Treatment should be directed toward the known pathogenic factors involved in acne. These include follicular hyperproliferation, excess sebum, Propionibacteriumacnes infection , and inflammation. The grade and severity of the acne help in determining which of the following treatments, alone or in combination, is most appropriate.
Current consensus recommends a combination of topical retinoid and antimicrobial therapy as first-line therapy for almost all patients with acne.  The superior efficacy of this combination, compared with either monotherapy, results from complementary mechanisms of action targeting different pathogenic factors. Retinoids reduce abnormal desquamation, are comedolytic, and have some anti-inflammatory effects, whereas benzoyl peroxide is antimicrobial with some keratolytic effects and antibiotics have anti-inflammatory and antimicrobial effects. 
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Topical retinoids are comedolytic and anti-inflammatory. They normalize follicular hyperproliferation and hyperkeratinization. Topical retinoids reduce the numbers of microcomedones, comedones, and inflammatory lesions.  Topical retinoids should be initiated as first-line therapy for both comedonal and inflammatory acne lesions and continued as maintenance therapy to inhibit further microcomedone formation. 
The most commonly prescribed topical retinoids for acne vulgaris include adapalene, tazarotene, and tretinoin. These retinoids should be applied once daily to clean, dry skin, but they may need to be applied less frequently if irritation occurs. Skin irritation with peeling and redness may be associated with the early use of topical retinoids and typically resolves within the first few weeks of use.  The use of mild, nonirritating cleansers and noncomedogenic moisturizers may help reduce this irritation.  Alternate-day dosing may be used if irritation persists.
Topical antibiotics are mainly used for their role against P acnes. They may also have anti-inflammatory properties. Topical antibiotics are not comedolytic, and bacterial resistance may develop to any of these agents. Commonly prescribed topical antibiotics for acne vulgaris include clindamycin (or less commonly erythromycin).
Antibiotic resistance in P acnes is common and is a significant threat to acne treatment.  Antimicrobials should be combined with a topical retinoids for greater clearing of lesions and shortened treatment and with benzoyl peroxide to reduce the likelihood of resistance.  Concurrent use of oral and topical antibiotics should be avoided and not be used as monotherapy. If acne relapses, use the same antibiotics if it was previously effective and it may also be helpful to use benzoyl peroxide for 5-7 days between antibiotic courses to reduce resistance in organisms on the skin. 
Benzoyl peroxide products are also effective against P acnes, and bacterial resistance to benzoyl peroxide has not been reported.  Benzoyl peroxide products are available over the counter and by prescription in a variety of topical forms, including soaps, washes, lotions, creams, and gels. Benzoyl peroxide products may be used once or twice a day. These agents may occasionally cause a true allergic contact dermatitis. More often, an irritant contact dermatitis develops, especially if used with tretinoin or when accompanied by aggressive washing methods.  If intensive erythema and pruritus develop, a patch test with benzoyl peroxide is indicated to rule out allergic contact dermatitis.
Systemic antibiotics are a mainstay in the treatment of moderate-to-severe inflammatory acne vulgaris.  . These agents have anti-inflammatory properties, and they are effective against P acnes. The tetracycline group of antibiotics is commonly prescribed for acne. The more lipophilic antibiotics, such as doxycycline and minocycline, are generally more effective than tetracycline. 
Greater efficacy may also be due to less P acnes resistance to minocycline. However, P acnes resistance is becoming more common with all classes of antibiotics currently used to treat acne vulgaris.  P acnes resistance to erythromycin has greatly reduced its usefulness in the treatment of acne.  Subantimicrobial therapy or concurrent treatment with topical benzoyl peroxide may reduce the emergence of resistant strains. 
Oral antibiotic use can lead to vaginal candidiasis; doxycycline can be associated with photosensitivity; and minocycline has been linked to pigment deposition of the skin, mucus membranes, and teeth. 
The emergence of antibiotic-resistant bacteria, other than P acnes is a contentious debate. An early study by Miller et al found increased skin carriage of coagulase-negative staphylococci in not only acne patients with prolonged use of antibiotics but also in their close contacts.  On the contrary, a study by Fanelli et al found that Staphylococcus aureus remained sensitive to tetracycline even after prolonged use of that antibiotic for acne. This has significant ramifications when considering efforts to control the spread of methicillin-resistant S aureus (MRSA), because tetracycline group antibiotics are currently one of the primary options for outpatient treatment of MRSA infection. 
Some hormonal therapies may be effective in the treatment of acne vulgaris. Estrogen can be used to decrease sebum production. Additionally, it reduces ovarian production of androgens by suppressing gonadotrophin release.  Oral contraceptives also increase hepatic synthesis of sex hormone–binding globulin, resulting in an overall decrease in circulating free testosterone. Combination birth control pills have shown efficacy in the treatment of acne vulgaris. 
Spironolactone may also be used in the treatment of acne vulgaris.  Spironolactone binds the androgen receptor and reduces androgen production. Adverse effects include dizziness, breast tenderness, and dysmenorrhea.  Dysmenorrhea may be lessened by coadministration with an oral contraceptive. Periodic evaluation of blood pressure and potassium levels is appropriate. Pregnancy must be avoided while taking spironolactone because of the risk of feminization of the male fetus. 
Isotretinoin is a systemic retinoid that is highly effective in the treatment of severe, recalcitrant acne vulgaris.  Isotretinoin causes normalization of epidermal differentiation, depresses sebum excretion by 70%, is anti-inflammatory, and even reduces the presence of P acnes. 
Isotretinoin therapy should be initiated at a dose of 0.5 mg/kg/d for 4 weeks and increased as tolerated until a cumulative dose of 120-150 mg/kg is achieved.  Coadministration with steroids at the onset of therapy may be useful in severe cases to prevent initial worsening.  Some patients may respond to doses lower than the standard recommendation dosages. A lower dose (0.25-0.4 mg/kg/d) may be as effective as the higher dose given for the same time period and with greater patient satisfaction.  Lower intermittent dosing schedules (1 wk/mo) are not as effective. 
Some patients only require one course of oral isotretinoin for complete acne remission, while others require more conventional or isotretinoin therapy. A study found 38% of the patients had no acne during 3-year follow up, and, among the remaining patients, 17% were controlled with further topical therapy, 25% with topical and oral antibiotics, and 20% with second course of isotretinoin.  Relapse is more likely in younger or female patients. 
Isotretinoin is a teratogen, so pregnancy must be avoided. Contraception counseling is mandatory, and 2 negative pregnancy test results are required prior to the initiation of therapy in women of childbearing potential. The baseline laboratory examination should also include cholesterol and triglyceride assessment, hepatic transaminase levels, and a CBC count. Pregnancy tests and laboratory examinations should be repeated monthly during treatment.  Other adverse effects include dry skin, lips, and eyes; muscle aches; and headaches. Patients experiencing severe headaches, decreased night vision, or adverse psychiatric events should stop taking isotretinoin immediately. 
Acne can be a very depressing situation. It can alter personality development in the adolescent stage and may create hostility, anger, and antisocial behavior. Associated mood changes and depression have also been reported during treatment. Isotretinoin may heighten feelings of depression and suicidal thoughts.  Do not administer isotretinoin to a depressed or suicidal teenager. Although a cause-and-effect relationship has not been established, patients should be informed of this potential effect and must sign a consent form acknowledging they are aware of this potential risk. 
A FDA-mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.
While using isotretinoin, the patient is considered at high risk for abnormal healing and the development of excessive granulation tissue following procedures.  Many dermatologists delay elective procedures, such as dermabrasion or laser resurfacing (eg, with carbon dioxide laser or erbium:YAG laser), for up to 1 year after completion of therapy. Other procedures to be avoided during therapy include tattoos, piercings, leg waxing, and other epilation procedures.
In December 2014, the US Food and Drug Administration (FDA) approved Bellafill, the first dermal filler indicated for acne scarring. Bellafill is a bovine collagen dermal filler.
Intralesional steroid injections have been found to be beneficial for large inflammatory lesions. Comedone removal does not affect the course of the disease, but it does improve the patient’s appearance.  Additionally, some patients may benefit from superficial peels that use glycolic or salicylic acid, although more research needs to be conducted to establish best practice for these modalities. Phototherapy using red or blue light and photodynamic therapy are being assessed as potential treatments for acne.  The usefulness of some fractional laser treatments in the management of acne is also being evaluated.
If the patient is feeling depressed while taking isotretinoin, refer him or her to a specialist for help.
Diet therapy has been suggested. Fulton et al performed a study on chocolate, having teenage patients with acne consume 1 bar of chocolate each day. Some of the patients improved and some worsened, but the vast majority were unchanged.  This study helped decrease the emphasis on diet as a causal factor in acne vulgaris. However, investigators always returned to the diet question. Data suggest that the westernization of certain Native American populations and the related consumption of unhealthy "junk" foods (eg, potato chips, soft drinks) has had a negative impact on general and skin health, resulting acne flares.
Investigators have also focused on a low-glycemic diet to avoid stress from high-carbohydrate diets and to reduce insulin levels. A study found that 12 weeks of a high-protein, low–glycemic load diet decreased the total amount of acne lesions, and this may lead to dermatologists recommending the South Beach Diet to patients with acne.  However, guideline groups have not found benefit in acne treatment or control with dietary restrictions. [26, 24]
Appropriate laboratory examinations (electrolyte evaluation, with particular attention to potassium levels and, when appropriate, pregnancy tests) may be considered when spironolactone is prescribed.
Baseline assessment of antinuclear antibody levels and hepatic transaminase levels has been recommended by some authors for patients expected to be on minocycline for more than 1 year. 
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