class X

• Medications for women only:
  • Oral contraceptives (1,2)[A]:
    • Norgestimate/ethinyl estradiol (Orth Tricyclen), norethindrone acetate/ethinyl estradiol (Estrostep), drospirenone/ethinyl estradiol (Yaz, Yasmin) are approved by FDA.
  • Spironolactone (Aldactone); 25–200 mg/d; antiandrogen; reduces sebum production
  • Flutamide (Eulexin) 250–500 mg/d; potentially hepatotoxic

Acne hyperpigmented macules:

• Topical hydroquinones (1.5–10%)
• Azelaic acid (20%) topically
• Topical retinoids as above
• Corticosteroids: Low dose, suppresses adrenal androgens (1)[B]
• Dapsone 5% gel (Aczone): topical, anti-infammatory, use in patients >12 years

Issue for Referral
Consider referral/consultation to dermatologist:

• Refractory lesions despite appropriate therapy
• Consideration of isotretinoin therapy
• Management of acne scars

Additional Therapies
Photodynamic therapy for 30–60 minutes with 5-aminolevulinic acid × 3 sessions is effective for inflammatory lesions.

• Zinc gluconate 30 mg/d may reduce inflammatory lesions (2)[B]:
  • Topical zinc is ineffective.
• Topical tree oil is effective, but has slow onset (1)[B].

• Comedo extraction after incising the layer of epithelium over comedo (1)[C]
• Incision and drainage for abscesses
• Inject large cystic lesions with 0.05–0.3 mL triamcinolone (Kenalog 2–5 mg/mL), use 30-g needle to inject and slightly distend cyst (1)[C].
• Acne scar treatment: Retinoids, steroid injections, cryosurgery, electrodessication, microdermabrasion, dermabrasion, chemical peels, laser resurfacing, grafting, subcutaneous incision, punch excision, punch elevation, tissue augmentation injections

Cleansing after sweating

Patient Monitoring

• Pretreatment and monthly lipids, liver function tests, and pregnancy tests when on isotretinoin
• Consider antibiotic resistance (60% overall) or gram-negative folliculitis if treatment fails.

Special diets do not diminish acne (1)[B].

• There may be a worsening of acne during 1st 2 weeks of treatment.
• Treatment takes a minimum of 4 weeks to show results.
• Topical agents can cause redness and drying of the skin.
• Picking at or popping lesions may increase inflammation and scarring.

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

• Acne conglobata: Severe confluent inflammatory acne with systemic symptoms
• Facial and psychological scarring
• Gram-negative folliculitis: Superinfection due to long-term oral antibiotic use; treatment with ampicillin, trimethoprim-sulfa, or isotretinoin

• HeymannWR. Oral contraceptives for the treatment of acne vulgaris.J Am Acad Dermatol. 2007;56:1056-7 [PMID:17504720]
• NestorMS. The use of photodynamic therapy for treatment of acne vulgaris.Dermatol Clin. 2007;25:47-57 [PMID:17126741]
• YanAC. Current concepts in acne management.Adolesc Med Clin. 2006;17:613-37; abstract x-xi [PMID:17030282]

Acne Rosacea
Algorithm: Acne

706.1 Other acne

88616000 Acne vulgaris (disorder)

• Expect worsening for the 1st 2 weeks. Full results take 8–12 weeks.
• Decrease topical frequency from b.i.d. to every day or every day to every other day for irritation; may also use a moisturizing soap and a moisturizer before treatment application.
• Acne resolves with age for most individuals, although 8% of 30-year-olds and 3% of 40-year-olds may have persistent lesions.
• Acne often appears more significant to adolescent than to doctor; may be "entry ticket" for other advice.

Gary I.Levine, MD

Figure 1-2

Inflammatory acne lesions. Papules, pustules, and closed comedones are all present on this patient.

Figure 1-3

Severe cystic acne. This patient was subsequently treated with isotretinoin (Accutane).

1. StraussJS, KrowchukDP, LeydenJJ et al. Guidelines of care for acne vulgaris management.J Am Acad Dermatol. 2007;56:651-63  [PMID:17276540]
2. FeldmanS, CarecciaRE, BarhamKL et al. Diagnosis and treatment of acne.Am Fam Physician. 2004;69:2123-30  [PMID:15152959]
3. Webster G. Mechanism-based treatment of acne vulgaris: The value of combination therapy. J Drugs and Dermatol. 2005;4(3):281–288.  [PMID:15304471]
4. HaiderA, ShawJC. Treatment of acne vulgaris.JAMA. 2004;292:726-35 [PMID:15304471]