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Acne Vulgaris

Key Points

  • Acne is a common condition affecting persons of almost all ages; it may begin as early as the neonatal period, and peaks between ages of 13-17. For some patients, acne will persist into the fourth or fifth decade of life.
  • Acne is a chronic disease that requires initial and long-term (i.e., maintenance) therapy.
  • Even though it is not a life threatening disease, acne can have significant impact on a patient’s quality of life, including physical & psychological scars.
  • Distribution, number, and severity of lesions (especially scarring) should influence the approach to acne treatment.
  • Expert consensus suggests that a topical retinoid is first-line initial and maintenance therapy for almost all acne patients (except the most severe forms).
  • Antibiotic resistance caused by antibiotic monotherapy is an emerging clinical problem in acne management; antibiotic resistance leads to acne treatment failure. Therefore, the use of topical or systemic antibiotic monotherapy, especially long-term use, is not recommended in either the initial or maintenance phase of treatment.
  • There are multiple strategies that can be employed to limit emergence of antibiotic resistance: combination of a topical retinoid and benzoyl peroxide, antibiotic and benzoyl peroxide, topical retinoid and antibiotic, and use of either topical retinoid or benzoyl peroxide alone. However, use of combination therapy in many cases is more effective for the treatment of acne and several combination formulations are available. The convenience of combination formulations may also improve patient adherence to their acne skin regimen.
  • A combination formulation containing a topical retinoid and the antimicrobial agent benzoyl peroxide (such as EpiDuo) may accomplish the treatment goal of providing a first-line topical retinoid and a strategy to prevent antibiotic resistance consistent with the best practice of avoiding long-term topical antibiotic use.

Acne vulgaris is characterized by comedones, papules, and pustules, or a combination of lesions. Nodules, cysts, and scarring are seen in more severe disease. Factors involved in the pathogenesis of acne include: alteration of follicular keratinization, presence of bacteria (Propionibacterium acnes), sex hormone production (androgens) and sebum production.

Initial Evaluation

Determine the type, severity, and location of acne, and presence of scarring.

Acne lesions

Non-inflammatory (comedones)

Inflammatory (papules-pustules-nodules)

Scars (Keloidal scarring is present on the central chest. The other three images show atrophic scarring on the face.)

Types of acne

Comedonal acne: Open (blackheads) and closed (whiteheads) 1-2 mm follicular-based papules. Some of the lesions are excoriated.

Inflammatory acne: The lesions of inflammatory acne include erythematous papules and pustules, nodules and cysts. These are often seen in conjunction with comedones.

Nodular acne: Nodules are present on the upper right forehead and bilateral medial cheeks, in addition to inflammatory papules, pustules, and scars.

Neonatal acne: Inflammatory papules and milia on the cheeks of an infant (left) and inflammatory papules and pustules (middle) and crusted papules (right).

Acne with scarring: Atrophic acne scars in the setting of inflammatory papules and pustules (left) and keloid formation (right).

Severity of acne

  • Mild-to-moderate: mostly facial, usually non-scarring, mostly comedones, papules, and pustules
  • Moderate-to-severe: numerous lesions, can also involve the trunk, may scar, comedones, papules, pustules, nodules or cysts present
  • Severe: presence of scarring in the setting of comedones, papules, pustules, nodules or cysts, involvement of trunk is common

See the chapter Acne Vulgaris in A Clinical Atlas of 101 Common Skin Diseases.

Exacerbating factors

  • Presence of hormonal imbalances (polycystic ovary syndrome, oral contraceptives, exogenous androgens) or clear history of exacerbation related to menses
  • Systemic medications (anabolic or corticosteroids, OCPs, psychiatric medications, chemotherapy)
  • Occlusive topical agents
  • Mechanical irritation
  • Self-manipulation of lesions (picking)
  • The role of diet, sun exposure, and smoking are controversial

Differential diagnosis

Rosacea

Seborrheic dermatitis

Pityrosporum or other infectious folliculitis

General Principles of Acne Management

  • The clinical subtype, severity, prior treatment, psychological impact, and presence of scarring should be considered for all patients with acne.
  • The treatment of acne usually involves initial therapy followed by long-term maintenance therapy.
  • Treatment should target as many pathophysiological causes as possible.
  • Comedonal versus inflammatory acne requires distinct therapeutic approaches.
  • There is strong evidence now recommending against the use of topical or systemic antibiotic monotherapy, as antibiotic resistance may develop as quickly as 6 weeks with the use of topical antibiotic monotherapy. Use of systemic antibiotic monotherapy may give rise to antibiotic-resistant colonizing bacteria on skin and at remote sites, including streptococcal colonization of the throat.
  • There are multiple strategies that can be employed to limit emergence of antibiotic resistance: combination of a topical retinoid and benzoyl peroxide, antibiotic and benzoyl peroxide, topical retinoid and antibiotic, and use of either topical retinoid or benzoyl peroxide alone. However, use of combination therapy in many cases is more effective for the treatment of acne and several combination formulations are available. The convenience of combination formulations may also improve patient adherence to their acne skin regimen.
  • Topical retinoids used alone or as part of a combination therapy is considered first-line in the initial treatment of all types of acne except for severe nodular disease, which requires systemic retinoid therapy.
  • A combination formulation containing a topical retinoid and the antimicrobial agent benzoyl peroxide (such as EpiDuo) may accomplish the treatment goal of providing a first-line topical retinoid and a strategy to prevent antibiotic resistance consistent with the best practice of avoiding long-term topical antibiotic use.
  • Severe disease–especially scarring or trunk involvement–requires systemic therapy.
  • Some female patients may benefit greatly from hormonally targeted treatment.
  • It is essential to align the treatment regimen with the patient’’s goals and preferences for treatment: systemic versus topical, complexity of regimen.

Treatment

Mild to moderate acne

  • First-line therapy (comedonal acne only): topical retinoid
  • First-line therapy (mild inflammatory acne): topical retinoid alone, topical retinoid + topical antimicrobial
  • Topical retinoids are considered first line treatment for all forms of acne. Examples are: tretinoin (such as Atralin, Avita, Refissa, Renova, Retin-A, Retin-A Micro, Tretin-X), adapalene (such as Differin), tazarotene (such as Tazorac).
  • For comedonal acne or mild inflammatory disease, use of a topical retinoid such as tretinoin cream (0.025%-0.05% for the face, 0.1% for the trunk) or gel (0.01% for the face, 0.025% for the trunk), or adapalene 0.1% cream or 0.1, 0.3% gel is first-line treatment. (See handout How to use topical retinoid medications)
  • For moderate disease, add a second topical agent:
    • antibiotic erythromycin 2% or clindamycin (such as Cleocin T, Clindagel, ClindaMax, Evoclin) 1% solution, lotion or gel, or dapsone (such as Aczone) 5% gel applied daily
    • benzoyl peroxide wash, gel, lotion, or pads (2.5-10%) (such as Benzac AC, Benzac W, Brevoxyl, Desquam-E, Desquam-X, Triaz, or Zoderm
    • glycolic acid wash, gel, lotion (2.5-20%)
  • Fixed formulations of topical retinoids mixed with antimicrobials are available:
    • adapalene 0.1%/ benzoyl peroxide 2.5% gel (such as EpiDuo)
    • clindamycin 1.2%/ tretinoin  0.025% (such as Ziana)
  • Fixed combination of 2 antimicrobials are available (can be used in conjunction with topical retinoids)
    • clindamycin 1%/ benzoyl peroxide 5% gel (such as Acanya, BenzaClin, or Duac)
    • erythromycin 3%/ benzoyl peroxide 5% gel (such as Benzamycin)
  • Antibiotic monotherapy is strongly discouraged. Use of benzoyl peroxide should always be considered when using topical antibiotics to limit emergence of antibiotic-resistant bacteria.
  • Maintenance therapy: topical retinoid

Moderate to severe acne (severe disease, involvement of the trunk, +/- scarring)

First-line therapy: topical retinoid + systemic antibiotic + benzoyl peroxide

  • Combine a systemic antibiotic with a topical retinoid such as tretinoin cream (0.025%-0.05% for the face, 0.1% for the trunk) or gel (0.01 % for the face, 0.025% for the trunk), or adapalene 0.1% cream or 0.1, 0.3% gel:
    • tetracycline 500 mg b.i.d, doxycycline hyclate (such as Adoxa, Doryx, Oracea) 100 mg q.d.-b.i.d.
    • minocycline (such as Minocin or Solodyn) 50-150 mg q.d.)
  • Alternative oral antibiotics:
    • Cefadroxil (such as Duricef) 500 mg b.i.d.
    • Trimethoprim-sulfamethoxazole double-strength tablet (such as Bactrim or Septra DS) q.d. or b.i.d. may work when other antibiotics fail. The high rate of allergic reactions to sulfa (3%) limits use of trimethoprim-sulfamethoxazole.
    • Amoxicillin 500 mg b.i.d.
  • Addition of benzoyl peroxide should always be considered to limit emergence of antibiotic-resistant bacteria.
  • Use systemic antibiotics when there are numerous inflammatory lesions, involvement of the trunk or any scarring resulting from acne.
  • Maintenance therapy: topical retinoid +/- benzoyl peroxide

Severe acne (severe disease, presence of nodules, involvement of the trunk, or any evidence of scarring)

  • First-line therapy: systemic isotretinoin (such as Accutane, Amnesteem, Claravis, or Sotret)
  • Referral to a dermatologist, where available, or systemic isotretinoin should strongly be considered.
  • Maintenance therapy: topical retinoid +/- benzoyl peroxide

Managing acne treatment

  • Treatment must be applied to the entire affected area, not just the lesions.
  • 2-3 months of treatment are necessary. Treatment of truncal lesions may take longer. Continue any effective treatment for at least 3-6 months before slowly tapering off to maintenance therapy.
  • Topical retinoids are the mainstay of maintenance therapy once the acne is clear. It can be used in combination with benzoyl peroxide products in previously moderate-to-severe disease.
  • Acne will often flare after 2-3 weeks of tretinoin use, resolving within 6-8 weeks. Tretinoin flares can be prevented by starting the applications every 2-3 nights only for the first month, and using a topical antibiotic in the mornings.
  • Topical retinoids may induce photosensitivity, so encourage the use of a non-comedogenic sunscreen. (See handout Choosing a Sunscreen)
  • Facial comedones (especially of the forehead) are often related to oily products applied to the scalp/hair as well as other facial products (make-up). (See handout Skin & hair care for acne patients.)
  • Dryness is a common side effect of many acne treatments. Choosing cream or lotion-based vehicles, minimizing use of soap-based or medicated facial washes, and use of a non-comedogenic moisturizer reduces excessive dryness. (See handout Skin & hair care for acne patients.)

Overzealous use of topical retinoids and/or benzoyl peroxide products may irritate skin. Only small amounts of topical retinoids (pea-sized for the entire face) should be applied. Strategies for reducing retinoid irritation are:

  • Only small amounts of topical retinoid (pea-sized for the entire face) should be applied.
  • Start by using 2-3 times a week only with slow increase in frequency as tolerated
  • Wait 20 minutes after washing skin to apply topical retinoid (skin is dry)
  • Short-contact exposure (apply for one hour and then rinse off)
  • Add a moisturizer directly on top of the topical retinoid one hour after application
  • Avoid application on eyelids or lips
  • Use a retinoid such as adapalene (See handout How to use topical retinoid medications.)

Principles of acne treatment in special patient populations

Children (see Acne Vulgaris for Pediatricians)

Pregnant women or women planning to conceive

  • Most acne treatments carry risk to fetal development. It is important to consider plans for pregnancy in the initial discussion of acne treatment with all female patients.
  • A general guideline is to discontinue all potentially teratogenic medications at least one month prior to attempts for conception.
  • Azelaic acid (15 or 20% cream) b.i.d. and topical or systemic erythromycin base are safe options in pregnant patients.

Situations requiring dermatologic consultation

  • Lack of response to treatment (6 months) or uncertain diagnosis
  • Scarring
  • Widespread involvement
  • Possible endocrine disorder or acne treatment in the setting of complex medical disease
  • Need for systemic retinoid therapy (isotretinoin). Systemic retinoid therapy is first-line therapy indicated for nodular or scarring acne.
  • Medication-induced acne

Pitfalls

  • Three external factors that trigger the acne must be avoided for therapy to be effective:
    • comedogenic medications (steroids, psychiatric medications, oral contraceptives, etc.)
    • comedogenic cosmetics and creams
    • friction (e.g., from rubbing or self-manipulation/picking)
  • In female patients with a clear premenstrual trigger, consider spironolactone (such as Aldactone) 50 mg to 100 mg daily with or without oral contraceptive pills. Common side effects of spironolactone include breast tenderness and menstrual spotting, and it is a teratogen, and thus should not be used in pregnant individuals. Oral contraceptives with ethinyl estradiol with drospirenone or norgestimate are optimal for acne, such as drosperinone 3 mg & 0.03 mg ethinyl estradiol; drosperinone 3mg & 0.02 mg ethinyl estradiol (such as Ocella, Yasmin, or Yaz); norgestimate + ethinyl estradiol 35 mcg (such as MonoNessa, OrthoTri-Cyclen, Ortho Tri-Cyclen Lo, Previfem, Sprintec, Tri-Lo Sprintec, Tri-Previfem, Tri-Sprintec, or TriNessa).
  • Amenorrhea, androgenetic alopecia, and/or hirsutism, are signs of a hyperandrogenic state, and endocrine evaluation and correction or suppression of the condition may lead to improvement of the acne when other approaches fail. Consider referral to a dermatologist and/or endocrinologist.

Clinical Cases

Case 1

Mild acne

  • 17-year-old female patient
  • First consultation
  • Regular menses
  • No previous acne treatment
  • Mainly comedones and few inflammatory acne lesions on the face, sensitive skin

Treatment

  • Wash skin with non-soap containing face wash
  • Apply adapalene 0.1% cream or gel, every night for 2 months; start by using 2-3 times per week and increasing frequency to daily use as tolerated
  • Use a non-comedogenic moisturizer, if needed
  • Control in 6-8 weeks.

Follow-up appointment at 6 weeks

  • Very few comedones and no other lesions
  • Continue adapalene for 3-6 months
  • Control in 6 months
  • Long-term maintenance with adapalene at night

Case 2

Moderate acne

  • 18-year-old female patient
  • Previous treatment: doxycycline and topical clindamycin for 8 weeks with some improvement but relapsed when stopping the drug
  • Inflammatory lesions, comedones on the face, also on the back and chest, no visible scars

Treatment

  • Wash skin with non-soap containing wash
  • Apply benzoyl peroxide gel in the morning and adapalene 0.1% or tretinoin 0.025% cream at night to the face; if skin gets irritated, use once every other night for 2 weeks
  • Alternatively, a fixed formulation of benzoyl peroxide mixed with topical retinoid can be used at night
  • Doxycycline hyclate 100 mg once or twice daily
  • Use a non-comedogenic moisturizer
  • Control in 6-8 weeks

Follow-up appointment at 8 weeks

  • Improvement of 70%
  • Some inflammatory lesions and comedones
  • Continue doxycycline 100 mg for 1 month + topical regimen for 3 months
  • Control in 3 months
  • Long-term maintenance with topical retinoid cream at night

Case 3

Severe acne

  • 18-year-old teenager
  • Previous treatment: systemic antibiotics (not routine use), over the counter topical products, topical medications
  • Last treatment: minocycline 100 mg daily + tretinoin 0.05% cream + benzoyl peroxide wash for 6 months, with improvement but relapse after stopping the drugs; no treatment for the last 2 months
  • Numerous inflammatory lesions, with cysts, nodules, and comedones on the face and trunk, also with scarring

Treatment

  • Referral to a dermatologist, if available
  • Oral isotretinoin is first-line therapy for scarring and severe acne: 0.5 mg/kg/d per iPledge program (See www.ipledgeprogram.com)
  • Stop other forms of acne treatment, if any
  • Non-comedogenic moisturizer, mild cleanser
  • Improvement in 1 month

Follow-up appointment at 1 month

  • Still with moderate number of inflammatory lesions, fewer cysts and nodules
  • Continue isotretinoin at 0.5 mg/kg/d or consider increase to 1mg/kg/d per iPledge program

Monthly follow-up appointment

  • Continue isotretinoin for goal dose of 100-150 mg/kg total dosing

Long-term maintenance with topical retinoid +/- benzoyl peroxide: Fixed formulations of topical retinoids mixed with antimicrobials such as benzoyl peroxide are available for patient convenience/adherence to regimen.

Suggested Reading

Bhate K, Williams HC (2013) Epidemiology of acne vulgaris, BJD, 168:474-485.

Del Rosso JQ, Kim G (2009) Optimizing use of oral antibiotics in acne vulgaris; Dermatol Clin, 27(1):33-42.

James WD (2005) Clinical practice. Acne; N Engl J Med, 352(14): 1463-1472.

Strauss et al (2007) Guidelines of care for acne vulgaris management; J Am Acad Derm, 56;4: 651-663.

Thiboutot D (2011) Dermatologists do not yet fully understand the clinical significance of antibiotic use and bacterial resistance in patients with acne, Arch Derm, 147:921-922.

Thiboutot et al (2009) New insights into the management of acne: an update from the Global Alliance to improve outcomes in acne group; J Am Acad Derm, 60(5 Suppl): S1-50.

Turowski CB, James WD (2007) The efficacy and safety of amoxicillin, trimethoprim-sulfamethoxazole, and spironolactone for treatment-resistant acne vulgaris; Adv Dermatol, 23: 155-63.