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Acne Vulgaris

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)

    • Newborn to 8 weeks; lesions limited to face; responds to topical ketoconazole 2% cream (3)

  • Infantile acne

    • Newborn to 1 year; lesions on face, neck, back, and chest; no Rx required (3)

  • Early-mid childhood acne

    • 1 to 7 years; rare; consider hyperandrogenism (3)

  • Preadolescent acne

    • 7 to 11 years; common, 47% of children, usually due to adrenal awakening

  • 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 sex
    • Male > 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 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) (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 type
    • Dry or sensitive skin: cream or ointment
    • Oily skin, humid weather: gel, solution, or wash
    • Hair-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

    • Effective; less irritation than tretinoin or tazarotene (7)[A]

    • May be combined with benzoyl peroxide (Epiduo)-very effective in skin of color

  • Tazarotene (Tazorac): apply at bedtime

    • Most effective and most irritating; teratogenic

  • 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 benzoyl peroxide (6,7)[A]

      • 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: irritation; may bleach clothes; photosensitivity

  • 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

    • Oral contraceptives (4,6,7)[A],(10)

      • Norgestimate/ethinyl estradiol (OrthoTricyclen), norethindrone acetate/ethinyl estradiol (Estrostep), drospirenone/ethinyl estradiol (Yaz, Yasmin) are USFDA approved.

      • Levonorgestrel /ethinyl estradiol (Alesse) and most combined contraceptives effective

  • 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%) 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

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.

SEE ALSO


  • Acne Rosacea
  • Algorithm: Acne

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.
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