Acne Vulgaris

- Comedonal (grade 1): keratinolytic agent (7)[A] (see as follows for specific agents) - Mild inflammatory acne (grade 2): benzoyl peroxide ± topical antibiotic + keratinolytic agent - Moderate inflammatory acne (grade 3): add systemic antibiotic to grade 2 regimen - Severe inflammatory acne (grade 4): as in grade 3, or isotretinoin(7)[A] - Topical retinoid plus a topical antimicrobial agent is 1st-line treatment for more than mild disease (8). - Topical retinoid + antibiotic (topical or PO) is better than either alone for mild/moderate acne (7)[A]. - Topical retinoids are 1st-line agents for maintenance. Avoid long-term antibiotics for maintenance. - Avoid topical antibiotics as monotherapy. - Recommended vehicle type - Dry or sensitive skin: cream or ointment - Oily skin, humid weather: gel, solution, or wash - Hair-bearing areas: lotion, hydrogel, or foam

- Acne hyperpigmented macules (11) - Topical hydroquinones (1.5-10%) - Azelaic acid (20%) topically - Topical retinoids - Corticosteroids: low dose, suppresses adrenal androgens (6)[B] - Dapsone 5% gel (Aczone): topical, anti-inflammatory; use in patients over 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 for 30 to 60 minutes with 5-aminolevulinic acid — 3 sessions is effective for inflammatory lesions. - Greatest use when used as adjunct to medications or if can't tolerate medications

para>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 teratogenic; pregnancy Category X
Avoid topical tretinoin as it may cause retinoid embryopathy; class C (1).
Contraindicated: isotretinoin, tazarotene, tetracycline, doxycycline, minocycline

Pediatric Considerations

Neonatal acne (neonatal cephalic pustulosis) (2)
Infantile acne
Early-mid childhood acne
Preadolescent acne
Do not use tetracycline in those <8 years of age (2,3); other therapies similar to adolescent acne

EPIDEMIOLOGY AND PATHOPHYSIOLOGY

Predominant age: early to late puberty, may persist in 20-40% of affected individuals into 4th decade
Predominant sexMale > female (adolescence)Female > male (adult)

Prevalence

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 and proliferation of keratinocytes in hair follicles (4).
Keratin plug obstructs follicle os, causing sebum accumulation and follicular distention.
Propionibacterium acnes, an anaerobe, colonizes and proliferates in the plugged follicle.
P. acnes promote proinflammatory mediators, causing inflammation of follicle and dermis.

Genetics

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)
Endocrine disorders: polycystic ovarian syndrome, Cushing syndrome, congenital adrenal hyperplasia, androgen-secreting tumors, acromegaly
Stress
High-glycemic load and possibly high-dairy diets may exacerbate acne (4,5).
Severe acne may worsen with smoking.

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
Beh §et syndrome, Apert syndrome
Dark-skinned patients: 50% keloidal scarring and 50% acne hyperpigmented macules

DIAGNOSIS

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"ť)
Scars: ice pick, rolling, boxcar, atrophic macules, hypertrophic, depressed, sinus tracts
Grading system (American Academy of Dermatology, 1990) (4)Mild: few papules/pustules; no nodulesModerate: some papules/pustules; few nodulesSevere: numerous papules/pustules; many nodulesVery 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) (4).

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

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

Only indicated if additional signs of androgen excess; if so, test for free and total testosterone, DHEA-S, LH, and FSH (6)

TREATMENT

Comedonal (grade 1): keratinolytic agent (7)[A] (see as follows for specific agents)
Mild inflammatory acne (grade 2): benzoyl peroxide ± topical antibiotic + keratinolytic agent
Moderate inflammatory acne (grade 3): add systemic antibiotic to grade 2 regimen
Severe inflammatory acne (grade 4): as in grade 3, or isotretinoin(7)[A]
Topical retinoid plus a topical antimicrobial agent is 1st-line treatment for more than mild disease (8).
Topical retinoid + antibiotic (topical or PO) is better than either alone for mild/moderate acne (7)[A].
Topical retinoids are 1st-line agents for maintenance. Avoid long-term antibiotics for maintenance.
Avoid topical antibiotics as monotherapy.
Recommended vehicle typeDry or sensitive skin: cream or ointmentOily skin, humid weather: gel, solution, or washHair-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 with keratinolytic agents.
Gentle cleanser and noncomedogenic moisturizer help decrease irritation.
Oil-free, noncomedogenic sunscreens
Stress management if acne flares with stress

MEDICATION

ALERT

Most prescription of topical medications are very expensive, costing from $100 to several hundred dollars per tube.

Keratinolytic agents (alpha-hydroxy acids, salicylic acid, azelaic acid) (side effects include dryness, erythema, and scaling; start with lower strength, increase as tolerated) (6,7)[A].
Tretinoin (Retin-A, Retin A Micro, Avita, Atralin) varying strengths and formulations: apply at bedtime; wash skin, let skin dry 30 minutes before application Retin-A Micro, Atralin and Avita are less irritating, and stable with BP May cause an initial flare of lesions; may be eased by 14-day course of oral antibiotics Avoid in pregnant and lactating women.
Adapalene (Differin): 0.1%, apply topically at night
Tazarotene (Tazorac): apply at bedtime
Azelaic acid (Azelex, Finevin): 20% topically, BID 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 Effective in postadolescent acne
Salicylic acid: 2%, less effective and less irritating than tretinoin
Alpha-hydroxy acids: available over-the-counter
Topical antibiotics and anti-inflammatories
Topical antibiotics (6,7)[A] Erythromycin 2% Clindamycin 1% Metronidazole gel or cream: apply once daily Azelaic acid (Azelex, Finevin): 20% cream: enhanced effect and decreased risk of resistance when used with zinc and benzoyl peroxide 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: may cause yellow/orange skin discoloration when mixed with benzoyl peroxide
Oral antibiotics: use for at least 6 to 8 weeks after initiation, discontinue after 12 to 18 weeks' duration; indicated when acne is more severe, trunk involvement, unresponsive to topical agents, or at greater risk for scarring (6,7,9)[A] Tetracycline: 500 to 1,000 mg/day divided BID; high dose initially, taper in 6 months. Side effects: photosensitivity, esophagitis Minocycline: 100 to 200 mg/day, divided daily-BID; side effects include photosensitivity, urticaria, gray-blue skin, vertigo, hepatitis Doxycycline: 50 to 200 mg/day, divided daily-BID; side effects include photosensitivity 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): 1 daily 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 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 (4,6,7)[A], 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, suicidal ideation, psychosis Avoid tetracyclines or vitamin A preparations during isotretinoin therapy. Monitor for pregnancy, psychiatric/mood changes, complete blood count (CBC), lipids, glucose, and liver function tests at baseline and every month. Must be registered and adhere to manufacturer's iPLEDGE program (www.ipledgeprogram.com)
Medications for women only
Spironolactone (Aldactone); 25 to 200 mg/day; antiandrogen; reduces sebum production

ISSUES FOR REFERRAL

Consider referral/consultation to dermatologist

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

ADDITIONAL THERAPIES

Acne hyperpigmented macules (11)Topical hydroquinones (1.5-10%)Azelaic acid (20%) topicallyTopical retinoidsCorticosteroids: low dose, suppresses adrenal androgens (6)[B]Dapsone 5% gel (Aczone): topical, anti-inflammatory; use in patients over 12 yearsSunscreen for prevention
Light-based treatmentsUltraviolet A/ultraviolet B (UVA/UVB), blue or blue/red light; pulse dye, KTP, or infrared laserPhotodynamic therapy for 30 to 60 minutes with 5-aminolevulinic acid — 3 sessions is effective for inflammatory lesions.Greatest use when used as adjunct to medications or if can't tolerate medications

SURGERY/OTHER PROCEDURES

Comedo extraction after incising the layer of epithelium over closed comedo (6)[C]
Inject large cystic lesions with 0.05 to 0.3 mL triamcinolone (Kenalog 2 to 5 mg/mL); use 30-gauge needle, inject through pore, slightly distend cyst (6)[C].
Acne scar treatment: retinoids, steroid injections, cryosurgery, electrodessication, micro/dermabrasion, chemical peels, laser resurfacing

COMPLEMENTARY & ALTERNATIVE MEDICINE

Evidence suggests tea tree oil, seaweed extract, Kampo formulations, Ayurvedic formulations, rose extract, basil extract, epigallocatechin gallate, and tea extract may be useful (12).

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Use oral or topical antibiotics for 3 months; taper as inflammatory lesions resolve. Do not use topical and oral antibiotic together.

DIET

Avoid high-glycemic index foods and milk (13)

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 and psychological distress, including anxiety, depression, and suicidal ideation (4)
Postinflammatory hyperpigmentation, keloids, and scars are more common in skin of color

REFERENCES

11 Pugashetti R, Shinkai K. Treatment of acne vulgaris in pregnant patients. Dermatol Ther. 2013;26(4):302-311.22 Friedlander SF, Baldwin HE, Mancini AJ, et al. The acne continuum: an age-based approach to therapy. Semin Cutan Med Surg. 2011;30(Suppl 3):S6-S11.33 Admani S, Barrio VR. Evaluation and treatment of acne from infancy to preadolescence. Dermatol Ther. 2013;26(6):462-466.44 Dawson AL, Dellavalle RP. Acne vulgaris. BMJ. 2013;346:f2634.55 Burris J, Rietkerk W, Woolf K. Acne: the role of medical nutrition therapy. J Acad Nutr Diet. 2013;113(3):416-430.66 Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol. 2007;56(4):651-663.77 Feldman S, Careccia RE, Barham KL, et al. Diagnosis and treatment of acne. Am Fam Physician. 2004;69(9):2123-2130.88 Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the management of acne: an update from the Global Alliance to improve outcomes in Acne group. J Am Acad Dermatol. 2009;60(5 Suppl):S1-S50.99 Del Rosso JQ, Kim G. Optimizing use of oral antibiotics in acne vulgaris. Dermatol Clin. 2009;27(1):33-42.1010 Heymann WR. Oral contraceptives for the treatment of acne vulgaris. J Am Acad Dermatol. 2007;56(6):1056-1057.1111 Woolery-Lloyd HC, Keri J, Doig S. Retinoids and azelaic acid to treat acne and hyperpigmentation in skin of color. J Drugs Dermatol. 2013;12(4):434-437.1212 Fisk WA, Lev-Tov HA, Sivamani RK. Botanical and phytochemical therapy of acne: a systematic review. Phytother Res. 2014;28(8):1137-1152.1313 Mahmood SN, Bowe WP. Diet and acne update: carbohydrates emerge as the main culprit. J Drugs Dermatol. 2014;13(4):428-435.

CODES

ICD10

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

ICD9

706.1 Other acne
706.0 Acne varioliformis

SNOMED

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

CLINICAL PEARLS

Expect worsening for the first 2 weeks of treatment. Full results for changes in therapy take 8 to 12 weeks.
Decrease topical frequency to every day or to every other day for irritation.
Use BP every time a topical or oral antibiotic is used.