Acne Vulgaris

Basics

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 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
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)

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/qualitative sebum changes and proliferation of keratinocytes in hair follicles (3).
  • Keratin plug obstructs follicle os, causing sebum accumulation and follicular distention.
  • Propionibacterium acnes, an anaerobe, colonizes and proliferates within a biofilm 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), lithium, phenytoin
  • 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 (3).
  • 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
  • Behçet 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”)
  • 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 (areas of greatest concentration of sebaceous glands) (3).
  • Adult female—mandibular and perioral lesion location

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 LH and FSH (PCOS).

Treatment

  • Comedonal (grade 1): keratinolytic agent (see as follows for specific agents)
  • Mild inflammatory acne (grade 2): benzoyl peroxide or topical retinoid or benzoyl peroxide +/− topical antibiotic +/− topical retinoid
  • Moderate inflammatory acne (grade 3): Add systemic antibiotic to grade 2 regimen.
  • Severe inflammatory acne (grade 4): as in grade 3, or isotretinoin
  • Topical retinoid plus a topical antimicrobial agent is first-line treatment for more than mild disease.
  • Topical retinoid + antibiotic (topical or PO) is better than either alone for mild/moderate acne.
  • Topical retinoids are first-line agents for maintenance. Avoid long-term antibiotics for maintenance.
  • Avoid topical antibiotics as monotherapy (4)[A].
  • Can use isotretinoin for treatment of resistant moderate acne (4)
  • Recommended vehicle type
    • Dry or sensitive skin: cream, lotion, 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 branded topical medications are very expensive, costing from $100 to several hundred dollars per tube.

  • Keratinolytic agents (α-hydroxy acids, salicylic acid, topical retinoids, azelaic acid) (side effects include dryness, erythema, and scaling; start with lower strength, increase as tolerated.)
  • 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 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)—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
  • 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
    • 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
      • 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: Do not use as monotherapy (4)[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: useful in adult females with inflammatory acne; may cause yellow/orange skin discoloration when mixed with BP; very rare methemoglobinemia
  • Oral antibiotics: use for shortest possible period, generally needs 8 to 12 weeks of therapy, reevaluate for discontinuation at 12 to 16 weeks duration (4); indicated when acne is more severe, trunk involvement, unresponsive to topical agents, or at greater risk for scarring (5)[A]
    • 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.
    • Doxycycline: 20 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 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)[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 due to risk of pseudotumor cerebri.
      • Monitor for pregnancy, psychiatric/mood changes, complete blood count (CBC), lipids, glucose, and liver function tests at baseline and every month.
      • Patient and provider must be registered and adhere to manufacturer’s iPLEDGE program (www.ipledgeprogram.com), two forms of effective contraception required.
  • Medications for women only
    • FDA-approved oral contraceptives (in order of possible effectiveness) (6)[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; may take months to become effective
  • Spironolactone (Aldactone); 25 to 200 mg/day; antiandrogen; reduces sebum production, not FDA-approved for acne Rx

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
    • Topical hydroquinones (1.5–10%)
    • Azelaic acid (20%) topically
    • Topical retinoids
    • Corticosteroids: low dose, suppresses adrenal androgens
    • Dapsone 5% gel (Aczone): topical, anti-inflammatory; use in patients >12 years.
    • Sunscreen for prevention
  • Light-based treatments (lack high quality evidence of effectiveness)
    • 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 for three 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
  • 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

Ongoing Care

Follow-up Recommendations

Use oral or topical antibiotics for 3 months; taper as inflammatory lesions resolve.

Diet

Data suggests that high-glycemic index foods and milk may influence 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 and psychological distress, including anxiety, depression, and suicidal ideation (3)
  • Postinflammatory hyperpigmentation, keloids, and scars are more common in skin of color.

Additional Reading

  • Nguyen HL, Tollefson MM. Endocrine disorders and hormonal therapy for adolescent acne. Curr Opin Pediatr. 2017;29(4):455–465. [PMID:28562419]

See Also

Codes

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)

Clinical Pearls

  • 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 benzoyl peroxide every time a topical or oral antibiotic is used.

Authors


Gary I. Levine, MD

Figures

Figure 1-2
Descriptive text is not available for this image

Inflammatory acne lesions. Papules, pustules, and closed comedones are all present on this patient.
Figure 1-3
Descriptive text is not available for this image

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

Bibliography

  1. Admani S, Barrio VR. Evaluation and treatment of acne from infancy to preadolescence. Dermatol Ther. 2013;26(6):462–466.  [PMID:26957383]
  2. Picardo M, Eichenfield LF, Tan J. Acne and rosacea. Dermatol Ther (Heidelb). 2017;7(Suppl 1):43–52.  [PMID:24552409]
  3. Dawson AL, Dellavalle RP. Acne vulgaris. BMJ. 2013;346:f2634.  [PMID:23657180]
  4. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945.e33–973.e33. [PMID:26897386]
  5. Del Rosso JQ, Kim G. Optimizing use of oral antibiotics in acne vulgaris. Dermatol Clin. 2009;27(1):33–42.  [PMID:18984366]
  6. Lortscher D, Admani S, Satur N, et al. Hormonal contraceptives and acne: a retrospective analysis of 2147 patients. J Drugs Dermatol. 2016;15(6):670–674.  [PMID:27272072]


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